Interleukin-8 as a Stratification Tool for Interventional Trials Involving Pediatric Septic Shock

Abstract

Rationale: Interventional clinical trials involving children with septic shock would benefit from an efficient preenrollment stratification strategy. Objectives: To test the predictive value of interleukin (IL)-8 for 28-day mortality in pediatric septic shock. Methods: A training data set (n 5 40) identified a serum IL-8 of greater than 220 pg/ml as having a 75% sensitivity and specificity for predicting 28-day mortality. This cutoff was then subjected to a series of validation steps. Measurements and Main Results: Subjects were drawn from two large, independent pediatric septic shock databases. Prospective application of the IL-8 cutoff to validation data set 1 (n 5 139) demonstrated 78% sensitivity and 64% specificity for 28-day mortality. A serum IL-8 level of 220 pg/ml or less, however, had a negative predictive value for 28-day mortality of 95% in validation data set 1, which was subsequently applied to an independently generated data set of children with septic shock (validation set 2, n 5 193). A serum IL-8 level of 220 pg/ml or less had a negative predictive value for 28-day mortality of 94% when applied to validation set 2. Conclusions: A serum IL-8 level of 220 pg/ml or less, obtained within 24 hours of admission, predicts a high likelihood of survival in children with septic shock. We propose that IL-8 can be used to exclude such patients from interventional clinical trials and ultimately derive a study population with a more favorable risk to benefit ratio when subjected to a study agent.

Bacterial Phenotype Variants in Group B Streptococcal Toxic Shock Syndrome1

“…In agreement with these results, the HH/LC phenotype induced a signifi cantly higher release of the proinfl ammatory chemokine IL-8 than did the LH/HC phenotype. Considering the strong association between IL-8 serum levels and severity of sepsis (33,34), as well as the previously reported contribution of the β-h/c to the severe manifestations of septicemia in animal models (13,(35)(36)(37), we compared the isolates in an in vivo sepsis model. Indeed, in a high-dose sepsis model in mice, the HH/LC phenotypic variant was associated with accelerated death, although blood CFU levels were lower than observed with the LH/ HC variant.…”

Clinical review: Sepsis and septic shock - the potential of gene arrays

“…Subsequent studies demonstrated that serum IL-8 protein levels, measured within 24 hours of presentation to the intensive care unit with septic shock, could predict survival in pediatric septic shock with a probability of 95% [54]. The ability of IL-8 to serve as a stratification biomarker was subsequently validated in a completely independent cohort of children with septic shock.…”

Prognostic markers for pediatric septic shock: which ones, when, and how?

“…Maintained elevated PCT values over a period of time identify a worsening of the inflammatory process due to the lack of septic shock control. Interleukin-8 can also predict outcome in pediatric septic shock with high negative but unacceptably low positive predictive values for mortality [11]. Other currently available clinical markers such as vasopressin and copeptin were not found to have utility for severity and outcome prediction in pediatric septic shock [12].…”