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 on 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 mL of 5% dextrose in water over 15 mins and then 50 mg/kg in 250 mL 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 (DO2) increased from 667 +/- 154 to 751 +/- 166 (SD) mL/min/m2, and oxygen consumption (VO2) improved in 13 of 15 patients (150 +/- 30 to 169 +/- 25 mL/min/m2) (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 (VO2 of >10% from baseline [n = 6; 40%]) had a significantly lower baseline consumption compared with that of nonresponders (133 vs. 162 mL/min/m2, p = .04). No clear relationship between the increments in VO2 and indocyanine green clearance was observed (r2 = .21; p = .08). Prostacyclin resulted in moderate improvements in systemic DO2 (but not VO2) and a nonsignificant increase in indocyanine green clearance. CONCLUSION: N-acetylcysteine increases systemic VO2 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.
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 on 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 mL of 5% dextrose in water over 15 mins and then 50 mg/kg in 250 mL 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 (DO2) increased from 667 +/- 154 to 751 +/- 166 (SD) mL/min/m2, and oxygen consumption (VO2) improved in 13 of 15 patients (150 +/- 30 to 169 +/- 25 mL/min/m2) (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 (VO2 of >10% from baseline [n = 6; 40%]) had a significantly lower baseline consumption compared with that of nonresponders (133 vs. 162 mL/min/m2, p = .04). No clear relationship between the increments in VO2 and indocyanine green clearance was observed (r2 = .21; p = .08). Prostacyclin resulted in moderate improvements in systemic DO2 (but not VO2) and a nonsignificant increase in indocyanine green clearance. CONCLUSION:N-acetylcysteine increases systemic VO2 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.
Authors: Alessandra Milesi-Hallé; Susan M Abdel-Rahman; Aliza Brown; Sandra S McCullough; Lynda Letzig; Jack A Hinson; Laura P James Journal: Chem Biol Interact Date: 2010-12-09 Impact factor: 5.192