The Pathogenesis of Septic Shock

Bart Chernow, MD; John W. Holaday, PhD
JAMA. 1984;252(2):208. doi:10.1001/jama.1984.03350020018009.
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To the Editor.—  The review on septic shock by Drs Parker and Parrillo1 nicely described the cardiovascular effects as well as potential mediators of septicemia. However, we believe they understated the role that endogenous opioid peptides (endorphins) play in the pathogenesis of septic shock. Since 1978, when endogenous opiates were first suggested as mediators for endotoxin-induced hypotension,2 many investigators have confirmed the importance of endogenous opiates and opiate-receptor antagonists in the pathogenesis and treatment of septic shock, respectively.3-5 In many species, including man, the use of opiate antagonists has allowed the inference that endogenous opioid peptides play an important role in the hemodynamic, hematologic, autonomic, metabolic, and endocrine responses to endotoxemia and sepsis.3-5 These effects may either be direct or indirect through other humoral mediators such as catecholamines, prostaglandins, activated complement components, kinins, and corticosteroids.6 We believe that the scientific foundation for endogenous opiate involvement


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