This study is a single-center, two-arm, equally randomized, patient-blinded, parallel-group, and clinical trial conducted in Korea. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Kyung Hee University Medical Center (IRB 1535-04-A1). Written informed consent was obtained from all subjects prior to initiation of the study.
Patient population Sixty-four women undergoing elective thyroidectomy at Kyunghee University Hospital, with an American Society of Anesthesiologists physical status of I or II, were recruited between January 2016 and November 2018. They ranged in age from 22 to 63 years. Exclusion criteria included: patients with a history of motion sickness or PONV, those with diabetes mellitus, gastrointestinal disease, or those who smoked, any patient that was menstruating, or any a patient who had taken antiemetics or steroids within 72 hours prior to surgery. The trial flow is outlined in Fig. 1.
Randomization and blinding Patients were assigned to either the acupuncture or the control group on the basis of random numbers generated by a computer. Only the acupuncturist was informed of the randomization allocation, just before the onset of acupuncture. None of the anesthesiologists, surgeons, or physicians in the post-anesthesia care unit were aware of the allocation.
EA protocol Acupuncture was performed by two experienced acupuncturists, approximately 1 h before and 6 h after surgery. Acupuncturists used 0.25 × 40-mm disposable sterile acupuncture needles (Dong Bang Acupuncture, Chungnam, South Korea) and disposable medical intradermal needles (0.18-mm diameter × 1.5-mm length) inserted at the ST36 and PC6 points. ST36 is located four-finger widths down from the bottom of the knee cap, along the outer boundary of the shin bone. PC6 is located on the anterior side of the forearm, 2 cun (about 5 cm) proximal to the palmar wrist crease, between the tendons of the palmaris longus and flexorcarpi radialis muscles (Fig. 2, I confirm that a written consent for the picture was obtained from the pictured subject). Acupuncture sessions lasted 30 min. In the EA patients, needles were stimulated using a dedicated electric stimulator. The stimulus was delivered in continuous waves at the intensity of 6–8 V and a frequency of 25 Hz.
Anaesthesia and perioperative management A standardized intravenous anesthetic protocol was used: Anesthesia was induced with fentanyl (100 mg), propofol 1% (2.5 mg/kg), and rocuronium (1.0 mg/kg). It was maintained with remifentanil and propofol 1% (5 mg/kg/h). Remifentanil was titrated from 0.05 to 1 mg/kg/min to obtain a bispectral index ranging between 40 and 60, which was monitored by a dedicated device.
Rescue antiemetics were given immediately when the patients showed vomiting or required rescue medications. The first-line rescue antiemetic was metoclopramide (6 mg), which was followed by palonosetron (0.05 mg) as a second-line treatment. Postoperative analgesia during the first 24 h after surgery was provided for all patients using a standardized drug treatment protocol that included intravenous administration of ketorolac (60 mg) and nefopam hydrochloride (100 mg). If additional pain control was necessary, tramadol hydrochloride (intravenous injection, TRAMADOL HCL INJ 50 mg/L, Shin Poong Pharm, Seoul, South Korea) was administered no more than once every 4–5 h, and the maximum dose did not exceed 400 mg/day.
Outcome The primary endpoint was the incidence of PONV and the severity of PONV. To assess nausea and vomiting, patients were monitored for 2 hours (h) in the post anesthesia control unit and interviewed in the general ward postoperatively at 6 and 24 h. PONV during the periods between 0 and 2 h, 2 and 4 h, 4 and 8 h, 8 and 12 h, 12 and 24 h, and 24 and 36 h after anesthesia were evaluated by a blinded researcher. Any episode of nausea or vomiting up to 36 h following surgery was considered an occurrence of PONV. The severity of PONV was recorded using a Visual Analog Scale (nausea- VAS; where 0 cm = no nausea and 10 cm = worst possible nausea). The secondary endpoints were the length of stay, pain, and postoperative in-hospital morbidity (wound infection, reoperation, bleeding, prolonged intubation, laryngeal nerve lesion, urinary retention, urinary tract infection, pulmonary infection, or gastrointestinal hemorrhage).
Statistical analysis The outcomes were evaluated using either a Student’s t-test or Wilcoxon rank sum test for continuous data or a χ2 test or Fisher’s exact test for categorical data. The severity of PONV over time between the groups was analyzed by repeated-measures analysis of variance (ANOVA). The level of significance for all statistical tests was set at 0.05.