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Endotoxemia and mortality prediction in ICU and other settings: underlying risk and co-detection of gram negative bacteremia are confounders

James C Hurley12*, Bertrand Guidet345, Georges Offenstadt345 and Eric Maury345

Author Affiliations

1 Rural Health Academic Center, Melbourne Medical School, 'Dunvegan' 806 Mair St., University of Melbourne, Ballarat, Victoria 3350, Australia

2 Division of Internal Medicine, Ballarat Health Services, 101 Drummond St., N, Ballarat, 3350, Victoria, Australia

3 Réanimation médicale, Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, 184 rue du Faubourg Saint Antoine, Paris, F-75012, France

4 UPMC Université Paris 06, 4 Place Jussieu, Paris, 75005, France

5 Inserm, Unité de Recherche en Épidémiologie Systèmes d'Information et Modélisation (U707), Paris, F-75012, France

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Critical Care 2012, 16:R148  doi:10.1186/cc11462

Published: 7 August 2012

Abstract

Introduction

The interdependence between endotoxemia, gram negative (GN) bacteremia and mortality has been extensively studied. Underlying patient risk and GN bacteremia types are possible confounders of the relationship.

Methods

Published studies with ≥10 patients in either ICU or non-ICU settings, endotoxemia detection by limulus assay, reporting mortality proportions and ≥1 GN bacteremia were included. Summary odds ratios (OR) for mortality were derived across all studies by meta-analysis for the following contrasts: sub-groups with either endotoxemia (group three), GN bacteremia (group two) or both (group one) each versus the group with neither detected (group four; reference group). The mortality proportion for group four is the proxy measure of study level risk within L'Abbé plots.

Results

Thirty-five studies were found. Among nine studies in an ICU setting, the OR for mortality was borderline (OR <2) or non-significantly increased for groups two (GN bacteremia alone) and three (endotoxemia alone) and patient group one (GN bacteremia and endotoxemia co-detected) each versus patient group four (neither endotoxemia nor GN bacteremia detected). The ORs were markedly higher for group one versus group four (OR 6.9; 95% confidence interval (CI), 4.4 -to 11.0 when derived from non-ICU studies. The distributions of Pseudomonas aeruginosa and Escherichia coli bacteremias among groups one versus two are significantly unequal.

Conclusions

The co-detection of GN bacteremia and endotoxemia is predictive of increased mortality risk versus the detection of neither but only in studies undertaken in a non-ICU setting. Variation in GN bacteremia species types and underlying risk are likely unrecognized confounders in the individual studies.