Date Published: November 11, 2014
Publisher: Public Library of Science
Author(s): Sarah J. Atkinson, Natalie Z. Cvijanovich, Neal J. Thomas, Geoffrey L. Allen, Nick Anas, Michael T. Bigham, Mark Hall, Robert J. Freishtat, Anita Sen, Keith Meyer, Paul A. Checchia, Thomas P. Shanley, Jeffrey Nowak, Michael Quasney, Scott L. Weiss, Sharon Banschbach, Eileen Beckman, Kelli Howard, Erin Frank, Kelli Harmon, Patrick Lahni, Christopher J. Lindsell, Hector R. Wong, Lyle L. Moldawer.
The potential benefits of corticosteroids for septic shock may depend on initial mortality risk.
We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk.
We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression was used to model the effects of corticosteroids on 28-day mortality and complicated course, defined as death within 28 days or persistence of two or more organ failures at 7 days.
Subjects who received corticosteroids had greater organ failure burden, higher illness severity, higher mortality, and a greater requirement for vasoactive medications, compared to subjects who did not receive corticosteroids. PERSEVERE-based mortality risk did not differ between the two groups. For the entire cohort, corticosteroids were associated with increased risk of mortality (OR 2.3, 95% CI 1.3–4.0, p = 0.004) and a complicated course (OR 1.7, 95% CI 1.1–2.5, p = 0.012). Within each PERSEVERE-based stratum, corticosteroid administration was not associated with improved outcomes. Similarly, corticosteroid administration was not associated with improved outcomes among patients with no comorbidities, nor in groups of patients stratified by PRISM.
Risk stratified analysis failed to demonstrate any benefit from corticosteroids in this pediatric septic shock cohort.
The controversy surrounding corticosteroid use in septic shock has yielded multiple adult randomized controlled trials, yet their results are conflicting and a consensus has yet to be reached –. The Surviving Sepsis Campaign guidelines recommend considering corticosteroid usage in patients with refractory shock, defined as those who continue to require vasopressors despite adequate fluid resuscitation . However, physician practices surrounding adjunctive corticosteroid administration vary significantly , . Practitioners must weigh the potential hemodynamic improvements seen with corticosteroids against the risks of diminished wound healing, gastrointestinal bleeding, hyperglycemia, and immune suppression , , .
We examined the association between corticosteroid administration and outcomes in a large, heterogeneous cohort of children with septic shock from multiple institutions across the United States. When including all subjects regardless of initial mortality risk, corticosteroids were associated with poorer outcomes. We note that subjects who received corticosteroids had greater illness severity as measured by PRISM score, mortality, organ failure burden, and requirement for vasoactive medications. Thus, the finding that corticosteroids were associated with poorer outcomes in the overall cohort is likely confounded by illness severity.