[Reprinted from the Medical and Surgical Reporter, May 30, 1896.] Reduced Period of Intubation by the Serum Treatment of Laryngeal Diphtheria.* EDWIN ROSENTHAL, M. D., PHILADELPHIA, FLA., At the last meeting of this society I had the honor of presenting a paper on the Treatment of Laryngeal Diphtheria by Diphtheria Antitoxin, with and with- out Intubation. Further experience in this method of treatment has so im- pressed me, that I am prompted to ap- pear and place before the society the results of my further personal observa- tions in the same character of cases, with this distinction—I shall limit my- self to those cases only that required intubation, and place in comparison cases that were intubated prior to the serum treatment and cases that requir- ed tracheotomy. To do this properly I have sought aid from the statistics of others, and, placing them side by side, wish to prove: 1st. That the operation of intubation is the most desirable, and is more favor- able than that of tracheotomy. 2d. That with the serum treatment of diphtheria tracheotomy will no longer be necessary in this disease. 3d. That the serum treatment in diphtheria has made a most marked and favorable reduction in the time the tube is worn in the larynx. As a basis I shall take the recoveries reported by me in a paper entitled, “A Report of 100 Cases of Diphtheria of the Larynx Treated by Intubation ”. {Med. Bulletin, September and October, 1894). Inasmuch as formerly the major op- eration of tracheotomy was indicated in those cases requiring intubation longer than 120 hours (five days), or where severe decubitus was present, I shall divide these statistics into percentages, representing under and above 120 hours. I shall also group my statistics into two divisions, representing American observers in the one part, and European observers in the other, and in a sum- mary, group them together. My reason for so doing is because the technique pursued is different. As O’Dwyer just- ly says : “ The best statistics on this point will come from the other side, where it is customary to leave the string attached and to remove the tube every twenty- four to forty-eight hours. I however do not consider it good practice unless the string is removed.” *Read before the Medical Society of the State of Penn- sylvania, May 21, 1896. 2 I may add that in my own practice I employ as many as five tubes of one size. So soon as the tube has been used I have it cleansed and re-gilded, and therefore use a comparatively new tube for each case. When the tubes are re- turned from my instrument makers, Messrs. Charles Lentz & Sons, Philada., they are thoroughly cleansed, boiled and then placed in my case for use. O’Dwyer’s technique is followed, but the one intubation is performed if possible, waiting until I think the time most proper to make the final extubation. The silk, in all cases, is removed at once, and the patient permitted as much freedom as is compatible with safety. This method is pursued by most Ameri- can operators, will explain the difference in the time between American and Eu- ropean statistics, and is the chief reason for the method of presenting my statis- tics. BEFORE THE USE OF SERUM. American—In my series of cases there were thirty-eight recoveries in 100 cases —a mortality of sixty-two per cent. The tube was worn : recoveries in which the tube was worn, as follows: 50 hours, 1 case 60 “ 1 “ 72 “ 1 “ 96 “ 1 “ 25 per cent. 148 “ 2 “ 152 “ 1 “ 164 “ 1 “ 184 “ 1 “ 192 “ 1 “ 212 “ 2 “ 340 “ 2 “ 524 “ 1 “ 624 “ 1 “ 75 per cent. The minimum duration in Fischer’s cases was fifty hours ; the maximum, G24 hours. Taking the number of hours, 2,818, and dividing by the number of cases, sixteen, the average time the tube was worn was 176£ hours. To summarize : Under 120 hours, 4 cases . . . . 25 per cent. Over 120 “ 12 “ .... 75 “ European—Gustav Baer ( Trachotomie and Intubation in Kinderspital Zurich, in- augural dissertation, Leipsic, 1892), performed final extubation in his cases of recovery at the Zurich Children’s Hospital, as follows : 1 day in 1 case 2 “ 5 “ 3 “ 6 “ 4 “ 3 “ 5 “ 5 “ 48 hours in 4 cases 60 “ “ 1 “ 72 “ 1‘ 1 11 96 “ “ 6 “ .31.40 Per cent. 64.50 per cent. 120 “ “ 6 “ 144 “ “ 6 “ 192 “ “ 5 “ 216 “ “ 5 “ 240 “ “ 2 “ 364 “ “ 1 “ 672 “ “ 1 “ 6 “ 1 “ 8 “ 3 “ q <« 9 « 10 “ 2 “ 33 “ 1 “ 34 “ 1 “ 52 “ 1 “ 68.60 Percent. 35.50 per cent. The minimum duration was forty- eight hours; the maximum, 672 hours. Taking the number of hours, 6,040, and dividing by the number of cases, thirty- eight, the average time the tube was worn was 185J hours. To summarize: Under 120 hours, 12 cases . .31.40 per cent. Over 120 “ 26 “ . . 68.60 Dillon Brown (June and July, 1887) places the time for final extubation at five days three and a half hours (123£ hours). O’Dwyer collected 158 recoveries in which the time the tube was worn was accurately stated and the average found o be six days and two or three hours (146-147 hours). Louis Fischer reports to me sixteen To summarize: Under 120 hours 64.50 per cent. Over 120 “ 35.50 “ Professor Yon Ranke (Munchener Med. Wochenschrift, 1895, No. 8), performed in those cases of recovery, before serum treatment, final extubation, as follows : Within 24 hours in 8 per ct. “ 48 “ 26 “ “ 72 “ 18.50 “ “ 96 “ 20 “ 72.50 per ct. Over 96 hours 27.50 per ct. Of Von Ranke’s cases 72.50 per cent, were extubated within ninety-six hours. Huebner (Klinishe Studien uber die be- handland der Diphtherie, Leipsig, 1895), in twenty-five cases of recovery, lias given 100 hours as an average when final extubation could be performed. Johan Bokai (Stephanie Kinder Hos- 3 pital, Buda-Pesth), reports 673 cases in- tubated by himself before the serum period, of which 223, that is per cent., were cured. Of these 223 cases, eight were trach- eotomized. If we subtract these, we have 215 cases in which the tubes were worn, as follows: Of these, one case (183 hours) was tracheotomized ; therefore, forty-four cases were treated by simple intubation. The duration of the intubation in these forty-four cases was as follows: 1 to 24 hours, 8 cases . . . 18.18 per cent. 24 “ 48 “ 18 “ ... 40.90 “ 48 “72 “ 8 “ . . . 18.18 “ 72 “96 “ 4 “ . . . 9.09 “ 96 “120 “ 2 “ ... 4.54 “ 120 “144 “ 1 “ ... 2.27 “ 144 “168 “ 3 “ ... 6.84 “ Total, 44 cases. In this group the minima was one and seven hours ; the maxima, 150, 154, 160 hours. Of these forty-four cases 77.26 per ct. were extubated within 72 hrs. 13.63 “ “ “ between 72 and 120 hrs. 9.11 “ “ “ after 120 hrs. To show the comparison between the two periods, before and after serum treatment, Bokai tabulates his cases a follows: From \ to 24 hours in 27 cases, 12.55% “ 24 to 48 “ 56 “ 26.04% “ 48 to 72 “ 52 “ 24.18% “ 72 to 96 “ 29 “ 15.50% “ 96 to 120 “ 13 “ 6.06% 82.33 % From 120 to 144 hours, 21 cases, “ 144 to 168 “ 6 “ “ 168 to 192 “ 1 “ “ 192 to 216 “ 2 “ “ 216 to 240 “ 1 “ Over ten (10) days 7 “ 17.67% The minimum duration in Bokai’s cases was: J, 1, 1J, 2, 6, 6J and 9 hours. The maximum duration was : 217, 218, 243, 247, 349, 353 and 368 hours. Taking the number of hours(17,050f), and dividing by the number of cases (215), the average duration the tube was worn would be seventy-nine hours. Bokai observes that in his hospital the removal was never attempted under forty - eight hours. In those cases (12.55 per cent), where the tube was worn not longer than twenty-four hours, the tube was either expectorated or withdrawn by pulling on the silk, which he always allowed to remain; and stenosis being relieved, no further intubation was practiced in that partic- ular case. PERIOD OF SERUM TREATMENT. European—In juxtaposition to these statistics, I will now give the statistics influenced by the serum treatment: Huebner (Klinishe Studien, etc.) re- ports ten intubation cases treated with antitoxin, where the average duration was thirty-seven hours. In Yon Ranke’s cases, the tube was removed Within 24 hours, in 18 cases . 18.5 per cent. “ 48 “ “ 48 “ . 48.1 “ “ 72 “ “ 11 “ . 11.1 “ “ 96 “ “ 10 “ . 10.0 “ Over 96 “ “ 3 “ . 3.7 “ Of ninety cases intubated by Bokai since the serum period, forty-five re- covered—fifty per cent. Duration of Intubation. BeforeSerumPeriod Per ct. of Cures. After Serum Period Per ct. of Cures. J to 24 hrs. 12.55 per cent. 18.18 per cent. 24 to 48 hrs. 26.04 U 40.90 “ 48 to 72 hrs. 24.18 a 18.18 “ 72 to 96 hrs. 13.50 u 9.09 “ 96 to 120 hrs. 6.06 a 4.54 “ 120 to 144 hrs. ' 2.27 “ 144 to 168 hrs. 6.04 “ 168 to 192 hrs. u 192 to 216 hrs. 216 to 240 hrs. Over 240 hrs. This table shows that the number in the first and second twenty-four hours has conspicuously increased. If we were to add the number of hours together, as in the former cases, we have 2683 hours, divided by forty- four (cases), the average is sixty-one hours against seventy-nine hours before the serum period. Therefore the serum treatment has lowered the duration of intubation eighteen hours. American—O’Dwyer intubated thirty cases since the serum period, of which twenty recovered—66§ per cent. The duration of the intubation in nineteen of these cases was as follows : 4 8 hours, 1 case 36 “ 1 “ 48 “ 1 “ 49 “ 1 “ 68 “ 1 “ ■ 69 “ 1 “ 76 “ 1 “ 84 “ 1 “ 88 “ 1 “ 91 “ 1 “ 92 “ 2 “ 93 “ 1 “ 107 “ 1 “ 112 “ 1 “ 115 “ 1 “ 128 hours, 1 case 140 “ 1 “ 156 “ 1 “ 164 “ 1 “ 192 “ 1 “ 240 “ 1 “ 246 “ 1 “ 284 “ 1 “ 296 “ 1 “ 324 “ 1 “ 408 “ 1 “ 36f per cent. 89J per cent. In this group the minimum was six- teen hours ; the maximum, 408 hours. 63J per cent, were extubated before 120 hrs. 36| “ “ “ over 120 hrs. To show the comparison between the two periods, before and after serum treatment, I tabulate Fischer’s cases the same as Bokai’s : Total . . 30 119 “ 1 “ 120 “ 2 “ 10J per cent. In this group the minimum was eight hours ; the maximum, 120 hours. Final extubation was performed in per cent, (seventeen cases) within 120 hours, and per cent, (two cases) at 120 hours. If we add the number of hours the tube was worn (1587) and divide by number of cases (nineteen) ,* it will give the average, hours, in comparison to 147 hours in such cases before the serum period. Therefore, the serum treatment has lessened the time of intubation hours. O’Dwyer has written me that the average duration of intubation since the serum period has been eighty hours, making his reduction, therefore, sixty- seven hours. Dr. Louis Fischer reports to me thirty cases of recoveries after intubation, since the use of the antitoxin. In his cases, the tube was worn as follows: Duration of Intubation. BeforeSeru m Period Percent, of Cures. After Serum Period Percent, of Cures. 16 to 24 hrs. 2 cases, 6‘ifo. 24 to 48 hrs. 4 “ 13i%. 48 to 72 hrs. 3 cases, 18.75%. 9 “ 30%. 72 to 96 hrs. 1 “ 6.25%. 3 “ 10%. 96 to 120 hrs. and over. 12 “ 75%. 12 “ 36f%. To summarize: Before . 120 hrs. . 25 per cent. 63J per cent. After . 120 hrs. . 75 “ 3o| “ This table shows that the number in the first three days has increased. If we were to add the number of hours together (3262) and divide by the num- ber of cases (thirty), the average time would be 108f hours. In comparison to the average time before the serum period, 176£, shows a reduction in the time tube was worn of sixty-eight hours. The cases intubated by me since the serum period were as follows: 16 hours, 1 case 24 (4 1 “ 36 ii 1 “ 48 a 3 “ 52 a 2 “ 64 u 6 “ 72 i < 1 “ 76 c< 1 “ 84 er. He con- tends that the tube may be removed much earlier when antitoxin is used than when it is not. In order to determine that fact, it is necessary frequent experiments should be made in removing the tube every day? both in the non-antitoxin and in the antitoxin cases, DISCUSSION. 7 to ascertain the earliest period of disease in which the patient can get along without the tube. No such experiment has been made. Before the introduction of antitoxin, we were told that it was necessary the tube should remain six, seven or eight days. O’Dwyer’s instruction is that the tube may be removed on the seventh day, unless the patient be a great distance; then it should be retained eight days, I think this was pretty generally followed before the introduction of antitoxin. But it is not known just how soon a patient can get along without a tube. That can be ascertained only by removing the tube and learning. Since antitoxin has come into practical use, some writers are claiming the patient can earlier dispense with the tube; and they have found by experiment that some cases get along without using the tube. This conclusion, however, is scarcely war- ranted, unless experiment is made of the two cases in precisely the same way. As to my own experience. I have tried re- moving the tube at an earlier period of the disease, but I have repeatedly found that I had to reintroduce it. We first thought that, with the use of the antitoxin, we could get along without the tube after four days ; but, often, we found that we had to hustle to get the tube back to save the child’s life. A patient in one of the wards of a hospital in Philadelphia wore a tube three months. During the three months the tube was re- moved or coughed up as often as seventy times, yet it was impossible to get along with- out it. The child, in its night clothes, often would run into the sleeping room of the res- ident physician, carrying in its hand the tube, which had been coughed out. The physician would reintroduce the tube, and the child would go back to bed. I have seen the child, and I am sure it would not have lived fifteen minutes if the tube had not been reintroduced. As 1 stated, that child was required to wear that tube three months. Frequently the tube has to be retained as long as three weeks, even where the antitoxin is used. Not long ago, a patient was sent to the hospital, who had already received antitoxin. A number of hours later—perhaps a day ; I think it was not so long as twenty-four hours after—intubation was necessary. It was found to give temporary relief. The child was then sent to the hospital in that condition. After six days we thought we might remove the tube, and did so. Serious symptoms at once developed ; the tube was reintroduced and worn four days longer. We thought then we could remove the tube, and did so. The resi- dent physician told me he had to make all possible haste from some other part of the in- stitution, and put the tube back, in order to save the child. The morning of the eleventh day, at about five o’clock, the child coughed out the tube. Its condition at once became serious, and the nurse telephoned to the other building for the resident physician. The lat- ter did not stop to change his shirt, but hur- ried across the grounds. Before he arrived, that child was dead. It was an antitoxin case. 1 have very frequently met with cases where the tube is coughed out and the child gets along very well, no matter whether it has taken the antitoxin or not. I frequently have had children do pretty well after the tube was introduced and taken out immediately. They breathed better for a time. Dr. T. D. Davis, Pittsburg:—I have had considerable experience, personally, in the use of antitoxin. We ourselves make it in Pittsburg, and we know it is good. We know its strength and we know the results. At the last meeting of the Allegheny Coun- ty Medical Society, the subject was up before the members. There was not one single re- mark made by any doctor present derogatory to its great efficiency. Some of the cases reported were little short of miraculous. In my personal practice 1 have seen two cases where the child was, as it were, snatched as “a brand from the burning,” by its use. You can use antitoxin, and you can use anti- toxin. There are various ways of doing it. Because a man says a case has been treated with antitoxin and dies, it does not follow, therefore, that antitoxin was of no value, nor that it could not have been of greater use in that individual case. A great deal depends on how it is used, the quality and quantity used, and the time of use. If you have a patient suffering with malaria and give one small dose of quinine, you treat the patient with quinine, but how ? The same applies to the treatment of diphtheria with antitoxin, If you adminis- ter 500 units when it requires 5000 units to neutralize the poisons or toxins, your patient will die ; not on account of the antitoxin, but because you have not given a sufficient amount. If our theory in regard to the serum is cor- rect, it is one of the few remedies that are beneficial whether it cures the diphtheria or not. It not only is harmless, but it is bene- ficial. You are putting food into the body. You cannot possibly cause injury by it, if it is pure and good. You absolutely benefit in the same way as by injecting milk or beef tea. Therefore, you are not using a dangerous remedy. In one of the cases reported at the Alle- gheny County Society, 142 cubic centimetres were used, within thirty-six hours, in the case of a child seven years of age, and with re- covery. In regard to the remarks just made : How would you know more by experiments made as suggested ? Antitoxin does not propose to remove spasm of the larynx, nor to reduce congestion, or an inflamed condition. Anti- toxin proposes to remove the diphtheria and not its results. I know, when I use it, when the membranes have disappeared I am free to say whether the tube can be removed or not. 8 I know that I have never seen a case, under the use of antitoxin, in which the membrane lasted over forty-eight hours. If this mem- brane was in the larynx and the intubation was solely on account of the membrane, I would then take it away. If there was spasm of the larynx and congestion remained, then such would have to be treated. The antitoxin would have no effect in such a condition, as it cures only the diphtheria. Dr. Rosenthal :—The statement made by my friend from Pittsburg is exactly what I wish to emphasize. Whilst antitoxin is a specific for diphtheria, one must know how to use it. If you give but one administration, the child may not recover. I have seen re- coveries in laryngeal diphtheria in almost hopeless cases that were intubated. I am ready to stand with the antitoxin or to go down with the antitoxin. While it is of sig- nal importance to employ antitoxin as early as possible, I never despair, even when called late. Of course, in such cases I give larger amounts of antitoxin—2,000 units as an initial dose. The antitoxin which I have presented here is exhibited in three grades of strength. If physicians will use it precisely as I have di- rected, and there are any failures, let them be attributed to me. I do not know much about the Philadelphia Municipal Hospital, but it stands unique in its mortality-record, which is the greatest in the world to-day, and it is the only institution that has not reduced its mortality-rate since the introduction of antitoxin. I have presented a number of cases whereby my conclusions are proven, and if the oppor- tunity were offered, I could demonstrate the same facts at the Philadelphia Municipal Hos- pital. I have daily reports made, with analy- ses of urine, etc., and in no case has albumin- uria been noted. I have not noted any joint pains. In a few instances a slight urticaria, which soon disappeared, was noted, but I have noted the like in cases treated by me before the serum period. Dr. J. S. Billings, Jr., asserts (Medical Record, April 25th) that the “ antitoxin treat- ment has no deleterious effects upon the blood corpuscles. On the contrary, it seems to pre- vent degenerative changes which would other- wise be brought about.” A knowledge of the duration of the period of intubation ought to be of some value. When I inject the antitoxin in quantity insuffi- cient to ascertain the result, I repeat with an increased number of units, and when the symptoms are favorable, I take the tube out. In one case it remained 148 hours, but this was not due to antitoxin. I do not like statistics that are incorrect, and long to have them made right. When one has exhibited antitoxin and, on the second day, the temperature again rises, it is because of insufficient use and indicates the further need of antitoxin. Then I give it in double or treble quantity ; if my first injection was of 1,000 units, I administer 2,000 units, and should the third injection be necessary, 3,000 units. But to use antitoxin for complications you may as well expect a dose of quinine to give beneficial results to a man who has an ab- scess of the liver. Antitoxin will cure diph- theria. And I know that it decreases the mortality, and that it reduces the time the tube must be worn. Dr. Fischer and Dr. O’Dwyer, of New York, the originator of the tubes I have shown, will maintain the same opinion. Dr. W. B. Ulrich, Chester:—Before the Doctor takes his seat, I would like to have this question answered by him and by Dr. Welch : Have you ever known of any harm- ful results from the use of antitoxin V I, my- self, would not feel, with my experience in its use, that I had done my whole duty if not using antitoxin in diphtheria, notwithstanding my skeptical views when antitoxin was first introduced. I would like to have this ques- tion answered before the Society. Dr. Kosenthal I have used as high as 13,000 units in one case, with curative results. Dr. Ulrich :—Have you had any harmful results ? Dr. Rosenthal :—No, sir ! Neither have I found any by examination of the urine. There is a difference in the injection, depend- ing upon the kind of antitoxin you use. Gibier’s antitoxin can be used in enormous amounts with scarcely any effect. Dr. Ulrich :—YVhat kind of antitoxin serum do you use ? Dr. Rosenthal :—I use Mulford’s exclu- sively in my practice. Of the Mulford prod- uct you can secure three different strengths: The “Standard,” containing 100 units to each c.c.; the “ Potent,” containing 250 units to each c.c.; and the “Extra Potent,” con- taining 500 units to each c.c., each of these strengths being supplied in vials of 500, 1000 and 2000 units. The charts I have shown the Society were of cases treated with the “ Potent ” and “Ex- tra Potent.” In one case the tube was with- drawn within seventy hours, and the child was cured ; in the other case within seventy-three hours, with like results. I have never seen an unfavorable symptom where Mulford’s antitoxin was administered. I now use it exclusively, because it has given me results more prompt than any other antitoxin I have ever employed. Dr. Welch :—I have never seen any fatal results, but I have seen some complications arising from urticaria and joint pains.