Brain edema and intracranial hypertension in fulminant hepatic failure: pathophysiology and management

Abstract

Intracranial hypertension is a major cause of morbidity and mortality of patients suffering from fulminant hepatic failure. The etiology of this intracranial hypertension is not fully determined, and is probably multifactorial, combining a cytotoxic brain edema due to the astrocytic accumulation of glutamine, and an increase in cerebral blood volume and cerebral blood flow, in part due to inflammation, to glutamine and to toxic products of the diseased liver. Validated methods to control intracranial hypertension in fulminant hepatic failure patients mainly include mannitol, hypertonic saline, indomethacin, thiopental, and hyperventilation. However all these measures are often not sufficient in absence of liver transplantation, the only curative treatment of intracranial hypertension in fulminant hepatic failure to date. Induced moderate hypothermia seems very promising in this setting, but has to be validated by a controlled, randomized study. Artificial liver support systems have been under investigation for many decades. The bioartificial liver, based on both detoxification and swine liver cells, has shown some efficacy on reduction of intracranial pressure but did not show survival benefit in a controlled, randomized study. The Molecular Adsorbents Recirculating System has shown some efficacy in decreasing intracranial pressure in an animal model of liver failure, but has still to be evaluated in a phase III trial.

Figure 1

Computed tomography (CT) (sagittal sections) of the brain of a 17-year old man who developed fulminant hepatic failure. A: First CT performed in encephalopathy stage IV; B: Control CT performed when the patient developed unilateral fixed midriasis, showing diffuse edema, compression of the fourth ventricle and of the brain stem. The patient developed brain stem death while waiting liver transplantation, despite medical therapy and MARS treatment.

Figure 2

Schematic representation of the hypotheses explaining intracranial hypertension and brain stem death in fulminant hepatic failure.