With fhe Author s Compliments. THE ANTIPYRETIC TREATMENT OF TYPHOID FEVER. BY G. C. SMYTHE, A.M..M.D., Professor of Principles and Practice of Medicine, Central College Physicians and Sur- geons, Indianapolis, Ind. A Paper read before the Medical Society of the Missis- sippi Valley, at Indianapolis, Sept. 19, 1S83, THE ANTIPYRETIC TREATMENT OK TYPHOID FEVER. A Paper read before the Medical Society of the Missis- sippi Valley, at Indianapolis, Sept. 19, 1883, by g.c SMYTHE> a,m;,m.d„ Professor of PmTcTpVef*SHd Practice of Medicine, Central College Physicians and Sur- geons, Indianapolis, Ind. CINCINNATI: Reprint front tup Cincinnati lancet a clinic, Oct. 6th, 1883. THE ANTIPYRETIC TREATMENT OF TYPHOID FEVER. By G. C. Smythe, A.M., M.D. Under the rules of your society, limiting each paper to twenty-five minutes, it will be impos- sible to discuss the subject of typhoid fever in its entirety, consequently I shall confine my remarks exclusively to its treatment, or rather to one par- ticular plan of treatment, the antipyretic, dis- cussing the pathology and symptomatology of the disease, so far only as may be necessary to fur- nish a rational basis for the plan which I propose to advocate. Death may result in this disease from a variety of causes depending upon the nature and ex- tent of the structural lesions, which take place in any given case. These lesions are very properly divided into primary and secondary, the former including the local hyperaemia which occurs in the mucous membrane of the small intestine, to- gether with the infiltration, softening and slough- ing of the solitary and agminated glands with the subsequent ulceration. These with some changes of minor importance, which take place in the mesenteric glands, spleen, etc., are the specific lesions of typhoid fever, and owe tlteir origin to the direct effects of the poison, 4 ANTIPYRETIC TREATMENT and are as necessary to the existence of a typical case as are the eruptions in the exanthemata or the specific lesions which occur in any of the in- fectious diseases. Death may take place from these structural changes. The necrobiotic pro- cesess in Peyer’s patches may open blood-vessels sufficiently large to cause death from hemorrhage, or perforation may take place followed by a fatal peritonitis. Only a small percentage of the mortality of this disease however can be charged to the speci- fic lesions. Tabulating all the statistics to which I have had access, I find that less than six per cent, of the total number of cases have hemor- rhage ; of these a little less than one-third die, or less than two per cent, of the whole. About one per cent, of the totality of cases has perforation of the bowel, and a small portion of these recover, so that the entire mortality of this disease, aris- ing from the specific lesions, is not far from three per cent. It is plain then that we must look to the group of secondary lesions or those caused by the gen- eral disease for the cause of the heavy mortality in typhoid fever. These structural changes do not belong exclusively to this disease, but may occur in any disease characterized by persistent ele- vation of temperature, to which they undoubtedly OF TYPHOID FEVER 5 owe their otgiii. Lucy consist ui inflammations and degenerations of important organs, and may include any organ or tissue in the body. Death may result from the sudden arrest of function of some important organ or organs as the heart, brain, or lungs, without the structural changes just mentioned, but be caused by the effect of elevation of temperature sufficient to pro- duce paralysis of these organs. Then we may have a fatal result occuring from three different sources in this disease. ist. From the effects of the primary or specific lesions, ulcerations, hemorrhage and perforation. 2nd. Directly from the effects of hyperpyrexia producing paralysis of heart, lungs or brain. 3rd. Indirectly, by the pathological changes in important organs caused by the persistent ele- vation of temperature. It is now a well established fact that the char- acteristic symptoms of typhoid fever such as low muttering delirium, picking at imaginary objects, sliding down in bed, subsultus tendinum, sordes, etc., are not the direct result of the specific poi- son of the disease, but rather the effect of the long continued elevation of temperature during which the structure and functions of important organs are effected by the heat, and the circula- 6 ANTIPYRETIC TREATMENT tion is poisoned by the detritus of rapidly oxydized tissue, which accumulates more rapidly than it can be eliminated; this group of symptoms, known as the typhoid condition, occurs in all dis- eases which are characterized by persistent ele- vation of temperature, such as typhus, yellow, and scarlet fevers, small-pox, measles, and even malarial fevers, when they become continued; under any and all circumstances these symptoms owe their origin to continued hyperpyrexia. The mortality of typhoid fever varies greatly in different epidemics and in different countries. It is exceedingly difficult to arrive at a satisfactory conclusion in regard to the exact death-rate. In the French Army from 1875 to inclusive, in 26,000 cases the death-rate was over 36 per cent. German statistics under the expectant plan of treatment which was used prior to 1862, gave a mortality of about 28 per cent.; the English and American death-rate is somewhat lower, but it will be safe to state without wading through long columns of dry figures, that the percentage of deaths tabulated from the statistics of the entire civilized world would be somewhere between 25 and 30 per cent. Less than five per cent, of these deaths are shown to be caused by the specific lesions of the fever, and the remain- ing 20 or 25 per cent, of deaths are due to the OF TYPHOID FEVER 7 secondary lesions, and are caused by tne long con- tinued pyietic condition present in the disease and can, and ought to be prevented by antipyretic treatment. The etiology of typhoid fever is imperfectly understood, but modern investigation however has a tendency to establish the truth of what has been discussed for ages as the germ theory, and the probabilities are that the causes of all the in- fectious diseases will be ultimately traced to low living vegetable organisms. We possess no specifics for the disease in the same sense that quinia is a specific for malarial diseases or that salicylic acid and its salts are specifics for acute articular rheumatism ; so we are compelled to adopt a symptomatic treatment, to combat unpleasant and dangerous symptoms and see that the patient does not die from complica- tions, inter-current diseases or sequelae. These objects are best subserved by the cool- ing treatment. The temperature in this disease controls the situation. The danger is proportion- ate to its height and persistency, and altnough the hyperpyretic condition is never free from danger however brief its duration (for death may take place in a few hours from paralysis of heart or brain), it is to its persistency that the danger in this disease owes its origin. A temperature of 8 ANTIPYRETIC TREATMENT 103° or 104°, which'is persistent for ,’a period of three or four weeks will work more pathological mischief than a 'temperature of 106° or 107°, which remits promptly, as in malarial and relap- sing fevers. Statistics show that with a purely expectant treatment, where the temperature did not reach 104°, in typhoid fever, the mortality was about 9 per cent.; where it passed 104°, but did not reach 105° the mortality was about 29 per cent—when it passed 105° but did not reach 106° the death-rate exceeded 50 per cent.; and where it passed 107° recovery was rare. In all febrile diseases one of two factors is present and in a majority of cases both; they are, 1st, ex- cessive heat production, and, 2nd, faulty heat elimination. Antipyretic treatment consists in the administration of medicine to prevent this excessive production ;—and the energetic appli- cation of cold water and other means to hasten its elimination by abstraction. In order to accomplish the best possible results by this plan of treatment it must be begun early and persisted in until the danger is passed. This is a four weeks’ fever. During the first week there is a gradual but persistent elevation of temperature, at the close of which in a vast majority of cases the maximum is reached, the OF TYPHOID FEVER temperature then is persistent with slight diur- nal variations until the latter part of the third week or beginning of the fourth when the dis- ease begins to decline, and the temperature is characterized by daily remissions of several de- grees. If this period is reached without any serious complication or intercurrent disease aris- ing from excessive heat, the patient ought to re- cover unless death takes place from the specific lesions of the disease, the manner of which has been already discussed. 9 In the application of cold water as a therapeu- tical agent, we are using a means of great power, and one that must be used with care or harm may follow. An agent that will lower the tem- perature in febrile conditions four or five degrees in ten or fifteen minutes, accomplishing this by actual abstraction of heat is not intended for the amusement of the patient and his friends, while nature cures the disease. In applying all thermo-therapeutical remedies, we should be guided largely, if not solely, by the revelation of the clinical thermometer. This in- strument was introduced into clinical medicine by Dr. Antonius de Haen, of Vienna, in 1754, but did not attract the attention it merited. Dr. James Currie of Liverpool, again brought it into notice in 1797, but the profession, always slow to indorse great improvements and new discoveries, failed to recognized its importance until nearly three quarters of a century later. I regard the revival of clinical thermometry with its daily ap- plication at the bedside of more importance to the sick than any improvement of the 19th century. ANTIPYRETIC TREATMENT Ileat may be abstracted by affusion, immersion, the cold pack, sponging, or the use of Kibbee’s cot. Affusion is the most effective, but is most unpleasant to the patient. This is Dr. Currie’s method as described in his work, published in England in 1797. He claimed that typhus fever could be aborted by this means and that scarlet fever and small-pox were rendered mild and tractable affections. His method consisted in dashing upon the naked body of the patient five or six gallons of cold water, the temperature of which was, in some cases which he reports with full particulars, as low as 440 Fahr. This pro- cess was always followed by a rapid reduction of temperature sometimes reaching the normal. I have used the cold affusion in malarial and scar- let fevers with the same happy effect described by Dr. Currie. I have treated one case only of typhoid fever in this way of which I shall speak more fully presently. I am convinced however, after a somewhat ex- tended trial of these different methods of abstrac- Uon, tuat wnai la the graduated bath of Von Ziemssen is most suitable for a ma- jority of cases, and this is especially so for chil- dren and old people, because the shock of this bath is much less to the patient, and if properly applied the abstraction is none the less perfect. Fifteen or twenty gallons of water, a Knowlton’s portable rubber bath-tub, a clinical and an ordi- nary thermometer, are all the implements neces- sary to administer these baths. The same water can be used if necessary for several immersions. The patient should be immersed at full length in the water, the temperature of which should be about ten degrees lower than that of his body, and after remaining two or three minutes, cold water should be added gradually until the tem- perature of the fluid in the tub is reduced to 70° or even 65° in obstinate cases. From fifteen to twenty minutes will be required to reduce the temperature of the patient to one hundred or be- low; while plunging him into cold water of 6o°, according to the method of Liebermeister, will ac- complish the reduction in ten or twelve minutes, but is much more unpleasant to the patient. The effect of a bath is to lower the pulse and respira- tion correspondingly with the temperature, but its effect is only temporary. In two or three hours, less in severe and obstinate cases, the tem- OF TYPHOID FEVER. 11 ANTIPYRETIC TREATMENT perature will be as high as before and the bath must be repeated and the process must be contin- ued as long and as often as the temperature approaches a dangerous point. This treatment should be inaugurated and superintended by the physician in person. If the baths are administered by inexperienced nurses more harm may be done than good ac- complished, for the baths stimulate the heat pro- ducing functions of the body, and unless the ab- straction is thorough the good effect will in this way be counteracted. The nurses must be in- structed thoroughly in the discharge of their duties. They must be taught how to take ob- servations of the temperature with the clinical thermometer; in bad cases it should be used hourly and the result recorded for the information of the medical attendant. They must be taught how to temper the bath and cool it down, which must be done by rap- idly drawing off the water as it is warmed by the abstraction of the heat from the patient’s body, and adding cold water. I have seen the temper- ature of the water in the bath-tub rise five or six degrees in less than that many minutes, so rapid is the abstraction. Nurses of ordinary intelli- gence will soon master the situation. As soon as the diagnosis is well established, or before, if hyperpyrexia is an element of danger, (for this treatment is appropriate for all diseases characterized by high temperature), this treat- ment should be begun. As soon as the tempera- ture of the patient in the axilla reaches 103° F. a full length bath should be administered and repeated as often as the temperature reaches that point. It may require a dozen or more baths per day in obstinate cases during the first few days of the fever. This treatment, even thus early in ajny given case, has to a certain extent a prognostic value ; for, if during the first week, we have a patient with an extremely high temperature which is controlled with difficulty we may confi- dently expect a severe case during the second and third weeks. Although these baths in most cases are agreeable to the patient, they some- times become irksome and distasteful long before the necessity for them ceases; fortunately we possess an article in that much abused drug, Sulph. Quinia, which supplements the action of the water and obviates the necessity for such fre- quent repetition of it. If given at the proper time and in sufficient quantity it not only pro- duces a full and complete remission, but prolongs it until the following day is well advanced, even in the early stages of this disease, and renders the bath unnecessary during the latter period of the OF TYPHOID FEVER. 13 case. So far as our present knowledge extends the sulph. quinia is by far the most valuable article in the materia medica for lowering temperature in hyperpyretic conditions, yet it has no power to cut short the disease, at least in doses which can safely be used. But in order to accomplish a good result it must be administered with an un- sparing hand and at the proper time of day, for little or no good will be accomplished by giving it .in small portions scattered throughout the twenty-four hours. It is folly to give it in any quantity in the morning in order to prevent the evening exacerbation, for it cannot be done in this disease. The patient will suffer all the in- conveniences of the remedy with no correspond- ing benefit. But, on the contrary, if it is given in one full dose of from 25 grs. to 50 grs. in the early evening it will strike the morning remission with the full force of the remedy, and the conse- quence will be that the temperature will approach the normal closely, and in the latter stages of the disease fall below with a cessation of all the dan- gerous symptoms which may have been present. This remission will continue from twelve to forty- eight hours, according to the obstinacy of the particular case or the period of disease at which it is administered, allowing time for the vital organs to cool off, thus preventing the conges- ANTIPYRETIC TREATMENT OF TYPHOID FEVER tions, inflammations and degenerations of tissue which is undoubtedly the cause of the heavy mortality of this disease. Quinia given in this way does not produce the unpleasant effects so often seen to follow the administration of small doses continued for several days. It is the ionic and not the sedative dose which produces the unpleasant cinchonism. No harm has ever been known to result from its use in this way. Lieber- meister has administered it over ten thousand times by this method, giving as much as forty-five grains at a single dose. Jurgensen gives seventy- seven grains as his maximum dose, and I have administered as much as seventy-two grains at a single portion. I have now administered this remedy in antipyretic doses about fifteen hundred times with no unpleasant effects, save a transient cinchonism, and when given in the evening the patient usually sleeps through this. 15 The changes produced in the appearance of a patient by this treatment are certainly remarkable. The disease is temporarily deprived of all those symptoms which we are accustomed to see in typhoid fever; and when the treatment is begun sufficiently early they fail to make their appear- ance. The low muttering delirium is gone, the hot dry skin, which we are accustomed to see, is bathed in a profuse perspiration ; the frequent 16 ANTIPYRETIC TREATMENT and feeble pulse of 120 or 130 drops to 75 or 80 p$r minute, is full and soft ; the tongue moistens with each remission, meteorism fails to appear or rapidly subsides under the influence of the bath or the quinia, The latter seldom fails to move the bowels several times each day subsequent to its administration and large quantities of fecal matter and flatus, which ought to be, are expelled, and the unabsorbed portion of the quinia thor- oughly disinfects these discharges and contri- butes something toward preventing the spread of the disease. Patients treated upon this plan retain their consciousness throughout the disease. They take an interest in surrounding events. They can describe all their subjective symptoms. They soon recognize the unpleasant effects of high temperature from their own sensations. They ask frequently for a repetition of the bath before the physician deems it advisable to use it. They beg for the administration of the quinia every day instead of each alternate day. It will readily be seen what an immense advan- tage in the struggle for life a patient in this con- dition will have over his fellow whose intellect is muddled and rendered obtuse by the typhoid condition, and how much easier it is for the physician to detect and counteract the dangers of OF TYPHOID FEVER. secondary lesions and intercurrent affections which are so fatal in this disease. 17 The application of the cold water simply ab- stracts the heat and does not interfere with the rapid oxidation of the tissues which produces the hyperpyrexia; the remission is of course much shorter than that produced by the quinia, which acts chemically and to a certain extent prevents oxidation, if only by its mere presence. Its power for good may be abused and if continued too long become an element of danger. It lowers temperature by arresting molecular changes in the blood and tissues of the body, thus seriously interfering with the processes of nutri- tion and assimilation. The profound impression wh:ch it makes should not be continued too long nor repeated too often, for if continued from day to day it is not altogether free from danger. The full benefit to be derived from it is obtained by the remission which it produces—allowing the organism to cool off and thus preventing serious organic lesions ; consequently it is not advisable to administer this medicine, as a rule, oftener than each alternate day, and frequently during the latter part of this disease, it will not be re- quired oftener than each third or fourth day with an occasional bath in the afternoon. It is best to begin the administration of quinia 18 ANTIPYRETIC TREATMENT with a 25 or 30 gr. dose. If this does not pro- duce a satisfactory remission it should be in- creased until the maximum is reached for the particular case under treatment. This quantity, whatever it proves to be, can be materially reduced in the latter stages of the disease. When this treatment is begun early, no other treatment is usually required. I am in a habit of presaging it with two or three cathartic doses of calomel ; this is an efficient cathartic and clears the alimentary canal thoroughly of any accumulations of feculent matter—is a parasiti- cide and prevents the absorption of any further infectious material from that source and is sup- posed to exert a favorable influence upon the subsequent course of the disease. It should not be administered after the typhoid condition is thoroughly developed for reasons which are suffi- ciently obvious without any explanation. Occa- sionally a case will occur where the baths and quinia do not produce satisfactory remissions. In these cases the administration of the quinia should be preceded by digitalis or veratria for a period of twenty-four or thirty-six hours. I have met but two cases of this kind out of sixty-three, in both of which a full dose of 45 grs. quinia following the digitalis was entirely satisfactory. Neither digitalis nor veratria should be given in OF TYPHOID FEVER 19 the latter stages of this diseases, for whatever may be said of the action of digitalis as a heart tonic in other diseases, it is certainly not a safe remedy in the latter weeks of typhoid fever. To Dr. James Currie, of Liverpool, is due the credit of first using cold water scientifically for the abstraction of heat in hyperpyretic conditions. To him is due the invention of the curved axil- lary thermometer, one of which has been pre- served in the British Museum. His method was adopted largely throughout the British Isles and on the Continent, in the English army and navy. His works were translated into French and German, and an edition was published in this country in Philadelphia. (Currie was a citizen of the colony of Virginia when the Revolutionary War broke out, but being loyal to the Crown he returned to England.) His rules for abstracting heat by water have been improved but little. Quinine had not been extracted from the bark in his day, yet he used the latter freely. The sud- denness with which Currrie’s plan of treatment was abandoned after his death,which occurred in 1805, is one of the unexplained mysteries of medicine. We are indebted to the Germans for reviving and establishing this plan of treatment on a sound philosophical basis. It is the most rational 20 as well as the most successful treatment that has ever been adopted in this fever, as is clearly shown by statistics. At Basle, Switzerland, Lie- bermeister reduced the death rate from 28 per cent, to 8 per cent. At Kiel under antipyretic treatment a little more vigorously and system- atically applied the mortality fell to 3.1 per cent. ANTIPYRETIC TREATMENT The analysis of the statistics of the German Army are valuable and convincing. From 1820 to 1844 the death rate was a little over 25 per cent. From 1868 to 1874, under partial and im- perfect antipyretic treatment, the rate per cent, of deaths was reduced to 15. From 1874 to 1880 the treatment was more general and the death rate was reduced to 8 per cent. In the Second Army Corps the cold water treatment was more thoroughly tested. When this treat- ment was begun by Dr. Abel, who is a strenuous upholder of this plan, the mortality rated at 20 per cent., which, however, soon fell to less than 5 per cent. Still more striking is the confirmation afforded by the five principal hospitals of this corps which were under the immediate and per- sonal supervision of Dr. Abel. In i860 the mor- tality had been 25 per cent., by 1877 it was low- ered to 7 per cent., and during the five years fol- lowing the immediate coming of Dr. Abel it fell to 14 deaths in 764 cases, or 1.8 per cent. ; these figures are taken from an article in the Review Scientifique from among many others all from offi- cial sources and all pointing to the same conclu- sion. OF TYPHOID FEVER 21 During an extensive epidemic which has re- cently prevailed in France this plan of treatment has been tried successfully in some localities, al- though the French, since the Franco-Prussian war, do not take kindly to German methods. In Paris the hospital physicians disagreed in regard to its utility upon theoretical grounds, and it was not used systematically and consequently gives no statistices of value. In the city of Lyons it was vigorously used, with a reduction of the mortality rate to 2 per cent. Our most favorable reports come, however, from private practice. Neither water-works nor bath-rooms are necessary to secure the best re- sults from this plan of treatment. Indeed, the latter cannot be used, for patients cannot be transported from the sick chamber to a bath- room, even though it might be in an adjoining apartment. I have treated upon this plan sixty- three cases with two deaths* Dr. J. R. Feather- stone, of Indianapolis, has treated fifty-seven cases with one death. Dr. W. H. Vanzant, of Carbon, Ind., has treated twenty-six jjcases with 22 no deaths. Dr. S. E. Earp, of Indianapolis, has treated eleven cases with no deaths. This gives a total of (157) one hundred and fifty-seven cases with three deaths only, or a rate per cent, of mortality of 1.9. ANTIPYRETIC TREATMENT The highest temperature reached by any of these cases was 107.750 It occurred during the death agony after severe and repeated hemorr- hages in a patient whose temperature previous to that time had not exceeded 104.50. One patient recovered whose temperature about the middle of the second week touched 107.50, another whose temperature reached 107° recovered. The tem- perature of sixteen of my cases went to 106° and beyond, some ranging as high as 107.50—all of these recovered, a result hardly to be expected from any other plan of treatment. Hemorrhage of the bowels occured in nine cases, or a little less than six (5.7) per cent. It has been claimed that hemorrhages are more fre- quent under this plan of treatment. Exactly the converse is true. The inflammation is less in the ulcerated mucous membrane, the bowel is not stretched and distended, and its capillaries torn by tympanitis. This is one of the complications which belongs more properly to the latter stages of the disease. More patients live to the period of the disease at which it occurs, which account? OF TYPHOID FEVER for the apparent increase in the number of cases suffering from this accident. 23 Of these one hundred and fifty-seven cases, eight relapsed, five and two-tenths per cent, of the whole. It is also claimed by the opponents of this plan that more relapses occur than when the expectant or do nothing'plan of treatment is adopted. It would be strange, indeed, if this were not true, twenty additional lives are saved out of each hundred treated by this method as compared with the expectant treatment. So the relapses ought to be one-fifth greater, having that much more material out of which relapses are liable to occur, while the 20 per cent, of dead under the can furnish none. Sixteen of Dr. Vanzant’s cases were treated by affusion and ten by immersion. Three of the former relapsed. His largest dose of quinia was fifty grs. Drs. Featherstone’s and Earp’s cases were treated by sponging, the cold pack, and an occa- sional bath. The largest dose of quinia admin- istered by the former was sixty grs., the latter fifty grs. All the cases which I have treated since 1878 have been immersed with the excep- tion of my last case, which was treated by affu- sion. I find that the water and quinia supple- ment the action of each other. The intermission produced by the quinia after the use of the bath is much more satisfactory and prolonged, while the quinia renders the necessity for the bath much less frequent. 24 TREATMENT OF TYPHOID FEVER. The case which I treated by affusion was a healthy male adult aged 19. He was the last one of eight cases which made their appearance in a club of Asbury students. The attack promised to be unusually severe, the temperature ascend- ing to 105° Farh. on the afternoon of the fourth day. At 3 p.m. he was stripped and placed in a large tub in the erect position and about five gal- lons of water, the temperature of which was 750, poured slowly over his body. Fifteen minutes afterwards his temperature was 990. At 7 p.m. his temperature had risen to 105.50, when the affusion was repeated with a similar result. Forty grains of quinia were administered at the same time. The patient perspired profusely through the night, slept well, and on the following morn- ing at 8 a.m. temperature normal, pulse 76, re- spiration 20. This condition continued for about thirty-six hours when the temperature gradually arose, but never exceeded 102 50 during the remainder of the disease. After this period of the disease had passed, 15 grs. of quinia produced a perfect remission, and no more water was used, but the duration of the fever was twen- ty-six days. Affusion should be used only during the first few days of the fever. Patients treated upon this plan have few or no sequelae and are able to resume their occupations in a few days after convalescence is established. Few conditions arise which contra-indicate its use : of course that perfect degree of rest necesary in hemorrhage ar>d perforation forbids its employ- ment in cases where these complications arise. Greencastle, Ind., September, 1883,