Interleukin-8 as a stratification tool for interventional trials involving pediatric septic shock.
BACKGROUND
Interventional clinical trials involving children with septic shock would benefit from an efficient preenrollment stratification strategy.


OBJECTIVE
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.


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.
Wong
Hector R
HR
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. hector.wong@cchmc.org
Cvijanovich
Natalie
N
Wheeler
Derek S
DS
Bigham
Michael T
MT
Monaco
Marie
M
Odoms
Kelli
K
Macias
William L
WL
Williams
Mark D
MD
D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D011237:Predictive Value of Tests; D012372:ROC Curve; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood* / Q000503:physiopathology; D016019:Survival Analysis
D015415:Biomarkers; D016209:Interleukin-8