Comment on "Survival Pattern in Patients with Acute Organophosphate Poisoning Receiving Intensive Care"

Abstract

To the Editor: Munidasa et al. observed that refractory hypotension was strongly associated with a high early mortality from organophosphate poisoning despite adequate respiratory support, inotropes, and intensive care (1). The authors speculated that the most likely mechanism was globally impaired myocardial function as these patients typically also had pulmonary oedema. However other smaller series of similar patients with invasive monitoring suggest other mechanisms may be important. We and others have found extremely low vascular resistance in OP poisoned patients with hypotension refractory to catecholamines (2 – 4). Despite the patients being clinically atropinised the low vascular resistence responded partially to very high doses of atropine but not to other vasopressors. We postulated that this vasodilation was due to stimulation of the vascular endothelial muscarinic receptor resulting in the release of nitric oxide (2). We have observed this repeatedly in subsequent patients, and the hypotension in most patients is usually associated with a high rather than a low cardiac output (similar to septic shock) (2 – 4). There are a number of other mechanisms that may contribute to hypotension in organophosphate poisoning. Despite causing generalized vasodilation, acetylcholine can also induce vasoconstriction at sites where the endothelium is damaged (5), and this might lead to myocardial ischemia. Cardiac oxygen demand may be higher, due to the high cardiac output state and excessive endogenous or exogenous catecholamines. As well as contributing to focal ischemia, this could lead to diffuse myocardial necrosis similar to that seen with phaeochromocytoma (6,7). In addition there may be diffuse endothelial injury or cardiotoxicity from reactive oxygen species (8) or cardiac effects may be secondary to acidosis or electrolyte abnormalities (9), and others have speculated that the hypotension may be centrally mediated (3), although generally central cholinesterase inhibition leads to a pressor response (10). We agree with Munidasa et al.’s implication that refractory hypotension is the leading cause of death in anticholinesterase poisonings that are receiving maximal supportive care. It is plausible that one, many or all of these different mechanisms are important. A rational approach to the management of patients with refractory hypotension depends on the development of a much better understanding of the pathophysiology. Only then will it be clearer what treatment options are appropriate, what investigations are required, and whether treatment needs to be individualized or if clinical trials of antidotes for the hypotension are feasible.