McQuiston (1951), and others that when the body temperature has been finally reduced by physical means the oxygen consumption of the tissues is markedly lowered. It is then possible to undertake surgical operations requiring the exclusion of the heart, or lungs, from the circulation for several minutes, without anoxic damage to the tissues.However, the application of ice-packs, refrigerated blankets, and other external cooling in itself constitutes a stimulus which calls the defence mechanism into action. This is shown by increased oxygen consumption and heart rate, and by shivering in order to maintain body temperature.Only when the defence mechanism is overcome do the body temperature and the oxygen consumption drop (Prec et al., 1949;Jaulmes, 1953). It is at this stage, on the way to final dissolution of the subject, that these operations can be performed.The artificial hibernation technique evolved by the French workers, Jaulmes, Laborit, Huguenard, and others owes little to physical cooling of the subject from without, but depends on the specific neuroplegic effect of drugs, mainly those of the phenthiazine group on the autonomic nervous system.The phenthiazine derivatives include the antihistamine drugs promethazine hydrochloride ("phenergan") and promethazine-8-chlortheophyllinate ("avomine "), which has a central action, particularly upon the vomiting centre, and chlorpromazine (" largactil "), which has no antihistaminic action. This drug seems to act centrally on the autonomic system as a neuroplegic, and it has a pronounced antiadrenaline effect and a direct depressant action on the temperature-regulating mechanism.Laborit et al. (1952) have described a detailed plan for producing a state of artificial hibernation which has guided us in our efforts to ameliorate the condition of patients subjected to major surgical procedures. He relies on the use of a " lytic mixture" consisting of 50 mg. of promethazine, 50 mg. of chlorpromazine, and 100 mg. of pethidine, which is administered intravenously in divided doses in the hour before operation. The hibernant state is maintained by giving, intravenously, one of three "cocktails " containing, among other drugs, aneurine, pethidine, promethazine, chlorpromazine, diethazine hydrochloride, sparteine sulphate, ascorbic acid, ethyl alcohol, and procaine. In addition acetosterandryl, neostigmine, and heparin are given intramuscularly.
Present InvestigationWe have attempted, so far as is practicable, to avoid the polypharmacy of our French colleagues. The technique which we now adopt and which has given excellent results in our hands in a variety of major surgical procedures is as follows. The patient is given 50 mg. of promethazine-8-chlortheophyllinate by mouth two hours pre-operatively. One hour later this is followed by a subcutaneous injection of100 mg. of pethidine with 1/150 gr. (0.43 mg.) of hyoscine hydrobromide. The patient is brought to the anaesthetic room and the mixture of promethazine, pethidine, and chlorpromazine, in the proportions advocated by L...