Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome
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 mec...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Critical Care |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13054-022-04019-8 |
| _version_ | 1811254258439290880 |
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| author | Pedro David Wendel-Garcia Rolf Erlebach Daniel Andrea Hofmaenner Giovanni Camen Reto Andreas Schuepbach Christoph Jüngst Beat Müllhaupt Jan Bartussek Philipp Karl Buehler Rea Andermatt Sascha David |
| author_facet | Pedro David Wendel-Garcia Rolf Erlebach Daniel Andrea Hofmaenner Giovanni Camen Reto Andreas Schuepbach Christoph Jüngst Beat Müllhaupt Jan Bartussek Philipp Karl Buehler Rea Andermatt Sascha David |
| author_sort | Pedro David Wendel-Garcia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T17:04:28Z |
| format | Article |
| id | doaj.art-95ad471b6c534d9a82c4ede44cd38214 |
| institution | Directory Open Access Journal |
| issn | 1364-8535 |
| language | English |
| last_indexed | 2024-04-12T17:04:28Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Critical Care |
| spelling | doaj.art-95ad471b6c534d9a82c4ede44cd382142022-12-22T03:23:59ZengBMCCritical Care1364-85352022-05-0126111210.1186/s13054-022-04019-8Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndromePedro David Wendel-Garcia0Rolf Erlebach1Daniel Andrea Hofmaenner2Giovanni Camen3Reto Andreas Schuepbach4Christoph Jüngst5Beat Müllhaupt6Jan Bartussek7Philipp Karl Buehler8Rea Andermatt9Sascha David10Institute of Intensive Care Medicine, University Hospital ZurichInstitute of Intensive Care Medicine, University Hospital ZurichInstitute of Intensive Care Medicine, University Hospital ZurichInstitute of Intensive Care Medicine, University Hospital ZurichInstitute of Intensive Care Medicine, University Hospital ZurichDepartment of Gastroenterology and Hepatology, University Hospital ZurichDepartment of Gastroenterology and Hepatology, University Hospital ZurichInstitute of Intensive Care Medicine, University Hospital ZurichInstitute of Intensive Care Medicine, University Hospital ZurichInstitute of Intensive Care Medicine, University Hospital ZurichInstitute of Intensive Care Medicine, University Hospital ZurichAbstract 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.https://doi.org/10.1186/s13054-022-04019-8Hypnotics and sedativesChemical and drug-induced liver injuryCholestasisCholangitisCholangiopathy |
| spellingShingle | Pedro David Wendel-Garcia Rolf Erlebach Daniel Andrea Hofmaenner Giovanni Camen Reto Andreas Schuepbach Christoph Jüngst Beat Müllhaupt Jan Bartussek Philipp Karl Buehler Rea Andermatt Sascha David Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome Critical Care Hypnotics and sedatives Chemical and drug-induced liver injury Cholestasis Cholangitis Cholangiopathy |
| title | Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome |
| title_full | Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome |
| title_fullStr | Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome |
| title_full_unstemmed | Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome |
| title_short | Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome |
| title_sort | long term ketamine infusion induced cholestatic liver injury in covid 19 associated acute respiratory distress syndrome |
| topic | Hypnotics and sedatives Chemical and drug-induced liver injury Cholestasis Cholangitis Cholangiopathy |
| url | https://doi.org/10.1186/s13054-022-04019-8 |
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