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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.None.Plasma interleukin-8 levels ≥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.