Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.

TitleDelayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.
Publication TypeJournal Article
Year of Publication2014
AuthorsWeiss SL, Fitzgerald JC, Balamuth F, Alpern ER, Lavelle J, Chilutti M, Grundmeier R, Nadkarni VM, Thomas NJ
JournalCrit Care Med
Volume42
Issue11
Pagination2409-17
Date Published11/2014
ISSN1530-0293
KeywordsAcademic Medical Centers, Adolescent, Anti-Bacterial Agents, Cause of Death, Child, Child, Preschool, Cohort Studies, Critical Illness, Drug Administration Schedule, Female, Hospital Mortality, Hospitals, Pediatric, Humans, Infant, Infusions, Intravenous, Intensive Care Units, Pediatric, Kaplan-Meier Estimate, Logistic Models, Male, Multiple Organ Failure, Multivariate Analysis, Philadelphia, Retrospective Studies, Risk Assessment, Sepsis, Shock, Septic, Survival Rate, Time Factors
Abstract

OBJECTIVES: Delayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock.

DESIGN: Retrospective observational study.

SETTING: PICU at an academic medical center.

PATIENTS: One hundred thirty patients treated for severe sepsis or septic shock.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure-free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74-277 min) and to first appropriate antimicrobial was 177 minutes (90-550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2) and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure-free days (16 [interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04).

CONCLUSIONS: Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.

DOI10.1097/CCM.0000000000000509
Alternate JournalCrit. Care Med.
PubMed ID25148597
PubMed Central IDPMC4213742
Grant ListK12 HD047349 / HD / NICHD NIH HHS / United States
K12 HL109009 / HL / NHLBI NIH HHS / United States
K12 HL109009 / HL / NHLBI NIH HHS / United States
L40 GM102883 / GM / NIGMS NIH HHS / United States