To the Editor:
We read with great interest the article by Mallet et al. on several cases of cholangiopathies occurring in patients with COVID-19.1 The authors hypothesized that use of ketamine led to biliary lesions due to precipitations of norketamine, a water-insoluble by-product produced in the liver by nitrogen demethylation. In addition to a potential ketamine-induced toxicity we postulate than vascular lesions may have contributed to the observed biliary lesions.
More specifically, arterial injuries supplying the bile ducts may result in ischemic lesions.2 Several lines of arguments support this hypothesis. First, all patients required mechanical ventilation for a long time (median: 40 days), a feature commonly observed in severely ill patients suffering from ischemic cholangiopathy.3 , 4 An inspired oxygen fraction greater than 80% and lung protective mechanical ventilation (low tidal volume, prone positioning, high positive end-expiratory pressure) are known to lower splanchnic blood flow. Whether patients required such measures was not reported by Mallet et al. Second, all patients received high doses of vasopressors which further reduced splanchnic blood flow.4 , 5 Third, the use of high doses of vasopressors implies severe hemodynamic instability as it has been observed in most of the patients with ischemic cholangiopathy occurring after a prolonged stay in intensive care. It is likely that this phenomenon compromised the blood supply to many organs including the bile ducts.5 Lastly, the lesions observed in the patient who underwent endoscopic retrograde cholangiopancreatography revealed contrast medium filling defects in the common bile duct and rarefication of the intrahepatic biliary tract, a feature often observed in patients suffering from ischemic cholangiopathy following liver transplantation.6
Cholangiopathy occurring after a prolonged stay in intensive care has been identified only in recent years. We believe that this pathophysiological mechanism is a plausible explanation for biliary lesions observed in patients with COVID-19.
Financial support
The authors received no financial support to produce this manuscript.
Authors’ contributions
Pierre Deltenre: study design; drafting the manuscript; critical revision of the manuscript for important intellectual content; study supervision. Christophe Moreno: critical revision of the manuscript for important intellectual content. Eric Trépo: critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript.
Conflict of interest
The authors declare no conflicts of interest that pertain to this work.
Please refer to the accompanying ICMJE disclosure forms for further details.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jhep.2021.02.036.
Supplementary data
The following is the supplementary data to this article:
References
- 1.Mallet V., The Keta-Cov research group Intravenous ketamine and progressive cholangiopathy in COVID-19 patients. J Hepatol. 2021;74:1243–1244. doi: 10.1016/j.jhep.2021.02.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Deltenre P., Valla D.C. Ischemic cholangiopathy. J Hepatol. 2006;44:806–817. doi: 10.1016/j.jhep.2006.01.009. [DOI] [PubMed] [Google Scholar]
- 3.Gelbmann C.M., Rummele P., Wimmer M., Hofstadter F., Gohlmann B., Endlicher E., et al. Ischemic-like cholangiopathy with secondary sclerosing cholangitis in critically ill patients. Am J Gastroenterol. 2007;102:1221–1229. doi: 10.1111/j.1572-0241.2007.01118.x. [DOI] [PubMed] [Google Scholar]
- 4.Lin T., Qu K., Xu X., Tian M., Gao J., Zhang C., et al. Sclerosing cholangitis in critically ill patients: an important and easily ignored problem based on a German experience. Front Med. 2014;8:118–126. doi: 10.1007/s11684-014-0306-6. [DOI] [PubMed] [Google Scholar]
- 5.Leonhardt S., Veltzke-Schlieker W., Adler A., Schott E., Hetzer R., Schaffartzik W., et al. Trigger mechanisms of secondary sclerosing cholangitis in critically ill patients. Crit Care. 2015;19:131. doi: 10.1186/s13054-015-0861-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Deltenre P., Valla D.C. Ischemic cholangiopathy. Semin Liver Dis. 2008;28:235–246. doi: 10.1055/s-0028-1085092. [DOI] [PubMed] [Google Scholar]
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