The effect of N-acetylcysteine on oxygen transport and uptake in patients with fulminant hepatic failure

We have investigated the effect of N-acetylcysteine on hemodynamic variables, oxygen delivery (Do(2)), oxygen consumption (Vo(2)), and oxygen extraction in patients with fulminant hepatic failure using independent methods of determining Do(2) and Vo(2), thereby eliminating the effect of mathematical coupling, which may have biased previous studies. in 11 patients with severe fulminant hepatic failure, we documented the hemodynamic effects of N-acetylcysteine during the first 5 hours of a standard infusion regime and simultaneously measured Vo(2) using a method based on respiratory gas analysis. We related physiological changes to plasma N-acetylcysteine concentrations, and compared this group with 7 patients who received placebo infusions. A variable hemodynamic response to N-acetylcysteine was observed that did not differ significantly in comparison with the placebo group, and did not correlate with plasma drug concentrations. The most significant relationship observed between Do(2) and Vo(2) in any patient predicted a 13-mL.min(-1).m(-2) increase in Vo(2) when Do(2) increased by 100 mL.min(-1).m(-2); in 8 patients, Vo(2) was independent of Do(2) over the range observed. Tn the group that received N-acetylcysteine, a small (mean 6 [SD 6] mL.min(-1).m(-2)) increase in Vo(2) occurred in comparison with baseline after 1 hour of infusion (P < .01), but changes were not significantly different from the placebo group and were not sustained. N-Acetylcysteine infusion did not increase oxygen extraction or result in an improvement in whole-blood lactate levels or base excess during the study period, We conclude that N-acetylcysteine infusion does not result in clinically relevant improvements in global Vo(2), or in clinical markers of tissue hypoxia in patients with severe fulminant hepatic failure.