Profile of liver cholestatic biomarkers following prolonged ketamine administration in patients with COVID-19

Abstract

Background To investigate the possible influence of prolonged ketamine (K) or esketamine (ESK) infusion on the profile of liver cholestatic biomarkers in patients with COVID-19 infection. Methods A retrospective analysis was performed on 135 patients with COVID-19 related ARDS who received prolonged K or ESK infusion. They were compared to 15 COVID-19 ICU patients who did not receive K/ESK while being mechanically ventilated and 108 COVID-19 patients who did not receive mechanical ventilation nor K/ESK. The profile of the liver function tests was analysed in the groups. Results Peak values of ALP, GGT and bilirubin were higher in the K/ESK group, but not for AST and ALT. Peak values of ALP were significantly higher among patients who underwent mechanical ventilation and who received K/ESK, compared with mechanically ventilated patients who did not receive K/ESK. There was a correlation between these peak values and the cumulative dose and duration of K/ESK therapy. Conclusions Based on the observations of biliary anomalies in chronic ketamine abusers, prolonged exposure to ketamine sedation during mechanical ventilation may also be involved, in addition to viral infection causing secondary sclerosing cholangitis. The safety of prolonged ketamine sedation on the biliary tract requires further investigations.

Distinct histopathological features of post-COVID-19 cholangiopathy

“…This modi cation in bile composition could potentially damage cholangiocytes. It is also suggested that the toxicity of ketamine may be associated with the altered bile composition [17][18][19][20][21]. An autopsy study had already suggested that norketamine tends to accumulate in the bile [22], and recent evidence has con rmed this by identifying the metabolites of ketamine in the biliary casts [22,23].…”

COVID-19 and the Liver: A Complex and Evolving Picture

“…89 Recent reports have implicated the use of intravenous ketamine for sedation in the genesis of COVID-associated SCC, but cases have also been described in people who have not required ICU admission and sedation. 90 Less information is available on the development of COVID-associated SSC in patients with underlying CLD. However, in a study undertaken in patients with predominantly MASLD/MASH, 23% developed cholestatic liver injury while 15% developed SSC; 87 the majority had severe COVID-19, but the development of progressive cholestatic injury was independent of the severity of the underlying liver disease.…”

“… 89 Recent reports have implicated the use of intravenous ketamine for sedation in the genesis of COVID-associated SCC, but cases have also been described in people who have not required ICU admission and sedation. 90 …”