Butyrylcholinesterase activity predicts in-hospital mortality in critically ill adults with sepsisButyrylcholinesterase levels help predict survival in patients with sepsis

Critical care explorations Published August 26, 2026 Study authors: Esper Treml Ricardo, Grillo Iago T C, Hrabovska Anna, Fazekas Tomas, Espeter Florian, Schmidt Karste… PubMed ↗ DOI ↗ Editorial oversight: Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

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Key Takeaway

Consider BChE as a prognostic adjunct in sepsis, but await validation of the 1615 U/L threshold.

This is an individual participant data meta-analysis of observational cohorts, including 482 critically ill adults with sepsis in the ICU. The review synthesized evidence on the association between butyrylcholinesterase (BChE) activity and in-hospital mortality, with a focus on admission and Day-1 levels.

Key findings: Admission BChE showed moderate discrimination for in-hospital mortality (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 associated with lower mortality (OR 0.979 per 100 U/L; 95% CI 0.967-0.990; p < 0.001). A significant ICU day interaction was observed (p = 0.029), suggesting time-dependent prognostic value. A BChE threshold below 1615 U/L predicted higher mortality (hazard ratio 1.69; 95% CI 1.11-2.59; log-rank p = 0.015).

The meta-analysis confirmed an inverse association between BChE and mortality (pooled OR per 1 SD 0.22; 95% CI 0.06-0.73; p = 0.023).

Limitations: The 1615 U/L threshold is exploratory and requires prospective external validation. The analysis is based on observational cohorts, so associations are not causal. Adverse events and follow-up duration were not reported.

Practice relevance: BChE may complement organ dysfunction scores as a time-dependent prognostic marker in sepsis, but it is not a validated diagnostic tool.

How this fits prior evidence

This meta-analysis extends prior coverage on sepsis biomarkers by focusing on butyrylcholinesterase activity as a prognostic marker. It complements prior findings on syndecan-1, which correlated with severity but lacked specificity, by offering a time-dependent marker with moderate discrimination (AUC 0.72). The inverse association with mortality aligns with the broader theme of metabolic and organ dysfunction in sepsis, similar to mitochondrial dysfunction's role. However, the exploratory threshold requires validation, consistent with the caution noted for other biomarkers.

When a patient develops sepsis, they are in a critical fight for their life. Doctors in the intensive care unit need every tool possible to understand how well a patient is doing. A large review of data from 482 critically ill adults suggests that measuring a specific enzyme called butyrylcholinesterase (BChE) could provide that extra layer of information.

The study found that BChE levels are linked to survival outcomes. Specifically, patients with lower BChE levels on the first day of treatment showed higher risks of mortality. Researchers even identified a specific threshold: when BChE levels fall below 1615 U/L, it predicts a higher risk of death. This makes the enzyme a promising marker for tracking how well a patient's body is handling the infection.

While these results are encouraging, there are important notes to keep in mind. The specific 1615 U/L cutoff is currently considered exploratory, meaning it needs more testing in real-world settings before it can be used as a standard tool. Additionally, this study shows an association between the enzyme and survival, not a direct cause. It could serve as a helpful addition to current organ health scores to help doctors monitor patients more closely.

What this means for you:

Lower butyrylcholinesterase levels in sepsis patients may signal a higher risk of death during hospital stays.

Common questions

What is butyrylcholinesterase and how does it relate to sepsis?

Butyrylcholinesterase (BChE) is an enzyme in the body. In this study of 482 critically ill adults, researchers looked at BChE as a way to predict mortality in patients with sepsis. The results showed that lower levels of this enzyme on the first day were associated with higher risks of death.

Is there a specific level of BChE that indicates a higher risk?

The study identified an exploratory threshold of 1615 U/L. When BChE levels fall below this number, it predicts a higher mortality rate for patients in the intensive care unit. However, because this is an exploratory finding, it requires more testing before it can be used as a standard tool.

How does this help doctors treat sepsis?

BChE may serve as a time-dependent marker to complement current scores used to measure organ dysfunction. By tracking these levels, doctors might better understand the progression of the disease in critically ill patients. You should speak with a medical professional regarding specific treatments for sepsis.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedSep 2026

PMID42640628

View Original Abstract ↓

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.

Butyrylcholinesterase activity predicts in-hospital mortality in critically ill adults with sepsisButyrylcholinesterase levels help predict survival in patients with sepsis

How this fits prior evidence

Common questions

Study Details

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Butyrylcholinesterase activity predicts in-hospital mortality in critically ill adults with sepsisButyrylcholinesterase levels help predict survival in patients with sepsis

How this fits prior evidence

Common questions

More on Sepsis

Study Details

Intraosseous route for out-of-hospital cardiac arrest linked to lower outcomes than intravenous access

Using a bone needle instead of a vein line lowers survival chances for cardiac arrest patients

Clinical research that matters. Delivered to your inbox.

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