Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure

Abstract

Background: Increased intracranial pressure as a complication of acute liver failure has a mortality of about 90% in patients who do not respond to treatment with mannitol and ultrafiltration. We investigated the safety and efficacy of moderate hypothermia for uncontrolled increase in intracranial pressure in patients with acute liver failure.

Methods: We studied seven consecutive patients aged 16-46 years (five women, four candidates for orthotopic liver transplantation [OLT]) with acute liver failure who fulfilled criteria for poor-prognosis liver failure and had increased intracranial pressure that was unresponsive to two treatments with mannitol and ultrafiltration. We used cooling blankets to lower the patients' core temperature to 32-33 degrees C. Patients who were not suitable candidates for OLT (patients 1-3) were cooled for 8 h and then gradually rewarmed over 1 h to a baseline temperature of 37 degrees C. Patients who were suitable candidates for OLT (patients 4-7) were cooled before and during the OLT procedure. We measured cerebral blood flow and metabolic indices before and after cooling.

Findings: The four patients who were candidates for OLT were successfully maintained until transplantation with 13 (range 10-14) h of hypothermia. The three patients who were unsuitable candidates for OLT died after rewarming. Intracranial pressure before cooling was 45 (25-49) mm Hg and was reduced in all patients to 16 (13-17) mm Hg (p<0.05). Cerebral blood flow decreased from 103 (25-134) mL 100 g(-1) min(-1) before cooling to 44 (24-75) mL 100 g(-1) min(-1) after cooling (p<0.05). The corresponding changes for cerebral perfusion pressure was an increase from 45 (37-56) mm Hg to 70 (60-78) mm Hg (p<0.05) and for cardiac index a decrease from 9.8 (7-13) to 5.1 (4.3-6.1) L per min per m2 of body surface area. During hypothermia there was no significant relapse of increased intracranial pressure. Arterial ammonia and cerebral uptake of ammonia were significantly reduced with cooling. No adverse effects of hypothermia were observed.

Interpretation: Moderate hypothermia is useful in the treatment of uncontrolled increase in intracranial pressure in patients with acute liver failure and may serve as a bridge to OLT.