Rescue Therapy with Hypernatremia/Hypothermia Protocol in Transplant-ineligible Patients with Advanced Cerebral Edema from Acetaminophen Toxicity: Case Series from Tertiary Care Center

Abstract

Purpose: The prevalence of acute liver failure is increasing, and acetaminophen is still the leading cause in the West, generating the highest risk of developing cerebral edema. Only around 53% of patients with acute liver failure are ever listed for transplant, and as many as 25% of listed patients die awaiting transplantation. There is only one case report using combined hypernatremia and hypothermia therapy in a patient not eligible for liver transplantation. We report our 5-year experience on advanced cerebral edema and impending cerebral herniation in transplant-ineligible patients with fulminant liver failure secondary to acetaminophen toxicity. Case 1: A 29-year-old female with a past medical history of depression presented with encephalopathy and severe coagulopathy, and reported acetaminophen overdoing 24 hours. She was a Jehovah's Witness and her family refused to consent to liver transplantation. Case 2: A 37-year-old female with a past medical history of ongoing alcohol dependence, with a similar presentation. Given refractory alcoholism, she was considered not a candidate for liver transplantation. Both patients were at highest risk for brain edema, as they developed coma, serum ammonia greater than 100 micromol/L, hyperacute progression of liver failure, the need for vasopressors, and renal replacement therapy. Their neurological status deteriorated with signs of impending central herniation, including extensor posturing, sustained clonus, and bilateral Babinskis. Brain CT confirmed brain edema in both cases. Both patients could not receive intracranial pressure monitoring (blood transfusion was refused in Case 1 and severe intractable coagulopathy in Case 2). In an effort to avoid catastrophic neurologic sequelae, hypernatremia (sodium 145-150 mmol/L) and hypothermia (32 °C) were urgently initiated. Timing of rewarming was based on neurologic findings, liver function, and findings on serial CT brain. Case 1 received the protocol for one day, while this was prolonged to six days in Case 2. Both patients were safely discharged home with complete neurologic recovery on hospital days 20 and 32, respectively. While liver transplantation is the treatment of choice for fulminant liver failure secondary to acetaminophen toxicity, a hypernatremia/hypothermia protocol can be successfully used as a rescue therapy in addition to standard of treatment (hyperventilation, N-acetylcysteine, and ICU status) in selected patients with severe brain edema from acute liver failure who are transplant-ineligible, but have good potential for liver recovery.