Plasma interleukin-8 is not an effective risk stratification tool for adults with vasopressor-dependent septic shock

Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, CA, USA.
Critical care medicine (Impact Factor: 6.31). 04/2010; 38(6):1436-41. DOI: 10.1097/CCM.0b013e3181de42ad
Source: PubMed


Plasma interleukin-8 levels of <220 pg/mL have an excellent negative predictive value (94% to 95%) for death at 28 days in children with septic shock and thus may be useful for risk stratification in clinical trial enrollment in this population. Whether plasma interleukin-8 would have similar utility in adults with septic shock is unknown.
Analysis of plasma interleukin-8 levels and prospectively collected clinical data from patients enrolled in two large randomized controlled trials of ventilator strategy for acute lung injury.
Intensive care units of university hospitals participating in the National Institutes of Health Acute Respiratory Distress Syndrome Network.
One hundred ninety-two adult patients with vasopressor-dependent septic shock.
Plasma interleukin-8 levels > or =220 pg/mL were significantly associated with death at 28 days in this cohort (odds ratio, 2.92; 95% confidence interval, 1.42 to 5.99; p = .001). However, in contrast to the findings in pediatric septic shock, a plasma interleukin-8 cutoff <220 pg/mL had a negative predictive value for death of only 74% (95% confidence interval, 66% to 81%) in adults with septic shock. Receiver operating characteristic analysis found an area under the curve of 0.59 for plasma interleukin-8, indicating that plasma interleukin-8 is a poor predictor of mortality in this group. In adults aged <40 yrs, a plasma interleukin-8 cutoff <220 pg/mL had a negative predictive value of 92%.
In contrast to similar pediatric patients, plasma interleukin-8 levels are not an effective risk stratification tool in older adults with septic shock. Future studies of biomarkers for risk stratification in critically ill subjects will need to be replicated in multiple different populations before being applied in screening for clinical trials.

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Available from: Lorraine Ware, Jun 09, 2015
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    • "While IL-6 and IL-8 levels have been shown to be elevated in sepsis and associated with severity and outcome [121], they have not been found to be superior to PCT as biomarkers [58, 70]. These cytokines have been found to be elevated in neutropenic fever [38] and neonatal sepsis [122] but have been less useful in the adult population [123]. "
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    03/2014; 2014:264351. DOI:10.1155/2014/264351
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    • "Consequently, it has been proposed that serum IL-8 levels can be used to exclude low risk patients from future pediatric septic shock interventional trials as a means to improve the risk to benefit ratio of a therapeutic intervention. Interestingly, IL-8 does not seem to be an effective stratification biomarker in adult septic shock, thus suggesting important biological and physiological differences between adult and pediatric septic shock (54). "
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    ABSTRACT: For nearly a decade, our research group has had the privilege of developing and mining a multi-center, microarray-based, genome-wide expression database of critically ill children (≤ 10 years of age) with septic shock. Using bioinformatic and systems biology approaches, the expression data generated through this discovery-oriented, exploratory approach have been leveraged for a variety of objectives, which will be reviewed. Fundamental observations include wide spread repression of gene programs corresponding to the adaptive immune system, and biologically significant differential patterns of gene expression across developmental age groups. The data have also identified gene expression-based subclasses of pediatric septic shock having clinically relevant phenotypic differences. The data have also been leveraged for the discovery of novel therapeutic targets, and for the discovery and development of novel stratification and diagnostic biomarkers. Almost a decade of genome-wide expression profiling in pediatric septic shock is now demonstrating tangible results. The studies have progressed from an initial discovery-oriented and exploratory phase, to a new phase where the data are being translated and applied to address several areas of clinical need.Pediatric Research (2013); doi:10.1038/pr.2013.11.
    Pediatric Research 01/2013; 73. DOI:10.1038/pr.2013.11 · 2.31 Impact Factor
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    • "This type of stratification strategy would be particularly applicable for an intervention that carries more than minimal risk. Interestingly, it appears that IL-8-based stratification may not perform in a similarly robust manner in adults with septic shock [55], thus providing another example of how developmental age contributes to septic shock heterogeneity. "
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