Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome.
Crit Care
; 26(1): 148, 2022 05 23.
Article
in English
| MEDLINE | ID: covidwho-1862142
ABSTRACT
BACKGROUND:
A higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose-response relationship between ketamine and bilirubin levels.METHODS:
Post hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure-effect relationship between ketamine infusion and total bilirubin levels.RESULTS:
Two-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9-2.0] mg/kg/h for 9 [4-18] days. The mixed-effects model revealed a positively correlated infusion duration-effect as well as dose-effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3-7.8] (p = 0.01).CONCLUSIONS:
A causally plausible, dose-effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Respiratory Distress Syndrome
/
Propofol
/
COVID-19
/
Ketamine
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Topics:
Long Covid
Limits:
Humans
Language:
English
Journal:
Crit Care
Year:
2022
Document Type:
Article
Affiliation country:
S13054-022-04019-8
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