Early Total Bilirubin Trajectories During the First 72 Hours After ICU Admission With Mechanical Ventilation and Short-Term Mortality: A Multicenter Cohort Study
Takuya Nishino, Hiroshi Mase, Shinji Sugita, Chol Kim, Takaya Tsueshita, Junichi Saito, Masae Iwasaki, Toru Takiguchi, Yutaka Igarashi, Ryuta Nakae, Shoji Yokobori, Yukihiro Kondo, Daqing Ma, Masashi IshikawaOBJECTIVES:
To determine whether early total bilirubin (T-Bil) trajectories during the first 72 hours after intubation identify trajectory-defined groups with distinct prognostic profiles associated with short-term mortality in mechanically ventilated ICU patients.
DESIGN:
Multicenter retrospective cohort study with a prespecified day 3 landmark design to mitigate immortal-time bias.
SETTING:
Mixed medical-surgical ICUs at four tertiary centers.
PATIENTS:
Adults receiving invasive mechanical ventilation who survived to the day 3 landmark and had serial T-Bil measurements on day 0 and day 3 (± 24 hr).
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Patients were classified according to baseline T-Bil (≤ 1.2 vs. > 1.2 mg/dL) and the direction of change between day 0 and day 3 (change in T-Bil [ΔT-Bil]), yielding four trajectory-defined groups. The primary outcome was 30-day all-cause mortality after the day 3 landmark; 90-day mortality was secondary. Conditional survival was assessed using Kaplan-Meier methods with log-rank tests. Multivariable Cox models adjusted for prespecified covariates available by day 3 (age, sex, body mass index, intubating department, baseline mean arterial pressure, log-transformed aspartate aminotransferase/alanine aminotransferase ratio and platelet count, creatinine, renal replacement therapy, and vasoactive support). Rising T-Bil trajectories were independently associated with higher 30-day mortality, with the strongest association among patients with normal baseline T-Bil who exhibited early increases. In contrast, elevated baseline T-Bil followed by early decline was not associated with excess risk. Findings were consistent in complete-case analyses, in models incorporating day 3 partial Sequential Organ Failure Assessment for severity adjustment, and in analyses of 90-day mortality. Restricted cubic spline analyses demonstrated a nonlinear dose-response relationship between ΔT-Bil and mortality.
CONCLUSIONS:
Early T-Bil dynamics within 72 hours after intubation were associated with distinct prognostic profiles beyond baseline bilirubin levels and may provide a pragmatic marker for early risk stratification in mechanically ventilated ICU patients.