Christian de Tymowski1, François Dépret2, Sabri Soussi3, Moreno Nabila4, Thomas Vauchel3, Maité Chaussard3, Mourad Benyamina3, Axelle Ferry3, Alexandru Cupaciu3, Marion Jully3, Haikel Oueslati3, Alexandre Fratani3, Maxime Coutrot5, Philippe Sogni6, Maurice Mimoun7, Marc Chaouat7, Anne-Marie Zagdanski8, Eric De Kerviler8, Alexandre Mebazaa2, Richard Moreau9, Vincent Mallet10, Matthieu Legrand11. 1. Assistance Publique - Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Department of Anesthesiology and Critical Care and Burn Unit, Paris, France; University Paris Diderot, Paris, France; INSERM U1149, Centre de Recherche sur l'Inflammation CRI, Paris, France; Laboratoire d'Excellence (Labex) Inflammex, ComUE Sorbonne Paris Cité, Paris, France. 2. Assistance Publique - Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Department of Anesthesiology and Critical Care and Burn Unit, Paris, France; University Paris Diderot, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), UMR INSERM 942, Lariboisière Hospital University Paris Diderot, F-75475, & F-CRIN INI-CRCT Network, Paris, France. 3. Assistance Publique - Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Department of Anesthesiology and Critical Care and Burn Unit, Paris, France. 4. Assistance Publique - Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Biochemistry Laboratory, Paris, France. 5. Assistance Publique - Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Department of Anesthesiology and Critical Care and Burn Unit, Paris, France; University Paris Diderot, Paris, France. 6. Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Cochin, Hepatology Service, Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1223; Institut Pasteur, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Paris, France. 7. University Paris Diderot, Paris, France; Assistance Publique - Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Plastic Surgery, Paris, France. 8. Assistance Publique - Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Radiology, Paris, France. 9. University Paris Diderot, Paris, France; INSERM U1149, Centre de Recherche sur l'Inflammation CRI, Paris, France; Laboratoire d'Excellence (Labex) Inflammex, ComUE Sorbonne Paris Cité, Paris, France; Département Hospitalo-Universitaire (DHU) UNITY, Service d'hépatologie, Hôpital beaujon APHP, Clichy, France. 10. Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Cochin, Hepatology Service, Paris, France; Institut National de la Santé et de la Recherche Médicale Unité 1223; Institut Pasteur, Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Paris, France. Electronic address: vincent.mallet@aphp.fr. 11. Assistance Publique - Hôpitaux de Paris (AP-HP), Groupe Hospitalier St-Louis-Lariboisière, Department of Anesthesiology and Critical Care and Burn Unit, Paris, France; University Paris Diderot, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM), UMR INSERM 942, Lariboisière Hospital University Paris Diderot, F-75475, & F-CRIN INI-CRCT Network, Paris, France. Electronic address: matthieu.legrand@aphp.fr.
Abstract
BACKGROUND & AIMS: Cholestasis often occurs after burn injuries. However, the prevalence of cholestasis and its effect on outcomes in patients with severe burn injuries are unknown. The aim of this study was to describe the course and the burden of cholestasis in a cohort of severely burned adult patients. METHODS: We investigated the relationship between burn-associated cholestasis (BAC) and clinical outcomes in a retrospective cohort of patients admitted to our unit for severe burn injuries between 2012 and 2015. BAC was defined as an increased level of serum alkaline phosphatase (ALP) ≥1.5x the upper limit of normal (ULN) with an increased level of gamma-glutamyltransferase (GGT) ≥3x ULN, or as an increased level of total bilirubin ≥2x ULN. RESULTS: A total of 214 patients were included: 111 (52%) patients developed BAC after a median (IQR) stay of 9 (5-16) days. At 90 days, the mortality rate was 20%, including 34 and 9 patients with and without BAC (p <0.001), respectively, which corresponded to a 2.5-fold higher (95% CI 1.2-5.2, p = 0.012) risk of 90-day mortality for patients with BAC. After being adjusted for severity of illness, patients with BAC, hyperbilirubinemia and without elevated ALP and GGT levels had a hazard ratio of 4.51 (95% CI 1.87-10.87) for 90-day mortality. BAC was associated with the severity of the burn injury, shock and bacteraemia. BAC was present in 38 (51%) patients at discharge, and 7 (18%) patients had secondary sclerosing cholangitis. These patients maintained elevated levels of ALP and GGT that were 5.8x (1.7-15) the ULN and 11x the ULN (4.5-22), respectively, 20 months (3.5-35) after discharge. CONCLUSION: BAC is prevalent among patients with severe burn injuries and is associated with worse short-term outcomes, especially when total bilirubin levels were increased without elevated ALP and GGT levels. BAC survivors are at risk of developing sclerosing cholangitis. LAY SUMMARY: Cholestasis is common after burn injuries and is associated with burn severity, sepsis, organ failure and mortality. Patients with hyperbilirubinemia without elevated alkaline phosphatase and gamma-glutamyltransferase levels after the burn injury have a poor prognosis. Patients with burn-associated cholestasis may develop sclerosing cholangitis and secondary biliary cirrhosis.
BACKGROUND & AIMS:Cholestasis often occurs after burn injuries. However, the prevalence of cholestasis and its effect on outcomes in patients with severe burn injuries are unknown. The aim of this study was to describe the course and the burden of cholestasis in a cohort of severely burned adult patients. METHODS: We investigated the relationship between burn-associated cholestasis (BAC) and clinical outcomes in a retrospective cohort of patients admitted to our unit for severe burn injuries between 2012 and 2015. BAC was defined as an increased level of serum alkaline phosphatase (ALP) ≥1.5x the upper limit of normal (ULN) with an increased level of gamma-glutamyltransferase (GGT) ≥3x ULN, or as an increased level of total bilirubin ≥2x ULN. RESULTS: A total of 214 patients were included: 111 (52%) patients developed BAC after a median (IQR) stay of 9 (5-16) days. At 90 days, the mortality rate was 20%, including 34 and 9 patients with and without BAC (p <0.001), respectively, which corresponded to a 2.5-fold higher (95% CI 1.2-5.2, p = 0.012) risk of 90-day mortality for patients with BAC. After being adjusted for severity of illness, patients with BAC, hyperbilirubinemia and without elevated ALP and GGT levels had a hazard ratio of 4.51 (95% CI 1.87-10.87) for 90-day mortality. BAC was associated with the severity of the burn injury, shock and bacteraemia. BAC was present in 38 (51%) patients at discharge, and 7 (18%) patients had secondary sclerosing cholangitis. These patients maintained elevated levels of ALP and GGT that were 5.8x (1.7-15) the ULN and 11x the ULN (4.5-22), respectively, 20 months (3.5-35) after discharge. CONCLUSION: BAC is prevalent among patients with severe burn injuries and is associated with worse short-term outcomes, especially when total bilirubin levels were increased without elevated ALP and GGT levels. BAC survivors are at risk of developing sclerosing cholangitis. LAY SUMMARY:Cholestasis is common after burn injuries and is associated with burn severity, sepsis, organ failure and mortality. Patients with hyperbilirubinemia without elevated alkaline phosphatase and gamma-glutamyltransferase levels after the burn injury have a poor prognosis. Patients with burn-associated cholestasis may develop sclerosing cholangitis and secondary biliary cirrhosis.
Authors: Pedro David Wendel-Garcia; Rolf Erlebach; Rea Andermatt; Sascha David; Daniel Andrea Hofmaenner; Giovanni Camen; Reto Andreas Schuepbach; Christoph Jüngst; Beat Müllhaupt; Jan Bartussek; Philipp Karl Buehler Journal: Crit Care Date: 2022-05-23 Impact factor: 19.334
Authors: Simon Bütikofer; Daniela Lenggenhager; Pedro D Wendel Garcia; Ewerton M Maggio; Martina Haberecker; Cäcilia S Reiner; Gregor Brüllmann; Philipp K Buehler; Christoph Gubler; Beat Müllhaupt; Christoph Jüngst; Bernhard Morell Journal: Liver Int Date: 2021-07-04 Impact factor: 8.754
Authors: Katarzyna Rachunek; Maja Krause; Johannes Tobias Thiel; Jonas Kolbenschlag; Adrien Daigeler; Andreas Bury Journal: Front Surg Date: 2021-12-17
Authors: Aritz Perez Ruiz de Garibay; Andreas Kortgen; Julia Leonhardt; Alexander Zipprich; Michael Bauer Journal: Crit Care Date: 2022-09-26 Impact factor: 19.334