Treatment of Brain Edema in Acute Liver Failure

Cerebral edema is very common in patients with acute liver failure and encephalopathy. In severe cases, it produces brain tissue shift and potentially fatal herniation. Brain swelling in acute liver failure is produced by a combination of cytotoxic (cellular) and vasogenic edema. Accumulation of ammonia and glutamine leads to disturbances in the regulation of cerebral osmolytes, increased free radical production and calcium-mediated mitochondrial injury, and alterations in glucose metabolism (inducing high levels of brain lactate), resulting in astrocyte swelling. Activation of inflammatory cytokines can cause increased blood-brain barrier permeability leading to vasogenic edema, although the relative contribution of vasogenic edema is probably minor compared with cellular swelling. Cerebral blood flow is disturbed and generally increased in patients with acute liver failure; persistent vasodilatation and loss of autoregulation may generate hyperemia, and the consequent augmentation in cerebral blood volume may exacerbate brain edema. Adequate management of intracranial hypertension demands continuous monitoring of intracranial pressure and cerebral perfusion pressure. Coagulation status should be assessed and bleeding diathesis should be treated prior to insertion of the intracranial pressure monitor. Standard treatment measures such as hyperventilation and osmotic agents (e.g., mannitol, hypertonic saline) remain useful first-line interventions. Although hypertonic saline may be preferred in patients with coexistent hyponatremia, the rate of correction of hyponatremia must be gradual to avoid the risk of osmotic demyelination. Barbiturate coma and intravenous indomethacin are available options in refractory cases. The most promising novel therapeutic alternative is the induction of moderate hypothermia (aiming for a core temperature of 32-34°C). However, the safety and efficacy of therapeutic hypothermia for brain swelling caused by liver failure still needs to be proven in randomized, controlled clinical trials. Management of intracranial pressure in patients with acute liver failure should be guided by well-defined treatment protocols.