Role of serum neuron-specific enolase levels in the early diagnosis and prognosis of sepsis-associated encephalopathy: a systematic review and meta-analysis

Abstract

Background: Sepsis-associated encephalopathy (SAE) is one of the most ubiquitous complications of sepsis and is characterized by cognitive impairment, poor prognosis, and a lack of uniform clinical diagnostic criteria. Therefore, this study investigated the early diagnostic and prognostic value of serum neuron-specific enolase (NSE) in SAE.

Methods: This systematic review and meta-analysis systematically searched for clinical trials with serum NSE information in patients with sepsis in the PubMed, Web of Science, Embase, and Cochrane databases from their inception to April 10, 2023. Included studies were assessed for quality and risk of bias using The Quality Assessment of Diagnostic Accuracy-2 tool. The meta-analysis of the included studies was performed using Stata 17.0 and Review Manager version 5.4.

Findings: Eleven studies were included in this meta-analysis involving 1259 serum samples from 947 patients with sepsis. Our results showed that the serum NSE levels of patients with SAE were higher than those of the non-encephalopathy sepsis group (mean deviation, MD,12.39[95% CI 8.27-16.50, Z = 5.9, p < 0.00001]), and the serum NSE levels of patients with sepsis who died were higher than those of survivors (MD,4.17[95% CI 2.66-5.68, Z = 5.41, p < 0.00001]).

Conclusion: Elevated serum NSE levels in patients with sepsis are associated with the early diagnosis of SAE and mortality; therefore, serum NSE probably is a valid biomarker for the early diagnosis and prognosis of patients with SAE.

Systematic review registration: This study was registered in PROSPERO, CRD42023433111.

Keywords: biomarker; meta-analysis; neuron-specific enolase; sepsis-associated encephalopathy; serum.

Figure 1

Study selection process.

Figure 2

Methodological quality summary.

Figure 3

Methodological quality graph.

Figure 4

Meta-analysis forest plot: relation between serum neuron-specific enolase level and patients with sepsis-associated encephalopathy.

Figure 5

Meta-analysis forest plot: relation between serum neuron-specific enolase level and poor outcomes of patients with sepsis.

Figure 6

Relation between serum neuron-specific enolase levels and sepsis-associated encephalopathy at various serum sample collection times following intensive care unit admission.

Figure 7

Relation between serum neuron-specific enolase level and sepsis-associated encephalopathy of varying ages.

Figure 8

(A) Begg’s funnel plot analysis of the studies that investigated the relation between serum neuron-specific enolase (NSE) level and sepsis-associated encephalopathy (SAE). (B) Egger’s funnel plot analysis of the studies that investigated the relation between serum NSE level and SAE. (C) Begg’s funnel plot analysis of the studies that investigated the relation between serum NSE level and poor outcomes of patients with sepsis. (D) Egger’s funnel plot analysis of studies that investigated the relation between serum NSE level and poor outcomes of patients with sepsis.

Figure 9

(A) Impact of a single study on combined mean deviation (MD) regarding the connection between serum neuron-specific enolase (NSE) level and sepsis-associated encephalopathy. (B) Impact of a single study on combined MD regarding the connection between serum NSE levels and the poor outcomes of patients with sepsis.

Figure 10

A full-text overview picture. (A) The invasion of pathogens into the human body causes systemic inflammatory response, resulting in sepsis. The major sepsis-associated encephalopathy (SAE) symptoms range from drowsiness to confusion, delirium, and coma. (B) Neuron-specific enolase (NSE) is a cell isoenzyme of enolase in glycolysis that can be detected in serum. (C) Our meta-analysis revealed that the SAE group had higher serum NSE levels than that in the NE group, and the sepsis mortality group had higher serum NSE levels than the survival group.