Failure of intravenous N-acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: A randomized controlled trial.
OBJECTIVE
To determine whether intravenous N -acetylcysteine (NAC) produces a clinically significant decline in sodium nitrite-induced methemoglobinemia in human volunteers.


METHODS
We conducted a randomized, control crossover trial with each subject serving as his own control. Methemoglobinemia was induced with intravenous sodium nitrite (4 mg/kg) administered over 10 minutes starting at time 0. At time 30 minutes, subjects were randomly assigned to treatment with intravenous NAC for 100 minutes (150 mg/kg over 1 hour followed by 14 mg/kg per 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 multiwavelength co-oximetry at time 0, 15, 30, 50, 70, 90, 110, and 130 minutes. 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 x min/dL) was significantly lower than the mean AUC for the treatment group (84.5+/-4.7 g x min/dL); P =.01).


CONCLUSIONS
Intravenous NAC failed to enhance methemoglobin reduction in this model.
Tanen
D A
DA
Department of Medical Toxicology, Good Samaritan Regional Medical Center, Phoenix, AZ, USA.
LoVecchio
F
F
Curry
S C
SC
D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007202:Indicators and Reagents / Q000009:adverse effects; D007262:Infusions, Intravenous; D008297:Male; D008706:Methemoglobin / Q000493:pharmacokinetics; D008708:Methemoglobinemia / Q000139:chemically induced / Q000188:drug therapy*; D012977:Sodium Nitrite / Q000009:adverse effects; D017211:Treatment Failure
D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D008706:Methemoglobin; D012977:Sodium Nitrite; D000111:Acetylcysteine