Abstract
IntroductionThe 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.MethodsPublished 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.ResultsThirty-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.ConclusionsThe 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.
Highlights
The interdependence between endotoxemia, gram negative (GN) bacteremia and mortality has been extensively studied
The following inclusion criteria were used; (1) limulus assay used for endotoxemia detection, (2) at least one patient with GN bacteremia, (3) at least ten patients in the study, (4) at least five patients in group four, (5) no anti-endotoxin intervention in use and (6) data was extractable into a 2 × 2 × 2 contingency table format in relation to the co-detection of GN bacteremia and endotoxemia and mortality proportions
After excluding studies restricted to specified infections, there were 497 GN bacteremias with species type known among which there was an uneven distribution of E. coli versus P. aeruginosa identified among the GN bacteremias of group one versus group
Summary
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. The impact of underlying risk of death is a key factor in the clinical setting [46,47] but is difficult to investigate in laboratory studies [48,49,50,51,52]. The objective here is to evaluate the GN bacteremia species type and underlying patient risk as possible confounding factors of the prognostic value of endotoxemia as detected using the limulus assay in published clinical studies of patients across a broad spectrum of risk
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