Background: N-acetylcysteine (NAC) is a precursor to glutathione synthesis, an endogenous antioxidant which may reduce methemoglobin (MHB).

Objective: To determine if NAC will reduce MHB in an in vitro model of nitrite-induced methemoglobinemia.

Methods: Five healthy volunteers donated blood which was divided equally into 2 test tubes in 3 ml aliquots. Seventy-five μl of 0.18 M sodium nitrite with 0.28 M dextrose were added to both tubes 1 and 2 to induce MHB formation. Tube 2 served as a control. After 15 minutes, 225 μl of NAC(20mg/ml) was added to tube 1, and 225 μl of phosphate buffer saline solution (PBS) was added to tube 2 as a volume control. Serial MHB levels were measured by co-oximetry at baseline and for 330 minutes after the addition of NAC or PBS. MHB levels are presented as a percentage of the total hemoglobin. The experiment was repeated for each of the five volunteers and mean MHB levels over time analysed.

Results: Table

Table 1

The difference in areas under time-concentration curves (AUC) was significant (p < 0.05). Analysis revealed zero order kinetics in NAC-nitrite samples, represented by the equation: (%change MHB) = 0.18 X (time in minutes).

Conclusion: In this in vitro model, NAC reduces chemically induced MHB. NAC may have clinical utility in the management of patients suffering from methemoglobinemia.