Clinical Subphenotypes and Short-Term Outcomes in PICU Patients Receiving Continuous Blood Purification.

OBJECTIVES: To characterize clinical heterogeneity among PICU patients receiving continuous blood purification (CBP) and identify data-driven subphenotypes associated with distinct short-term outcomes. DESIGN: Multicenter, retrospective cohort study. SETTING: Fifteen PICUs (from January 2019 to August 2024). PATIENTS: Children (1 mo to 18 yr) receiving CBP during PICU hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In this multicenter cohort of 598 CBP-treated children, unsupervised clustering at CBP initiation identified three reproducible subphenotypes using a seven-variable signature comprising aspartate aminotransferase, hemoglobin, oxygenation index, Pediatric Logistic Organ Dysfunction-2 score, procalcitonin, weight, and pH. These subphenotypes showed distinct multidomain physiologic profiles rather than a simple severity gradient. Subphenotype I had the most favorable short-term survival profile, subphenotype II had the poorest survival, and subphenotype III showed an intermediate pattern, with significant separation in 28-day survival across groups. Subphenotypes also differed in ICU length of stay, and exploratory analyses suggested subphenotype-dependent associations between high-volume hemofiltration exposure and ICU discharge. Cross-validated supervised models showed high discriminability of subphenotype assignment. CONCLUSIONS: CBP-treated children exhibited distinct subphenotypes at CBP initiation with divergent short-term prognoses, highlighting marked heterogeneity at this treatment stage. Subphenotype-based stratification may support risk characterization and trial enrichment and facilitate hypothesis generation regarding heterogeneity of treatment associations. Prospective validation is warranted.