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

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.