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exhibits hyperæmia and perspiration. Phenols exert their influence even when the lower part of the cortex is irritated by a puncture, and show a general influence on other cerebral centres, for instance by promoting analgesia.
There are those who object to the use of antipyretics altogether on the ground that high temperatures, mainly those of the infectious fevers, are required for the formation of antitoxins, and thus for recovery.
There can be no doubt that even the apparently worst cases may get well spontaneously, those of typhoid for instance, or of cholera or of plague. It is said their high temperatures kill bacilli and form antitoxin. But this killing is an unreliable postulate. While they form toxin, they need not be themselves destroyed. Typhoid bacilli outlive their toxin, and their possible antitoxin. And indeed if they succeed in killing bacilli they kill cells also; with the unwelcome tenants the suffering host. If according to that theory they develop antitoxin after awhile, that while is often too long for the muscles and nerves and epithelia to endure both the heat and the disintegration. Wait for the beneficent effect of heat in sunstroke and you have a corpse to take care of. If typhoid and plague get well it is not the persistence of high temperatures that saves one-half or less, it is the vitality of the patient which endures and overcomes it all. Indeed the mortality rises with the height and permanence of temperatures. These however may be ever so high; provided they are interrupted, they are endurable. Pneumonias and typhoids with fair remissions permit of favorable prognoses. While plague with persistent temperatures kills fifty or sixty per cent., relapsing fevers of long duration, and with very high temperatures, have a mortality of only two or three per cent. because they have long intermissions.
Continuous hyperthermy does not only as Marfan says show the presence of danger as indicated in the condition of the pulse, in the presence of thirst, asthenia, dry mucous membranes, inactive liver, defective excretions, and depressed or excited cerebrum, it is a danger by itself, and should be fought by water, or by chemicals, as the case may be, until the danger line is recrossed backwards in the direction of a euphoric condition of the sensorium, of appetite, of respiration, and circulation and diuresis.
The multiplicity of the causes of fever prove its nature. It is not an entity but a symptom, the treatment of which should not be guided by iron-clad rules. Rises of temperature are not by themselves injurious, on the contrary there are those which seem to have as suggested before an immunizing effect. At all events a temperature which may be an annoyance or a danger to one individual, is an indifferent matter to another; and a temperature which is badly tolerated on the first day of an illness, may be easily borne later on, and vice versa. It all depends on the patient, not on the thermometer. Besides some causes of fever will prove temporary, others permanent; while for instance some of the bacilli are dangerous a certain time only, other microbes like plasmodia, become the more detrimental the longer they remain undisturbed. Thus in the treatment of many fevers it is their causes that require consideration; in others however their relations to, and influence on the body are the main consideration. When the condition of the latter is fair, and no danger is incurred by the fever, it should be left alone; when the rise of temperature, however. by itself is injurious, it should be interfered with. At all events however, the treatment of the symptom "fever” gives us no hope of shortening the disease in which it occurs or of which it forms a part; on the other hand, it is a satisfaction to kncw, that while we increase the comfort and diminish the immediate dangers, the natural healing process is not disturbed. In this way both the justification and the limitation of the so called expectant treatment become evident. To allow a high temperature to deteriorate tissues and exhaust the heart or brain, is as injudicious as is the custom of emphasizing the number of degrees of Fahrenheit as the only valuable part of a morbid process. To be satisfied with depressing temperature is a grave mistake, but to allow pneumonia to run its deleterious course of high temperatures unchecked with their full influence on the rapidity of respiration and the action of the heart and on the increase of waste, is equally injudicious.
In their injurious influence on nutrition protracted fevers act like direct losses or like starvation, or rather more than these. The vounger the patient, the greater is the danger from that source. That is why a high temperature without any or trifling remission should not be allowed to last, though its immediate effect may not appear very ominous. When a high temperature results in a convulsion we never hesitate to reduce it; here we admit there is a vital indication. Why, then, not reduce it while there is the danger of a possibility or probability of their occurrence? I dare say however that more infants and children die of the slow results of protracted high temperatures during what is called convalescence than there are destroyed by their effects in the onset of the disease. This danger may be averted by early attention to very high temperature. Amongst the tissues the blood is injured at an early date.
An acute anæmia is more easily overcome than a chronic one which undermines the vitality and strength of all the organs while it slowly robs them of their nutrition. To this latter class belong those anæmias which result from such diseases as are attended with sudden losses, high fevers, and starvation. It is mainly infants that when thus stricken recover but slowly or not at all, the less so the younger they are. Young animals resist starvation, which acts similarly to infectious fevers, to a less degree than old ones. A dog two days old bore starvation in Magendie's laboratory two days only; a dog of six years, thirty days. Similar results were obtained on pigeons, by Chossat. Thoroughly anamic and delicate babies, having become so by a protracted disease and ill-nutrition, rarely recover, entirely, like starving young animals that never obtained this normal condition though they were carefully fed afterwards.
Add to these facts the disposition of the young to inanition which is caused by two main factors. The first is their rapid metabolism, the second and principal one is the relative almost universal insufficiency of the young organism. Without my going into details, its blood is less in quantity compared with the adult. In the former the relation of its weight to the total body weight is 1 : 19.5, in the latter 1:13. This blood in the young has less fibrin, less salts, less hæmoglobin (except in the newly born), less soluble albumin, less specific gravity (1.0451,049 : 1.055 in the adult), and more leucocytes than in later life. All of which suggest the facility with which hydræmia is developed by injurious influences.
Moreover we should not forget that most of our antipyretics are at the same time nervines, analgesics and diaphoretics, thus improving comfort and metabolism. They are surely indicated when bathing is not sufficiently efficient; in that case they may act as adjuvants, as combinations, and procure sleep and remissions ; or when baths are contraindicated, as in most cases of intestinal hemorrhages, in peritonitis, in utter cardiac failure, and when the extremities are persistently cold. If I add that there are, however, contraindications to the use of medicinal antipyretics because of possible idiosyncrasies, and of the debilitating effects many of the antipyretic drugs are apt to exhibit, I merely say what all have experienced, and what everybody should remember, viz., that no degree of Fahrenheit, and no Greek name of a morbid process are the subjects of our medication, but an individual patient.
Quinin affects bacteria but little, those of anthrax for instance in a solution of 1-625 only. In water solutions of quinin fungi will grow as shown microscopically by their increasing turpidity. Only infusoria and turbellaria are influenced by solution of I : 20,000-100,000. It diminishes the metabolism of albuminoids and the amount of uric acid, also the number of circulating leucocytes and their ameboid movements. In normal conditions it reduces the daily oscillations of the body temperature, in abnormal ones the latter is affected quite gradually in accordar.ce with the absorbability of the drug, the elimination of which commences within half an hour, and is finished within twenty-four hours after its administration. In small quantities it accelerates the pulse and increases blood pressure, in larger ones occasionally even in relatively small doses, it may cause uticaria or other exanthemata or renal irritation with albuminuria or hematuria; fit also diminishes, as Piorry showed first more than fifty years ago, the size of the spleen, not however through any effect on the central nervous system, for the same effect is obtained when the nerve has been previously cut Nervous symptoms such as tinnitus, and difficult hearing and impairment of sight, even collapse and convulsions with affection of the centres of respiration and circulation, are also rather original disorders of circulation than of innervation.
In fair doses it is certainly antipyretic. When now and then in malaria infection a single large dose has been observed to cause an attack (sometimes the very first), this should be attribuIted to the rapid contraction of the spleen, which has the effect of suddenly deluging the circulation with the bloodcells containing plasmodia that were stowed away in the sponge-like tissue. It is the same observation I have sometimes made, under the same circumstances, and described in the Transactions of the Climatological Association of 1898, when administering ergot in cases of chronic malaria infection without previous chills.
Besides malaria, feverish diseases with a remittent type such as typhoid fever, and pneumonia with a marked morning remission are mostly amenable to the antipyretic action of quinin. If at all it should be given during the remission. In malaria it should be administered during the period of sporulation, that is from three to five hours previous to an attack, but not as Golgi and Koch recommeaded, in the decline of the paroxysm, when the parasites are large. The sporules are most easily killed, the young ameboid forms of the plasmodia are more obstinate, the crescent (Sizygia) varieties however should be treated with more frequent doses.
In accordance with his rule, according to Golgi, Marchiafava and Bignami, the tertian malaria fever is readily influenced by the administration of quinin just before the paroxysm in such a way that the following paroxysm is either prevented or delayed. In the quartan type when administered four or five hours before segmentation ("sporulation”), it readily kills the young forms, but not the adult, so that the following paroxysms are not interfered with.
It is desirable to secure prompt absorption which is retarded when there is vomiting, diarrhoea, gastric catarrh or obstinate constipation. Now and then the combination with bitters and tonics acts favorably under such circumstances. It is here perhaps where Beverley Robinson and others have their principal successes with the tincture, in preference to the salts of the alkaloid. Absorption is certainly aided by the addition of diluted alcohol, or of spices. That regard should be had to the taste of medicines, is self understood in the cases of infants and children, and not infrequently solubility has to be sacrificed in the interest of taste. In very urgent cases the subcutaneous and intravenous administration yields the best results; then the solutions must be neutral. The carbamide (bimuriate with urea) may be injected into the subcutaneous tissue in warm solution of one to four or five; muriate of quinin three parts, with antipyrin two parts, with enough water to make six parts, is highly spoken of as painless and not liable to cause necrosis. That painlessness I have not been able to confirm. My preference is for the bimuriate with urea.