N-acetylcysteine improves indocyanine green extraction and oxygen transport during hepatic dysfunction

Objectives: To investigate whether the beneficial systemic hemodynamic effects of N-acetylcysteine, an agent that increases cyclic guanosine monophosphate (cGMP) concentration in fulminant hepatic failure, are present in a range of liver disorders and what concurrent effect this agent has an the hepatic-splanchnic circulation. Setting: Liver Failure Unit, King's College Hospital, London, UK. Patients: Fifteen patients with hepatic dysfunction who were mechanically ventilated, either after liver transplantation or during an acute or decompensated chronic liver disorder. Interventions: Prostacyclin was administered at a continuous infusion rate of 5 ng/kg/min for 60 mins. After a washout period, the hemodynamic effects of this infusion were compared with the effects present during infusion of N-acetylcysteine at 150 mg/kg in 250 mt of 5% dextrose in water over 15 mins and then 50 mg/kg in 250 mt of 5% dextrose for 45 mins at an infusion rate of 62.5 mL/hr. Measurements and Main Results: Following N-acetylcysteine infusion, the baseline oxygen delivery (Do(2)) increased from 667 +/- 154 to 751 +/- 166 (SD) mL/min/m(2), and oxygen consumption (ib,) improved in 13 of 15 patients (150 +/- 30 to 169 +/- 25 mL/min/m(2)) (p < .01). Indocyanine green clearance, as determined by a fiberoptic physiologic monitoring system, also improved In 13 of 15 patients (7.3 +/- 4.2% to 11.8 +/- 4.0% [mean change 100%, 95% confidence interval 9 to 256]) (p = .002). Patients who were defined as responders in relation to systemic hemodynamics (Vo(2) of > 10% from baseline [n = 6; 40%]) had a significantly lower baseline consumption compared with that of nonresponders (133 vs. 162 mL/min/m(2), p = .04). No clear relationship between the increments in ib, and indocyanine green clearance was observed (r(2) = .21; p = .08). Prostacyclin resulted in moderate improvements in systemic bo, (but not Vo(2)) and a nonsignificant increase in indocyanine green clearance. Conclusion: N-acetylcysteine increases systemic ire, in a proportion of patients with a wide variety of hepatic disorders. In addition, N-acetylcysteine elicits an Improvement in indocyanine green clearance. These properties may be clinically useful in a range of critical illnesses where systemic or hepatic-splanchnic circulations are compromised.