Observational studyCritical care (London, England)2022
Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome.
Observational study in Critical care (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Association of esketamine exposure with secondary sclerosing cholangitis in critically ill patients: a retrospective cohort analysis of 20,000 ICU cases.Journal of intensive care · 2026Article
- Characterisation and Prognostic Implication of Cholestasis After Burn Injury.Alimentary pharmacology & therapeutics · 2026Article
- Chronic ketamine use resulting in a reversible cholangiopathy: A case series from a single Canadian centre and review of the literature.Canadian liver journal · 2026Article
- Review
- Ketamine Hepatotoxicity: An Underappreciated Cause of Liver Damage - Analysis by RUCAM.Journal of clinical and translational hepatology · 2025Article
- Adverse Effects Associated With High-Dose Ketamine Infusions For Refractory Pain And Psychiatric Conditions.Current pain and headache reports · 2025Review
- Establishment and Validation of a Risk Prediction Model for Sepsis-Associated Liver Injury in ICU Patients: A Retrospective Cohort Study.Infection and drug resistance · 2025Article
- Article
- Esketamine Regulates Mitophagy through ULK1/FUNDC1 Signaling Pathway to Improve LPS-induced Acute Respiratory Distress Syndrome.Current pharmaceutical design · 2025Article
- Presence of cholestasis and its impact on survival in SARS-CoV-2 associated acute respiratory distress syndrome.Scientific reports · 2024Article
- Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study.Critical care explorations · 2024Article
- "Dosis sola facit venenum"-Evidence for causality in the association between ketamine and cholestatic liver injury.Hepatology international · 2024Article
- Intensive Care Unit-Related Cholangiopathy-Induced Biliary Cast Syndrome Without Liver Transplantation: A Rare Entity.ACG case reports journal · 2024Article
- Ketamine restriction correlates with reduced cholestatic liver injury and improved outcomes in critically ill patients with burn injury.JHEP reports : innovation in hepatology · 2024Article
- Continuous Infusion of Ketamine in Mechanically Ventilated Patients with SARS-CoV-2.Critical care research and practice · 2024Article
- A Case of Hepatotoxicity Induced by Therapeutic Ketamine Use for Sedation.Case reports in critical care · 2024Article
- Post-COVID-19 cholangiopathy: Systematic review.World journal of methodology · 2023Article
- Profile of liver cholestatic biomarkers following prolonged ketamine administration in patients with COVID-19.BMC anesthesiology · 2023Article
- Secondary Sclerosing Cholangitis After SARS-CoV2: ICU Ketamine Use or Virus-Specific Biliary Tropism and Injury in the Context of Biliary Ischemia in Critically Ill Patients?Hepatic medicine : evidence and research · 2023Article
- COVID-Associated Cast-Forming Cholangiopathy: A Commentary on Disease Mechanism, Treatment, and Prognosis.Hepatic medicine : evidence and research · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA 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.
methodsPost 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.
resultsTwo-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).
conclusionsA 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.