NOTES ON THE TREATMENT OF WHOOPING-COUGH WITH ANTIPYRINE. BY J. P. CROZER GRIFFITH, M.D., ASSISTANT PHYSICIAN TO THE HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA ; PATHOLOGIST TO THE PRESBYTERIAN HOSPITAL. REPRINTED FROM THE TRANSACTIONS OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA, JANUARY 4, 1888. PHILADELPHIA: WM. J. DORNAN, PRINTER. 1888. NOTES ON THE TREATMENT OF WHOOPING-COUGH WITH ANTIPYRINE. BY J. P. CROZER GRIFFITH," M.D., ASSISTANT PHYSICIAN TO THE HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA ; PATHOLOGIST TO THE PRESBYTERIAN HOSPITAL. REPRINTED FROM THE TRANSACTIONS OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA, JANUARY 4, 1888. PHILADELPHIA: WM. J. DORNAN, PRINTER. . 1888. NOTES ON THE TREATMENT OF WHOOPING-COUGH WITH ANTIPYRINE. By J. P. CROZER GRIFFITH, M.D., ASSISTANT PHYSICIAN TO THE HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA; PATHOLOGIST TO THE PRESBYTERIAN HOSPITAL. [Read January 4, 1888.] That whooping-cough is one of the opprobria of medicine scarcely needs to be remarked; and were this not admitted, the long list of therapeutic measures which have been employed in its treatment would prove that none of them has given satisfaction. Among the means of treatment which have been proposed and tried may be mentioned the use of belladonna, alum, quinine, opium, chloral, the bromides, cocaine, carbolic acid, cochineal, quebracho, gelsemium, salicylic acid, turpen- tine, resorcin, castanea, hydrocyanic acid, sulphur both internally and by fumigation, compressed air, asafoetida, peroxide of hydrogen, change- of climate, cannabis Indica, inhalation of the vapors from the purifying chambers of gas-works, boracic acid and other drugs 4 GRIFFITH, by insufflation, pyridin, and amylene hydrate, which by no means closes the list. Even the laity have learned to know, or to suspect, how helpless the pro- fession is in the treatment of many cases of the disease, and either let the malady run its course, or employ some of the patent medicines so widely advertised. This helplessness is, indeed, acknowledged by many of the ablest writers on the subject. Wiederhofer states that nearly all the drugs in the Pharmacopoeia have been used in the convulsive stage with little or no effect. He says further, that new specifics are proposed toward the end of nearly every epidemic, but at the beginning of the next outbreak they are heard of no more, this being due to the fact that the medicine was only useful in the third stage. He claims, too, that the disease is never cured by change of climate. Henoch says, "You will, unfortunately, gain no honor by your treatment." He deems the affection incurable, and thinks that there is no plan of treatment which will cut short the parox- ysmal stage, while in the third stage almost any drug seems to do good. It does not come within the province of these notes to inquire into the nature of the disease. Although most probably of a myotic origin, the antiseptic plan of treatment, as such, does not seem to have much effect. Whooping-cough is, I need not say, usually divided into three periods not very sharply separated from each other. The first or catarrhal stage lasts an uncertain time, but averages, according to Meigs and Pepper, two weeks. Squire says the duration is about one week, while Gerhardt gives it as varying from a few days to four or five weeks. The second or paroxysmal stage stretches over thirty to forty days or even a longer TREATMENT OF WHOOPING-COUGH WITH ANTIPYRINE. 5 time, during which there is no amelioration to be ob- served. The third stage, or stadium decrement^ begins with the evidences of decline in the severity of the symptoms, the cough becoming less paroxysmal and bronchial in character. The length of this period is very uncertain, continuing from ten to fifteen* days to perhaps several months. The total duration of the disease Henoch puts at an average of eight to nine weeks. The malady is certainly not one to be regarded with indifference or to be let alone. Biermer calculates that 7.6 per cent, of the cases die, though Loschner's estimate of one in twenty-seven or thirty is adopted by Gerhardt. In England and Wales between the years 1858 and 1867, 120,000 persons died of the disease, and in Prussia, between 1875 and 1880, 85,000 succumbed. Any means of treatment, therefore, affording a reason- able expectation of checking its course in severe cases cannot but be heartily welcomed by the profession; but in testing it it is evidently of the highest importance that it be applied during the first or second stage. In this connection the article of Sonnenberger (Deutsche med. Wbchenschr., 280, 1887) on the use of antipyrine in whooping-cough is of so great value and interest that a short account of his results may not be out of place here. This author had under observation since 1884 two large epidemics of the disease at Worms, and becoming greatly dissatisfied with the usual methods of treatment he determined to experiment with antipyrine. As a check upon his results he treated some members of a family with this drug, and to others, taken sick at the same time, he gave quinine or chloral, or the bro- mides, or some other well-recognized plan of treatment. In other instances he administered antipyrine for a few 6 GRIFFITH, days, then allowed an interval to pass in which no medicine was given, and finally returned to antipyrine. In a short time it became clear to him that this drug exceeded in value all others which he had yet employed for the malady in question, and he has continued to use it up to the present time, a period of two and a half to three years. He treated about seventy cases of the disease with antipyrine alone, giving it in doses of one- seventh of a grain in quite young children, up to seven- fifteenths of a grain for larger children or adults, three times a day, though he believes much larger amounts might be given. A most important fact is that the best results were obtained when the course of treatment was commenced at the beginning of the disease. Under these circum- stances the affection lasted in all but three to five weeks, and was of a mild character with not more than six or seven slight paroxysms in the twenty-four hours. When it is remembered that an average case has, according to Eichhorst, twenty to thirty paroxysms in a day, while in a severe case the number may reach a hundred, it will be recognized what an improvement this is. But even when the treatment was introduced at the acme, and with the most unfavorable hygienic sur- roundings good results were obtained. The paroxysms often became less violent after the first dose, and after several days occurred less frequently. When the drug was stopped the symptoms grew worse, showing that the effect was actually due to its use. In only five cases did he observe complications, and there was no instance of antipyrine-collapse. It would seem then pure cavil to deny that in antipyrine we have a drug capable of influencing whooping-cough most power- TREATMENT OF WHOOPING-COUGH WITH ANTIPYRINE. 7 fully, especially in the first and second stages, where other means so often fail. Encouraged by Sonnenberger's success, I have ad- ministered antipyrine in several instances of whooping- cough, and with excellent results. The number of cases is not large enough to be of great value except as confirming the author's statements, but it seemed to me better to report them now, rather than to wait with the object of adding to them. My experience agrees with that of Sonnenberger, that the drug is most efficient when given early in the disease. I make no claim, of course, that antipyrine is an absolute specific; indeed, the first of the cases briefly reported below is an instance, though the only one, of the total failure of the drug. Most of the cases show, I think, that it may prove of great value in this disease, though in some of them the treatment was begun too near the third stage to offer a decisive test. Case I.-August 5, 1887. Thomas R., aged four years, has had a cough for three to four weeks, but has only whooped this week. Ordered antipyrine grs. ij t. d. 12^A. Condition is much the same; increased dose to grs. iv t. d. 18^,. Ho marked change. Ordered grs. iij every three hours. 19/A. Ko improvement: the child had paroxysms every one to one and a half hours last night; the chest is full of mucous rales. Ordered grs. iv antipyrine every three hours together with an expectorant mixture. September 12. The child has quite recovered. Antipyrine proved absolutely useless in this instance. Case II.-August 5. Nellie D., aged four years, is said to have had a cough for five or six weeks, and has whooped for 8 GRIFFITH, two weeks. Coughs up a little blood with mucus. A sedative expectorant mixture has had no effect; added to it to-day tr. belladonnse gtt. iv t. d. 12ZA. Slight improvement only. Belladonna mixture stopped, and ordered antipyrine grs. ij t.d. and quinine gr. ij t. d. 18^. Certainly better, though she still whoops badly and vomits after it. Gave antipyrine grs. iij every three hours. 19dA. Decidedly improving; observation ceased at this date. The improvement in this case, though not very marked, was fully equal or greater than that following the use of belladonna. Case III.-August 5. Carrie H., aged five years, has coughed for six or seven weeks, though the whoop was first heard about three wTeeks ago, and the paroxysms are now long, frequent, and followed by vomiting of mouthfuls of blood. Ordered antipyrine grs. ij t. d. 12th. Improvement began at once and was marked. The paroxysms are less frequent and severe, and no more blood has been vomited. 18^A. There are not more than four or five kinks a day. Increased dose to grs. ij every three hours. 22d. Does not cough at all at night, and only once or twice in the day. Although well advanced in the second stage, the sudden and permanent improvement shows the good effect of the drug. Patient nearly well in two weeks. Case IV.-August 12. Willie P., aged four years, has coughed for three or four weeks and whooped for seven to ten days. The paroxysms are severe and frequent and he vomits very often. A few rales are heard in the chest. Ordered antipyrine grs. iij t. d. 18^A. Both whooping and vomiting have entirely ceased. Increased dose to grs. iij every three hours. TREATMENT OF WHOOPING-COUGH WITH ANTIPYRINE. 9 22d. Still coughs occasionally, but does not whoop. Vomits only rarely. This case is a beautiful example of the effect of the drug at the beginning of the second stage, with virtually complete recovery in six days. Case V.-August 12. Frank McGr., aged two years, has coughed for some time, but has not wThooped. Continued an expectorant mixture which he had been taking. l&A. The child commenced at about the time of my last visit to whoop three or four times a day, and his nurse has to go to him often at night on this account. Ordered antipyrine grs. iss every three hours. 22d. The paroxysms are decidedly lessened in number. For two nights he has needed no attention at all. Medicine continued. A decided action on the part of the drug. The patient suffered later from a severe bronchitis for which treatment was required, but the paroxysmal character did not return. Case VI.-August 5. Mary B., aged seven years, has coughed for two weeks, and the paroxysmal stage is just beginning, as she has whooped and vomited for a few days only. Ordered antipyrine grs. iv every three hours. 12/A. Very greatly improved; coughs but seldom and the kinks have nearly disappeared. Medicine continued. 18^. Does not cough at all. Medicine stopped. A remarkable case in which the disease appears to have been aborted in the second stage, lasting scarcely two weeks. 10 GRIFFITH, Case VII.-August 15. Edward S., aged two years and ten months, has been whooping for a few days only, but severely, and vomits about four times in the day. The mother says she is up with him all night. Gave antipyrine grs. ij every three hours. 18ZA. The mother declares " the medicine worked like magic," and that the improvement has been the talk of all the neighborhood. The child has vomited only twice since the 15th, and does not whoop more than twice a day. The improvement began on the first night after treatment was commenced, and the mother did not need to be up either that night or any since. Medicine continued. There can surely be no question that the very striking result experienced here, occurring as it did so early in the disease, was certainly due to the influence of the medicine. Case VIII.-October 19. Annie M., aged fifteen months. A not very intelligent mother states that six or seven weeks ago the child coughed and whooped, but did not vomit. She grew better, but later became worse again, and for three weeks has had paroxysms every hour, followed by vomiting. Sleep is poor. Ordered antipyrine gr. j every three hours. 21st No vomiting since last seen, and has " slept elegant." The child whoops still, but not so often. Increased dose to grs. iss every three hours. November 2. Medicine continued until 28th ult. Child has been much better. Since that date no medicine has been given, but condition has remained improved. 25th. Cough had entirely disappeared; but a week ago the child became thickly covered with the eruption of varicella, and the paroxysms returned in full force, being very long and severe, though not very frequent, and not followed by vomiting. Ordered antipyrine grs. iss every three hours, which seemed promptly to relieve them. TREATMENT OF WHOOPING-COUGH WITH ANTIPYRINE. 11 The very sudden improvement when first adminis- tered indicated the power of the treatment, though the disease was probably too far advanced to offer a suffi- ciently severe test. The cessation of the paroxysms after November 25th would probably have followed the disappearance of the eruption in any case. Case IX.-October 28. George B., aged three years, has coughed for two weeks, but has had no kinks until the last seven days, and is constantly grooving worse. The paroxysms are not very frequent, but are sometimes very severe, and are often followed by vomiting. Ordered antipyrine grs. iss every three hours. November 4. The child coughs a great deal less, and has only vomited once during the night since he was last seen. Sleeps so much better that he does not need the powders at night. No medicine has been given to-day, and but two doses yesterday, and to-day the child has commenced to whoop and vomit more than usual. Medicine renewed. 14Z/n Improvement again followed the use of the powders, but none has been given since the 10th, and the patient is, perhaps, a little worse, though greatly better than at the begin- ning of the treatment. We have here an instance of aggravation of the symptoms following an intermission in treatment, and of permanent benefit after its renewal. Desiring to make as thorough a trial of the value of the drug as was possible, I requested several medical friends to administer it in such cases of whooping- cough under their care as they might think best. The remaining notes are the result of their very kind assent. The first three cases were under the care of Dr. George E. Shoemaker, the next two under that of Dr. T. 12 GRIFFITH, Hewson Bradford, and the last under that of Dr. Wm. C. Lott. Case X.-August 16. Sophie M., aged four years, has been whooping for from two to three weeks. Ordered potas. bromidi grs. ij, ext. quebracho fid. iv, tr. belladonna gtt. ij, every three hours. 23d. No better. Medicine stopped, and ordered antipyrine grs. ij every three hours. 26/lA. Practically well. Improvement began at once and has gone on steadily since the powders were first given. She has cough occasionally, and only at night, and the paroxysms are not violent. Though, it is true, well on in the second stage, anti- pyrine was at once effectual where other remedies had failed. Case XI.-August 6. Maggie S., aged sixteen months, has had a severe cough for sometime. ^th. Characteristic paroxysms began about this date. Given tr. belladonnas gtt. iij every three hours. IBA. No improvement, and paroxysms are very severe and frequent. Ordered alumin. gr. ij t. d. 16th. Condition unchanged. Ordered tr. belladonnas gtt. ij, ext. quebracho fid. gtt. ij, potas. bromidi gr. ij, every three hours. 23d. The patient is slightly better, the paroxysms being reduced to about one every half hour. Substituted antipyrine grs. iss every two hours for other treatment. %lth. The paroxysms are much less frequent both by night and by day, and the mother declares the child to be much better. A case where several of the well-accepted remedies totally failed, and where antipyrine was a decided success, and at once. TREATMENT OF WHOOPING-COUGH WITH ANTIPYRINE. 13 Case XII.- October, 1887. A child of five years. Had been under unknown treatment for two weeks or more without benefit. Whooping-cough well developed, with frequent daily and nightly paroxysms preventing the proper amount of sleep. Gave antipyrine grs. iss every two hours with immediate improvement as regards the severity and duration of the paroxysms, and with entire abolition of the attacks at night. The subsequent course of the disease is unknown, except that the father later expressed himself as highly delighted with the action of the medicine. Another instance of sudden and great improvement at the acme of the disease. Case XIII.-September 24. M. I., aged two and a half years. The disease had lasted through probably twenty-one days of the second stage. Ordered antipyrine grs. ij every three hours. October 3. The mother reports that the child was much relieved after the first dose, and the paroxysms have continued to diminish in number and violence. Medicine continued. WA. The improvement is still marked. Case XIV.-October 1. J. H., aged one year, had been sick three weeks when first seen. Ordered antipyrine grs. ij every two hours. 3d. Mother reports marked improvement. Both of these cases were, perhaps, too far advanced in the disease to constitute sufficiently severe tests; nevertheless, the first especially would seem to offer good evidence of the activity of antipyrine. Case XV.-August, 1887. Robert H., aged three years. The disease had commenced six weeks before he was first seen by Dr. Lott. In the first week of observation the paroxysms 14 TREATMENT OF WHOOPING-COUGH WITH ANTIPYRINE. were frequent and violent, and often followed by vomiting of food taken, and by severe epistaxis, so that the child soon became • very weak from starvation and from loss of blood. The usual methods of treatment were employed for a week, but without the slightest relief. Antipyrine grs. ij every three hours was then ordered, and other treatment stopped. After twelve hours amelioration began, and in two days the paroxysms were reduced to six or eight in the twenty-four hours, epistaxis and vomiting ceased, and the appetite returned. At the end of one week's treatment with antipyrine the paroxysms were brought down to three or four in twenty-four hours, and attendance was discontinued. Although, perhaps, somewhat advanced in the disease, yet this case was an excellent example of the superiority of antipyrine to other plans of treatment. Such rapid and complete improvement following the administration of the medicine in so severe a case could scarcely be a mere coincidence.