Failure of intravenous N-acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: A randomized controlled trial

Study objective: To determine whether intravenous N-acetylcysteine (NAC) pr oduces a clinically significant decline in sodium nitrite-induced methemogl obinemia in human volunteers. Methods: We conducted a randomized, control crossover trial with each subje ct serving as his own control. Methemoglobinemia was induced with intraveno us sodium nitrite (4 mg/kg) administered over 10 minutes starting at time 0 . At time 30 minutes, subjects were randomly assigned to treatment with int ravenous NAC for 100 minutes (150 mg/kg over 1 hour followed by 14 mg/kg pe r hour for 40 minutes) or administration of an equal volume of 5% dextrose in water. Each subject received the alternative treatment after an interval of at least 1 week. Blood methemoglobin concentrations were measured by mu ltiwavelength co-oximetry at time 0, 15, 30, 50, 70, 90, 110, and 130 minut es. Area under the methemoglobin concentration-time curve (AUC) between 30 and 130 minutes was compared between groups using a 2-tailed, paired t test . Results: There were no statistically significant differences in the control and treatment groups with respect to baseline hemoglobin or methemoglobin concentrations, as well as nitrite-induced methemoglobin concentrations at the initiation of treatment (0.85+/-0.06 g/dL, 0.88+/-0.04 g/dL; mean+/-SEM ; P=.31). Mean AUC for the control group (77.1+/-5.7 g.min/dL) was signific antly lower than the mean AUC for the treatment group (84.5+/-4.7 g.min/dL) ; P=.01). Conclusion: Intravenous NAC did not enhance methemoglobin reduction in this model.