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

Publisher Website
Google Scholar
Abstract
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−2increase 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. In 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.