Association of Hyperinflammatory and Hypoinflammatory Sepsis Phenotypes with ICU Mortality and Length of Stay: A Prospective Cohort Study

Abstract

Sepsis is biologically heterogeneous, and inflammatory phenotypes may provide clinically relevant prognostic information in addition to conventional severity assessment, although their incremental prognostic value requires further evaluation. This study evaluated the association of hyperinflammatory and hypoinflammatory sepsis phenotypes with ICU mortality and length of stay. This prospective cohort study included adults with sepsis admitted to the ICU of Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia, from July to September 2026. Phenotypes were assigned by a prespecified algorithm using laboratory and clinical parameters within 24 hours of diagnosis. Analyses compared hyperinflammatory and hypoinflammatory patients; intermediate or unclassified phenotypes were described separately. ICU mortality, length of stay, and classification stability were assessed. Among 108 patients, 45 (41.7%) were hyperinflammatory, 52 (48.1%) hypoinflammatory, and 11 (10.2%) intermediate or unclassified. Analysis included 97 patients. ICU mortality was higher in the hyperinflammatory than hypoinflammatory group (31.1% vs 13.5%; unadjusted risk ratio, 2.31 [95% CI, 1.02–5.22]; p = 0.035), and ICU stay was longer (median, 12 vs 10 days; p = 0.009). Bootstrap showed phenotype proportions, and sensitivity showed substantial-to-almost-perfect agreement after sequential exclusion. In this single-centre cohort, hyperinflammatory sepsis was associated with higher observed ICU mortality and longer ICU length of stay than hypoinflammatory sepsis. Independent external validation and assessment of incremental prognostic value beyond established severity scores are required before clinical implementation.