Circulatory, respiratory, cerebral, and renal derangements in acute liver failure: Pathophysiology and management

Many of the hemodynamic abnormalities seen in acute liver failure (ALF) have now been characterized. A lowered systemic vascular resistance with a raised cardiac output are prominent features, which in part are modulated by niti ic oxide (NO). At a cellular level, oxygen supply and utilization are impaired by changes in vascular tone, plugging of nutritive vessels, and pathological shunting. The use of N-acetylcysteine (NAG) and prostacyclin, a vasodilator, have been shown to increase oxygen utilization in the microcirculation. NAC may act by enhancing the effect of NO on guanylate cyclase, increasing the formation of cyclic 3',5'-guanosine monophosphate (cGMP), and thereby resulting in vasodilatation. This suggests that despite overproduction of NO in ALF, there is a shortage/failure of utilization at a cellular level. Appropriate management of these patients should be based on a good knowledge of the underlying pathophysiology, and thus on monitoring, during the course of the disease.