Keeping cool in acute liver failure: rationale for the use of mild hypothermia

J Hepatol. 2005 Dec;43(6):1067-77. doi: 10.1016/j.jhep.2005.05.039. Epub 2005 Oct 10.


Encephalopathy, brain edema and intracranial hypertension are neurological complications responsible for substantial morbidity/mortality in patients with acute liver failure (ALF), where, aside from liver transplantation, there is currently a paucity of effective therapies. Mirroring its cerebro-protective effects in other clinical conditions, the induction of mild hypothermia may provide a potential therapeutic approach to the management of ALF. A solid mechanistic rationale for the use of mild hypothermia is provided by clinical and experimental studies showing its beneficial effects in relation to many of the key factors that determine the development of brain edema and intracranial hypertension in ALF, namely the delivery of ammonia to the brain, the disturbances of brain organic osmolytes and brain extracellular amino acids, cerebro-vascular haemodynamics, brain glucose metabolism, inflammation, subclinical seizure activity and alterations of gene expression. Initial uncontrolled clinical studies of mild hypothermia in patients with ALF suggest that it is an effective, feasible and safe approach. Randomized controlled clinical trials are now needed to adequately assess its efficacy, safety, clinical impact on global outcomes and to provide the guidelines for its use in ALF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain Edema / etiology
  • Brain Edema / therapy
  • Hepatic Encephalopathy / etiology
  • Hepatic Encephalopathy / therapy
  • Humans
  • Hypothermia, Induced / methods*
  • Intracranial Hypertension / etiology
  • Intracranial Hypertension / therapy
  • Liver Failure, Acute / complications
  • Liver Failure, Acute / therapy*