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Randomized Controlled Trial
. 2015 Dec 4;10(12):e0144278.
doi: 10.1371/journal.pone.0144278. eCollection 2015.

Early Hepatic Dysfunction Is Associated with a Worse Outcome in Patients Presenting with Acute Respiratory Distress Syndrome: A Post-Hoc Analysis of the ACURASYS and PROSEVA Studies

Stéphanie Dizier  1   2 , Jean-Marie Forel  1   2 , Louis Ayzac  3 , Jean-Christophe Richard  4 , Sami Hraiech  1   2 , Samuel Lehingue  1   2 , Anderson Loundou  5 , Antoine Roch  1   2 , Claude Guerin  4 , Laurent Papazian  1   2 ; ACURASYS study investigators; PROSEVA Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Early Hepatic Dysfunction Is Associated with a Worse Outcome in Patients Presenting with Acute Respiratory Distress Syndrome: A Post-Hoc Analysis of the ACURASYS and PROSEVA Studies

Stéphanie Dizier et al. PLoS One. .

Abstract

Introduction: Bilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS.

Methods: The data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate.

Results: The 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS.

Conclusion: Bilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate.

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Conflict of interest statement

Competing Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: The authors declare that they have no conflict of interest relevant to this article to disclose. PROSEVA authors report several conflicts of interest. Dr. Guérin receiving grant support from Air Liquide; Dr. Mercat, receiving consulting fees from Faron Pharmaceuticals, grant support from Covidien and General Electric, patent royalties on a method for evaluating positive end-expiratory pressure that is licensed to General Electric, and reimbursement for travel expenses from Covidien and Maquet; Dr. Jaber, receiving consulting fees from Maquet and Dräger, lecture fees from Fisher and Paykel, Abbott Laboratories, and Philips Respironics, and reimbursement for travel expenses from Pfizer; and Dr. Mancebo, receiving fees for serving on the data and safety monitoring board of Air Liquide, consulting fees from Faron Pharmaceuticals, ALung, and Philips Respironics, and grant support to his institution from Covidien and General Electric. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Evolution of serum bilirubin level in survivors and non survivors.
Mean ± SEM. *: p value <0.001 (survivors vs. non-survivors).
Fig 2
Fig 2. Probability of survival in ARDS patients according to the bilirubin level at inclusion.
*: p <0.001 (comparisons between each strata of serum bilirubin level, bilirubin < 20 μmol/L was used as the reference curve).
See this image and copyright information in PMC

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