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

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.

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).

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.

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.

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).

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.