Respiratory
Adherence to Positive End-Expiratory Pressure Protocols Across Sepsis Phenotypes among Ventilated Critically Ill Children Lucia Petito* Ngoc Duong Duong Duong Department of Preventive Medicine, Northwestern University
Background: Pediatric sepsis is clinically heterogeneous, and emerging evidence suggests that treatment responses may differ by clinical phenotype. We evaluated 7-day risks of multiple organ dysfunction syndrome (MODS) or death under varying adherence to Acute Respiratory Distress Syndrome (ARDSNet) Positive End-Expiratory Pressure (PEEP)-to-FiO₂ targets and whether these varied based on high- vs. low-risk Pheonix Sepsis phenotype defined at admission.
Methods: We analyzed harmonized data from 13 U.S. pediatric intensive care units (2012–2018). The outcome was persistent multiple organ dysfunction syndrome (MODS) on day 7 or death within 7 days. Patients discharged before day 7 were assumed outcome negative. We compared risk under a hypothetical “always adherent” strategy (PEEP within ARDSNet target range >80% of hours per 12-hours when FiO₂>0.21) versus the natural course risk. We adjusted for baseline and time-varying confounders using the parametric g-formula; nonparametric bootstrap (B=200) was used to generate 95% confidence intervals.
Results: Of 13,728 patients (observed for 79,556 person-days) with suspected infection requiring mechanical ventilation within the first 12 hours of PICU admission, 9,675 (70.5%) and 4,053 (29.5%) belonged to the high- vs low-risk phenotype. Of these, 52.8% met PEEP target at PICU admission, increasing to 80% on day 7. Estimated 7-day risk of MODS or death was 33.1% under the natural course versus 29.5% under the “always adherent” strategy (risk difference [RD] -3.6%; 95% CI: -4.8% to -2.5%). This effect varied by Phoenix Sepsis phenotype (high risk RD -5.1%; 95% CI: -6.7% to -2.8%; low risk phenotype RD -0.2%; 95% CI: -0.7% to 0.2%).
Conclusions: Adherence to ARDSNet PEEP/FiO₂ targets was associated with lower day-7 persistent MODS or death compared to natural course risk, with heterogeneity by Phoenix Sepsis phenotype underscoring the particular importance of adherence to ventilation targets among the highest risk phenotype.
