INTRODUCTION: About 2000 cases of fulminant hepatic failure occur annually in the United States and the mortality rate ranges from 30–80% despite maximal supportive care. The most feared complication is the development of cerebral edema leading to raised intracranial tension and subsequent brain herniation and death. The prognosis of patients with raised ICP in the setting of acute liver failure remains grim without emergent liver transplantation. Therapeutic mild hypothermia has been used as a bridge to transplantation, but has not been studied as an independent therapeutic measure in this setting. We report a case of fulminant liver failure and cerebral edema from acetaminophen which was treated with moderate hypothermia.
CASE PRESENTATION: Our index patient was admitted to the medical ICU of our tertiary care institution after being found unresponsive with acetaminophen toxicity. She had ingested 56 grams of acetaminophen over a 2 day period. On initial presentation, patient had stage 3 hepatic encephalopathy, and her depressed mental status was noted 24 hours preceding admission. Initial evaluation confirmed fulminant hepatic failure from acetaminophen, and cerebral edema. Our patient was treated with hyperosmolar therapy, hyperventilation, sedation and chemical paralysis. Her intracranial pressure (ICP) remained elevated despite maximal medical therapy. Therapeutic hypothermia was initiated at that point, with patient listed for emergency orthotropic liver transplantation. Over the next few days, her hepatic synthetic functions began to improve, but continued to have high ICP whenever reversal of hypothermia was attempted on days three and four. On day five she tolerated re-warming well without increase in her ICP. She was transferred out of the ICU on day 9, and discharged on day 16 from the hospital. On the day of discharge she had near complete recovery of neurological and hepatic functions.
DISCUSSIONS: There is an emerging body of literature that supports the use of mild to moderate therapeutic hypothermia for the therapy of cerebral edema and intracranial hypertension associated with FHF. Although data on the impact of raised ICP on survival in liver failure are scant, a mortality of more than 90% is expected in patients whose ICP cannot be controlled by conventional means (1). In a study of 315 patients with acute liver injury secondary to Tylenol overdose, 50% of deaths in the group that did not meet liver transplantation criteria and were deemed to have a good prognosis otherwise expired from cerebral herniation (2). These data suggest that brain herniation can occur even in those whose liver is recovering. The only definitive treatment for patients whose hepatic function is unlikely to recover is liver transplantation. It is thus imperative to aggressively control ICP in patients who are suitable transplantation candidates as a bridge to liver transplant. This intervention also permits those who have a good prognosis adequate time for hepatic recovery.
CONCLUSION: In patients with fulminant hepatic failure and cerebral edema from the same, prolonged therapeutic hypothermia could potentially be used as a life saving therapy without liver transplantation. Therapeutic hypothermia decreases cerebral edema by multiple mechanisms. A clinical trial of hypothermia in patients with acute liver failure is warranted to further evaluate the use of this potentially lifesaving therapy.
DISCLOSURE: Shibin Jacob, No Financial Disclosure Information; No Product/Research Disclosure Information