Pediatric sepsis: challenges and adjunctive therapies

Abstract

Sepsis remains an important challenge in pediatric critical care medicine. This review provides an appraisal of adjunctive therapies for sepsis and highlights opportunities for meeting selected challenges in the field. Future clinical studies should address long-term and functional outcomes as well as acute outcomes. Potential adjunctive therapies such as corticosteroids, hemofiltration, hemoadsorption, and plasmapheresis may have important roles, but still require formal and more rigorous testing by way of clinical trials. Finally, the design of future clinical trials should consider novel approaches for stratifying outcome risks as a means of improving the risk-to-benefit ratio of experimental therapies.

Figure 1

Schematic illustrating the hypothalamic-pituitary-adrenal axis.

Figure 2

Schematic illustrating the recommendations for adjunctive corticosteroid administration in septic shock. The adult recommendations do not include the use of serum cortisol concentrations or corticotropin stimulation testing [16]. The pediatric recommendations, however, recommend measurement of serum cortisol concentrations and corticotropin stimulation testing [5].

Figure 3

Schematic highlighting the major differences between hemofiltration, hemoadsorption, and plasmapheresis as blood purification strategies for sepsis.

Figure 4

The classification tree for PERSEVERE based on 355 subjects [10]. The classification tree consists of 6 biomarker-based decision rules, 1 age-based decision rule, and 14 daughter nodes. The classification tree includes 5 stratification biomarkers: C-C chemokine ligand 3 (CCL3), heat shock protein 70 kDa 1B (HSPA1B), interleukin-8 (IL8), granzyme B (GZMB), and matrix metalloproteinase-8 (MMP8). Each node provides the total number of subjects in the node, the biomarker serum concentration- or age-based decision rule, and the number of survivors and non-survivors with the respective rates. The serum concentrations of all stratification biomarkers are provided in pg/ml. Terminal nodes 7, 11, and 14 are low risk nodes, with mortality probabilities ranging from 0.0 to 2.5%. Terminal nodes 4, 8, 10, 12, and 13 are high-risk terminal nodes, with mortality probabilities ranging from 18.2 to 62.5%.