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


METHODS
Liver Failure Unit, King's College Hospital, London, UK.


METHODS
Fifteen patients with hepatic dysfunction who were mechanically ventilated, either after liver transplantation or during an acute or decompensated chronic liver disorder.


METHODS
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.


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.


CONCLUSIONS
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.
Devlin
J
J
Institute of Liver Studies, King's College School of Medicine and Dentistry, London, UK.
Ellis
A E
AE
McPeake
J
J
Heaton
N
N
Wendon
J A
JA
Williams
R
R
D000111:Acetylcysteine / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007208:Indocyanine Green / Q000378:metabolism*; D007262:Infusions, Intravenous; D008107:Liver Diseases / Q000378:metabolism* / Q000628:therapy*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption
D000959:Antihypertensive Agents; D016166:Free Radical Scavengers; D011464:Epoprostenol; D007208:Indocyanine Green; D000111:Acetylcysteine