Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis

Delphine Weil, Eric Levesque, Marc McPhail, Rodrigo Cavallazzi, Eleni Theocharidou, Evangelos Cholongitas, Arnaud Galbois, Heng Chih Pan, Constantine J Karvellas, Bertrand Sauneuf, René Robert, Jérome Fichet, Gaël Piton, Thierry Thevenot, Gilles Capellier, Vincent Di Martino, METAREACIR Group, Vincent Di Martino, Delphine Weil, Thierry Thévenot, Jean-Paul Cervoni, Carine Richou, Claire Vanlemmens, Stavros Dritsas, Gilles Capellier, Gaël Piton, Claire Chaignat, Sébastien Pili-Floury, Gilles Blasco, Emmanuel Samain, Didier Samuel, Eric Levesque, Faouzi Saliba, Philippe Ichaï, Arnaud Galbois, Bertrand Guidet, Vincent Das, Bertrand Sauneuf, Jean-Paul Mira, Dominique Perrotin, Benoit Champigneulle, Frédéric Pene, René Robert, Bruno Filloux, Christine Silvain, Jérome Fichet, Marc McPhail, Julia Wendon, Debbie Shawcross, William Bernal, Eleni Theocharidou, Banwari Agarwal, Andrew K Burroughs, Evangelos Cholongitas, Rodrigo Cavallazzi, Constantine J Karvellas, Heng Chih Pan, Yung-Chang Chen, Ming-Hung Tsai, Delphine Weil, Eric Levesque, Marc McPhail, Rodrigo Cavallazzi, Eleni Theocharidou, Evangelos Cholongitas, Arnaud Galbois, Heng Chih Pan, Constantine J Karvellas, Bertrand Sauneuf, René Robert, Jérome Fichet, Gaël Piton, Thierry Thevenot, Gilles Capellier, Vincent Di Martino, METAREACIR Group, Vincent Di Martino, Delphine Weil, Thierry Thévenot, Jean-Paul Cervoni, Carine Richou, Claire Vanlemmens, Stavros Dritsas, Gilles Capellier, Gaël Piton, Claire Chaignat, Sébastien Pili-Floury, Gilles Blasco, Emmanuel Samain, Didier Samuel, Eric Levesque, Faouzi Saliba, Philippe Ichaï, Arnaud Galbois, Bertrand Guidet, Vincent Das, Bertrand Sauneuf, Jean-Paul Mira, Dominique Perrotin, Benoit Champigneulle, Frédéric Pene, René Robert, Bruno Filloux, Christine Silvain, Jérome Fichet, Marc McPhail, Julia Wendon, Debbie Shawcross, William Bernal, Eleni Theocharidou, Banwari Agarwal, Andrew K Burroughs, Evangelos Cholongitas, Rodrigo Cavallazzi, Constantine J Karvellas, Heng Chih Pan, Yung-Chang Chen, Ming-Hung Tsai

Abstract

Background: The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown.

Methods: We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores).

Results: In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36-0.59; p < 0.001) and higher in patients with SOFA > 19 at baseline (OR 8.54; 95% CI 2.09-34.91; p < 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64-3.65; p < 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47-3.22; p < 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07-27.63; p < 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11-17.24; p < 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02-10.27; p < 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32-23.96; p < 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68-9.42; p < 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22-3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mortality without heterogeneity. In ICU survivors, eight markers of liver and renal failure predicted 6-month mortality, including Child-Pugh stage C (OR 2.43; 95% CI 1.44-4.10; p < 0.001; PPV = 0.57), baseline MELD > 26 (OR 3.97; 95% CI 1.92-8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24-17.64; p = 0.022; PPV = 0.88).

Conclusions: Prognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child-Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality.

Keywords: CLIF-SOFA; Cirrhosis; Extrahepatic organ failure; MELD; Mortality; Organ replacement therapy; Prognostic scores.

Figures

Fig. 1
Fig. 1
Overall survival. In-ICU, in-hospital, 3-month, and 6-month survival rates are reported for each study included (thin and dotted lines) and for the whole study population (heavy black line). On the x-axis, the timescale is not complied, given the variable length of stay in ICU and hospital
Fig. 2
Fig. 2
Predictors of in-ICU mortality. For each variable, combined weight-adjusted odds ratios (filled triangle) and their 95% confidence intervals (horizontal line) obtained from forest plots of pooled analyses are reported, together with the p value, the number of cirrhotic patients with variable present, and the total number of patients with available data. Odds ratios >1 correspond to variables associated with higher mortality. Odds ratios <1 correspond to variables associated with better survival. Odds ratios with a 95% CI containing 1 correspond to nonsignificant results. (*) indicates heterogeneous results. APACHE Acute Physiology and Chronic Health Evaluation, CRP C-reactive protein, GNB Gram-negative Bacilli, GPB Gram-positive Bacilli, MARS molecular adsorbents recirculation system, MELD model of end-stage liver disease, NHOF non-hematologic organ failure, NS not significant, SIRS systemic inflammatory response syndrome, TIPS transjugular intrahepatic portosystemic shunt, SOFA Sequential Organ Failure Assessment, mSOFA modified SOFA, CLIF-SOFA modified SOFA according to the Chronic Liver Failure Consortium of the European Association for the Study of the Liver
Fig. 3
Fig. 3
Some remarkable results regarding in-ICU mortality (forest plots of odds ratios)
Fig. 4
Fig. 4
Predictors of 6-month mortality in ICU survivors. For each variable, combined weight-adjusted odds ratios (filled triangle) and their 95% confidence intervals (horizontal line) obtained from forest plots of pooled analyses are reported, together with the p value, the number of cirrhotic patients with variable present, and the total number of patients with available data. Odds ratios >1 correspond to variables associated with higher mortality. Odds ratios <1 correspond to variables associated with better survival. Odds ratios with a 95% CI containing 1 correspond to nonsignificant results. (*) indicates heterogeneous results. APACHE Acute Physiology and Chronic Health Evaluation, CRP C-reactive protein, GNB Gram-negative Bacilli, GPB Gram-positive Bacilli, MARS molecular adsorbents recirculation system, MELD model of end-stage liver disease, NHOF non-hematologic organ failure, NS not significant, SIRS systemic inflammatory response syndrome, TIPS transjugular intrahepatic portosystemic shunt, SOFA Sequential Organ Failure Assessment, mSOFA modified SOFA, CLIF-SOFA modified SOFA according to the Chronic Liver Failure Consortium of the European Association for the Study of the Liver
Fig. 5
Fig. 5
Some remarkable results regarding the impact of characteristics recorded on ICU admission on the 6-month mortality in ICU survivors (forest plots of odds ratios)

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