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

Intracranial Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00670124
• Other study ID #: ALFHypothermia01
• Status: Completed
• Phase: N/A
• First received: April 29, 2008
• Last updated: November 4, 2014
• Start date: January 2005
• Est. completion date: June 2011

Study information

• Verified date: November 2014
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Liver Failure
• Hypothermia
• Intracranial Hypertension
• Liver Failure
• Liver Failure, Acute

Intervention

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.

Locations

Country	Name	City	State
Denmark	Department of hepatology, Rigshospitalet	Copenhagen
United Kingdom	Dept. of Intensive Care	Birmingham
United Kingdom	Institute for Liver Studies, King`s College Hospital	London
United States	Division of Hepatology, Feinberg School of Medicine, Northwestern University	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Feinberg School of Medicine, Northwestern University, University Hospital Birmingham

Countries where clinical trial is conducted

United States,  Denmark,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The effect of hypothermia on preventing development of ICP higher than 25 mmHg		72 hours	No
Secondary	The effect of hypothermia on preserving normal cerebral oxidative metabolism evaluated by cerebral microdialysis		72 hours	No
Secondary	The effect of hypothermia on severity of infections		1 week	No