Study setting {9}
The study will be conducted at the Second Affiliated Hospital of Army Medical University, PLA. Participant enrollment began in February 2023. The protocol adheres to the principles outlined in the Declaration of Helsinki and follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT).
Eligibility criteria {10}
Inclusion criteria
Patients will undergo a face-to-face screening 1 day prior to surgery based on the following eligibility criteria:
(1) Adult patients aged40–70 years
(2) ASA II ~ IV classification
(3) Patients planning to undergo transapical TAVI under general anesthesia
(4) Patients expressing willingness to participate in this study and signed informed consent.
Exclusion criteria
Patients meeting any of the following criteria will be excluded from the study:
(1) Allergy to Las
(2) History of mental illness or taking psychotropic drugs
(3) Severe abnormalities in coagulation function
(4) Long-term use of analgesics or sedatives
(5) History of drug abuse, alcohol, or opioid abuse
(6) Recent acute pain or chronic pain
(7) Postoperative mechanical ventilation ≥ 24 hours
(8) Decline to participate in the study
(9) Participants retain the right to withdraw from the study at their discretion for any reason or if researchers determine their inclusion is inappropriate.
Who will take informed consent? {26a}
Enrollment of eligible participants will be supervised by a designated member of the research team. Following a comprehensive oral explanation of the study, including its potential benefits and risks, patients or their legally authorized representative will be asked to sign the informed consent form approved by the institutional review committee. Participants and their legal authorized representatives will be informed that participation is entirely voluntary, and they have the right to withdraw from the trial at any time.
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Not applicable. We will not utilize the date and biological specimens of participants for ancillary studies.
Interventions
Explanation for the choice of comparators {6b}
Currently, there is limited research on the analgesic effectiveness of SAPB in transapical TAVI. Establishing a direct correlation between SAPB and the quality of recovery following transapical TAVI surgery requires more prospective data for validation. This study aims to investigate the impact of SAPB on the postoperative early recovery quality and analgesic efficacy in patients undergoing transapical TAVI surgery, and to solve the contradiction between the patients who can't tolerate large doses of opioids and the huge hemodynamic changes due to pain and subsequently affecting postoperative recovery quality. The study seeks to optimize the multi-mode analgesia and ERAS for this operation, with the goal of enhancing the postoperative recovery quality and optimizing the medical resources utilization.
Currently, other studies on regional block have used 0.9% saline as control, making it ethically feasible to have a blank control group in this study.
Intervention description {11a}
Ultrasound-guided SAPB will be conducted after induction of general anesthesia. Patient will be positioned supine with the upper limb abducted, and the ultrasonic probe will be located in the 5th intercostal space along the left axillary line. The probe’s direction will be adjusted to identify the tissue structures such as latissimus dorsi, pectoralis major, pectoralis minor and serratus anterior. Using an in-plane technique, a 22-G nerve block needle will be advanced to the surface of the serratus anterior muscle and aspirated to ensure no blood and gas. Subsequently, 2 ml of local anesthetic mixture (0.4% ropivacaine + 10 mg dexamethasone) will be slowly injected. The injection will be performed while observing the spread of the anesthetic between the fascia layers, as indicated by a hypoechoic area on ultrasound and additional mixture will be slowly injected. The control group will be given 40ml normal saline.
Criteria for discontinuing or modifying allocated interventions {11b}
Withdrawal criteria are as the follows:
(1) Patient or legal representative requests to withdraw from the study
(2) Changes in the surgical procedure may occur during surgery
(3) The investigator may decide to terminate the trial due to other unforeseen reasons.
Strategies to improve adherence to interventions {11c}
All SAPB procedures, surgeries, and assessments will be consistently performed by the same anesthesiologist, surgeon, and assessor, respectively. Randomization and monitoring processes will be conducted by independent researchers to ensure fairness and protocol adherence. The principal investigator will be responsible for all aspects of the recruitment process and any amendment to the study. All the experiments will strictly adhere to the research plan, ensuring reliability and effectiveness of our results.
Relevant concomitant care permitted or prohibited during the trial {11d}
Patients will be prepared in accordance with cardiopulmonary bypass, and standard monitoring will be established, including electrocardiograph (ECG), non-invasive blood pressure (NIBP), pulse oxygen saturation (SpO2), body temperature (T), bispectral index (BIS) and cerebral oxygen, with an external automatic defibrillation patch attached. Radial artery and right internal jugular vein catheterization, under local anesthesia, will facilitate monitoring of invasive arteriovenous pressure. General anesthesia induction will involve midazolam (0.03 ~ 0.08 mg/kg), etomidate (0.2 ~ 0.6 mg/kg), rocuronium (0.6 ~ 0.9 mg/kg), sufentanil (0.3 ~ 0.4 µg/kg). Tracheal tubes will be inserted when the BIS value decreased to 40 ~ 50, initiating mechanical ventilation with a tidal volume of 6 to 8 mL/kg, respiratory rate of 12 to 15/min, and a 1:1 air-oxygen mixture, maintaining ETCO2 between 35 and 45 mmHg.
The anesthesia will be maintained with propofol (4 ~ 6 mg/kg/h), remifentanil (0.08 ~ 0.3 ug/kg/min), and sevoflurane (1 ~ 2 vol%). Heart rate and mean arterial pressure will be maintained within ± 20% of baseline, except during rapid ventricular pacing. Blood potassium level will be maintained between 4.5 ~ 5.5 mmol/L and BIS will be kept between 40 ~ 60 throughout operation.
Patients will be delivered to cardiac surgery intensive care unit postoperatively for standardized monitoring and management. A postoperative patient-controlled intravenous analgesia (PCIA) regimen will be established as part of a multimodal pain regimen, with sufentanil (2.5 µg/ml, limit dose 200 ug) combined with dexmetomidine (3 ug/ml, limit dose 200 ug) and tropisetron 5 mg. The PCIA pump will be programmed for a 2mL bolus with a lockout interval of 15 min and a basal infusion of 4 mL/h. Rescue analgesia will include paracetamol and tramadol hydrochloride tablets (one tablet, p.o) for VAS > 4 at rest, and 1mg of hydromorphone intravenously for severe pain (VAS > 7). Patients will be educated on PCIA pump usage.
Provisions for post-trial care {30}
All study participants will receive standard care. We will closely monitor them throughout the postoperative period to promptly identify any potential complications and implement intervention measures as necessary.
Outcomes {12}
Primary and secondary outcomes
The primary outcome will assess the quality of recovery at 24 h and 48 h, measured using the QoR-40 scale.
The secondary outcomes include:
(1) VAS pain scores: assessment at rest and during coughing at 6 h, 12 h, 24 h, and 48 h post-surgery
(2) Frequency of PCA utilization: evaluation at 24 h and 48 h following surgery
(3) Opioid consumption: quantification at 24 h and 48 h post-surgery
(4) Time and frequency of rescue analgesia and severe pain: analysis at 24 h and 48 h after surgery
(5) Incidence of nausea and vomiting: determination at 48 h post-surgery, along with the dosage of antiemetic drugs.
Participant timeline {13}
The schedule of enrollment, interventions, and assessments is shown in Fig. 2.
| | Enrolment | Allocation | Post-allocation |
| TIMEPOINT** | -1 day | Surgery day | 6 h after surgery | 12 h after surgery | 24 h after surgery | 48 h after surgery |
| Enrollment | | | | | | |
| Eligibility screen | X | | | | | |
| Informed consent | X | | | | | |
| Allocation | | X | | | | |
| INTERVENTIONS: | | | | | | |
| SAPB group | | X | | | | |
| Control group | | X | | | | |
| ASSESSMENTS: | | | | | | |
| QOR-40 | X | | | | X | X |
| VAS pain scores | | | X | X | X | X |
| Times of PCA | | | | | X | X |
| Opioid consumption | | | | | X | X |
| Rescue analgesia | | | | | X | X |
| Severe pain | | | | | | X |
| Nausea | | | | | | X |
| Vomit | | | | | | X |
| Dosage of antiemetic drugs | | | | | | X |
Figure 2 Participant timeline. SAPB: Serratus Anterior Plane Block; QOR-40: Quality of Recovery-40 scale; PCA: patient-controlled analgesia
Sample size {14}
The sample size calculation is based on the primary outcome. According to a prior publication, where mean of group 1 was 167 and the mean of group 2 was 184, with known group standard deviations of 23 [13], a sample size of 33 for each group (66 in total) will be required to achieve a power of 80% to detect the difference at a two-side α level of 0.05, taking into account a dropout rate of 10%. Ultimately, we plan to include 35 participants in each group.
Recruitment {15}
Patients will be provided with comprehensive information about the research procedures, including potential risks, the benefits and postoperative follow-up, during pre-anesthesia clinic consultations to ensure thorough understanding and enhance patient compliance. Recruitment will be conducted at the Second Affiliated Hospital of Army Medical University, PLA.
Assignment of interventions: allocation
Sequence generation {16a}
Eligible patients will be randomly allocated to either the ultrasound-guided SAPB group or the control group at a 1:1 allocation ratio after providing
written informed consent. The randomization sequence will be generated by an independent researcher using SPSS software version 26.0 (IBM, New York, USA).
Concealment mechanism {16b}
The randomized results will be securely sealed in opaque envelopes and stored separately until the end of the study. To maintain unbiased assignment and minimize potential confounding factors, the investigators responsible for generating the random sequences will not be involved in recruitment, anesthesia administration, and outcome evaluation. Preoperative interview researchers, unaware of the random allocation number, will screen and recruit participants and completed the QOR-40 scale one day before surgery.
Implementation {16c}
As soon as the patients enters the operation room, the attending anesthesiologist will open the corresponding numbered envelope, verify the patient’s allocation and proceed to implement the corresponding anesthesia plan accordingly.
Assignment of interventions: Blinding
Who will be blinded {17a}
Due to the nature of the study, blinging of the attending anesthesiologist is not feasible. However, patients, outcome assessors, surgeons and nursing staff will remain blinded until the completion of the study analysis.
Procedure for unblinding if needed {17b}
While we do not anticipate the need for unblinding, if necessary, such as the occurrence of a research-related serious adverse event, the principal investigator or data manager will have access to the group assignment and will report any unblinding promptly.
Data collection and management
Plans for assessment and collection of outcomes {18a}
Research data for this study will be collected from electronic medical records systems or case report forms (CRFs). Preoperative date, including demographics, medical history, medication history, supplementary examinations, and pre-operative assessment, will be completed by pre-operative visitors. The anesthesiologist will record intraoperative date. The QOR-40 scale one day before surgery and postoperative outcomes assessment will be collected by a dedicated assessor. To ensure scientific rigor of our study, all researchers will be trained on how to collect, record and store date before the trial start. All information will be strictly confidential and used solely for research purpose. After data collection, it will be double-entered into Microsoft Excel system and check by two researchers. The principal investigator will conduct a thorough check for any defects in the raw date again. Participants’ personal information will be kept confidential.
Plans to promote participant retention and complete follow-up {18b}
During the preoperative visit, researchers will provide detailed explanation of the intraoperative management and postoperative follow-up process.
Data management {19}
All date will be anonymized, with CRFs abbreviated as initials, and electronic date is coded. Electronic date will be stored on a dedicated computer with double password protection, while paper CRFs will be securely stored in our research center with password-locks. All original documents will be retained for 5 years after the study is completed
Confidentiality {27}
Patients will continue to be enrolled until the required number is reached. All date will be anonymized, with CRFs abbreviated as initials, and electronic date is coded. All original documents will only be accessible to researchers with the original ID and password.
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Not applicable. No samples will be collected for this study.
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
All normally distributed continuous variables will be expressed as mean ± standard deviation and analyzed with Student’s t-test. For non-normal distributed date, the Mann-Whitney U test will be used, and results will be presented as median and interquartile interval. Categorical variables will be described with frequencies (%) and compared using the chi-square test or Fisher’s exact test. A 95% confidence interval (CI) for differences in means (for continuous outcomes) or relative risks (for categorical outcomes) will be calculated. A P-value < 0.05 will be considered statistically significant. Statistical analyses will be performed using SPSS software version 26 (IBM, New York, USA).
Interim analyses {21b}
No interim analyses will be conducted due to the small number of patients and the expected low incidence of serious adverse events.
Methods for additional analyses (e.g. subgroup analyses) {20b}
No subgroup analyses are planned.
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
The likelihood of missing values in our primary outcome is very low. If missing date occur, multiple imputation techniques will be employed to accurately estimate them.
Plans to give access to the full protocol, participant level-data and statistical code {31c}
Date sets, statistical codes, and complete protocols analyzed by the institute will be available upon reasonable request to the principal investigator. This approach ensures accuracy, repeatability and promotes further study and cooperation.
Oversight and monitoring
Composition of the coordinating centre and trial steering committee {5d}
The steering committee, composed of principal investigator, sub- investigator and two clinicians, will guided and supervise the implementation and progress of the trial. Quarterly meetings will be convened to monitor the latest developments in the trial, ensuring that the research design and interpretation of remain relevant to current clinical practice. The committee has the authority to make decisions regarding trial modifications based on specific circumstances and assumes medical responsibility for the patients involved.
Composition of the data monitoring committee, its role and reporting structure {21a}
This trial is a single-center RCT with relatively small sample size and low intervention risk, and there is no date monitoring committee established. The principal investigator will review all the summarized date, and an independent auditor with expertise will conduct monthly audit. The steering committee will monitor study development quarterly, while the ethics committee will conduct an annual follow-up review.
Adverse event reporting and harms {22}
SAPB, integrated into our multi-mode analgesia approach, will be conducted under precise visual ultrasound guidance and standardized skilled operation. Anesthesia safety will be strictly controlled by experienced anesthesiologists within the team. Any adverse effects or unpredictable complications will be diligently documented and promptly reported to the Ethics Committee as part of our annual report.
Frequency and plans for auditing trial conduct {23}
There is no Data Monitoring Committee (DMC) established for this study. Instead, an independent auditor with expertise will conduct monthly audits. Additionally, the steering committee and auditor will perform repeated audits every three months to ensure the accuracy and validity of the date. Furthermore, the ethics committee will conduct an annual follow-up review.
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}
Any modifications to the research plan (version 1.0) will be promptly communicated to the principal investigator and the research ethics committee of the second affiliated hospital of army military medical university. A revised plan will be issued following thorough examination and approval.
Dissemination plans {31a}
The study aims to optimize multi-mode analgesia and enhance ERAS for transapical TAVI, aligning with diagnosis related groups (DRG) in medical management. Results will be disseminated at relevant academic conferences and published in peer-reviewed journals. Both positive and negative findings will be reported.