Clinical trial NCT00670124: Hypothermia to Prevent High Intracranial Pressure in Patients With Acute Liver Failure
Official title: Pilot Trial on the Effect of Mild Hypothermia on Intracranial Pressure in Patients With Hyperacute Liver Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Liver Failure
Intracranial Hypertension
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: University Hospital Birmingham
name: Northwestern University Feinberg School of Medicine
First posted: 2008-05-01
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The effect of hypothermia on preventing development of ICP higher than 25 mmHg
timeFrame: 72 hours
Secondary outcomes:
measure: The effect of hypothermia on preserving normal cerebral oxidative metabolism evaluated by cerebral microdialysis
timeFrame: 72 hours
measure: The effect of hypothermia on severity of infections
timeFrame: 1 week
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Division of Hepatology, Feinberg School of Medicine, Northwestern University
state: Illinois
city: Copenhagen
country: Denmark
facility: Department of hepatology, Rigshospitalet
city: Birmingham
country: United Kingdom
facility: Dept. of Intensive Care
city: London
country: United Kingdom
facility: Institute for Liver Studies, King's College Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Fin S Larsen, MD
role: PRINCIPAL_INVESTIGATOR
References: