N-acetylcysteine increases cerebral perfusion pressure in pigs with fulminant hepatic failure

Abstract

Objective: Intravenous administration of N-acetylcysteine beyond 15 hrs reduces mortality rates in patients suffering from paracetamol-induced fulminant hepatic failure, although the mechanism of the therapeutic benefit remains unclear. We hypothesized increased survival to be caused by improved hemodynamic performance. The main objective for the study was to explore the effect of N-acetylcysteine on hemodynamics, oxygen transport, and regional blood flow in pigs with fulminant hepatic failure.

Design: Prospective, randomized, controlled trial.

Setting: Surgical research laboratory in a university hospital.

Subjects: Female Norwegian Landrace pigs.

Interventions: Fulminant hepatic failure was induced by a total liver devascularization procedure. Five hours later, the pigs were allocated to N-acetylcysteine treatment (150 mg.kg-1 in 100 mL of 0.9% saline over 15 mins, followed by 50 mg.kg-1 in 500 mL of 0.9% saline over a period of 4 hrs) or placebo.

Measurements and main results: Mean arterial pressure stabilized in the N-acetylcysteine group and increased slightly during the last 2 hrs (pGT =.009). Thus, mean arterial pressure was significantly higher compared with placebo after 3 hrs (p =.01). Cerebral perfusion pressure was significantly higher during the last 2 hrs in the N-acetylcysteine group (pGT =.033). Common carotid artery flow also increased and was maintained at a higher level compared with placebo (pG =.027). Systemic vascular resistance index initially decreased but then gradually increased (pGT <.001). Cardiac index increased after 15 mins of N-acetylcysteine infusion, causing a significant interaction (pGT =.038), but did not differ after 3 hrs. No significant differences in hindleg and mesentery hemodynamics were found. A short-lived increase in oxygen delivery caused by a temporary increase in cardiac index was observed but without any corresponding increase in oxygen consumption.

Conclusions: Intravenous N-acetylcysteine infusion increases cerebral perfusion pressure in pigs with fulminant hepatic failure. Earlier reported effects on oxygen transport and uptake could not be confirmed.