Therapeutic hypothermia in acute liver failure: A multicenter retrospective cohort analysis

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 = 582) and non‐APAP patients (n = 613). For APAP patients, the Model for End‐Stage Liver Disease [MELD; odds ratio (OR) = 0.91 per increment, 95% confidence interval (CI) = 0.89‐0.94, P  < 0.001] and vasopressors (OR = 0.16, 95% CI = 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 = 2.735, 95% CI = 1.001‐7.467) but worsened for APAP patients who were 64 years old or older (age of 64 years: OR = 0.167, 95% CI = 0.028‐0.999). For non‐APAP patients, MELD (OR = 0.93 per increment, 95% CI = 0.91‐0.95, P  < 0.001) and vasopressors (OR = 0.60, 95% CI = 0.40‐0.90, P  = 0.01) were associated with worse outcomes, whereas TH had no impact ( P  = 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 . © 2014 AASLD.