Objectives: To evaluate risk factors for poor functional outcome in 28-day survivors after an episode of severe sepsis.
Design: Retrospective cohort study examining data from the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective trial (NCT00049764).
Setting: One hundred and four pediatric centers in 18 countries.
Subjects: Children with severe sepsis who required both vasoactive-inotropic infusions and mechanical ventilation and who survived to 28 days (n = 384).
Measurements and Main Results: Poor functional outcome was defined as a Pediatric Overall Performance Category score greater than or equal to 3 and an increase from baseline when measured 28 days after trial enrollment. Median Pediatric Overall Performance Category at enrollment was 1 (interquartile range, 1–2). Median Pediatric Overall Performance Category at 28 days was 2 (interquartile range, 1–4). Thirty-four percent of survivors had decline in their functional status at 28 days, and 18% were determined to have a “poor” functional outcome. Hispanic ethnicity was associated with poor functional outcome compared to the white referent group (risk ratio = 1.9; 95% CI: 1.0–3.0). Clinical factors associated with increased risk of poor outcome included CNS and intra-abdominal infection sources compared to the lung infection referent category (risk ratio = 3.3; 95% CI: 1.4–5.6 and 2.4; 95% CI: 1.0–4.5, respectively); a history of recent trauma (risk ratio = 3.9; 95% CI: 1.4–5.4); receipt of cardiopulmonary resuscitation prior to enrollment (risk ratio = 5.1; 95% CI: 2.9–5.7); and baseline Pediatric Risk of Mortality III score of 20–29 (risk ratio = 2.8; 95% CI: 1.2–5.2) and Pediatric Risk of Mortality III greater than or equal to 30 (risk ratio = 4.5; 95% CI: 1.6–8.0) compared to the referent group with Pediatric Risk of Mortality III scores of 0–9.
Conclusions: In this sample of 28-day survivors of pediatric severe sepsis diminished functional status was common. This analysis provides evidence that particular patient characteristics and aspects of an individual’s clinical course are associated with poor functional outcome 28 days after onset of severe sepsis. These characteristics may provide opportunity for intervention in order to improve functional outcome in pediatric patients with severe sepsis. Decline in functional status 28 days after onset of severe sepsis is a frequent and potentially clinically meaningful event. Utilization of functional status as the primary outcome in future pediatric sepsis clinical trials should be considered.
1Division of Critical Care Medicine, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, WA.
2Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.
* See also p. 893.
Dr. Weiss provided expert testimony for various law firms, received grant support from the National Cancer Institute, and received royalties from Oxford University Press. Dr. Zimmerman has received funding from the NIH/Eunice Kennedy Striver NICHD Collaborative Pediatric Critical Care Research Network and served as a board member for the Society of Critical Care Medicine. Dr. Farris disclosed that he does not have any potential conflicts of interest.
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