Coronary artery bypass grafting (CABG) accounts for nearly half of all adult cardiac surgeries [1]. CABG is commonly associated with persistent postoperative chest pain, which causes significant discomfort and negatively impacts the patients’ quality of life. In follow-up visits, many CABG patients report persistent chest pain upon movement or even when at rest [2,3]. The insertion of chest tubes, surgical incisions, intercostal nerve injuries, and pleura stimulation during thoracotomies, stimulates many nociceptors, resulting in chronic postoperative pain [4]. Pain is also caused by inflammation mediators, such as prostaglandins, ions, cytokines, and growth factors, resulting in peripheral sensitization and reduced nociceptor thresholds [5]. Effective pain management is critical because pain affects the patients’ physical and psychological wellbeing and may increase morbidity and mortality [6]. There are numerous pain management methods, and they all have side effects. The main method of pain management is the use of analgesics, such as narcotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Long term use of systemic analgesics can lead to adverse side effects, including gastrointestinal distress, ileus, dizziness, pruritus, urinary retention, and depressive symptoms [7]. Therefore, complementary non-pharmacological strategies, such as acupuncture, have been used to improve postoperative pain management and to reduce the use of systemic analgesics [6]. The use of acupuncture dates back by about 2,500 years in China. It is based on the paradigm that each visceral organ is associated with a specific acupuncture point and that internal disorders can be treated by stimulating these points [8], usually by inserting needles through these acupuncture points. Acupuncture is thought to mediate its analgesic effects by stimulating the central nervous system, especially through its short- and long-term effects on µ-opioid receptors, and the subsequent control of neurotransmitters, hormones, and blood flow in the meridians [9]. Neuropeptides with anti-inflammatory and anti-apoptotic properties, such as the calcitonin gene-related peptide and the vasoactive intestinal polypeptide (VIP), may also mediate the analgesic effects of acupuncture. It has also been reported that acupuncture has a vagal cholinergic anti-inflammatory effect and increases the release of enkephalins and β-endorphins at the central level [5]. Here, we investigated the effects of acupuncture on pain control, postoperative outcomes and the quality of life of CABG patients, as well as on the side effects of using large amounts of analgesics. Our analysis aimed to investigate acupuncture as a non-invasive pain relief strategy without systemic side effects when compared with the control group that was treated using exercise therapy and oral analgesics only.

1. Ethical approval and trial registration

This clinical trial study was approved by the Medical Ethics Committee of Shiraz University of Medical Sciences (approval No. IR.SUMS.MED.REC.1397.108) and the Iranian Registry of Clinical Trials (IRCT, registration number: IRCT20180530039913N1). All study participants gave written informed consent after receiving an explanation of the study aims, methods, and procedures.

2. Study design

Thirty eligible cases referred to the cardiac rehabilitation unit of Shahid Faghihi Hospital, which is affiliated to the Department of Physical Medicine and Rehabilitation, Shiraz University of Medical Sciences were recruited in 2018.

3. Inclusion criteria

The patients’ ages ranged from 40-70 years. All patients who had undergone CABG 3-6 months before the study were included.

4. Exclusion criteria

Patients with uncontrolled cardiac arrhythmias, decompensated heart failure, grade III atrioventricular conduction block, acute systemic disease with fever, skin lesions, ulcerations or inflammation at the acupuncture site (for the intervention group only), diabetes mellitus, lung disease, known psychiatric diseases (e.g., major depression disorder), a body mass index of > 30, smoking, use of illicit drugs, use of opium or alcohol, and bleeding tendencies, were excluded.

5. Randomization and blinding

Patients were randomly grouped into two groups (15 patients per group) using block randomization assignment. The randomization sequence was generated using Microsoft Excel at a 1:1 allocation and a random block size of six. The researchers who followed the patients, using questionnaires were blinded to treatment allocation. We emphasized that patients in both groups would receive reasonable treatment using similar protocols. Patients in the control group were blinded to the acupuncture procedures (such as the number and location of acupoints) that the case group would undergo.

6. Interventions

In both groups, exercise therapy, including a gentle active range of motion of the shoulders (including flexion, abduction by less than 90 degrees, and external and internal rotations). Sets of three scar massages, repeated 10 times, as well as analgesic use (acetaminophen at a maximal dosage of 500 mg) every six hours were recommended. For the control group, the exercise program and analgesic use were recommended as described above. The intervention group also received bilateral acupuncture using 25 × 25 disposable Dong Bang Korean needles at distinct acupoints under sterile conditions with the patient in a supine, comfortable position. The acupoints through the meridian pathways included HT3 (at the middle point of the line between the medial end the transverse cubital crease and the medial epicondyle of the humorous), HT4, HT5, and HT6 (1.5, 1, and 0.5 cun above the transverse crease of the wrist, respectively, on the radial side of the flexor carpi ulnaris muscle), HT7 (at the ulnar end of the transverse crease of the wrist in the depression on the radial side of the flexor carpi ulnaris muscle), PC3 (at the ulnar side of the tendon of biceps brachii muscle on the transverse cubital crease), PC5 and PC6 (3 and 2 cun above the transverse crease of the wrist between the tendons of the palmaris longus and flexor carpi radialis muscles), and PC7 (at the middle point of the most distal crease of the wrist between the radius and the ulnar bones), in each side of the body. Needles were inserted vertically at a 0.5-cm depth. This procedure was repeated for 10 daily 30-minute sessions constantly and completed in two weeks. During each session, patients were observed for symptoms like dizziness, bleeding, erythema, or itching (allergic reactions). Both groups were observed by researchers and asked about any complication during the treatment.

7. Outcome measurements

Visual analog scale (VAS) scores and the rate of analgesic use (mean number of 500 mg acetaminophen pills taken daily, and not exceeding six pills or 3,000 mg per day) were evaluated in both groups as the primary outcome measurements at baseline and after treatments were completed (ten days after treatment initiation). During the treatment period, patients were instructed not to use any other types of analgesics or dosage. The study’s consort diagram is shown on Fig. 1.

Figure 1. Consort 2010 flow diagram.

8. Statistical analysis

Statistical analysis was done on SPSS version 18. The sample size (30 patients) was determined using the Med-Calc software using alpha = 0.5 and 1-Beta = 0.9, and an effect size of 0.67 based on the Cochrane formula. Quantitative variables, such as mean VAS score and analgesic use between the two groups were evaluated using the Mann–Whitney U test. The interaction effect (time by group effect) was investigated using two-way ANOVA. Statistical differences between the variables within each group were compare using paired t-test with p < 0.05 indicating statistically significant differences.

We randomly divided thirty participants into the acupuncture group and the control group. The participants’ demographic data are shown on Table 1. The participants’ mean age was 55.7 ± 7.47 years and the male-to-female ratio was 0.76 (43.3% males and 56.6% females). The number of days since surgery did not differ significantly between the two groups (p = 0.547). In general, the demographic data did not differ significantly between the two groups.

SD = standard deviation..

&md=tbl&idx=1' data-target="#file-modal"">Table 1

Participant demographic and baseline characteristics.

	Acupuncture group	Control group	p-value
Sex, n (%)
Male	6 (40%)	7 (46.7%)	-
Female	9 (60%)	8 (53.3%)	-
Age, mean ± SD (year)	55.7 ± 6.67	55.33 ± 8.41	-
Days after surgery (days, mean ± SD)	49.33 ± 3.99	50.33 ± 4.94	0.547

SD = standard deviation..

1. Comparison of VAS scores within and between two groups

Although the VAS scores decreased significantly in both groups after treatment, the intervention group exhibited a markedly higher decrease than the control group (p < 0.001). Before treatment, there were no significant differences between the two groups (p = 0.967 and 0.816, respectively). Before treatment, the mean VAS score in the intervention group was 7.8 ± 0.77, which improved by a mean of 2.6 ± 0.74 after acupuncture (p < 0.001). VAS scores also decreased in the control group, but the change was greater in the acupuncture group (37% vs. 66%). Analysis of the interaction effect revealed a significant difference between the two groups, with the acupuncture group exhibiting a greater effect (p < 0.001, Table 2).

Table 2

Comparison of visual analogue scale (VAS) scores and mean scores of analgesic use between acupuncture and control groups before and after treatment.

Outcome measurements	Groups	Timing		Difference (interaction effect) between groups
		Before treatment	After treatment
VAS (score, mean ± SD)	Acupuncture	7.8 ± 0.77	2.6 ± 0.74	–5.2 ± 0.56
	Control	7.8 ± 0.68	4.9 ± 0.8	–2.8 ± 0.63
p-value between 2 groups		0.967	< 0.001	< 0.001
Analgesic use (per day, mean ± SD)	Acupuncture	2.6 ± 0.38 (1,300 ± 190 mg/day)	0.43 ± 0.56 (215 ± 80 mg/day)	–2.16 ± 0.61
	Control	2.6 ± 0.39 (1,300 ± 195 mg/day)	1.83 ± 0.36 (915 ± 180 mg/day)	–0.8 ± 0.19
p-value between 2 groups		0.818	< 0.001	< 0.001

2. Comparison of the rate of analgesic use between both groups

The mean score of analgesic use before acupuncture was 2.6 ± 0.38 (1,300 ± 190 mg/day), which improved by 83% after acupuncture in the treatment group to a mean score of 0.43 ± 0.56 (215 ± 80 mg/day) when compared with the control group (p < 0.001). Interaction effect analysis revealed a significant decrease in the mean score of analgesic use in the acupuncture group when compared with the control group (p < 0.001, Table 2).

Thoracic surgery is one of the most painful surgical procedures and coronary artery bypass grafting (CABG) accounts for more than half of adult cardiac surgeries worldwide [3,10]. Post-operative persistent pain with normal findings on several assessments and laboratory work-up may be caused by musculoskeletal problems, resulting in chronic post-surgical pain [3]. Post thoracotomy pain relief not only improves patient comfort but also decreases the post-operative morbidity and mortality of pulmonary and cardiac complications [11]. Thus, developing treatment methods that relieve pain with the highest efficacy and minimal side effects is critical. Acupuncture is a complementary, easy to apply, non-invasive procedure with few or no complications. Multiple mechanisms are thought to underlie the effects of acupuncture on pain relief, including control of neurotransmitters, hormones, and blood flow in the meridian pathways by stimulating µ-opioid receptors in the CNS, the release of calcitonin gene-related peptide and vasoactive intestinal polypeptide with anti-inflammatory and anti-apoptotic effects, and the activation of a vagal cholinergic peptide, which results in the release of enkephalins and β-endorphins in the CNS [9]. This study investigated the effectiveness of acupuncture in reducing chest pain in CABG patients. We find that average VAS scores were significantly decreased after treatment in both the acupuncture group and the control group, but the reduction was greater in the acupuncture group (p < 0.001). Furthermore, analgesic use was significantly decreased after acupuncture when compared with the control group (p < 0.001). Several previous studies have reported the effects of acupuncture on pain reduction after surgery. For example, two studies by Tavakoli et al. showed that acupuncture significantly reduced pain after open kidney and inguinal surgeries [12,13]. Another study by Mikashima et al. showed that acupuncture reduced pain and swelling in the post-acute phase of rehabilitation after total knee arthroplasty [14]. Nevertheless, Deng et al. reported that acupuncture had no effect on pain after thoracotomy [15]. These discrepancies might be due to the differences in sample size, type of the surgery, and evaluation methods, when compared with our study. Improving sleep and mental health is reported as an acupuncture benefit in patients recovering from breast cancer [16]. However, our study is limited by the lack of longer follow-up, the lack of a more comprehensive questionnaire for evaluating pain and patients’ function, and the small sample size. Although we excluded patients with confounding factors, such as known previous psychiatric disorders, smoking, use of illicit drugs, and BMIs of > 30, we did not evaluate the level of anxiety and stress, which might influence pain and response to treatment after surgery. Additionally, the knowledge by patients in the control group that those in the intervention group received acupuncture might have influenced the outcomes.

Our findings indicate that acupuncture can reduce pain and analgesic use after CABG. Considering the safety and limited side effects of acupuncture, it may be beneficial when used along with other pain relief managements. However, further studies are needed to confirm these findings.

Acupuncture might be an appropriate alternative method of controlling post-operative chest pain and reducing the use of analgesics, which may have many side effects in CABG patients.

This study was part of a thesis of Dr. Yas Haririan (No.12691) approved by the Medical Ethics Committee of Shiraz University of Medical Sciences (SUMS) and Iranian Registry Clinical Trial (IRCT) with the reference numbers “IR.SUMS.MED.REC.1397.108” and “IRCT20180530039913N1” respectively. The authors would like to thank center for development of clinical research of Namazee hospital for cooperation in data analysis.

The authors received no financial support for the research, authorship or publication of this article.

Authors had equal contribution in all aspects of this trial.

The authors declare no conflict of interest.