Admission chemokine (C-C motif) ligand 4 levels predict survival in pediatric septic shock

OBJECTIVE:: Stratification with an effective outcome biomarker could improve the design of interventional trials in pediatric septic shock. The objective of this study was to test the usefulness of chemokine (C-C motif) ligand 4 as an outcome biomarker for mortality in pediatric septic shock. DESIGN:: A cross-sectional, observational study. SETTING:: Eighteen pediatric intensive care units in the United States. PATIENTS:: One hundred fifty-six pediatric patients with septic shock. INTERVENTIONS:: Serum samples were obtained within 24 hrs of admission to the pediatric intensive care unit. Serum levels of chemokine (C-C motif) ligand 4 were measured by enzyme-linked immunosorbent assay and compared with mortality in a training set of 34 patients. These data were used to generate a cutoff value whose usefulness was evaluated through prospective application-without post hoc modification-to a larger validation set of 122 patients. MEASUREMENTS AND MAIN RESULTS:: On inspection of the training set data, a cutoff value of 140 pg/mL was chosen. When applied to the validation set, serum chemokine (C-C motif) ligand 4 levels >140 pg/mL yielded a sensitivity of 92% and a specificity of 40% for mortality. A serum level of ≤140 pg/mL had a negative predictive value for mortality of 98%. CONCLUSIONS:: A serum level of chemokine (C-C motif) ligand 4 of ≤140 pg/mL, when obtained within 24 hrs of admission, predicts a very high likelihood of survival in pediatric septic shock. Exclusion of patients with a chemokine (C-C motif) ligand 4 level of ≤140 pg/mL from interventional clinical trials in pediatric septic shock could create a study population in which survival benefit from the study agent could be more readily demonstrated.