Hemodynamic and metabolic manifestations of acute endotoxin infusion in pigs with and without the malignant hyperthermia mutation

Background: The hypermetabolic state induced by acute endotoxemia and malig nant hyperthermia (MH) may be indistinguishable, The aims of this study wer e (1) to investigate the differences between MH and sepsis, (2) to determin e whether acute endotoxemia can trigger MH, and (3) to establish the effect s of dantrolene in these two disorders. Methods: Three groups of swine were studied. All pigs were invasively monit ored and initially anesthetized with nontriggering agents. A placebo Mil-su sceptible group (n = 5) received normal saline whereas the endotoxin groups (MH-susceptible, n = 6; MH-negative, n = 4) received intravenous endotoxin (250 mu g/kg total) during 2.5 h. Halothane (1.5%) and succinylcholine (2- 4 mg/kg) were then administered, followed by two doses of dantrolene (4 mg/ kg total), Results: Endotoxin infusion resulted in pulmonary hypertension and systemic hypotension in pigs with and without the MH mutation, but did not trigger MH. Halothane and succinylcholine triggered MH, evidenced by a markedly hig her oxygen consumption in the MH-susceptible pigs that received endotoxin(3 25 +/- 196 ml/min) and those that did not (374 +/- 110 ml/min) compared to the MH-negative pigs (69 +/- 15 ml/min, P < 0.0003), as well as muscular ri gidity in the susceptible animals. Dantrolene reversed these changes. Three of the six MH-susceptible pigs that received endotoxin died; two died soon after triggering and one after dantrolene administration, In contrast, non e of the MH-negative pigs or the MH-susceptible pigs that did not receive e ndotoxin died (0 of 3 vs. 3 of 6, P = 0.044). Conclusion: Endotoxemia does not trigger MH, but may worsen outcome if it o ccurs.