Electroacupuncture-inspired neuroimmune modulation in sepsis: evidence appraisal and ICU trial-design priorities

Electroacupuncture (EA) has emerged as a biologically plausible adjunctive strategy for modulating neuroimmune dysregulation in sepsis. However, several recent reviews have already summarized anti-inflammatory mechanisms, ST36-centered animal evidence, organ-protective effects, and pooled clinical signals of acupuncture or EA in experimental and clinical sepsis. The unmet need is therefore not another catalog of positive pathways, but a critical translational framework that asks when, in whom, and how EA-inspired neuromodulation should be evaluated within the clinical complexity of septic intensive care. This review integrates mechanistic, preclinical, clinical, safety, and trial-design literature to appraise the evidence hierarchy, clarify sepsis immunophenotype-based patient-selection logic, and identify ICU-specific barriers to clinical translation. We emphasize somato-autonomic reflexes, inflammatory reflex signaling, vagal-adrenal and cholinergic anti-inflammatory pathways, macrophage and T-cell regulation, gut barrier immunity, immune suppression, and biomarker-guided stratification. Current clinical evidence suggests possible adjunctive signals, particularly in sepsis-associated gastrointestinal dysfunction and inflammatory biomarker modulation, but available trials are small, heterogeneous, frequently unblinded, and often use usual-care rather than sham comparators. Accordingly, reported mortality signals should be interpreted as hypothesis-generating rather than established clinical efficacy. We propose that future research should prioritize phenotype-specific, sham-controlled, multicenter trials with standardized stimulation protocols, organ-specific endpoints, immune and barrier biomarkers, and rigorous ICU safety governance, with gastrointestinal dysfunction serving as the most actionable initial indication. Closed-loop or artificial intelligence-guided EA should be regarded only as a future, physician-supervised engineering perspective. EA remains a biologically plausible but clinically unproven adjunctive neuromodulatory strategy in sepsis; its value for hard outcomes such as mortality, durable organ protection, and long-term recovery requires confirmation in rigorously designed ICU trials.