Adrenergic blocking agents in shock

Abstract

IN RECENT YEARS a number of agents have been developed which block the sympathetm nervous system These agents can be dwided into two groups according to their site of action, ganghonic blocking agents block the transmission of impulses at the ganghonm synapses, adrenergic blocking agents act on the sympathetic end organs and reduce or reverse the pressor effect of adrenahn The latter group includes agents hke dlbenamine, dlbenzyhne, regitme, priscoline, hydergine, and chlorpromazme (Largactil) Especially for chlorpromazme and more recently for hydergine, claims hay6 been made that these agents would prevent shock caused by haemorrhage and severe trauma or would at least delay the onset of an irreversible state of shock Laborit's (15) concept of artificml hibernation, m which Largactd plays the principle role, has received wide publicitT, parbcuIarly in regard to its apphcation in shock. Chmcally, adrenergic or ganglionic blocking agents have been advocated for protection against shock and, m addibon to blood volume replacement, for the treatment of existang shodk (3,7,17) The reports of such treatments appear to be noteworthy and one has the impressmn that adrenergic blocking agents in combination with blood volume replacement would give better results than the present treatment of shock with transfusions and supportive measures The value of many of the pubhcations, particularly those from Europe, is discounted because they are written in a flowery language with specially invented terminology, and because the argumentabon is frequently based on very theoretical grounds.The basic concept for tins new approach appears to be this. A dimimshed blood volume leads to a decrease in venous rebn-n and a reduced cardiac out-put The resulting fall in blood pressure is counteIacted by peripheral vasoconstriction, which is induced and possibly maintained by the activity of the sympathetic nervous system including the adrenal medula. This vasoconstrmtion in reducing the blood flow produces bssue hypoxia, which leads to an increased capillary permeability. Leakage from the capillaries reduces the blood volume fitrther and thus a vicious cycle is set into operation (Fig. 1 ).The important concept in this "shockwheel" is that compensatory mechanisms contribute to the progress of shock. Erlanger .and Gasser (6) in 1919 expressed the view that the increased adrenergic acbvity in shock was an important factor in the deterioration of the organism. It was later on demonstrated that a continuous infusion of adrenahn could produce shock (8), and a marked rise of the blood level of adrenalm was observed following haemorrhage in dogs (23) 1Presented at the combined meeting of Section of Anaesthema, ()ntaxao Medacal Associalaon, and the Ontario Dlvlmon of the Canadaan Anaesthetasts' Socmty, October 5, 1957, m Hamilton, Ont. 2Departuaent