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. 2023 Feb 7;23(1):44.
doi: 10.1186/s12871-023-02006-2.

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

Julie Henrie  1 , Ludovic Gerard  1 , Caroline Declerfayt  1 , Adrienne Lejeune  1 , Pamela Baldin  2 , Arnaud Robert  1 , Pierre-François Laterre  1 , Philippe Hantson  3   4
Affiliations

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

Julie Henrie et al. BMC Anesthesiol. .

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.

Keywords: ARDS; COVID-19; Cholangitis; Cholestasis; Ketamine/esketamine; Mechanical ventilation; Prolonged infusion.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Comparison of peak ALP, GGT, bilirubin, AST and ALT in the ketamine/esketamine (E/ESK) + or – groups (upper part). Results expressed according to invasive mechanical ventilation (IMV) + or -, and K/ESK + or – (lower part).* indicates p < 0.05; ** indicates p < 0.005; *** indicates p < 0.0005; **** indicates p < 0.0001
Fig. 2
Fig. 2
Peak of ALP, GGT and bilirubin according to the cumulative dose of K/ESK (left) and duration of K/ESK therapy (right). Cumulative dose was not calculated for the patients who received combined K/ESK therapy
Fig. 3
Fig. 3
Evolution of plasma ALP in the 30-year-old cirrhotic woman who received both K and ESK over 28 days (left). Ultrastructural examination of the explanted liver (right). The histological sections on the explanted liver showed a nodular architecture associated with sinusoidal congestion (A, H&E 5X), bilirubinostasis with biliary thrombi (B, H&E 20X) and septal fibrosis (C, Masson Trichrome 5X). Not significant inflammation was observed in portal tracts. Immunohistochemistry for cytokeratin 7 showed a severe cholestasis and canalicular proliferation (CK7, 5X)
See this image and copyright information in PMC

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