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

¹ Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; ² Division of Critical Care Medicine, Children's Hospital and Research Center Oakland, Oakland, California; and ³ Eli Lilly Research Laboratories, Indianapolis, Indiana

Correspondence and requests for reprints should be addressed to Hector R. Wong, M.D., Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. E-mail: hector.wong{at}cchmc.org

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 = 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 = 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 = 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.

Key Words: pediatrics • septic shock • biomarkers • interleukin-8 • stratification

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The development of an effective biomarker would be a useful stratification tool for clinical studies involving children with septic shock. What This Study Adds to the Field Serum interleukin-8 serum level, obtained within 24 hours of admission, has a 95% negative predictive value for mortality in children with septic shock.

 

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