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. 2010 Mar;11(2):213-6.
doi: 10.1097/PCC.0b013e3181b8076c.

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

Jeffrey E Nowak  1 , Derek S Wheeler, Kelli K Harmon, Hector R Wong
Affiliations

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

Jeffrey E Nowak et al. Pediatr Crit Care Med. 2010 Mar.

Abstract

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 < or =140 pg/mL had a negative predictive value for mortality of 98%.

Conclusions: A serum level of chemokine (C-C motif) ligand 4 of < or =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 < or =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.

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Figures

Figure 1
Figure 1
Receiver operating curve (ROC) of chemokine (C-C motif) ligand 4 protein level as a predictor of 28-day mortality in the training set of 34 children with septic shock (7 non-survivors). Area under the curve = 0.698; 95% confidence interval = 0.513–0.844.
Figure 2
Figure 2
Receiver operating curve (ROC) of chemokine (C-C motif) ligand 4 protein level as a predictor of 28-day mortality in the validation set of 122 children with septic shock (13 non-survivors). Area under the curve = 0.798; 95% confidence interval = 0.713–0.863.
Figure 3
Figure 3
Contingency table depicting sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of chemokine (C-C motif) ligand 4 (CCL4) cut-off of 140 pg/mL for 28-day mortality when prospectively applied to the validation data set.
Figure 4
Figure 4
A chemokine (C-C motif) ligand 4 (CCL4) cutoff value of 140 pg/mL separates children with septic shock into two groups with significantly different risks for 28-day mortality (p=0.01, χ2). Data generated from 156 patients (combining training and validation data sets).
See this image and copyright information in PMC

Comment in

  • It's not cherry-picking, it's bridging the gap.
    de Carvalho WB, Machado Fonseca MC. de Carvalho WB, et al. Pediatr Crit Care Med. 2010 Mar;11(2):304-5. doi: 10.1097/PCC.0b013e3181cbdd48. Pediatr Crit Care Med. 2010. PMID: 20216178 No abstract available.

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