Hydrocortisone for Preventing Adverse Drug Reactions to Snake Antivenom: A Meta-Analysis

OBJECTIVE: Pretreatment with hydrocortisone (prehydrocortisone) has been used to protect against adverse drug reactions (ADRs) following antivenom administration after snakebite. However, controversial results have been reported in studies evaluating its efficacy. Herein, we conducted a meta-analysis to evaluate the effect of prehydrocortisone on the risk of ADRs. METHODS: We conducted a systematic search of PubMed, Embase, and Cochrane for relevant studies on the literature published up to December 6, 2020, with no language restrictions. Premedications, including hydrocortisone with or without other drugs, were compared with placebo or no premedication. Our primary end point was the risk of ADRs, which was reported as the number of patients who developed ADRs divided by the total number of snakebite patients administered with antivenom separately for the prehydrocortisone and control groups for each study. We evaluated pooled data using of a random-effects model. RESULTS: Among 831 identified studies, 4 were eligible and included in our analysis (N = 1348 participants). Upon combining all eight comparisons from the four selected studies, the overall pooled odds ratio (OR) for ADRs was 0.47 (95% CI 0.19, 1.17; p=0.11; I(2) = 68%). When the analysis was restricted to only articles using hydrocortisone with other drugs, the pooled OR was 0.19 (95% CI 0.05, 0.75; p=0.02; I(2) = 55%). The result was not statistically significant when the analysis was restricted to studies using prehydrocortisone alone, or randomized controlled designs, or cohorts. Our study was limited by heterogeneity, quality, and a paucity of data. CONCLUSIONS: The findings in this study revealed that prehydrocortisone alone was ineffective. However, the substantial beneficial effect of prehydrocortisone combinations with premedications (injectable antihistamines or adrenaline) used against ADRs cannot be excluded. Therefore, the use of prehydrocortisone combinations with premedications (injectable antihistamines or adrenaline) as a prophylaxis may reduce the ADRs to antivenom.