Enhancing Postoperative Analgesia in Open Orthopedic Surgery Through Acupoint Catgut Embedding.

To the Editor: The acupoint catgut embedding (ACE) is a traditional external therapy originating from acupuncture therapy in China and has been widely used to treat acute and chronic diseases.[1] This single-center, randomized, single-blind prospective study aims to investigate the efficacy and safety of ACE for postoperative analgesia in the patients undergoing open orthopedic surgery. The study protocol received approvals from the Ethics Committee of the Shanghai Fourth People's Hospital (No. 2019112-001) and were registered at the Chinese Clinical Trial Registry (ChiCTR2000034008). The written informed consents were obtained from all the patients before study enrollment. The study included the patients aged 18–80 years, with an American Society of Anesthesiologists score of I or II, body mass index (BMI) between 18 kg/m2 and 30 kg/m2, and those who underwent open orthopedic surgery under general anesthesia at Shanghai Fourth People's Hospital, School of Medicine, Tongji University from June 2020 to December 2021. The surgery procedure time was more than one hour, but less than six hours. The informed consent was obtained by a researcher in the pain assessments and questionnaire surveys. The patients with central nervous system disease or mental illness, uncontrollable hypertension, diabetes mellitus, coronary heart disease or cardiac insufficiency, severe liver or kidney dysfunction, preoperative blood hemoglobin <90 g/L were excluded from the trial. The ACE contradiction treatments (such as local cutaneous injury or infection), the history of fainting during acupuncture and the history of drug or alcohol abuse or study enrollment in other clinical trials were recorded. All the patients were randomly assigned to either the acupoint embedding group (ACE group) or the false acupoint embedding group (Sham group) in a 1:1 ratio using a computer-generated blocked randomization scheme. Both the catgut embedding and acupuncture treatments at the specific acupoint were administered one hour before administration of general anesthesia by the same practitioner with > three years of clinical experience in acupuncture. The practitioner was not involved in assessing postoperative pain. In the ACE group, puncture was conducted with catgut embedding, whereas puncture was conducted without catgut embedding in the Sham group. Throughout the acupuncture procedure, the patients were masked using eye patches, and the acupoint site and surrounding areas were covered with opaque adhesives. After skin disinfection, the needle was inserted vertically into the skin with a depth of 15–20 mm. The needle core was advanced until the sensation of soreness known as "De Qi" was achieved. Once the catgut was adequately embedded in the acupoint and the patient experienced needle sensation, the needle was swiftly withdrawn from the skin. The puncture site was examined and then covered with sterilized gauze, remaining dry for 2 hours after operation. In the Sham group, the puncture was conducted without catgut embedding. Throughout the operation, the standardized anesthesia protocols were employed, and target-controlled infusion of propofol and remifentanil was used to maintain anesthesia. Remifentanil administration was halted until 15 minutes before the conclusion of the surgery, and intravenous fentanyl was administered (1 μg/kg). Following surgery, after the removal of the tracheal catheter, the assessment of the sedation-agitation scale (SAS) was conducted 5 minutes later.[2] An electronic patient-controlled analgesia (PCA) pump was employed for postoperative analgesia, delivering fentanyl as a solution of 30 μg/kg in 0.9% sodium chloride (total volume 150 mL). The PCA parameters were set as follows: 0 mL background infusion dose, 2 mL for bolus, 5 min for locked time, and 150 μg for the maximal dose per hour. The infusion pump was removed 72 h after surgery. Postoperative pain was assessed using the Numerical Rating Scale (NRS) scores.[3] If the NRS score was ≥ 4 points, a bolus infusion of fentanyl (0.4 μg/kg) was administered by the anesthesiologist or nurse in the postanesthesia care unit (PACU). If necessary, this procedure was repeated after 5 min until the NRS score reached <4 points. The patients were followed up at the specified time points (6, 12, 18, 24, 48, and 72 h after surgery) or until discharge. The adverse events, including infection, fainting during acupuncture, bleeding, pain, and nerve injury at the puncture sites, respiratory depression, excessive sedation, nausea (0 = no nausea, 1 = mild nausea, 2 = moderate nausea, 3 = severe nausea), and vomiting (0 = no vomiting, 1 = vomiting) were recorded. The primary outcome of this study was the postoperative NRS score at rest. The analysis of the primary outcome was performed in the intent-to-treat (ITT) population. A mixed-effects model was employed for the preliminary investigation to assess the differences between the Sham and ACE groups. The composite effect model estimated the least squares-means (LS-means) differences along with their 95% confidence intervals. For the missing data, the last observation carried forward (LOCF) imputation was utilized as a sensitivity analysis. A mixed-effects model was used to analyze the change in the NRS score on movement for the secondary outcome. All the statistical tests were two-sided, with a P-value <0.05 indicating the statistical significance. The SAS software (version 9.4, Cary, N.C., USA) was utilized for all the statistical analyses. A total of 160 patients were recruited from the Shanghai Fourth People's Hospital between June 2020 and December 2021 who were included in the analysis set, with 80 patients in each group [Supplementary Figure 1, https://links.lww.com/CM9/C22]. The demographic data, incision length, duration, and surgery type were not statistically significantly different between the two groups [Supplementary Table 1, https://links.lww.com/CM9/C22]. The results from the mixed-effects model indicated a statistically significant difference in the NRS scores between the ACE and Sham groups (treatment effect: t = 2.14, P = 0.03). In the ACE group, after multiple imputation(MI), the NRS scores at rest were significantly lower than those in the Sham group (P = 0.04, 0.01, 0.04, and 0.03, respectively) at 18 h, 24 h, 48 h, and 72 h after surgery [Table 1]. The primary outcome measures were employed using a mixed-effects model to control for the amount of fentanyl, showing a statistically significant difference between the two groups (P < 0.001) [Supplementary Table 2, https://links.lww.com/CM9/C22]. The LS-means differences (95% confidence interval, CI) of the NRS scores at rest between the two groups at 18, 24, 48 and 72 h after surgery were 0.42 (0.02, 0.81), 0.45 (0.09, 0.80), 0.38 (0.03, 0.73), and 0.35 (0.03, 0.67), respectively. No statistically significant differences between the groups were observed at 6 h and 12 h [Supplementary Figure 2, https://links.lww.com/CM9/C22]. Table 1 - The comparisons of NRS scores at rest/on movement between the two groups. Parameters Sham group (N = 80) ACE group (N = 80) LS-means difference P-value NRSrest 6 h 2.96 (2.67, 3.26) 2.64 (2.33, 2.94) 0.33 (–0.10, 0.75) 0.13 12 h 2.76 (2.48, 3.05) 2.43 (2.14, 2.71) 0.34 (–0.05, 0.73) 0.09 18 h 2.36 (2.06, 2.66) 1.94 (1.66, 2.23) 0.42 (0.02, 0.81) 0.04 24 h 2.00 (1.74, 2.26) 1.56 (1.29, 1.82) 0.45 (0.09, 0.80) 0.01 48 h 1.51 (1.24, 1.77) 1.13 (0.87, 1.39) 0.38 (0.03, 0.73) 0.03 72 h 1.29 (1.04, 1.54) 0.94 (0.72, 1.16) 0.35 (0.03, 0.67) 0.03 NRSmovement 6 h 4.18 (3.83, 4.54) 4.07 (3.72, 4.41) 0.12 (–0.36, 0.59) 0.62 12 h 3.96 (3.60, 4.31) 3.92 (3.57, 4.26) 0.04 (–0.44, 0.52) 0.86 18 h 3.75 (3.41, 4.08) 3.58 (3.27, 3.88) 0.17 (–0.26, 0.61) 0.43 24 h 3.57 (3.27, 3.88) 3.20 (2.94, 3.46) 0.37 (–0.01, 0.76) 0.05 48 h 3.40 (3.09, 3.71) 2.95 (2.70, 3.20) 0.44 (0.06, 0.83) 0.02 72 h 2.89 (2.65, 3.13) 2.58 (2.33, 2.83) 0.31 (–0.02, 0.63) 0.06 Data are shown as median (Q1, Q3). ACE: Acupoint catgut embedding; LS-means: Least squares means; NRS: Numerical Rating Scale. No significant differences were noted in the NRS scores on movement between the two groups (treatment effect of the mixed-effects model: t = 1.82, P = 0.07). However, in the ACE group, the NRS score on movement was significantly lower than that in the Sham group at 48 h after surgery (P = 0.02). No significant differences were observed at 6 h, 12 h, 18 h, 24 h, and 72 h after surgery between the two groups [Table 1 and Supplementary Figure 3, https://links.lww.com/CM9/C22]. The cumulative PCA fentanyl consumption at 72 h after surgery was similar between the two groups, with the ACE group requiring a median (IQR) of 468.0 (310.0–870.6) μg vs. the Sham group requiring 640.6 (349.9–911.5) μg (P = 0.07). The SAS scores during anesthesia emergence and the time needed to get out of bed after surgery were comparable between the two groups (P = 0.16 and 0.92) [Supplementary Table 3, https://links.lww.com/CM9/C22]. The adverse effects associated with ACE include injection site discomfort, local hematoma or subcutaneous hemorrhage, local infection, local pain, thread-related rejection, and an increase in body temperature. The published studies consistently affirmed the safety of ACE in clinical practice, reporting fewer adverse events across all the included articles without any associated serious adverse effects.[4] In this study, no discernible between-group differences in adverse effects, encompassing infection, fainting during acupuncture, bleeding, pain and nerve injury at the puncture sites, respiratory depression, excessive sedation, and nausea and vomiting were observed. This trial demonstrated that ACE was effective in the treatments of postoperative analgesia following open orthopedic surgery. The maximum resting NRS scores in the ACE group were significantly lower than those in the Sham group from 18 h to 72 h following surgery. No adverse effects were observed. In summary, ACE treatments were demonstrated to be effective and safe with acceptable patient compliance. It seems particularly suitable for postoperative analgesia in ambulatory surgery or day surgery settings, where safety is paramount and the postoperative pain is mild to moderate.[5] The data on postoperative pain were evaluated only within three days without a longer observation period for the ACE analgesic effect. As a single-center trial with a relatively small sample size, the analgesic effects of ACE should be further demonstrated with large randomized controlled studies with extended follow-ups, especially in the context of daytime or outpatient surgery. Funding This work was partially supported by the Major Program of the National Natural Science Foundation of China [No. 82130121 to L.X.], the second round of the three-year action plan for "strengthening and promoting Traditional Chinese Medicine" of Hongkou District [HKGYQYXM-2022-06 to L.X.], the National Natural Science Foundation of China [No. 81971042 to H.C.], and the Hongkou district key specialist construction projects (No. HKZK2020A06 to H.C). Conflicts of interest None.