Integrative acupoint stimulation within enhanced recovery after surgery: Harnessing the neuroimmune axis for enhanced gastrointestinal recovery

Abstract

Enhanced recovery after surgery (ERAS) programs have transformed perioperative care, yet delayed gastrointestinal function and excessive neuroendocrine stress remain major obstacles to optimal recovery. Hong et al’s randomized controlled trial embedded acupoint-based neuromodulation - meridian-timed acupoint application combined with transcutaneous electrical acupoint stimulation - within an ERAS framework and demonstrated accelerated gastrointestinal recovery accompanied by endocrine attenuation. This article offers a structured critical appraisal of the trial, emphasizing methodological rigor, mechanistic plausibility, and alignment with ERAS core principles of stress mitigation, functional restoration, and patient experience. The observed reductions in norepinephrine, cortisol, and aldosterone suggest modulation of the hypothalamic-pituitary-adrenal axis as a key mediator of benefit. Future research priorities include multicenter, sham-controlled validation; integration of autonomic and inflammatory biomarkers (heart rate variability, interleukin-6, tumor necrosis factor-α, C-reactive protein); and pragmatic evaluation of cost-effectiveness and acceptability. Positioning acupoint stimulation within precision-integrative perioperative care could advance ERAS from a recovery protocol to a system of host-response modulation. Integrative acupoint neuromodulation thus represents a biologically coherent, low-risk, and scalable strategy for enhancing resilience, accelerating gastrointestinal recovery, and improving surgical outcomes worldwide.

Key Words: Enhanced recovery after surgery; Acupoint stimulation; Gastrointestinal recovery; Neuroimmune modulation; Perioperative care

Core Tip: Integrative acupoint stimulation, combining meridian flow injection and transcutaneous electrical acupoint stimulation, enhances postoperative gastrointestinal recovery within enhanced recovery after surgery protocols by modulating the neuroimmune axis. This approach accelerates return of bowel function, attenuates stress hormone surges, reduces complications, and improves patient satisfaction. By bridging traditional therapies with modern mechanistic understanding, it exemplifies a precision supportive care strategy in gastrointestinal surgery and highlights the potential of multimodal perioperative interventions to optimize recovery, resilience, and long-term outcomes.

INTRODUCTION

Esophageal and other gastrointestinal malignancies remain among the leading causes of global cancer mortality despite substantial advances achieved through enhanced recovery after surgery (ERAS) programs[1-4]. Even within optimized perioperative pathways, delayed gastrointestinal function, heightened neuroendocrine stress responses, and persistent symptom burden continue to prolong hospitalization and compromise quality of recovery[5-8]. Against this backdrop, Hong et al’s randomized controlled trial[9] stands out for embedding acupoint-based neuromodulation - specifically, meridian-timed acupoint application combined with transcutaneous electrical acupoint stimulation (TEAS) - within an ERAS framework, thereby linking endocrine modulation to accelerated postoperative milestones.

Postoperative recovery is increasingly understood as a neuro-immune process, wherein autonomic imbalance and stress-induced inflammatory cascades critically shape clinical outcomes[10,11]. By demonstrating that targeted acupoint stimulation can attenuate these responses, Hong et al[9] contribute valuable mechanistic and translational evidence supporting neuroimmune modulation as an actionable dimension of perioperative care. This article provides a concise critical appraisal of their trial, identifies methodological and mechanistic priorities for refinement, and outlines a pragmatic agenda for multicenter validation and implementation within modern ERAS protocols.

CRITICAL APPRAISAL

The randomized controlled trial by Hong et al[9] represents a noteworthy contribution to perioperative science by rigorously evaluating a structured acupoint-based intervention - meridian-timed acupoint application combined with TEAS - in the context of gastroenteroscopy. Several aspects of its design and outcomes warrant critical analysis, both for their methodological rigor and their implications for advancing integrative perioperative care within ERAS frameworks.

Methodological strengths

The trial was anchored in a mechanistically explicit hypothesis. By aligning acupoint stimulation with the chronobiological rhythm of meridian qi flow and augmenting it through electrical modulation, the investigators directly targeted the gut-brain-immune axis - a regulatory pathway increasingly recognized as central to postoperative recovery[12,13].

Methodological rigor was strengthened by stratified block randomization, allocation concealment, and oversight by independent staff - features that minimize selection bias, a common limitation in complementary therapy research[14]. Inclusion of a conventional-care control arm ensured clinical realism and enhanced interpretability within standard ERAS pathways.

Equally important, the trial employed a multidimensional outcome framework encompassing functional, biochemical, and patient-reported measures: Gastrointestinal recovery metrics, endocrine markers (gastrin, norepinephrine, cortisol, aldosterone), complication rates, and satisfaction scores. The observed concordance across physiologic and experiential domains reinforces biological plausibility and supports the internal consistency of the findings[9,15]. In this revision, these endpoints are explicitly mapped to ERAS core domains - physiologic stress attenuation, gastrointestinal recovery, and patient experience - highlighting how convergence across these axes strengthens causal inference in early-phase research.

Key findings and interpretation

The acupoint-TEAS group demonstrated accelerated gastrointestinal recovery, with shorter times to first bowel movement and oral intake[9]. Such functional gains are clinically meaningful, as delayed recovery remains a major obstacle to ERAS optimization[16]. Concurrently, reductions in stress-related hormones (norepinephrine, cortisol, aldosterone) indicate suppression of sympathetic outflow and hypothalamic-pituitary-adrenal reactivity[9,17]. Given that excessive endocrine stress impairs motility, augments inflammation, and increases complications[11,13,18], these results substantiate the concept that acupoint stimulation exerts systemic neuroendocrine modulation beyond local effects.

The accompanying decreases in complication rates and improvements in patient satisfaction[9] further underscore multidimensional benefit. Taken together, endocrine attenuation emerges as a plausible mediator of enhanced gastrointestinal recovery - a mechanistic pathway that can be formally tested in subsequent trials integrating autonomic (heart rate variability) and inflammatory endpoints with standardized clinical outcomes.

Innovation and alignment with ERAS principles

Hong et al[9] innovatively positioned acupoint neuromodulation within a contemporary ERAS framework. Rather than treating it as an ancillary or empiric adjunct, the intervention was protocolized and evaluated under CONSORT and STRICTA criteria for non-pharmacologic trials[12,13]. This approach demonstrates that traditional modalities can be subjected to the same methodological discipline as pharmacologic or surgical innovations.

Conceptually, the study aligns with the multimodal, mechanism-driven ethos of ERAS - integrating nutrition, analgesia, early mobilization, and now targeted neuroimmune modulation - to mitigate surgical stress and expedite rehabilitation[15,17]. For reproducibility and translation, acupoint selection, timing relative to surgery, TEAS frequency/intensity, and session number should be prospectively standardized according to STRICTA guidelines.

Limitations and caveats

Despite its rigor, several limitations temper interpretation: (1) Single-center design and limited sample size restrict external validity; multicenter replication is essential[14]; (2) Active components in the control (e.g., massage or topical stimulation) may have attenuated between-group contrasts[14]; (3) Incomplete blinding introduces potential expectancy bias for subjective endpoints; prior evidence suggests unblinded designs can overestimate treatment effects[19,20]; (4) Short-term follow-up (3 days) precludes assessment of durability at 30 days or 90 days; validated instruments such as Quality of Recovery-15 (QoR-15) and EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) should be used[15,21]; (5) Mechanistic inference was indirect; incorporation of autonomic, cytokine, and neuroimmune markers would provide stronger causal linkage[17]; and (6) Trial registration and prespecified outcomes should adhere to CONSORT/STRICTA standards[12,13]. Each limitation suggests a tangible improvement path: Incorporation of assessor blinding and, where feasible, sham comparators; adoption of core outcome sets [Gastrointestinal Recovery Index (GI-2), QoR-15, QLQ-C30]; extended follow-up for durability; and mechanistic assays to bridge physiologic and patient-reported endpoints.

Integration with broader evidence

Within the wider evidence landscape, Hong et al’s findings[9] resonate with data demonstrating that perioperative neuromodulation - including TEAS and acupoint stimulation - can reduce postoperative nausea, ileus, and inflammatory stress[10,16-18]. Meta-analyses such as the Cochrane review of P6 stimulation support its safety and cost-effectiveness when embedded in ERAS pathways[16]. Mapping the present trial’s endpoints onto established core outcome frameworks facilitates meta-analytic synthesis and future health-economic modeling focused on clinically relevant metrics such as hospital stay and readmission.

Synthesis

Collectively, the trial provides credible early-phase evidence that integrative acupoint stimulation enhances gastrointestinal recovery, attenuates neuroendocrine stress, and reduces complications - findings methodologically aligned with CONSORT/STRICTA principles and outcome validation literature[12,13,15,21]. Nevertheless, its generalizability, blinding rigor, and mechanistic depth require strengthening through multicenter, mechanistically enriched designs[14,17,19,20].

By bridging traditional modalities with evidence-based surgical frameworks, this study exemplifies an emerging paradigm in perioperative medicine: One that views recovery as a modifiable, system-level process rather than a passive consequence of surgical technique. Such a perspective holds promise for improving resilience, functional independence, and long-term quality of life. Building on this foundation, future multicenter investigations should explicitly link autonomic and inflammatory signatures to patient-centered and resource-based outcomes, establishing an empirical pathway toward pragmatic, precision-based ERAS implementation.

FUTURE PERSPECTIVES

The findings of Hong et al[9] outline a credible proof-of-concept for acupoint-based neuromodulation within an ERAS framework. The next phase of inquiry must extend beyond efficacy signals toward mechanistic verification, multimodal synergy, and implementation readiness. Postoperative recovery is not merely the consequence of surgical craftsmanship but a dynamic interplay of neuroendocrine, immune, and behavioral systems. Accordingly, we propose an actionable roadmap encompassing methodological refinement, biological validation, multimodal integration, and pragmatic translation.

Methodological priorities

Future research should consolidate methodological rigor to ensure reproducibility and generalizability. Multicenter, adequately powered randomized controlled trials are required to validate the current findings across varied patient populations, surgical procedures, and institutional contexts[19]. Whenever feasible, sham-controlled or blinded-assessor designs should be employed to mitigate expectancy effects[20]. Although full patient blinding remains challenging for acupoint interventions, standardized assessor blinding and centralized randomization can meaningfully reduce bias.

Outcome assessment must also mature. Validated metrics such as the GI-2, QoR-15, and EORTC QLQ-C30 should replace non-validated satisfaction scores[15,21]. Longer follow-up intervals - at 30 days and 90 days - are essential to determine whether early physiological and endocrine improvements translate into sustained functional and quality-of-life benefits[22]. Pre-registration with prespecified endpoints, covariate sets, and clearly defined TEAS/acupoint dosing parameters will maximize transparency and enable meta-analytic synthesis across future trials.

Mechanistic exploration

The mechanistic underpinnings of acupoint stimulation warrant rigorous exploration. Integrative trials should incorporate objective autonomic indices, such as heart rate variability, to quantify vagal activation and sympathetic modulation[23]. Parallel measurement of inflammatory biomarkers - including interleukin-6, tumor necrosis factor-α, and C-reactive protein - would clarify whether endocrine attenuation coincides with dampened systemic inflammation[24]. Emerging omics approaches - metabolomics, proteomics, and microbiome profiling - offer opportunities to delineate global host-response signatures[25]. Prospective mediation analyses linking these mechanistic variables to GI-2 scores, postoperative ileus incidence, and length of stay will strengthen causal inference and guide precision targeting.

Multimodal integration

The future of ERAS lies in synergy. Acupoint stimulation should be investigated as part of a convergent strategy that integrates multiple neuroimmune-modulating modalities[4,5]. Combining it with immunonutrition - such as perioperative supplementation with omega-3 fatty acids, arginine, and nucleotides - may enhance anti-inflammatory and mucosal-protective effects[26]. Parallel optimization of sleep through circadian-aligned melatonin therapy or behavioral interventions can further stabilize neuroendocrine tone[27]. Embedding psychological resilience training into the perioperative timeline could augment coping capacity and dampen maladaptive stress responses[2]. A factorial or adaptive platform design would allow simultaneous testing of these complementary components - evaluating synergy, dose–response, and resource impact within a unified ERAS bundle.

Implementation science and global translation

To achieve real-world impact, acupoint neuromodulation must progress from controlled environments to pragmatic, system-level implementation[22]. Trials embedded in routine surgical workflows can evaluate effectiveness, scalability, and contextual adaptability. Health-economic analyses will be vital to determine cost-effectiveness and inform payer adoption[19]. Equally crucial is understanding patient and provider perspectives: Qualitative research exploring acceptability, perceived benefit, and cultural alignment will guide dissemination in diverse health systems[27]. In parallel, early incorporation of fidelity monitoring, structured training protocols, and cost-consequence analyses will anticipate scale-up barriers and support evidence-based guideline development.

A broader vision

Collectively, these priorities converge on a broader paradigm for perioperative medicine - one that dissolves the artificial divide between “traditional” and “modern” therapies. Validated and mechanistically grounded, acupoint stimulation could evolve from a complementary adjunct to a cornerstone of precision supportive care. By stratifying patients according to autonomic or inflammatory phenotype, clinicians may ultimately tailor integrative interventions to maximize benefit. Such a precision-integrative model redefines ERAS not simply as a recovery protocol but as a dynamic system for modulating host resilience across surgery, oncology, and rehabilitation.

CONCLUSION

The randomized trial by Hong et al[9] makes a substantive contribution to the evolving field of perioperative medicine by demonstrating that integrative acupoint stimulation can expedite gastrointestinal recovery, attenuate neuroendocrine stress responses, and enhance patient-centered outcomes. More broadly, the study exemplifies a paradigm shift in surgical science: Postoperative trajectories are governed not only by technical proficiency but also by the complex interaction between tissue trauma, host physiology, and neuroimmune regulation. The implications extend beyond any single modality. When rigorously standardized and embedded within ERAS pathways, acupoint-based therapies illustrate how non-pharmacologic, culturally rooted interventions can satisfy contemporary scientific and clinical benchmarks. By directly engaging the neuroimmune axis, these techniques offer a biologically coherent and clinically feasible route to strengthen resilience, reduce complications, and potentially influence long-term oncologic and functional outcomes. Moving forward, multicenter trials integrating autonomic and inflammatory biomarkers with validated outcome sets are essential to delineate responder phenotypes and establish optimized implementation strategies within ERAS frameworks.