The benefit of therapeutic hypothermia (TH) in acute liver failure (ALF) has not been previously demonstrated in a controlled fashion. This study sought to determine the impact of TH on 21-day survival and complications in ALF patients at high risk for cerebral edema. This was a retrospective cohort study of ALF patients in the US Acute Liver Failure Study Group with grade III or IV hepatic encephalopathy. TH (32- C-35- C) was used in 97 patients (8%); 1135 (92%) who were not cooled were controls. Intracranial pressure was monitored in 38 TH ALF patients (39.2% versus 22% of controls, P < 0.001). Rates of bleeding (12% for both) and bloodstream (17% versus 18%) and tracheal infections (21% versus 23%, P > 0.5 for all) were similar. Unadjusted 21-day overall (62% versus 60%) and transplant-free survival rates (45% versus 39%, P > 0.4 for both) were similar. Multivariate models were created for acetaminophen (APAP) patients (n 5 582) and non-APAP patients (n 5 613). For APAP patients, the Model for End-Stage Liver Disease [MELD; odds ratio (OR) 5 0.91 per increment, 95% confidence interval (CI) 5 0.89-0.94, P < 0.001] and vasopressors (OR 5 0.16, 95% CI 5 0.11-0.24, P < 0.001) were associated with decreased 21-day spontaneous survival. Survival was improved with TH in APAP patients who were < 25 years old (age of 25 years: OR 5 2.735, 95% CI 5 1.001-7.467) but worsened for APAP patients who were 64 years old or older (age of 64 years: OR 5 0.167, 95% CI 5 0.028-0.999). For non-APAP patients, MELD (OR 5 0.93 per increment, 95% CI 5 0.91-0.95, P < 0.001) and vasopressors (OR 5 0.60, 95% CI 5 0.40-0.90, P 5 0.01) were associated with worse outcomes, whereas TH had no impact (P 5 0.93). In conclusion, TH in ALF was not associated with increased bleeding or infections. Although young APAP ALF patients may benefit, TH did not consistently affect 21-day survival. A prospective trial is required to clarify the utility of TH in ALF patients. Liver Transpl 21:4-12, 2015. VC 2014 AASLD.
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