USES AND ABUSES OF ANTIPYRETIC THERAPY By Alan K. Done, M.D. Department of Pediatrics, Stanford University School of Medicine F undoubtedly the most common ben of points which deserve consideration symptom confronting the physician before one elects to use an antipyretic. who treats children. It is fought as though DuBois’ summarized a lifetime of study it were the patient’s primary disease, and on fever and the regulation of body tem. its mere presence is often accepted as being penature with the statement: “Fever is only sufficient indication for the institution of a symptom and we are not sure that it is antipyretic therapy. It is not surprising, an enemy. Perhaps it is a friend.” The litena- therefore, that therapeutists and pharma- tune concerning the possible role of fever in ceutical concerns have energetically sought body defenses is extensive and inconclusive. new and better drugs for the control of There is little question that artificially in- fever. In the past few years there has ap- duced fever is of some value in the treat- peared on the market a number of new ment of such diseases as neurosyphilis, cer- formulations which are purported to offer tam inflammations of the eye, and arthritis. distinct advantages in terms of antipyretic In animal experiments, elevation of body potency, acceptance by children, and/or temperature has been shown to be of im- reduced toxicity. portance in resistance to certain infections.2 It is axiomatic that virtually any claim Body temperatures of greater than 106#{176}F regarding a drug can be supported by pub- (41.1#{176}C) rarely occur except under highly lished data, if the proper study is selected anomalous circumstances, and this level is and interpretation is sufficiently influenced probably safely below the point at which by conviction. Particularly is this true of temperature itself poses an immediate antipyretic-analgesic drugs, where such fac- threat to the individual.3 Circumstances tons as lability in the case of fever and lack which may lead to higher temperatures in- of objectivity in the case of pain, make elude: exposure to a sudden overwhelming evaluation difficult. The claims and counter- heat load, such as injection of pynogen or claims which have been made concerning placement in a steam cabinet; excessively antipynetic drugs have led to considerable prolonged exposure to a heat load with re- confusion and misunderstanding on the part sultant “exhaustion” of temperature-regulat- of clinicians in general. The purpose of this ing processes; and the loss of temperature presentation is to attempt to provide some regulation seen in association with severe clarification of this problem. brain damage and in moribund patients. It has been postulated that, except under cm- IS ANTIPYRESIS INDICATED? cumstances such as these, an “emergency More critical than the choice of an anti- regulatory mechanism” in fever operates to pyretic is the question of whether or not prevent the elevation of body temperature such therapy is indicated in the individual to levels at which fever per se is life- case, for there is little doubt that these threatening.3 drugs are grossly overused, at times to the It is doubtful whether body temperatures detriment of the patient. Therefore, before in the range of 104#{176}F(40.0#{176}C) are harm- discussing the antipyretics themselves, it ful, even if prolonged for several days.1 In- seems appropriate to review briefly a num- deed, this is the temperature level found in Presented, in part, before the Annual Meeting of the American Academy of Pediatrics, October 20, 1958. ADDRESS: 2351 Clay Street, San Francisco 15, California. PEDIATRICS, April 1959 774 Downloaded from www.aappublications.org/news by guest on September 23, 2021 AMERICAN ACADEMY OF PEDIATRICS - PROCEEDINGS 775 athletes during hard exercise. Thus, the disaster. Moreover, each time a drug is re- rationale for the administration of antipy- moved from its usual storage place, the retics is open to serious question, except in likelthood that it will be ingested acciden- rare instances of severe hyperthemia and tally by a child is markedly increased. In in patients in whom the increased circula- recent studies on the epidemiology of ac- tory demands imposed by fever may be un- cidental poisonings in childhoods it was desirable; for example, children with myo- found that in the majority of instances of cardial disease. In the child who has a his- accidental ingestion of drugs by children, tory of convulsions, the administration of the material involved had been removed an anticonvulsant during febrile illnesses is from its usual place of storage to be ad- more rational and effective as a prophylac- ministered either to the child who ulti- tic measure against convulsions than the mately ingested it or to another member of routine use of antipyretics, and it permits the family. Of course, there is the addi- preservation of fever as a diagnostic and tional danger that therapeutic overdosage prognostic index. may occur despite (or because of) specific instructions from the physician. DISADVANTAGES OF ANTIPYRETIC DRUGS 5) Antipyresis is not the only therapeutic The potential disadvantages of the use effect of antipyretic drugs and the addi- of antipyretic drugs deserve consideration: tional effects may “mask” or suppress signs 1) The temperature course can be a valu- and symptoms which could be of diagnostic able diagnostic clue and an indicator of the importance. Most antipyretic drugs are an- severity or duration of illness, the adequacy algesics to a greater or lesser degree and of therapeutic response and the occurrence can therefore prevent the occurrence of of complications or relapse. It is rather in- pain. Most antipyretic drugs also have an- congruous that we should be so hesitant tirheumatic properties and will prevent the about administering an analgesic to a pa- development of such overt manifestations tient with unexplained abdominal pain, but as arthritis in the patient with rheumatic so willing to order an antipyretic for the fever, without altering the progression of patient whose only apparent abnormality at carditis. For this reason, their use in the the moment is unexplained fever. After a patient with unexplained fever, in whom diagnosis is established, fever may be the rheumatic fever is a diagnostic possibility, best, or the only, available sign for follow- is contraindicated until such time as this ing the course of illness. For example, sub- diagnosis is definitely confirmed or elimi- sidence of fever is a valuable indicator of nated. effectiveness of antibiotic therapy. 6) Finally, and perhaps most important, 2) There is, of course, the previously antipyretic therapy all too frequently is al- mentioned possibility that fever may actu- lowed to replace or delay efforts to estab- ally be a “friend” rather than an “enemy.” lish a definitive diagnosis and to institute The possibility that body defenses are specific treatment. strengthened in the presence of fever has The foregoing was not intended to imply neither been proved nor refuted. that sick children should not be made com- 3) The fact that severe allergic or idio- fortable. Although there is considerable syncratic reactions are relatively uncommon question whether fever per se is responsi- is little comfort to the patient who has one, ble for malaise, aches and pains, every or to his physician, particularly when mdi- physician has occasionally seen utter misery cations for the use of the drug were ques- give way to relaxation and sleep upon the tionable at best. administration of an antipyretic to a fe- 4) Where there are children, the mere bnile child. On the other hand, children presence of a potentially toxic substance often feel surprisingly well despite high (and this includes all antipyretics) invites fevers, and antipyretic therapy is employed Downloaded from www.aappublications.org/news by guest on September 23, 2021 776 ANTIPYRETIC THERAPY more for the benefit of the parents or the lowing the environmental temperature to physician than the child. Recent publicity rise. This resulted in a gradual increase in has sensitized parents somewhat to the body temperature to 104#{176}F(40.0#{176}C). Re- dangers of the indiscriminate use of drugs, ducing the environmental temperature by and a word of explanation as to why treat- replacing ice in the enclosure was sufficient ment is being withheld will usually be ac- alone to cause a rapid reduction in fever. cepted and respected. An additional factor which is of impon- tance in determining heat diffusion is the OTHER MEASURES TO LOWER degree of hydration of the patient. Every BODY TEMPERATURE physician has observed children whose In the home care of the febnile child, fevers diminished when adequate hydration much of what is done actually interferes was accomplished. It has been shown that with heat diffusion from the body and tends heat loss through perspiration varies di- to elevate temperature further. Fever oc- recfly with the degree of hydration.5 curs because heat production exceeds heat Simple measures, such as those men- loss; the latter being dependent primarily tioned, will help to prevent the develop- upon conduction, convection and evapora- ment of excessive fever and, furthermore, tion. As the only factor which will diminish will increase the reliability of fever as a heat production is subsidence of the basic diagnostic and prognostic clue. Such steps disease process, any other reduction of body are important even when antipyretic drugs temperature must come about through en- are being used, as these compounds act hancement of heat loss. through the central nervous system to ne- The common practice of bundling the duce febnile temperatures by promoting febnile child in heavy blankets interferes heat 1085.6 with heat loss through evaporation, con- When it is deemed necessary to institute duction and convection.