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Abstract
Background Patients often experience postoperative nausea and vomiting (PONV) after catheter ablation of atrial fibrillation (AF) because of the use of opioids for anaesthesia and analgesia during the procedure. Some clinical trials have demonstrated that acupuncture-assisted anaesthesia (AAA) reduces opioid consumption and prevents PONV. Although several studies have been conducted on AAA, its safety and efficacy in AF catheter ablation remain unclear due to small sample sizes and a paucity of methodologically rigorous designs. Therefore, this trial was designed to evaluate the safety and efficacy of AAA in reducing PONV and morphine hydrochloride consumption during catheter ablation.
Methods This single-centre, patient-blinded, randomised, non-penetrating sham-controlled trial will be conducted in China. A total of 100 patients will be randomly assigned to the AAA and conventional anaesthesia (CA) groups in a ratio of 1:1. The patients will receive AAA or CA plus sham acupuncture during catheter ablation and will be followed up for 30 days. The primary outcomes include the total amount of morphine hydrochloride consumed during catheter ablation and PONV within the first 24 hours after the procedure. The secondary outcomes include pain, nausea and vomiting, anxiety, patient’s ability to cope during catheter ablation, AF recurrence and quality of life, as assessed using the numeric rating scale. Adverse events will be recorded and their influence will be analysed at the end of the trial.
Discussion This study will help in evaluating the safety and efficacy of AAA applied for AF catheter ablation in reducing opioid doses during the procedure and the occurrence of PONV.
Ethics and dissemination The study has been approved by the Medical Ethics Committee of Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine. The results of the study will be published in peer-reviewed journals and presented at conferences if possible.
Trial registration number ChiCTR 2100042646; Chinese Clinical Trial Registry.
- COMPLEMENTARY MEDICINE
- Clinical trials
- CARDIOLOGY
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Strengths and limitations of this study
This is the first randomised controlled trial to evaluate the safety and efficacy of acupuncture-assisted anaesthesia applied for atrial fibrillation (AF) catheter ablation in reducing morphine hydrochloride consumption and preventing postoperative nausea and vomiting (PONV).
This study will explore a potential sedation method for patients with AF undergoing radiofrequency catheter ablation with decreased PONV.
Considering the convenience and comfort of patients and clinicians, PC6 (Neiguan) located below the elbow indicates more operability in AF catheter ablation.
In this study, blinding the acupuncturists is difficult because acupuncture requires manual intervention.
Introduction
The prevalence and incidence of atrial fibrillation (AF) are gradually increasing, with an incidence rate of 2%–4% in adults.1 Catheter ablation is the first-line treatment for patients with AF to maintain sinus rhythm and improve symptoms,2 and it has become one of the most common electrophysiological procedures worldwide. During the complex and lengthy procedure of AF ablation, patients often experience unbearable pain when ablation reaches the autonomic nerve distribution area or the oesophageal area. Therefore, anaesthesia and analgesia are required to reduce pain, avoid body movements and maintain catheter stability. In China, the most commonly used drugs in AF ablation include fentanyl, morphine3 and other opioids. However, opioids produce adverse effects, such as postoperative nausea and vomiting (PONV), respiratory depression, dependence and abuse liability.4 Using higher opioid doses is usually related to higher risks of adverse reactions, morbidity, longer recovery time and higher costs.5 6 PONV causes pain and suffering among affected patients. Although PONV is not life threatening and self limiting, it is sometimes perceived to be more undesirable than incisional pain.4 7 The use of more than one modality has gained increasing attention to achieve better anaesthetic and analgesic effects while reducing adverse effects.
Acupuncture-assisted anaesthesia (AAA) is a procedure in which anaesthetists combine acupuncture and anaesthetic techniques to enhance the sedative and analgesic effects of pharmaceuticals.8 AAA is generally considered safe, with only mild adverse events (AEs), including haematoma, bleeding and pain.9 It is an important part of multimodal non-opioid analgesia and has been applied to parturition, surgery and minimally invasive procedures.10 11 Such analgesic effects might be mediated by encephalin and endorphin following the use of AAA with electrical stimulation. Encephalin and endorphin relieve pain-related emotions by upregulating the expression of neuropeptide S and its receptor in the anterior cingulate cortex and hypothalamus.12 While the mechanism of acupuncture underlying PONV prevention has not been well elucidated, it may reduce PONV by releasing beta-endorphin or altering the transmission of serotonin.13 Clinical trials and existing reviews indicate that AAA helps reduce the consumption of anaesthetic and analgesic agents, prevent PONV and relieve anxiety during surgery.8 14 15 Although several studies have been conducted on AAA applied for catheter ablation, the safety and effectiveness of AAA in AF catheter ablation remain unclear due to small sample sizes and a paucity of methodologically rigorous designs.16–18
For these reasons, we designed a randomised controlled trial (RCT) to evaluate the safety and efficacy of AAA applied for radiofrequency catheter ablation (RFCA). The study aims to (1) determine differences in the occurrence of PONV and the consumption of opioids during AF catheter ablation between patients receiving AAA and those receiving conventional anaesthesia (CA) plus sham acupuncture and (2) examine the safety of AAA in patients during AF catheter ablation.
Methods
Study design
This single-centre, patient-blinded, analyst-blinded, randomised, non-penetrating sham-controlled trial will be conducted at a tertiary hospital in China, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine. The patients will be randomly assigned to the AAA group or the CA group in a 1:1 ratio and will be followed up for 30 days from the day of ablation. Patients in the AAA and CA groups will receive AAA and CA plus non-penetrating sham acupuncture, respectively. The trial flow diagram is presented in figure 1. The consort statement19 and Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture20 will be used as the guiding frameworks for the study design. The protocol is reported following the Standard Protocol Items for Clinical Trials (SPIRIT) guidelines21 (the SPIRIT checklist is shown in online supplemental file 1) and SPIRIT with Traditional Chinese Medicine Extension.22 The study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine (approval no. 2020-046-01) and registered at the Chinese Clinical Trial Registry.
Supplemental material
Trial flow diagram. AAA, acupuncture-assisted AF, atrial fibrillation; CA, conventional anaesthesia; PONY, postoperative nausea and vomiting.
Sample size
CA was used as a positive control. We hypothesised that the incidence of PONV in patients received AAA would be lower than that in patients received CA. The alpha level will be set at 0.05 and the 1-β level will be set at 80%. The ratio of patients in the two groups will be 1:1. According to the results of a previous study,23 the incidence of PONV was approximately 63% in the CA group and approximately 33% in the AAA group, and 40 patients should be enrolled in each group. Assuming a loss-to-follow-up rate of 20%, 100 patients (50 in the AAA group and 50 in the CA group) should be enrolled in this study. The sample size was calculated using Power Analysis & Sample Size (V.15.0).
Recruitment
Patients diagnosed with paroxysmal AF during their visit to the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from August 2022 to July 2023 and scheduled to undergo AF catheter ablation in this hospital will be recruited in this RCT. The potential patients will be referred to cardiologists and screened by dedicated examiners according to the inclusion and exclusion criteria. A research assistant will obtain written informed consent from the patients who meet the inclusion criteria. The included patients will be randomly assigned to the AAA or CA group(online supplemental file 2). The schedule of enrollment, intervention and assessments is detailed in table 1.
Supplemental material
Study schedule
Patients
Patients with paroxysmal AF will be diagnosed and managed according to the 2020 European Society of Cardiology Guidelines.24 Paroxysmal AF is defined as AF that terminates spontaneously or with intervention within 7 days of onset.
The inclusion criteria are as follows: (1) patients diagnosed with paroxysmal AF and already scheduled for AF catheter ablation within the next 2 weeks, (2) those with American Society of Anesthesiologists physical status of I–II, (3) those aged between 18 and 75 years (men or women) and (4) those who provided written informed consent to participate in the trial.
The exclusion criteria are as follows: (1) patients with severe coagulation disorders and a tendency of spontaneous bleeding, (2) pregnant or lactating patients, (3) patients allergic to morphine hydrochloride, (4) patients with a severe psychiatric disease or cognitive impairment, (5) patients who are unable to understand the trial and provide responses about the outcome measurement, (6) patients who had received acupuncture treatment within a month, (7) patients with severe lung, liver or kidney disease or other serious primary diseases and (8) patients who cannot receive acupuncture.
Randomisation and blinding
A random sequence will be generated by an independent statistician using the R statistical package, and the randomised cards will be sealed in ordered envelopes. After completion of the screening process and baseline assessment, the patients will be randomly assigned to the AAA or CA group in a 1:1 ratio according to the random numbers in opaque envelopes. The acupuncturist who will perform the treatment will know the group allocation 2 hours before catheter ablation; the envelopes will not be opened before that time. The patients will not be informed of their group and will be instructed to wear an eye mask during catheter ablation. The principal investigator, data analysts and statisticians will remain blinded.
Ablation procedure
Senior physicians who have at least 10 years of experience and have completed more than 100 RFCA procedures will perform ablations in this trial. Patients with CHA2DS2-VASc scores ≥3, either women or men, will be administered warfarin or novel oral anticoagulants for at least 3 weeks before RFCA. All enrolled patients will receive lidocaine injections for local anaesthesia before the RFCA procedure. Transesophageal echocardiography will be performed on the day of the RFCA procedure or 1 day before RFCA administration to rule out left atrial thrombosis. All patients will undergo pulmonary vein isolation (PVI). The selection of the type of ablation catheter, settings of power and irrigation and the use of three-dimensional mapping systems will be determined by the physician performing the RFCA procedure. Complete entrance and exit block of all pulmonary vein antra in PVI will be considered as the endpoint.
Following transseptal puncture, the patients will be given half of the standard dose of intravenous morphine hydrochloride (0.005 mg/kg). The anaesthesiologist will add a dose of morphine hydrochloride and administer injections when the patients report the pain or show significant limb movement. Morphine hydrochloride injections (Shenyang First Pharmaceutical Factory, Shenyang, China) will be used in this study. The heart rhythm, blood pressure, ECG and oxygen saturation will be monitored during the procedure to ensure patient safety and prompt detection of anomalies. The patients will remain conscious under partial sedation throughout the procedure. Electrical cardioversion will be performed if the patient remains in a state of AF after PVI. In addition, oxygen saturation and mean arterial pressure will be recorded at the time when the patient enters the operating room, at the beginning of the procedure, at the time of ablation, and at the end of the procedure. The operation time of the entire RFCA procedure will also be recorded.
Interventions
Training will be imparted to trial examiners, assessors and acupuncturists by the principal investigator (HJ) before the formal implementation to ensure the quality of this trial. This training will cover the screening criteria and electroacupuncture (EA) operation during the ablation procedure.25 Registered acupuncturists who have at least 3 years of experience in practicing acupuncture will perform all acupuncture operations. They will be particularly trained in the standardised operating procedure of EA, which includes the timing of acupuncture during the ablation procedure, accurate positioning of acupoints, depth of needling and so on. Detailed information of the standardised operation will be compiled and provided to the acupuncturist for reference.
The AAA group
The acupuncture protocol is based on previous clinical studies and case reports of acupuncture anaesthesia.9 16 During the ablation procedure, the patients will be placed in the supine position and will be asked to expose their left upper arm and wear an eye mask. Before the ablation procedure and local anaesthesia, the upper limb will be massaged along the pericardium and lung meridians for 5 min. After routine disinfection, the patients will receive stimulation at Neiguan (PC 6) with disposable acupuncture needles (0.30×40 mm, Huatuo Brand; Suzhou Medical Appliance, Suzhou, Jiangsu, China). Acupoints will be selected based on previous clinical studies. According to the National Standard of People’s Republic of China, 2006 (GB/T 12 346–2006), Neiguan (PC 6) is located in the anterior aspect of the forearm, which is between the tendons of the palmaris longus and the flexor carpi radialis and two cun proximal to the palmar wrist crease. Acupuncture needles will be inserted to a depth of 30–40 mm at an angle of 90°. A reinforcing–reducing technique, which includes lifting, thrusting, twisting and rotating the needles moderately, will be performed manually to achieve needling sensations (deqi sensation). Then, the needles will be connected to an EA apparatus (type GB6805-2, Huayi Medical Instrument, China), with a continuous wave frequency of 15 Hz and comfortable current intensity. AAA will be used throughout the operation. The diagram of the operation of AAA group has been shown in online supplemental file 3. At the end, the acupuncturist will switch off the EA apparatus and remove the needles using dry sterilised cotton balls by pressing the needles on the skin area to avoid bleeding.
Supplemental material
The CA group
Patients in the CA group will receive CA with non-penetrating sham acupuncture. The settings of the CA group will be similar to those of the AAA group. The patients in the CA group will also be asked to expose their left upper arm and wear an eye mask. The tip of blunt-tipped needles will touch the area 1.5 cun lateral and posterior to PC6 (Neiguan) without penetrating the skin.26 This sham acupuncture device, called the Streitberger placebo needle, has been broadly used and validated.27 The EA apparatus will be placed besides the patient and will be switched on. However, the electrodes will not be connected to the needles.
Postablation management
All patients will receive a routine medication regimen after the RFCA procedure. The medication regimen includes anticoagulants (continued for at least 8 weeks after RFCA), antiarrhythmic drugs (continued for 3 months after RFCA) and proton pump inhibitors (continued for 4 weeks after RFCA). Patients who experience AF recurrence and those with recurrent AF will be allowed to restart or resume AAA or undergo another ablation. In addition, data on concomitant medication after ablation, including name, duration and dose, will be recorded.
Study withdrawal
The patients can cancel their consent for any reason without harm or penalty in any way and at any time, even during the AF ablation procedure. If a patient withdraws consent during the AF ablation procedure, all acupuncture procedures would be immediately stopped or cancelled according to their intention. The researchers may remove the participant from the study at any time for the following reasons: (1) the acupuncturists or physicians did not follow the study procedures, (2) for the benefits of the patients and (3) the physicians believe that it is not safe for the patient to continue the study. Withdrawal reasons and process details will be recorded.
Outcome measures
The primary outcomes are the presence of PONV within the first 24 hours after the procedure. The secondary outcomes include the total amount of morphine hydrochloride consumed, pain, anxiety, participant’s ability to cope during and after the RFCA procedure, overall recovery, AF recurrence and quality of life, as assessed using the numeric rating scale (NRS).
Primary outcome measurement
Presence of PONV within the 24 hour
PONV is defined as at least one episode of nausea or vomiting within 24 hour after leaving the operating room. The patients will be asked whether they experienced PONV during this period, and the proportion of patients who experience PONV will be calculated at the end of the study.
Key secondary outcome measurement
Total consumption amount of morphine hydrochloride
The difference in the total amount of intravenous morphine hydrochloride consumed during the procedure is one of the primary outcome measures. The total amount of morphine hydrochloride consumed will be recorded immediately after the procedure and will be checked by the anaesthetist.
Other secondary outcome measurements
Number of push injections of morphine hydrochloride
The number of push injections of morphine hydrochloride during RFCA will also be recorded by the assessor.
Pain, nausea and vomiting, anxiety and patient’s ability to cope during the procedure
Immediately after the procedure, the patients will be asked to rate how much pain, anxiety and nausea they experienced and their ability to cope during the procedure. These outcomes will be measured using the NRS, which is a commonly used scale to grade pain degree. A score of 0 on NRS indicates no pain and a score of 10 indicates the worst possible pain. The NRS will also be used to measure nausea, anxiety levels and patient’s ability to cope during the procedure. Regarding nausea and anxiety levels, a score of 0 indicates absence of nausea and anxiety and a score of 10 indicates the highest nausea and anxiety levels. Furthermore, regarding the patient’s ability to cope during the procedure, a score of 0 indicates ‘no ability to cope’ and a score of 10 indicates ‘completely able to cope’. The NRS scores for pain, nausea and vomiting and patient’s ability to cope will be assessed at 6 hours, 24 hours and 48 hours after the procedure.
Overall recovery
The overall recovery will be rated on a 7-point Likert scale, which ranges from ‘completely recovered from catheter ablation’ to ‘worse than ever’. The scale details are shown in online supplemental file 4 . The patients will be asked to rate their recovery experience on the scale at 6 hours, 24 hours and 48 hours after the procedure.
Supplemental material
AF recurrence
All patients will be followed up for 30 days after discharge via phone calls or outpatient visits, and postoperative recurrence will be evaluated based on ECG or ambulatory ECG results.
Quality of life
The quality of life will be assessed using the Atrial Fibrillation Effect and Quality of Life Scale (AFEQT) at the 1-month follow-up.28 A Chinese translated version of AFEQT will be used in this study.29 AFEQT consists of 20 items, which are evaluated by four dimensions (measure patients’ symptoms, daily activities, treatment concern and satisfaction). All items will be rated on a 7-point Likert scale. The total raw scores of the first three dimensions will be transformed into a scale of 0–100, and a higher score indicates a better quality of life.
Safety assessment
Possible AEs include broken needles, local haematoma, abscess, palpitations, dizziness, headache and any other symptoms after acupuncture treatment. Any AEs during the study will be recorded by the researchers. The heart rate, blood pressure and respiratory rate will be recorded at the time when AEs occur during the procedure. The details of AEs will be reported in a case report form (CRF). If any severe AE occurs during the procedure, the acupuncturist will stop the EA or sham acupuncture immediately. Serious AEs will be reported within 48 hours to the principal investigator and the ethics committee. In the event of an unexpectedly high AE rate, a decision may be made by the steering committee to unblind, pause or stop the trial at any time, as necessary. At the end of the trial, independent clinical researchers will judge the degree of severity (low, medium and high) and the relationship between AEs and acupuncture (unrelated, probably related and related). The occurrence rate of AEs in the two groups will be calculated and compared.
Blinding assessment
After the RFCA procedure, the patients will be asked to guess which group they have been assigned to evaluate the blinding success.
Data management and quality control
In addition to the aforementioned training for intervention-related personnel, we will train all researchers in data recording, CRF filling and data management. We will hold regular meetings to discuss the difficulties arising from the trial to obtain appropriate solutions. The patients’ information collected in this study will not be publicly available and will only be reviewed by the researchers. To ensure data security, two independent inspectors will review each original CRF every month and write a data security report after each review. The Data Monitoring Committee of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine will periodically monitor the recruitment and screening of patients, data collection and entry and the monitoring of AEs to ensure that the trial is conducted according to the approved protocol.
Statistical analyses
An independent statistician blinded to group assignment will perform all statistical analyses using Statistical Package for the Social Sciences, V.25.0. The analyses will be based on the intention-to-treat principle and include data from any patients who dropped out of the trial. Data will be presented as means with SD, medians and ranges or medians with SD, as appropriate. All demographic and baseline characteristics of the patients will be analysed using descriptive statistics. The homogeneity of demographic characteristics and study variables between the two groups will be identified. The primary outcomes, total amount of morphine hydrochloride consumed and the incidence of PONV will be determined using independent samples t test or Wilcoxon rank-sum test and χ2 test. The area under the curve of the NRS scores will be calculated using the trapezoidal method. The secondary outcomes and incidence of AEs will be compared between the two groups using χ2 test, t test or Wilcoxon rank-sum test. All reported p values will be two-sided, and p values of <0.05 will be used to denote statistical significance.
All data in the main statistical analysis will be collected within 24 hours after the RFCA procedure and by the 30-day follow-up. If data cannot be collected, the time and reason for missing information will be recorded and the assumed missing data mechanism will be analysed. For these missing data, a multiple imputation adjustment approach will be used. After the main analysis, sensitivity analysis will be performed for various data sets to assess the impact of missing data on the results.
Patient and public involvement
Patients and the public will not be involved in design of this study.
Discussion
The anaesthetic and analgesic effects of opioids in AF catheter ablation remain to be improved, particularly in terms of reducing the consumption of anaesthetic and analgesic agents and the occurrence of AEs. We chose to study AAA applied to AF catheter ablation because it can potentially provide an analgesic effect similar to that of opioids, with reduced anaesthetic drug use and fewer AEs, according to evidence from existing clinical trials.
This study will be the first RCT to evaluate the safety of AAA applied for AF catheter ablation and its efficacy to reduce the consumption of morphine hydrochloride and the occurrence of PONV. If this study shows that AAA is effective and safe in AF catheter ablation, its potential indication could be explored as a sedation method for patients with AF undergoing RFCA. It could provode a better RFCA experience with less PONV for these patients. Since AAA reduces the opioid dose for anaesthesia and lowers the incidence of AEs, it is considered a cost-effective procedure. The lower incidence of PONV is expected to reduce the use of rescue antiemetics and overall expenditure.
For this clinical trial protocol, we selected EA at the PC6 (Neiguan) acupoint to achieve AAA. In previous studies, the acupoint selection methods and techniques used to stimulate acupoints applied to AAA were not the same in each study. PC6 (Neiguan) is the most frequently used point in AAA, and its analgesic efficacy and ability to reduce PONV have been widely proven.11 14 Considering the convenience and the comfort of patients and clinicians, PC6 (Neiguan) located below the elbow is also suitable in AF catheter ablation. Furthermore, studies have shown that electrical stimulation provides better analgesia.30 This is a major reason why we chose EA.
This study has several limitations and challenges. First, the number of morphine hydrochloride injections is controlled by the anesthesiologist. After the standard initial injection, the number will be increased or decreased according to the pain experienced by the patient. Because this control is artificial, there may be deviations in the injection volume, leading to additional bias. We will analyse pain during the procedure using NRS to explore the influence of potential deviations on the primary outcomes. Second, blinding the acupuncturists is difficult because acupuncture requires manual intervention. Furthermore, it is not easy to blind patients during acupuncture. The patients who had received acupuncture treatment within a month will be excluded because these individuals are more likely to notice whether they have received sham acupuncture. For the same purpose, all patients will be required to wear an eye mask during ablation. Third, there may be some difficulties in patient recruitment; we will recruit more patients from other new clinical centres, if necessary.
Ethics statements
Patient consent for publication
Acknowledgments
The authors would like to thank all the members in group for their support and help.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors HJ, QW and XZ conceived the study. YJ and ZH provided practical suggestions on the design of the study during its development. YJ and QM completed the table, figure and supplements. XZ drafted the manuscript, while YD, WD and MZ and other authors critically revised it.
Funding The study is supported by the Qilu Dragon Tiger Fighting Analgesia Acupuncture with Chinese Medicine Characteristics (20214515) and National Natural Science Foundation of China (81973695). The funder played no role in the research.
Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.