Therapeutic hypothermia in acute liver failure

a multicenter retrospective cohort analysis

Constantine J. Karvellas, R. Todd Stravitz, Holly Battenhouse, William M. Lee, Michael L. Schilsky

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

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Induced Hypothermia
Acute Liver Failure
Cohort Studies
Acetaminophen
Odds Ratio
Confidence Intervals
Survival
End Stage Liver Disease
Hepatic Encephalopathy
Brain Edema
Intracranial Pressure
Survival Rate

ASJC Scopus subject areas

  • Medicine(all)

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Therapeutic hypothermia in acute liver failure : a multicenter retrospective cohort analysis. / Karvellas, Constantine J.; Stravitz, R. Todd; Battenhouse, Holly; Lee, William M.; Schilsky, Michael L.

In: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, Vol. 21, No. 1, 01.01.2015, p. 4-12.

Research output: Contribution to journalArticle

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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.",
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AU - Schilsky, Michael L.

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N2 - 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.

AB - 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.

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