Exploring circulatory shock and mortality in viper envenomation: a prospective observational study from India

Background: Viper envenomation contributes to nearly 50% of snake-bite deaths in India, chiefly due to circulatory shock. The mechanisms leading to circulatory shock include bleeding, capillary leak syndrome (CLS) and myocardial depression. Pituitary-adrenal axis involvement in circulatory shock, though described, has not been fully elucidated. Aim: To identify predictors of circulatory shock and mortality in viper envenomation and explore the role of pituitary-adrenal axis in circulatory shock. Design: Prospective hospital-based observational study. Methods: Once a syndromic diagnosis of viper envenomation was made, relevant clinical and laboratory data were collected. Serum cortisol was estimated in those with circulatory shock. Post-mortem examination of pituitary, kidneys and adrenals was performed. Adjusted odds-ratios were calculated for respective risk-factors for shock and mortality using multivariable logistic regression with backward elimination strategy. Results: Of 248 patients of viper envenomation treated at our hospital, circulatory shock was present in 19% and in-hospital mortality was 23%. CLS, circulatory shock, bleeding and requirement of > 20 vials of antivenom predicted mortality. Ischaemic and haemorrhagic necrosis of pituitary or adrenals was present in 51% of post-mortem specimens. Disseminated intravascular coagulation (DIC) and CLS were strong predictors of pituitary haemorrhage. Conclusion: Predictors of mortality - bleeding, CLS and requirement of high antivenom doses are warning signs which can alert clinicians to patients who may have poor outcomes. Our study points to a definite role of pituitary-adrenal axis in circulatory shock supports the hypothesis that pituitary involvement in viper envenomation closely resembles Sheehan syndrome. The mechanism of pituitary involvement appears to be a result of increased susceptibility of the swollen gland secondary to CLS and micro thrombi deposition in DIC.