Subnormal Temperatures from Poisoning in Relation to Toxicity Determination

Abstract

It seems important, especially in connection with toxicity determination, to point out that toxic doses of many substances may produce fall of temperature before death or recovery. An old clinical direction calls for note of the body temperature in case of poisoning and special arrangements if needed to reduce heat loss. Incidentally, the statement, “quinine has no significant effect on the normal temperature in man or in animals”, 1 appears to need revision, the statement, “in toxic doses the fall is proportional to the collapse”, 2 being truer. Quinine has produced subnormal temperatures in man, 3 and in the rabbit fall of 12°C., 4 and the related cinchonine fall of 14°C. in this animal. 5

We were led to note rectal temperatures in guinea pigs, used for preliminary toxicity determinations on cinchona bases, by unwittingly repeating an old observation, 6 finding live animals, sometimes quite active, cadaverously cold to the touch. The drugs were given subcutaneously in the flank, in doses mostly in the lethal range, which is for most of these bases 100–400 mg. per kg. Using an average of about 7 animals in each series, we found in the case of each of 22 cinchona bases at least one animal in each series showing fall of 6° C. or more before death or recovery. The phenomenon seems common to all members of the group, including quinine, and is not limited to the cinchona series, for we found it also with morphine and quinoline, and Louvier 7 has noted it with phenobarbital. The fall is not necessarily premortal: thus, one of our animals recovered completely after fall of 9°C. from hydrocinchonine; Simpson 8 reported recovery of a monkey after fall of 24.6°C. from ether anesthesia and chilling.