title: Therapeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis.
abstract: 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.
authors.affiliation: Divisions of Hepatology, University of Alberta, Edmonton, Canada; Critical Care Medicine, University of Alberta, Edmonton, Canada.
authors.forename: Constantine J
authors.initials: CJ
authors.lastname: Karvellas
authors.forename: R
authors.initials: R
authors.lastname: Todd Stravitz
authors.forename: Holly
authors.initials: H
authors.lastname: Battenhouse
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Michael L
authors.initials: ML
authors.lastname: Schilsky
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects; D001929:Brain Edema / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects / Q000401:mortality; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen