COLUMBIA LIBRARIES OFFSITE HEALTH SCIENCES ST . AN ° ARD . HX64154122 RC1 38 .B49 Diptheria, its natur RECAP wife JHBHBH f^CvVi ^2>*c$ Columbia Mmtozv&ify in tfte Citp of i^ehi |?crfe College of S^fypgitims ano burgeons! Reference Htbrarp >u Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/diptheriaitsnatuOObill DIPHTHERIA Its Nature and Treatment BY C. E. BILLINGTON, M.D. AND Intubation in Croup AND OTHER ACUTE AND CHRONIC FORMS OF STENOSIS OF THE LARYNX BY JOSEPH O'DWYER, M.D. NEW YORK WILLIAM WOOD AND COMPANY 56 & 58 LAFAYETTE PLACE 1889 Copyright, 1889. WILLIAM WOOD & COMPANY. PRESS OF THE PUBLISHERS' PRINTING COMPANY, 157-159 WILLIAM STREET, NEW YORK. PREFACE. I have been emboldened to offer the present work to the Profession by the many gratifying assurances which I have received that my previous writings, which appeared in 1876 and at several subsequent times, have been of service to some. Those writings consisted mainly in statements of my own clinical observations and experience. My chief motive in add- ing the present one has been a desire to express my views on various important points somewhat more fully than was possible in them, and in connection with related facts in the history, the etiology, and the pathology of the disease, and recent advances in its therapeutics. To have made this an exhaustive treatise would have been impossible, in view of the great variety of aspects which have been assumed by the disease and its complications in occasional epidemics and individual cases, the wide diversity of the views which have been entertained as to its pathology, and of agents and methods which have been employed in its treatment, the resulting vastness of the literature relating to it, and the limitations of the time and space at my disposal. I have, however, endeavored to present a clear and succinct state- ment of those facts in existing knowledge which are most es- sential to the formation of an intelligent opinion as to its nature, and of those therapeutical principles and details, the IV PREFACE. comprehension and application of which will, as I believe, en- able the physician to treat it most successfully. It affords me much pleasure that Dr. O'Dwyer has kindly consented to treat, in this connection, of that very important addition made by him to our therapeutical resources in deal- ing- with the most distressing" and fatal form of diphtheria, — intubation of the larynx. C. E. BlLLINGTON. New York, April 15, CONTEXTS. CHAPTER I. PAGE Definition and History 1 CHAPTER II. Etiology 16 CHAPTER III. Pathology 46 CHAPTER IV. Symptoms 68 CHAPTER V. The Primary Nature of Diphtheria 96 CHAPTER VI. Secondary Diphtheria. 104 CHAPTER VII. Diphtheritic Paralysis 108 CHAPTER VIII. Diagnosis 121 CHAPTER IX. Prognosis 139 CHAPTER X. Prophylaxis 145 CHAPTER XL Treatment 150 APPENDIX. Etiology 259 INTUBATION IN CROUP And other Acute and Chronic Forms of Stenosis of the Larvnx 265 DIPHTHERIA; ITS isTATTTEE AOT) TREATMENT. CHAPTER I. DEFINITION AND HISTORY. Diphtheria is a specific disease which occurs sporadically, endemic ally and epidemically, and is contagious and infectious, its essential characteristic being- an inflammation of mucous membranes, or of the surface of wounds and the adjoining in- tegument, which tends, by cellular proliferation and degenera- tion and by fibrinous exudation, to the formation of a false membrane, and also to the production of a poison which, when absorbed into the circulation, causes morbid changes in the blood and in various organs of the body. The name diphtheria was first suggested by Bretonneau, who in his earlier publications employed the term diphtherite, derived from the Greek 8ijc) signifying inflammation, and the compound word thus admirably describing the "specific phlegmasia" wmich constitutes the local affection; but in his fifth memoir he adopted instead from Trousseau the name diphtherie, which, without the limiting suffix, more fitly designates the entire disease with its train of local and constitutional phenomena. The equivalent name, diphtheria, was thence adopted by Dr. W. Farr, Register General of England, and has since been universally emploved by writers in the English language. 2 diphtheria; its nature and treatment. Although this name and much of the more exact knowl- edge of the disease which has accompanied and followed its introduction are of recent origin, there is abundant evidence that the malady itself has prevailed widely among mankind since the most ancient times. In the sixth century B.C. or thereabouts, D'havantare, an Indian physician, in his " System of Medicine/' written in Sanskrit, described the symptoms of an incurable disease called " closing of the throat," and " aris- ing from phlegm combined with blood," which could hardly have been other than diphtheria. 1 The assertion, which has been made by some, that the disease is referred to in the Hippocratic writings, 2 rests on very inconclusive evidence. Asclepiades, in the first century B.C., is said to have performed laryngotomy. Aretaeus of Cappadocia, in the first century a.d., gives a graphic and unmistakable description of faucial and ' laryngeal diphtheria under the names ulcera ^gyptiaca and ulcera Syriaca, which are significant of its wide preva- lence. He says that "some ulcers on ths tonsils are mild and others are pestilential and deadly." The latter are " exten- sive, deep, putrid and coated with white, livid or black concre- tions." He then describes the development and extension of this form of the disease in the throat and the mouth and as a phlegmon on the neck, and its fatal result in "not many days," and adds, " But if this malady invades the chest through the windpipe, it causes suffocation on the same day." He then vividly depicts the symptoms and the struggles which are too often witnessed in the later stages of a fatal case of diphthe- ritic croup and completes the nosological picture by adding, "Children up to the age of puberty are chiefly affected by this disease." 3 Galen probably referred to diphtheria when he mentioned the expectoration of false membrane from the 1 Quoted in "Diphtheria, its Nature and Treatment," by Morell Mackenzie, M.D., p. 14. 2 Hippocrates: " de Epidemicis," lib. v. cap. iv., and "de Dentitione." 3 Aretaeus : " De Causis et Signis Acutorum Morborum," lib. 1. cap. 9. DEFINITION AND HISTORY. ■ 6 pharynx ana the air-passages. 1 Ccelius Aurelianusin the third century depicted the symptoms of diphtheritic laryngitis and also mentioned the imperfect articulation and the regurgita- tion of liquids through the nose in swallowing, which result from diphtheritic faucial paralysis. 2 Aetius of Amida in the fifth century described a disease of children, in which the whitish and grayish faucial appearances, the dysphagia, the suffocation, the characteristic symptoms of resulting palatal paralysis, sudden death after apparent recovery, and intoler- ance of too harsh local treatment form a complete clinical picture of diphtheria. 3 The probability, from some passages in the historians, that severe epidemics of this disease may have occurred in antiquity, of which we have no record by medical writers, is illustrated by Bretonneau (second memoir) in the instance that Macrobius in the year 380 a.d. speaks, according to Julius Modestus, of sacrifices which were insti- tuted in honor of a heathen goddess, "ut populus E-omanus morbo qui Angina dicitur, promisso voto, sit liberatus." For an interval of more than a thousand years, which con- stituted the " Dark Ages/' there is no distinct record of the disease, probably not from its non-occurrence, but from a lack of competent observers. It is with good reason supposed that some of the "plagues" of the Middle Ages may have been epidemics of diphtheria. Among these were the pest called " esquinancie/' a form of angina maligna mentioned in the chronicle of St. Denis for the year 580, and a destructive "pes- tilentia faucium " at Rome in 856, and another in 1004 recorded by Baronius, and a fatal " cynanche " in the Byzantine empire in 1037 recorded by Cedrenus, and an angina which carried off many children in England in 1389, referred to by Short. 4 In the sixteenth century records of the occurrence of epi- lf 'De Locis Affectis," lib. 1. cap. 9. 2 "De Aeutis Morbis," lib. iii., cap. 2 et cap. iv. 3 Petrabibl. Serrao viii. , cap. 46. 4 Cited by Hirsch, Greog. and Hist. Pathol., vol. iii. 4 diphtheria; its nature and treatment. demies of diphtheria beg-in rapidly to multiply. Among- these an epidemic in Holland in 1557 was described by Peter Forest * as an "angina maligna contagiosa," rapidly fatal by strangu- lation, and another in 1564 and 1576 mentioned by Van Wier 2 as an " angina maligna," particularly common among children and fatal in from one to seven days; others occurred in the Rhenish provinces and in North Germany, and one in Naples and Sicily. An epidemic in Paris in 1576 was described by Baillou, 3 who mentioned false membrane as observed in an autopsy : " Pituita lenta contumax quae instar rnembranae cu- jusdam arterige asperse erat obtenta." In Spain a great epidemic, or succession of epidemics, of angina maligna, there known under the popular name of gar rotillo, raged from 1583 to 1618, and was well described by a number of medical writers. Beginning in Seville in the former year, it reached its widest diffusion over the country about 1610, and in 1613 the mortality was so frightful that that year has since borne the name of "anno de los garrotillos." Among the best descriptions of the disease were that of Villa Real, 4 who minutely described false membrane as seen by him, not only in many cases during life, but also in autopsies; that of Herrera, 5 who also observed diphtheritic false membrane in autopsies, and described diphtheria of the skin and of wounds ; that of Mercado, 6 physician to Philip II. and Philip III., who noted the slight degree of fever present in some very grave cases, described diphtheritic cervical adenitis, and mentioned an instance of a child communicating the disease to its father '"Observat. et Curat. Medic." lib. vi., observ. ii., schol. Lugd. Bat., 1591. 2 Van Wier : Observat. lib. i, sec. 3. ^Epideiiiiorum, lib. ii., Grenev. 1762. 4 Villa Real : " De Signis Causis, Essentia, Prognostico et Curatione Morbi Suffocantis," Compluti 1611. 5 " De Essentia, Causis, Notis, Presagio, Curatione et Precautione Morbi Suffocantis Garrotillo Hispane Appellati," auctore Doctore Herrera, Matriti, 1615. "Consult, med. lib. cons, xiv., in opp. Frankf. 1620. DEFINITION AND HISTORY. O by biting- his finger; and of Heredia, 1 physician to Philip IV., who distinguished the two forms of the disease, the suffocative and the asthenic, observed paralysis of the palate, the pharynx and the limbs, believed in a secondary infection by the resorp- tion of morbid products, and recommended for its prevention the early employment of cauterization. An epidemic in Portugal in 1626 is described by Bar- bosa. 2 In Italy malignant sore throat, having been prevalent in Mantua and Lombardy in 1610, 3 broke out in the city of Naples in 1617, gradually overran the kingdom of the Two Sicilies and the States of the Church, and prevailed in various epi- demics and recurrences in many parts of Italy until 1650. Among the accounts of these epidemics are that of Sgambatus, 4 Carnevale, 5 Aetius Cletus, 6 who vividly described not only pseudo-membrane in the fauces, but the gangrenous, the laryn- geal, the toxaamic, the asthenic, and the nasal forms of the disease, and also the protracted debility and the paralysis of the vocal organs of those who recovered; and Severino, 7 who described diphtheritic membrane as seen in an autopsy, and diphtherial paralysis. In the eighteenth century angina maligna was even more prevalent than in the seventeenth, occurring in nearly every country of Europe and in some portions of America. Many localities in Spain and Portugal were invaded by it between the years 1701 and 1786. It prevailed in Paris and in many other towns in France in 1743-50; again in Paris in 1758-9 and in 1762. The first of these epidemics was described by Marteau 1 " De Alorbis Acutis," lib. ii., sec. iii., cap. 5. Lyon, 1685. 2 " Estudios sobre o garrotilho ou croup." Lisbon, 1861. 3 Corradi "Annali delle Epideinie occorse in Italia," iii. 16. 4 "De Pestilente Fauciuni Affectu, Neapoli Sceviente Opusculum," auctore Andrea Sgambato. Neapoli, 1620. 5 " De Epidemico Strangulatorio Affectu," etc. Neapoli, 1620. 6 " De Morbo Strangulatorio opus." Roinae, 1636. '• " De Pedauchone Maligna," etc. Neapoli, 1643. 6 diphtheria; its nature and treatment. de Grandvilliers, 1 and by Chomel, 2 who accurately described paralysis of the soft palate, and a case of diphtheritic strabis- mus. Epidemics occurred in various portions of Italy between 1747 and 1786. One which prevailed in Palermo in 1747-8 was described by Ghisi, 3 who observed laryngeal croup and pharyn- geal angina gangrenosa as each occurred separately, and when both were united in the same patient, and noted the phenom- ena of diphtheritic paralysis. Epidemic outbreaks occurred in Holland between 1745 and 1770. In Great Britain an epi- demic of angina maligna, was described in 1713 by Dr. Patrick Blair, 4 under the name of "the croops" as "universal" at Coupar Angus. In 1748 a fatal outbreak in London of scar- latina anginosa, which was complicated with diphtheria, was described by Dr. Fothergill. 5 In 1745-8 a "morbus strangula- torius," which presented the characteristic features of malig- nant diphtheria, prevailed in Cornwall, and was described by Starr. 6 In 1765 appeared the treatise on croup by Francis Home of Scotland. 7 This work is very important, not only from the completeness of its descriptions and the logical force of its de- ductions, but also from the fact that it, for the first time, clearly depicts a form of pseudo-membranous disease which was regarded by him and has since been regarded bj r many others as distinct from diphtheritic angina. According to him croup, or, as he names it, " suffocatio stridula," is a dis- ease which " belongs peculiarly to children." It " has a local 1 " Dissertation Historique sur l'espece de Mai de Gorge Grangreneux qui a regne' parmi les Enfants l'annee derniere." Paris, 1749. 2 "Dissert. Hist, sur l'aspect du Mai de Gorge Grangreneux," etc., Paris, 1749. 8 " Lettere Mediche del Dottore Martino Grhisi." Cremona, 1749. 4 " Observations in the Practice of Physic," etc. London, 1713. 5 "An Account of the Sore Throat Attended with Ulcers," by Dr. John Fothergill. London, 1748. 6 " Philosophical Transactions," 1750, t. xlvi., p. 435. 1 "An Inquiry into the Nature, Causes and Cure of Croup," by Fran- cis Home, M.D. Edinburgh, 1765. DEFINITION AND HISTORY. 7 situation," being- "seldom found at any great distance from the sea-shore/' though " very wet and marshy situations some- times produce it." Its occurrence is also favored by cold and damp weather, and recent attacks of measles, whooping-cough or small-pox predispose to it. It is " a disease of an inflam- matory nature," which " appears to be confined chiefly to the trachea, as the patients have no pain in deglutition, and as the fauces are at most but a little redder." " The place first and most particularly affected is the upper part of the trachea, about an inch below the glottis." " The cause of this disease is a preternatural white, tough, thick membranous crust cov- ering often for many inches the inside of the trachea." " This membrane is not attached to the parts below, but is easily separated from them, as there is always matter behind it." There are two forms of the disease, " the inflammatory and less dangerous, and the less inflammatory and highly danger- ous." This description is based on twelve cases, of which three were of the former or catarrhal variety, and terminated in recovery, and are given as examples of those which are "common." The other nine were fatal ones, and in all of these autopsies were made, the membrane as above described being found in every one. In only one, which he regarded as com- plicated with " angina," the throat and tonsils were inflamed and " covered with mucus." There is no mention of an epi- demic character nor of contagiousness in the disease described, but it is possibly worthy of note that two of the fatal cases (IV. and V.) were those of a brother and sister, the former having been attacked September 29th, 1760, the latter, Octo- ber 5th. The treatment he advises consists of blood-letting, blisters, emollient fomentations and cataplasms around the neck, inhalation of the steam of water and vinegar, and gentle sudorifics. Emetics he had not found useful. When the mem- brane has formed he recommends bronchotomy. Diphtheria again prevailed in London and in some other localities in England in 1790-1793. 8 DIPHTHERIA; ITS NATURE AND TREATMENT. Epidemics occurred in Germany in 1752, 1755 and 1790. In 1778 Michaelis 1 in Gottingen wrote in confirmation of the de- scriptions and views of Home. The disease prevailed in the Simmenthal, Switzerland, in 1752, and in many places in Sweden in the years 1755-62. In the latter country Wilcke in 1757 described pseudo-membranous angina. 2 In New England an epidemic occurred in 1735, which was described by Dr. "William Douglas 3 as originating in Kings- ton township, about fifty miles eastward of Boston, and after prevailing with great fatality in the surrounding country, at length reaching Boston, where it was much milder. The symptoms of this malady, which are fully detailed, are clearly those of scarlatina, but in many instances there was evidently a complicating or secondary diphtheria. Two years later a similar epidemic is described in a letter from Rev. J. Dickinson, 4 dated " Elizabeth Town, New Jersey, February 20, 1738-*9," as having occurred in that place some time previously, a portion of which description is so vivid as to be worthy of quotation. He describes the disease in six forms, the first being evidently scarlatina, or possibly in some cases measles. The second form "frequently begins with a slight indisposition, much resembling an ordinary cold, with a listless habit, a slow and scarce discernible fever, some sore- ness of the throat and tumefaction of the tonsils; and perhaps a running of the nose, the countenance pale and the eyes dull and heavy. The patient is not confined, nor any danger ap- 1 " De Angina Polyposa Membranacea." Grottingen, 1778. 2 "Diss. Med. de Angina Infantum." Upsala, 1764. 3 "The Practical History of a New Epidemical Eruptive Miliary Fever with an Angina Ulcusculosa which prevailed in Boston, New England, in the years 1735 and 1736. Printed and Sold by Thomas Fleet. 4 " Observations on that Terrible Disease, Vulgarly called the Throat- Distemper, with Advices as to the Method of Cure." In a Letter to a Friend. By J. Dickinson, A.M. Boston : Printed and Sold by S. Knee- land and T. Green in Queenstreet over against the Prison, 1740." Jon- athan Dickinson was the first President of Princeton College and the first pastor of the Presbyterian church of Elizabeth, N. J. DEFINITION AND HISTUKY. 9 prehended for some days, until the fever gradually increases, the whole throat and sometimes the roof of the mouth and nostrils are covered with a cankerous crust, which corrodes the contiguous parts and frequently terminates in a mortal gangrene. When the lungs are thus affected the patient is first afflicted with a dry, hollow cough, which is quickly suc- ceeded with an extraordinary hoarseness and total loss of the voice, with the most distressing asthmatic symptoms and difficulty of breathing, under which the poor miserable creat- ure struggles until released by a perfect suffocation or stop- page of breath. This last has been the fatal symptom under which the most have sunk that have died in these parts. All that I have seen to get over this dreadful symptom have ' by their perpetual cough expectorated incredible quantities of a tough whitish slough from their lungs/' Dr. Cadwallader Colden 1 traces the progress of the epi- demic from Kingston westward, it appearing " first in those places where the people of New England chiefly resorted for trade, and in the places through which they travelled " until it "spread over all the British colonies in the Continent," "children and young people" being "only subject to it; " but he adds nothing of importance to the two descriptions of the disease just quoted. In 1771 appeared the classical treatise of Dr. Samuel Bard 2 of New York, who described with clearness and accuracy pharyngeal, laryngeal and cutaneous diphtheria, occurring separately and in the same patients, from clinical observation 1 " Extract of Letter from Cadwallader Colden, Esq., to Dr. Fothergill concerning the Throat Distemper," dated Coldenham in New York, 1753. Published in London Observations and Inquiries, vol. i., p. 211. ' 2 "An Enquiry into the Nature, Cause and Cure of the Angina Suffo- eativa or Sore-Throat Distemper as it is commonly called by the In- habitants of this City and Colony. By Samuel Bard, M.D., and Pro- fessor of Medicine in King's College, New York. Printed by S. Inslee and A. Car, at the New Printing-Offlce in Beaver Street, MDCCLXXI." Reprinted in Transactions of the American Philosophical Society, Philadelphia, 1789. 10 DIPHTHERIA; ITS NATURE AND TREATMENT. and post-mortem examination, as pseudo-membranous but not gangrenous affections, and believed that these various forms of disease, with those described by the Italian writers and by- Home, Fothergill, Huxham and Douglas, were essentially re- lated and "arise from the same leaven." He also described consecutive paralysis affecting- deglutition, speech and locomo- tion, and emphasized the infectiousness of the disease and the importance of isolating the sick. Although the masterpiece of Bard has in recent times been appreciated at its true value, it does not seem to have com- manded the contemporaneous attention which it merited, and the ideas of Home maintained their ascendancy. Their influence is illustrated in a "letter on the croup" from P. Middleton, 1 M.D., to Mr. Richard Bayley, surgeon, New York, dated New York, November 30, 1780. He says, "When I first came (from Scotland) to this city in 1752,1 found complaints of the throat not infrequent, but most of them were usually considered as having a malignant tendency if not actually angina? gangrenosa?, and in consequence of this general belief antiseptics were the remedies used in preference to all evacuants except perhaps emetics." He proceeds to state his belief that croup is " totally distinct from malignant sore throat/' and asserts that though the two affections may be united, he has never seen such an instance. Similar views appear in a letter on the croup from Professor Richard Bayley 2 to William Hunter, M.D., London, published about 1781. He quotes with approval the post-mortem obser- vations of Bard, but regards angina trachealis as an " inflam- matory " affection, and, like Dr. Middleton, has treated it suc- cessfully, even in its advanced stages, by the vigorous employ- ment of venesection, blisters, mercurial evacuants and emetics. Dr. John Archer, 3 in a letter to Benjamin Smith Barton, 1 Medical Repository, New York, vol. xiv., p. 347. 2 Medical Repository, New York, vol. xii., p. 331, and vol. xiv., p. 345. 3 Medical Repository, New York, vol. ii. p. 27. DEFINITION AND HISTORY. 11 M.D., of Philadelphia, dated Hartford County, Maryland, March IT, 1798, likewise considers croup as a "topical disease, confined to the trachea arteria, and the several ramifications thereof." In France, also, at this period most writers held the same views regarding the distinct nature of croup and angina ma- ligna. Several members of the imperial family having died of the former disease, a prize was offered by Napoleon I. for the best essay upon it. This prize was divided between Jurine, of Geneva, and Albers, of Bremen. Jurine recognized the fact of the frequent concurrence of croup with angina gangrenosa, and expressed doubt as to the actual existence of gangrene in the majority of cases of the latter disease. At length appeared the writings of Bretonneau, which may be said to have founded on a firm and broad basis the modern knowledge of diphtheria. Many of the facts which he an- nounced respecting the disease had, as we have seen, been previously observed and stated ~by others. It was his glorious achievement to establish them by incontrovertible demonstra- tion and to present them in their true relations. The principal writings of Bretonneau * consist of five papers or memoirs, the first t\\ o of which were read at the Academie Royale de Mede- cine in 1821; the last was published in 1855. His studies of the disease were principally made in three great epidemics, that of Tours in 1818, de la Ferriere in 1825, and Chenusson in 1826. The most distinctive feature of Bretonneau's work was the great amount of necroscopic research which it comprised, sixty autopsies being referred to in the first epidemic alone. Among the most important points established by his observa- tions were the absence of gangrene in most cases of diphtheria, 1 " Des inflammations speciales du tissu muqueux et en particulier de la diphtherite, ou inflammation pelliculaire connue sous le nom de croup, d'angine inaligne, d'angine gangreneuse, etc., Paris, 1826." " Sur les ruoyens de prevenir le developpement et les progres de la diphtherie," Archives Gren^rales de Medecine, 1855. 12 DIPHTHERIA; ITS NATURE AND TREATMENT. the nature and the relations of pseudo-membrane, its frequent continuity and its essential unity in the buccal, the naso- pharyngeal and the laryngotracheal regions, the specificity of the diphtheritic inflammation in distinction from the catar- rhal and from other specific phlegmasia?, the non-identity of membranous and "spasmodic"' croup, and the true relation of sequence and causation between the local and the constitu- tional phenomena of diphtheria, which he expressed in the phrases, " localized primitive diphtheria " and " the secondary or constitutional affection." 1 The teachings of Bretonneau were ably seconded and am- plified by various writers, among the earliest of whom were Guersant, 2 Louis, 3 Gendron 4 and Mackenzie, 5 the two latter of whom were among the earliest advocates of the topical use of nitrate of silver. During the earlier half of the present century the prev- alence of diphtheria greatly diminished, except in France where numerous epidemics occurred between 1810 and 1843, and again from 1846 to 1855. In other European countries and on this continent it was either unknown or occurred only sporadically or in occasional and limited epidemics. In 1856, an outbreak having occurred at Boulogne, in France, which was especially fatal among the resident English, the disease was conveyed to England and prevailed there in numerous and fatal epidemics until 1863. At about the same time a new and more general outbreak than had ever before occurred began not only in Europe and America, but also in Asia, Africa, Australia and Polynesia; and that general prevalence of the disease has since continued, though often in a greatly 1 Fifth Memoir. 2 Dictionnaire de M6decine, Articles "Angine Couenneuse," t. ii., "Croup," t. vi., and " Stomatite Couenneuse," t. xix. 3 " Du Croup consider^ chez l'adulte," Arch. Gen., t. iv., pp. 1 and 369. 4 " Observations sur une Angine Couenneuse," Journal Compl^men- taire du Diction, des Sciences Med., t. xxiii., p. 346. 6 "On the Symptoms and Cure of Croup," Edin. Med. and Surg. Journ., vol. xxiii., p. 294. DEFINITION AND HISTORY. 13 mitigated form, until the present time, so that in most of the cities of the world at the present day diphtheria contributes a considerable annual quota to the list of mortality. Under these circumstances it is not surprising- that the literature of the disease has assumed enormous proportions, and is less and less occupied with accounts of particular epi- demics and more and more with questions relating to etiolog} 7 , pathology, and therapeutics. As various writers will necessarily be referred to in the chapters on these subjects, but few additional ones need now be enumerated. Deslandes, in 1827, 1 in considering the ques- tion of the identity of pseudo-membranous angina and croup, gave a minute and valuable historical review of the subject of epidemic sore throat. His views on the question referred to accord affirmatively with those of Bretonneau. The doctrine that diphtheria is a primarily constitutional affection was advocated by Emangard, 2 who attacked the views of Breton neau from the point of view of the "physiological" school, maintaining that the disease is of malarial origin and of kin- dred nature to typhus— a " gastro-enteric angina." Fuchs 3 also, after a historical review of the subject, held that angina maligna was a " typhus " identical with the pulpous form of hospital gangrene. Both of these questions, namely that of the identity or di- versity of membranous croup and diphtheria and that of the primarily local or constitutional nature of diphtheria, have since been discussed by many writers from opposite points of view, representing a diversity of opinion which continues to the present day. Trousseau, 4 the friend and pupil of Bretonneau, was his 1 Journal des Progres des Sc. Med., t. L, p. 152. 2 " Examen Critique du Traits de la Diphtherie par M. Bretonneau. " Paris, 1829. 3 " Historische Untersuchungen uber Angina Maligna und ihr Ver- haltniss zu Scarlach und Croup." Wtirzburg, 1828. 4 "Memoir sur une epid^mie d'Angine Couenneuse Scarlatineuse," 14 DIPHTHERIA; ITS NATURE AND TREATMENT. worthy continuator, and supplemented his work by adding from 1829 to 1858 observations which were necessary to the complete description of diphtheria, especially in reference to its cutaneous form and its constitutional manifestations, in- cluding" albuminuria and the various forms of resultant paral- ysis. Trousseau was, moreover, like Bretonneau, a warm ad- vocate of tracheotomy, and devoted much attention to perfect- ing- its method and details. The statement of Bretonneau that diphtheria is never accompanied by true gangrene, was shown to be subject to many exceptions by Trousseau and also by Becquerel, 1 Billiet and Barthez, 2 and Simon. 3 The occurrence of albuminuria in connection with diphtheria was first discovered in 1857 by Dr. W. F. Wade, 4 of Birming- ham, and was soon after independently observed by Dr. Ger- main See, of Paris. 5 Diphtheritic conjunctivitis was first elaborately treated of by Yon Graefe 6 in 1857. His publication was closely followed by that of Prichard. 7 The first important publication on the subject of diphthe- ritic paralysis was that of Maingault. 8 The first precise description of the anatomical distinctions between the different forms of inflammation of mucous mem- branes by Virchow in 1847, and the first announcement of the discovery of a supposed bacterial cause of diphtheria by Lay- Arch. Gen., t. xxi., p. 541 ; " De la Diphtherite Cutanee," ibid., t. xxiii., p. 383; " Lecons Cliniques sur les Angines," Gaz. des H6p., Nos. 86, 89, 100, 104, 109, 115, 119, etc. 1 " Relation d'une Epidemie d' Affections Pseudo-rnembraneuses et Gangreneuses qui a regne a l'Hopital des Enfants," Gaz. Med., Nos. 43, 44, 45, 46. 2 "Maladies des Enfants," t. i., pp. 285, 316. 3 Considerations sur l'Angine Gangr6neuse et de son traitement," Bull, de Therap., t. xxiv., p. 401. 4 Midland Quarterly Journal of the Medical Sciences, April, 1858. 5 Union M6dicale, 1858, p. 497. 6 Archiv. f. Ophthal., b. 1, s. 168. 1 British Med. Journ., 1857, p. 981. 8 These de Paris, 1854. DEFINITION AND HISTORY. 15 cock in 1858, and many important subsequent pathological and etiological investigations by others, will be more appro- priately referred to elsewhere in this work. In treatment, hydrochloric acid, alum, and later nitrate of silver, were locally employed by Bretonneau, and in some cases mercury internally. Tonics were advocated by Becquerel * in 1813; alkaline treatment by Baron 2 in 1851; chlorate of po- tassa by A. Smith 3 in 1855; iodine by Lecointe, 4 and bromine by Ozanam 5 in 1856; muriated tincture of iron internally by Heslop in 1858 ; 6 iron and chlorate of potassa by Kingsford; 7 sulphur by Duche 8 in the same year, and turpentine by Perry 9 in 1859. A method of intubation of the larynx having been devised and warmly advocated by Bouchut, a report on the subject was presented to the Academie de Medecine by Trousseau in 1858, so unfavorable that the procedure was condemned by the general verdict of professional opinion, was abandoned by its author, and fell into such oblivion that when Dr. Joseph O'Dwyer, of New York, a quarter of a century later, invented and perfected the method of intubation which has rapidly won acceptance among the great therapeutical improvements of the age, he did so in ignorance of the fact that his idea had been anticipated. 1 Op. cit. 2 Gazette He'd., 1851, p. 524. 3 Dublin Hosp. Gazette, vol. ii., p. 149. 4 Bulletin de Therap., t. i., p. 70. 5 Coinptes Rendus de FAead. des Sci., t. xlii., p. 102, and Hon. des Hop., p. 551. 6 Med. Times and Gazette, vol. xxxvii., p. 552. ' Lancet, 1858, p. 484. 8 Gaz. des Hop., Nos. 125 and 133. 9 Med. Times and Gaz., vol. xxxix., p. 245. CHAPTER II. ETIOLOGY. The causes of diphtheria are not fully known. The knowl- edge which we have respecting" them is derived from the ob- servation of the circumstances under which the disease naturally occurs, the results of experiments for its artificial production, and certain facts in its pathology. Among the circumstances which ordinarily influence the occurrence of diphtheria, one of the most noteworthy is that of age. While no period of life is absolutely exempt from its attacks, it is in the great majority of cases a disease of child- hood. Among nearly 70,000 fatal cases comprised in the re- turns of the Registrar General of England, and analyzed by Dr. Tbursfield, 1 the numbers per thousand of the different ages were as follows: — Under 1 year, . 90 From 1 to 5 years, 450 5 " 10 " . 260 " 10 " 15 " . 90 " 15 " 25 " . 50 " 25 " 45 " . 35 45 years and upwards, 25 The following table, compiled from the records of the Board of Health, shows the ages in 14,688 fatal cases of diphtheria which occurred in this city during the ten years, 1873-1882. It will be seen that over eight per cent, of all were under one year, over seventy-three per cent, of all under five years, and over ninety-five per cent, of all, under ten years. 1 London Lancet, August 3, 1878. ETIOLOGY. 17 Under 1 year of age, . Over " " " and under 5, Total under 5, Over 5 years and under 10, Total under 10, Over 10 years and under 15, 1,214 9,622 • 10,836 3,212 14,048 311 87 53 37 34 28 25 16 12 12 8 3 6 6 2 14,688 In some local outbreaks of diphtheria, however, of excep- tional malignancy, the proportion of adults affected has been much g'reater. The reason of this comparative defencelessness of children against the invasion of diphtheria is doubtless mainly the softness and delicacy of their mucous membranes, which are consequently especially susceptible to irritating- influences, penetrable by morbific poisons, and liable to inflammatory affections in general. Diphtheria occurs by marked preference in connection with various pre-existing diseases, especially those which produce inflammation, erosion or ulceration of the mucous membranes of the outer air -passages. 15 n it a 20, 20 a tt it 25, 25 a ti ti 30, 30 tt it ti 35, 35 tt n it 40, 40 n it n 45, 45 tt tt tt 50, 50 n tt tt 55, 55 n a tt 60, 60 ti tt a 65, 65 n tt tt 70, 70 »( a it 75, 75 ti tt it SO, 80 it tt tt 85, 85 a ti it 90, Total . 18 diphtheria; its nature and treatment. For similar reasons the invasion of the skin by diphtheritic inflammation is rendered practicable by the removal of the epidermis by wounds, blisters, etc. Diphtheria occurs by preference in some persons through individual or family predisposition. Some instances of great mortality in families which have been cited by authors in sup- port of this statement were probably merely illustrations of the action of intense endemic influences, but I have known in- dividuals and families of children to suffer from repeated attacks of the disease in the apparent absence of such influ- ences, in several successive places of residence, and when others living in exactly the same conditions were exempt. One attack of diphtheria affords a temporary immunity from subsequent ones; but this is usually, at least, of com- paratively short duration. Second attacks of diphtheria after an interval of a year or more are not uncommon. The sever- ity of recurrences of the disease does not seem to differ in any way from that of primary attacks. Diphtheria occurs under the most Avidely varying condi- tions of climate, temperature and season, being dependent upon none; but its occurrence is nevertheless favored by cold and dampness. In support of the former assertion it may be stated that diphtheria prevails in tropical countries, such as Tunis, Algiers, Egypt and the East Indies, as well as in Iceland and Labra- dor; during periods of drought as well as of humidity; in summer as well as in winter. The other assertion, viz., that the occurrence of diphtheria is as a general rule favored by cold and by humidity, is proved \)j the fact that it is more prevalent in those regions and at those seasons of the year in which those conditions are in the ascendant. In reference to its occurrence in different climates, Hirsch says, 1 " Its predominance in the temperate and cold zones compared with its rarity in the equatorial and sub- 1 Op. eit. p. 100. ETIOLOGY 19 tropical regions is great enough to be significant, even if we assume that those differences are only in part real and in part to he accounted for by the defective data from countries of the latter class."' With reference to seasons of the year he states, " In 124 epidemics of which we have exact data in regard to their dura- tion, all of them being closely circumscribed in place and of no more than a few months' continuance, the outbreaks reached their height as follows : 32 in the spring. 21 " summer. 30 " autumn. 38 " winter." Of 18,688 fatal cases which occurred in this city in the thirteen years from January 1, 1871, to December 31, 1886, according to the records of the Board of Health, 10,769 oc- curred in the half years beginning with October, and 7,919 in those beginning with April. The distribution by months is shown in the folio winer table : Years Jan. Feb. M'ch. April. May. June. July Aug. Sept. Oct. Nov. 251 Dec. Yearly Totals. 1874 140 97 Ill 115 102 99 109 103 108 201 229 1,665 1875 232 196 180 189 165 195 167 147 175 206 210 267 2,329 1876 274 242 209 158 186 130 81 79 68 103 102 118 1,750 1877 72 70 84 79 67 50 56 53 85 111 116 108 951 1878 132 94 105 90 81 72 50 47 55 75 101 105 1,007 1879 97 69 58 36 46 46 32 39 30 71 76 71 671 1880 72 77 65 81 76 61 89 97 125 199 234 214 1,390 1881 212 160 180 164 190 209 197 173 173 203 178 210 2,249 1882 218 169 181 154 156 133 95 78 63 88 97 93 1,525 1883 104 87 88 92 92 82 66 73 62 82 81 100 1,009 1884 79 82 73 77 83 92 70 62 55 127 139 151 1,090 1885 108 121 121 115 102 115 101 71 87 87 122j 175 1,325 1886 155 149 134 124 142 130 133 1,246 104 85 165 288 218 1,727 M'fchly Totals. 1,895 1,613 1,589 1,474 1,488 1,414 1,126 1,171 1,618 1,9952,059 18,688 Gold and dampness undoubtedly favor the occurrence of diphtheria mainly as predisposing causes, by their tendency to excite catarrhal affections, the relation of which to diph- theria has already been referred to. 20 diphtheria; its nature and treatment. A relation of cause and effect between conditions of soil and situation and the occurrence of diphtheria is asserted by some authorities and denied by others. Hirsch 1 presents an accu- mulation of testimony from observers in different countries to the effect that the development and epidemic diffusion of the disease are absolutely independent of such conditions, the evi- dence showing- that high and low, dry and damp situations and all geological formations have been equally the seat of its prevalence, and that the instances in which it has preferred low, damp, and ill-drained locations are fully offset by others in which it has apparently made the opposite choice. The full acceptance of these facts is, nevertheless, not in- consistent with the view that local dampness does favor the occurrence of diphtheria. Dr. 1ST. M. Thursfield, whose careful attention to this sub- ject, and exceptional opportunities for observation in his ca- pacity as Health Officer of a district comprising a large urban and rural population, entitle his views to the most respectful consideration, says : 2 " While I believe that no very close connection can be traced between the incidence of diphtheria and what are broadly known as geological formations, there is the closest connection between certain conditions of subsoil and situation of the house, and the disease. Whatever promotes dampness of habitation, the result is the same. " M. Trousseau appears to have formed his opinion that the disease had no connection with local surroundings, from the fact that he had seen it raging equally on low undrained local- ities and on breezy heights, I have been called upon on sev- eral occasions to investigate outbreaks of diphtheria on ele- vated open localities, and have invariably found the same condition of dampness of habitation, caused by faulty con- struction of the houses in localities where there was a stagna- 1 Op. eit. p. 104. ■ London Lancet, August 10, 1878. ETIOLOGY. 21 tion of water, either from a flat table-land with an impervious sub-soil, or, more frequently, from the locality being- the divi- sion of a water-shed, which is always a cause of stag-nation of water." Diphtheria, as a general rule, prevails with greater fatality in rural regions than in cities. This fact, which has been noted in the history of many epidemics, is illustrated by Dr. Thurs- field * in tables which show a much larger percentage of deaths from diphtheria to population in ten rural counties than in ten principal cities of England throughout a series of years. Dr. Thursfield remarks, " Whatever conditions seem to favor fun- goid growth would seem to favor the incidence and persistence of diphtheria, and the explanation of the comparative freedom of towns from the disease may be the presence of something in their atmosphere inimical to such growth." May not a partial explanation, however, be found in the fact that the inhabitants of cities are, upon the whole, better sheltered from the inclemencies of the weather and less ex- posed to " dampness of habitation " than those of the country? Diphtheria may occur independently of insanitary condi- tions. Indeed in some epidemics it has seemed to find most of its victims in circumstances where the action of such causes could least be suspected. There is, nevertheless, abundant evidence that its occurrence is favored by them. The instances of its outbreak and prevalence in the country in direct connec- tion with such sources of infection as damp and filthy cellars, stagnant pools reeking with the products of the decomposition of animal and vegetable substances, foul privies, wells con- taminated with excrementitious matter, etc., and, in cities, with bad sewerage and defective plumbing and ventilation, and the combined results of poverty, filth and overcrowding of habitations, are too numerous and striking to be rationally regarded as mere coincidences. As out-door visiting plrysician to the Demilt Dispensary in 1 Loc. eit. 22 DIPHTHERIA; ITS NATURE AND TREATMENT. the twenty-first ward of this city through a number of years, I have had many opportunities of observing- the relation of occurrences of diphtheria to this class of causes, and was long ago impressed with its tendency to occur and recur in certain tenement-houses where some of these conditions were most marked — such especially as foul and ill-drained cellars, neg- lected and sometimes overflowing cess-pools, and bad plumb- ing, with untrapped sinks and no air-shafts. The relation of cause to effect in these instances has been demonstrated by the fact that in some of these buildings, which had come to be looked upon by me and by my assistants as diphtheria nests, there has been no recurrence of the disease for quite a number of years since the evils referred to were removed through the efforts of the Board of Health. It is probable, moreover, that it is, in some degree, at least, a result of the removal of these foci of the disease that the mortality from diphtheria in this district, which was in 1875 in proportion to population among the greatest in the city, has for quite a number of years been among the least. In estimating the validity of the argument which has been urged against this view, from the fact, already referred to, that in many epidemics diphtheria has been observed to prevail among all classes indifferently, or even in some instances es- pecially among the classes whose hygienic surroundings were the best, it may be remarked that insanitary conditions are only one among many causes of diphtheria, and are certainly not essential to its occurrence; that they constitute the most potent factors in its endemic prevalence, but that when it is epidemic other causes, more direct and potent and yet to be considered, are often the efficient ones; and again, it is a seri- ous and dangerous error to assume that insanitary conditions are found only in the abodes of the poor. Unfortunately the application of sanitary science to the construction of dwellings has not yet attained such perfection, nor is its assistance so generally and so intelligently invoked even in the abodes of the ETIOLOGY. 23 wealthy, that any absolute line of demarcation can be drawn between them and the dwelling's of the poor, either in city or countiw, in respect to their liability to or exemption from the causes of zymotic disease. In some instances the elaborate and luxurious appliances of modern plumbing have seemed to multiply, rather than to obviate, the insidious dangers from noxious miasms. While, as I have already stated, I have seen many cases of diphtheria, evidently resulting from insanitary conditions in the abodes of the poor, I have also seen equally striking instances of this connection in the homes of the well- to-do and in the mansions of the rich. Insanitary conditions may favor the occurrence of diphthe- ria in two ways : by producing diseases which predispose to the reception of the special poison which causes diphtheria, and by the endemic perpetuation and reproduction of that poison, or possibly by its generation de novo. Diphtheria, or a disease which closely resembles it etiolog- ically and pathologically, occurs in various kinds of animals, poultry and birds, and seems to be intercommunicable between them and man. Facts confirming this statement have been published in great numbers by Mcati, 1 Friedberger, 2 Wood and Formacl, 3 Turner, 4 Delthil, 5 Paulinis 6 and many others. The following- instance was published by Gerhardt : 7 " In the village of Messelhausen, near Landa in Baden, a chicken-farm had been started into which 2,600 chickens had been brought from the country near Verona, Italy. A few of these had diphtheria, and within the 'first six weeks 600 of them died of the disease, and, later on, 800 more. The follow- ^'Compt. rend." 1879, torn. 88, No. 6. 2 Zeitschr. f. Thierniedecin und vergl. Pathol., 1879, v. 161. 3 National Board of Health Bulletin, 1882; Supplement No. 7. 4 Report to the Local Government Board of London, 1887. 5 Journ. de MeU, Feb. 19, 1888. 6 Bull. M<5d., Jan. 22, 1888. 7 Verhandlung d. Cong, f . innere Medicin. Wiesbaden, 1883. 24 DIPHTHERIA; ITS NATURE AND TREATMENT. ing summer 1000 chickens were hatched from eggs laid by these hens, and all of these died of diphtheria within the first six weeks. Five cats succumbed to the same disease at this farm, and a parrot also took the disease, but was saved. In November, 1881, an Italian rooster, about to be touched up with carbolic acid, bit one of the attendants in the left hand and foot. The man was taken sick with high fever and both wounds were covered with diphtheritic membranes. The wounds healed very slowly, the disease lasting three weeks. Two-thirds of the farm hands became affected with diphtheria, and at the same time not a case occurred in the neighboring village." Paulinis relates that on an island in the Greek Archipelago on which diphtheria had been previously unknown, an epidemic among its population resulted from taking thither turkeys affected with the disease. The contagion seemed to be trans- mitted through the atmosphere. The affection in the turkeys resembled in all its features the human disease. One of them which recovered was affected with paralysis and was unable to walk. Diphtheria occurs as the result of contagion and infection. This is abundantly demonstrated. Volumes might be filled with the recorded facts which illustrate it, such as the first introduction of the disease into a family or a school or a neigh- borhood by the arrival of a person suffering from it, and its subsequent dissemination by communication from one to an- other throughout the community, or its introduction into one country from another in the same manner, and its subsequent epidemic diffusion through that country along lines of travel and from one centre of infection to another. Such instances are far too numerous and precise to admit of explanation merely by endemic or epidemic influences. Nor is their force in the least weakened by the fact that many cases and epi- demics have occurred which could not be thus accounted for. Diphtheria is contagious, though all cases of diphtheria are not due to contagion. ETIOLOGY. 25 Diphtheria is contagious in a less degree than scarlatina or measles or small-pox or whooping-cough; it is less infectious than scarlatina or variola or typhoid fever; nevertheless in many instances it manifests both these qualities in an extreme degree. Diphtheria is communicated in a variety of ways. The first of these is by direct contact or the deposition of diphthe- ritic matter on the mucous membrane or upon wounds in the skin. Examples of this mode of transmission are furnished by numerous well-known instances in which physicians have con- tracted the disease by sucking out tracheotomy tubes, or by receiving the secretions of the patient in the mouth or nares; also by such instances as that related by M. See, 1 in which a woman who wet-nursed a child affected with diphtheria, com- municated labial diphtheria to her own child, which she also nursed, and received the same affection from the latter by fre- cpientty kissing it. The demonstration afforded by the instances referred to is not at all weakened by the fact that many other physicians have sucked out tracheotomy tubes and have received diph- theritic secretions in their mouths and nares, or that other mothers have suckled and kissed infants affected with diph- theria, or that M. Peter 2 and others have painted their own fauces with solutions of false membrane without diphtheria resulting. The power of resistance of the healthy mucous membranes, especially in adults, to diphtheritic infection, is, undoubtedly, very great, and the infective power of diphthe- ritic material from different sources, as will be shown further on, varies very much. Under these circumstances a limited number of positive examples of the communication of diph- theria by direct contact, among many negative ones, is all the proof of its occurrence that could rationally be demanded. 'Bulletin de la Soc. Med. des Hop., t. iv., p. 378. 2 Trousseau, Op. cit., vol. i. 26 DIPHTHERIA; ITS NATURE AND TREATMENT. Diphtheria may be communicated by inoculation. Indeed this is implied in the fact of its communicability by direct contact, since in that mode of transmission penetration of the epithelium by the infecting- matter is evidently an essential condition. The communicability of diphtheria by inoculation is illus- trated in such instances as that related by Dr. Paterson, 1 of the disease being - communicated to a wound on a finger which was thrust down the throat of a child who was suffering from it. In other instances inoculation has been effected by the biting of the finger by the child. I witnessed not long since an instance of auto-inoculation by transplantation. A lady whom I saw in consultation with Dr. C L. Lang of this city had labial diphtheria. She was also suffering from eczematous spots on her lower limbs which annoyed her by itching and burning. To allay this discomfort she placed upon one of them, which was particularly accessi- ble and troublesome, a bit of blotting-paper moistened with her saliva. In a day or two this patch became diphtheritic and continued so for some days, but none of the neighboring patches was similarly affected. That the communication of diphtheria by inoculation is at- tended with difficulty and uncertainty, is shown by the fact that Trousseau, Peter and Duchamp scarified their own fauces with scalpels charged with diphtheritic matter without result. Experiments in the inoculation of animals with diphtheritic matter have been attended with very varying results. These have been negative in many instances, as in the attempts of Bretonneau, Reynal, Harley and others. Trendelenberg, 2 in sixty-eight operations in which he introduced diphtheritic pseudo-membrane into the trachea of rabbits and pigeons, produced tracheal diphtheria in eleven, most of which died of croupal asphyxia. With the membrane obtained from these 1 Med. Times and Gazette, 1866. 2 Arch, fur Klin. Chir., t. x., 1869. ETIOLOGY. 27 victims he performed a second series of experiments with sim- ilar results. Oertel, 1 in twelve similar experiments upon rab- bits, produced tracheal diphtheria in eight, five of which died by asphyxia, and three from toxaemia, the autopsies showing" capillary hemorrhages in various organs, and marked renal congestion. With the membrane obtained from these rabbits he produced similar results in a second series of operations, and repeated them in a third. Drs. H. C. Wood and Henry F. Formad 2 performed intra-tracheal inoculation upon rabbits with like results in a small proportion of instances. Hueter and Tommasi and Oertel introduced diphtheritic matter into the muscles of rabbits. The result 3 was a diph- theritic layer on the edges of the wounds, hemorrhagic inflam- mation of the muscles and a general disease which proved fatal after one or two days. ISTassilofT and Eberth, 4 by inoculating the cornea, produced diphtheritic keratitis which was accom- panied with a general affection which proved fat' 1 1 on the fourth or fifth day. The evidence that the affection induced in these instances was true diphtheria has been regarded as inconclusive by many. Drs. Curtis and Satterthwaite 5 repeated these opera- tions. In those made upon the cornea by them the result was negative. Of thirty-eight rabbits inoculated by them with diphtheritic matter in the muscles or by subcutaneous injection twenty-one died after periods varying from thirty hours to thirty-eight days. In these cases the authors "failed to see anything specifically resembling diphtheria as it occurs in the human subject. The whole story seemed to be one of local irritant poisoning which always tended toward the production of an abscess at the site of the inoculation, with greater or less concomitant hyperemia, ecchymoses and serous infiltration of ^eutsch. Arch, fur Klin. Med., 1871. 2 National Board of Health Bulletin, 1882; Supplement No. 17. 3 Ziemssen's Cyclopaedia, vol. i. 4 Correspondenzblatt, 1872. 5 "Report of Investigations into the Pathogeny of Diphtheria," by Edward M. Curtis and Thomas E. Satterthwaite. New York, 1877. 28 diphtheria; its nature axd treatment. neighboring" tissues according to the degree of virulence of the inoculated poison." Drs. Wood and Formad, 1 on the other hand, in a small pro- portion of their subcutaneous and intra -muscular inoculations of rabbits with diphtheritic matter, produced a rapidly fatal local and general affection, which strikingly resembled diph- theria, and which they regarded as probably essentially iden- tical with it. In the recorded experiments for the communication of diphtheria to the lower animals by inoculation it is to be ob- served that the operation is attended with great uncertainty, succeeding in only a small proportion of all cases; that it has usually failed when attempted in the mucous membrane of the mouth and fauces, but has much more often succeeded in the trachea. Diphtheria may be communicated from one person to another through the circumambient air. This is undoubtedly its most usual mode of communication, as has been illustrated in the numerous instances in which the disease has been contracted by persons entering rooms or houses in which were patients suffering from it, or has been brought hy those affected with it to persons or families previously exempt from it. The distance to which the disease can be thus conveyed by the atmosphere is ordinarily very small, though in some epidemics it has seemed to be wafted by the winds to considerable distances. The contagion from patients affected with diphtheria seems to accumulate in their rooms, to adhere to walls and furniture, and often to linger for a considerable time after their recovery, as has been shown by numerous instances in which persons have taken diphtheria in rooms in which cases of the disease had occurred weeks or months before, It seems also to linger about the persons or in the clothing of those who have had the disease for some time after their recovery. Some recorded instances also seem to show that the contagion may 1 Loc. cit. ETIOLOGY. 29 be carried in the clothing- of those who have been exposed to the infection of the disease, but not affected with it themselves, and communicated by them to others. The following- is one of many such instances : Dr. J. H. Sal- ter ! states that in a farm-house situated in a high and dry localit}', and several hundred yards from any other house, a boy of eleven years was attacked with diphtheria on October 24th, and within the next six days his father, another child and three servants came down with the disease. There was no epidemic in the neighborhood. It was learned on investigation that on October 19th a woman fromanotbi r village, two miles away, had brought back some needlework from her cottage, which contained at the time two sick children. One child had died rather suddenly from what was called "bronchitis." The other was seen by the health-officer with well-marked diphthe- ria. There were no other cases for miles around. The infec- tion seems to have been carried by the woman in her clothing or in the needlework. She did not herself have the disease. The contagion of diphtheria may probably be conveyed by articles of food and drink, such as milk, etc. Observations in some epidemics of diphtheria have seemed to establish some connection between its occurrence and the milk-supply. Some have thought it probable that the disease known as garget in cattle might be a source of diphtheritic infection. The agency of such substances as carriers of diphtheria is, however, not fully demonstrated and is probably not among the very fre- quent causes of the disease. That diphtheria occurs epidemically is one of the most notable facts in connection with its etiology. It is evident that at such times the contagion of the disease is more potent than at others, as it is propagated and disseminated by the various modes of communication which have just been enumer- ated independently of local conditions, and with an intensity and certainty of action which is rarely seen in connection with 1 British Medical Journal, Dec 1, 1883. 30 . diphtheria; its nature and treatment. the endemic and sporadic forms of the disease. This differ- ence in respect to virulence of contagion between epidemic and sporadic or endemic cases is strikingly illustrated in the results of the experiments of Drs. Wood and Formad already referred to. Of thirty-two rabbits inoculated with diphtheritic matter from endemic cases only six died, and none of those from diphtheria; of fifteen, inoculated with matter from the Lu- dington epidemic, eleven died, and four of these with abundant diphtheritic exudation at the site of inoculation. It is not im- probable that many of the discrepancies in the results of ex- posures to contagion and of inoculation-experiments may be thus accounted for. It is next in order to inquire what is the nature of the contagium of diphtheria. It seems probable that a materies morbi which may be communicated by direct contact and by inoculation, which may be suspended in and conveyed by the atmosphere and by gases and liquids, which may be shut up in apartments and adheres for a considerable time to walls and furniture and persons and clothing, and which is repro- duced and disseminated in the course of tbe disease is in the form of solid particles, rather than of a liquid or a gas, or at least is conveyed by such particles. This may also be in- ferred from the manner in which the disease usually commences upon the mucous membrane of the throat, the nares or the mouth, namely, in points or in small limited non-symmetrical areas rather than with the general diffusion which would characterize the action of an inhaled poisonous gas or vapor either acting from without or from within through the circu- lation. This probability is also sustained by the results of ex- periments. Curtis and Satterthwaite 1 state that " Thorough filtration of a proven virulent aqueous infusion of diphtheritic membrane removes the infectious property of the same." And the same results have been reached by many others. Is this contagium a chemical poison or is it a micro-organ- 1 Loc. cit. ETIOLOGY. 31 ism, or, what is practically equivalent to the latter, is it a chemical poison which is the product of such an organism? Such convincing- arguments have of late } T ears been brought forward to prove that the phenomena of contagious and in- fectious diseases can be fully accounted for by the agency of micro-organisms and in no other way — arguments which are too familiar to need present repetition — that the microbe of diphtheria has long been eagerly sought for by many and its ultimate discovery confidently anticipated by the majority of the profession. No such discovery yet supposed to have been made has met with unchallenged and universal acceptance; yet in the course of the search various facts have been elicited of such interest that a brief review of them is essential to our present inquiry. Professor Laycock, 1 in 1858, was the first to find a supposed parasitic cause for diphtheria in the oidium albicans. Other microscopists subsequently observed other organisms in con- nection with the disease, as the zygodesmus fuse as of Letze- rich 2 and the leptothrix buccalis of Jaffe, 3 which were in turn found to be common to other diseases, or even present in con- ditions of health. In 1868 the micrococcus, — an organism previously observed by Buhl — was brought forward by Oertel 4 as the specific mi- crobe of diphtheria. The micrococcus is a minute, point-like, dark-contoured, round or oval immovable body, occurring singly, in chains, or in zooglea (masses). According to the earlier observations of Oertel the micro- coccus was always accompanied in diphtheria by a small form of the bacterium termo (a rod-bacterium). He stated that these organisms were always to be seen in rapidly increasing numbers upon the mucous membrane at points where diph- theritic false membrane was about to develop, but were 1 Med. Times and Gazette, vol. xxxviii., p. 548. 2 Virchow's Arch. B. xlv. et seq. 3 Schmidt's Jahrbuch, 1862. 4 Studien tiber Diph. Aertzl. Int., 1868. No. 34. 32 diphtheria; its nature ant> treatment. never present in other forms of inflammation, that they pene- trated into the tissues, caused the dissolution of the young cells, filled and obstructed the "blood and lymph -vessels, appeared heaped up in the miniferous tubules and the Malpighian cor- puscles of the kidneys, and, in short, were found in the most diverse situations and were inseparable from the diphtheritic process. The observations of Oertel were more or less fully corroborated by those of Von Recklinghausen, JSTassiloff, Wald- eyer, itlebs, Eberth, Heiberg, Trendelenberg and Letzerich. These views were controverted by Beale, 1 Senator, 2 Bill- roth, 3 Curtis and Satterthwaite 4 and others, who denied the Fig. 1.— Diphtheritic False Membrane Containing Micrococci, z, Zooglea formed by small micrococci; s', Zooglea formed by larger micrococci; m, Isolated microbes. X 500. (Cornil and Babes.) specific character and the pathogenic function of these para- sites in diphtheria. The observations of Wood and Formad, already referred to, were in some respects in accordance with those of Oertel, though their conclusions were somewhat different. In freshly removed false membrane micrococci only were found by them. Other forms of bacteria were found in membrane which had been removed some hours previously or which was removed post-mortem. In examinations of the blood of human beings during life, micrococci were found in one of seven cases of sporadic diph- 1 Disease Germs. London, 1872. 2 Archiv. Mr pathol. Anat. und Physiol., t. lvi., 1872. 3 Untersuchungen tiber Vegetations-forinen der Cocco-baeteria Sep- tica, etc. Berlin, 1874. 4 Op. eit. ETIOLOGY. 33 theria, and in seven of fourteen of epidemic diphtheria. The seven of the latter class in which they were not found were mild or in the stage of convalescence. Micrococci were, how- ever, also found in the blood during- life of one case of unknown disease in hospital which resulted fatally, and in two of scar- latina anginosa with exudation. " Both septic animal matter and non-organic irritants placed in the trachea cause pseudo-membranous tracheitis, which we have failed to distinguish from diphtheritic tracheitis, the membrane in both cases containing micrococci. The occur- rence of a false membrane in the trachea is the result not of the specific character but of the intensity of the inflammation. " The micrococci of diphtheria do not differ, so far as ob- served, from the micrococci of furred tongue, etc., except in their tendency to grow in culture fluids. "The micrococci of furred tongue or ordinar} 7 sore throat have a less tendency to grow under culture than have the micrococci of endemic non-malignant diphtheria ; and the lat- ter much less than the micrococci of malignant diphtheria. " The rapidity of the growth of the micrococci is in direct proportion to the malignancy of the case yielding them and its contagiousness. " On exposure to the air diphtheritic membrane of the most virulent type loses its contagious power, and the micrococci, pari passu, lose their power of growing in culture-fluids. " Under successive generations of artificial culture the diph- theria micrococci lose their growth activity and also their power of infecting the rabbit. " It has not been experimentally directly proven, but is a necessary inference from the two facts just stated, that under certain favoring circumstances the sluggish micrococcus puts on growth activity and in all probability poisonous properties. "Every grade of case may be found in man, from a simple sore throat through simple membranous pharyngitis and tra- cheitis up to malignant diphtheria. 34 diphtheria; its nature and treatment. "Any inflammation of the trachea of sufficient intensity- may cause the formation of a pseudo-membrane. "A case may beg-in as one of sthenic ' pseudo-membranous croup/ and end as one of adynamic diphtheria with blood- poisoning-, and in cases of this character not infrequently no exposure to contagion is discoverable, and there is clinically every reason to believe that the e blood-poison ' has been devel- oped within the body of the patient. The theory of the disease which we would deduce from these facts is that the micro- coccus which directly or indirectly causes the diphtheria is not a specific organism different from that common to healthy and inflamed throats, but is an active state of that organism ; that certain circumstances outside of the human body are capable of throwing this micrococcus into this condition of active growth and engendering an epidemic of diphtheria. When diphtheria is thus epidemic the micrococci light upon a throat, and, if the throat have little resisting power, as in the child, inflame it, or increase a catarrh already existing into a violent inflammation, and also rapidly enter the blood and cause systemic poisoning. On the other hand, a catarrh in a weakly subject may in the beginning be simply an inflamma- tion from cold, but the ordinary micrococci in the mouth and throat, favored by the special conditions, may gradually change from the dormant to the active state, and by and by act upon the throat and at last force their way into the system, and a self -generated diphtheria be formed out of a cold." This theory is in essential accordance with that stated by Bindfleisch : x " The apparently sudden outbreak of devastating plagues, like cholera, syphilis or diphtheria, is best explained by supposing that a fungus growing as an epiphyte has sud- denly gained the power of growing as an endophyte, thus cre- ating an apparently new infection." Other forms of bacteria have been found by various inves- tigators in apparent pathogenic relation to diphtheria. Among " Elements of Pathology." ETIOLOGY. 35 these is the " tilletia diphtheritica," a later discovery of Letze- rich l than the zygodesmus fuscus. Another is the " microspo- ron diphtheriticum-/' described by Klebs 2 as consisting- of small micrococci compacted in round balls, surrounded with a thin layer of gelatinous matter. These subsequently develop into minute motile bacilli, and finally into tufts of mycelium. Klebs stated at the German Medical Congress in 1883, that he had found this form of bacteria in connection with a grave form of diphtheria at Prague, which was characterized by prominent nervous symptoms and hemorrhagic formations in the brain and spinal cord on post-mortem examination. As he had found these organisms transmittible to the cornea, he had regarded them as the specific fungi of diphtheria. Later, however, at Zurich he had seen cases of diphtheria of an entirelj* different character. The false membrane of the throat had a great tendency to extend into the larynx and trachea, followed by interstitial inflammatory processes in in- ternal organs. The micro-organisms in these cases were of an entirely different character from those found in former ones. Instead of being globular they were exclusively bacil- lar formations. Hence he had distinguished two forms of diph- theria — the diphtheria microsporon and diphtheria bacillaris. M. Talamon, in January, 1881, gave to the Anatomical So- ciety of Paris a minute description of still a different bacterium which he- had discovered in connection with diphtheria, and which appears under the form of mycelia and characteristic spores. Talamon had produced diphtheria (or an affection having all its essential features) in rabbits, guinea-pigs, cocks and pigeons by inoculating them with this fungus, and in frogs by simply feeding them with it. Emmerich 3 arrived at yet different results. The organism which he found to occur distinctively in the diphtheritic lesions of both man and pigeons was neither a coccus nor a bacillus, 'Loc. cit. 2 Archiv. f. exper. Pathol, und Therap., vol. iv., p. 191. 3 Deutsch. Med. Wochenschr. 1884, No. 38. 36 DIPHTHERIA; ITS NATURE AND TREATMENT. but a short thick bacterium. Inoculated from cultures into pig-eons, rabbits and mice, these bacteria produced character- istic local diphtheritic lesions and a rapidly fatal general dis- ease. The most important bacteriological investigations which have yet been made in connection with diphtheria are those of Dr. Friedrich Loeffler. 1 Attributing the unsatisfactory re- sults of previous attempts to discover the specific microbe of diphtheria to the inherent difficulties attending them, from the great number of different fungi present in the disease, and also to the insufficient methods which had been employed, since only impure material had been used in cultures and in- oculations without separation of the different organisms, he was therefore induced to apply the more accurate methods of Koch to the investigation. He first made histological exami- nations, with an improved method of staining, of the affected mucous membranes and internal organs of twenty-seven pa- tients who had died of diphtheria, including five cases of scar- latinal diphtheria. In these examinations he found two forms of bacteria especially numerous, viz., micrococcci in chains (streptococci) and a form of bacillus. The micrococci were not present in all cases. They were probably the same which had previously been so generally observed in diphtheria. They were found not only on and in the affected mucous membranes in some cases, but also in the lymphatics, whence they penetrated to every part of the body, causing necrosis of the tissues. Micrococci morphologically identical with these are, however, also found in various other diseases which are accompanied with lesions of the mucous membranes, such as variola, typhoid and puerperal fever, etc., in which diseases their presence is regarded as entirely accidental. : Mittheilungen aus dem k. Gresundheitsante, Berlin, vol. ii., 1884. Abstracted by Dr. J. W. Hiine in " Microparasites in Disease," New Sydenham Soc, 1886, and by Dr. M. Putnam- Jacobi, in the Quarterly Bulletin of the Clinical Society of the New York Post-Graduate Medi- cal School and Hospital, August, 1885. ETIOLOGY. 37 The bacilli were probably the same which had been first described by Klebs. They are non-motile, either straight or curved, about the length of the bacillus of tubercle, but twice as thick. They were found exclusively in those typical cases of diphtheria which were characterized by thick false mem- raft /ft&A Fi&. 2.— The Streptococci found by Loeffler in Diphtheria. X 1250. brane in the fauces, larynx and trachea. In this false mem- brane they were very numerous, and they were found in deeper layers of it than were the micrococci and other accidental bac- teria, which only occurred superficially. The bacilli were not found in the internal organs, the blood-vessels or the lymphat- ics, and if they are really the cause of diphtheria, they are so not by themselves penetrating 1 the system, but by producing a poison which first acts locally, producing tissue necrosis, vascular paralysis and dilatation, and exudation of fibrogenous ^_, r /§; "v.;. .;;,-"% ~~ ' ^"^^ ^ci-IiTv, "■'■■7-' Fig. 3. — Bacilli on the Surface of False Membrane of Vulvar Diphtheria, and in a Crevice between the Filaments of Fibrin which compose it. X 400. (Cornil and Babes.) lymph, and then entering the circulation causes the constitu- tional disease. The bacilli were not found in all typical cases. It was, however, possible that they might have been present, but have died and been eliminated before the patient's death. The re- 38 DIPHTHERIA; ITS NATURE AND TREATMENT. suits of the histological investigations were upon the whole in- conclusive. The bacteria described were next cultivated by the usual processes for isolation from the fourth to the twenty-fifth gen- eration. The products of these cultures were then inoculated upon mice, guinea-pigs, rabbits, monkeys and birds. Inoculations with the streptococci in no instance produced a disease even resembling diphtheria. For this and other rea- sons Loeffler concluded that they cannot be regarded as the specific cause of the disease, though it is probable that they may under some circumstances produce a disease resembling diphtheria. Cultivations of the bacilli introduced beneath the skin of guinea-pigs and small birds killed them, producing- whitish or hemorrhagic exudations at the point of inoculation, and exten- sive subcutaneous oedema, the internal organs being unaffected. Inoculated in the trachea of rabbits, fowls and pigeons, or the vagina of guinea-pigs, the poison produced a false membrane. There was also the characteristic alteration of the vascular walls which shows itself by bloody oedema, hemorrhage into the tissue of the lymphatic glands and effusion into the pleural cavity. The bacilli have, therefore, the same effect as the diphtheritic virus. Their specific character is seemingly opposed by.the follow- ing facts : They were absent in a number of undoubted cases of diphtheria; they were not present in typical quantity and arrangement in the artificially produced pseudo-membranes; they had no effect when applied to the uninjured surface of mucous membranes in some animals otherwise susceptible to their action; animals which survived showed no paralysis; identical bacilli were found in the saliva of healthy children. Proof that these bacilli are the cause of diphtheria is therefore incomplete, though the possibility of their being so is not ex- cluded. ETIOLOGY. 39 The investigations of Babes * in twenty-four cases of diph- theria confirmed in a general sense the observations of Loeffler. In every case there were streptococci and the bacilli of Loeffler. In the cultures made from false membranes the streptococci were more numerous, but the bacilli invaded and overwhelmed them, remaining- finally the sole masters of the field. The bacilli were found in the depth of the tonsils in dense masses, and sometimes in the retro-pharyngeal g-anglia. In the bronchial ganglia streptococci only were found. These bacteria were in some cases accompanied by other pathog-enic microbes — the staphylococcus aureus and an encapsulated mi- crobe resembling that of pneumonia. In cutaneous diphtheria bacilli were observed not only in the false membrane, but also on the free surface of the papilla?, and in smaller numbers in the connective tissue and the di- lated vessels of the inflamed papilla?, and more rarely in the tissue of the derma. In reference to the organisms of human diphtheria, Cornil and Babes say: "We think that the bacilli of Klebsand Loeff- ler ma3 r be regarded as the most important agents in the production of the false membrane of true diphtheria, but it must be admitted that physiological researches in the case of that disease have not yet given their final response/' Dr. A. D'Espine, 2 President of the Medical Society of Ge- neva, has found the bacillus of Loeffler in every one of fourteen cases of diphtheria and croup, and absent in all of twenty-four cases of simple anginas studied by him. In a case of croup a pure culture was obtained which preserved its pathogenic powers through twenty-five generations, as was proved by inoculation experiments. Dr. D'Espine believes that this is the pathogenic organism of diphtheria and croup, that it pro- 1 *' Les Bacteries et leur role dans ranatornie et l'histologie patholog- iques des maladies infectieuses," par A. V. Cornil et V. Babes. Paris. 18S6, p. 458. - Revue Medieale de la Suisse Romande, No. 1. January. 1888, p. 49. 40 DIPHTHERIA; ITS NATURE AND TREATMENT. duces a leucomaine which, when absorbed, gives rise to the systemic poisoning, and that its presence or absence may be a reliable diagnostic criterion. On the other hand, Von Hoffmann- Wellenhoff x has found the bacillus of diphtheria of Loeffler in seven cases of pharyn- geal diphtheria, in three cases of measles, in six out of nineteen cases of pharyngitis complicating scarlatina, and in four out of eleven cases which had no perceptible abnormalities. Tests in regard to the virulence of cultures of these bacteria showed that a number of those which were obtained from diphtheritic as well as non-diphtheritic cases caused in animals the symp- toms described by Loeffler, while other cultures morpholog- ically identical with them were perfectly harmless in the ex- periments made. • Oertel in his late important work, Die Pathogenese der Epidemischen Diphtherie, Leipzig, 1887, page 141, et seq., re- ferring to his former statement (previously quoted) that he had always found the micrococcus accompanied in diphtheria by a rod-bacterium, states that this rod-bacterium and the bacillus of Klebs and Loeffler very nearly coincide in their measurements, and also in the knobbed appearance of one or both of their extremities, and are in all probability iden- tical. A new series of observations by Oertel on the micro-organ- isms present in diphtheritic membrane, maybe roughly stated as in general correspondence with those of Loeffler. In a recent series of post-mortem examinations Oertel has failed to find micrococci present in the kidneys in any case. This difference from his earlier observations he explains by the fact that the more recent cases have been of a less markedly septic type than the former ones. While these facts obviously suggest the hypothesis that diphtheria is the result of a mixed infection by specific bacilli Archives of Paediatrics, January, 1889, from Jahrb. f. Kinderh., xxviii., 3. ETIOLOGY. 41 and septic micrococci, Oer- tel does not consider that this conclusion is as yet ful- ly established. Oertel also states that no bacteria can be found in diphtheria in the interior of the diseased cells in any sit- uation, nor in the necrobio- tic foci at any stage, nor in the parenchyma of the in- ternal organs, nor on their surface in such situations as make it probable that they are the immediate cause of the disease. Hence it is to be inferred that their mor- bific action must be due to the chemical poisons or ptomaines which they cause to - be produced in the sub- stances in which they live. He believes that this poison or virus first passes into and through the epithelium, induces alterations in the tissue -fluids, excites irrita- tion and inflammation, and thus inaugurates the train of morbid and necrobiotic processes which is elsewhere described. In the course of these processes the poison is reproduced both by the multiplication of bacteria FN. ££-_ '.,„ -^' ■•-:- C-'-% v \ fBZ. Fig. 4.— The Extension of Bacteria into the Fi- brinous Exudation. (Oertel.) B. V., bacterial vege- tations; F.N., fibrinous network; L, leucocytes, their degeneration, division and disintegration be- ing indicated to a slight extent only; B.Z , chains of rod-shaped bacteria with knobbed extremities. 42 DIPHTHERIA; ITS NATURE AST) TREATMENT. and by fermentation-changes in the decomposing- substances, and becomes more and more widely diffused. Diphtheria, as a general rule which is subject to relatively very few exceptions, occurs only on those surfaces of the body which are exposed to the access of the air. This suggests that among the conditions which are usually necessary to produce it is the presence of free oxygen. Bacteria, according as the presence of free oxygen is necessary or hurtful to them, are classed as aerobious or anaerobious. From the circumstance just referred to it has been inferred that the bacterium of diph- theria is aerobious. Dr. B. K. Bachford, 1 in taking this view, suggests that the occasional, but rare, occurrence of diphthe- ria in the stomach and intestines, where free oxygen is not present, may take place under exceptional conditions in which oxygen is supplied in some unstable combination in which it may be utilized for the sustenance of the bacteria of the dis- ease, and that that condition may be one of congestion and erosion of the gastric or intestinal mucous membrane, in which the oxygen is thus supplied by the oxyhemoglobin of the blood. In proof that this explanation is not far-fetched he cites the fact that strictly aerobic germs, such as anthrax, live and mul- tiply in the body, deriving their oxygen from this source. The search for the specific bacterium of diphtheria has been stimulated by the general belief that diphtheria is a specific disease like scarlatina or small-pox, which, according to prev- alent theories, must have a single parasitical cause. The Iry- pothesis that it may, on the other hand, include several gen- erically related and resembling septic processes with specific differences and dependent on the action not of one but of vari- ous bacteria, has been entertained by some and is perhaps, at the present imperfect stage of our knowledge, worthy of a moment's consideration It is not inconceivable that croupous and diphtheritic inflammation maybe capable of being excited by the action of more than one kind of bacterium, as it is 1 Medical News, Feb. 2, 1889. ETIOLOGY. 43 known that morbid processes closely resembling" them may be by various chemical and mechanical agencies. This supposition is favored by the remarkable differences which have been observed in the form and course of these proc- esses. The differences in the clinical features and the patho- logical lesions of constitutional diphtheria are even more strik- ing, and although in the majority of cases they conform to certain general types, yet the deviations from those types are in some instances so wide that they would seem to be more readily explicable by the hypothesis of different infections, or " mixed " infections, than by any other. That mixed infections or intoxications should occur through a favorable habitat being afforded to some pathogenic organisms by tissue changes previously caused by others, or the conversion thereby of pre- viously innocuous to pathogenic ones is in accordance with many known facts. It can hardly be doubted that the important questions thus suggested respecting the etiology of the various forms and complications of diphtheria, will ere long be finally an- swered by the multiplication of precise investigations. The following conclusions from facts and considerations which have now been presented may be regarded as probable : 1. Diphtheria is caused by a parasite which has the follow- ing characteristics : Its growth and multiplication outside of the body are favored by dampness and insanitary conditions, and it is reproduced in the disease; its presence on mucous membranes is sometimes innocuous; its vital activity is greatly increased under the conditions which prevail during an epi- demic; its pathogenic action is greatly favored by pre-existing morbid conditions of the body, and especially those involving lesions of the epithelium ; it is transmitted from one person to another by the various processes which are most usually in- cluded under the terms contagion and infection. 2. This parasite causes diphtheria by being implanted on a mucous membrane or a wounded surface of the body or in its 44 diphtheria; its nature and treatment. more superficial tissues, and there producing- a chemical poi- son, or ptomaine. 3. This poison, or ptomaine, toy its direct action on the tis- sues and vessels causes the local diphtheritic process, in the course of which it is reproduced and more and more widely diffused, and toy its absorption from this source into the gen- eral circulation causes the constitutional disease. 4. This morbid process is often accompanied or followed toy the invasion of the toody by other pathogenic bacteria, to which various complications are due. 5. No toacterium thus far discovered in connection with diphtheria can furnish toy its presence or its atosence a reliatole criterion for diagnosis. Incubation. — The period of incubation in diphtheria — that is, the time from the actual reception of the contagium into the system to the appearance of the disease — is for otovious reasons in the great majority of cases impossible to ascertain. The only cases in which it can be accurately estimated are those in which the disease is known to result from a single ex- posure of short duration, and even in these cases there is an ele- ment of uncertainty, since there is reason to believe that the germ of the disease may toe carried about the person innocu- ously — perhaps even on the buccal mucous membrane — for some time before it begins to exert a morbific influence. There are, however, abundant data for estimating the min- imum period of incubation in instances in which the disease has been brought to the members of a family or a school, or the inmates of a hospital, by persons affected with it. My own observation in many such instances corroborates that of most authors that the minimum period of incubation is usually about two cla3 r s. Dr. Morell Mackenzie 1 relates an instance in which a child had the disease with abundance of false membrane the next morning subsequent to the afternoon of her first exposure, and another, equally definite, in which the interval between ex- 1 Op. cit. p. 29. ETIOLOGY. -15 posure and the development of the disease was fifteen days. A child in a family which had a few weeks before removed from a village in Pennsylvania where there had been no diphtheria to a neighborhood in this city where diphtheria was endemic, took the disease. During her illness her father, who had re- mained behind, joined his family and at once devoted himself to the care of the child. The second morning (less than two days) after his arrival he came to me complaining of sore throat, and proved to be suffering from diphtheria. The usual period of incubation in diphtheria, in the sense in which the term is defined above, is probably from two to five or six days, though the interval between exposure and the resultant disease may be several weeks. In 1876 I saw, with Dr. J. E. Janvrin, of this city, a case of diphtheria at Dobbs' Ferry, of which the history was as follows : Mrs. H., with her son, aged seven, and his nurse, went on Sep- tember 1st to a hotel at Long Branch. On September 10th Mrs. H. was there attacked with diphtheria. There had pre- viously been other cases in the hotel. The child and nurse were at once sent to their home at Dobbs' Ferry, and Mrs. H. came to a hotel in this city, where she was attended by Dr. Janvrin from September 11th to 19th through a severe attack of pharyngeal diphtheria. She returned to her home on October 1st. On October 24th her son was attacked with a most malignant form of the disease, which terminated fatally. The probabilities in this case were either that the child had carried about himself the germs of the dis- ease for forty-four days or that he had received them from his mother within the twenty-three days before his attack and at least twelve days after her recovery. There had been no pre- vious cases of the disease at that time at Dobbs' Ferry. [Some recent important contributions to the etiology of diphtheria are appended at page 259.] CHAPTER III. PATHOLOGY. Diphtheritic false membrane may be generally described as a somewhat tough, firm, compact, elastic substance. Its color is a yellowish or grayish white. In thickness it varies from that of a mere pellicle to two or three millimetres, and in extent from a minute patch to a coating of the whole surface of the mouth and throat or a lining of the air-passages. In texture it is usually irregularly fibrillated, but is sometimes amorphous or granular or lamellated, and these conditions are often intermingled. It is tasteless and odorless, is insoluble in water, is dissolved by caustic alkalies, swells up and be- comes transparent under the addition of acetic acid, and in its physical and chemical properties closely resembles fibrin. Under the microscope false membrane is seen to consist of a network of fibrinous threads of varying thickness and close- ness, in the meshes or interstices of which are cells, namely leucocytes, red globules or epithelial cells, which have usually undergone a peculiar necrotic transformation. The relative proportions of these elements vary greatly in different cases. Diphtheritic false-membrane was regarded by the older writers as a gangrenous eschar, by Samuel Bard as altered and inspissated mucus, by Bretonneau and his successors as a coagulated fibrinous exudation analogous to that which occurs on the surface of serous membranes. It will be seen that there was an element of truth in all of these views. According to E. Wagner 1 false membrane is the result of a peculiar necrobiotic metamorphosis in the epithelial cells, 1 Archiv. f. Heilkunde, 1866, Bd. vii., p. 481. PATHOLOGY. 47 which become enlarged, porous and irregular in shape, sending" out peripheral projections which unite with those of adjoining- cells, forming a homogeneous network in which nuclei can no longer be detected, and an accompanying infiltration of the corion, and, in some cases, the subjacent tissues, with new cells and nuclei and sometimes extravasated blood. Buhl 1 observed also an infiltration of the tissue of the mu- cosa, even in situations where it was not covered by false membrane, with cellular or nucleolar bodies. This infiltration he found widely diffused through various organs and regarded as characteristic of diphtheria. Boldyrew 2 and Steudener 3 opposed the views of Wagner as not confirmed by their observation, and assigned a leading place in the formation of diphtheritic membrane to vascular exudation. Both of the processes just referred to, namely, fibrinous exudation and the necrotic metamorphosis of cells and tissues, are included in more recent views of the formation of diphthe- ritic membrane. The precise circumstances which in all cases favor or pre- vent the coagulation of inflammatory exudations upon the surface of mucous membranes are not fully known. Weigert 4 has shown that in order that it may take place the epithelium must be wholly or partially destroyed. The coagulation of fibrin is not a mere solidification of a substance which previously existed as such in solution in the effused fluids, but is a new formation from the fibrin-generators which they contain. According to Alexander Schmidt the plasma of the blood contains fibrinogen, and the white corpus- cles and probably other cells furnish fibrinoplastin and a fer- ment. When the white corpuscles die and are dissolved in the plasma the result is the production of fibrin. 'Zeitsehr. f. Biol., Bd. iii., S. 349. 1867. 2 Archiv. f. Anat. u. Phys., 1872. p. 75. 3 Virch. Archiv., 1872, liv., p. 500. 4 Virch. Archiv., Bd. lxxix. 48 diphtheria; its nature and treatment. The peculiar metamorphosis of cells and tissues which occurs in the formation of pseudo-membrane was named by Cohnheim coagnlative necrosis, and its nature was made known to us chiefly by Weigert. It is a coagulation which occurs not only in effused vital fluids, but in the substance of cells and tissues. That it shall take place it is necessary that the cells or tissue elements shall die or be in the process of necrotic de- generation, and that then effused lymph shall flow through them. Fibrin is formed within the tissue by the union of its two components just referred to. The death of the cells or tis- sues may be the result of injury from physical or chemical or thermal agencies or from arrested nutrition; the effusion of lymph is due to the vascular changes which accompany inflam- mation. Rindfleisch 1 says: " Coagulation necrosis is to be distinguished from the sim- ple death of a part by the presence of a coagulated albuminous liquid which accompanies the transition from life to death in the cells and tissues. This liquid bears such a strong resem- blance to coagulated fibrin that one is tempted to consider them the same, except that the macroscopical and microscopi- cal examination proves that the coagulation is chiefly present in the interior of the cells and in other constituents of the tis- sues. The microscope shows a peculiar homogeneous tendancy of the cell-protoplasm, accompanied by a total disappearance of the nucleus. Thus the cells lose their sharp outline and be- come flaky masses, inclined to adhere to each other and fall into large irregular formations of membranous consistency. The frequent wax-like appearance of these coagulations is a peculiar feature, indicating their thorough impregnation with a strong refractive albuminous body." Virchow divided the process by which false membrane is produced, and the resulting false membranes themselves, into two principal classes, the croupal and the diphtheritic. Croupal 1 " Elements of Pathology." PATHOLOGY. 49 false membrane may be roughly stated to be that which lies superficially and loosely upon the mucous membrane affected, and is mainly a fibrinous exudation; the diphtheritic that which penetrates it more or less deeply, and is in reality an eschar in it or even beneath it. This classification is now gen- erally admitted to be based on differences in degree and in ana- tomical relations rather than in essential pathological nature. Ziegler describes the various processes by which false mem- brane is formed and their products, according to views now- prevailing, with such clearness that I shall quote from his statements : "Croupous Inflammation. 1 — When a mucous membrane Fig. 5.- Croupous Membrane from the Trachea, (x 250.) a, section through the false membrane; b, upper layer of the mucous membrane, infiltrated, with pus-corpuscles (d); c, filaments and granules of fibrin; d, pus-corpuscles. is so injured that its epithelium is here and there partially de- stroyed, and at the same time its blood-vessels are so damaged that an abundant exudation is poured out on the surface, co- agulation of the latter may take place. In this way a pale yellowish membrane is formed on the surface, consisting of fibrinous filaments and granules beset with pus-corpuscles, or of shining homogeneous blocks representing cells which have undergone coagulative necrosis. This false membrane is con- nected with the underlying structures by fibrinous threads, but is usually loosely adherent and can be readily stripped off, disclosing the reel hyperamiic mucous membrane beneath. 1 " Text Book on Pathological Anatomy and Pathogenesis," Section 423. 4 50 DIPHTHERIA; ITS NATURE AND TREATMENT. The epithelial cells are always more or less injured, being either necrotic or in process of degeneration and desquammation. The fibrous structure of the inflamed mucous membrane al- ways contains liquid and cellular exudations. " Diphtheritic Inflammation. — When a mucous membrane is injured in such a way that its epithelium dies without des- quamation, while its blood-vessels are damaged and pour out an abundant exudation, it sometimes happens that the dead epithelial cells become saturated with the exuded liquid and e J> e Fig. 6. — Section through the Uvula in Diphtheritis Faucium. (Aniline-brown staining; X 75.) a, normal epithelium; 6, normal areolar tissue; c, necrosed epithelium transformed into a coarse mesh-work; d, areolar tissue infiltrated with fibrin and leucocytes; e, blood- vessels; /. haemorrhage; g, heaps of micrococci. then pass into a peculiar condition of rigidity akin to coagula- tion. The seat of this change appears to the naked eye as a dull grayish raised patch surrounded by red and swollen mucous membrane. The exudation is rich in albumen and the trans- formed cells take on the appearance of a kind of coarse mesh- work almost or altogether devoid of nuclei. The sub-epithelial areolar tissue is beset with filaments of fibrin and leucocytes. Haemorrhages are not uncommon. Inflammations of this kind, in which the tissue itself coagulates into a solid mass, are called diphtheritic. When the necrosis and coagulation extend PATHOLOGY. 51 only to the epithelium we may speak of the process as super- ficial diphtheritis. It is by no means necessary " either in croupous or in diphtheritic inflammation, " that the whole of the epithelium should perish at the outset; some part of ib at least may perish secondarily in consequence of the inflamma- tion." The anatomical and histological distinction between the croupous and the most superficial form of diphtheritic false membrane is, therefore, that the former consists mainly of coagulated fibrin and lies superficially over the epithelial cells (sometimes among or beneath them) being connected to the mucous membrane only by filamentous attachments which are easily broken ; while the latter, even when superficial and thin, consists mainly of transformed epithelium which remains in close apposition to the inflamed living tissues beneath it, so that if it be torn from them or destroyed by chemical agents a raw and bleeding surface is exposed. " Deep or parenchymatous diphtheria is characterized by the coagulation, not merely of the epithelium but also of the underlying connective tissue. The epithelium in some cases is lost altogether, and then the diphtheritic patch consists of dead connective tissue only. The patch is turbid and granular in texture, or it may be homogeneous or composed of amor- phous hyaline blocks. The nuclei are always more or less com- pletely lost. The small vessels which permeate the patch show signs of a homogeneous transformation of their walls. The dead tissue is separated from the living by a zone of cellular infiltration. Fibrinous filaments are seen here and there through the mass. The lymphatics in the neighborhood con- tain coagula and leucocytes." (See Fig. 7.) Oertel * in his latest work presents with great minuteness and detail the results of his researches into the histological changes which occur in diphtheria. These consist primarily and essentially in a characteristic degenerative metamorpho- '"Die Pathogenese der Epideinischen Diphtherie." Leipzig, 1887. 52 diphtheria; its nature and treatment. sis in the cells and the,ir nuclei. This takes place especially in the cells " which are derived from the white blood corpuscles, and are known under the collective name of leucocytes." The nucleus shows signs of retrogressive metamorphosis. The nuclear membrane breaks up; the nuclear and the cellular substance run into one mass, and the different forms of chro- matin undergo a similar change. The longer this process has continued the fewer are the colorable fragments Of nucleus, vesicles, granules, etc. The nuclei or granules exhibit peculiar W Fig. 7. — Section of the Uvula in a Case of Diphtheritis Faucium. (The epithelium has been shed ; aniline-brown staining ; x 100) a, micrococci ; 6, submucous tissue changed into amorphous blocks ; c, extravasated leucocytes ; d, fibrinous exudation ; e, blood-vessels ; /, lymphatic vessel containing cells and fibrin. forms, as if ligatured and partially divided in two ; free nuclear and granular vesicles are seen, and others which are connected by minute threads. The protoplasm and the nuclei are trans- formed into a homogeneous fluid and finally coagulating sub- stance. Explanation of Figure 8. — Section of a Diphtheritic Pharyngeal Mucous Membrane. False membrane invade 1 by typical rod-shaped bacteria. Cells in different stages of de- composition and division. Necrosis of these cells and of the upper layers of the mucous membrane. Advancement of normal cells from the deeper layers, a, necrotic zone; b, dis eased zone; c, apparently normal tissue; F.N., fibrinous network; B.Y., bacterial vegeta- tions; K.B , vesicular nuclei with parietal arrangement of colorable nuclear substance; Z. K., granular detritus; 8ch., mucous membrane; d.A., direct division of the nuclei, as if by ligature, ("Kernabschniirung'"); i.F., cells with indirect nuclear fragmentation— Poly- morphous nuclei; L, leucocytes in the deeper layers of the mucosa and submucosa. 0V-: A3 »V,*&V? *v f^ : l '^ a ^-- m^m. ~&# Lsf j-/^ -/y &&■ fCl *T< 3 |i|. n - 3? ■ i^ *w^ e \ •-, — */Z4 »«2 ' ^ '■— ' •.«gf"--'c e I **(\ y.> /O '% ■#f^R !$? *•* | €: / Trypsin, 3 ss. Sodas bicarbonatis, . . . . gr. x. Glycerini, 3 ss. Aquas destillatae, . . . . ad 3 j. To make a smooth mixture the trypsin should be rubbed down with the water added little by little. When it is used with a brush a little should be poured out in a saucer for the purpose, in order to avoid returning the brush into the solu- tion after using it. "When it is used in spray the best method is to fit the atomizing instrument to a small narrow bottle or a test-tube, into which a drachm or two of the mixture may be poured. This may now be immersed in a glass of hot water until its contents are warm, and then the spray may be ap- plied. Trypsin acts more rapidly when at a temperature slightly above that of the body. The remainder of the mixt- ure should be kept in a well-stopped bottle. These directions accompany the trypsin of Fairchild, which has been referred to as being especially efficient. Trypsin should be applied very frequently — every ten or fifteen minutes being not too often. Papayotin is efficient in an alkaline or a neutral medium, and less so when the reaction is acid. Neither of the solvents last referred to has any specific TREATMENT. 169 action upon false membrane, but they are simply ferments which act with great power in dissolving- coagulated albumen. Papayotin has usually been employed in a five per cent, solution in water, sometimes with the addition of an antisep- tic, as a small proportion of salicylic acid, applied hourly or half -hourly, by brush, irrigation or spray. Dr. A. Jacobi 1 rec- ommends its use in the proportions, papayotin one part, glycerine and water, each two to four parts, applied hourly. Rossbach 2 says that in order to be most effective the solution should be applied to the parts every five minutes, a few drops being placed upon the tongue or in the nose. Very young children may be allowed to suck a napkin which is moistened with a sweetened solution, or it may be inhaled after atomiza- tion. By this plan the membrane often becomes dissolved in two or three hours. He believes that if this substance is properly used it will obviate the necessity for tracheotomy. There is a general concurrence of testimony in respect to both papayotin and trypsin, that though they do in some cases at least, especially in the early stage of diphtheria, exert a favor- able and limiting effect upon its course, yet they are not spe- cifics for the disease, that they are without curative effect upon its infiltrated form, and that the constitutional disease when once established may go on to a fatal termination in spite of the dissolution of the false membrane. There is also a general agreement that both of these agents are innocuous to mucous membranes. The following is a suitable formula for the use of papayo- tin : 5 Papayotin, . gr. xxv. Glycerini, 3 ss. Aquae destillatae, . .• . . ad f j. M. The powerful tendency of jaborandi and pilocarpine to in- 1 Therapeutic Gazette, 1886, 145. 2 Deutsches Arch. f. Klin. Med.,Bd. XXXVI., H. 3 and 4. 170 diphtheeia; its natuee and teeatmeistt. crease the secretion of mucous membranes has led to their administration for the purpose of thus causing" the maceration of diphtheritic membranes, and hastening- their detachment. Its successful use in many cases has been reported by G. Guttmann J and others. Lax 2 recommends the following for- mula IJ Pilocarpini hydrochlorat., . gr. iij. Pepsinas, . . . . gr. j.. Aquae dest., . . . . fl. § ij 3 iss. Acidi hydrochlorici, . . gtt. ij. M. Dose, a small or large spoonful to be given according to age and effect. Since pilocarpine is liable to cause depression of the heart's action, collapse, nausea and vomiting and albuminuria, and since the copious salivation and perspiration which it produces are necessarily weakening, its continued use for a long enough time to fufill the above-mentioned indication is now generally condemned as dangerous. ANTISEPTICS. Cleanliness. In the " Instructions for Disinfection " by the New York Board of Health, from which quotation has been made in the preceding chapter, it is well remarked that " disinfectants " {i.e. chemical agents) " should not be relied upon to correct condi- tions due to dirt, decomposition, defective ventilation and neglect." This principle, so true in reference to the disinfec- tion of apartments, premises, etc., is equally applicable to the disinfection of the living body in the treatment of diphtheria. The thorough cleansing by suitable means of all surfaces affected by the disease, or liable to become so, in the mouth, the throat, the nasal passages and elsewhere, is of far greater Berlin. Klin. Wochenschr., 1880, No. 40, p. 569. 2 Journal de Medicine de Paris, Feb. 6, 1887. TREATMENT. 171 practical importance in the whole number of cases than the mere administration of antiseptic drugs, and the use of the latter, though important, can in no case atone for neglect or inefficiency in the former. The Resistance op the Organism. Bacteria and their spores, which invade the blood and tis- sues, are attacked, digested, and destroyed by the cells, 1 or in case of their overwhelming number and vigor destroy the cells. When the body is weak or exhausted by hunger or fatigue the power of thus destroying invading organisms is proportionally small. From this fact it appears that nutritive and sustaining measures in the treatment of infectious diseases may properly be regarded as measures of disinfection, that the use of antiseptic drugs which may be weakening to the patient should be carefully avoided, and that an agent which merely diminishes in a slight degree the vital activity of bac- teria may turn the scale in the conflict between them and the cells, provided that it is less poisonous to the latter than to the former. The Salts op Mercury. Among bactericidal drugs, the one which is efficient in the greatest dilution is the bichloride of mercury. According to the experiments of Koch 2 it hinders the development of an- thrax bacilli (a comparatively resistant organism) in the strength of 10 ooo oo in the nutrient solution, prevents it in the strength of -3-3x33-3, kills the spores of the bacilli in ten minutes in the strength of g0 ^ 00 , and with one wetting in the strength of ToW Other salts of mercury, as the sulphate, the nitrate, the cyanide and the iodides are also very efficient bactericides, though in a somewhat less degree than the bichloride. 1 Metschnikoff , Virch. Archiv. vol. xcvi., p. 177, and xcvii., p. 502, and Fodor, Arch. f. Hygiene, Bel. 134, p. 149. 2 Mittheilungen aus dem k. Gresundheitsante, vol. i. 172 diphtheria; its nature and treatment. For prompt and certain local antiseptic effect corrosive sublimate is applied in a solution of the strength of from ^ \ to -g^-Q by brush, swab or atomizer. * In order that this effect shall be produced it is necessary that the bacteria and their spores be actually wetted with the solution in its full strength or nearly so. If the affected sur- faces are covered with profuse and viscid secretions, as is often the case, they should first be cleansed by spraying- or irrigation, and afterwards dried by touching them lightly with absorbent cotton. A still greater obstacle is usually presented in the false membrane. If this be exceptionally thin, superficial, and loose of texture, the solution may penetrate to its under surface with no very great dilution; but in proportion as it is thicker and denser this becomes impossible. But even if the false membrane have previously been re- moved, the fact remains that the fungi of the disease, so far as we have means of judging, do not lie merely on the surface of the mucous membrane or the denuded tissues, except at a very early stage of the disease or in its more superficial forms, but also beneath the epithelial layers or even in still deeper structures. It follows from these considerations that the eradication of diphtheria in its really deeper and graver forms, except at a very early stage, even by the local use of this most powerful of bactericides must often be opposed by insuperable obsta- cles, and this conclusion is confirmed by experience. For exam- ple, W. W. Cheyne 1 has employed the following treatment: He first removes as much of the membrane as is possible with forceps, and then applies to the denuded surface a watery solu- tion of bichloride (one in five hundred) with a brush every two hours, especial attention being directed to the margin of the affected region. In the intervals a gargle of bichloride in the strength of one two-thousandth is used. This treatment has 1 British Medical Journal, March 5, 1887, p. 504. TREATMENT. 173 " quickly and completely arrested " the disease in several adult cases which were " taken early/' but in the case of children " the results are not so good." Corrosive sublimate is also employed in higher dilution — that of 3oVo> TuViT or Tui to~ f° r local antiseptic effect by fre- quent internal administration, gargling, irrigation and atomi- zation. That a solution of one grain of corrosive sublimate in the pint of water is a safe and useful antiseptic wash in many cases of diphtheria cannot be doubted; yet even in that dilu- tion the effect of its frequent application to diphtheriticalty inflamed surfaces has seemed to me less beneficial and more liable to be irritating than that of other substances yet to be mentioned. It should also be borne in mind that in spraying the throat and irrigating the nasal passages of children, even with a solution of this strength, caution is needed that a dan- gerous quantity of the poisonous salt be not swallowed. In view of the enormous dilution in which corrosive subli- mate diminishes the vital activity of bacteria, the idea that it may be introduced into the circulation in sufficient quanthVy, even making allowance for its constant elimination, to have some influence in the struggle between the living body and its pathogenic invaders is probably not altogether chimerical. This view is favored by the results of the experiments of Cash, 1 who found that the continued administration of minute doses of sublimate to animals rendered them capable of resisting the effects of the subsequent inoculation of anthrax. There is reason to believe that the salts of mercury, inter- nally administered, have a tendency to oppose the occurrence of fibrinous exudation in the air-passages, and to promote its detachment when formed. Reports of the successful treat- ment of membranous croup with calomel have been too nu- merous in the medical literature of this and other countries to be easily explained by the theory of mere coincidence. Though 1 Proceedings of the Physiological Society, Dec. 12, 1885. Journal of Physiology, vol. vii. 174 diphtheria; its nature and treatment. that treatment, having- heen found in many cases disappoint- ing- in its result and injurious in its effects, was long ago gen- erally abandoned, yet testimony to its efficacy continues occa- sionally to appear. Heroic dosage is an element in its em- ployment by some, as for instance in the successful treatment of three children suffering from laryngeal diphtheria, twenty grains of calomel was given at first, followed by ten grains hourly — seven hundred and twenty grains having been taken by a child twenty-eight months old in three clays ! x It is a relief to learn that diphtheria has been successfully treated by the use of two to five grains of calomel every one to three hours until the dejections are frequent and green, then continuing the same doses at lengthened intervals so as to keep up the catharsis, 2 and even by doses of one sixth of a grain every hour, increased in the presence of threatening laryngeal symptoms to one third of a grain every hour, and then to one grain every two hours for five hours, in a patient eighteen months old, 3 and in thirty-six consecutive cases by the following method : The diseased part is first wetted with a two to five per cent, solution of common salt — then two to four tenths of a grain of calomel are blown over it twice daily, the throat being in' the mean time gargled every two hours with the salt solution. A portion of the calomel becomes bi- chloride, and the remainder passes into the stomach and pro- duces free catharsis. 4 There is a concurrence of testimony from many judicious practitioners as to the benefit which may be derived from pur- gative doses of calomel at the early stage of diphtheria, es- pecially in cases in which there is high fever with deficient secretions and marked nervous disturbance — a benefit which 1 Dr. J. P. Klingensmith, of Blairsville, Pa., New York Medical Record, July 12, 1884, p. 36. 2 Dr. W. H. Daly, of Pittsburg, New York Med. Record, June 12, 1886, p. 692. 3 Dr. Geo. B. Fowler, New York Med. Record, Nov. 19, 1887, p. 647. 4 Kotzuski, Jahrb. f. Kinderh., xxi., p. 272. TREATMENT. 175 I have observed in many cases, and which was referred to in my first publication (1876). It may be given in a single dose of from two to ten grains, or in doses of a fraction of a grain (one tenth to one half) repeated frequently (from every twenty minutes to every two hours) until its characteristic purgative effect is produced. At the present time mercury is most generally employed in the treatment of diphtheria in the form of the bichloride. Its use in large doses (one quarter to one-half grain or more daily) has been advocated in this country by Dr. W. Pepper, 1 (and hence widely known as the "Pepper treatment") and subsequently by Dr. A. Jacobi 2 and by many others. Of its efficacy in diphtheritic croup, Dr. Jacobi 3 says, " I have never since 1863 seen so many cases of tracheotomy get- ting well as between 1882 and 1886, when the bichloride was constantly used as mentioned I can name a dozen of New York physicians, some of whom have often performed tracheotomy, who can confirm the above statements from their own observations. Nor does the opinion of those differ who constantly perform intubation. I know that O'Dwyer, Dillon Brown and Huber have come to the same conclusions." The doses referred to by Dr. Jacobi are "from one sixtieth to one fortieth of a grain and sometimes more," given hourly in a tablespoonful of water, milk or other compatible fluid. To the valuable efficacy of the bichloride of mercury (as, indeed, of most other prominent remedies used in the treat- ment of diphtheria) there is in recent literature a striking array of testimony, of which the following examples are given mainly to illustrate different modes of employing it : Dr. E. C. Carter, Assistant Surgeon United States Army/ 1 Transactions of the American Medical Association, 1881. ■ " The Medicinal, mainly Mercurial, Treatment of Pseudo-Membra- nous Croup," New York Medical Record, 1884, vol. 25, p. 573; and "A System of Medicine by American Authors," Phila., 1885, p. 705. 3 " Therapeutics of Diphtheria," Medical News, June 10, 1888, p. 663. 4 Medical News, Nov. 27, 1886, p. 593. 176 DIPHTHERIA; ITS NATURE AXD TREATMENT. in an epidemic of diphtheria near Fort Thomas, Arizona, hav- ing treated the first eleven cases with other remedies with four fatal results, gave bichloride in thirty -four subsequent cases in doses varying- from one sixty-second to one twenty- fourth of a grain with unvarying success. That they were genuine cases of diphtheria seems to be attested by the fact stated that twelve of the patients who recovered had paraly- sis. Dr. P. Werner, 1 having previously lost between sixty and seventy per cent, of ninety cases, employed bichloride treat- ment in the succeeding seventeen — mostly severe ones — with only two fatal results, and those in cases seen only a few hours before death. He gave doses of 2x0 to ^ of a grain (ac- cording to age), well diluted in water, every twenty or thirty minutes while the patients were awake, so that one quarter of a grain was taken daily by young children, one half by older ones, and three quarters by adults. J. Stumpf, 2 having in the early part of an epidemic lost twenty-two out of twenty-nine cases, employed in the succeed- ing thirty-one cases the bichloride of mercmy only, with fav- orable result in all but two. He administered in spray one fluid drachm of a solution of the strength of -^-q, yqqq or toW (according to age) hourly for five times, then every two hours for five times, and subsequently every three hours. Dr. E. L. Oatman, 3 of ISTyack, N. Y., having previously lost ten out of twenty-three cases under treatment with iron in large doses and free stimulation, has, since the addition of local treatment with the bichloride, lost only one out of thirty- four cases. Dr. Oatman prepares a number of swabs by firmly twisting absorbent cotton around the end of a small stick. Every hour one of these is dipped into a solution of the bichloride (two grains to the pint) and passed into the throat 'St, Petersburg Med. Wochenschr., 1886, r. F. III., p. 81. 2 Muenchener Med. Wochenschr., 1887, p. 219. 3 New York Med. Record, April 23, 1887, p. 465. TREATMENT. 177 until it touches the posterior wall of the pharynx and then in- stantly withdrawn and burnt, no swab being- used a second time. More or less of the membrane always adheres to the swab. This procedure is repeated hourly until the disease be- gins to subside, which it usually does in forty-eight hours. If the nares are affected, the nose is syringed. The biniodide of mercury is regarded as especially effica- cious by some. It is employed by Dr. C. G. Rothe, 1 of Alten- burg, in the following formula : r> Hydrargyri biniodidi, . . gr. £. Potassii iodidi, .... gr. iij — gr. ivss. Aquae destillatas, . . . fl. 3 j 3 vij. Tincturae aconiti, ... . th, xv. M. A teaspoonful is given hourly to a child under three years of age. Dr. Rothe has thus treated successfully forty cases. Extraordinarily favorable results from the use of the cya- nide of mercury are reported by Dr. J. Bree 2 and by Dr. H. Sellden, 3 a Swedish provincial medical officer. The latter re- ports fourteen hundred cases treated by himself and his col- leagues, with a total mortality of sixty-nine, or 4.9 per cent. The formula he recommends is as follows : Cyanide of mercury, two centigrammes (gr. ^) ; tincture of aconite, two grammes (Til xxx.); honey, fifty grammes (f j. 3 ivss.); distilled water one hundred and fifty grammes ( § iv. 3 vss.). Mix and give a teaspoonful every fifteen, thirty or sixty minutes, according to the patient's age. A gargle of the cyanide in peppermint water in the strength of T o,Voo i s a l so to be used frequently. Inunction of mercurial ointment has also been much em- ployed in the treatment of diphtheria. For its more rapid 1 Journ. de MM., June 5, 1887. 2 " Behandlung der Diphtherie mit Quecksilbercyan," Dissertation, Berlin, 1886. 3 London Lancet, March 24, 1888, p. 591. 12 178 DIPHTHEKIA ; . ITS JSTATUKE AND TKEATMENT. absorption the oleate is recommended by Dr. A. Jacobi * — ten or twelve drops to be rubbed into the skin every hour or two. The hypodermic injection of corrosive sublimate is recom- mended by the same author — four or five drops of a one-half or one per cent, solution to be so used from four to six times a day or more. Dr. F. P. Henry 2 states that the hypodermatic injection of corrosive sublimate is so painful that few will con- sent to its repetition, and prefers the bicyanide of mercury, since it is compatible with cocaine, which the former is not. He has found its employment in many cases by the following formula comparatively painless : 5 Hydrarg. bicyanid., .... gr. ij. Cocain. hydrochlorat., . . . gr. iv. Aquas destillat., fl. § ss. M. Fifteen minims to be injected beneath the skin in the case of an adult. Mercury by fumigation has been used in the treatment of diphtheritic croup with remarkable success by Dr. J. Corbin, 3 of Brooklyn. The child is placed in a crib under a tent pre- pared with barrel-hoops and blankets. Calomel is volatilized in the tent by heat, from forty to sixty grains being used in the case of a child eight or ten years of age. The lamp should be powerful enough to volatilize a drachm of calomel in one minute in order to avoid overheating the air in the tent. The child is kept under the canopy for twenty minutes, when the blanket is removed. This is repeated every two or three hours during the first day. After that period the cough is usually loosened, and the intervals between the fumigations are lengthened, but they should be at once resumed if the cough tightens. In some cases two or three fumigations daily J A System of Practical Medicine by American Authors, vol. i., p. 705. 2 Medical News, Nov. 3, 1888. 3 New York Medical Journal, March 10, 1888, p. 261. TREATMENT. 179 have been continued for over a week. The aphonia may not disappear for a week or more, but that need excite no alarm. This treatment is not a substitute for tracheotomy or intuba- tion. Including- sixteen cases thus treated by himself, and four- teen by three other physicians, Dr. Corbin reports thirty cases, of which twent3^-five, or about 84 per cent., recovered. In one of the fatal cases the treatment was abandoned by the family. In none of the other four did death result from ob- struction of respiration, but from the effects of toxasmia. The valuable action of mercury in the treatment of diph- theria, like that of most other remedies, is greatest when it is employed at an early stage of the disease. Then it has a ten- dency (in some cases at least) to limit the extension and mod- erate the intensity of the affection, and thus to diminish the subsequent constitutional poisoning. But when the septic condition is once established it has not the power to arrest it, but if excessively or too long used is very liable to aggra- vate it. In the internal administration of the salts of mercury it is most important to remember that these valuable therapeuti- cal agents, when used beyond certain limits as to frequency, quantity and continuance, are dangerous irritant and depress- ing poisons; that this action of them must be especially dele- terious in a disease which is in itself so depressing as diph- theria, and is particularly liable to be overlooked from being- attributed to the disease. In a judicious and timely protest against the abuse of mer- curials in the treatment of diphtheria, Dr. J. E. Winters 1 says, " I know that as the result of the inconsiderate use of mercurials in the treatment of diphtheria, physicians are often called upon to treat the consequences of their want of cau- tion ; while they have blindly ascribed the rapidly progressive ^'Diphtheria and its Management," New York Medical Record, Dec. 5, 1885, p. 617. 180 DIPHTHERIA; ITS NATURE AND TREATMENT. anasmia, prostration, marasmus and death to the disease alone. . . . "I have unequivocal and direct evidence of the injurious effects of bichloride of mercury from two intelligent physicians who have had diphtheria, and who both experienced the de- pressing- effect of the drug-. They told me that they felt de- pressed as soon as the mercurial began to have an appreciable action on the intestinal tract, and* that there was a feeling- of nausea and sinking even preceding this. I may add that after the discontinuance of the bichloride both patients felt within three hours the strengthening effect of the tincture of iron in full doses given hourly/' Carbolic Acid. Carbolic acid is a far less powerful bactericide than corro- sive sublimate. An aqueous solution of it in a strength of y-gVo hinders the growth of anthrax bacilli: -^ prevents it; y^j- to 4-J~o prevents the growth of other bacteria; a five per cent, solution requires more than twenty -four hours to kill the spores of anthrax bacilli, though a one per cent, solution de- stroys the bacilli themselves in ten minutes. Its use in full strength or with slight dilution as a caustic has already been referred to (page 158). Carbolic acid has great utility in the local treatment of diphtheria, since in suitable dilution it is not only an efficient antiseptic but also has a valuable sedative and antiphlogistic action. Dr. T. M. Pruclden 1 has shown that a solution of car- bolic acid of the strength of t^t, locally applied under condi- tions in which inflammatory changes commonly occur, modi- fies those changes by preventing any considerable emigration or locomotion of white blood-cells. Salicylic Acid. Salicylic acid is an efficient antiseptic. It hinders the growth of bacteria in a solution of the strength of ■ s -^wo> P re ~ 'American Journal of the Medical Sciences, Jan., 1881, p. 82. TREATMENT. 181 vents it in that of Y^Vnrj and kills bacteria in that of F V Suc- cessful results have been claimed from its use in powder by insufflation and by brushing- it over the parts affected. 1 The following formula for its use is recommended by M. Ory : • 1^ Acidi salicylici, . . . gr. v. Glycerini, fl. 3 iij. Aquas lauro-cerasi, . tt[ xvi. Inf us. eucalypti, . . . . fl. 3 iijss. M. To be applied by brush every hour by day and every two or three hours at night. It is said to hasten the disappearance of false membrane. Salicylic acid is more irritating to inflamed surfaces than carbolic acid. According to the statistics of Schiiler, 3 in 41 cases treated with chlorate of potassium there were 6 deaths; in 23 cases treated with carbolic acid there was 1 death; in 15 cases treated with salicylic acid there were 7 deaths. Dr. A. d'Espine 4 has ascertained by experiments that sali- cylic acid, even in a solution of 1 : 2000, is an excellent parasiti- cide of the bacillus of diphtheria. Its harmlessness in this dilution makes it a very available application by irrigations, which should be repeated hourly. The especial utility of this employment of it would obviously be in the early stage of the disease and as a prophylactic. Crinoline. Chinoline is a powerful antiseptic,, and in strong concen- trations is sharply caustic. Its local effect in the treatment of diphtheria has been favorably reported upon by Dr. O. 1 Noeldechen of Pforta, Deutsche Med. Zeitung, Nos. 33-36, 1886. 2 Revue Gen. de Clinique et de Therapeutique, July 5, 1888. 3 Berlin Klin. Woch., 40. 4 Medical News, 1889, 54, p. 187, from Revue M6dicale de la Suisse Romande, Jan. 20, 1889. 182 diphtheria; its nature and treatment. Seifert 1 and others. Dr. Seifert used it in a five per cent, solution in equal parts of alcohol and water applied by brush- ing- from twice daily to every three hours, and as a gurgle in the following' solution: chinoline 1.0 (15 grains); water, 500 (1 pint); alcohol 50. (1| ounces); oil of peppermint, two drops. Prof. Ahlfeld, 2 however, in one hundred and ten cases of chil- dren treated by this method, reported a mortalitj 7 of 28 per cent., and Dr. Lunin under similar treatment lost fifteen of twenty-eight patients. Resorcine. Resorcine is also a powerful antiseptic, and is less caustic than carbolic acid. It has been employed by Liblond 3 in solu- tion in glycerine (one in ten to fifteen parts) applied locally every two hours with favorable results, and like results from a similar use of it have been reported by Fraigniaud, 4 and H. Callias. 5 The latter employed a five to ten per cent, solution in water with a little glycerine by pencilling hourly, and a two per cent, solution every two hours by spraying. On the other hand Dr. Lunin lost nineteen of twenty-nine patients treated with resorcine. Sulphur. Sulphur has long been much employed in the treatment of diphtheria, mainly by insufflation, and its effects have been lauded by many. When thus used a portion of it is changed into sulphurous acid or sulphuretted hydrogen, both of which are powerful bactericides. Insufflation is a difficult procedure in the cases of young ^children, and the remedy itself is un- pleasant. Dr. H. V. Knaggs, of London, 6 recommends the fol- lowing preparation as palatable and readily taken by children : 1 Jahrb. f. Kinderh., 1884, p. 462. 2 Jahrb. f. Kinderh., 1884, p. 463. 3 Journ. de MeU de Paris, Dec. 20, 1884. 4 Union M6dicale, 1885, p. 493. 5 Quoted by Le Gendre, Archiv. de Laryngol., No. 1, 1887. B Therapeutic Gazette, March 15, 1888, p. 153. TREATMENT. 183 fy Precipitated sulphur (pure), . . 3 jss. Chocolate powder, . . . . 3 j. Cinnamon-water (concentrated, 1 in 40), fl. 3 j. Grycerine, fl. 1 iij- Mix the powders in a mortar; then gradually add the glyc- erine with constant trituration, and lastly the cinnamon- water. Dose, half a teaspoonful to a teaspoonful every hour or oftener. Dr. Knaggs reports the treatment of seventy-five cases of diphtheria by this drug- alone, with no fatal result. Rapid disappearance of membrane and corresponding gen- eral improvement are said to have followed the use of sulphur- ous acid in teaspoonful doses every half-hour to every two hours according to the gravity of the case. 1 Hyposulphite of soda has been used during the past year by Dr. J. H. Fruitnight, 2 of this city, in connection with iron and other appropriate treatment in thirty cases with success- ful result in all but two. The remedy has been used in the strength of 3 j — 3 jss — 3 ij (according to the age of the patient) in two fluid-ounces of water, and of this a teaspoonful has been given every two hours. In a few of the cases the solu- tion has been applied with a brush or with the atomizer, the gentlest possible mode of application being always preferred. Chlorine, Bromine, and Iodine. Free chlorine, bromine, and iodine are among the most powerful bactericides. Chlorine kills bacteria in a watery solution of the strength of -^foo" 5 bromine in that of -^V o> an( ^ iodine in that of 15 1 00 . In internal use their germicidal effect is greatly diminished by their conversion in vital fluids which contain alkalies (as, for example, blood-serum) into chlorides, bromides and iodides. Their principal utility as antiseptics in the treatment of diphtheria is therefore in their local effect. For cleansing and deodorizing a foul diphtheritic throat, 1 Dr. H. L. Snow, British Medical Journal, Oct. 8, 1887, p. 773. 2 Archives of Paediatrics, October, 1888, p. 601. 184 DIPHTHERIA; ITS NATURE AND TREATMENT. solutions of chlorine have long been much prized, and are among- the most efficient agents in our possession. The best of these is the liquor soda? chloratse, from two to four fluid- drachms of which in eight fluid-ounces of water may be applied every hour or two by gargling, irrigation or atomization. There has been much testimony to the successful employ- ment of bromine in the treatment of diphtheria ; but this ex- perience of its utility has been by no means universal. Like many other powerful antiseptics it may doubtless be in skillful hands an effective therapeutical weapon against diphtheria; but its use in full strength or slight dilution is opposed by the considerations which have been referred to in regard to cor- rosive and irritating applications generally, and in high dilu- tions it has not been shown to have greater curative efficacy than other less disagreeable remedies. It is recommended by Dr. Hiller * in the following combination : 3 Potassii bromidi, Bromi, aa gr. iv. Aquas dest., I vj. 3 ij. M. To be applied by brush to the pharynx every two or three hours and also used by inhalation. Dr. P. Hesse, 2 from his experience with one hundred and fifty cases, regards bromine as the most valuable local appli- cation in diphtheria. He used a solution of five decigrammes (gr. |) each of bromine and bromide of potassium in two hun- dred grammes ( ? vj. 3 ij.) of water applied locally every two or three hours and also dropped on the sponge of an inhaler and so used for five minutes every half-hour. Latterly he used the solution by inhalation only, varying its strength according to the severity of the case. Dr. W. H. Thomson has employed bromine successfully in the treatment of a large number of cases of diphtheria, by a 1 Deutsche Med. Wochenschr., 1882, ix., 22, p. 328. 2 Deutsches Archiv. f. Klin. Med., 1885-6, xxxviii., p. 479. TREATMENT. 185 method of which the following- account is abbreviated from a fuller statement by himself which is contained in "A Treatise on Diphtheria " by Dr. A. Jacobi : Lawrence Smith's solutio bromini is first prepared by the following- method : " Take two ounces of a saturated solution of bromid. potass, in water; add to this, in a bottle, with constant shaking, one ounce of bro- mine. It is better to add a part and then let it stand awhile before adding the rest. Then fill up gradually, and with con- stant shaking, with water, until it measures four ounces." It should not be ordered in a mixture with either glycerine or sugar, as it is thereby decomposed. If not exposed to too strong' a light it keeps for several days. Locally this solution, mixed with an equal part of glycerine, or, in some cases, in full strength, is applied to the membrane with a hair-pencil as gently as possible. If the membrane is very extensive and the parts much swollen or difficult to reach, one half a drachm to one drachm of the solution to the pint of warm water is applied by douching with a Davidson's S3^ringe. Internally from six to twelve drops of Smith's solution in a tablespoonful of sweetened water is given every hour, two, or three hours, according to the urgency of the case, and contin- uously, no other medicine being taken until the disappearance of the membrane. It should be swallowed promptly, as the disagreeableness of bromine is due much more to its fumes than its taste. Tincture of iodine has long been much employed as a local application in diphtheria, and many reports attest its efficacy as a caustic and antiseptic in causing the shrivelling and rapid disappearance of membrane. It has also been much used in such combinations as the following: x 5 Tinct. iodi., Tinct. ferri chloridi, . . . aa fl. 3 j. Acidi carbolici, gr. x. Glycerini, fl. § ss. M. Apply by brush several times daily. 'Dr. Keating, Boston Med. and Su*g. Journ., 1885, Jan. 22. 186 diphtheria; its nature and treatment. It has also been used internally; as by Dr. E. Aclainson 1 who treated fifty-five cases, including- some very bad ones, with doses of two or three minims in syrup aurantii and water every two hours to a child of six years with only two fatal results. The same remarks as to its great utility and its infe- rior eligibility to some other drugs in the treatment of diph- theria, both in stronger and weaker solutions, apply to iodine as to bromine, though in a somewhat less degree. Iodoform. " It is now regarded as an established fact that iodoform is not a parasiticide. ... It is believed by some to have a de- structive effect on the ptomaines generated b3 T the bacteria through the action of the free iodine or iodine compound which is liberated." 2 It cannot be doubted that iodoform has a val- uable antiseptic action, and its local ansesthetic effect and ten- dency to diminish secretion render it valuable in the treat- ment of diphtheria. It is important, however, that its use should be preceded or accompanied by other disinfectant measures. It may be applied in powder, by brush or insufflator, pure or mixed with half its weight of starch or with three parts of sugar. Good results- in preventing the extension of membrane down the trachea after tracheotomy, by the insufflation of iodoform through the tube, have been reported by George Shirres 3 (who thus used ten to fifteen grains eA~ery four hours in two cases) and others. The following solution to be applied by pencilling is recom- mended by Le Gendre : 4 Iodoform . . 2.50 grammes (38 grains). Balsam of tolu . 5 " (75 minims). Ether . . .25. " (6 ± drachms). 1 Practitioner, London, July, 1885, p. 16. 2 American Journal of the Medical Sciences, October, 1888, p. 401. 3 London Lancet, July 24, 1886, p. 164. 4 Archiv. de Laryngol., No. 1, 1887. TREATMENT. 187 Dr. Gr. Mundie ' prefers the application of iodoform to the throat in ethereal solution by spraying*. The ether appears to constringe the congested capillaries, and the iodoform is deposited in a thick film on the surface. Iodoform has been regarded by many as an especially val- uable agent in the treatment of the diphtheria of wounds. Its successful use in diphtheritic invasion of the tracheotomy wound has been reported by Plenio 2 and others in the form of powder, iodoform-vaseline or iodoform-collodion. It may be mixed with either of these excipients in the proportion of one to eight. Iodol has a similar action and like applicabilities to those of iodoform. Chloral. Hydrate of Chloral, first recommended in the local treat- ment of diphtheria by Dr. Accetella, 3 of Italy, has since been much employed and highly prized by many. It is an efficient antiseptic, hindering the development of bacteria in the strength of tqVo". It is also a powerful irritant to raw or especially sensitive surfaces. Applied to the affected part by brush every hour or two in the form of the officinal syrup of chloral of the British Pharmacopoeia (ten grains to the drachm), it promptly arrests fcetor and is said to cause the rapid solution and disappearance of membrane. Dr. A. Mercier 4 gives internally the syrup of chloral of the French codex (one in twenty) in doses of two, three or five grammes every half-hour or hour, no drink being allowed for some time afterward. In forty-eight hours after the treat- ment is begun the false membrane has dissolved and disap- peared, when the further use of the chloral becomes painful. 1 London Lancet, June 5, 1886, p. 1103. 2 Jahrb. f. Kinderh., Bd. xxii., H. 4. 3 Campania Medica, No. 12, 1873. 4 Le Concours MM., Aug. 27, 1887, p. 411. 188 diphtheria; its nature and treatment. By this treatment, Dr. Mercier has saved ninety-five out of one hundred cases. Oxygen. Oxygen is one of the most powerful of disinfectants and antiseptics. It has been principally employed in the treat- ment of diphtheria, locally by means of the permanganate of potassium, locally and internally in peroxide of hydrogen, and as convej^ed through the blood to the tissues by means of the salts of iron. From the readiness with which it parts with oxygen, per- manganate of potassium is a powerful antiseptic, and in a solution of the strength of from three to five grains to the ounce of water is a most valuable local application in the treatment of diphtheria. Dr. Mason 1 prepares a stock solu- tion of two drachms of the permanganate in three ounces of distilled water, and uses a teaspoonful of this solution in one ounce and a half or two ounces of water as spray. It promptly arrests foetor, which does not return. Peroxide of hydrogen, though not a new substance, has of late been brought prominently forward as an especially valu- able antiseptic in the treatment of diphtheria, and in the hands of some has, like most new remedies, produced brilliant therapeutical results. Such results have been claimed by Vogelsang 2 and by Hofmokl. 3 Dr. M. P. Hatfield, 4 of Chicago, has used it successfully in eighteen cases, applied by swab every two hours, or a spray of the liquid diluted with seven times its bulk of water. He states that it neither acts as a solvent to, nor prevents the formation of, false membrane, bat neutralizes its poison. The form in which this agent has been most generally used in this city is the Marchand solution, which contains fifteen 1 Brooklyn Medical Journal, May, 1888. 2 Archiv. f. Kinderh., B. viii., H. 2, p. 113. 3 Wiener Med. Presse, 1886, xxvii., 18, 19. 4 Archives of Paediatrics, Feb., 1888, p. 102. TREATMENT. 189 volumes of the gas. Dr. H. Gifford, 1 having- in a series of ex- periments demonstrated that this preparation promptly kills bacteria and their spores, adds, " The instructions accompany- ing- the Marchand solution advise diluting with about four times its bulk of water for use on ' mucous membranes as in- jections, etc' A dilution of this strength was found not to have killed the pus cocci after an exposure for thirty minutes, a result which practically bars it as a germicide, though for its cleansing action it may still be valuable The fifteen volume solution is sharply irritating to the conjunctiva and nasal mucous membrane, and even the weakest solution men- tioned in the announcement, instead of being ' bland as water,' causes considerable smarting of the eyes and nose for a few minutes." I have tried the Marchand solution in several cases of diphtheria, including one adult one, and my experience with it accords with that of Dr. Gifford as to its somewhat irritating and unpleasant effect when used with only slight dilution. In each case it was a relief to the patient and therapeutically advantageous when its use was discontinued and my usual spray of carbolic acid and lime-water was resumed. In a case related to me by another physician in which the peroxide was employed early and frequently both as spray and internally, the duration of the disease was not shortened thereby, and the patient died just at the time of apparent re- covery from the usual effects of toxic absorption, which the remedy had failed to counteract. In so far as I have been able to judge of its effects the peroxide of hydrogen, though it is a valuable antiseptic, has no greater curative efficiency in the treatment of diphtheria than the solutions of chlorine or of permanganate of potas- sium, with which remedies it may be classed; but is to be pre- ferred to them on account of its less disagreeable taste. The application of ozone by the inhalation of ozonized air 1 New York Medical Record, Sept. 1, 18S8, p. 243. 190 diphtheria; its nature and treatment. has been from time to time recommended in the treatment of diphtheria — the ozone being- produced by a chemical process in an inhaler. Dr. Seneca D. Powell a few years since exhibited to the Post-graduate Clinical Society of this city an inhaler in which ozone is generated by the action of electricity, and which he had used with good effect in various diseases, among which was diphtheria in several cases — its effect having been the rapid disappearance of false membrane and the correspond- ingly rapid reduction of temperature. I am informed by the deviser of this instrument, Mr. Harvey Lufkin of the C. & C. Electric Motor Company, that it will soon be manufactured # and offered for sale. Benzoate of Sodium. Benzoate of Sodium has only a mild antiseptic action, since in a solution of ^oir i* merely hinders the growth of anthrax bacilli (Koch). Letzerich, having been led by the experiments of Graham Brown to the conclusion that it is fatal to the microbe of diphtheria, and consequently a specific for that dis- ease, employed it therapeutically with nearby uniform success by the following formula : # Sodii benzoat, . . . . 3 j. gr. xv. Syr. aurantii, . . . . 3 ijss. Aquae menthae pip., Aquae dest., . . . aa § j., 3 ij. M. To be given in divided hourly doses in the twenty-four hours. He subsequently increased the daily dosage to from 1| to 3| drachms to children under fifteen years, and from 3| to 5^ drachms for older patients. From this and similar uses of it favorable results have been reported by Kien, Ferreol and manj^ others, the most notable being those related by Brondel, 1 who claimed to have treated two hundred cases with uniform success by the fol- 1 Bulletin Gen. de Therap., Nov. 15, 1886, p. 416. TREATMENT. 191 lowing- method : He gave hourly a tablespoonful of a solution of the benzoate (fifteen grains to the fluid ounce), together with one sixth of a grain of the sulphide of calcium in syrup or granule, and sprayed the throat every half-hour with a ten per cent, solution of the benzoate. He also employed vapori- zation of water containing carbolic acid, turpentine and oil of eucalyptus. Favorable results from the use of the benzoate of sodium have not, however, been obtained by all who have employed it. Thus Guandige, of Vienna, 1 among seventeen children treated by the method of Letzerich, had eight deaths. While there is reason to believe that this agent has positive therapeutical value, the hope that it would prove to be the desired specific has not been realized. Chlorate of Potassium. Chlorate of Potassium has long held a leading place among- valuable remedies in the treatment of diphtheria. It is a mild antiseptic, and its effect in favorably modify- ing catarrhal inflammation in the mucous membrane of the mouth and throat is well established. It is to this effect upon the inflammation that its utility in the treatment of diph- theria is doubtless mainly due. The important fact that chlorate of potassium is in exces- sive doses a most dangerous poison has been illustrated in quite numerous instances. Dr. V. Afanasieff 2 has collected from international literature fifty-one such cases, forty-six of which were fatal. He has also found by experiments on ani- mals that in acute cases of poisoning by the chlorate of potash there is rapid and profound disorganization of the blood, its detritus accumulating in the liver, spleen, lymphatic glands, bone-marrow and kidneys, the urinary tubules becoming 1 Quoted by Le Gendre, loe. cit. 5 "St. Petersburg Inaugural Dissertation," 1885, Abstracted in Pro- vincial Medical Journal, March, 1888, p. 134. 192 DIPHTHERIA; ITS NATURE AND TREATMENT. blocked up and impassable, the renal functions ceasing and acute parenchymatous nephritis with ureemic poisoning- re- sulting-. In chronic Papain, . . . . .. • 3 ij. Hydronaphthal, gr. iij. Acidi hydrochlorici dil., . . . gtt. xv. Aq. destil., ad § iv. M. This was applied by " spraying the throat every half -hour until temperature is reduced and breathing is easy; then every hour, unless asleep. In these cases, when the spray was used thoroughly, the temperature fell in from four to eight hours." To be effective, the spray must be thoroughly and directly applied to the affected surfaces. In the seven cases referred to, the result of the treatment was favorable in all but one— a laryngeal case in which cyanosis was present when treatment was begun. 1 Archives of Pediatrics. February, 1889, p. 97. TREATMENT. 201 The Chloride of Iron. So great a mass of clinical evidence as to the value of the chloride of iron in the treatment of diphtheria has "been pre- sented to the profession, and that value is now so generally recognized, that it would he superfluous to adduce statistics to prove it. The occasional denials of its efficacy, based on expe- rience of its unsuccessful employment, which appear in medi- cal literature, may he regarded as merely illustrating the indisputable fact that it is not a specific, and that its useful- ness is subject to limitations. The local astringent action of the drug has already been referred to ; it is also a valuahle local antiseptic. Internally it is undoubtedly the most efficient known antidote to the poi- sonous action of the putrefaction -products of diphtheria in the system at large. It evidently does not produce this effect by destroying the microbes of the disease, hut by reinforcing the vital processes by means of which the poisons produced by them are resisted, destroyed and eliminated. The tendency of these poisons, when absorbed into the circulation, is to the rapid production of anaemia and haemic disorganization, nerv- ous prostration, and the consequent arrest of all vital func- tions. " Ferric salts, after absorption into the blood, increase not only the number of the blood-corpuscles, but also the per- centage of haemoglobin contained in them, and may also cause a little free iron to be contained in the serum. By thus in- creasing oxidation in the tissues they increase the functional activity of all the organs Iron also circulates with the bile, and it is probable that the beneficial effects of large doses may be due to the action of the iron upon the liver." (Brun- ton.) Iron is also a tonic to the vascular system, and ferric chloride has been supposed to have an especial stimulant action on the nervous sytem. The internal administration of the chloride of iron has lit- tle effect on the duration of the membranous affection. In the 202 diphtheria; its nature and treatment. laryngeal form of the disease it is probably useless, except to oppose concomitant blood-poisoning, and as a tonic. In the distinctively inflammatory stage and form of diphtheria its value is mainly limited to its local astringent and antiseptic action in the pharynx. Its special and unequalled utility is seen in its preventing or limiting the occurrence of constitu- tional poisoning and counteracting its effects in the septic form or stage of the disease. Its power to accomplish this object is, however, not unlimited. It is inadequate in cases in which the constitutional poisoning is especially rapid and in- tense, and in many cases in which other essential antiseptic measures are neglected, as, for instance, the cleansing of the nares in nasal' diphtheria. There are unfortunately other limitations to its utility. In quite a number of cases it is irritating to an especially sensi- tive throat, and it sometimes causes vomiting. These effects may depend on the injudicious manner of its administration, but in some cases its use in any form is inadmissible. The administration of large amounts of the drug is con- sidered by many a sine qua non to obtaining its beneficial local and constitutional effect. Dr. Aubrun, 1 in 1860, recommended its use in very frequent doses. His usual mode of administering it was to have from twentj T to forty drops of an aqueous solution of the perchlo- ride, consisting of one part of the anhydrous salt in three parts of water, put into a cup of water, and of this two teaspoonfuls were taken by the patient every five minutes while awake, and every fifteen minutes while sleeping. Robert Druitt, 2 in 1861, practiced and recommended giving it in doses as large as two drachms every two hours. Both of these physicians reported favorable results from this heroic medication, and like results from similar practice have been reported by many subsequent writers. 1 Gaz. Med. de Paris, Nov. 26, 1860, p. 765. 2 British Medical Journal, Feb. 23, 1861, p. 208. TREATMENT. 203 Dr. A. Jacobi ' says, "To be of any efficacy muriate of iron must be given in large doses, frequently repeated. Five to fifteen drops every quarter, half, or every hour is a dose that alone fairly tests the effective powers of the medicine." Dr. J. E. Winters 2 makes the important discrimination that " where there is marked sepsis and tendency to capillary haemorrhages the dose should be larger than in a case of a less septic and more marked inflammatory character," and recommends that in the former type of the disease at least one drachm of the tincture should be administered every hour to a child two to five years old. In those cases in which a marked tendency to septic poi- soning" is manifested the use of the drug should, if necessar}^, be pushed toward the limit of tolerance, and from one to three ounces daily may succeed where less would fail. But such heroic dosage is, in actual practice, especially in the treatment of young children, attended with grave difficulties, and is for- tunately in the great majority of cases unnecessary. When other appropriate treatment is employed, from one and a half to three drachms of the tincture of iron given daily will usu- ally have the desired effect. It has also been considered necessary by some that the tincture of iron be administered in concentrated form. While this may doubtless enhance its beneficial local effect in some cases, it may have an irritating effect in others. But the great objection to administering it in this form to children is the fact that its unpleasant acrid and styptic taste, and the smarting which it often occasions is very liable to arouse their violent opposition to taking it and necessitate struggles, the undesirableness of which has already been alluded to. That this is no merely fanciful or unusual result I know from obser- vation in many cases. The evil referred to may be obviated in most cases by giving the tincture of iron in six or eight parts of glycerine. (See formula page 220.) 1 American Journal of Obstetrics, 1875, p. 660. 2 Loe. cit. 204 diphtheria; its nature and treatment. Quinine. Quinine lias been much employed in the treatment of diph- theria as an antiseptic, an antipyretic and a tonic. It hinders the growth of anthrax bacilli in a solution of the strength of -g^- and prevents it in that of -^j. It may doubt- less exert a valuable local antiseptic action, but is inferior in this respect to other agents which are less disagreeable to the taste. High temperature is generally limited to the early and in- flammatory stage of the disease, and then other measures for reducing it are more efficient and appropriate than antipyretic doses of quinine. For tonic effect in the later stage of the disease, and in the period of convalescence, quinine, in doses of from half a grain to a grain or two, three or four times a day, or the compound tincture or wine of cinchona, or the elixir of calisaya, may be very useful. The unpleasant bitterness of quinine and its consequent tendency to excite nausea are important obstacles to its use in the treatment of diphtheria in young children. Alcohol. The antizymotic and antiseptic actions of alcohol are well known. It hinders the growth of anthrax bacilli in a dilution of 1 : 100, and prevents it in that of 1 : 12.5. Its main utility, however, in the treatment of diphtheria probably results from its assisting to maintain nutrition and opposing the tendency to adynamia and heart-failure by its action as a food and a stimulant. The principal indications for its use are the following : When milk or other food is refused by the patient or taken only in insufficient quantities, the addition of a little brandy or wine will sometimes cause it to be relished and taken more freely and will also promote its digestion. TREATMENT. 205 In marked depression of the vital powers from the com- bined effects of fever, prolonged suffering-, fatigue, loss of sleep, and an insufficiency of nourishing- food, even if the symp- toms of septic poisoning are absent, alcoholic stimulants, care- fully and moderately administered, may have a valuable sus- taining effect, as in other diseases. At the first appearance of symptoms which denote consti- tutional poisoning by the septic products of the disease, such as pallor with weakness, enfeebled heart-action, etc., alcoholic stimulants should be administered. The quantity and fre- quency of the doses must depend on the gravity of the symp- toms, the effect of the remedy in controlling them, and the tolerance of the stomach. The symptom to be especially regarded is the pulse. If that be feeble and • unduly slow or rapid or irregular the amount of stimulant given must be increased, if possible, until its favorable effect is manifested. Intoxication in the ordinary sense of the term is not usually produced under these circumstances. The amount given must often be large, and may sometimes be heroic. I have in many instances given three or four ounces of brandy or whiskey daily in teaspoonful doses, well diluted, every hour or half hour to children under five years of age, without injurious effect, and in some cases with evident benefit. I have repeatedly seen it given in more than twice that quantity, but although favora- ble results are reported from this use of it where less has failed, I have never seen an instance of them. Brandy or whiskey may be given in the form of milk punch or made into a toddy or diluted with carbonated waters; or egg-nog or wine-whey, or Malaga, Burgundy or port wine may be more acceptable to the patient, and sometimes cham- pagne has a particularly good effect. The most important limitation to the giving of alcoholic stimulants in diphtheria results from the intolerance of them by the stomach. When in every form they are found to excite repugnance or nausea and to thus prevent the taking of other 206 diphtheria; its nature and treatment. food, persistence in their use can only be injurious. The pos- sibility of causing subacute gastritis by giving too strong and too frequent doses of alcoholics should not be forgotten. " Sometimes when given very freely to support the failing cir- culation, they have this effect, the result of which is that both food and stimulants are vomited, and the patient is brought to death's door." (Brunton.) In view of the close sympathy which is well known to exist between the condition of the stomach and the function of the heart through the nervous system, it is evident that the irritation or overtaxing of the former by too heroic stimulation may inhibit the latter, and thus produce the very condition of heart-failure which it was intended to prevent. The indications for the use of alcohol which have been stated by no means justify its indiscriminate use in the treat- ment of diphtheria. It is not called for in the early stages of most cases. It is in no sense a specific for diphtheria. It should be remembered that when it is used without indication or in excess of the quantity indicated, though it may in some cases be well tolerated, it is yet a poison. It is especially liable to be so to the dehcate organizations of children. "Ab- sorbed into the blood it lessens oxidation, and will conse- quently diminish oxidation in the tissues." (Brunton.) " In cer- tain circumstances, such as febrile diseases, it may be a very useful food; but in health, when other foods are abundant, it is unnecessary, and as it interferes with oxidation it may be a very inconvenient kind of food." (Ibid.) " By increasing the circulation it may stimulate the functions of all the nerve- centres and render them for the time being capable of greater activity, .... but its action on the nerve-centres themselves is a paralyzing one Its action on the nerve-tissues seems to be one of progressive paralysis." (Ibid.) " In the Ashan- tee campaign the effect of alcohol as a stimulant compared with beef -tea was carefully tested. It was found that when a ration of rum was served out the soldier at first marched TREATMENT. 207 more briskly, but after about three miles had been traversed the effect of it seemed to be worn off, and he then lagged more than before. If a second ration was then given its effect was less marked, and wore off sooner than that of the first. A ration of beef-tea, however, seemed to have as great a stimu- lating power as one of rum, and not to be followed by any secondary depression." (Ibid.) The wise therapeutist, in the treatment of diphtheria, as of other diseases, will reserve this most valuable agent to aid him in tiding his patient over those crises in which its use is definitely indicated, rather than attempt by its early, indis- criminate and excessive administration to prevent their occur- rence — an attempt which will too often tend to defeat its own object. In proportion as other and more appropriate measures for preventing the occurrence of serious septic poisoning' and sus- taining the strength of the patient are early and efficiently carried out, the proportion of cases in which the use of alco- holic stimulants is called for is diminished. I was thus enabled to say in my second report (see page 212 ) : " The large major- ity of cases in the present series, as in those that I have previ- ously reported, have been treated absolutely without them." That the cases of which this could be stated were neither doubtful nor trivial ones was conclusively shown in the re- ports referred to. All my subsequent experience and obser- vation have tended to confirm my belief that in a large majority of all cases of diphtheria which are early and well treated the indications for the use of alcoholic stimulants which have been referred to do not present themselves, and that their use without those indications is not advantageous, but the reverse. Dr. J. Lewis Smith 1 relates the following typical experi- ence : "Although an advocate of the liberal use of alcohol, I cannot regard this agent as a specific. When I commenced 1 Diseases of Children, p. 319. 208 'diphtheria; its nature and treatment. serving- in the New York Foundling- Asylum in May, 1878, the quarantine wards contained four children between the ages of three and five years who had been sick a few days with severe diphtheria, and it was evident at a glance that they must soon perish with the ordinary mild sustaining treatment. Quinine, iron, the most sustaining food and a moderate amount of alcoholic stimulants were being given, and we de- termined to increase the Bourbon whiskey to a teaspoonful every twenty to thirty minutes, day and night. Neverthe- less, whatever the result might have been with the earlier commencement of this treatment, the blood-poisoning was now too profound, and one after the other died." Those who, unlike Dr. Smith, regard the heroic use of alcohol as a specific for diphtheria, explain such failures by the lateness and insufficiency of its administration. I know of no ground for the assumption, either in our knowledge of its action or the statistics of treatment. I have seen quite a number of cases, some of them in my own earlier practice and others in consultation, in which as. free use of alcohol as that just referred to was begun at the outset of grave and malig- nant cases, and failed as signally to arrest the fatal progress of the disease. Our main dependence for effecting that object must be on the early employment of other and more appro- priate measures, to which alcoholic stimulants may often be a most valuable, and sometimes an indispensable, adjuvant. Specifics. Copaiba and Cubebs. Copaiba and cubebs were formerly very extensively used, especially in France, in the treatment of diphtheria. Dr. Trideau x claimed to have employed them with rapidly success- ful effect in more than three hundred cases. The former remedy having been generally abandoned on account of its ir- ritant effect upon the digestive organs the latter continued to J Traitement de l'angine couenneuse par les balsamiques, Paris, 1874. TREATMENT. 209 be much used. It was given in the form of the oleoresin, either in capsules or in emulsion with syrup of acacia, in doses of from 1.50 grammes (22^ minims) to 3 grammes (45 minims) daily. M. Sanne, 1 having employed this treatment in a great number of cases, states that he has never observed from it any well demonstrated action which can compensate for the disgust which it inspires in patients and its tendency to excite purgation. Cardiac Depressants. Veratrum Viride. The employment of depressing remedies, except to fulfill some imperative and temporary indication, is generally con- demned and avoided in the modern treatment of diphtheria. From what has been stated elsewhere (page 71) as to the usual character of the disease in its early stages, it is evident that this exclusion should not be too indiscriminate and arbitrary. The following statements by Dr. J. M. Boyd, 2 of Knoxville, Tennessee, in so far, at least, as they relate to the early stage of certain types of the disease, are worthy of consideration : The characteristic pulse of diphtheria is described as " rapid," " small," " hard," " tense," " wiry." The speedy re- duction of this rapidity to the normal or sub-normal rate has in his experience been followed by the mitigation of the in- flammatory process and the melting away of false membrane. He employs for this purpose the tincture of veratrum viride, commencing with moderate doses, according to the age of the patient, and increasing them until the desired effect upon the pulse is produced. To an adult he gives three drops of Nor- wood's tincture every two hours, increasing by one drop at each dose until the pulse-rate is brought down to sixty or seventy per minute. One child two years of age required five drops and another seven drops every two hours to bring the ! Op. cit., p. 402. 2 New York Medical Record, 1888, 33, p. 627. 14 210 DIPHTHERIA; ITS NATURE AND TREATMENT. pulse under control. When nausea results the dose must be increased cautiously and omitted occasionally. Dr. Boyd re- gards this practice as unattended with danger. He accom- panies it with the use of other appropriate remedies. In proof of its value he refers to his successful employment of it in sixty-seven cases of unquestionable diphtheria, including a fair share of malignant ones. He finds the most probable ex- planation of its efficacy in the view that by slowing the tired heart, it gives the rest which is so important to the recupera- tion of nerve-force. The Treatment of Diphtheria by Irrigation. Dr. G. Guelpa 1 advocates the treatment of diphtheria by the early, persistent, copious and very frequent washing of the parts which are affected by the disease or are threatened with its extension, whether in the pharynx, nares or else- where. The medicinal agent to be employed is a secondary consideration. Mild solutions of the chloride of iron have proved most successful in his hands, but he admits that other solutions, as of lime, carbolic acid or boric acid may be equally serviceable. The fountain-syringe or nasal douche may be used in the milder cases, but when the resistance to the passage of fluid requires it, more forcible methods should be resorted to. The irrigations should be practiced every quarter of an hour by day and every half-hour at night. Dr. Guelpa reports the successful employment of this method in a long series of cases at different periods. The Method op Treatment which has been Employed by the Author. In a paper read before the New York Academy of Medi- cine in March, 1876, 2 I presented statistics of one hundred and 'Bulletin Gen. de Therap., 1887, pages 255, 313, 362. 2 " Diphtheria and its Treatment, with Statistics of One Hundred and Seventy-nine Cases," Transactions of the New York Academy of Medicine, 1876, p. 286. TREATMENT. 211 seventy-nine cases of diphtheria, one hundred and twenty-four of which had been visited by me in the North District of the Demilt Dispensarj^ (the eastern part of the Twenty -first Ward of this chYy) in an epidemic of the disease which occurred in 1875. That the epidemic in that locality had been especially severe was shown in the paper referred to and the subsequent discussion by statistics of the Board of Health and also by the testimony of other physicians. 1 The results of the treatment employed in these cases were that in ninety-eight of the one hundred and twenty-four dis- pensary cases in which it was tested with some degree of fair- ness, though under very unfavorable conditions, there were ten deaths, or about ten per cent. In the remaining- fifty-five cases which were treated by the same method under more favorable conditions by the late Dr. E. J. Darken, Dr. W. E. Bullard and myself, there were only two fatal results. In a communication to the New York Medical Record (January 12, 1878, page 21) I reported the statistics of thirty- seven dispensary cases which had been treated by my assist- ant physicians, Dr. W. E. Bullard and Dr. D. C. Comstock, and myself in 1876 — the results being that in thirty-two of them in which the treatment had been tested with some degree of fairness there had been three deaths, or, again, a little less than ten per cent. That these very favorable results might not be confounded 1 Dr. H. T. Hanks said : " Dr. Billington's success was truly remark- able, for he well knew the type of the disease as it had appeared in the Twenty-first Ward, having had, in his private practice during the last five years in that district, from twenty to thirty cases every year. He knew that many of the cases attended by Dr. Billington had been severe, and not a few malignant. Therefore when the large per cent, of recoveries was considered a cause must be looked for; and he be- lieved that two excellent reasons could be found for this satisfactory result. One was the kind of medicaments used locally and internally, and the other was the great care he bestowed in teaching the parents or nurses the proper manner of administering the remedies presented. This carrying out to the letter every little detail has had much to do, more than many have been led to suppose, in the cure of diphtheria. " 212 DIPHTHERIA; ITS NATURE AND TREATMENT. with the numerous reports of brilliant therapeutical triumphs based on inaccurate diagnosis or the exceptional mildness of the cases treated, I again in 18S0 presented to the Academy a report * of equally good results obtained by the same methods of treatment in forty consecutive dispensary cases, the genu- ineness of which and the severity of a large proportion were kindly attested from personal examination either by Dr. A. H. Smith or Dr. W. T. White, most of the cases having also been seen by a number of other competent physicians. The treatment described in the first of the reports referred to consisted mainly in the use of the tincture of the chloride of iron, potassium chlorate, salicylic acid (in solution with the sulphite of soda), glycerine and lime-water, by frequent in- ternal administration, carbolic acid and lime-water by very frequent spraying, and the thorough cleansing of the nares in nasal diphtheria by syringing them with tepid salt water. Its most essential features are: (1) the most efficient possible local disinfection, (2) without irritation, (3) by frequent appli- cations, which are (4) so pleasant as not to arouse the opposi- tion of children nor unnecessarily to annoy and fatigue older patients, this being accomplished (5) by means of formulas and other details which were precisely stated and their importance insisted on. To avoid unnecessary repetition, these particulars and their application in the treatment of the various stages and forms of diphtheria will be subsequently stated in connection with such additional therapeutical measures as my own later ex- perience and the experience of others have shown to be most worthy of confidence. 2 Those which are now especially referred to may be found on pages 215, 216, 219, 220, 225 and 226. 1 " Forty Attested Cases of Diphtheria, with Remarks on Diagnosis and Treatment," New York Medical Eeeord, March 27, 1880, p. 333. 2 It is proper to state in this connection that Dr. A. Jacobi, in a paper entitled " Contributions to the Pathology and Therapeutics of Diphtheria," which was read before the New York County Medical Society in December, 1874, — more than a year before the reading of my TREATMENT. 2.13 Testimony to their successful employment of this mode of treatment has been given by many physicians either in pub- lished statements or in letters which have been received by me from all parts of this country and Canada. Some of these letters have borne witness to «its efficacy not only in diphtheria as it occurs in this city, but also in malignant epidemics in distant localities. An especially in- teresting- and instructive statement to that effect from Dr. T. Clowes Brown, of Fredericton, New Brunswick, Canada, was published by me, with his permission, in the New York Medical Record, January 12, 1878, page 23. first paper— and published in the American Journal of Obstetrics, vol. vii., page 628, advocated the treatment of the severer forms of diph- theria by large and frequent doses of the tincture of iron ; the treat- ment of "simple tonsillar diphtheria" with "frequent small doses of a chlorate combined with lime-water, or tinct. ferr. mur. 3 ss — 3 ij. a day, and generally mixed with a little glycerine, principally for the purpose of keeping the remedy in longer contact with the diseased surface, if not for its own antifermentative effect ; " and the treatment of nasal diphtheria by thorough cleansing and disinfection of the nares by syringing them every hour or every half hour with " two to four grains of carbolic acid to the ounce of water," or, " where there is no smell, lime-water, pure or somewhat diluted, for its solvent effect." This mention is made proper by the priority of Dr. Jacobi's publica- tion, and the coincidence in our therapeutical recommendations in res- pect to the drugs principally employed and the distinctive principles which I have above enumerated as 1, 2, and 3. In reference to these circumstances I made, in a foot-note to my first report above referred to, the following statement : — " There is, in my opinion, more essential and valuable truth in this little monograph " (Dr. Jacobi's) " than can easily be found elsewhere. It should be care- fully perused by all students of this much perplexed subject. It is pi'oper to state that while I coincide with Dr. Jacobi's views in almost every particular I am not his ' follower,' except in the order of publi- cation. My own pathological conclusions and my present mode of treatment were independently arrived at (as many of my friends know) before his paper was written or I knew anything of its author's views." In the New York Medical Record, Feb. 23, 1878, page 158, I pub- lished a letter from the late Dr. E. J. Darken, who was House-Physician to Demilt Dispensary from 1869 until his death in 1886, which gave precise confirmation to the latter statement. 214 'diphtheria; its nature and treatment. The Treatment of the Early Stage of Pharyngeal Diphtheria. The special indications at this stage of the disease are local disinfection, the subduing- of inflammation and the reduction of fever. The patient should be put to bed in a clean, well- ventilated and yet sufficiently warmed apartment, from which unneces- sary articles of furniture have been removed. If the attack shows a tendency to severity and is attended with marked febrile symptoms, calomel should be given, either in a single purgative dose of from two to ten grains according to age, or, preferably in most cases, in divided doses of from one fourth of a grain to one grain mixed with sugar and placed upon the tongue every half hour, everj^ hour or every two hours, until a purgative effect is produced. Ice in small pieces, or in the form of water-ices, is usually grateful to the patient and should be given frequently, and he should be permitted to drink ice-cold water freely if he craves it. Frequent cool sponging, especially about the head, face and neck, is often soothing and agreeable. If there is a marked tendency to glandular swelling, compresses frequently wrung out of ice-water, or ice-bags, may be applied over the affected region. If the patient is seen at the initial stage of the disease when the false membrane has not yet acquired much thickness or density, and if his age and the accessible location of the affection make it practicable, its abortive treatment may be attempted. The affected spot or spots, having been cleansed by spraying or irrigation and then dried by gently touch- ing them with absorbent cotton, may be carefully touched with a solution of the bichloride of mercury (yoVo to Too) Dv means of a camel's hair brush or a soft swab applied with gentle pressure. This may be repeated every two hours (a mild antiseptic or solvent spray being frequently emplo3 T ed TREATMENT. . 215 in the intervals) if its effect seems to be good, but if, in spite of a few such applications, the local affection increases, its further use should be abandoned as only likely to aggravate the irritation. For the purpose of rapidly dissolving the false membrane solutions of pepsine, trypsin or papain may in some cases be advantageously employed at this stage of the disease by very frequent topical applications or spraying, as has been described on pages 167 et seq. Under the same circumstances the application of various caustic or astringent antiseptic agents, such as the nitrate of silver, the tincture of iodine, concentrated solutions of carbolic or salicylic acid, resorcin or chloral, which have been referred to in the preceding portions of this chapter and the mode of using them described, may doubtless in some cases arrest the disease at its outset. The favorable experience of some in the use of such agents has been stated, and also its limitations and dangers. It has formed no part of my usual treatment. My favorable experience in this use of Monsel's solution or the tincture of the chloride of iron has been referred to, but even that may be ineffective and irritating. If the patient is old enough to permit it, the throat should be sprayed with some mild, solvent, antiseptic and antiphlo- gistic liquid as frequently as is practicable. I know of none which so admirably combines these qualities or has so good an effect under ordinary circumstances as the following mixt- ure: 1 B Acidi carbolici, t\[ x. Aquas calcis, fl. § iv. M. S. — To be applied by spraying for some minutes every half-hour. This mixture has the important advantage of being more agreeable to the patient in its taste and after-effect than any other that I know of. Many children will permit its use that 1 This formula was published by me in 1876. 216 diphtheria; its nature and treatment. would oppose that of any other. The proportions are impor- tant, since the addition of a few drops more of the carbolic acid makes it pungent and disagreeable. That in a solution of this strength ( T | s ) carbolic acid is an efficient antiseptic and antiphlogistic has been shown on page 180. The valuable utility of lime-water has also been shown on page 165. The spray thus administered should be fine, as coarse sprays are unpleasant and irritating to diphtheritica] ly inflamed surfaces. Some atomizers which are now in very general use are ob- jectionable in the treatment of diphtheria for this reason. Fig. 10.— The Delano (No. 558) Atomizer. The Delano atomizer makes a fine spray, and is in every respect a convenient and suitable instrument. All atomizers which throw a fine spray are liable to be ob- structed' by solid particles. Nurses should always be taught how to remove this obstruction by means of the fine wire which comes in the box with the atomizer, or with a bristle. When the Delano atomizer cannot be obtained, the Davidson instrument will serve a very good purpose, and has, indeed, some special advantages. The point of the atomizer should not usually be thrust into the throat of the patient, but should be held several inches TREATMENT. 217 from the open mouth. The spray is thus diffused over the whole surface of the palate and pharynx. In most cases in which the mouth is opened widely, the spray, if good aim is taken, reaches the pharynx freely. In some cases, however, it is necessaiy to carry the point of the atomizer further back over the tongue or to depress the tongue. The patient, when old enough, can usually he taught to do this, using a tongue- depressor in which the handle is at a right or obtuse angle to the blade. Nurses or parents must always be carefully in- structed in the proper use of the atomizer. Other mild antiseptic sprays may render valuable service in cleansing and disinfecting the mouth and throat, as, for in- CAVIDSON RUBBER CO. DAVIDSON RUBBER CO. Fig. 11. — Davidson Anatomizer, No. 59. Fig. 12. — Davidson Anatomizer, No. 6. stance, solutions of permanganate of potassium (3 to 5 grains to the ounce), peroxide of hydrogen (one in four of water), bichloride of mercury (one in 4000 to 10,000), borax or boracic acid (one to three per cent, solution), salicylic acid (one in 500 to 2000), etc. The special utilities and drawbacks of these and other valuable substances, and also the manner in which they may be employed, have already been stated. "When the solvent ferments are applied by spraying, the point of the atomizer should be carried nearer the membrane to be dissolved than has been directed in other cases, that the solvent may be concentrated upon it. When the patient is too young to voluntarily permit the use of the spray (most children over three j^ears of age can 218 diphtheria; its nature and treatment. with tact be taught to take the pleasant one I have described) its use should not he attempted, and reliance must be placed on internal administration and irrigation. Mild antiseptic washes can be applied by the latter method when their use is indicated by the presence of viscid and offensive secretions in the mouth and throat. A hard -rubber syringe with a straight, slender, and smoothly rounded tip should be used. According to the valuable suggestion of Dr. Gruelpa 1 it is not necessary to force the teeth open, but the tip of the syringe may be slipped between the teeth and the cheek, toward the angle of the jaw, and fluid injected will freely enter the mouth and pharynx behind the last molars. The utmost gentleness should be observed in doing this ; it should not be repeated oftener than once in two or three hours, and never unless it is indicated by the presence of offending material which cannot be otherwise readily dislodged. I once shared the enthusiasm of Dr. Guelpa for the treatment of pharyngeal diphtheria by irrigation, but my own further experience has been that while it has valuable uses, it may easily be made excessive, irritating and injurious. Warm salt-water (one drachm to the pint) or either of the mild antiseptic solutions just referred to is a suitable liquid to employ. The necessary cleansing of the throat may usually be ef- fected by the frequent internal administration of suitable remedies. Internal Medication. — Antipyretics. — It should be remem- bered that high fever at this stage of the disease in primary and uncomplicated cases is the concomitant of the inflamma- tion, and that its reduction is to be sought mainly by the em- ployment of the antiseptic and antiphlogistic measures which have now been referred to. When it is excessive and persist- ent I know of no antipyretic drug which will usually, according to my experience, yield such satisfactory results as the sali- cylate of soda. It may be given in doses of from two to fifteen ! Op. cit. TREATMENT. 219 grains in from a teaspoonfnl to a tablespoonful of water hourly or every two hours, according- to the age of the patient and the degree of fever, which doses may be increased, diminished or discontinued according to the effect produced. With a suit- able diet its tendency to excite nausea will not often be mani- fested, and this may be further counteracted by adding- to each dose of the solution, when given, an equal quantity of cold Vichy or seltzer-water from a siphon -bottle. If the patient is robust, aconite, in doses of a fraction of a drop of the officinal tincture every half hour or oftener may sometimes be advantageously given for a short time at this stage of the disease. In case the salicylate of sodium is not tolerated or proves ineffective, antipyrin or antifebrin may be resorted to if its effect is urgently called for. The former may be given in doses of one and a half grains for every year of the child's age, every hour for three times, if necessary, and the latter in one fourth of these doses. I have never found the use of either of these drugs necessary except in diphtheria complicating or following scarlatina. Cold or warm sponging is often a useful and agreeable adjuvant. Quinine in antipyretic doses is rarely if ever appropriate in the early stage of diphtheria. In the great majority of cases I prescribe from the outset the chlorate of potassium and the chloride of iron. The utility of these drugs has been remarked upon on pages 191 and 200. I have most usually prescribed them separately and in alternation in the following mixtures, 1 which are espec- ially appropriate and pleasant, and are usually readily taken by young Children : No. 1. 1> Potassii chloratis, . . . 3ij. — 3iv. Glycerini, fl. § ss. Aquge calcis, fl. § iijss. M. S. — A teaspoonful every hour. 1 These formulae are identical with those published by me in 1876. 220 diphtheria; its nature and treatment. No. 2. IJ Tinct. ferri chloridi, . . fl. 3 ij. — 3 iij. Glycerini, . . . . fl. 3 ij. Aquas, .... ad. fl. §" iv. M. S. — A teaspoonful every hour. Number two is given in half-hourly alternation with num- ber one. The weaker form should generally be used for chil- dren under three years of age. Or the two drugs may be thus combined : No. 3. 5 Tinct. ferri chloridi, . . fl. 3 ij. — 3 iij. Potassii chloratis, . . , 3ij- — 3iv. Glycerini, fl. § ij. Aquae, .... ad. fl. 3 iv. M. Dose, a teaspoonful every hour, or every half -hour. The proportion of glycerine in these formulae is important — especially in the treatment of children — not merely for its demulcent and slightly solvent action, but mainly for its cov- ering the unpleasant acridity of the tincture of iron. The indications for discontinuing or increasing the doses of the tincture of iron have been pointed out on pages 201 and 202. "When it is desired to increase them, this should be done, in the case of children, not by increasing the proportion of iron in the mixture, but by giving larger quantities of the mixture at a dose, and at shorter intervals. In some cases the use of the following mixture * at an early stage of the disease has seemed to have a particularly good effect in causing the rapid disappearance of membrane and reducing fever : IJ Acidi salicylici, .... gr. x. — 3j. Sodae sulphitis, .... 3 ss. — 3 j. Glycerini, fl. 3 ss. Aquas, fl. § ijss. M. S. — A teaspoonful every hour. 1 This formula was published by me in 1876. TREATMENT. 221 In this solution the antiseptic action of the salicylic acid is retained. It may be given instead of number one in half- hourly alternation with number two or number three. I have used it only during' the first two or three days of the disease. Number one is usually to be preferred in the case of young children. The bichloride of mercury may be given in connection with the treatment already described. Its valuable effect is un- doubtedly the greater the earlier its use is begun. Its use is not indicated in mild cases of simple pharyngeal diphtheria, but is appropriate in the early stage of severe ones, and es- pecially in those in which laryngeal implication is threatened, either by the symptoms of the patient or the character of the prevailing epidemic. Its special utility and dangers and the va- rious modes of administering it have been referred to on pages 175-177. It should, under the circumstances now considered, be given in doses of from T fo to -^ of a grain, according to age and the severity of the disease, hourly, in at least a dessert- spoonful or a tablespoonful of water, milk or other beverage, or, preferably, in many cases, according to the experience of Dr. F. Huber, in half these doses half-hourly. Or, to avoid the unnecessary multiplication of doses, it may be added to formula number two or number three, as in the following pre- scriptions : IJ Hydrargyri bichloridi, . gr. j 2 ^ — gr. -£$. Or, P> Tinct. ferri chloridi, . . fl. 3 ij. — 3 iij Glycerini, . . . fl. iij. Aquas, ad. fl. 3 iv. M. Hydrargyri bichloridi, cry 2 T-p 3 Tinct. ferri chloridi, . fl. 3 ij. — 3 iij. Potassii chloratis, . 3iv. Glycerini, . fl. iij. Aquas, . ad. fl. 3 iv. M. 222 diphtheria; its nature and treatment. From one one-hundred-and-fiftieth to one one-hundredth of a grain of the bichloride is thus given in each teaspoonful. From one to two teaspoonfuls may be given hourly or half-hourly. It should preferably be given after the taking of food or drink. It cannot be too often repeated that its effect must be care- fully watched. Its use should not ordinarily be continued longer than three or four days. The strong evidence in favor of the valuable utility of the internal use of oil of turpentine has been referred to (see page 194). That I have never employed it is due to my aversion to the use of measures in the treatment of diphtheria which are in themselves repugnant to the patient, and tend to produce nausea and disturbance of the digestive functions. Since it need usually be given only once a day it must be admitted that this objection thereby loses much of its force. Its special applicability seems to be/ like that of mercury, rather to the more superficial or " fibrinous " rather than the deeper or " phlegmonous " form of the disease, and consequently to laryn- geal rather than pharyngeal diphtheria. Its most valuable effect is obtained from its early employment. The usual dose is from a teaspoonful to a tablespoonful in milk or emulsion. Various other remedies which have been referred to and the manner of employing them described on preceding pages of this chapter may be internally administered or locally applied at this stage of the disease with valuable effect, such as the cyanide or the biniodide of mercury (see page 17?), sulphur, sulphurous acid, the hyposulphite of soda (pages 182 and 183), iodine (page 185), iodoform (page 186), chloral (page 187), benzoate of sodium (page 190), peroxide of hydro- gen (page 188). One or another of these drags may doubtless in some cases be advantageously substituted for, or used in connection with, those which have now been especially recommended; but it is important to remember that the undue multiplication of rem- edies is particularly undesirable in the treatment of diphtheria, TREATMENT. 223 and that from among- those which promise equal efficiency the one which is the most pleasant to the taste, the most accepta- ble to the stomach, and the least irritating- in its local effect should always be chosen. The diet in pharyngeal diphtheria should always consist of liquids or semi-solids. In the early stage of the disease it should be bland and simple, but nutritious. Milk has been my principal reliance in the great majority of cases, especially of children. It should be given, if possible, in the quantity of from four to six or eight ounces every two hours, but when only smaller quantities can be taken at once the frequency with which it is given must be proportionally increased. The physician must himself realize, arid impress upon his patients and nurses, that the taking- of sufficient nourishment is a matter of prime and vital importance. It must be insisted on, however difficult and painful the' effort of swallowing may be. The ingenuity and perseverance of the physician and the nurse must often be exerted to the utmost degree to effect this object. Even when the act of swallowing is most painful and repugnant to a child, he can usually be induced to take a little milk or other food after each dose of medicine or spraying of the throat or syringing of the nose. If milk is rejected by the stomach, the addition to it of lime-water in smaller or larger proportions, up to one-half, will often have a good effect. It may sometimes be advanta- geously alternated with beef, mutton or chicken-tea, or oyster or clam-broth. Though abundant nutrition is imperatively demanded in diphtheria, it is a serious error to overload the stomach with rich or concentrated foods during the febrile stage of the disease. In those cases in which milk is unfort- unately not tolerated, it may sometimes (though too rarely) be made available by peptonizing it, or koumyss may be a valuable resource, or the addition to milk of a little brandy or whiskey with or without sweetening may furnish the solution to the problem. When milk in no form is tolerated the reli- 224 DIPHTHERIA; ITS NATURE AND TREATMENT. ance must be on farinacious gruels, meat-teas, juices, extracts and broths, beef-peptones, light custards, egg-nog, etc., the skill of the nurse in such devices being an important element of success. All other methods failing, nourishment by the rectum is indeed a resource — but a desperate one. The use of alcoholic stimulants is not usually indicated in the earlier stage of pharyngeal diphtheria, except under the circumstances and in the manner just referred to. In excep- tional cases in which the strength of the patient has been re- duced by previous illness, or in those malignant types of the disease in which septic poisoning with its depressing constitu- tional effects is evident from the first, the indication for their use is obvious and imperative. In order to economize to the utmost the strength of the patient, the administration of medicines and nourishment, which, in the treatment of diphtheria, is necessarily frequent, should be as systematic and reg-ular as is practicable, and should be so arranged as to give the patient the longest possi- ble intervals of rest between them. The giving of medicine, the use of the spray, and the taking of nourishment should for this reason usually come in immediate succession (though sometimes in the opposite order), that the remainder of the half-hour may be appropriated to rest. But the patient must be promptly aroused at its termination, and this punctuality and regularity must be insisted on, except at night, when an hour's undisturbed sleep may in most cases be occasionally permitted. In order to secure the cooperation of tender hearted parents in this apparent cruelty, it is important to strongly impress upon their minds its absolute necessity. The Treatment of Nasal Diphtheria. As nasal diphtheria is a very frequent complication of the more serious forms of the pharyngeal affection, its treatment should be considered before proceeding to that of the later stage of the disease. TREATMENT. 225 From the special danger of septic infection which attends this form of diphtheria, results the imperative indication of the cleansing* and disinfection of the nasal passages. It is essential that the physician realize that this is to be effected, not by the introduction into them of a little mildly antiseptic fluid, but by the most thorough removal from them of their poisonous contents which is practicable. It is also highly im- portant that this be accomplished with the least possible irri- tation, annoyance or fatigue. The instruments which may be employed for the purpose are the syringe or douche or the nasal atomizer. The use of the latter requires for its efficiency a coarse spray forcibly driven, the effect of which, in the treatment of diphtheria, is at once more irritating- and less thorough than that of a stream from a syringe properly used. The syringing of the nares is necessarily somewhat un- pleasant to the patient, and usually provokes the violent re- sistance of young children. When bunglingly performed it may be most distressing, ineffective and injurious. The struggles of young children and the consequent danger of exhaustion and injury are best prevented by the well di- rected use of overmastering force combined with manual dex- terity and gentleness. Much experience has taught me the advantages of the following method : The assistance of two persons is required. The child is seated across the lap of one of these persons, who secures his hands with one of her own, and with the other holds a basin to receive the discharge. The other person stands behind the child, takes his head between the palms of her hands, and, leaning forward, holds it firmly against her breast. A third person who should, when possible, be a physician, can then easily make the injection into the child's nostrils without dan- ger of injury to them by its sudden movements. When the child is thus firmly held, or in the case of older patients, any small syringe will answer in careful and skilful 15 226 diphtheria; its nature and treatment. hands; but under other circumstances one should be used which has a blunt and soft tip. It should also have a ring" in the handle, that it may be conveniently manipulated by one Fig. 13.— Manner of Holding a Child for Nasal Syringing. hand. The hard rubber half-ounce ear-syringe is in most re- spects a very suitable instrument; but its tip should either be cut off, as Avas suggested by Dr. S. W. Smith, 1 or, still better, should be padded, — a device which was recommended by Bre- 1 New York Medical Record, 1886, 29, p. 354. TREATMENT. 227 tonneau. 1 This is easily clone by surrounding it with absorb- ent or other cotton and fastening- over this a perforated piece of rubber-cloth, oiled silk, chamois-leather or muslin, as is Fig. 14.— Hard Rubber Half-Ounce Ear-Syringe. (Reduced Size.) I Fig. 15. — Ear-Syringe Padded. shown in figure 16. As this requires but a moment, the pad- ding- may be changed after each syringing. A glass syringe expressly designed for this purpose, the Fig. 16. — Peerless Syringe, No. 4. nozzle of which is protected by a covering of soft rubber, is manufactured by R. Van der Emde, 323 Bowery, New York, and is called " Peerless Syringe, No. 4." Fig. 17.— Universal Syringe. An instrument which will serve very well in most cases is the "universal syring'e" made by Tiemann & Co., which is en- tirely of soft rubber. 1 Fifth Memoir. 228 diphtheria; its nature and treatment. Warm salt-water (one drachm to the pint) is admirably suited to the purpose. The addition to it of bichloride of mer- cury (one grain to the pint) or of borax (one or two drachms to the pint) or of salicylic acid (four grains to the pint) is re- garded as an improvement by some. The fluid should be thrown with force enough to make it flow out, partly by the other nostril and partly by the throat, if the passages are pervious. If they are not so, more forcible injections may be employed, and these, with a little persever- ance, will usually succeed. Undesirable as these may seem, the removal of the obstructing mass should be regarded as imperative. Tearing away or boring through the membrane should not be resorted to on account of the great danger of its causing epistaxis. The very frequent application of pepsin, trypsin or papayotin by means of a medicine-dropper may be of service in very obstinate cases. The injections should be repeated on each occasion until the passages are thoroughly cleansed. From two or three to five or six applications to each nostril are usually sufficient to ac- complish this. When the operation is thus thoroughly performed, I have found by experience in many cases that its repetition from two to four times in the twenty-four hours is usually sufficient to secure the desired effect. Its repetition with unnecessary frequency is to be deprecated, since it is more or less unpleas- ant and irritating and consequently fatiguing, even to adults, from the especial susceptibility of the nasal mucous mem- brane, and much more so to children who have to be coerced, and in the treatment of bad cases of this disease the strength cannot be too carefully economized. When it is only partially or imperfectly done, as it must be by only a single injection into each nostril on each occasion, as is practiced by some, it of course becomes necessary much oftener. When the syringing of the nares has to be entrusted to nurses, they must be carefully instructed by the physician as TREATMENT. 229 to all its details, such as the angle (more nearly horizontal than perpendicular) at which the syringe is to be introduced, etc., and even then he will too often have the pain of finding- that it has been very imperfectly or badly executed. I have dwelt at such length on the details of nasal syring- ing, because, whatever may be thought of the utility of vari- ous other therapeutical measures in the treatment of diph- theria, there can be no doubt that upon this one the saving of many hundreds of lives every year directly depends. If it is neglected in severe cases of nasal diphtheria the patient is almost sure to die; if it is efficiently performed the greater proportion recover. The Treatment of the Later Stage of Pharyngeal and Nasal Diphtheria. The special indications for treatment in the later stage of diphtheria are : 1. To continue local measures for antiseptic effect. 2. To counteract the effects of constitutional poisoning. 3. To sustain the strength of the patient. 4. To appropriately deal with complications which may arise. In a large majority of all cases which have been treated early and efficiently by the methods already described, the disease will have been so favorably modified by them, in limit- ing the extension and moderating the intensity of the local affection and preventing or minimizing the absorption of poison, that they may be without difficulty conducted to com- plete recovery, after a duration of from four to twelve days, by the continuance of the mild solvent and antiseptic local treatment, the internal administration of chloride of iron and the chlorate of potash and the measures for nutrition and rest which have been recommended. In a much smaller proportion of cases, which, however, 230 DIPHTHERIA; ITS NATURE AND TREATMENT. varies considerably in different epidemics, in which the disease is from the outset of especial severity or malignancy, and of the deeply infiltrated or " phlegmonous-septic " type, and in other cases in which treatment is begun only at an advanced stage of the malady, an arduous and prolonged conflict with it is yet to be waged. At this stage in such cases, hyperpyrexia has usually dis- appeared along with the acute intensity and tendency to rapid extension of the local inflammation, and evidences of constitu- tional or septic poisoning present themselves. It is of the utmost importance that the physician realize that his chief resource in order to prevent the system being fatally overwhelmed by this poison is in diminishing the amount introduced into the circulation by the most thorough possible cleansing of the sources from which it is absorbed. The means for effecting this object, namely, washing them with suitable antiseptic solutions, applied by internal admin- istration, spraying and irrigation, have already been described. If they are neglected or only inefficiently employed, it will too often be found that no amount of stimulation or other internal medication will avail to save the patient. I have in many instances, after beginning the treatment of a case at this stage of the disease, seen the pallor and sallow- ness of the skin soon replaced by natural tints, apathy and somnolence disappear, nausea and vomiting cease, the dull eye become bright, the feeble and flickering pulse become full and regular, simply or mainly from the effect of these meas- ures. In some of them heroic stimulation and medication, previously employed under other direction, had failed to pro- duce an} r favorable effect. This good effect is often manifested in spite of the persist- ent presence of quite extensive membranous deposits. In this case the effect of the antiseptic washes is doubtless exerted not only by their removing from all the surfaces much poison- ous material which would otherwise be absorbed, but also by TREATMENT. 231 their penetrating" in some degree the false membrane itself, and thus causing, by osmotic action and the interchange of fluids, more or less diminution, dilution and disinfection of the noxious products of the disease lying beneath it. The denser and thicker the false membrane is, the less, of- course, can the latter effect be produced. Hence the difficul- ties in the way of thorough local disinfection are often very great and sometimes insuperable, especially in the cases of young children. When masses of thick membrane oppose it, these may, if accessible, be softened and thinned by the fre- quent application of the solvents which have been referred to, or in some cases by the careful application of such agents as MonseFs solution, which tend to shrivel and disintegrate them and restore tone to the relaxed and infiltrated tissues. Adenitis, in such cases, often presents a serious obstacle to antiseptic endeavors, since the diphtheritically inflamed glands are in themselves inaccessible foci of infection. In the treat- ment of this complication, it must still be remembered that the first indication is by the local antiseptic measures just re- ferred to, to prevent or limit the absorption of more poison through the lymphatics into the glands. The adenitis itself may be let alone or treated with cold or warm applications. If there is febrile temperature and the adenitis is increasing, ice-bags may be applied. If the adenitis is no longer increas- ing and is not especially annoying, it is best let alone. If, in the later stage of the disease, the tumors are large and painful or show a tendency to suppuration, they should be treated with warm poultices. The application of ointments of iodine or iodoform or mercury is probably useless. All irri- tant applications to the skin should be avoided. The applica- tion of the linimentum belladonna?, mixed with half the quan- tity of glycerine, has in some cases seemed to me to have a soothing and beneficial effect. The second and third indications above referred to, though distinct, are yet to be mainly fulfilled by the same means, 232 diphtheria; its nature and treatment. namely, the chloride of iron, abundant nourishment, alcoholic stimulants and appropriate tonics. The pre-eminent utility of the chloride of iron in enabling' the system to withstand the effects of diphtheritic poisoning- has been remarked upon on page 200. When this condition is present it must be freely administered. Formula number two (page 220) should be used, and of this mixture from one to two teaspoonfuls may be given every half-hour, according to age and tolerance, or in very urgent cases, every twenty minutes. The maintenance of abundant nutrition is of primary im- portance. Not only is this essential for sustaining the strength, but it is practically an antiseptic measure, since the less is the suppty of nourishment to the system, the greater is the ab- sorption of poison. If milk is freely taken it is still the most suitable food, but, in view of the tendency to the failure of strength, more stimulating articles may often be advanta- geously added to the dietary. Among the most useful of these is the freshly expressed juice of underdone beef in small quantities, or Valentine's beef-juice. Concentrated and pre- digested food-preparations, such as the various "beef-pep- tones," "liquid peptonoids," etc., may often be serviceable. Other suitable additions to the dietary have been already re- ferred to (page 223). Discretion in the administering of rich or concentrated foods is, however, very important, since the digestive function too often shares in the general enfeeble- ment, and may be easily deranged. Excessive or injudicious feeding may thus defeat the very object for which it is em- ployed. Alcoholic stimulants are required in most bad cases at this stage of the disease, and must in many cases be given freely. Their utility in the treatment of diphtheria, and its limitations, have been remarked upon on page 203 et seq. Valuable assistance in promoting appetite and digestion and combatting the tendency to debility which attends the later stage of diphtheria and the period of convalescence, may TREATMENT. 233 be obtained from various tonics, especially the preparations and alkaloids of cinchona bark and mix vomica. Among standard preparations, the compound tincture of cinchona or the elixir or wine of calisaya, the elixir of pepsin, bismuth and strychnine, the elixir of the phosphates of iron, quinine and strychnine given in doses appropriate to the age, have obvious applications and utilities in this as in other diseases. The same in true of quinine in tonic doses of from one fourth of a grain to two grains three or four times a day. I have been enabled to obviate the important difficulty arising from its unpleasant bitterness in many cases of young children by the use of chocolate lozenges, each of which contains one grain of the tannate of quinine, and which are prepared by Caswell and Massey of this city. They are generally liked by children. Quinine may also in many cases be advantageously adminis- tered to young children in rectal suppositories. Two or three grains of the sulphate of quinine in five or six grains of the butter of cacao in each suppository is a convenient size. Their introduction is facilitated by the use of a small hard-rubber tube-and-piston depositor which is made for the purpose. In conditions of extreme debility with accompanying pro- gressive heart-failure, alcoholic stimulants given freely, but with careful regard to the limit of their tolerance by the stom- ach, are our most valuable resource. If the pulse is feeble and rapid or irregular, the tincture of digitalis may be given in small doses, the effect of which is to be carefully watched, and strychnine in small doses (from -^ to 3V of a grain) may be useful. Except in the case of very sensitive children, to whom the shock and fright caused by the operation may be injurious, the hypodermic administration of either of these remedies is to be preferred on account of its more prompt and certain effect. Freshly made coffee in teaspoonful doses may also be serviceable. Fresh beef-juice in similar doses may have a val- uable stimulant effect. The predigested foods already referred to may be useful aids in maintaining nutrition. The great 234 diphtheria; its nature and treatment. importance of the most abundant supply of fresh air should never be forgotten. If such bulky and unpleasant drugs as musk are employed in the case of children, their administra- tion by enema is for obvious reasons to be preferred. The patient must be strictly kept in the recumbent posture and all unnecessary exertion and agitation avoided. The mere fact of the occurrence of albuminuria does not ordinarily call for special treatment. Indeed, since its pres- ence at this stage is usually the result of the irritation of the kidneys by the noxious products of the disease which have been absorbed into the general circulation; the indication which it furnishes is the continuance of the antiseptic and sustaining measures which have been already referred to. The same indication remains equally in force in those graver forms of the affection in which the urine more or less suddenly becomes scanty and dark and of high specific gravity, and contains a large percentage of albumin with casts and blood-corpuscles, with accompanying febrile symptoms and marked evidences of ursemic poisoning; but the complication itself is so liable to be rapidly fatal, that prompt measures must be employed for its removal. These measures are the same as when nephritis occurs in other conditions, but the weakness and prostration of the patient often make their energetic employment impracticable. In cases in which this weakness and prostration are not too marked for its use to be admissible, and especially if the bowels are constipated, purga- tion by a single dose of from one to five grains of calomel or by doses of a quarter of a grain given in frequent succession or by a grain of calomel with from six to ten grains of com- pound jalap powder to a child from three to five years old, or to feebler patients a wine-glassful of citrate of magnesia re- peated every hour or two if necessary, will often have a promptly favorable effect. Dry cups may be applied over the kidneys. The mode of producing at once a revulsive and diaphoretic TREATMENT. 235 effect which I have found especially valuable in many cases of scarlatinal and diphtherial nephritis is to envelop the entire circumference of the loins and abdomen with a warm flax-seed poultice, which should be frequently renewed. The use of the ordinary diaphoretic and diuretic drugs is often impracticable on account of the tendency to nausea and vomiting- and the weakness of the patient. Digitalis may be given in the form of the infusion with citrate or acetate of potash if the stomach will retain it; but otherwise in the form of the tincture, of which a suitable dose may be added to other medicines or administered hypodermically. Throughout the entire treatment of a case of diphtheria, great importance should be attached to maintaining the strict- est cleanliness of the patient himself and all his surroundings. His clothing and the bed-linen should be frequently changed and thorough disinfection of all vessels and utensils practiced, as directed in the chapter on prophylaxis. The room should be frequently and thoroughly aired. In order that the patient may not take cold while this is being done the alternate use of two adjoining rooms, when practicable, is an advantage in the colder season of the year. In some persistent cases the removal of the patient to a fresh apartment has seemed to exert a favorable influence. When the climate and other cir- cumstances make it practicable, the patient may sometimes be advantageously kept in the open air. The Treatment of Laryngeal Diphtheria. Medical Treatment in reference to laryngeal diphtheria is (1) preventive and (2) mitigating or curative. The liability of pharyngeal and nasal diphtheria to extend downward into the larynx, especially during the first few days, suggests the employment of measures in their early stage which may diminish that liability. These measures are : 1. Those which tend to moderate the intensity and check the spread of the primary affection, since that result diminishes 236 DIPHTHERIA; ITS NATURE AND TREATMENT. the probability of its extension into the larynx. These meas- ures have already been referred to. In the treatment of young- children all irritating- applica- tions and unpleasant remedies which cause crying and strug- gling are especially contra-indicated, since in such crying and struggling the irritating drug or diphtheritic matter is liable to be drawn into the larynx and favor the extension of the disease thither. 2. Those which have a special tendency to prevent laryn- geal implication. — These measures are the inhalation of un- irritating antiseptic and astringent spray or vapor and also the internal use of certain drugs, especially mercurials and the oil of turpentine. These have also been referred to in connec- tion with the treatment of pharyngeal diphtheria. My own experience of the valuable effect of this use of the spray of carbolic acid and lime-water was stated in my first published report as follows : " Out of fully one hundred cases, including Dr. Darken's, in which the spray of carbolic acid and lime-water has been employed, there has been no instance of the subsequent occurrence of serious laryngeal complication, though in several of them it has been threatened by croupy cough, hoarseness and aphonia. That the inhalation of the spray has acted as a preventive in some of these is, I think, not improbable." Much subsequent experience of myself and others has confirmed me in this belief. The composition of this spray and the mode of using it have been stated on page 215. In the case of children too young to take the spray, the in- halation of antiseptic vapor, especially that of the oil of tur- pentine, may be employed as a preventive. Mitigating and Curative Measures. — The earliest possible recognition and treatment of laryngeal diphtheria is of great importance. The physician should pay careful attention to the slightest huskiness or hoarseness of the voice which may be its premonitory symptom. Many cases may doubtless be cut short or prevented from becoming severe when properly TREATMENT. 237 treated at their first slight beginning's, which would later defy all remedies. When the symptoms of laryngeal diphtheria are present the measures to be employed depend somewhat upon their gravity and the rapidity with which they increase. In esti- mating at the outset the probability of their becoming severe, the fact elsewhere referred to may be remembered, that as a general (though not invariable) rule this probability is greater the earlier the laryngeal affection appears. The remedies which may be employed comprise mercurials, solvent, antiseptic and astringent sprays and vapors, steam, expectorants and emetics. The mildly solvent and antiphlogistic effect of the pleasant spray of carbolic acid and lime-water has been found sufficient in quite a number of cases of slight or moderate severity. In my first paper 1 I reported in detail a case of unquestionable laryngeal diphtheria accompanying pharyngeal diphtheria in a child of four years, in which very serious and constant dyspnoea in both acts, with marked depression over the clavi- cles with inspiration, continued for eleven days, but which finally recovered without operation under the very frequent use of this spray. I have since seen several almost as striking cases of recovery under the use of the same remedy. The fact has been referred to that the solvent power of lime-water may be increased by adding to it another alkali, as, for instance, one per cent, of liquor potassa?, or bicarbonate of soda, but at the expense of making its frequent and contin- ued use somewhat irritating to mucous membranes. Hence this method should be employed only where the necessity for a rapid solvent effect is urgent. The testimony in favor of the utility of trypsin and papay- otin as solvents of false membrane has been referred to, and the manner of employing them has been described on pages 168 and 169. The solution should be carefully prepared by transactions of N. Y. Academy of Medicine, 1876, p. 210. 238 DIPHTHERIA; ITS NATURE AND TREATMENT. rubbing- the solvent in a mortar and, if necessary, afterward straining- it, so that a fine spray may be used, and the solu- tion should be of the most unirritating character, so as not to excite cough and dyspnoea. It must be remembered that the spray can effectively reach the interior of the larynx only by being carried thither by the inspired air. The atomizer should therefore be held at some little distance from the mouth (which must be widely opened and the tongue depressed if necessary) so that the atomized particles, having lost their first impetus, may be carried downward in the current of the breath. This necessitates some moistening of the face with the spray, but even quite young children, with proper management, soon become accustomed to it and tolerate it. The same principle is applied in instruments called " nebu- lizers," or " vaporizing atomizers," which have recently been brought into use, by which the particles are so suspended in the air as to be readily carried into the air-passages by the breath. Liquids, in order to be " nebulized," require to be given a certain consistency by the addition of not less than one- eighth part of glycerine, or some similar substance. In the limited opportunities which I have as yet had for experiment- ing with these instruments I have not been able to satisfy myself that the amount of medicated fluid which can be so in- troduced is sufficient to be effective in the treatment of croup, but I think it not improbable that they may be found to have some utility. One of the best of them is the "vaporizing atomizer, No. 169," made by Codman and Shurtleff. Though the use of the hand -atomizer has obvious advanta- ges in point of convenience, yet in most cases in which it is practicable the application of spray together with warm vapor, by means of the steam-atomizer, is to be preferred. Unfortunately, the impracticability of applying spray to very young children precludes its employment in a considera- ble proportion of our worst cases. The evils attending its ap- TREATMENT. 239 plication by force more than counterbalance its benefits. I have made many attempts to overcome this difficulty by vari- ous expedients, but never with satisfactory results. In cases in which the efficient use of spray is impracticable, Fig. 18.— Vaporizing Atomizer. and in most cases whicli are serious or show a tendency to become so, the inhalation of steam should be resorted to. The most efficient method of doing- this is the construction of a tent over the crib or bed with blankets and barrel-hoops or Fig. 19.— Steam Atomizer. other supports. There should be an opening- in one side of the tent for ventilation. The air within the tent may be kept saturated with warm vapor by means of a tube from a croup- kettle, which should be placed outside of it. 240 diphtheria; its nature and treatment. The air in the tent being- thus maintained at an equable warmth, and draughts being excluded, the room can safely be ventilated by opening the window or otherwise, and the evil effect of the impairment of the air by the burning of the alco- hol or other combustible employed, be in great measure ob- viated. In the absence of a croup-kettle, an ordinary tea-kettle and a gas or oil-stove may be made to answer the purpose. When Fiq. 20.— Croup-kettle. india-rubber tubing cannot be obtained, a substitute may be made with stiff paper or pasteboard surrounded with some fabric, as a roller-bandage. Or a small room in which boiling water can be kept con- stantly running from the pipes, or in which steam-pipes can be tapped, may be utilized. The solvent effect of lime on the false membrane may be additionally obtained by putting pieces of quick-lime into the water in the croup-kettle every hour or two. It should TREATMENT. 2<±1 always be remembered that the boiling- of lime-water for this purpose, which is often recommended, is useless. The vapor may be made the vehicle of various drugs for their antiseptic or specific effect. The most valuable of these is the oil of turpentine. This may be added, a tablespoonful at a time, to the water in the croup-kettle, every hour or two, or it may be volatilized in the air of the room by the method of Dr. Delthil, described on page 197. Its good effect may perhaps be aided by adding a teaspoonful or two of the oil of eucalyptus. The abundant evidence of the special utility of the bi- chloride of mercury in the treatment of this form of diphtheria, and the importance of its early employment, have been already referred to. When the drug is given to avert threatened laryngeal stenosis, the indication is, of course, to bring the system of the patient as rapidly under its influence as is con- sistent with safety. In such circumstances it is important to know that the tolerance of it is, in many children, remarkably great. Dr. Jacobi states * that " a baby a year old may take one-half grain every day many days in succession with very little if any intestinal disorder and with no stomatitis," if it be given in proper dilution. This is equivalent to one forty- eighth of a grain every hour. Dr. O'Dwyer, who has employed this remedy in many cases of croup, and regards it as very valuable, begins with about one eightieth of a grain at that age, and gradually increases to the dose mentioned by Dr. Jacobi, if the case threatens to run a rapid course. He very seldom begins at any age with more than one fiftieth of a grain hourly, and increases or not according to the progress of the case. He also attaches much importance to proper dilution, having known one fiftieth of a grain dissolved in two drachms of water to give rise to severe pains in the stomach, which did not recur when the dilution was increased to half an ounce. He has yet to see any serious gastric or intestinal 1 Loc. cit. 16 242 diphtheria; its nature and treatment. disturbance, or more than the slightest amount of stomatitis, from the sublimate administered in this manner, even when continued so long- as a week. A moderate looseness of the bowels is, according' to his experience, easily controlled by the addition of a mild opiate, but directions should always be left with the attendant to suspend the medicine on the occurrence of any severe diarrhoea or much pain in the stomach or bowels. The advantage, when large doses are being administered, of giving them in half the quantity every half -hour, has been referred to on page 221. The administration of mercury by inunction, by hypodermic injection, and by volatilization and inhalation, has been re- ferred to on pages 177, and 178. The internal administration of the oil of turpentine has also been referred to on pages 195 and 222. Emetics have a well established utility in the treatment of croup, whether catarrhal or diphtheritic; but they should be used with discretion — not too often, nor usually in the later stages of the disease, nor ever in conditions of marked weak- ness, systemic infection or cyanosis. They are beneficial mainly by their expectorant effect, producing increased secre- tion of mucus and the expectoration of that which has accu- mulated, and sometimes causing the throwing off of membrane which is only loosely attached. They usually give temporary relief, at least. While the syrup of ipecacuanha, or of ipecacuanha and squills, in doses of half a teaspoonful to a teaspoonful, or sul- phate of copper in doses of two to five grains, repeated, if necessary, in fifteen minutes, will render excellent service in many cases, the yellow sulphate of mercury is usually to be preferred as being most reliable, prompt and thorough in its action. The dose is from three to five grains. To much pre- viously published testimony to the especial utility of this emetic I am permitted to add the following statement by Dr. O'Dwyer: "In what may be called sthenic cases, when the TREATMENT. 243 dyspnoea becomes urgent and abiding 1 , or, in other words, when it is time to operate, prompt vigorous emesis, such as is pro- duced by the yellow sulphate of mercury, often gives marked relief, which sometimes lasts long enough to render a repeti- tion of the vomiting safe, if stimulants and nourishment be ad- ministered in the interim. By this means I have succeeded in getting a good many cases through, especially those that had been placed on the bichloride treatment at the commencement of the disease, that would otherwise have required intubation." In asphyxia emetics usually fail to acfc. In this condition it is said that the emetic action of apomorphia is not interfered with. It should be freshly prepared. Its hypodermic admin- istration in doses not to exceed one centigramme is recom- mended b} r Mufioz. 1 In this condition, however, it need hardly be said that not an emetic, but intubation or tracheotomy, is the remedy which should be employed. In those cases in which a frequent, harsh and painful cough is accompanied with recurrent paroxysmal dyspnoea, an opiate is useful — as, for. instance, Dover's powder or its liquid equiva- lent, the tinct. ipecacuanhas et opii of the Pharmacopoeia, in doses proportionate to the age and the amount of pain and irritation. The good effect of the remedy may be aided by the application of warm flax-seed poultices, to which a small pro- portion of mustard has been added. The remarks made as to the importance and the methods of maintaining nutrition in other forms of diphtheria are equally applicable in reference to this one. In proportion as the strength is taxed by the persistent dyspnoea, and in pro- portion as the amount of nutritious food which the patient will take is diminished, the giving of alcoholic stimulants be- comes the more necessary, and is consequently required in most cases of any severity or duration. After tracheotomy or intubation, this necessity usually becomes, from the latter of the reasons referred to, even more imperative. ! E1 Prog. Grinecol., July 10, 1887. 214. diphtheria; its nature and treatment. Laryngeal diphtheria may doubtless be prevented or cured by the early employment of the measures which have now been referred to, in a considerable proportion of cases; but since its initial symptoms, such as huskiness of the voice and croupy cough, even when they occur in connection with other forms of the disea se, can by no means be regarded as pathog- nomonic signs pf a pseudo-membranous affection of the larynx, these results cannot be statistically estimated. It must be admitted that in a large proportion of all cases of unquestion- able laryngeal diphtheria, medical treatment alone is inade- quate to prevent a fatal termination. This proportion has been estimated by Morell Mackenzie 1 at ninety per cent. Sanne 2 states that in 2809 cases of croup which have been en- tered at the Hopital Sainte Eugenie, 240, that is 1 in 13, have recovered without operation. Tracheotomy. When the respiration is so seriously interfered with in laryngeal diphtheria that asphyxia is imminent, operative in- terference is usually the only resource by which the life of the patient can be saved. There can be no doubt that intubation will in the future, to a greater or less extent, take the place of tracheotomy in fulfilling this indication ; but since that opera- tion, as it is now practiced, with its general and special indica- tions, will be subsequently treated of by its inventor, Dr. Joseph O'Dwyer, I shall confine my remarks to tracheotomy. The utility of tracheotomy as a means of saving life is, in a general sense, sufficiently illustrated by comparing with the estimate just quoted of the ratio of recoveries in cases of membranous croup not operated upon, the following statistics of the recoveries in " all available reported cases " in which tracheotomy had been performed previous to 1887, as compiled 1 Op. eit., p. 89. 2 Op. cit., p. 490. TREATMENT. 245 in an interesting- and instructive paper by Drs. Lovett and Munro : * Total. Recovered. Died. Per Cent Recovered. German authors .... German hospitals .... British authors French authors Various countries .... American authors .... 5795 3063 433 9242 1993 1327 1851 939 138 2242 657 308 3944 2124 295 6834 .1336 1019 31 30 31 24 32 23 21,853 6135 15,552 28 Tracheotomy has, in many considerable series of cases, been attended with a much larger proportion of recoveries, as is illustrated in the folio wing" examples : Per cent, of Operations Recoveries Recoveries 60 48 T ", To 34 63 82 f 2- 2 - 13 72- 3 - '"'10 Surgical Clinic in Konigsberg, 1878-1882, (Plenio 2 ) . .. . 123 Tracheotomies by H. Ranke, 3 Munich, April 1, 1878, to Sept. 1, 1885. . 54 Tracheotomies by A. Caselli 4 . . 132 Ibid (with improved instruments) . 18 The results of tracheotomy differ widely according to a great variety of circumstances, of which the following are especially important : 1. The methods and skill employed in the operation and the after-treatment. 2. The age of the patient. — The results of tracheotomy are very unfavorable in infants, and in older children improve in 1 "A Consideration of the Results in 327 Cases of Tracheotomy Per- formed at the Boston City Hospital from 1864 to 1887 ; by Robert W. Lovett, M.D., and John C. Munro, M.D.," American Journal of the Medical Sciences, 1887, vol. xciv., p. 160. 2 Jahrb. f. Kinderh., Bd. xxii., H. 4. 3 Jahrb. f. Kinderh., Bd. xxiv., p. 225. 4 Gaz. Med. Ital. Loinb., 1887, p. 198. 246 diphtheria; its nature and treatment. proportion to the age. Dr. Gustav. Chagin 1 has collected the .statistics of 977 operations in infants, of whom only 15 per cent, recovered. M. Sanne 2 thus states the results of tracheotomies at the Hopital Sainte Eugenie according to the age of the patients: Age. Cases. Recoveries. Percent. 1 to 2 years 653 88 13.6 3 " 5 " . . 1298 285 21.9 6 " 10 " . . 335 127 37.8 1 " 15 " . 26 9 32.3 Dr. H. Settegast 3 has tabulated the results of tracheoto- mies in the Krankenhause Bethanien (1861 to 1877) as follows: 2 to 3 " 4 " 5 " 6 " Age. 3 years, 4 " 5 " 6 " 9 9 10 Cases. Recoveries. Per cent 93 22 23.65 165 47 28.45 175 54 30.85 107 39 35.45 90 34 OI.il 59 17 38.86 24 11 45.83 . 15 6 40 3. The type, as to fatality, of the prevailing disease. — This has been remarked by most writers on the subject. Lovett and Munro 4 state that the tracheotomy death-rate at the Boston City Hospital from 1881 to 1885 inclusive, varied by the month in the closest correspondence to the mortality per cent, of diphtheria for the same time in the whole city of Boston. 4. The season of the year. — The writers just quoted from state that during the same five 3-ears (1881-1885) not twenty per cent, recovered of those operated upon in December, Jan- uary, February and March, "while from the latter month the 'Archiv. f. Kinderh., Bd. iv. 2 Op. cit., p. 485. 3 Langen beck's Archives, Bd. xxii., p. 882. 4 Loc. cit. TREATMENT. 247 recovery rate rises until July, when about sixty per cent, of all cases operated upon get well." M. Sanne states that the results of all the tracheotomies at the Sainte Eugenie up to 1876 give the following ratios of recoveries: for June, 1 to 3.31; for August, 1 to 3.56; for No- vember, 1 to 7.19; for December, 1 to 6.18; and for January, 1 to 5.04. 5. The stage of the disease. — It is a well-established fact that the prospect of the successful result of tracheotomy is the greater the earlier it is performed after the nature of the disease requiring it is recognized. This is further illustrated by the following figures in the article of Lovett and Munro from which I have previously quoted: The time is reckoned from the beginning of obstructed respiration. Day of Operation. 1 . 2 . 3 . 4 . 6. The condition of the patient. — The most favorable re- sults from tracheotomy may be expected when the previous health of the patient has been good and the disease is primary and uncomplicated. The prospect of success is generally bad in secondary diphtheria, and when the laryngeal affection ac- companies a malignant or septic form of diphtheria, or is at- tended with pseudo-membranous bronchitis, broncho-pneumo- nia or other grave complications. These unfavorable conditions are regarded by some as contra-indications to the operation. This may doubtless in- sure the avoidance of many bad results. Dr. J. Lewis Smith states that a surgeon of this city (Dr. A. E. Robinson) who carefully selects his cases, operates early and deliberately, and supervises by frequent visits the after-management, has saved since 1880 eleven in thirteen consecutive cases of un- ises. Recoveries. Per cent 23 40 32.5 86 24 28.0 33 8 25.3 7 1 14.0 Extension. Septicaemia. 1 2 to 1 34 to 1 H to 1 248 DIPHTHERIA; ITS NATURE AiTD TREATMENT. doubted membranous croup. Yet since the primary object of tracheotomy is simply to relieve asphyxia, and since there have been instances of subsequent recovery under the most unfavorable conditions, it would seem to be property indicated in all cases in which it is probable that death by suffocation would take place without it. Another indication for the operation is often urged, namely, that even if it fails to save life it will secure euthanasia. The statements of Lovett and Munro on this point are important. In 232 fatal cases the proportion of deaths from the extension of the disease downward into the trachea and bronchi to those from septicaemia were as follows : In all the fatal cases In children under 2 years In children from 2 to 10 years The writers remark, " It will be seen from this that young children are particularly liable to that distressing cause of death, extension of the process to the bronchi. When this happens there is no euthanasia; death is the slowest and most painful of suffocations, and only when septicaemia to the point of stupefaction is present at the same time does the child es- cape a horrible amount of suffering." In favor of early tracheotomj" the unquestionable fact is urged that, in the words of Trousseau, " the earlier the opera- tion is performed the greater are the chances of success," and that the danger of the unexpectedly rapid occurrence of fatal asphyxia is thereby avoided. On the other hand it is argued that in a certain proportion of cases recovery does take place without operation, and that when the patient can be vigilantly watched and the operator can be promptly summoned in case of need, medical treatment should first be tried, and the opera- tion performed only when asphyxia is imminent. This ques- tion must be decided in each particular case by a due consid- TREATMENT. 249 eration of the circumstances attending- it. That an ersor in the direction of unnecessary earliness is a safer one than that of too great procrastination, has been illustrated in many mel- ancholy instances. Now that the alternative of intubation is available, man}^ of the perplexities which formerly beset the ohysician in making this decision are happily removed. Another indication for the early performance of tracheo- tomy has lately been suggested which will, in my opinion, assume greater prominence the more our knowledge of the pathology and treatment of the disease is perfected. Mr. W. W. Chejme, 1 in view of the pathological fact that " in almost all cases the membrane appears first in the larynx and spreads thence continuously down the trachea/' proposes that trache- otomy be performed with the greatest possible antiseptic pre- cautions as soon as it is evident that there is a membranous affection of the larynx, with the object of preventing, by suita- ble disinfectant treatment applied through the tracheal open- ing to the mucous membrane of the larynx and trachea, the downward spread of the diphtheritic process. In order to accomplish this it is necessary that the trachea be opened more freely than is usual, so that through the opening the interior of the trachea may be inspected and antiseptic appli- cations may be made upward into the larynx and over the mucous membrane of the trachea. The details of one case are given, in which by removing the advancing membrane in the trachea by dissecting forceps and sponging the surface with a 1 in 500 solution of bichloride of mercury, its progress was arrested. A different application of the same principle is reported by Roser. 2 At the Marburg surgical clinic the cannula used in tracheotomy has been surrounded with an antiseptic tampon prepared in the following manner : The cannula is wound with a muslin bandage which has first been moistened with a solu- 1 British Medical Journal, March 5, 1887, p. 505. 2 Revue Mens, des Mai. de TEnf., June, 1888. 250 DIPHTHERIA; ITS NATURE AND TREATMENT. tion of sublimate. While it is still moist it is sprinkled with powdered iodoform. This, when dry, forms a crust which ad- heres to the cannula. When the instrument thus prepared is inserted into the trachea, the muslin swells again and forms a tampon. Its calibre must be such as to exactly fill the trachea. Thus is constituted an antiseptic barrier which the advancing diphtheritic process cannot pass. It is left in the trachea two days, and is then replaced by a fresh one, which is left until the fifth day. Of forty-seven tracheotomized diphtheritic patients thus treated during- the past three years there have been fifty- three per cent, of recoveries. The Operation. The high operation, in which the opening is made into the upper portion of the trachea, is now generally preferred as the easier, safer and more expeditious one. The patient, wrapped in a blanket, should be laid on his back on a table so placed that his left side shall be toward the window or artificial light, and his neck should be extended by having placed under it an ordinary wine-bottle wrapped in a napkin. Then chloroform should be given, unless the patient is already asphyxiated or narcotized by septic-poisoning. - The operator should stand to the right of the patient. An incision through the skin should be made downward from the cricoid cartilage exactly in the median line for one and one-half inches, or more, if necessary. The tissues should then, under ordinary circumstances, be carefully and deliberately dissected down to the trachea, the edges of the wound being separated by retractors, and vessels being avoided and put aside. If the isthmus of the thyroid body is unusually high, it may be displaced downward, the muscular and ligamentous bands by which it is attached to the hyoid bone and thyroid carti- lage above having first been divided with curved scissors on TREATMENT. 251 either side of the incision opposite the first ring- of the trachea. 1 " But in the immense majority of cases," says Sanne, "this por- tion of the gland is only a thin strip which passes unnoticed." Fig. 21.— Pilcher's Retractor. All bleeding should be arrested by the forceps, clamps or ligature before the trachea is opened. Then the point of the knife should be carried into the trachea, and the two or three upper rings divided. Fig. 23.— Double Trachea Tube. Blovable Plate. Silver. The opening of the trachea is announced by the escape of air. Fragments of false membrane sometimes present them- selves at the opening and are coughed out, or may be extracted by forceps. It is often advisable, before introducing the can- Fig. 23.— Trousseau's Dilator. nula, to excite coughing by inserting a feather downward into the trachea, that blood, mucus or fragments of false mem- brane may be expelled. ^r. J. A. Wyeth: "A Text Book on Surgery. 1 ' p. 453. 252 DIPHTHERIA; ITS NATURE AND TREATMENT. The cannula may be introduced by using the nail of the left index-finger as a guide into the tracheal incision, or by the aid of the dilator. Difficulties in doing this should be overcome by repeated gentle efforts, but never by force. A rapid operation is practiced and described by Sanne, 1 and advocated by Renault. 2 The trachea is grasped by its sides at the level of the thyroid cartilage, between the thumb and middle fingers of the left hand, while the index-finger of that hand finds the cricoid cartilage, the finger-nail being placed upon its lower border. This hand must not be removed until the cannula has been inserted. The incision having been made through the skin downward from the point indicated by the finger-nail, a few additional strokes of the knife bring one to the trachea. The bleeding is not usually of any importance in this situation. The trachea, being felt by the left index-finger, is punctured and incised. Then the cannula is taken in the right hand, and, guided by the left index-finger, which remains in the wound, is inserted into the tracheal opening. In this operation the prompt insertion of the cannula is relied 'upon to arrest the haemorrhage; but this promptness requires that the operator be expert in tracheotomy. Except when the rapid completion of the operation is especially called for, the more deliberate method should be preferred. To prevent infection of the wound it should be sponged with an antiseptic solution before the trachea is incised, and at the completion of the operation should be dusted with iodo- form and dressed with two thicknesses of linen, which should be moistened every hour with a solution of the bichloride of mercury (one in two thousand). In the after-treatment it is very important that the air of the room be kept at a proper and uniform degree of warmth and moisture. The diffusion through it of unirritating anti- >Op. cit.,p. 522. 2 "Manuel de Tracheotoniie," by Dr. P. Renault; Gr. Steinheil, 6diteur. TREATMENT. 258 septic vapors, such as have already been referred to (page 197), is a valuable addition. The tube must be vigilantly and intelligently watched. Whenever it becomes obstructed by the discharges or frag- ments of false membrane, the inner tube must be withdrawn and cleansed. The use of mild antiseptic atomized solutions administered with the inspired air through the tube may be practiced. The spray of carbolic acid and lime-water (page 215) is es- pecially appropriate. Mild solutions of borax or boracic acid may be similarly used, or insufflations of iodoform, as referred to on page 186. If there is false membrane below the tube, the frequent in- Fig. 24.— Trousseau's Tracheal Forceps. troduction of solutions of trypsin or papayotin in spray, or by means of a slender quill, may be resorted to. The dislodgment and removal of obstructing membrane below the tube has in some cases been effected by means of forceps or the croup-brush, or an instrument which is made by surrounding the end of a soft flexible urethral catheter with a ring five or six millimetres in diameter. 1 After the expiration of twent3 T -four hours from the opera- tion, and at such subsequent intervals as are requisite, the cannula should be removed to facilitate the ejection of ac- cumulated matter from the trachea and the inspection and dressing of the wound. When air begins to pass through the larynx, the cannula may be removed for a short time, which may be repeated and the time extended as the patient becomes more able to dis- 1 Roser, Loc. cit. 254 diphtheria; its nature and treatment. pense with it, until it is finally removed altogether. The length of time from the first insertion to the final removal of the cannula varies very greatly in different cases. In a large majority of all cases this period does not exceed eight days, hut in some instances it is several months or even years. The Treatment of Diphtheritic Paralysis. Since diphtheritic paralysis is due to the immediate or remote effect upon the nervous system of the diphtheritic poison, and since it usually disappears pari passu with the accompanying anaemia, the measures especially indicated in its treatment are those which tend to counteract the former and remove the latter. These are rest, fresh air and a restora- tive regimen. Among drugs the tincture of the chloride of iron, the actions of which as a haemic restorativej a stimulant tonic, and an eminently efficient antidote to the debilitating poison of diphtheria have been elsewhere referred to, is in- comparably the most useful. My own experience in the treat- ment of quite a large number of cases has furnished a striking illustration of this fact. The medicinal treatment of these cases has invariably consisted mainly in the continued fre- quent administration of iron by one of the formulae given on page 220. The rapidity with which the paralysis has disap- peared, even in some grave cases, has been remarkable. The tendency of the affection, in the great majority of cases, to early recovery, and, even in the more severe and persistent ones, to an ultimate restoration of function, which is often rapid when it has once commenced, would naturally lead to the attributing of special curative virtues to whatever drug or method of treatment might chance to have been employed. Hence strychnine and electricity have received a large meed of credit for many recoveries. With regard to the beneficial effect of electricity experience and opinions differ. Dr. A. D. Rockwell, of this city, informs me that according to his experience in a considerable number TREATMENT. 255 of cases it has seemed to shorten the duration of the affection. Seeligmiiller ' attaches much importance to its use. The con- stant current should be employed. When the velum palati is affected the positive pole should be placed on the nucha, the negative one under the inferior maxilla; in ocular paralysis, the positive pole on the nucha, and the negative in the vicinity of the paralyzed muscles; in paralysis of the lower extremities, the positive over the lumbar region and the negative over the nerves which are to be excited. Gowers a recommends the use, in severe cases, of the voltaic current, slowly interrupted, in such strength, if possible, as will cause the affected muscles to contract; but in the case of children the use of a weaker cur- rent is far preferable to the exciting of distress and alarm by a stronger one, "since the utmost good that electricity can do is very small compared with the harmful influence of a daily fright." Gentle friction or massage over the affected region often seems to be beneficial, but any violent or fatiguing pro- cedures of the kind are strongly contra-indicated. Strychnine in small doses may doubtless render valuable service in aiding to restore the tone and activity of the diges- tive organs. Gowers 3 says that while it sometimes seems to be of service " it is certainly powerless to neutralize the mor- bid process in its early stages, and seems to be without influ- ence on the spread of the disease. Moreover it is not wise to give large doses of a drug that stimulates the nerve-cells so powerfully." In cases of extreme paralysis of the muscles of deglutition and respiration, its hypodermic use has seemed to be beneficial. Reinard, 4 reports a favorable result of the daily injection of one milligramme (^ grain) of sulphate of strych- nia in a desperate case of general diphtheritic paralysis in- volving the muscles of respiration. After the first injection respiration was easier, and a cure was effected in fifteen days. 1 E. Adler : Med. Chirurg. Rundschau, No. 4, 1886. 2 Diseases of the Nervous System, p. 1236. 3 Loc. cit. "Deutsche Med. Wochenschrift, 1885, No. 9. 256 diphtheria; its natube and treatment. Dr. W. H. Thomson 1 has found the recourse to strych- nia and electricity very disappointing-; but he states that topical irritants seem occasionally to be quite effective. In palatine and pharyngeal paralysis he brushes the parts every few tours with a paste of black pepper and honey, with a view to awakening their lost reflex excitability. In paraly- sis of the limbs, trunk, etc., he has the parts enveloped twice a day in a pack of infusion of capsicum of the strength of a drachm of the powder to a pint of boiling water, the applica- tion to last from ten to twenty minutes. The difficulty of deglutition is, in some cases, one of the most serious complications to overcome. When the paralysis is in the palate, solid or semi-solid food can be swallowed ; but when the muscles of the pharynx and upper part of the larynx are affected, with insensibility of the epiglottis, the administering of food by the ordinary means becomes dangerous or impossi- ble from its tendency to enter the larynx. In such cases resort must be had to the oesophageal tube or a large catheter or to rectal enemas. The necessity of giving nourishment by one or both of these methods is imperative in order to avoid the danger of exhaustion. In the case of serious dyspnoea and danger of suffocation from the accumulation of mucus in the bronchial tubes in paralysis of the respiratory muscles, resort to artificial respira- tion may tide the patient over a dangerous emergency. Dr. W. H. Thomson suggests that in such cases the treatment which is so successful in cases of bronchial palsy be tried. " The patient should be let down on his hands from the bed with his head down, and encouraged to cough, and frequently a short recourse to this measure will result in expelling a quantity of suffocative fluids from the trachea with great relief to the respiration for some time." In such cases the applica- tion of the- f aradic current to the skin of the back of the chest 1 Medical News, June 4, 188,8, p. 635. TREATMENT. 257 with a view to the reflex stimulation of the respiratory centre has been found promptly serviceable by Duchenne. 1 For the sudden heart-failure which sometimes occurs in the first or second week of diphtheria, all remedies are too often unavailing-. The patient must be kept strictly quiet in the recumbent position. A hot poultice, over which mustard has been dusted, should be applied over the cardiac region. Warm stimulating applications and rubbing should be kept up over the extremities. Brandy or whiskey should at once be given hypodermically, and small doses of digitalis may be given in the same manner. Faradization over the cardiac region is recommended by Duchenne as a powerful cardiac stimulant under such circumstances. Ammonia, camphor, musk, and other stimulants are recommended, but are of doubtful utility, especially as the tolerance of the stomach for drugs and food is usually very limited, and should be carefully economized. I have seen small doses of coffee and of beef-juice, and cham- pagne given pretty freely, well retained and beneficial. By the judicious use of the measures referred to, the patient may sometimes be carried through an alarming emergency, though too often their good effect is only transient. The milder forms of cardiac paralysis, which usually appear at a later period in connection with other forms of diphtheritic palsy, may be treated by the remedies which have been already referred to as appropriate for that condition, with the addition of small doses of digitalis; and the special danger of any vio- lent exertion or even of suddenly rising from the recumbent position should always be borne in mind. Diphtheritic Conjunctivitis. In the treatment of diphtheritic conjunctivitis, the follow- ing measures are indicated : In the first stage, small pieces of lint, cooled on a block of ice, should be laid over the eye and changed ever}^ minute or J " Selections from the Works of Duchenne," by Dr. Poore, p. 350. 17 258 diphtheria; its nature and treatment. two; in the second stage warm or moderately cold applica- tions should be used according- to the sensations of the patient. Antiseptic solutions, such as mercuric bichloride (1 in 8000), carbolic acid (30 minims to the pint), or boric acid (one to four drachms to the pint) should be dropped into the eye hourly. The most thorough cleanliness must also be maintained by irrigation with the same or weaker solutions, used warm or tepid. Dusting iodoform into the eye has been recommended. In the third stage astringent solutions, as of nitrate of silver (5 — 10 grains to the ounce), or tannin (20 grains to the ounce) applied once or twice a day are useful. In case of great pressure upon the cornea from the swell- ing of the eyelid, canthoplasty should be performed. The greatest care must be taken to prevent the infection of the sound eye, by protecting it with an impermeable cover- ing. Cutaneous Diphtheria. The ordinary forms of cutaneous diphtheria usually recover rapidly when simply kept clean, dusted over with iodoform, and covered with lint, which is kept moistened with a mild antiseptic solution, as of bichloride or carbolic acid. The more serious forms of wound-diphtheria, which some- times occur in hospitals, should be treated on the same princi- ples as hospital gangrene. The false membrane and necrosed tissues should first be destroyed or removed. This may be done by means of the gal vano-cautery ; or they may be dis- sected away as completely as possible, after which bromine is applied, and then the wound is covered with iodoform, and dressed antiseptically. APPENDIX. A recent contribution to the etiology of diphtheria * by MM. Roux and Yersin of the Pasteur Institute, Paris, has reached me too late for its statements to be incorporated into the chapter on that subject; but those statements are, prima facie, so important in view of the corroboration which they furnish to previous observations which have been referred to in that chapter, that a summary of them is here appended. MM. Roux and Yersin have found the bacillus of Klebs and Loeffler (described on page 37) in the false membranes in every one of fifteen cases of human diphtheria examined by them. They have isolated it in pure cultures by methods nearly iden- tical with those of Loeffler. They state that it is freely repro- duced in the absence of air, but less energetically than in its presence. It maintains its vitality for a long time in nutritive media, having been thus preserved for more than six months in tubes hermetically sealed. The cultures made by the authors have been more active than were those of Loeffler, the effect of their inoculation into animals having been more uniform and more fatal, but in most other respects the results of their experiments have been iden- tical with those described by him. In inoculations of the culture upon mucous membranes they have found it necessary to first excoriate them; merely smear- ing it over healthy mucous membranes produces no result. 1 "Contribution a l'Etude de la Diphtherie, par E. Roux et A. Yer- sin," Annales de Tlnstitut Pasteur, Deeeuibre, 1888. 260 diphtheria; its nature and treatment. The affection produced by inoculations in the trachea of the rabbit strikingly recalls the features of human croup — conges- tion of the mucous membrane, false membrane, cedematous swelling of the tissues and the glands of the neck, dyspnoea, stridulous breathing, asphyxia. Injections of the culture beneath the skin of pigeons, rab- bits and guinea-pigs, in sufficient quantity, caused their death in from thirty-six hours to five days, the period varying accord- ing to the susceptibility of the animal and the amount of the culture introduced. In the rabbit the autopsy showed at the point of inoculation an extensive oedema infiltrating a tissue indurated with hemorrhagic points, swelling of glands, con- gestion of the omentum and mesenter3 r , with small ecchymoses along the vessels ; the liver friable, of ' a yellow tint, and the seat of a grayish degeneration. In guinea-pigs, which are the most susceptible to the action of the bacillus of diphtheria, the post-mortem lesions consisted in a grayish membranous coat- ing at the point of inoculation, a gelatinous oedema of greater or less extent, a general dilatation of blood-vessels, congestion of glands and internal organs, especially of the suprarenal capsules, the pleurae being often filled with a serous effusion and the pulmonary tissue sometimes in a state of splenization. After intravenous injections in rabbits of one cubic centi- metre of the culture, the animals usually died within sixty hours. The lesions found at the autopsy were a general con- gestion of the abdominal organs, dilatation of vessels, swelling of glands, acute nephritis, and the hepatic degeneration already referred to. Is the bacillus from a very infectious case of human diph- theria more active than those from a benign case ? Without being able to definitively answer that question, the authors state that a culture from the false membrane of a very benign case was found to be very active when inoculated into rabbits. From the results of a large number of careful examinations the authors confirm the observations of Loeffier and others APPENDIX. 261 that the bacillus of diphtheria is to be found only in the false membranes and at the point of inoculation, and never in the blood or the organs, except transient^ and accidentally (as, for instance, within a few hours after intravenous injections) and it is never reproduced there. In rabbits, after intravenous injection, the microbes had entirely disappeared within sixteen hours ; yet the malady pursued its course, and the rabbits died in from thirty to thirty-six hours. Diphtheritic Paralysis. — MM. Roux and Yersin have been the first to succeed in experimentally producing- diphtheritic paralysis in animals. They have produced this result by in- tratracheal, subcutaneous or intravenous inoculations in nu- merous instances in which the animal did not succumb to a too rapid intoxication. Paralysis commenced in a pigeon three weeks after inoculation in the pharynx, when the false mem- branes had disappeared and the animal seemed to have com- pletely recovered. The powerlessness of the feet and the wings was almost complete. When this muscular feebleness had continued for a week there was an amelioration in the move- ments of the feet, but the rabbit died five weeks after the in- oculation. The autopsy showed no lesion, either of the articu- lations or of the nervous system, to account for the symptoms. Man}^ of the localizations which occur in human diphtheritic paralysis were observed in various cases. In rabbits the first invasion of the paralysis was usually by the posterior extrem- ities, and it progressed so rapidly that in a clay or two it affected the whole body, and the animal died by failure of the respiration or of the heart's action. In rarer instances the paralysis in rabbits began in the muscles of the neck, the rab- bit being unable to raise the head from the ground, or in the larynx, causing hoarseness of the voice. The authors remark : " The occurrence of these paralyses, following the introduction of the microbe of Klebs and Loeffier, completes the resemblance of the experimental disease to the natural malady, and estab- lishes with certainty the specific role of that bacillus." 262 diphtheria; its nature and treatment. The Diphtheritic Poison. — The truth of the conclusion which has been reached by Loeffler and others that the bacillus exerts its morbific effect \>y means of an active poison which is produced by the microbe at the seat of the local affection and thence diffused through the system, has also been demon- strated by the experiments of MM. Roux and Yersin. They have done this, not by isolating- the poison, but by pursuing the following method: Filtering through porcelain a pure culture of the bacillus in bouillon of veal, which is seven days' old, all the microbes are retained by the filter, and the liquid obtained is perfectly limpid and slightly acid. If this liquid is introduced in doses of from two to four cubic centimetres beneath the skin of animals, it does not make them ill. If, however, a dose of 35 c.c. is injected into the peritoneal cavity of a guinea-pig or the veins of a rabbit, the animal for a time appears to be well, but after two or three days becomes inquiet and trembles, is increasingly feeble, is seized with a profuse diarrhoea, the respiration becomes labored and irregular, he is no longer able to move, and dies without convulsions five or six hours after the commencement of the symptoms. A guinea-pig which has received 35 c.c. of the same liquid into the peritoneum dies after about ten hours, having experienced great difficulty in respiration. The autopsy shows the char- acteristic congestion of the viscera, especially the kidneys and the suprarenal capsules, and there is often a pleuritic effusion. If quantities of the filtered liquid, varying from \ c.c. to 2 c.c, are introduced under the skin of guinea-pigs, they are presently seized with the same symptoms, and die in the same manner, as those which have been inoculated with the living culture, after periods varying from twenty-four hours to three days, according to the dose administered. The lesions are also the same, except that false membrane is wanting. There is the same oedema, the same indurated tissue at the point of inocu- lation, the same hemorrhagic congestion of the organs, espe- cially of the kidneys and the suprarenal capsules, and the same APPENDIX. 263 pleuritic effusion. In short, "the malady — both symptoms and lesions — is communicated as certainly by the injection of the filtered poison as by the inoculation of the bacillus." The symptoms produced by the inoculations of the filtered fluid, vary according" to the dose of the poison contained in the culture. In the case of a guinea-pig- dyspnoea began on the fifth day, and continued for a week; the respiration was dia- phragmatic and jerking. When the animal was obliged to run, the oppression became so great that he fell, almost as- phyxiated. These symptoms amended gradually, and he re- covered. In rabbits the same commencement of the paralysis in the posterior extremities and its rapidly fatal generaliza- tion, which has been already described, occurred. When the intoxication is less severe, the paralysis may remain for some time limited to a group of muscles. Animals which, like rats and mice, are not affected by the inoculation of the bacilli, show the same resistance to the fil- tered poison. Is the diphtheritic poison an alkaloid or a diastase ? While not yet prepared to definitively answer that question, the au- thors state that the activity of the toxic matter is greatly diminished by heat, and also by exposure to the air — circum- stances which favor the latter hypothesis. The first part of a study of the etiology of diphtheria 1 by Dr. T. M. Prudden, which is very important both from the com- pleteness and precision of its methods of investigation and the definiteness of its results, appears just as this work is going to press. It consists of bacterial examinations, morphological and by cultures, in twenty-four fatal cases of diphtheria. In most of the morphological examinations micrococci, usually in large numbers, were found in all parts of the false mem- branes, including their deeper layers, in the necrosed epithe- lium, in some instances in the lymph-spaces of the mucosa and 1 " On the Etiology of Diphtheria," by T. Mitchell Prudden, M.D., American Journal of the Medical Sciences, April, 1889. 264: diphtheria; its nature and treatment. submucosa, and in one instance extending- deeply into the sub- mucous tissues, accompanied, when abundant, with necrosis. The cocci in the false membrane were accompanied by other bacteria, among* which in some of the cases, are mentioned various forms of bacilli ; but these are usually described as few, scattering, and limited to the more superficial portions of the false membranes. In two exceptional cases micrococci were wanting, and bacilli were numerous. In most of the cultures from the false membranes strepto- cocci, usually in great numbers, and, in some instances, in nearly pure cultures, appeared. The other bacteria, including the various forms of bacilli, were not uniformly present and were, in most cases, in much smaller numbers. In the two ex- ceptional instances already referred to (in which the larynx and trachea were lined with dense firm false membrane, but there was no false membrane in the pharynx) no colonies of streptococci appeared in the cultures, but "short, stout, round- encl bacilli " were numerous. In seven cases, cultures of strep- tococci, in most instances pure, were developed from one or more of the internal organs, namely the kidneys, the spleen, the lungs and the liver. These observations, as is remarked by the author, seem to point to the importance of the streptococcus. A study by him of its characters and life-history will be subsequently published. INTUBATION IN CROUP AND OTHEK ACUTE AND CHROHIO FORMS OF STE- NOSIS OF THE LARYNX. The earliest record of catheterization of the larynx is found in the writings of Hippocrates, who suggested that in cases of inflammatory cynanche, cannulas should he carried into the throat along the jaws so that air might he drawn into the lungs. This suggestion was adopted by many of the' ancient phy- sicians until the discovery of bronchotomy (tracheotomy) by Asclebiades about a century before the Christian era. Cathe- terization was then lost sight of until 1780, when it was revived by Chaussier, who proposed the use of a laryngeal tube in the asphyxia of the new-born and to overcome obstruction due to disease. Several attempts were made about this time to retain a catheter in the larynx but were unsuccessful owing to the sensibility of the parts. Dissault in ] 801, and many others after his time, appear to have had some measure of success in the treatment of laryn- geal stenosis by this method, particularly in adults. But the 266 INTUBATION IN CROUP AND OTHER retention of one end of a tube in the trachea, while the other protrudes either from the mouth or nose, is obviously imprac- ticable in children. The first and only attempt before my own to use a short tube in the larynx, that would allow the epiglottis to close over it, was made by Bouchut in 1858. His failure after a limited trial was due principally to his extravagant claims for the new operation as a substitute for opening the trachea before he had any results to show, and to his bitter denunciation of Trousseau's pet operation, tracheotomy, which Bouchut claimed had considerably increased the death rate from croup instead of diminishing it. Personal enmities therefore played a more important part than the merits or demerits of the new procedure in determining the final decision of the Acad- emy against it. A very complete bibliography of this subject under the titles of catheterization of the larjmx, tubage of the glottis, and intubation will be found in a paper by Dr. Dillon Brown in the Transactions of the 9th International Medical Congress, section on Diseases of Children. DESCRIPTION OF INTUBATION INSTRUMENTS. A set of instruments for children, under the age of puberty, consists of six tubes (1) of different sizes and varying in length from one and a half to two and a half inches; an introducer, (fig. 2), an extractor, (fig. 3), a mouth gag (fig. 4), and scale of years (fig. 5). Each tube is provided with a separate ob- turator for the purpose of attaching it to the introducer and, by projecting somewhat beyond the distal extremity, produces a probe-point which prevents injury to the tissues on the de tachment of pseudo-membrane during the operation. The numbers on the scale (fig. 5) represent years, and indicate ap- proximately the ages for which the corresponding tubes are suitable. FORMS OF STENOSIS OF THE LARYNX. 267 Fig. 1. Fig. 2. Fig. 3. G.TIEMANNKO. ■HI 268 INTUBATION IN CEO UP AND OTHER The smallest tube when applied to the scale will reach the line marked 1, and is suitable for children of one year and under. In children of fifteen months, small for age, this size is preferable to the two-year size, and it can be used at eighteen months, or even two years, without the slightest danger of passing through, but is apt to be coughed out. The next size, which reaches the line on the scale marked 2, is intended for children between one and two years, but can also be used at two and a half or three years with objection referred to above. The third size, marked 3-4 on the scale, should be used in cases over two and up to four years, and so on. The female larynx in children as well as in adults is smaller than the male, which should also be considered in selecting the proper tube to be used. Owing to the rapid increase in the size of the larynx at the age of puberty, the string should be left attached to the largest tube when used after this period of life. In measuring the tubes to select the proper size, the heads are of course included. The tube indicated by the scale of years, is never too large to pass through any form of acute stenosis, except in rare cases of extreme subglottic infiltration of the mucous mem- brane, in which a smaller size may have to be used. Fig. 6 shows a specimen of this kind, with cross section through cri- coid cartilage less than a quarter of an inch below the vocal cords. To pass the proper sized tube through a stricture of this nature, surrounded as it is by an unyielding cartilaginous ring, requires more or less force, and these are the only cases in which it is justifiable. Fig. 7 represents the normal lumen of the subglottic division of the larynx from a child of the same age, and Fig. 8 a section from the trachea of the same showing the great difference in the caliber of the air passage at these points. I have used the 5-7 tube at two years of age either to ob- tain the benefit of the increased length or larger head, and FORMS OF STENOSIS OF THE LARYNX. 269 this can be adopted where there is pseudo-membrane produc- ing- obstruction at the lower extremity or swollen tissue over- lapping the head of the smaller tube. Greater interference with deglutition and the danger of ulceration if the tube be long retained, are the only objections to this plan. All such indications could be met by a greater variety of tubes. When the proper tube for the case to be operated on has been selected, a strong thread of silk, or linen is passed through the small eyelet intended for this purpose, and the ends tied together. Braided silk is the best, as it will not unravel if one Fig. 6. Fig. 7. Fig. 8. strand should cut and thus block the opening, which sometimes happens with the twisted variety. Leaving this string too short has been the cause of much annoyance to several opera- tors and alarm to the friends of the patient by allowing the tube, when placed in the oesophagus, to slip into the stomach, which it quickly does if the malposition be not recognized. This accident can always be avoided by leaving the thread long enough to reach the stomach and still leave a portion protruding from the mouth. The obturator is then screwed firmly on the introducer to prevent the tube from rotating while being inserted, which would be liable to bring the pos- terior projecting portion of the flange under the epiglottis. 270 INTUBATION IN CROUP AND OTHER The upper end of the tube is curved backward and the shoulder removed anteriorly to allow greater freedom to the epiglottis during- the act of swallowing. The long diameter of the tube when applied and ready for use, should be in a line with the handle of the introducing in- strument. If found to turn too far, as usually happens after considerable use, a washer of writing paper, of one or more thicknesses, is sufficient to hold the obturator in the proper position. If the lower extremity of the obturator does not project far enough beyond the tube to make a smooth blunt point, it will be found that the thread is too thick or is not in the groove corresponding to the hole in the tube. In most of the instruments made at present, the eyelet is in the left an- terior part of the shoulder, which removes this difficulty. Indications for Intubation. — The indications for intuba- tion are the same as for tracheotomy. There is no reason why one should be performed earlier than the other. The be- ginning of the third or suffocative stage is the proper time to interfere. This is marked by more or less sinking in of the yielding portions of the chest, lower ribs and sternum, episternal notch, and supra-clavicular regions with inspiration. It means simply that air cannot gain admission to the lungs in sufficient quantity to fill the partial vacuum created by the expansion of the chest, and the walls recede under the weight of the at- mosphere. It is more marked in very young or rachitic chil- dren owing to the greater elasticity of the ribs. But it should be remembered that this symptom is not peculiar to stenosis of the larynx and trachea, as it is produced to a lesser degree by obstruction in any part of the respiratory tract that inter- feres with the free inflation of the lungs. It is found in capil- lary bronchitis, extensive deposits of pseudo-membrane in the bronchi, atelectasis, and to some extent even in broncho-pneu- monia. Recessions at the root of the neck are more significant than those below, as the violent contractions of the diaphragm aid in drawing- in the free border of the ribs and sternum. FORMS OF STENOSIS OF THE • LARYNX. 271 . When recessions are marked there is little or no respira- tory murmur over the posterior portion of the chest, but this symptom is not always available owing- to the laryngeal stridor. Atelectasis with excessive quantity of blood in the lungs, as would naturally be expected, is the result of death from ob- struction in the larynx, but there are exceptions to this rule, and these organs are occasionally found distended with air and containing less than the normal amount of blood. This acute general emphysema, which produces bulging of the parts that usually recede, is caused by greater impediment to expiration than inspiration, and air accumulates in the lungs in the same manner as in spasmodic asthma. It is not com- mon in croup, but is worth remembering. It is also occasion- ally found in capillary bronchitis. The downward movement of the larynx with inspiration is pathognomonic of serious obstruction in this organ, and is also the result of atmospheric pressure, the air being prevented from entering with sufficient rapidity to fill the partial vacuum below. It is readily detected in adults, but not so in children, owing to the deeper situation of the larynx in the latter. This symptom is not present in stenosis of the trachea, owing to the great elasticity of this tube, which permits of considerable motion on itself without displacing the larynx, Abiding cyanosis is too late a symptom to wait for, and, besides, it is uncertain, as fatal obstruction may exist in the glottis with extreme pallor of the surface. This pallor of asphyxia is produced by the excessive quantity of blood drawn into and stored in the lungs by the cupping-glass action of in- spiration when the air is almost excluded. The blood in the cutaneous capillaries is thus reduced to a minimum, and this, although highly charged with carbonic acid, only serves to increase the paleness, on the principle that the addition of a little blue makes a clearer white. The temporary cyanosis which comes and g-oes with the 272 INTUBATION IN CROUP AND OTHER paroxysmal dyspnoea of the second stage of croup is of no particular significance. Children seldom remain long in one position when suffering severely from want of breath, and continued restlessness, if consciousness be unimpaired, is therefore an important indica- tion that it is time to afford relief. As far as the necessity for intubation is concerned, it mat- ters little as to the nature of the obstruction provided it be in the larynx and not a foreign body. It may be croup, simple laryngitis, oedema of the glottis, paralysis, spasm, or even a neoplasm. In the latter it will tide over the immediate danger of asphyxia, and leave more breathing room to facilitate the radical operation. Method of Operating. — The nurse or person who holds the child should be seated on a solid chair with low back, and the patient placed on the lap with head resting on left shoulder of nurse in order to leave the gag free. The hands can either be held, or, still better, secured by the sides hj a towel or sheet passed around the body and left in that position until the tube is inserted and the string removed. Fastening the hands in front of the chest or thick garments in the same location ren- ders it more difficult to depress the handle of the introducer sufficiently to carry the tube over the dorsum of the tongue. The gag (fig. 4) is then inserted well back behind or be- tween the teeth in the left angle of the mouth and opened widely, care being taken not to do it too suddenty or to use too much force. In children who have not at least one bi- cuspid on the left side, the gag should not be used, as it slips forward on the gums, and, besides being in the way, is liable to injure the incisor teeth. There is little difficult}^ in these cases in keeping the mouth sufficiently open with the finger, if car- ried far enough to the patient's right to be out of range of the front teeth. Allowing the child to compress the finger be- tween the gums for a few seconds until the jaws relax, before carrying it into the fauces, avoids the necessity for using force. FORMS OF STENOSIS OF THE LARYNX. 273 The Denharclt gag, which is the one shown in the cut, holds better than the one originally devised by the author, the handle of which projects downward and is liable to be knocked Fig. 9, shows the positions of assistant, nurse and patient with gag in position. out of place by coming in contact with the shoulder in the movements of the child's head. An assistant stands behind the patient and holds the head firmly by placing one hand on either side, and at the same time slightly elevates the chin. The person who holds the 18 274 INTUBATION IN CROUP AND OTHER head, if without any experience, should be requested not to touch the gag, as this, if properly placed, retains its hold by the pressure of the teeth. The operator stands in front of the patient holding- the introducer lightly between the thumb and fingers of the right hand, the thumb resting on the upper surface of the handle just behind the knob that serves to detach the tube and the index finger in front of the trigger support underneath. Held in this manner it is impossible to use force enough to make a false passage, while if firmly grasped in the hand the beginner may, unconsciously, exert sufficient force to lacerate the tissues. The index finger of the left hand is carried well down in the pharynx or beginning of oesophagus and then brought forward in the median line, raising and fixing the epiglottis, while the tube is guided along beside it into the larynx. If any difficulty is experienced in locating the epiglottis, it is better to search for the cavity of the larynx, a cul de sac into which the tip of the finger readily enters and which cannot be mistaken for anything else. Once in this cavity the epiglottis must be in front of the finger and the latter is then raised and pressed towards the patient's right to leave room for the tube to pass beside it. The distal extremity of the tube should be kept in contact with the finger, and even directing it a little obliquely towards the right side of the larynx is necessary to get inside the left ary-epiglottic fold, especially in very young children. The handle of the introducer is held close to the patient's chest in the beginning of the operation, and rapidly raised as soon as the lower end of the tube has passed behind the epi- glottis, otherwise it will slip over the larynx into the oesopha- gus. Some operators hold the introducing instrument in the horizontal position until the tube is well back in the fauces, and then swing it around to the middle line and complete the FORMS OF STENOSIS OF THE LARYNX. 275 operation in the usual manner. The beginner is liable to for- get the latter movement, which is the only objection to this plan. As soon as the cannula is inserted it is detached by press- ing forward the button on the upper surface of the handle with the thumb, while counter-pressure is made with the index finger on the trigger beneath. In removing the obturator — the joint in the shank of which is intended to facilitate this part of the operation — the movements required for insertion are reversed. To prevent the tube from being also withdrawn, the finger must be kept in contact with its shoulder either on the side or posteriorly. The tube should be carried well down in. the larynx before detaching it, otherwise the lower aperture will be left open and liable to strip off pseudo-membrane as it is subsequent^ pushed home with the finger. The gag is removed as soon as the tube is in place, but the string is allowed to remain long enough to be certain that the dyspnoea is relieved and that no loose membrane exists in the lower portion of the trachea. In some cases the presence of the thread is desirable because it excites more cough, which is necessary to expel accumulated secretions and to inflate any collapse of the lungs that may have taken place. In re- moving the string the finger must be re-inserted to hold the tube down, but the gag is rarely necessary, as children old enough to understand readily open the mouth for this purpose. In withdrawing the tube the child is held in the same posi- tion, and the extractor is guided along the side of the finger, which is brought in contact with the head of the cannula and then pressed toward the patient's right in order to uncover the aperture and allow the instrument to enter in a straight line. Dr. Waxham and others pass the extractor under the finger, that is, between it and the epiglottis, and intubate in the same manner. I have not tried this method and cannot therefore express an opinion as to its merits. No attempt at 276 INTUBATION IN CROUP AND OTHER extraction should be made until the head of the tube is felt, which can always be done no matter how extensive the swell- ing- of the epiglottis and ary-epiglottic folds may be. Many times the tissues have been lacerated by repeated attempts to remove a tube from the larynx which was somewhere else, most likely in the bed or ejected, unobserved, into a vessel during the act of vomiting, and thrown out. The tubal cough is characteristic, and when once heard cannot be mistaken, but it sometimes assumes a hoarse or croupy quality from loose membrane below or overlapping tissues above, and in such cases the presence of the tube must be demonstrated by the sense of touch. To place a tube in the larynx of a struggling, choking child, in the brief space of time that is compatible with safety, is a difficult thing to do, and should not be attempted, except in case of emergency, without previous practice on the cadaver. Those only who possess an extraordinary amount of dexterity combined with coolness will succeed without such practice. The operator has so many things to think of and so many movements to make with both hands, all in a few seconds, that unless he have had sufficient practice to make some of these movements to a certain extent automatic, he cannot operate with safety to his patient or with credit to himself. The epiglottis must be found, raised and held in this position, as the tube is glided down in contact with the finger, other- wise the operator does not know where it is ; it must be slipped off at the right moment and held down while the obturator is withdrawn, all to be accomplished in ten seconds or less. It is this important element of time, therefore, that converts an otherwise simple operation into a very difficult one. Practice on the cadaver is within the reach of compara- tively few, but a larynx from any of the smaller animals can be procured by every one; and repeated practice on this, placed upright in the neck of a bottle or other convenient receptacle, is an excellent substitute. I have always advised those to FORMS OF STENOSIS OF THE LARYNX. 277 whom I have given practical instruction on this subject to continue this kind of practice at frequent intervals, because a few lessons on the cadaver are not sufficient to insure pro- ficiency and have only the advantage over this method of learning to operate in the same small space that exists in the living subject. The larynx should be placed in the same position it occu- pied in the body, the operator going through the different steps of inserting and removing the tube solely by the sense of touch without watching his own movements, and when any obstacle is encountered holding the introducer or extractor in position until he investigate the cause of the difficulty. An hour's rehearsal of this kind just before going to remove a tube from a patient is of the greatest advantage, and gives an amount of confidence that contributes largely to a successful result. I have found the greatest difficulty in overcoming the habit, always adopted by beginners, of placing the thumb on the lever of the extractor while guiding it into the tube. The most expert operator cannot do this without running the risk of unconsciously making slight pressure too soon, thus sepa- rating the nibs, which are very liable to seize some of the tis- sues as they close, besides otherwise interfering with the success of the operation. The thumb should be constantly " occupied by placing it on the upper surface of the handle until the instrument is introduced, then transferred to the lever and continuous pressure kept up while the tube is being removed. Intermittent pressure will allow the tube to drop off into the pharynx and possibly to enter the stomach. Intubation performed by an expert is an operation that may be witnessed by the most sympathetic mother without material shock to her nervous system, while in the hands of the novice there are few operations more repulsive even to the uninterested spectator. A small percentage of the amount of practice required to make a good marksman, billiard -player, 278 INTUBATION IN CROUP AND OTHER etc., if expended in the manner above indicated, would impart sufficient dexterity to obtain the best results with intubation, and at the same time avoid a great deal of unnecessary suffer- ing- and some loss of life also. The proper time for removing the tube from the larynx will depend on the age of the patient, the character of the dis- ease, whether of slow or rapid development, and the progress of the case. . In one hundred and fifty-eight recoveries from croup, in which the exact time was recorded, the average retention of the tubes amounted to five days and two hours. In my own forty-nine recoveries, the longest time a tube was retained was fourteen days, and the shortest time in which pseudo- membrane was demonstrated to have been present was four- teen hours. The younger the patient, as a rule, the longer the tube will be required. In children under two years of age it is better to leave it in seven days. When the disease has developed slowly, and has therefore run a greater part of its course before calling for operative interference, the tube can be dispensed with earlier — sometimes as soon as the second or third day. If the case be at such a distance as to render it impossible to reach it in a reasonable time, it is safer, if progressing fav- orably, to leave the tube in position for seven or eight days, and the exceptions are few in which it will be necessary to re- insert it after this time. The tube should always be removed on the recurrence of severe dyspnoea, because it is sometimes impossible to ascer- tain with certainty whether it be partially obstructed or not. The best evidence to the contrary is a good respiratory murmur or numerous rales over the lower posterior portion of the lungs. Even under these circumstances I have occa- sionally found the lumen of the tube seriously encroached upon by firmly adherent secretions. FOEMS OF STENOSIS OF THE LARYNX. 279 In one case of this kind, complicated with extensive broncho- pneumonia to which the dyspnoea was attributed, the tube when removed appeared to be completely occluded through its whole length, 3 r et an opening must have existed in it some- where. Had I found it in this condition on its removal after death I would certainly have attributed the fatal result to this cause. Such cases — and I have seen several similar ones — prove that sufficient air to sustain life can be admitted through an ex- tremely small opening. The adhesion of tenacious secretions to the inside of the tube is more liable to occur in very young children, owing to their comparatively feeble power of cough- ing, and for the same reason they are more prone to pulmonary complications. In older children who are strong and can be induced to cough vigorously such accumulations are rare. They are also favored by a high temperature, which is usually attended with scanty secretion, and particularly if at the same time both nostrils are occluded, necessitating mouth breath- ing. I have never known any serious diminution of the lumen of the tube to occur suddenly from secretions. It is a process that usually requires at least many hours and sometimes days. The development of a high temperature, especially if accom- panied with any considerable amount of bronchitis, on the third or fourth day, is a sufficient reason for removing the cannula, as it can sometimes be permanently dispensed with as early as this, and even if left out for only a few hours without urgent dyspnoea, is of great benefit, as it affords an opportunity to unload the bronchi of secretions by permitting complete closure of the glottis and thus giving full effect to the act of cough- ing. In those cases that refuse nourishment after intubation or that cannot be induced to take a sufficient quantity, it is useless to remove the tube for the purpose of feeding, unless it have been in long enough to give some reasonable hope that its further use will not be necessary, as it is difficult to con- 280 INTUBATION IN CROUP AND OTHER vince children for some time that they can swallow any better than before. If no dyspnoea recur in half an hour after the extraction of the tube, it is safe to leave the patient, if not at too great a distance to be reached within two or three hours. Accidents and Dangers of Intubation. — The most serious of the accidents incident to this operation is apncea from pro- longed attempts to introduce the tube. This can be avoided only by acquiring- thorough familiarity with the use of the in- struments in the manner already pointed out. The beginner, unless he possess an unusual amount of coolness, is liable to forget that while his finger is in the throat, the patient cannot breathe, and that a fatal asphyxia may be produced in a very few seconds. Ten seconds is the longest time that should be occupied in each attempt, if the child be suffering from urgent dyspnoea at the time. If the finger be then removed from the mouth, and the patient be given a chance to get its breath, many failures to properly place the tube can be made without danger. The expert seldom requires more than five seconds to com- plete the operation, except in difficult cases, such as a very small mouth and throat, marked increase in the size of the tonsils, especially if chronic, extreme tumefaction of the epi- glottis and ary-epiglottic fold which changes or obliterates the usual landmarks, and the struggles and resistance some- times offered by older children when intractable. In the latter, although I have never had to resort to it, the administration of an anaesthetic would be less injurious than the exhaustion and cyanosis induced by a prolonged struggle without it. If the tube has once passed on the outside of the larynx, and this is recognized before it is detached from the obturator, it is useless to try to rectify the position without first depress- ing the handle of the introducer as in the beginning of the operation, because owing' to the length of the tube the palate arrests the upward movement before the distal extremity reaches the level of the glottic opening. FORMS OF STENOSIS OF THE LARYNX. 281 In croup the ventricles of the larynx are usually obliterated by swelling- of the tissues and covered over by the pseudo- membrane, and therefore seldom offer any obstacle to the passage of the tube on the first introduction; but when the stenosis persists longer than usual and reintroduction becomes necessary, it is well to remember that this may be a source of obstruction. The tube once having entered a ventricle, a moderate amount of force is all that is necessary to make a false passage. I have known this accident to occur when the operator was unconscious of having used any force whatever. If the patient's head be thrown too far back, the tube may also be arrested by coming in contact with the anterior wall of the larynx or trachea. Pushing down membrane before the tube is the most seri- ous of the unavoida ble accidents attending this operation. It has happened in only three of my own two hundred and nine cases of croup, so far intubated, on the first introduction. In two of these apncea was complete, and the tubes had to be removed immediately and were followed by complete casts of the trachea. In the third case expiration only was seriously obstructed, and the tube was allowed to remain about ten minutes in order to allow the lungs to become fully inflated, and to make more room in the glottis for the passage of the pseudo-membranous mass. As traction was made on the thread, the patient was directed to cough, and with the same result as in the others. In none of these cases was the dyspnoea relieved in the least by the rejection of the membranes, and the immediate reintroduction of the tube was necessary in each. Had the ob- struction existed in the trachea, the relief would have been prompt, but it was in the glottis, where the fibrinous exuda- tion remains long adherent and where the principal cause of the stenosis is the infiltration of the mucous membrane and underlying tissues and not the film of adventitious material on the surface. 282 INTUBATION IN CROUP AND OTHER The trachea being- so much larger than is required for the free passage of air to and from the lungs that no amount of fibrinous exudation, however thick, while still adherent, can produce serious impediment to respiration, this accident can only occur when a cast, or partial cast, lying loose in the trachea accumulates before the tube in its downward course, or the membrane being adherent above and detached below may •close around the distal extremity of the tube, and partially or completely suspend expiration. I have had three deaths from the latter cause in two hundred and nine cases, occurring from One to three days after intubation. In two of these the pres- ence of membrane below the tube was recognized immediately after the operation, but as it did not interfere with respiration at the time, the precaution of leaving the string attached was not taken, and both children were old enough to render this plan feasible. Pushing down pseudo-membrane is more liable to occur in cases of slow development, because it has had time to become detached, and for the same reason on reintroducing the tube after its removal for any cause. When not held below by processes extending into the bronchi, it is almost invariably expelled on again removing the tube. In some cases I have succeeded in breaking up such adhesions by in- serting a longer tube or by inserting and removing the tube several times in succession. I have devised and tried several instruments for the re- moval of pseudo-membrane from the trachea, which have not proved satisfactory. The one shown in the cut (fig. 10) I have not 3'et used. It is introduced closed and expands with a spring below and hugs the sides of the trachea while being withdrawn. It is of sufficient length to reach to the bifurca- tion and therefore much more difficult to insert than a tube. Even if completely successful in accomplishing the object in- tended, it would be useless, if not dangerous, in the hands of any but an expert. Other means of minimizing the danger of sudden occlusion of the tube by loose membrane in the lower FORMS OF STENOSIS OF THE LARYNX. 283 portion of the trachea are available and within the reach of all. The most important of these for older children who are under control has already been referred to. It consists in leaving- the string* attached and fastening it behind the ear in cases in which the existence of pseudo-membrane below the tube is demonstrated, immediately after the operation, by a hoarse or croupy quality of the cough or a flapping sound with respiration or coughing. In only one out of several cases in which I resorted to this plan during the past year was it necessary for the attendant to remove the tube. The patient was seven years old, and Fig. 10. made no complaint of suffering or annoyance from the string. A cast of the trachea had been expelled several days before the operation was necessary, and another had formed, its presence being manifested not only by the symptoms given above, but also by the occasional complete arrest of the escape of air during violent expiratory efforts, such as coughing. During quiet breathing, neither respiratory act was inter- fered with. The patient was warned against touching the thread or cutting it with the teeth. The father who acted as nurse was directed to watch her closely, and in case of sudden choking to pull out the tube. During a fit of coughing in the night, sudden dyspnosa developed, the father did as directed, 284: INTUBATION IN CROUP AND OTHER and a cast of the trachea was expelled. The next day the tube had to be reinserted for a short time, but the patient re- covered, having retained the tube in the larynx in all only fourteen hours. It is difficult to leave the string- attached in young children, for if they do not succeed in seizing it with the hands they will soon chew it apart. The latter difficulty may be overcome when there is room to pass the thread between two of the double teeth. When this plan cannot be adopted, a smaller tube than the one suitable for the age should be used, which seldom fails to be rejected if obstructed. In a child between one and two years of age, for example, the No. 2 tube should be removed and the smallest one substituted; at six and a half or seven years the 5-7 size should be replaced by the 3-4. In the prac- tice of this method, the worst that can happen is the rejection of the tube when it is not necessary. Should this occur too frequently, a larger size would have to be used. In some few cases even the proper size for the age as indicated by the scale is coughed out so often that a larger one must be inserted. Either of these plans should be resorted to in case the symptoms of loose membrane in the lower part of the wind- pipe, absent at the time of operation, subsequently show them- selves. In the event of sudden asphyxia, the nurse should be in- structed to quickly grasp the child and hold it head down- wards, at the same time shaking it vigorously, the weight of the tube being sometimes sufficient to displace it. The obstruction in the great majority of these cases is to expiration only, inspiration being free. Air in excessive quan- tity therefore rapidly accumulates in the lungs, and this may be used as the expelling power by causing some of it to escape suddenly, in imitation of the act of coughing, by a forcible blow or slap with the open hand on the front of the chest, at the same time preventing the descent of the diaphragm by pressure of the other hand on the abdomen. It will be more FORMS OF STENOSIS OF THE LARYNX. 285 likely to succeed if the patient be placed across the knees or other hard surface than if practiced on the bed. If complete occlusion exists death probably results in less than one minute, and whatever is done must be done quickly, and by the nurse, as there is no time to summon the physician. During- the fit of coughing" that immediately succeeds intu- bation, pieces of pseudo-membrane are frequently expelled. These are usually only fragments detached from, the chink of the glottis or anterior wall of the trachea and carried down with the tube, but they sometimes amount to considerable masses; even a cylindrical cast almost an inch long I have known to be forced through the small opening in one of the medium-sized tubes. I have never known any serious obstruction to result from loose membrane above the tube, but extreme tumefaction of the epiglottis and ary-epiglottic folds does in rare cases give rise to dangerous constriction at this point. In one case I recognized this condition from the noisy ob- structed inspiration, and easily detected the overlapping tissues by inserting the finger. This difficulty can be overcome by coating the head of the tube with several layers of collodion, which, if allowed sufficient time to dry, will adhere for a con- siderable length of time, or a larger tube can be used. Gradual accumulation of tenacious mucus sometimes mixed with milk-curd occasionally takes place in the tube and renders its removal for the purpose of cleaning necessary. It is more liable to occur in those cases that cough but little, also in very young children or where there is marked prostration, because the expulsive power of the cough under these circumstances is slight. For the same reason, when the lumen of the tube has been seriously encroached upon in this manner it is seldom expelled, as the volume of air admitted at any one time is comparatively small. Coughing out the tube when it is free from obstruction and before the stenosis has been permanently relieved does not 286 INTUBATION IN CROUP AND OTHEE often occur when the proper size has been used, and is seldom attended with any danger, as the dyspnoea does not return im- mediately, except in those rare cases in which there is exten- sive oedema of the glottis or complete paralysis of the abductor muscles of the cords. In either of these conditions, when recognized, a larger tube than that suitable for the age should be used ; or, what is still better, a tube specially constructed for the case, with extra large retaining-swell. This is particularly important in paralysis, which is likely to persist for a consid- erable length of time, because the retaining power which re- sides principally in the vocal cords must be transferred to the subglottic division of the larynx. The tube is more liable to be expelled in the act of vomit- ing than by coughing, as the vocal cords in the latter are con- tracted, while in the former the weight of the tube sometimes favors its rejection from the position the patient, if permitted, is apt to assume, with the head on a level with or lower than the body. Owing to the difference in the size of the larynx in different children of the same age, it is impossible to adjust the tubes so that they will be retained under all circumstances while clear, and at the same time permit of their rejection when suddenly occluded. The most serious injury may be done to the larynx in at- tempting to remove the tube if the extractor be passed down beside instead of into the opening, and it is often impossible even for the expert to locate the point of the instrument with certainty before separating the blades. It is important there- fore to remember that no force whatever is required to remove the tube, and that any resistance to the withdrawal of the ex- tractor proves that it is caught in the tissues on the outside. By forcibly removing the instrument under these circumstances I have known sufficient laceration to be produced to allow the tube to drop in the trachea, and this is the only way in which this accident can occur with the large-headed tubes now in use. FORMS OF STENOSIS OF THE LARYNX. 287 To minimize this danger as far as possible a regulating screw has heen added to the extractor, which prevents the blades from opening any wider than is required to hold the tube with sufficient firmness to prevent slipping, and can be adjusted to suit the different sizes. Most of the old instru- ments are too slight, and therefore too elastic, to render the addition of this screw of any service. Attention to the following points will enable every one to detect the most serious defects found in many of the tubes still in the market. The head or shoulder which rests in the vestibule of the larynx, and which is firmly grasped by the surrounding tis- sues during every act of swallowing, should be absolutely free from any roughness or sharp edges that would cut into or irritate the intensely inflamed mucous membrane. This por- tion of the tube — about one-fourth of an inch — has a slight backward curve which, if not apparent, can readily be detected by placing the anterior edge in contact with any level surface. Its object is to give greater freedom to the epiglottis in pre- venting the entrance of food during the act of swallowing, and to avoid ulceration, which was not an uncommon occur- rence with the straight tubes first used. For the same reason there is no flange anteriorly, and the metal here is left thick enough to prevent the formation of a cutting edge, as the epi- glottis is pressed with considerable force on this part with each deglutition. Those not familiar with the object of this con- sider it a serious defect because occupying room that should be devoted to the calibre. The metal on the anterior surface of the lower extremity should be even thicker than above, and smoothly rounded off so that it will glide up and down over the mucous membrane without cutting it. The upper extremity of the tube being fixed, is raised with the larynx and at the same time pressed backwards by the base of the tongue, which pushes the epiglottis before it. This lever action brings the distal extremity in contact with the 288 INTUBATION IN CROUP AND OTHER anterior wall of the trachea, and instead of occupying a fixed position, as it does above, moves about half an inch in a verti- cal direction. The upward movement, coincident with closure of the epiglottis while swallowing-, is harmless, but the injury is inflicted as the tube, still in contact with the mucous membrane, returns to what may be called its respiratory posi- tion. If long worn, even the most perfect tube will produce some abrasion of the inflamed and infiltrated tissues at the point indicated, from the frequent rubbing, which occurs with every act of swallowing, either of saliva or of food, and probably amounting to over a hundred times daily. If the tube be rough or have a sharp edge at this point, it will inflict serious injury on the mucous membrane even to laying bare the carti- laginous rings. The ulceration thus produced is sometimes the cause of dysphagia, and is in all probability the source of the blood that occasionally tinges the expectoration several days after intubation. The retaining-swell protects the sides of the trachea, and therefore the metal on the lateral aspects of the distal end should be thin in order to leave the entering portion of the tube small to facilitate its introduction. As the tube seldom impinges on the posterior wail the metal at this point need not be so thick as in front, but suffi- ciently so to make it blunt and smooth. Another very serious defect, and a very common one, is the imperfect fitting of the obturator in the tube both above and below. If this exist below, it fails to make a perfect probe- point and is liable to injure the tissues of the larynx or scrape off pseudo-membrane in its downward course. If above, it allows the tube to wobble when attached to the introducer, and if the operator fail to place it in the larynx on the first attempt the tube is certain to slip off, and besides the annoy- ance, he is obliged to lose valuable time in readjusting it. This FORMS OF STENOSIS OF THE LARYNX. 289 is even liable to happen in striking the base of the tongue or other part before the larynx is reached. If properly made.the tube and introducing instrument, when united and ready for use, should be as free from motion as if constructed of one piece, and this, owing to the joint in the shank of the obturator and the curve in the upper part of the bore of the tube, is diffi- cult to obtain. I have also noticed that the lines indicating the years on the scale do not always correspond to the length of the tubes, rendering it difficult for the beginner to select the proper size. By observing the following rule the scale can be dispensed with. The smallest tube is suitable for the first year of life, the second for the second year, the third from two to four years, and the others for two years each. No instrument -maker has yet succeeded in constructing these tubes properly without repeated instructions and many failures. It is therefore not surprising that those who never received any instruction whatever should turn out such grossly imperfect instruments as are constantly to be found in the market. Diagnosis of Croup. — Croup, from its characteristic symp- toms, should be one of the easiest of all diseases to diagnos- ticate, and as a rule it is, but in cases seen for the first time, when moribund or nearly so, the cough having ceased and nothing remaining but the labored breathing, it is sometimes impossible with the imperfect history obtainable from the ex- cited parents or friends to differentiate dyspnoea due to this disease from that produced by other causes. While doubt under such circumstances is justifiable, I know from personal experience that mistakes for which there is no excuse are oc- casionally made and that would never occur, were a little attention paid to the prominent symptoms of croup. These symptoms in the order of their importance are the following: The peculiar character of the cough, of the breath- ing, the hoarseness or aphonia and dyspncea. The croupy 19 290 INTUBATION IN CROUP AND OTHER cough may be called a constant and characteristic symptom, for the cases in which it is absent with pseudo-membrane in the larynx can safely be excluded on their rarity. The croupy or noisy breathing- is almost always present, but not marked in the early stage of the disease. Hoarseness is a very early symptom, and occasionally pre- cedes the croupy cough by a considerable length of time. It is almost always followed by aphonia or complete loss of voice, except with violent effort, when it is usually possible to pro- duce a distinct sound. Aphonia in children should always be regarded with grave suspicion, as in rare cases it is the only evidence of laryngeal diphtheria; while, on the other hand, a fatal stenosis may exist in the narrow portion of the larynx just below the vocal cords without material alteration of the voice. It is particularly liable to occur in the ascending cases, in which the disease begins in the trachea and sometimes pro- duces sufficient infiltration and thickening of the mucous membrane of the subglottic region to cause apncea before any fibrinous exudation whatever has been thrown out. The cut (fig. 6) represents a specimen from a case of this kind. The voice, with the exception of weakness toward the end, was not altered and no pseudo-membrane existed at the seat of greatest constriction. Dyspnoea, except that due to spasm which may occur at any stage of the diesase, is a late symptom, and is at first mainly inspiratory, but later, when the respiration assumes a sawing character, both respiratory acts are about equally ob- structed, and occasionally the exit of air is more impeded than its entrance. In the latter case acute general emphysema is the result, with modification of some of the ordinary physical signs previously described. It may be put down as a general rule that any impediment to respiration situated in the larynx or trachea, or produced by pressure on these parts from the outside, gives rise to greater obstruction to inspiration than to expiration. The re- FORMS OF STENOSIS OF THE LARYNX. 291 verse is also true in several of the respiratory diseases located below these points, such as spasmodic asthma, emphysema, capillary bronchitis, and the pressure of enlarged bronchial giands on or in the immediate vicinity of the bifurcation. In two cases of the latter which I have observed and verified, the dyspnoea was markedly expiratory or asthmatic, and while it is not probable that this always obtains, it is worth remember- ing- as an aid to diagnosis in obscure cases. The following diseases are those most commonly mistaken for croup, according to my own experience : Naso-pharyngeal obstruction from intense tumefaction of the tonsils and other tissues at the entrance of the fauces, with co-existing occlusion of the nares. In two out of several such cases seen during the past year, all malignant forms of diphtheria, there was marked cyanosis, which disappeared as the swelling subsided under the influence of warm, mildly astringent irrigations; but all eventually proved fatal from the severity of the disease. The noisy breathing simulates that of croup, but the cough and voice are unaffected. I have seen some cases in which croup complicated this condition where it was difficult to determine as to how much of the dyspnoea was laryngeal and how much pharyngeal. Temporarily conveying the air beyond the pillars of the fauces by the insertion of a large catheter or other means would under these circumstances be decisive. It should be remembered also that with such a degree of malignancy, the intense inflammatory oedema of the surround- ing tissues may dip into the vestibule of the larynx and produce fatal stenosis without implicating the cords and be- fore pseudo-membrane has had time to form. The introduc- tion of an educated finger is the best aid to diagnosis in this case. To be able to locate the seat of the impediment to respira- tion when called upon to intubate, and to decide whether the operation, which cannot remove obstruction in the phar3*nx, 292 INTUBATION IN CROUP AND OTHER be indicated or not, is the only advantage to be derived from exact diagnosis in this class of cases, as tbey always prove fatal as far as I have seen. Retro-pharyngeal abscess is more liable to be confounded with oedema of the glottis than with croup, for the reason that in both inspiration only is obstructed, but deglutition is also interfered with in the former. Abscess in this location is likely to be overlooked simply because being comparatively rare it is not thought of. The attention once having been called to it, the diagnosis is easily made either by sight or by the sense of touch. The finger comes in contact with a soft doughy swelling instead of the hard posterior wall of the pharynx. All the cases of retro- pharyngeal abscess seen by the author were in children under two years of age, and some of them were infants only a few months old. Primary idiopathic oedema of the glottis is one of the rarest of diseases in children, and if mistaken for croup is of no importance as far as intubation is concerned. Paralysis of the abductor muscles of the glottis only ob- structs inspiration, and the more forcible this act the more closely the cords are approximated. It is almost exclusively a sequel of diphtheria, and in young children produces asphyxia in a very short time. Larjmgismus stridulus, or spasm of the glottis, is charac- terized by its sudden onset, crowing inspiration, and croupy cough. It is only the local manifestation of a general de- rangement of the nervous system, and often ends in convul- sions. Intubation is sometimes indicated, but the paroxysm usually subsides or proves fatal before there is time to sum-' mon medical aid. Laryngeal polypi are of slow development, and affect the voice for a considerable length of time before the breathing. In cases with obscure history and unusual symptoms it is well to remember that various kinds of foreign bodies may FORMS OF STEXOSIS OF THE LARYNX. 293 gain admission to the larynx and be retained for some time without producing 1 complete asphyxia. There is no possible excuse for any error in diagnosis be- tween pulmonary or bronchial affections and croup which I have known to be made. To differentiate simple catarrhal croup and fibrinous laryn- gitis is a matter of little importance as regards intubation, because the former rarely endangers life or calls for surgical interference, while only a small percentage of the latter re- cover without it. False croup usually makes its appearance suddenly in the night, followed by marked improvement or complete intermission during the day. Fibrinous croup, on the contrary, except in fulminant cases, is rather slow and in- sidious in its development, but steadily progressive, presenting at first only slight hoarseness with croupy cough, and attended with little constitutional disturbances, when neither nose nor pharynx is involved. A sharp rise of temperature, such as 104°, points rather to false than true croup. Albuminuria is diagnostic of the latter. Medical advice is usually sought more promptly in the false variety, because it presents more alarming symptoms at the outset, than in the fibrinous form, which is often regarded with indifference until the breathing has become affected. The much-vexed question of the identity or non-identity of croup and diphtheria would not be a subject of much practical importance, were it not for the fact that many lives are sacri- ficed every year on account of the duality theory. When a case is once diagnosticated as membranous croup, no precau- tions are taken to protect other members of the family, because it is not a contagious disease. I can safely say that at least one-fourth of all the cases that I have been called upon to intubate were regarded as simple fibrinous laryngitis by the attending physicians. In many instances other children in these families subsequently developed diphtheria with fatal results in not a few. 294: INTUBATION IN CROUP AND OTHER When we consider the frequency with which diphtheria begins in the air-passages, and the number of physicians — which I know from personal experience to be in the majority — who still believe in the distinction between membranous and diphtheritic croup, the extent of the danger of unrestricted intercourse between the sick and the well can be readily appreciated. While there may be, and probably is, such a disease as acute non-specific membranous croup in children, there is not a single sign or symptom by which it can be distinguished from diph- theria beginning in the glottis. The only plan, therefore, com- patible with safety, is to isolate every case in which there is even a suspicion that pseudo-membrane may be developing in the larynx, and then contradictory opinions may be entertained without injury to any one. The principal arguments advanced in favor of the duality of croup and diphtheria are that in the former the disease is confined to the air passages, and is not attended with the usual symptoms of the latter, viz. : asthenia, systemic infec- tion, glandular enlargements, albuminuria and paralyses. Those, on the contrary, who maintain the identity of these diseases regard the location or starting-point of the exudation as of no importance, and attribute the greater exemption from general infection and the absence of glandular enlargements to the smaller surface involved and the limited communica- tion of the absorbent vessels of the mucous membrane of the larynx and trachea with the glands of the neck. My own experience has led me to the conclusion that if we have a simple fibrinous croup in New York City or vicinity, it must be extremety rare. A very small percentage of the cases I have seen might have been of this nature, for any evidence to the contrary. Most of those so diagnosticated by the at- tending phj^sicians were subsequently demonstrated to have been diphtheritic in the manner previously pointed out or by the presence of a large amount of albumin in the urine, as FORMS OF STENOSIS OF THE LARYNX. 295 there is no reason for the latter complication in simple mem- branous laryngitis. During- fifteen years' service at the New York Foundling- Asylum;, I have observed that when that institution was free from diphtheria it was also free from croup, and that the prevalence of the latter always bore a direct proportion to that of the former. The same rule has also applied to private practice. While we have no positive evidence, either clinical or patho- logical, that there are two forms of acute membranous laryn- gitis in children, yet there are some facts which demonstrate that diphtheria has not the exclusive right to produce this kind of exudation. Such, for example, is the false membrane that sometimes forms on blistered, burned or other wounded surfaces, and which has the same gross and microscopical appearances as that of diphtheria. Also that which occurs in the bronchi in chronic fibrinous bronchitis, which may last for months and even years, the duration alone being sufficient to exclude any possible connection with diphtheria, unless we admit the existence of a chronic form of this disease. The following case is of particular interest in this connec- tion. A few months ago, I was requested by a physician of this city to visit a relative of his who resided in one of the neighboring States, with a view to practicing intubation for the purpose of getting rid of a tracheal cannula that had been retained for some time. The patient was a man about thirty years of age, in excellent health, with the exception of the laryngeal stenosis. Five months before I saw him he had a severe attack of acute laryngitis, following exposure to cold, which in the course of two or three days necessitated the per- formance of tracheotomy to avert threatened asphyxia. The attending physician, in relating the history of the case, fre- quently referred to what he called sloughs, that had been ejected daily from the beginning of the attack, and were sup- posed to have come from the larynx. I requested the patient, 296 INTUBATION IN CROUP AND OTHER if possible, to produce one of the so-called sloughs in my pres- ence, which he did after a good deal of effort. I found it to be a piece of pseudo-membrane, almost square, and about half an inch in diameter, somewhat thinner than that ordinarily found in croup. I submitted one of these specimens to Dr. W. P. Northrup, pathologist to the New York Foundling Asylum, for micro- scopical examination, who pronounced it identical in every particular with the fibrinous exudation of diphtheria. In the mirror the deposit could be seen about equally dis- tributed over both vocal cords and nowhere else. When questioned on the subject, the patient denied syphilis, because fully convinced that he never had it ; but he had a node on the shin at the time, which had been painful at night, and this, together with the laryngitis, was the only manifestation of the disease that had ever existed. Under the influence of mercury and the iodide, the pseudo- membrane disappeared in four days, and never returned. Making all due allowance for the fact that the inflamma- tory trouble in the larynx was syphilitic, the rapid cure of the fibrinous element, which had persisted for five months unin- fluenced by a variety of local applications, argues forcibly in favor of the mercurial treatment of croup. This patient was in daily contact with children during the whole course of his disease, none of whom suffered from any affection of the throat. Prognosis. — Diphtheritic or fibrinous croup without the aid of intubation or tracheotomy proves fatal in from 90 to 95 per cent, of the cases. About 10 per cent, of those that I have been called to in- tubate finally struggled through without it, and in private practice, 27 per cent, with intubation. This makes a total of 37 per cent., which may be taken as the best results that can be obtained in a large number of cases extending over a suffi- FOliMS OF STENOSIS OF THE LAKVXX. 297 cient period of time to include all types of the disease, mild and severe. Those who practice either operation early, of course, include the cases that would otherwise recover if not interfered with, but this does not materially alter the average just given. The latest intubation statistics are those compiled by Dr. Dillon Brown, who in the month of November, 1888, collected 2372 cases from 159 operators, with 646 recoveries, or 27.2 per cent. The age of the patient, the character of the epidemic, the origin, nature, and extent of the exudation and the complica- tions, are the important factors to be considered in estimating the probable termination in any given case. Of these, age is by all odds the most important. Although several recoveries following intubation for croup in children under one year of age have already been reported, the percentage is very small. During the second year of life, there is a marked improvement in the results, and so on with increasing age, until the period of puberty is approached, when the statistics so far indicate a falling off in the percent- age of recoveries. This may be explained by the fact that the liability to croup decreases with age, and that the number of older children so far intubated is too limited to warrant any conclusion on this subject. Furthermore, owing to the larger size of the larynx in these cases, recovery more frequently re- sults without operation than in young children, and intubation is therefore only called for in the worst forms of the disease. For the same reason, when laryngeal diphtheria in the adult produces sufficient stenosis to require surgical aid, it indicates a malignancy of the disease that is seldom recovered from. Croup that prevails during fatal epidemics of pharyngeal diphtheria is proportionately fatal and principally from the same causes, viz., greater frequency of systemic infection, of nephritis, pneumonia, and also greater tendency to invade the bronchial tubes. The latter is much more liable to occur when 298 INTUBATION IN CROUP AND OTHER the disease begins in the larynx, than in those cases in which the exudation has existed for several days in the fauces, thus having run part of its course before invading* the air-passages. For this reason the prognosis is less favorable in the so-called membranous croup than in the form that is recognized by all as diphtheritic. Distribution of the pseudo-membrane over a large surface, as when with the larynx the nose as well as the fauces is in- volved, thick deposit, dark color of the exudation, foul odor, great tumefaction of the tissues in the throat and of the glands on the outside are unfavorable to recovery. Cases with scanty secretion of urine with a perceptible amount of blood or large quantity of albumin, such as fifty per cent, or over, almost invariably terminate fatally. A more copious secretion with the same amount of albumin is of less serious import. I have never known albumin to be absent in severe cases, but it must be looked for daily, as the urine may be free from it one day, and loaded the next. A high temperature on the second or third day after intubation is an evil omen, because it usually indicates extension of the disease to the bronchi, sepsis, or pneumonia or all combined. When the laryngeal stenosis has persisted for some time, and is suffi- ciently pronounced to call for surgical interference, the tem- perature in the great majority of cases is little above the normal. This, to some extent, at least, is due to diminished oxidation in the tissues from the limited supply of air admitted to the lungs, and explains the rapid rise of temperature that not unfrequently occurs soon after intubation, and before sufficient time has elapsed for the development of any com- plication. Fever coming on in this manner is not so liable to persist, and does not possess the same prognostic significance as when it shows itself one or more days after the operation. Children in the neighborhood of four or five years of age breathe, in health, about twenty-five times per minute. An increase in the number of respirations to forty or more usually FORMS OF STENOSIS OF THE LARYNX. 299 indicates either a narrowing- of the calibre of the bronchi by pseudo-membrane or pneumonia, the latter being" a later de- velopment. Any considerable invasion of the lower air-passages by the disease, almost invariably occludes some of the bronchial tubes, which is followed by collapse of the corresponding por- tions of the lungs, and this, together with the decrease in the lumen of the others, sufficiently explains the acceleration of the breathing when no pneumonia exists. In young children it is not uncommon for the respirations under these circumstances to run as high as from eighty to one hundred or more per minute. Treatment of Croup. — In estimating the value of any remedy in the treatment of croup, a disease so fatal under all circumstances and attended by so many grave complications, it is important to resist the temptation of being influenced by the result obtained in a few cases, whether it be favorable or otherwise. The mortality from diphtheria, and consequently that from croup, varies so much in different epidemics, that it is neces- sary before arriving at any conclusion not only to observe a large number of cases, but also that these should extend over a sufficient period of time to include all types of the disease. As my own views on the medicinal treatment of diphtheria and croup coincide so perfectly with those of the author of this work it is only necessary for me to indorse the method advocated by Dr. Billington, to which the reader is referred, and give some directions for the management of laryngeal diphtheria following intubation. Of the many therapeutic agents that have been, and are still employed in the treatment of croup, I believe the bi- chloride of mercury deserves the first place. Very few, if &ny, of those who have used it, after having had sufficient experi- ence with other remedies to render their opinion of much value, have abandoned its use after a fair trial. 300 INTUBATION" IN CROUP AND OTHER After intubation the same treatment is continued, with the exception of an interval of two or three hours following- the operation, during which nothing is given by the mouth, in order to allow time for the larynx to become accustomed to the presence of the foreign body. In some cases I have found it necessary to administer small doses of whisky or brandy undiluted soon after placing a tube in the larynx, for the pur- pose of exciting sufficient cough to expel accumulated secre- tions and loose membrane, the tube with string attached fail- ing to accomplish this. With a properly fitting tube in the larynx, the difficulty of swallowing is due principally to swollen condition of the epi- glottis, which is common in croup. This is demonstrated by the fact that in other forms of stenosis in which the epiglottis is not involved, the difficulty of deglutition is soon overcome. Some of the liquids swallowed undoubtedly gain admission to the trachea through the tube, but are promptly expelled by the coughing thus excited, and are therefore harmless. But should the sensibility be so much blunted that no reflex action follows the contact of extraneous matter with the lining membrane of the air-passages, there is nothing to prevent the gravitation of whatever passes through the tube to the smaller bronchi and alveoli. The impaired sensibility in such cases is due to some form of toxasmia which precludes any reasonable chance of recover} 7 , and it is therefore scarcely worth subjecting the patient to the annoyance of feeding by stomach tube. But there are some cases that suppress the cough because it is painful, and in these the plan of feeding suggested by Dr. Cas- tleberry, of Chicago, may be tried. It consists in overcoming gravitation by placing the head considerably lower than the body, and drinking through a glass tube, nursing bottle, etc., which allows any fluid that enters the tube to escape without coughing. Some patients swallow better by taking a small quantity in the mouth at a time, others by filling the mouth. Infants FORMS OF STENOSIS OF THE LARYNX. 301 at the breast swallow better than older children, and most cases can drink better from a nursing' bottle than from a cup or glass, and on the same principle by sucking through a tube. Patients with high temperature, suffering from great thirst, will take a long drink without stopping to cough, although the desire to do so be very great. This should not be per- mitted, as it gives time for some of the liquid to enter the bronchi. The glass should be removed after every two or three acts of swallowing, and the child encouraged to cough. These precautions do not apply to cases that swallow well, which is not uncommon after the tube has remained in the larynx for a few days, if the functions of the epiglottis be not much impaired. Nourishment in the solid and semi-solid forms, which are swallowed better than liquids, should be given the preference when children can be induced to take them. Rectal feeding should be resorted to in case a sufficient amount of nutriment cannot be given by the mouth. Warm milk with whisky, to which the albumen of one or two eggs can be added, is the most convenient for this purpose. Pep- tonized milk or the expressed juice of meat is still better. The Leube Rosenthal solution of meat, dissolved in warm water, is readily absorbed by the rectum if retained long enough, as I have demonstrated many times. These injections should not be given oftener than once in three or four hours, or in larger quantities than one or two ounces to a child four or five years old, otherwise thej 7- are soon rejected. When the bowel becomes irritable, tolerance for small quantities is sometimes re-established by a large injec- tion of warm water; and should this fail, a few drops of lauda- num in warm sweet-oil or starch can be injected with a small S3 T ringe and allowed to remain about three quarters of an hour before using the nutrient enema. In this manner the bowel can be used many days in succession, and aids wonder- fully in sustaining the vital powers until the patient can be 302 INTUBATION IN CROUP AND OTHER induced to take a sufficient quantity of nourishment by the mouth. Intubation cases are not the only ones that call for rectal alimentation. It is not uncommon for children suffering from diphtheria or scarlet fever to refuse all kinds of nourishment for several days in succession, and if compelled to take it or it is given by the stomach tube, it is almost immediately rejected. Rectal feeding is just as urgently demanded under these circum- stances as if the inability to take food were due to a tube in the larynx. The most fatal of all the complications of croup is un- doubtedly the extension of the disease to the lower air-passages, or fibrinous bronchitis ; for the prevention of which there is no remedy known at present. Mercury, especially the bichloride, probably exerts some limiting or controlling power over the fibrinous exudation, which would sufficiently explain the more favorable results obtained with this than with any other remedy. Nephritis is often a serious complication, but is usually in proportion to the severity of the diphtheria and the amount of systemic infection. Thorough disinfection of the absorbing surfaces in the throat and nose is therefore an important part of the treatment. The improvement in the albuminuria goes hand in hand with that of the original disease, and rapid recovery follows as soon as the poison is completely eliminated from the circulation. From the physiological fact that urea is a constant con- stituent of normal sweat, and that its quantity is largely in- creased when there is a deficient elimination by the kidneys, free action of the skin is a rational and valuable means of carrying off excrementitious products that would otherwise accumulate in the blood and tissues when the function of the kidneys is seriously impaired. There is no better method of accomplishing free diaphoresis than that necessarily produced FORMS OF STENOSIS OF THE LARYNX. 606 by the steam treatment under a tent. Under these circum- stances the temperature of the air immediately surrounding the patient can be kept as high as 80° with advantage. With- out the kidney complication, 75° is sufficient. The high temperature that usually accompanies the pneu- monia, fibrinous bronchitis, and sepsis can, in most cases, be kept within bounds by the use of antipyrin or antifebrin com- bined with digitalis, which, even if they accomplish nothing in the way of saving life, contribute a good deal to the comfort of the patient, by allaying the thirst and restlessness produced by the fever. A sufficient amount of sleep should always be procured, and it is much better to give an anodyne for this purpose than to allow a child to pass a restless, wakeful night. If due to pain or irritation from the tube in the larynx or excessive cough, an opiate is the only remedy that will afford relief, otherwise sulphonal, in doses of from three to five grains, or a mixture of bromide and chloral, will answer the same purpose. Many times in answer to the question whether the little patient had obtained any sleep during the night, I have been told by the mother that it would have slept, had she not been obliged to administer the medicine every half-hour or hour. Nervous, irritable children who remain wakeful for some time after having been roused to take their dose, should be allowed at least three hours of uninterrupted sleep every night. From the unsatisfactory results obtained with any of the remedies at present within reach, I believe it is much safer to temporarily suspend medication than to seriously interfere with sleep. Intubation in the Adult. — The operator who has acquired proficiency in performing intubation in children, will experi- ence great difficulty when called upon for the first time to operate on the adult. The difference is due to the larger size of the larynx in the latter, but particularly to its greater dis- tance from the mouth. It is only necessary to reach far 304 INTUBATION IN CROUP AND OTHER enough behind the epiglottis to hold it erect, and this can usually be done by crowding the finger well back in the right angle of the mouth. In one case I failed absolutely, after re- peated attempts, to do more than touch the tip of the epiglottis without inserting two fingers, which filled the pharynx and left no room for the passage of the tube. Intubation was finally accomplished in this patient by the aid of the mirror, which will probably prove the better plan for those familiar with laryngoscopic manipulations. In the latter case it is necessary to drop the mirror and quickly insert the finger to push the tube home and hold it down while the obturator is being removed, for if the thickest portion of the retaining-swell be not carried well below the cords, which is often impossible while still attached to the introducer, the tube is immediately rejected. The removal of the tube from the adult larynx can be accomplished with greater ease, and with less discomfort to the patient, by guiding the extractor into it by the aid of the mirror, than by the finger, as is necessary in children. Very little practice with the laryngoscope is required for this purpose. For any form of acute stenosis of the larynx in the adult, two tubes of different sizes, the smaller for the female, the larger for the male, I believe will prove sufficient. But for the dilatation of chronic stricture, especially the cicatricial form, a set of about ten tubes will be required, and the larger of these can be used in acute cases in the adult male, the medium sizes in the adult female, and the smallest during the years of adolescence. A special introducer and extractor, longer and much stronger than those used for children, are necessary. 1 Intubation has already been successfully practiced in almost all the different varieties of stenosis that occur in the adult Niemann & Co., of this city, is the only firm at present manufact- uring tubes and accessory instruments suitable for adults. FOKMS OF STENOSIS OF THE LARYNX. 805 larynx, viz.: — Acute oedema of the glottis, erysipelatous in- flammation, laryngeal diphtheria, perichondritis, syphilitic and tubercular laryngitis, paralysis of the abductor muscles of the cords, and temporarily, in neoplasm. In cases requiring the retention of a tube for several months, it is important to change the points of pressure in the vestibule of the larynx about once in two weeks, in order to prevent erosion of the mucous membrane, with consequent sprouting of fungous granulations, which is liable to occur from the compression exerted by the constrictor muscles dur- ing every act of swallowing. The larger head that goes with the increase in the size of the tubes required for the dilatation of the stricture, accomplishes this purpose until the maximum size has been reached, when the pressure can be transferred to other points by changing the shape of the shoulder of the tube. It can, for example, be lifted higher in the larynx by increasing the thickness in the vertical direction, having the diameter the same. A hard-rubber tube may be allowed to remain in the larynx for a much longer time than one constructed of metal, because, owing to its lightness, it does not occupy a fixed position, but moves upward by coughing, and is again pressed downward by the act of swallowing. Another objection to the long retention of a metallic tube is the fact that the gold-plating soon disappears in places, followed by erosion of the metal and the deposit of calcareous matter, which produces a good deal of irritation. I have occasionally found some calcareous granules on tubes that were not long retained, and on which the plating- appeared to have been intact. The difficulty of deglutition that follows intubation in croup, and that often persists as long as the tube remains in the larynx, is not a prominent feature in chronic stenosis. The epiglottis being usually in a normal condition, soon learns to 20 306 INTUBATION IN CROUP AND OTHER. assume the whole duty of protecting- the larynx, and accom- plishes this purpose very perfectly, after a little time, without the aid afforded "by the constriction of the latter, which, I "be- lieve, is the more important of the two. With a properly fitting- tube, a healthy epiglottis, and free- dom from much inflammation or thickening above the vocal cords, the difficulty of swallowing at first experienced is usu- ally completely overcome in about a week. In the treatment of chronic stenosis of the larynx in chil- dren, the set of croup tubes will do to begin with, but the cali- bre of these is only sufficient for free respiration in a state of rest, and therefore not large enough to supply the increased demand for oxygen produced by the active exercise that these little patients take, which is not materially different from that of ordinary health. In the beginning, therefore, when it is only possible to pass a small tube through the stricture, it will be necessary to restrict the amount of exercise or even confine the patient to bed in order to avoid dyspnoea. Unlike the conditions present in croup, with its intense inflainmator\ T infiltration of the mucous membrane, which often leads to spontaneous ulceration, the larynx in these cases, aside from the constriction, is usually normal, and the same danger of injury from pressure does not exist. Much larger tubes, and more nearly cylindrical if required, can there- fore be used with perfect safety. The length of time required for the dilatation of chronic stenosis of the larynx will depend on the degree of constric- tion, its cause, and duration. In complete occlusion, atrophied muscles and anchylosed joints, the necessary result of sus- pended function, render such cases the most unfavorable for speedy cure. Even a very small opening in the larynx, that allows the entrance of some air, which keeps the arytenoids and the mus- cles that move them in use, gives a better prospect of recovery in a reasonable time. FORMS OF STENOSIS OF THE LARYNX. 807 Cases in which a tracheal cannula has been retained as long- as a year or more will usually require dilatation for several months to effect a permanent cure. Where complete closure of the larynx exists, divulsion should be practiced through the tracheal wound from below, because owing to the gradual inclination of the vocal cords from the circumference towards the centre in this situation, there is no danger of passing the sound or other instrument used anywhere else than in the line of the original opening; while if done from above, through the mouth, there can be no certainty that the point of the instrument is not in one of the ventricles, which it would penetrate with the employment of less force than would be required to pass through the cicatri- cial tissue uniting the vocal cords. In the majority of the cases so far treated by myself and others, syphilis, usually in its tertiary form, was the cause of the stenosis. In two children, one a constriction, the other a complete occlusion, the cause was high tracheotomy for croup. The operation in both of these cases involved at least the subglottic division of the larynx, which is often selected because, being less deeply seated, it is more accessible than the trachea. In one adult, also, who had worn a tracheal cannula for two years, the opening had been made in the cricothyroid space, and in another immediately below the cricoid cartilage. The lumen of the trachea is large, while that of the larynx is comparatively small, and, besides the delicate articular and muscular apparatus of the latter is liable to serious injury from the irritation of a cannula if long retained. There is therefore no excuse for laryngotomy or high tracheotomy, ex- cept for the removal of a foreign body or neoplasm, and possi- bly when pressed for time in case of threatened asphyxia, as these operations are undoubtedly the most frequent cause of retained cannulas in croup and other forms of obstruction that recover in a short time. 308 INTUBATION IN CROUP, ETC. To insure success in management of chronic stenosis of the larynx, some ingenuity and a great deal of patience and per- severance are necessary in order to overcome the many diffi- culties encountered. No set of instruments, however complete, will he sufficient for all cases, no two of which are alike, and the construction of tubes adapted to special peculiarities will sometimes be required. INDEX. Abbrcrombie, albuminuria in diphtheritic paralysis, 115. lesions found in diphtheritic paralysis, 67. Abscess, retro-pharyngeal, mis- taken for croup, 292. Accommodation, defective, in diphtheritic paralysis, 109. Acid, boracic, in the treatment of diphtheria, 194. carbolic, local use of, 180. citric, local use of, 199. lactic, as a solvent of false membrane, 164. salicylic, formula for internal administration of, 220. local use of, 180. sulphurous, internal use of, 183, 222. Aconite, 219. Adamson, E., internal use of tincture of iodine, 186. Adenitis in diphtheria, treatment of, 231. in nasal diphtheria, 74. in pharyngeal diphtheria, 71. prognostic significance of, 142. Adult, intubation in the, 303. Aerotherapy, antiseptic, 197. Aetius Cletus, epidemic of diph- theria described by, 5. Aetius of Amida, description of diphtheria by, 3. Afanasieff, V., poisoning by chlo- rate of potassium, 191. Age, in relation to success of in- tubation, 297. influencing the occurrence of diphtheria, 16. Air, communication of diphtheria through the, 28. Albuminuria, complicating diph- theria, 89, 302,. duration of, 92.* in diphtheritic paralysis, 115. Albuminuria in relation to prog- nosis, 91, 298. of diphtheria and of scarla- tina, differences between, 92. therapeutic indications fur- nished by, 234. time of occurrence of, 90. Alcohol in heart failure, 233. in laryngeal diphtheria, 243. , in the treatment of diphthe- ria, 204. Alum, local employment of, 161. Amaurosis, diphtheritic, 113. America, early epidemics of diph- theria in, 8. Angina, diphtheroid, in scarla- tina, 104. maligna, 3. ulcero-membranous, diagnosis of, from diphtheria. 123. Animals, diphtheria in, 23 inoculation experiments on, 26. Antifebrin, 219, 303. Antipyretics in the early stage of pharyngeal diphtheria, 218. •Antipyrin, 219, 303. Antiseptic aerotherapy, 197. fumigations, 198. tracheotomy in the preven- tion of bronchial diphthe- ria, 249. treatment, prophylactic value of, 147. Antiseptics in the treatment of diphtheria, 170. Anus, diphtheria of the, 88. Appendix, 259. Applications, local, 156. Apomorphia in laryngeal diph- theria, 243. Archambault-Reverdy, 159. Aretceus of Cappadocia, diphthe- ria described by, 2. 310 INDEX. Aretseus of Cappadocia, on the use of caustics, 157. recommended the use of alum and tannin, 161. Articulation, difficult, in diphthe- ritic paralysis, 109, 111 Artificial feeding after intubation, 301. in diphtheritic paralysis, 256. respiration in diphtheritic pa- ralysis, 256. Asclepiades, 2, 265. Asthenia in constitutional poison- ing, 76. Asthenopia in diphtheritic par- alysis, 109. Astringents, local employment of, 161. Ataxia, diphtheritic, 110. Atomizers for use in the treat- ment of laryngeal diptheria, 238. for use in spraying the phar- ynx, 216. Aubrun, perchloride of iron in diptheria, 202. Aurelianus, Coelius, description of diphtheria by, 3. Author's conclusions as to the etiology of diphtheria, 43. treatment of diphtheria, 210. views as to the non -identity of croup and diphtheria, 61. views as to the primary na- ture of diphtheria, 96. Auto-inoculation of diphtheria, 25. Babes, bacteriological investiga- tions of, 39. Bacillus of Klebs and Loeffler, 259. Bacteria, absence of, in artifici-_ ally produced pseudo-mem- ' brane, 59. aerobic and anerobic, 42. in diphtheritic membrane, 31, 259, 263. resistance of the organism to invasion by, 171. Baillou, epidemic of diphtheria described by, 4. Barbosa, epidemic of diphtheria described by, 5. Bard, Samuel, treatise on diph- theria by, 9. Baruch, S., internal use of oil of turpentine, 196. Beale, micro-organisms in diph- theria, 32. Becquerel, 14. Beef -tea and alcohol, comparative effects of, as stimulants, 206. Benzoate of sodium in the treat- ment of diphtheria, 190, 222. Bernhardt, loss of knee-jerk in convalescence from diphtheria, 114. Billroth, micro-organisms in diph- theria, 32. Birds, diphtheria in, 23. Bladder, diphtheria of, 88. . diphtheritic paralysis of the. 113. Blair, Patrick, epidemic of " croops " described by, 6. Bloebaum, employment of galva- » no-cautery by, 159. Blood changes in diphtheria, 62. micrococci in the, 32. Boissarie quoted by Growers, cases of paralysis occurring simul- taneously with other cases of diphtheria, 118. Boldyrew, views of, 47. Boracic acid in the treatment of diphtheria, 194. Borax in the treatment of diph- theria, 193. Bosse, internal use of oil of tur- pentine, 195. Bouchut, favorable results from the use of nitrate of silver, 158. method of intubation of the larynx devised by, 15, 266. Boyd, J. M., veratrum viride in diphtheria, 209. Braddon, L., local use of oil of peppermint, 199. Brain, changes in, 65. Breath, foetor of, in pharyngeal diphtheria, 70. Breathing in laryngeal diph- theria, 82, 84, 290. Bree, J., internal use of cyanide of mercury, 177. Bretonneau, limitations in the use of caustics, 157. artificial production of pseu- do-membrane, 58. syringe for nasal use, 226. term diphtherite proposed by, 1. treatises on diphtheria by, 11. unsuccessful attempt at inoc- ulating animals by, 26. use of alum by, 161. Bromine in the treatment of diph- theria, 184, 196. Bronchitis, catarrhal, in diphthe- ria, 64. INDEX. 311 Bronchitis, diphtheritic, 137, 802. pseudo-membranous, in diph- theria, 64. Broncho-pneumonia in diphthe- ria, 64. Brondel, treatment of diphtheria by benzoate of sodium, 190. Brown, Dillon, quoted by Jacobi, internal use of bichlo- ride of mercury, 175. reference to bibliography on intubation prepared by, 266. statistics of intubation, 297. Graham, parasiticidal action of benzoate of sodium in diphtheria, 190. Lenox, rhinoscopic view o'f posterior nares in naso- pharyngeal diphtheria, 134. T. Clowes, successful treat- ment by, 213. Brunton, action of iron, 201. advantages of nitrate of sil- ver, 159. on alcohol, 206. Buhl, lesions found in diphthe- ritic paralysis, 66. tissue infiltration observed by, 47. Bullard, W. E., cases treated by, 211. Buzzard, T., the pathology of diphtheritic paralysis, 117. Cadet de Gassicourt, diphthe- ritic paralysis of the heart, 112. heart-clots in diphtheria, 63. albuminuria in diphtheria, 91. Caldwell, W. C, local use of hydronaphthal with papain, 200. Calomel, fumigations with, 178. in the treatment of diphthe- ria, 173. Cannula, tracheal, 251. Carbolic acid, local use of, 180, 236, 237. Cardiac complications, symptoms of, 93. depressants in the treatment of diphtheria, 209. Carmichael, quoted by Holt, 128. Carter, E. C, use of bichloride of mercury, 175. Caselli, A., statistics of trache- otomy, 245. Castleberry, plan of feeding after intubation, 300. Casts in the urine, prognostic sig- nificance of, 92. Catheterization of the larynx, 265. Causation of diphtheria, 16, 259. Caustics, use of, in diphtheria, 157, Cautery, actual, use of, 158. galvano-, use of, 159. Cells, degenerative metamorpho- sis of, in diphtheria, 51. Chaff ey, W. C, heart-clots as a cause of death, 63. Chagin, Gustav, statistics of trach- eotomy in infants, 246. Chapin, H. D., trypsin as a solv- ent of false membrane, 164, 167. Charcot and Vulpian, peripheral lesions in diphtheritic paraly- sis, 65. Chaussier, on catheterization of the larynx, 265. Cheyne, W. W., antiseptic trach- eotomy, 249. antiseptic treatment employ- ed by, 172. Childhood, diphtheria mainly a disease of, 16. Children, special therapeutic in- dications in the case of, 152. why diphtheria attacks chief- ly, 17. Chinoline, local use of, 181, 196. Chittenden, R. H., pepsine as a solvent of false membrane, 167. Chloral in the treatment of diph- theria, 187, 222. Chlorate of potassium, formula for internal administra- tion of, 219. in the treatment of diph- theria, 191. poisonous action of, 191. Chloride of iron, formula for in- ternal administration of, 220. internal use of, 196, 201. limitations to its utility, 202. Chlorine in the treatment of diph- theria, 183. Cholewa, on the local use of men- thol, 199. Chomel, epidemic of diphtheria described by, 6. Cinchona in diphtheria, 233. Citric acid, local use of. 199. Clark, C. C. P., on the employ- ment of Monsel's solution, 161. Cleanliness, necessity of, 170. 312 INDEX. Climate in relation to diphtheria, 18, 60. Clothing, conveyance of the con- tagion of diphtheria by, 28. disinfection of, 148. Coagula in heart and large vessels 63. Coagulation-necrosis, 48. caused by temporary cutting off of the blood supply, 58. Coffee in heart failure, 233. Cohnheim, production of coagula- tion-necrosis by temporary arrest of the circulation, 58. Cold, catching, membranous croup from, 59. favoring attacks of diph- theria, 18. Colden, Cadwallader, epidemic of diphtheria described by, 9. Cologne water, pseudo-membrane caused by local application of, 57. Comstock, D. C, cases treated by, 211. Congestion, pulmonary, in diph- theria, 64. Conjunctivitis, diphtheritic, 14. sj'mptoms of, 86. treatment of, 257. Constitutional poisoning from concealed nasal or bron- chial diphtheria, 99. not dependent upon pu- trefactive decomposi- tion of the false mem- brane, 76. Constitutional symptoms often relieved by local treatment, 102. Contagion, occurrence of diph- theria by, 24. of diphtheria, conveyance of by food and drink, 29. difference in virulence of, in epidemic or sporadic and endemic cases, 30. nature of, 30. retention of, in furniture and clothing, 28. Convalescence, tonics during, 232. Copaiba in the treatment of diph- theria, 208. Copper sulphate as a caustic in diphtheria, 158 Corbin, J., mercurial fumigations, 178. Cornil and Babes, bacteriological investigations, of, 39. Corrosive sublimate, formulae for the internal administration of, 221. Corrosive sublimate, internal ad- ministration of, 175, 241, 299 local use of, 171, 196. Cough after intubation, 276. in larvngeal diphtheria, 82, 83, 289. Croup and diphtheria, question of identity of, 59, 61, 293. catarrhal and membranous, differential diagnosis, 136, 293. diagnosis of, 289. intubation in, 265. See In- tubation, membranous and diphtheri- tic, differential diagnosis, 137 prognosis of, 296. relation of season to, 60. simple membranous, from " catching cold," 59. treatment of, 299. after intubation, 300. Croup-kettle, 240. Croupal false membrane, 48. Croupous inflammation, 49. possibility of multiple causes for, 42, Cubebs in the treatment of diph- theria, 208. Curtis and Satterthwaite, inocu- lation experiments by, 27. micro-organisms in diphthe- ria, 32. Cvanosis in laryngeal diphtheria, 84. an uncertain indication of in- tubation, 271. Da Costa, local use of thymol, 199. ulcero-membranous angina, 123. Daly, W. H , calomel in the treat- ment of diphtheria, 174. Dampness favoring attacks of diphtheria, 18. Darken, E. J., cases treated by, 211. Death in laryngeal diphtheria, 84. Deglutition, difficult, after intu- bation, 300. after intubation, not promi- nent feature in adults, 305. in diphtheritic paralysis, 109, 111. management of, 256. Dejerine, lesions found in diph- theritic paralysis, 66. Delavan, D. Bryson, anatomy of the tonsils, 124. INDEX. 313 Delavan, D. Bryson, constitu- tional infection following nasal diphtheria, 99. Delirium, prognostic significance of, 143. Delthil, account of diphtheria in animals by, 23. turpentine inhalations, 197, 241. Deslandes, 13. D'Espine, A., bacteriological in- vestigations of, 39. parasiticidal action of salicy- lic acid, 181. Details, necessity of attention to, 153. Diagnosis of croup, 289. of diphtheria, 121 et seq. Dickinson, J., epidemic of diph- theria described by, 8. Diet in diphtheria, 223, 232. Digitalis in albuminuria with ursemic symptoms, 235. in fever, 303. in heart failure, 233. Diphtheria a constitutional dis- ease, arguments in support of, 97. a local disease, arguments in support of, 96. ages of those attacked by, 16. albuminuria in, 89, 302. and croup, question of iden- tity of, 59, 61, 293. and follicular tonsillitis, dif- ferential diagnosis, 130. and membranous croup, dif- ferential diagnosis, 137. and membranous pharyngi- tis, differential diagnosis, 123. and scarlatina, differential di- agnosis, 135. bronchial, diagnosis, 137. prevention of, by early tracheotomy, 249. symptoms of, 85. treatment, 302. cardiac complications, symp- toms of, 93. classification of, 68. climate in relation to, 18. communication of, by a bite, 4. through the air, 28. constitutional, alcohol in the treatment of, 205. recovery following, 77. relapses in, 78. signs of approaching death in, 77. symptoms of, 75. Diphtheria, constitutional, treat- ment of, 230. contagion of, 24. convalescence from, 78. cutaneous, 89. treatment, 258. deep, 51. definition, 1. derivation of term, 1. diagnosis, 121 et seq. endemic prevalence, insani- tary conditions a potent factor in, 22. epidemics of, in the middle ages, 3. eruptions in, 94. etiology of, 16, 259. gangrene in, 81. gangrenous, prognosis of, 143. histological changes in, 51. history, 2. in animals, 23. incubation of, 44. infection of, 24. influence of season upon the occurrence of, 19. inoculation of, 26. intestinal, diagnosis of, 137. symptoms of, 88. laryngeal, diagnosis of, 289. emetics in, 242. intubation in, 265. See Intubation. prevention of, 235. prognosis of, 296. symptoms of, 82. terminations of, 84. tracheotomv in, 244. treatment of, 235, 299. treatment of, after intu- bation, 300. malignant, 79. micro-organisms in, 31, 259. mortality, statistics of, 139. nasal, diagnosis of, 135. especially liable to be at- tended with constitu- tional poisoning, 74. prognosis of, 143. symptoms, 73. nature of contagium of, 30. nephritis in, 89. of the anus, 88. of the digestive tract, expla- nation of the rarity of, 97, of the ear, symptoms of, 85. of the Eustachian tubes, 85. of the eye, symptoms of, 86. treatment of, 257. of the genito-urinary organs, 314 INDEX. Diphtheria of the mouth, 75. of the oesophagus, diagnosis of, 137. symptoms of, 87. of the stomach, diagnosis of, 137. symptoms of, 88. of the vulva, 88. of wounds, 89. paralysis following, 108. parenchymatous, 51. pathology, 46 et seq. pharyngeal, diet in, 223. symptoms, 68. of catarrhal stage, 69. of stage of pseudo- membranous forma- tion, 70. terminations of, 72. treatment of early stage of. 214. of later stage of, 229. poison of, 262. predisposition, individual, or family, to, 18. primary nature of, 96. prognosis of, 139 et seq. prophylaxis of, 145 et seq. pulmonary complications, symptoms of, 93. second attacks of, 18. secondary, 104. location of pseudo-mem- brane in, 107. septic, recovery following, 77. relapses in, 78. signs of approaching death in, 77. symptoms of, 75. superficial. 51, 78. symptoms, 68 et seq. tonsillar, explanation of fre- quency of, 56. tracheal, symptoms of, 85. transmission of, by direct con- tact, 25. treatment, 150 et seq. two forms of, 35. vaginal, 88. without a diphthera, improb- able, 123. Diphtheritic and scarlatinal al- buminuria, differences be- tween, 92. false membrane. See Pseudo- membrane, inflammation, 50. process, mode of extension of, 54. paralysis, 108. See Paraly- sis, diphtheritic. Diphtheritic sore-throat, a term too vaguely applied, 122. Diphtheritis, superficial, 51. Diplopia in diphtheritic paralysis, 109. Disinfectants, how to use, 148. list of necessary, 147. Disinfection, efficiency of, in pro- phylaxis, 149. instructions for, 147, 170. Dissault, on catheterization of the larynx, 265. Donders, paralysis of ciliary muscles following diphtheria, 107. Douglas, William, 8. Drain-throat, 123. Druitt, Robert, perchloride of iron in diphtheria, 202. Duchenne, use of the faradic cur- rent in the dyspnoea of diphthe- ritic paralysis, 256. Dwellings, insanitary condition of, favoring the occurrence of diphtheria, 21. Dysesthesia, in diphtheritic par- alysis, 110. Dyspnoea as an indication for in- tubation, 270. . for the removal of the tube after intubation, 278. for tracheotomy, 244. from tumefaction of the ton- sils, 291. in diphtheritic paralysis, management of, 256. in laryngeal diphtheria, 82, 84, 290. Ear, diphtheria of, symptoms of, 85. Eau-de-Cologne, p s e u d o-m e m- brane caused by local applica- tion of, 57. Electrical reactions in diphtheri- tic paralysis, 114. Electricity in diphtheritic paraly- sis, 254. Emangard, 13. Emboli causing infarctions in diphtheria, 63. Emetics, failure of, in asphyxia, 243. in croup, caution in the use of, 242. Emmerich, micro-organism de- scribed by, 35. Emphysema, acute general, some- times present in croup, 271. INDEX. 815 Emphysema, pulmonary, in diph- theria, 64. Endemic prevalence of diphthe- ria, 22. Endocarditis not a frequent com- plication, 64. Engelmann, local use of vinegar, 199. Epidemic occurrence of diphthe- ria, 29. Epidemics of diphtheria in the middle ages, 3. Epistaxis in nasal diphtheria, 74. Epithelial changes in diphtheria 51. Epithelium, normal, of mouth and throat, impermeable by bacteria, 56. Eruptions, diphtheritic, 94. Etiology of diphtheria, 16, 259 Eucalyptus, vapors of. in the treatment of diphtheria, 198. Eustachian tubes, diphtheria of, 85. Euthanasia not always afforded by tracheotomy, 248. Eye, diphtheria of the, 86, 257. Fagge, Hilton, membranous laryngitis caused by local injury 57. Feeding after intubation, 300. artificial, after intubation, 301. in diphtheritic paralysis, 256. error of over-, in diphtheria, 223, 232. Fever as an indication for re- moval of the tube* after in- tubation, 279. in constitutional poisoning, 76. in pharyngeal diphtheria 69, 71, 79. not necessarily a sign of con- stitutional infection, 98. prognostic significance of, 142. treatment of, 218, 303. Fieuzal, local use of lemon juice, 199. Foetor of the breath in pharyn- geal diphtheria, 70. Food and drink, aversion to, in constitutional poisoning, 77. contagion of diphtheria con- veyed by, 29. to be given at regular inter- vals, 224. Forceps, tracheal, 253. Formulae, see under Treatment. Fothergill, John, epidemic de- scribed by, 6. Fowler, Geo. B., calomel in the treatment of diphtheria, 174. Fox, quoted by Lefferts, spread- ing quinsy, 127. Fruitnight, J. H., internal use of hyposulphite of soda, 183. Fumigation of rooms, 148. Fumigations, antiseptic, 198. mercurial, 178. Furniture, retention of the con- tagion of diphtheria, in, 28. Gag, mouth, in intubation, 266. Galvano-cautery, use of, 159. Gangrene, occurrence of, in diph- theria, 81. Gangrenous diphtheria, prognosis of, 143. Gargling, availability of, 155. Garrotillo, 4. Gaucher, lesions found in diph- theritic paralysis, 67. Genito-urinary organs, diphtheria of, 88. Gerhardt, account of diphtheria in animals by, 23. Gibney, quoted by Holt, 126. Gifford, H. , on the Marchand solu- tion of per-oxide of hydrogen, 189. Glands, swollen, in diphtheria, treatment of, 231. in nasal diphtheria, 74. in pharyngeal diphtheria, 71. Glottis, intubation of 'the, 265. See Intubation, oedema of, mistaken for croup, 292. Glycerine, advantage of, in cover- ing the acridity of tincture of iron, 220. Gowers, frequency of diphtheritic paralysis, 108. on electricity and strychnine in diphtheritic paralysis, 255. v. Graefe, diphtheritic conjunc- tivitis described by, 14. Guelpa, G., irrigation in the treatment of diphtheria,210. method of employing irriga- tion, 218. Guersant, articles on diphtheria by, 12. Guttmann, G., successful use of pilocarpine, 170. Hemorrhages in malignant diphtheria, 80. 316 INDEX. Haig-Brown, quoted bv Holt, 126. Hanks, H. T., remarks by, 211. Hatfield, M. P., use of peroxide of hydrogen, 188. Health Department of New York City, instructions for disin- fection, 147, 170. statistics of diphtheria, 16, 19, 139 Heart, affections of, in diphtheria, 93. changes in diphtheria, 63. clots as a cause of death in diphtheria, 63. diphtheritic paralysis of, 110. failure, treatment of, 233, 257. Henoch, employment of galvano- cautery by, 159. mortality of diphtheria, 140. Henry, F. P., hypodermic injec- tions of bicyanide of mercurv, 178. Hepatic lesions in diphtheria, 65. Herpetic sore throat, diagnosis of, from diphtheria, 123. Heslop, 15. Hesse, P., local use of bromine, 184. Heubner, O., absence of bacteria in artificially produced pseudo-membrane, 59. production of false membrane by temporary arrest of cir- culation in the part, 58. scarlatinal diphtheria, 106. Hiller. local use of bromine, 184. Hippocrates, on catheterization of the larynx, 265. Hirsch, relation of croup to the season, 60. Histological changes in diphthe- ria, 51. History of diphtheria, 2. of intubation, 265. Hoarseness in croup, 290. v. Hoffmann-Wellenhoff, bacte- riological investigations of, 40. Hofmokl, use of peroxide of hy- drogen, 188. Holt, L. Emmet, croupous tonsil- litis, 128. follicular tonsillitis and diph- theria not related, 126. necessity of correct diagnosis in estimating the results of treatment, 154. Home, Francis, treatise on croup by, 6. Huber, F., bichloride of mercury, 175, 221. Hueter, 27. Hullmann, therapeutic value of chlorate of potassium, 192. Humidity favoring attacks of diphtheria, 18. Hutton, T. J., use of nitrate of silver by, 159. Hvdrogen peroxide, local use of, 188, 222. Hydronaphthal, local use of, 200. Immunity, temporary, afforded by one attack of diphtheria, 18. Incubation, period of, 44. Indications to be met in the treatment of diphtheria, 150. Infection, general, mode of pro- duction of, 62. not necessary to the produc- tion of croupous or diph- theritic inflammation, 57, 60. occurrence of diphtheria by, 24. Inflammation, croupous, 49. diphtheritic, 50. Injection, hypodermic, of mer- curial salts, 178. nasal, fluids for, 228. Inoculation, diphtheria com- municated by, 26. with cultures of Loeffler's ba- cillus, 259. Insanitary conditions favoring the occurrence of diphtheria. 21. Internal administration of rem- edies, 155. Intestines, diphtheria of the, diag- nosis of, 137. symptoms of, 88. diphtheritic paralvsis of the, 113. Intubation in croup and other acute and chronic forms of stenosis of the larynx, 265. accidents and dangers of, 280. abrasious of mucous mem- brane, 288. accumulation of tenacious mucus, 285. contact of tube with the anterior Avail of the larynx or trachea, 281. coughing out the tube, 285. false passage, 280. passage of extractor beside the tube, 286. pushing down false mem- brane, 281. tumefaction of epiglottis and aryepiglottic folds, 285. INDEX. 317 Intubation, ulceration caused by the tube, 288. caution as to the manner of extraction of the tube, 277. cough after, 276 defects in the tubes, 287. description of instruments for, 266. difficulty of deglutition after, 300. feeding after, 300. history, 265. in chronic stenosis in children, 306. in the adult, 303. indications for, 270. for removal of the tube, 278. instruments for, 266. in adults, 304. introduction of the tube, 274. method of operation, 272. obstruction of the tube, 278. practice on larynx of a small animal useful, 276. removal of obturators, 275. statistics of, 297. time for performing, 270. for removing the tube, 278. required for, 280. treatment of croup after, 300. withdrawal of the tube, 275. Inunctions, mercurial, 177. Iodine, use of, in diphtheria, 185, 222. Iodoform, local use of, 186, 222. Iodol, 187. Ipecacuanha, syrup of, in laryn- geal diphtheria, 242. Iron, chloride of, formula for in- ternal administration of, 220. internal use of, in the treatment of diphthe- ria, 196, 201. limitations to its utility, 202. local employment of, 162. solution of the subsulphate, local employment of, 161. Irrigation in the treatment of diphtheria, 210, 218. means of effecting, 156. Irritants, topical, in diphtheritic • paralysis, 256. Irritation, necessity of avoiding, in the treatment, 152. Isolation, efficiency of, in pro- phylaxis, 149. necessity of, 146. Jaborandi, use of, to loosen the false membrane, 169. Jacobi, A., chloride of iron in diphtheria, 203. diphtheritic paralysis not the result of the same cause in every case, 120. disadvantages of the employ- ment of steam, 164. internal use of bichloride of mercury, 175. inunctions with oleate of mer- cury, 178. method of treatment advo- cated by, 212. tolerance of corrosive subli- mate by children, 241. use of papayotin, 169. Keating, local use of tincture of iodine, 185. Kidd, Percy, lesions found in diphtheritic paralysis, 67. Kidneys, changes in, 65. Klebs and Loeffler, bacillus of, 259. Klebs, micro-organisms in diph- theria, 32. microsporon diphtheriticum of, 35. Klingensmith, J. P., large doses of calomel in the treatment of diphtheria, 174. Knaggs, H. V., internal use of sulphur, 182. Knee-jerk, loss of, following diphtheria, 114. Koch, antiseptic action of ben- zoate of sodium, 190. antiseptic action of lime- water, 166. bactericidal action of bi- chloride of mercury, 171. Kotzuski, calomel in the treatment of diphtheria, 174. Lactic acid as a solvent of false membrane, 164. Landouzy, influence of age in the occurrence of diphtheritic par- alysis, 100. Laryngeal diphtheria. See Diph- theria. Laryngismus stridulus, mistaken for croup, 292. Laryngitis, catarrhal and mem- branous, differential diag- nosis, 136. croupous and diphtheritic, differential diagnosis, 137. 318 INDEX. Laryngitis, membranous, of non- specific origin, 57, 60. syphilitic, false membrane in, 295. Laryngoscope, use of, in intuba tion in the adult, 304. Laryngoscopic appearances in diphtheritic paralysis of the vocal cords, 111. Larynx, chronic stenosis of. in children, intubation for,S.0o. downward movement of, dur- ing inspiration pathogno- monic of obstruction, 271. extension of membrane to the, prevention of, 235. intubation of, 265. lumen of subglottic division of the, 268. stenosis of, intubation in, 265. Lax, formula for the employ- ment of pilocarpine, 170. Lefferts, Geo. M., follicular ton- sillitis, 127. Le Gendre, formula for the em- ployment of borax, 193. local use of iodoform, 186. Lemon juice, local use of, 199. Lepine, lesions found in diphthe- ritic paralysis, 66. Letzerich, internal use of benzo- ate of sodium, 190. tilletia diphtheritica of, 35. zygodesmus fuscus of, 31. Leyden, lesions found in diphthe- ritic paralysis, 66. Liblond, local use of resorcine, 182. Lime, slacking, for inhalation in laryngeal diphtheria, 241. Lime-water and carbolic-acid spray in laryngeal diphthe- ria, 236, 237. as a solvent of false mem- brane, 164. therapeutic value of, in diph- theria, 165. vapor of, is simply steam, 164. Liouville, lesions found in diph- theritic paralysis, 66. Liquor sodse chlorate, local use of, 184. potass* as a local application, 166. Liver, changes in, in diphtheria, 65. Local applications, 156. Local disease, diphtheria prima- rily a, 96. Locomotor ataxia and diphtheri- tic paralysis, differential diag- nosis, 138. Loeffler, bacillus of, 259. Loeffler, Friederich, bacterio- logical investigations of, 36. Loomis, A. L. , heart-clots in diph- theria, 63. Lorain and Lepine, lesions found in diphtheritic paralysis, 66. Lovett and Munro, statistics of tracheotomy, 245, 246, 247, 248. Lunar caustic, local applications of, 157, 159. Lungs, affections of, complicating diphtheria, 93. changes in, in diphtheria, 64. Lunin, comparative statistics of the results of treatment by va- rious remedies, 196. McDonnell, R. L., loss of knee- jerk in diphtheria, 115. Mackenzie, early advocacy of the topical use of nitrate of sil- ver by, 12. use of nitrate of silver intro- duced by, 157. Mackenzie, Morell, confluent her- pes of the throat, 123. inadequacy of medical treatment alone in laryngeal diphtheria, 244. instances of varying periods of incubation in diphtheria, 44. Maingault, diphtheritic paralysis described by, 14. Malignant diphtheria, 79. Marchand, solution of peroxide of hydrogen, 188. Mason, local use of permanganate of potassium, 188. Membrane, false. See Pseudo- membrane. Mendel, lesions found in diph- theritic paralysis, 67. Menthol, local use of, 199. Mercier, A., choral in the treat- ment of diphtheria, 187. Mercurial ointment, inunctions of, 177. Mercury, acid nitrate of, as a caustic in diphtheria, 158. bichloride of, formulae for the internal administration of, 221. in diphtheria, 299. in laryngeal diphtheria, 241. local use of, 171, 196. . biniodide of, 177, 222. cyanide of, 171,177, 222. INDEX. 319 Mercury, fumigations of, 178. iodides of, 171. mild chloride of, internally, 173. oleateof, inunctions with, 177. salts of, fumigations with, 178. hypodermic injections of, 178. injurious effects from the abuse of, 179. internal use of, 173, 222. local use of, 171, 222. may aggravate constitu- tional symptoms, 179. yellow sulphate of, as an emetic in laryngeal diph- theria, 242. v. Mering, quoted by Seeligmul- ler, 192: Metschnikoff, destruction of bac- teria by the cells, 171. Meyer, lesions found in diphthe- ritic paralysis, 67. Micrococcus of Oertel, 31. Micro-organisms in diphtheria, 31, 259. in the blood of diphtheritic patients, 32. ■ Milk, contagion of diphtheria con- veyed by, 29. Milk diet in pharyngeal diphthe- ria, 223. Monsel's solution, local employ- ment of, 161. Moore, W. 0., rarity of ocular diphtheria, 87. Mott, lesions found in diphtheritic paralysis, 67. Mouth, diphtheria of the, 75. Mouth-gag in intubation, 266. Mundie, GL, ethereal solution of iodoform for local use, 187. Mufioz, apomorphine in laryngeal diphtheria, 243. Murray Gribbes, J., eucalyptus vapors, 198. Nares, cleansing of the, 225. Nasal diphtheria, diagnosis of, 135. especially liable to be attended with constitu- tional poisoning, 74. • prognosis of, 143. symptoms, 73. treatment of, 224. Nature, primary, of diphtheria, 96. Nephritis in diphtheria, 65, 89, 302. Nerve lesions in diphtheritic pa- ralysis, 65, 115. Neuritis, interstitial, in diphthe- ritic paralysis, 116. migrans found by Leyden in diphtheritic paralysis, 66. parenchymatous, in diphthe- ritic paralysis, 115. Nicati, account of diphtheria in animals by, 23. Nitrate of silver, local applica- tions of, 157, 159. Nitric acid as a caustic in ("iph- theria, 158. Noel, internal use of borax, 194. Northrup, W. P., examination of false membrane by, 296. Norwood's tincture of veratrum viride in diphtheria, 209. Nuclei, degenerative metamor- phosis of, in diphtheria, 52. Oatman, E. L., local use of bi- chloride of mercury, 176. CVDwyer, Joseph, dose of bichlo- ride of mercury in croup, 241. emetics in laryngeal diphthe- ria, 242. method of intubation of the larynx devised by, 15. quoted by Jacobi, internal use of bichloride of mercury, 175. (Edema in diphtheritic albumi- nuria, 92. of the glottis mistaken for croup, 292. Oertel, M. J., artificial production of false membrane, 58. bacteriological investigations of, 40. histological changes in diph- theria, 51. inoculation experiments by, 27. lesions found in diphtheritic paralysis, 66. micrococcus of, 31. warm vapor recommended by, 163. (Esophageal diphtheria, diagno- sis of, 137. explanation of rarity of, 98. symptoms of, 87. usually secondary, 107. Ory, formula for local applica- tions of salicylic acid, 181. Otitis media, diphtheritic. 85. Oxygen in the treatment of diph- theria, 188 Ozone, inhalations of, 189. 320 INDEX. Pain in pharyngeal diphtheria, 70. Palate, soft, diphtheria of, 68. paralysis of, 108. Papayotin as a solvent of false membrane, 168, 200. Paralysis, acute atrophic and diphtheritic, differential diagnosis, 138. beginning in the extremities after cutaneous diphtheria, 116. cardiac, treatment of, 257. diphtheritic, 108. albuminuria in, 115. causation of, 117. diagnosis of, 188. disturbances of vision in, 109. duration, 108-114. early mention of, 5 et seq. electricity in, 254. experimental production of, 261. involving the extremities, 110. nerve lesions in, 115. of special senses, 113. of the bladder, 113. of the heart, 110. treatment of, 257. of the intestines, 113. of the larynx, 110. of the muscles of the neck and trunk, 111. pathology, 65, 115. post-mortem changes in 65. prognosis of, 144. strychnine in, 255. symptoms, 108. tendency to spontaneous recovery, 254. treatment, 254, Pathology of diphtheria, 46 et seq. Paulinus, account of diphtheria in animals by, 24. Pepper, W., internal use of bi- chloride of mercury, 175. Peppermint, oil of, local use of, 199. Pepsin as a solvent of false mem- brane, 166. Permanganate of potassium, local use of, 188. Peroxide of hydrogen, local use of, 188-222. Pharyngeal diphtheria, mild or benign form, symptoms of, 72. Pharyngeal diphtheria, severe form, symptoms of, 72. symptoms in stage of pseudomembranous formation, 70. symptoms of catarrhal stage, 69. terminations of, 72. treatment of, 214, 229. Pharynx and soft palate, diph- theria of, symptoms, 68. Pierret, lesions found in diph- theritic paralysis, 66. Pilocarpine, use of, 169. Pitres, lesions found in diphthe- ritic paralysis, 67. Plenio, statistics of tracheotomy, • 245. use of iodoform in diphthe- ritic invasion of the trache- otomy wound, 187. Pneumonia in diphtheria, 64. Poison, diphtheritic, 262. channels of absorption of, 62. Potash, caustic, local use of, in diphtheria, 158. Potassium, chlorate, formula for internal administration of, 219. in the treatment of diph- theria, 191. poisoning by, 191. permanganate, local use of, 188. Poultry, diphtheria in, 23. Powell, Seneca D., inhalations of ozone in diphtheria, 190. Predisposition, individual or fam- ily, to diphtheria, 18. Primary nature of diphtheria, 96. Prognosis of diphtheria, 139 etseq. Prophylaxis of diphtheria, 145 et seq. of laryngeal diphtheria, 235. Prudden, T. M. , action of carbolic acid in inflammatory con- ditions ,180. etiology of diphtheria, 263. Pseudo-membrane, agents used for the destruction of, 162. artificial production of, in an- imals, 58. croupal, 48. diphtheritic, 49. diphtheritic, appearance of, 70. description of, 46. distribution of, 69. extraction of, from the tra- chea, 282. INDEX. 321 Pseudo-membrane, formation of, through coagulation-necro- sis, 48. in "croupous tonsillitis," 128. in syphilitic laryngitis, 296. necessity of removal of, in nasal diphtheria, 225. production of, 46. as a result of local injury, 57. by temporary cutting off of blood supply, 58. pushed down by tube in in- tubation, 287. solvents of, 163. the pathognomonic sign of diphtheria, 123. Ptomaines, action of, 41, 117. Pulse in constitutional poisoning, ■ 76. in pharyngeal diphtheria, 69, 71. prognostic significance of, 143. Purpura hemorrhagica in diph- theria, 80, 95. prognostic significance of 143. Quinine in the later stages of diphtheria, 233. in the treatment of diphthe- ria, 204. seldom useful as an antipy- retic in diphtheria, 219. Quinoline in the treatment of diphtheria, 181, 196. Quinsy, spreading, 127. Rachford, B. K.,42. Ranke, H., statistics of tracheot- omy, 245. Reactions, electrical, in diphthe- ritic paralysis, 114. Rectum, feeding by the, 224, 301. Reed, unusual order of occurrence of diphtheritic paralysis, 113. Reflex, patellar tendon, loss of, following diphtheria, 114. Reinard on strychnine in diph- theritic paralysis, 255. Relapses, 78. Remedies, modes of employing, 155. to be given at regular inter- vals, 224. Renault, P., rapid tracheotomy, 252. Renou, method of antiseptic serotherapy, 198. Resorcine, local use of, 182,196. 21 Respiration, artificial, in diphthe- ritic paralysis, 256. character of, in laryngeal diphtheria, 82, 84, 290. Rhinoscopic view of posterior nares in naso-pharyngeal diph- theria, 134. Rindfleisch, 34, 48. Robinson, A. R., quoted by J. Lewis Smith, 247. Robinson, Beverly, heart-clots as a cause of death, 63. Rockwell, A. D., 112, 254. Roese's treatment of diphtheria, 195. Roser, antiseptic tampon of the trachea, 249. dislodgment of false mem- brane below the trachea tube, 253. Rossbach, use of papayotin locally, 169. Rothe, C. Gr., internal use of binio- dide of mercury, 177. Roux, E., and Yersin, A., on the etiology of diphtheria, 259. Rural districts, greater fatality of diphtheria in, 21. Salicylate of sodium as an anti- pyretic, 218. Salicylic acid, formula for inter- nal administration of, 220. local use of, 180. Salter, J. H., 29. Sanne, alleged analogy between diphtheria and syphilis, 103. cubebs in the treatment of diphtheria, 209. diphtheritic eruptions, 94. frequency of albuminuria, 90. diphtheritic paralysis, 180, heart-clots in diphtheria, 63. isthmus of the thyroid, 251. mortality of diphtheria fol- lowing measles, 107. diphtheritic albuminuria, 91. proportion of recovery, with- out operation, in croup, 244. rapid tracheotomy, 252. relation of season to the re- sults of tracheotomy, 247. statistics of tracheotomy, 246. views of, as to the primary nature of diphtheria, 97, 99. Satlow, internal use of oil of tur- pentine, 195. 322 INDEX. Satterthwaite, 27, 32. Scarlatina and diphtheria, differ- ential diagnosis, 135. diphtheria secondary to, 104. nature of pseudo-membrane in, 104. Schmiedler, local use of oil of tur- pentine, 195. Schiiler, comparative effects of chlorate of potassium, carbolic acid and salicylic acid, 181. Season in relation to croup, 60. to diphtheria, 19. to the results of trache- otomy, 246. Secondary diphtheria, 104. S6e, Germain, 14, 25. Seeligmuller, H., chlorate of po- tassium, 192. electricity in diphtheritic par- alysis, 255. Seifert, O., use of chinoline, 181. Selden, H., use of cyanide of mer- cury, 177. Senator, 32. Sensory disturbances in diphthe- ritic paralysis, 110. Settegast, statistics of tracheoto- my, 246. Severino, 5. Sgambatus, 5. Shirres, George, use of iodoform after tracheotomy, 186. Sigel, A., internal use of oil of turpentine, 195. Silver nitrate, local applications of, 157, 159. Simon, Jules, method of local treatment of diphtheria, «199. Skin, diphtheria of the, 89, 258. eruptions on the, in diphthe- ria, 94. Sleep, necessity of, 303. Smith, A., 15. Smith, A. H., examination of author's cases by, 212. Smith, J. Lewis, action of ptomaines in the prod- uction of diphtheritic paralysis, 119. addition of liquor potassee to lime - water recom- mended by, 166. condition of the patient as affecting the results of tracheotomy, 247. efficiency of lime-water not destroyed by car- bonic acid, 165. experience with alcohol as a stimulant, 207. Smith, J. Lewis, influence of al- buminuria upon the mortality from diphthe- ria, 92. follicular tonsillitis and diphtheria not related, 126. frequency of albuminaria, 90. Smith, S. W., syringe for nasal use, 226. Snow, H. L., internal use of sul- phurous acid, 183. Sodium benzoate in the treatment of diphtheria, 190, 222. biborate in the treatment of diphtheria, 193. bicarbonate, local application of, 166. hyposulphite, internal use of, 183, 222. salicylate, as an antipyretic, 218. Soil in relation to diphtheria, 20. Solis-Cohen, J., herpetic sore- throat, 123. on the local employment of chloride of iron, 162. Solis-Cohen, S., drain-throat, 123. Sore throat, common membra- nous, diagnosis of, from diph- theria, 123. Spain, great epidemic of diphthe- ria in, 4. Spalding, G. A., quoted by Holt, 126. Specifics in the treatment of diph- theria, 208. Spinal cord, lesions of, in diph- ritic paralysis, 66. Spleen, changes in, 65. Spray, antiseptic, in the preven- tion of laryngeal involve- ment, 236. method of application in la- ryngeal diphtheria, 238. Spraying, advantages of, 155. Sprays in the treatment of diph- theria, 215. Squills, syrup of, in laryngeal diphtheria, 242. Starr, epidemic of diphtheria de- scribed by, 6. Statistics, comparative, of the re- sults of treatment by bi- chloride of mercury, chlor- ide of iron, chinoline, resor- cin, bromine, and turpen- tine, 196. mortality of diphtheria, 91, 139. INDEX. 323 Statistics of diphtheria in regard to age of occurrence, 1G. of diphtheria in regard to season, 19. of intubation, 297. of tracheotomy, 245. Steam, inhalations of, for loosen- ing the false membrane, 163. in laryngeal diphtheria, 239. Steam-atomizer, 239. Stenosis of the larvnx, intubation in, 265. Steudener, views of, 47. Stimulants, alcoholic, in diphthe- ria, 204. in heart-failure, 233. in laryngeal diphtheria, 243. Stohr, Ph., peculiarity of the ton- sillar epithelium, 56. Stomach, diphtheria of, diagnosis, 137. symptoms of, 88. usually secondary, 107. Strabismus in diphtheritic par- alysis, 109. Streptococci in diphtheria, 36, 264. Strychnine in diphtheritic par- alysis, 255. in the later stage of diphthe- ria, 233. Stumpf, J., use of bichloride of mercury, 176. Sulphur, employment of, 182, 222. fumigation with, 148. Sulphurous acid, internal use of, 183, 222. Symptoms, 68 et seq. Syphilis and diphtheria, alleged analogy between, 103. Syphilitic laryngitis, false mem- brane in, 295. stenosis of the larynx in chil- dren, 307. Syringe for nasal use, 227. Syringing the nares, method of, Tactile sensation, disturbances of, in diphtheritic paralysis, 110. Talamon, micro-organism de- scribed by, 35. Tannin, local employment of, 161. Tedeschi, employment of galvano- cautery by, 159. Temperature in constitutional poisoning, 76. in pharyngeal diphtheria, 69, 71, 79" Tendon reflex, patellar, loss of, following diphtheria, 114. Therapeutics of diphtheria, 150 et seq. Thomson, "W. H., action of ptomaines in the produc- tion of diphtheritic paraly- sis, 118. management of dyspnoea in diphtheritic paralysis, 256. on the treatment of diphthe- ritic paralysis, 256. use of bromine in diphtheria, 184. Throat, confluent herpes of the, diagnosis of, from diphthe- ria, 121. inspection of the, in a case of suspected diphtheria, 121. Thursfield, N. M., 16, 20. Thymol, local use of, 199. Thromboses, venous, in diphthe- ria, 63. Tonics in the later stage of diph- theria, 232. Tonsillar diphtheria, explana- tion of frequency of, 58. Tonsillitis, acute follicular or lac- unal, 124. diagnosis of, from diphtheria, 130. croupous, 128. follicular, contagiousness of, 124. Tonsils, frequency of diphtheria of the, 68. openings in the epithelium covering the, 56. tumefaction of, mistaken for croup, 291. Trachea, antiseptic tampon of the, 249. extraction of false membrane from, 282. lumen of, compared with that of larynx, 269. Tracheal diphtheria, symptoms of, 85. tube, 251. Tracheotomy, 244. after-treatment, 252. antiseptic, in the prevention of bronchial diphtheria, 249. conditions affecting the re- sults of, 245. early, advantages of, 248. operation of, 250. rapid operation, 252. statistics of, 245. Treatment, 150 et seq. actual cautery, 158. 324 INDEX. Treatment, agents for the destruc- tion of false membrane, 162. alcohol, 204, 233, 243. alum, 161. antifebrin, 219, 303. antipyretics in the early stage of pharyngeal diphtheria, 21S antipyrin, 219, 303. antiseptic serotherapy, 197. antiseptics, 147, 170. astringents, 161. author's method of, 210. benzoate of sodium, 190, 222. bichloride of mercury, 171, 175, 196, 221, 241, 299. boracic acid, 194. borax, 193. bromine, locally, 184, 196. calomel, 173, 178. carbolic acid, locally, 180, 236. cardiac depressants, 209. caustics, 157. chinoline, locally, 181, 196. chloral, 187, 222. chlorate of potassium, 191, 219. chloride of iron, 162, 196, 201, 220. chlorine, locally, 183. citric acid, locally, 199. coffee, 233. copaiba, 208. copper sulphate, 158. cubebs, 208. disinfectants, 147. emetics, 242. eucalyptus vapors, 198. Formulae : antiseptic fumigations, 198. benzoate of sodium solution for internal use, 190. bicyanide of mercury for hypodermic use, 178. biniodide of mercury for in- ternal use, 177. borax, chlorate of potassium and carbolic acid, for local use, 193. bromine solution for local use, 184. bromine solution (Lawrence Smith's), 185. carbolic acid and lime-water spray, 215. chinoline solution for local use, 182. chlorate of potassium mixt- ure, 219. chloride of iron mixture, 220. corrosive sublimate for in- ternal administi'ation, 221. Formulae : cyanide of mercury for in- ternal use, 177. hydronaphthal with papain for local use, 200. iodine, chloride of iron, and carbolic acid, for local use, 185. iodoform solution for local use, 186. papayotin solution for local use, 169. pepsin solution for local ap- plication, 167. pilocarpine solution for in- ternal use, 170. salicylic acid and sulphite of soda mixture, 220. solution for local use, 181. sulphur mixture for internal use, 183. thymol gargle or spray, 199. trypsin solution for local application, 168. fumigations, antiseptic, 198. mercurial, 178. galvano-cautery, 159. general principles of, 151. hypodermic injection of mer- curial salts, 178. hyposulphite of soda, inter- nally, 183. indications to be used in the, 150. inhalations, 197. intubation, 265. inunctions, mercurial, 177. iodoform, locally, 186, 222. iodol, locally, 187. iron, chloride of, 162, 196, 201, 220. irrigation, 210, 218. jaborandi, 169 lactic acid, locally, 164. lemon-juice, locally, 199. lime-water, locally, 164, 236. local applications, 156. menthol, locally, 199. mercury, salts of, 171, 173, 178, 222. modes of employing remedies, 155. of adenitis in diphtheria, ■ 231. of constitutional diphtheria, 230. of diphtheritic paralysis, 254. of heart-failure, 233. of laryngeal diphtheria, 235. 299. of nasal diphtheria, 224. INDEX. 325 Treatment of pharyngeal diph- theria, early stage, 214. later stage, 229. oil ol peppermint locally, 199. oil of turpentine, 194. oxygen, 188. ozone inhalation, 189. papayotin, locally, 168, 237. pepsin, locally, 166. permanganate of potassium, locally, 188. peroxide of hydrogen, 188, 999 pilocarpine, 169. prophylactic, of laryngeal diphtheria, 285. quinine, 204, 219, 233. resorcine, 182, 196. results of, 153. salicylate of sodium, 218. salicylic acid, 180, 220. special indications to be met in the case of children, 152. specifics, 208. sprays, 155, 215, 236, 238. steam inhalations, 163, 239. sulphur, 182, 222. thymol, local use of, 199. tracheotomy, 244. trypsin, 167, 237. turpentine, 194, 197, 222, 241. turpeth mineral, 242. vapor, 163, 197, 238. veratrum viride, 209. vinegar, locally, 199. Trendelenberg, 26, 32, 58. Trideau, cubebs and copaiba in diphtheria, 208. Trousseau, oedema in diphtheritic albuminuria, 92. on the advantages of early tracheotomy, 248. paralysis beginning in the ex- tremities after cutaneous diphtheria, 116. term diphtherie suggested by, 1. unsuccessful attempt at inoc- ulation by, 26. use of actual cautery by, 158. use of alum and tannin by, 161. views concerning the prog- nostic significance of albu- minuria, 92. writings on diphtheria by, 13. Trousseau's tracheal dilator, 251. tracheal forceps, 253. Trypsin as a solvent of false mem- brane, 167. in laryngeal diphtheria, 237. Turpentine, applicable rather to laryngeal than to pharyn- geal diphtheria, 222. in the treatment of diphthe- ria, 194. inhalations, 197. vapor in laryngeal diphthe- ria, 241. Turpeth mineral in laryngeal diphtheria, 242. Urjemic poisoning, treatment of, 234. Urine, albumin in, in diphtheria, 89. Vagina, diphtheria of, 88. Van Wier, 4. Vapor, warm, use of, for loosening the false membrane, 163. Vaporization, advantages of, 156. Vaporizing atomizers, 238. Vapors, antiseptic, in the treat- ment of diphtheria, 197. Velpeau, 158. Veratrum viride in the treatment of diphtheria, 209. Villa Real, 4. Vinegar, local use of, 199. Virchow, classification of false membranes, 48. forms of inflammation of mu- cous membranes anatomi- cally distinguished by, 14. views of, concerning the non- identity of diphtheria and croup, 61. Vogelsang, local use of peroxide of hydrogen, 188. Voice, character of, in croup, 290. in diphtheritic paralysis, 108, 111. in laryngeal diphtheria, 82, 83. Vomiting in pharyngeal diph- theria, 70. prognostic significance of, 142. Vulva, diphtheria of, 88. Wade, W. F., discovery of the occurrence of albuminuria with diphtheria by, 14. Wagner, E., views of, concerning the nature of false membrane, 46. Waxham, F. E., method of intu- bating, 275. relative efficacy of different solvents of false membrane, 164. Weigert, artificial production of false membrane, 58. 326 INDEX. Weigert. views of. concerning the production of false membrane, 47. Werner, P.. internal use of bi- chloride of mercury. 176. White, W. T.. examination of author's eases by, 212. Winters, J. E.. abuse of mercuri- als in the treatment of diph- theria, 179. on the dose of chloride of iron, 203. Wood and Formad, account of diphtheria in animals by, 23. artificial production of false membrane, 58. conclusions of. concern- ing micro-organisms in diphtheria, 32. Wood and Formad. inoculation- experiments by. 27, 30. Wounds, diphtheria of, 89. Wveth. J. A., on tracheotome 351. Ziegler, location of the pseudo- membrane, in secondary diphtheria, 107. mode of formation of false membrane, 49. v. Ziemssen. electrical reactions in diphtheritic paralvsis. 114. explanation of the rarity of oesophageal inflammation, 98. Zooglea. in diphtheritic mem- brane, 32. 1 2 mm