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Reconciling Conflicting Results From Pediatric Sepsis Studies: The Need for Context-Specific Sepsis Bundles.

Unauthorized reproduction of this article is prohibited 594 www.pccmjournal.org June 2018 • Volume 19 • Number 6 A sepsis bundle is a set of patient management elements that, when implemented as a whole, have been associated with significant improvements in outcomes (1, 2). Bundle effectiveness is determined by adherence and the individual elements; unfortunately, poor bundle adherence has limited utilization (2, 3). The Surviving Sepsis Campaign has advocated for universal implementation of the Pediatric Advanced Life Support (PALS) algorithm for the initial management of pediatric septic shock (4–6), the core of which is rapid, large-volume fluid resuscitation, and early antibiotic administration (6), both of which have subsequently become essential elements in pediatric sepsis bundles. More recently, the American College of Critical Care Medicine has proposed three complementary pediatric sepsis bundles: a recognition bundle with a “trigger tool” to rapidly identify patients, a “resuscitation and stabilization bundle” based on institutional best practice, and a “performance bundle” to improve and maintain adherence (7). In this issue of Pediatric Critical Care Medicine, Fernández-Sarmiento et al (8) report sepsis bundle adherence and outcomes in children with severe sepsis and septic shock at a referral hospital in Colombia before and after an educational intervention. The bundle, based on the 2010 PALS algorithm (6), included: 1) identifying sepsis within 5 minutes, 2) securing vascular access within 15 minutes, 3) administering fluid boluses within 60 minutes, 4) starting antibiotics within 60 minutes, and 5) initiating vasoactives, if indicated, within 60 minutes. The intervention was a 40-minute lectureand casebased program that reinforced PALS guidelines and bundle elements with emergency department staff. Surprisingly, bundle adherence decreased (27.7% to 19.2%; p = 0.17) after the intervention (8). Despite poor adherence, there was a significant reduction in hospital length of stay following the intervention (11.6 vs 7.9 d; p = 0.01). In a multivariable model, however, only the relative risk of mechanical ventilation was favorably impacted post intervention; there were no significant differences between groups in terms of mortality, length of ICU stay, or, importantly, length of hospital stay (8). A subgroup analysis showed that length of stay was significantly shorter post versus pre intervention in the adherent subgroup, which could be interpreted as evidence that the educational strategy positively affected length of stay. These results are similar to a pediatric study in the United States in which researchers observed poor sepsis guideline adherence but a meaningful decrease in length of stay in the adherent subgroup (2). This group of researchers then implemented an intensive quality improvement process and achieved a dramatic and sustainable increase in sepsis guideline adherence (9). Obtaining and maintaining sepsis bundle adherence are challenging, but dedicated quality improvement efforts appear superior to simple educational interventions. Fernández-Sarmiento et al (8) attributed the improvement in length of stay to two bundle elements: early fluid resuscitation and earlier antibiotic administration. Post intervention, the median time to fluid bolus administration markedly decreased (247 to 5 min; p = 0.001), whereas the median time to antibiotic administration modestly improved (343 to 271 min; p = 0.03) (8). Post intervention, there was an increase in the proportion of patients who received a fluid bolus (51% vs 94.2%) and antibiotics (38% vs 49.5%) within the 60-minute bundle target (8). Interestingly, the median time to sepsis identification was significantly delayed and did not improve after the intervention (approximately 600 min in both groups). Despite long delays in identification and antibiotic administration, the observed in-hospital mortality was low (4% vs 1.3%, p = 0.25, preand post intervention, respectively) (8). This was notably different from a recent pediatric study that observed an increased risk of mortality for each hour of delay between sepsis identification and antibiotic administration, culminating in 21.2% mortality in patients who received antibiotics after 180 minutes (10). It is possible that early fluid resuscitation contributed to a shorter length of stay in Fernández-Sarmiento et al (8), but we doubt that the small improvement in time to antibiotics had a meaningful impact. Sepsis bundles have the potential to improve management and outcomes in septic children regardless of the setting, but we would like to interject a word of caution: a single bundle should not be thought of as universal. Rather, a sepsis bundle is intended to be tailored to the local setting and patient population. We need to carefully consider—and study—the elements that comprise sepsis bundles in diverse settings, especially fluid bolus administration. Teresa Kortz, MD, MS Department of Pediatrics University of California San Francisco, CA