Therapeutic Hypothermia for Acute Liver Failure: Toward a Randomized, Controlled Trial in Patients with Advanced Hepatic Encephalopathy

Abstract

Acute liver failure (ALF), the abrupt loss of liver function in a patient without previous liver disease, remains a highly mortal condition. Patients with ALF often succumb to their liver injury after the development of cerebral edema, resulting in intracranial hypertension and brain herniation. While the management of cerebral edema in ALF always includes the administration of osmotically active agents, osmotherapy often reduces intracranial pressure (ICP) insufficiently, such that herniation may be delayed but not prevented. Therapeutic hypothermia, the intentional reduction of body core temperature, has been increasingly used to treat cerebral edema in patients with traumatic and hypoxic brain injury. Data in animal models of ALF also suggest that hypothermia is effective in the prevention and treatment of cerebral edema, and case reports in humans have suggested that hypothermia is an effective bridge to orthotopic liver transplantation. A randomized, controlled trial comparing the management of ALF patients under normothermic and hypothermic conditions is a logical extension of these preliminary observations. Herein, we consider the many difficulties which will be encountered in the design of such a trial in patients with ALF at high risk of developing cerebral edema.