Effects of perioperative transcutaneous electrical acupoint stimulation on monocytic HLA-DR expression in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass: study protocol for a double-blind randomized controlled trial

Wen-Ting Chen, Jin-Feng Wei, Lan Wang, Deng-Wen Zhang, Wei Tang, Jian Wang, Yue Yong, Jing Wang, Ya-Lan Zhou, Lan Yuan, Guo-Qiang Fu, Sheng Wang, Jian-Gang Song, Wen-Ting Chen, Jin-Feng Wei, Lan Wang, Deng-Wen Zhang, Wei Tang, Jian Wang, Yue Yong, Jing Wang, Ya-Lan Zhou, Lan Yuan, Guo-Qiang Fu, Sheng Wang, Jian-Gang Song

Abstract

Background: Cardiac surgery involving cardiopulmonary bypass (CPB) is known to be associated with a transient postoperative immunosuppression. When severe and persistent, this immune dysfunction predisposes patients to infectious complications, which contributes to a prolonged stay in the intensive care unit (ICU), and even mortality. Effective prevention and treatment methods are still lacking. Recent studies revealed that acupuncture-related techniques, such as electroacupuncture and transcutaneous electrical acupoint stimulation (TEAS), are able to produce effective cardioprotection and immunomodulation in adult and pediatric patients undergoing cardiac surgery with CPB, which leads to enhanced recovery. However, whether perioperative application of TEAS, a non-invasive technique, is able to improve immunosuppression of the patients with post-cardiosurgical conditions is unknown. Thus, as a preliminary study, the main objective is to evaluate the effects of TEAS on the postoperative expression of monocytic human leukocyte antigen (-D related) (mHLA-DR), a standardized "global" biomarker of injury or sepsis-associated immunosuppression, in patients receiving on-pump coronary artery bypass grafting (CABG).

Methods: This study is a single-center clinical trial. The 88 patients scheduled to receive CABG under CPB will be randomized into two groups: the group receiving TEAS, and the group receiving transcutaneous acupoint pseudo-electric stimulation (Sham TEAS). Expression of mHLA-DR serves as a primary endpoint, and other laboratory parameters (e.g., interleukin [IL]-6, IL-10) and clinical outcomes (e.g., postoperative infectious complications, ICU stay time, and mortality) as the secondary endpoints. In addition, immune indicators, such as high mobility group box 1 protein and regulatory T cells will also be measured.

Discussion: The current study is a preliminary monocentric clinical trial with a non-clinical primary endpoint, expression of mHLA-DR, aiming at determining whether perioperative application of TEAS has a potential to reverse CABG-associated immunosuppression. Although the immediate clinical impact of this study is limited, its results would inform further large-sample clinical trials using relevant patient-centered clinical outcomes as primary endpoints.

Trial registration: ClinicalTrials.gov, NCT02933996. Registered on 13 October 2016.

Keywords: CABG; Immunosuppression; TEAS; mHLA-DR.

Conflict of interest statement

The authors declare that they have no competing interests. The Ethics Committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine is independent from the sponsor and competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the study
Fig. 2
Fig. 2
Zusanli location: outside of the shank, 3 cun(10 cm) below Dubi acupoint and a finger’s width (middle finger) to tibial front edge
Fig. 3
Fig. 3
Shenshu location: below the spinous process of the second lumbar vertebra, 1.5 cun (5 cm) to the central line
Fig. 4
Fig. 4
The patients will receive TEAS therapy 30 min before anesthesia (one stimulation for 30 min), during the period of surgery (stimulation for the whole course) and within 24h after surgery (four times of stimulation, each for 30min)
Fig. 5
Fig. 5
We will use Low-frequency electronic pulse therapeutic device G6805-2 (Huayi, Shanghai, China) for TEAS therapy, the frequency will be 2/100 Hz alternating and the intensity will be 15mA
Fig. 6
Fig. 6
a: Patient received TEAS therapy at bilateral Zusanli acupoint (ST36) and Shenshu acupoint (BL23) during the perioperative period. b: Zusanli acupoint (ST36) is identified. c: Shenshu acupoint (BL23) is identified

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