The Efficacy of N-acetylcysteine as an Adjunct in the Management of Acute Zinc Phosphide Poisoning: A Randomized Double-Blind Controlled Trial

Background and objective Acute zinc phosphide poisoning is a life-threatening toxicological emergency with high mortality, primarily caused by phosphine-induced oxidative stress and mitochondrial dysfunction. In the absence of a specific antidote, identifying effective adjunctive therapies is critical. This study aimed to evaluate whether intravenous N-acetylcysteine (NAC) can improve clinical outcomes when added to standard supportive care. Methods A prospective, randomized, double-blind, placebo-controlled trial was conducted in a single tertiary care emergency department in Northwest India from April 2024 to March 2025. This trial was registered with the Clinical Trials Registry - India (CTRI/2024/03/064278). Sixty adults (18-70 years) with confirmed zinc phosphide poisoning were randomly assigned to receive either standard supportive care with intravenous NAC (300 mg/kg over 20 hours) or standard care with a 5% dextrose placebo. Baseline demographic and clinical characteristics were comparable between the two groups. Severity at presentation, assessed by the requirement for inotropic support at admission, was also comparable between groups, with nine patients (30.0%) in the NAC group and eight patients (26.7%) in the placebo group requiring inotropic support at baseline (p = 0.83). The primary outcome was in-hospital mortality. Secondary outcomes included need for vasoactive support at admission and 24 hours, and changes in systolic blood pressure, arterial potential of hydrogen (arterial pH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase-MB isoenzyme (CK-MB). Results Baseline characteristics were comparable between groups. The NAC group showed lower in-hospital mortality than the placebo group (6.7% vs. 20.0%; Fisher’s exact p = 0.254; relative risk (RR): 0.33, 95% confidence interval (CI): 0.07-1.52; absolute risk reduction (ARR): 13.3%) and reduced requirement for inotropic support at 24 hours (6.7% vs. 23.3%; Fisher’s exact p = 0.145; RR: 0.29, 95% CI: 0.07-1.27; ARR: 16.6%); however, neither difference reached statistical significance. Serum ALT and AST levels were significantly lower in the NAC group than in the placebo group, with median ALT values of 92 IU/L versus 205 IU/L and median AST values of 48 IU/L versus 150 IU/L, respectively (p < 0.001 for both). No significant differences were observed in arterial pH or CK-MB levels. No adverse effects related to NAC were reported. Conclusions In this preliminary single-center trial, adjunctive intravenous NAC was not associated with a statistically significant reduction in in-hospital mortality or the requirement for inotropic support; however, a clinically meaningful trend was observed. Larger multicenter randomized trials are needed to determine the role of NAC in acute zinc phosphide poisoning.