Effectiveness of Acupuncture for Pain Control After Cesarean Delivery

This randomized clinical trial examines the safety and efficacy of acupuncture as a supplemental preoperative treatment for pain in women who will undergo cesarean birth.


Postoperative pain relief
Despite advances in knowledge of pathophysiology, pharmacology of analgesics and the development of more effective techniques for perioperative analgesia, many patients continue to experience distressing pain after elective surgery (1,2). It is well known that inadequately controlled pain results in an increased postoperative morbidity, delayed recovery, a delayed return to normal daily living and reduced patient satisfaction (3). The standard method of pain control after major surgery -pharmacotherapy with opioid analgesics -is often accompanied with the side effects such as respiratory depression, decreased intestinal motility, nausea, vomiting and itching (4)(5)(6).
Postoperative pain (POP) therapy in patients after caesarian section (CS) often remains insufficient and can be improved (7). Recently, using the data from the annual audits within the quality management system (QMS) in POP treatment in our institution, we observed that the patients after CS reported more pain on movement than the patients after other surgical procedures: mean 6.1 vs. 4.2 (VRS-11; p<0.0001) (8). This can be explained by the fact that pharmacological treatment in the obstetrical wards worldwide (including our institution) is restricted due to peculiarities of this patients' category (7). POP treatment should not interfere with the mother's ability to care for her baby and should be free from adverse neonatal effects in breast-feeding women. Thus, only few analgesic drugs match these requirements and are recommended for postoperative analgesia after CS (7,9).

Acupuncture for postoperative pain control
Acupuncture is one of the non-pharmacological techniques, which can be used for complementary analgesia after surgery (10). During last decade AA became increasingly popular in perioperative medicine (11). In a recent systematic review Sun et al. found out that perioperative acupuncture allowed to reduce the consumption of postoperative opioid analgesics and reduced the intensity of postoperative pain. Also acupuncture was associated with a lower incidence of opioid-related side effects such as nausea, dizziness, sedation, pruritus and urinary retention (12). Using the acupuncture methods, described in the review and our own expertise in perioperative acupuncture (13,14), we applied body and ear acupuncture for treatment of POP in several patients scheduled for elective CS. The promising results included the reduction of POP intensity and dose of analgesics as well as the increased satisfaction with POP treatment (15).
In the present project we are going to test the methodology of acupuncture analgesia after CS and generate the data to calculate the sample size for the subsequent randomised controlled trial (RCT). In RCT we aim to investigate the effectiveness of acupuncture added to standard therapy for pain control in patients after elective CS. We try to develop a protocol for a simple complementary method for acute pain relief, which can be easily applied in clinical routine by anaesthesiologists who have no prior knowledge on acupuncture.

Primary objective:
To investigate the effectiveness of acupuncture added to standard therapy for pain control in patients after elective CS.

Secondary objective:
To investigate whether acupuncture added to standard therapy for pain control also influences the side effects of standard postoperative analgesia in patients after elective CS.

ETHICAL ASPECTS
The present study protocol complies with the requirements of the following directives and guidelines: •

Benefit-risk consideration
The patients receiving acupuncture are expected to have benefit in reduction of pain intensity and analgesic requirement; thus a decrease in the rate of typical adverse effects of analgesics is hypothesised. The prognosis for the beneficial effect of acupuncture is based on the results of randomised controlled studies (10)(11)(12)(13)(14)(15).
Since the body acupuncture will be performed using the indwelling permanent needles with 5 mm length, we did not expect the serious complications attributed to body acupuncture such as pneumo-and haematothorax and haemopericard (16). The patients will receive acupuncture in supine position, therefore the traumatic consequences of vasovagal reaction can be excluded (16). The most common side effects of auricular acupuncture, described in case reports, were endocarditis and perichondritis (16)(17)(18). Therefore, we shall exclude the patients at risk (with damaged or prosthetic cardiac valves) for endocarditis from our investigation. In cases of acupuncture-associated perichondritis the treatment including parenteral antibiotics and surgical intervention were described (18). We did not observe serious side effects of AA in more than 600 patients treated with indwelling fixed needles during the prospective clinical trials on analgesic effects of AA (19).
In this planned study the investigators will examine the indwelling fixed acupuncture needles on the day following surgery and the needles will be withdrawn on the 2 nd postoperative day. The careful inspection along with the adequate disinfection of the skin before needle insertion enables the early detection and therapy of side effects and complications of acupuncture due to local inflammation and potential infection.

Ethics Committee
The protocol including the copies of the "Informed Consent

Patient information
The patients will be informed both orally and in a written form about the study procedure, potential benefits and risks of the participation in the study, the right to withdraw from the study at any time, and to obtain written informed consent prior to any study procedures.

Insurance
The question of additional insurance, covering the costs of potential injuries due to various aspects of clinical trial, will be clarified with the Allianz Insurance Company.

STUDY DESIGN
This will be a prospective randomised, patient-blinded, placebo-controlled clinical study with non-randomised arm of standard therapy at one centre -the Department of Gynaecology and Obstetrics, University Medicine of Greifswald. The duration of the study will be 3 days for each patient. Local ethics committee should approve the design of the study. A total of one hundred and eighty patients scheduled for elective CS will be recruited according to patients' selection criteria. 3. All patients are free to withdraw from participation in this study at any time, for any reason, specified or non-specified, and without penalty or loss of benefits to which the patient is otherwise entitled 6. TREATMENT PLAN

Pilot Study
A pilot case series investigation was performed to refine the methodology of acupuncture analgesia in patients after elective CS and to generate the data to calculate the sample size for the randomized controlled trial.
The retrospective data from the previous case series (15)

Group Allocation
Following the signing of the informed consent for participation in this study (Appendix A) the study patients will be randomly allocated to receive acupuncture (60 patients) or placebo acupuncture (60 patients) in addition to standard therapy of POP. Randomisation will be performed using the method of sealed envelopes. Patients who will not wish to receive acupuncture will be asked to take part in a routine internal audit within the quality assurance activity on POP treatment (Appendix B) and thus will constitute the non-randomised arm of "standard therapy alone" in our investigation. and BL25-27 will be needled bilaterally using the indwelling intradermal 0.14 x 5 mm needles and will be attached with self-adhesive tape -New Pyonex placebo needles, originally designed for placebo control procedure.

Acupuncture and placebo intervention
The New Pyonex placebo needles will be used for placebo acupuncture intervention and will be applied to the same areas, as the real acupuncture needles, however without subsequent stimulation by the means of massage.
The acupuncture needles or placebo needles will be placed in the morning before surgery and retained in situ 3 days following the SC surgery. Before the needle insertion, the skin will be completely disinfected with alcohol swabs.

Spinal anaesthesia and postoperative analgesia
All study patients will receive a standardised spinal anaesthesia with 7. The patients will be instructed by the acupuncturist to stimulate acupuncture needles by the means of massage in case they feel the pain intensity higher than 4 measured using Verbal Rating Scale 11 (where 0=no pain; 10=maximal pain imaginable). The patients will be unaware of their allocation either to acupuncture or placebo acupuncture group. The success of patient's blinding should be tested at the end of the study.

Outcome Measures (Appendix E)
Primary

SAMPLE SIZE AND STATISTICS
In order to calculate the appropriate sample size we set the level of significance to 0.05 and power at 90%. Based on the results of our pilot investigation and recently evaluated audit (8) and thus expecting to find a 30% difference in pain intensity on movement on the 1 st day following surgery between acupuncture group and placebo group and 30% difference between placebo group and standard therapy group (with standard deviation 50% from mean value) the number of patients was calculated to be 55 per group (taking account the Bonferroniadjustment for multiple comparisons among 3 study groups). Since the drop-out/withdrawal rate may reach the 10-15% in clinical studies on postoperative pain relief with acupuncture (12,13), the sample size was set to a 60 patients per group and a total of 180 patients.
Normally distributed continuous data will be compared using the Student's t-test and an analysis of variance, as appropriate. Skewed data will be compared using Kruskall-Wallis and Friedman test. Chi-square test will be used to analyse the success of patients' blinding and the incidence of analgesia-related side effects. SPSSStatistics Software for Mac (Version 22.0) will be used for data analysis.