The Effect of Percutaneous Auricular Vagus Nerve Stimulation on Postoperative Delirium in Elderly Patients Undergoing Colorectal Cancer Surgery

Technical Summary: The Effect of Percutaneous Auricular Vagus Nerve Stimulation on Postoperative Delirium

Problem Statement
Postoperative delirium (POD) is a prevalent and severe complication among elderly patients undergoing colorectal cancer surgery, associated with adverse clinical outcomes, prolonged recovery, and increased mortality. While pharmacological interventions exist to mitigate central nervous system inflammation, they are often limited by side effects. Although physical therapies like vagus nerve stimulation (VNS) show promise, direct surgical VNS carries high risks, and the efficacy of non-invasive transcutaneous auricular vagus nerve stimulation (TAVNS) specifically for POD in elderly colorectal cancer patients remains under-explored. This study addresses the gap in understanding whether TAVNS can effectively reduce POD incidence and elucidates its potential mechanisms regarding neuroprotection and anti-inflammatory responses.

Methodology
The study was a single-center, prospective investigation conducted at The First Affiliated Hospital of Hebei North University involving 180 elderly patients (age ≥ 65, ASA grade I–II) scheduled for elective laparoscopic radical resection of colorectal cancer. Participants were randomly assigned to three groups (60 per group):

1. TAVNS Group: Received daily electrical stimulation of the auricular concha region (targeting vagus nerve distribution) from one day pre-surgery to three days post-surgery. Parameters included 30 minutes duration, 1 mA intensity, and 20–30 Hz frequency.
2. Sham Stimulation Group: Received electrical stimulation with identical parameters but applied to non-vagus nerve areas of the auricle.
3. Blank Control Group: Received no intervention.

Data Collection and Analysis:

• Primary Outcome: The incidence of POD was assessed using the 3-Minute Diagnostic Interview for CAM-Defined Delirium (3D-CAM) at baseline (1 day pre-op) and postoperative days 1, 3, and 7.
• Secondary Outcomes: Serum levels of brain injury markers (Neuron-Specific Enolase [NSE] and S100β protein) and inflammatory cytokines (Tumor Necrosis Factor-α [TNF-α] and Interleukin-6 [IL-6]) were measured via ELISA at preoperative, immediate postoperative, and postoperative days 1 and 3.
• Statistical Approach: Data were analyzed using SPSS 21.0. Comparisons between groups utilized one-way ANOVA or Wilcoxon rank-sum tests, while within-group comparisons used paired t-tests. A significance level of α = 0.05 was applied.

Key Results
Out of 180 enrolled patients, 174 completed the study (58 per group) after exclusions due to prolonged surgery, conversion to open surgery, or refusal of follow-up. Baseline characteristics were comparable across groups.

• POD Incidence: The TAVNS group demonstrated a significantly lower incidence of POD on postoperative days 1, 3, and 7 compared to both the sham and blank control groups (P < 0.05). No statistically significant difference was observed between the sham and blank control groups (P > 0.05).
  • Day 7 POD Rates: TAVNS (1.72%) vs. Sham (5.17%) vs. Blank (6.89%).
• Biomarker Levels:
  • Brain Injury Markers: Postoperative levels of NSE and S100β were significantly lower in the TAVNS group on days 1 and 3 compared to the other two groups (P < 0.05). The sham and blank groups showed no significant difference from each other.
  • Inflammatory Cytokines: Similarly, serum TNF-α and IL-6 levels were significantly reduced in the TAVNS group on postoperative days 1 and 3 relative to the control groups (P < 0.05). Again, no significant difference existed between the sham and blank groups.

Key Contributions
This study provides clinical evidence that non-invasive TAVNS is effective in reducing the incidence of postoperative delirium in elderly colorectal cancer patients. It distinguishes the therapeutic effect of vagus nerve stimulation from non-specific electrical stimulation by utilizing a sham control group, demonstrating that the specific anatomical targeting of the auricular concha is critical for efficacy. Furthermore, the study correlates the clinical improvement with biochemical changes, suggesting that TAVNS exerts its protective effects by simultaneously inhibiting central nervous system injury markers and systemic inflammatory responses.

Significance and Claims
The authors claim that TAVNS offers a viable, low-risk, and side-effect-free physical therapy alternative for managing POD in high-risk surgical populations. The study posits that the mechanism of action involves the activation of the cholinergic anti-inflammatory pathway via afferent vagal fibers in the concha region. This activation leads to the inhibition of pro-inflammatory cytokines (TNF-α, IL-6) and the mitigation of blood-brain barrier damage and neuronal injury (indicated by reduced NSE and S100β). The findings suggest that TAVNS could be integrated into perioperative care protocols to improve neurological outcomes in elderly patients, addressing a critical gap where pharmacological options are limited by toxicity. The study concludes that the specific stimulation of the auricular vagus nerve distribution area is necessary to achieve these neuroprotective and anti-inflammatory benefits.