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 Citation1. 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 Citation2-4. 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 Citation2. 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) Citation2-4.
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 Citation5, 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 Citation6&7. In addition there may be diffuse endothelial injury or cardiotoxicity from reactive oxygen species Citation8 or cardiac effects may be secondary to acidosis or electrolyte abnormalities Citation9, and others have speculated that the hypotension may be centrally mediated Citation3, although generally central cholinesterase inhibition leads to a pressor response Citation10.
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.
Andrew Dawson
University of Peradeniya
Sri Lanka
Nick Buckley
Dept. Clinical Pharmacology
Canberra Hospital
Australia
References
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