key: cord-0842733-foatrlz1
authors: de Tymowski, Christian; Dépret, François; Dudoignon, Emmanuel; Legrand, Matthieu; Mallet, Vincent
title: Ketamine-induced cholangiopathy in ARDS patients
date: 2021-07-27
journal: Intensive Care Med
DOI: 10.1007/s00134-021-06482-3
sha: ddf7618e1e93144f2ac2cab8c07e8113908ae512
doc_id: 842733
cord_uid: foatrlz1

nan

kg/h). In 2017, the French National Agency for the Safety of Medicine issued an alert on potential liver toxicities of ketamine. [5] Ketamine prescriptions were restricted (restrictive period: 0.01-0.05 mg/kg/h) thereafter. The liberal and the restrictive periods comprised 219 (75%) and 74 (25%) patients, respectively. Patient severity (i.e., age, total body surface area burned, abbreviated burned severity index, SAPS II score, initial prescription of norepinephrine) was identical (all p values > 0.2). Cholestasis at discharge was more frequent during the liberal compared to the restrictive period (33% vs 20% respectively, p = 0.04). This difference was particularly striking for the more severe cholestasis (i.e., Alkaline phosphate ≥ 4 N) (Fig. 1 ). Finally, 9 (7.4%) SCC were diagnosed during the liberal period vs only 1 (1.4%) during the restricted period (p = 0.092). We speculate that critically ill COVID-19 patients with SCC were overexposed to ketamine, leading to biliary precipitations of norketamine, biliary obstructions and cholangitis. Ketamine could act as a second hit in a previously injured biliary tract, either by SARS-CoV-2, (there is little, inconsistent, evidence that SARS-CoV-2 can infect biliary cells); by other medications; the systemic inflammatory response syndrome; and/or by ischemia. Providing the total cumulative dose of ketamine used during the ICU stay in the cases reported would be important to explore this potential contributing factor. Furthermore, a registry of critically ill patients with SCC including the dose of ketamine received seems necessary to better explore this potential severe side effect. Meanwhile, we do believe that ketamine-induced cholangiopathy should be suspected in COVID-19 patients with prolonged utilization or high doses of ketamine and increasing bilirubin. 

sur l'inflammation, Inserm, UMR 1149

Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de recherche sur l'inflammation, Inserm, UMR 1149

Service de Biostatistique et information médicale

Hôpital Necker Enfants Malades, Département d' Anesthésie Réanimation

DMU Cancérologie et spécialités médico-chirurgicales, Service d'Hépatologie

Secondary sclerosing cholangitis: an emerging complication in critically ill COVID-19 patients

Intravenous ketamine and progressive cholangiopathy in COVID-19 patients

Analgesia and sedation in patients with ARDS

Secondary sclerosing cholangitis as cause of persistent jaundice in patients with severe COVID-19

Kétamine: risque d'atteintes hépatiques graves lors d'utilisations prolongées et/ou à doses élevées-lettre aux professionnels de santé

FD: conception of the study, acquisition, analysis and interpretation of the data, draft of the manuscript; CT, FD, ED, ML, VM: conception of the study, acquisition, analysis and interpretation of the data, edition of the manuscript. The authors declare they have seen and approved the final version of the manuscript. All members of the Keta-Cov group facilitated the study or took care of the reported patients.

The study did not receive any external funding.

None.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Accepted: 14 July 2021