Hypothermia to Prevent High Intracranial Pressure in Patients With Acute Liver Failure

Pilot Trial on the Effect of Mild Hypothermia on Intracranial Pressure in Patients With Hyperacute Liver Failure

Treatment options in patients with high intracranial pressure due to acute liver failure are limited. This study intends to evaluate the effect of prophylactic hypothermia on preventing high intracranial pressure and compromised cerebral oxidative metabolism.

Study Overview

• Status: Completed
• Conditions: Intracranial Hypertension; Acute Liver Failure
• Intervention / Treatment: Device: Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero

Detailed Description

Acute liver failure (ALF) is associated with a high mortality. With severe hepatic encephalopathy and elevated arterial ammonia concentration (< 200 micromol/L) more than 50% of the patients will develop high intracranial pressure (ICP) and risk cerebral incarceration and death. The therapeutic options are limited in treating and preventing this condition and new interventions are much sought after. As in hypothermia used for patients after cardiac resuscitation it could be speculated that hypothermia and the reduced cerebral metabolic rate would contribute to neuroprotection and reduce the risk of cerebral hypertension in patients with ALF. We have designed this open, randomized and unblinded study in order to evaluate the effect of prophylactic hypothermia on ICP, cerebral hemodynamics and oxidative metabolism. Patients are randomized to standard medical treatment (SMT) or SMT and hypothermia 33° C for 72 hours using a cooling mattress (Blanketrol II, Cincinnati Sub-Zero). All patients will receive mechanical ventilation, antibiotics, inotropic support and monitored with invasive and non-invasive equipment in accordance to local guidelines. In Copenhagen monitoring cerebral hemodynamics includes:

Placement of a intracranial pressure measuring catheter (Camino (R), Integra) for monitoring ICP. Furthermore, a microdialysis catheter (CMA-70) placed in brain cortex is used for monitoring brain metabolism. Finally, cerebral perfusion can be monitored by measuring mean flow velocity using transcranial doppler and/or oxygen saturation in blood from the jugular vein.

Ethical considerations:

The Helsinki II declaration will be followed and informed consent is mandatory for enrollment. In any patient where hypothermia is believed or suspected to be harmful the study should be stopped and the primary investigator should be notified immediately. All adverse effects will be recorded and published together with the full paper.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Department of hepatology, Rigshospitalet
• United Kingdom
  • Birmingham, United Kingdom
    • Dept. of Intensive Care
  • London, United Kingdom
    • Institute for Liver Studies, King's College Hospital
• United States
  • Illinois
    • Chicago, Illinois, United States, 60610
      • Division of Hepatology, Feinberg School of Medicine, Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• acute liver failure
• and hepatic encephalopathy stage 3 or 4
• and informed and written consent by closest relative(s)
• and arterial ammonia concentration above 150 micromol/L or clinical suspicion of cerebral edema
• and an ICP-measuring device

Exclusion Criteria:

• no or withdrawn informed consent
• pregnant or breast feeding women
• uncontrollable infection
• hemodynamically instable patients
• active bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: 1; Standard medical treatment
ACTIVE_COMPARATOR: 2; Standard medical treatment plus hypothermia (33°C) maintained for 72 hours	Device: Hypothermia by the use of Blanketrol II, Cincinnati Sub-Zero; The patients are placed on a cooling mattress and body-core temperature is regulated to 33° C.; Other Names: Cooling device: Blanketrol II, Cincinnati Sub-Zero

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The effect of hypothermia on preventing development of ICP higher than 25 mmHg	72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
The effect of hypothermia on preserving normal cerebral oxidative metabolism evaluated by cerebral microdialysis	72 hours
The effect of hypothermia on severity of infections	1 week

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Northwestern University Feinberg School of Medicine; University Hospital Birmingham
• Investigators: Principal Investigator: Fin S Larsen, MD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (ACTUAL): January 1, 2011
• Study Completion (ACTUAL): June 1, 2011

Study Registration Dates

• First Submitted: April 29, 2008
• First Submitted That Met QC Criteria: April 29, 2008
• First Posted (ESTIMATE): May 1, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): November 5, 2014
• Last Update Submitted That Met QC Criteria: November 4, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Body Temperature Changes; Liver Failure; Hepatic Insufficiency; Intracranial Hypertension; Hypothermia; Liver Failure, Acute
• Other Study ID Numbers: ALFHypothermia01