# Impact of Neuromuscular Electrical Stimulation on Biological Markers in Critically Ill Patients: A Systematic Review and Meta‐Analysis

## TL;DR

NMES may help reduce inflammation in critically ill patients, showing early anti-inflammatory effects and later reductions in inflammation markers.

## Contribution

This study provides the first meta-analysis on NMES effects on inflammatory biomarkers in critically ill patients.

## Key findings

- NMES significantly increased interleukin-10 levels shortly after application.
- NMES led to a delayed reduction in serum C-reactive protein levels.
- NMES appears safe and effective in modulating systemic inflammation in critically ill patients.

## Abstract

Neuromuscular electrical stimulation (NMES) has been increasingly used to preserve or restore neuromuscular function in critically ill patients. However, its effects on inflammatory biomarkers and its safety require to be fully elucidated. This study aimed to analyze the available evidence on the impact of NMES on biological markers in critically ill patients.

This systematic review followed a preregistered protocol (PROSPERO: CRD42023424413). A comprehensive search was conducted in PubMed, EMBASE, Web of Science, Scopus, PEDro, CENTRAL, and Google Scholar to identify randomized controlled trials (RCTs) comparing NMES with control interventions and reporting outcomes related to biological markers.

Ten RCTs were included in this review. Meta‐analyses revealed a significant acute increase in interleukin‐10 levels (SMD: 0.60; 95% CI: 0.11 to 1.08; p = 0.02) and a delayed reduction in serum C‐reactive protein levels (SMD: −0.74; 95% CI: −1.09 to −0.40; p < 0.0001) following NMES application.

Available evidence suggests that NMES can modulate systemic inflammation in mechanically ventilated critically ill patients, with early anti‐inflammatory effects (IL‐10 elevation) and subsequent attenuation of inflammation (CRP reduction). These findings support the safety of NMES during active phases of critical illness. Further high‐quality RCTs are warranted to standardize stimulation protocols, characterize biomarker dynamics, and elucidate the underlying mechanisms to guide evidence‐based clinical use.