Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension

doi:10.1053/j.gastro.2004.08.005

Gastroenterology

Volume 127, Issue 5, November 2004, Pages 1338-1346

Although the data obtained and gathered during the transplant operations in 3 patients included in the present study were also reported in Transplantation (Transplantation 2003;75:2034–2039), none of the data are duplicated in the 2 reports.

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Background & Aims: About 20% of patients with acute liver failure (ALF) die from increased intracranial pressure (ICP) while awaiting transplantation. This study evaluates the clinical effects and pathophysiologic basis of hypothermia in patients with ALF and intracranial hypertension that is unresponsive to standard medical therapy. Methods: Fourteen patients with ALF who were awaiting orthotopic liver transplantation (OLT) and had increased ICP that was unresponsive to standard medical therapy were studied. Core temperature was reduced to 32°C–33°C using cooling blankets. Results: Thirteen patients were successfully bridged to OLT with a median of 32 hours (range, 10–118 hours) of cooling. They underwent OLT with no significant complications related to cooling either before or after OLT and had complete neurologic recovery. ICP before cooling was 36.5 ± 2.7 mm Hg and was reduced to 16.3 ± .7 mm Hg at 4 hours, which was sustained at 24 hours (16.8 ± 1.5 mm Hg) (P < .0001). Mean arterial pressure and cerebral perfusion pressure increased significantly, and the requirement for inotropes was reduced significantly. Hypothermia produced sustained and significant reduction in arterial ammonia concentration and its brain metabolism, cerebral blood flow, brain cytokine production, and markers of oxidative stress. Conclusions: Moderate hypothermia is an effective and safe bridge to OLT in patients with ALF who have increased ICP that is resistant to standard medical therapy. Hypothermia reduces ICP by impacting on multiple pathophysiologic mechanisms that are believed to be important in its pathogenesis. A large multicenter trial of hypothermia in ALF is justified.

Section snippets

Patients and methods

Studies were undertaken with the approval of the local research ethics committee and with written informed consent from the next of kin of each patient and were in accordance with the Declaration of Helsinki (1951) of the World Medical Association.

Patients

Patient details are summarized in Table 1. The core temperature was reduced from 36.3°C ± .2°C to 33.1°C ± .5°C within 1 hour of starting cooling and remained lowered at 32.6°C ± .4°C at 24 hours. However, the effect of cooling on ICP was evident within the first hour of starting cooling, even before the target temperature of 32°C was reached. Cooling was associated with a significant and sustained increase in systemic vascular resistance (P < .01), mean arterial pressure (P < .001), and

Discussion

The results of this study extend and confirm those of our pilot study suggesting that in patients with ALF who have uncontrolled intracranial hypertension and are at immediate risk of cerebral herniation, moderate hypothermia can be used successfully and safely to control ICP, improve neurologic end points, and possibly improve survival by bridging patients to OLT.⁵

Brain herniation from the effects of elevated ICP is the immediate cause of death in 35% of patients with ALF who fulfill criteria

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: Supported by a grant from the Wellcome Trust (UK) (to S.W.M.O.D.).

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Clinical-liver, pancreas, and biliary tractModerate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension

Section snippets

Patients and methods

Patients

Discussion

Gastroenterology

Lancet

Gastroenterology

Gastroenterology

Hepatology

Hepatology

Gastroenterology

Gastroenterology

Hepatology

Brain Res

Hepatology

Free Radic Biol Med

Lancet

J Hepatol

Gastroenterology

J Hepatol

J Hepatol

J Hepatol

Hepatology

J Hepatol

J Hepatol

The management of fulminant hepatic failure

Intracranial hypertension in acute liver failurepathophysiological basis of rational management

Semin Liver Dis

Clinical-liver, pancreas, and biliary tract
Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension