Butyrylcholinesterase Activity as a Mortality Marker in ICU Patients: An Individual Participant Data Meta-Analysis

OBJECTIVES: To determine whether butyrylcholinesterase (BChE) activity independently predicts in-hospital mortality in critically ill adults and to derive a prognostic threshold from patient-level data. DATA SOURCES: Six databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, Cochrane CENTRAL) were searched from inception to data lock. The protocol was registered with PROSPERO (CRD42024558631); reporting followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses of individual participant data (IPD). STUDY SELECTION: Eligible studies were observational cohorts of critically ill adults measuring BChE by the Ellman or Worek method. Six prospective European and South American ICU cohorts contributed 482 adults (92.9% with sepsis; in-hospital mortality, 39%). Risk of bias was appraised with the Quality in Prognosis Studies tool. DATA EXTRACTION: Deidentified IPD from corresponding authors and one public repository were checked for integrity, harmonized, and converted to U/L. Variables included demographics, sepsis status, severity indices (Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II), and biochemical markers. DATA SYNTHESIS: Analyses included receiver operating characteristic curves (DeLong area under the curve [AUC], bias-corrected bootstrap), multivariable logistic regression, generalized estimating equation models, Kaplan-Meier and Cox regression, and random-effects meta-analysis (Hartung–Knapp). Admission BChE was lower among non-survivors, with moderate discrimination (pooled AUC, 0.72; 95% CI, 0.65–0.83; DeLong AUC, 0.671; 95% CI, 0.644–0.697). Higher Day-1 BChE was independently associated with lower mortality (odds ratio [OR] per 100 U/L, 0.979; 95% CI, 0.967–0.990; p < 0.001), with a significant ICU day interaction ( p = 0.029) and attenuation by Day 4. BChE below 1615 U/L predicted higher mortality (hazard ratio, 1.69; 95% CI, 1.11–2.59; log-rank p = 0.015). Meta-analysis confirmed the inverse association (pooled OR per 1 sd , 0.22; 95% CI, 0.06–0.73; p = 0.023). CONCLUSIONS: BChE enzymatic activity was an integrative, time-dependent prognostic marker of in-hospital mortality, particularly in sepsis. Reduced ICU admission levels and persistently suppressed trajectories identified higher-risk patients. BChE may complement organ dysfunction scores; the 1615 U/L threshold is exploratory and requires prospective external validation.