Ultrasound-guided pecto-intercostal fascial plane block for chronic postoperative pain after cardiac surgery via median sternotomy: study protocol for a randomized controlled trial

Abstract

Background

Median sternotomy As per our journal style, article titles should not include capitalised letters unless these are proper nouns/acronyms. We have therefore used the article title "Ultrasound-guided Pecto-intercostal fascial plane block for chronic postoperative pain after cardiac surgery via median sternotomy: study protocol for a randomized controlled trial" as opposed to "Ultrasound-guided Pecto-intercostal Fascial Plane Block for Chronic Postoperative Pain after Cardiac Surgery via Median Sternotomy: study protocol for a randomized controlled trial". Please check if this is correct.remains the preferred incision technique for cardiac surgery. Consequently, postoperative pain is a prevalent complication following such procedures, potentially leading to delayed recovery and a diminished quality of life for patients. The parasternal intercostal fascial plane block (PIFPB) is a superficial regional anesthetic technique targeting the interfacial plane between the pectoralis major and internal intercostal muscles. Currently, no randomized controlled trials have evaluated the impact of PIFPB on chronic pain following cardiac surgery via median sternotomy. To address this knowledge gap, we conducted a prospective, randomized, double-blind, placebo-controlled trial specifically designed to evaluate the effect of preoperative PIFPB on chronic pain incidence in patients undergoing median sternotomy for cardiac surgery.

Methods

This study protocol has been approved by the Ethics Review Committee of Zhongda Hospital, Southeast University. We plan to enroll 304 adult patients scheduled for cardiac surgery via median sternotomy under general anesthesia. Participants will be randomly allocated to one of two groups: the PIFPB group will receive a single injection of 40 ml of 0.375% ropivacaine hydrochloride administered, while the control group will receive an equivalent volume of 0.9% saline placebo. The primary outcome is the incidence of chronic pain at 3 months post-surgery.

Discussion

This is a novel randomized controlled trial designed to evaluate the impact of preoperative ultrasound-guided single parasternal intercostal fascia plane block on the incidence of chronic post-surgical pain (CPSP) in patients undergoing cardiac surgery via median sternotomy. The study will comprehensively describe the severity of postoperative acute and chronic pain, as well as associated clinical outcomes, in this patient population. Our findings may provide a foundation for optimizing analgesic strategies in cardiac surgery via median thoracotomy, further elucidate the role of regional anesthesia in postoperative chronic pain development, and ultimately improve postoperative quality of life for these patients.

Trial registration

The trial protocol was prospectively registered with the China Clinical Trial Registry on June 16, 2025, (trial identifier: ChiCTR2500104378).

Administrative information

Title {1}	Ultrasound-guided Pecto-intercostal Fascial Plane Block for Chronic Postoperative Pain after Cardiac Surgery via Median Sternotomy: study protocol for a randomized controlled trial
Trial registration {2a and 2b}	The trial protocol was prospectively registered with the China Clinical Trial Registry (http://www.chictr.org.cn) on June 16, 2025, (trial identifier: ChiCTR2500104378)
Protocol version {3}	Protocol Version 02, dated March 8, 2025
Funding {4}	Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Construction Funds (Grant No.YKK24267)
Author details {5a}	Juan Yao1, Fangming Shen1, Yajing Chen1, Wenlan Cai1, Xinjian Lu1, Zhen Wang1, Bin Li1, Jue Xie1, Xiaoxiang Tan1, Jie Sun* 1Department of Anesthesiology & Key Laboratory of Clinical Science and Research, Zhongda Hospital, Southeast University, No. 87 Dingjiaqiao, Nanjing City 210,009, Jiangsu Province, China E-mail address: Juan Yao: yaojuanmazui@163.com; Jie Sun: dgsunjie@hotmail.com * Correspondence to: Jie Sun Roles and responsibilities: Juan Yao and Jie Sun designed the study; Juan Yao authored the manuscript; data analysis was conducted by Fangming Shen and Yajing Chen; Jue Xie and Xiao-Xiang Tan contributed to the study execution; Wenlan Cai and Xinjian Lu gathered the data; and Zhen Wang and Bin Li edited the manuscript. The manuscript will be reviewed by all the authors
Name and contact information for the trial sponsor {5b}	Jie Sun, Department of Anesthesiology & Key Laboratory of Clinical Science and Research, Zhongda Hospital, Southeast University, No. 87 Dingjiaqiao, Nanjing City 210,009, Jiangsu Province, China. E-mail: dgsunjie@hotmail.com
Role of sponsor {5c}	This study represents an experiment initiated by researchers, with Jie Sun serving as the primary initiator and being actively engaged in its planning and design. The research design, data collection, data analysis, data interpretation, manuscript preparation, and publication decisions are conducted independently of the funding agency

Introduction

Background and rationale {6a}

The global annual volume of open-heart surgeries has surpassed 2 million cases [1]. Owing to advancements in surgical and anesthetic techniques, postoperative mortality following cardiac surgery has markedly declined. Consequently, current research efforts are increasingly directed toward minimizing postoperative complications and enhancing patients’ quality of life. The median sternotomy continues to be the preferred surgical approach for cardiac procedures. Postoperative pain is a frequently encountered complication, with studies indicating that between 10 and 50% of patients experience persistent incisional pain following cardiac surgery. Notably, at least one-third of these cases involve moderate to severe pain, which significantly impairs patients’ quality of life [2–4]. Chronic post-surgical pain (CPSP), as defined by the International Association for the Study of Pain, refers to pain persisting for a minimum of three months after surgery, after excluding other potential causes [5]. Approximately 37% of patients report persistent pain at six months post-cardiac surgery, and 17% continue to experience such symptoms beyond two years. Recent studies have reported a higher incidence of CPSP within the first six months following thoracotomy compared to earlier findings [6]. The precise etiology of CPSP remains incompletely understood; however, a plausible mechanism involves the release of inflammatory mediators in response to tissue injury at the surgical site. Furthermore, inadequate management of acute postoperative pain and the presence of persistent pain within the first 30 days post-surgery are recognized as critical contributors to the development of chronic pain lasting from six months to two years after sternotomy [7]. Evidence from prior research also suggests that effective management of acute pain may reduce both the incidence and severity of CPSP [8].

CPSP following cardiac surgery is a prevalent issue that can lead to various long-term adverse effects in patients, such as reduced functional capacity in activities of daily living, mental health disorders, diminished quality of life, increased healthcare costs, a higher risk of adverse cardiovascular events, and elevated mortality rates [9]. Therefore, effective management of postoperative pain in patients undergoing cardiac surgery via median sternotomy is of critical importance in mitigating these complications, particularly in reducing postoperative morbidity and mortality.

Currently, with the advancement of multimodal analgesia and enhanced recovery after surgery (ERAS) concepts, nerve block techniques are considered a relatively effective solution. The efficacy of thoracic epidural analgesia and thoracic paravertebral block techniques for perioperative analgesia following cardiac surgery has been substantiated [10]. However, the application of thoracic epidural techniques by anesthesiologists for perioperative analgesia in cardiac surgery is limited due to the unique requirements of cardiopulmonary bypass, which necessitates heparinization, and the potential risk of spinal cord hematoma resulting from blood dilution [11]. The transversus thoracic muscle plane block (TTMPB) was initially introduced by Ueshima et al. in 2015. In a cadaveric study, they demonstrated that local anesthetics administered between the internal intercostal muscles and the transverse thoracic muscles could effectively target the T2-T6 intercostal nerves. This study serves as a preliminary investigation into the efficacy of TTMPB for managing sternotomy pain [12]. Clinical trials have demonstrated that TTMPB exhibits significant analgesic effects in patients undergoing mastectomy, cardiac device implantation, internal fixation of sternum fractures, and those experiencing chronic sternum pain. Evidence indicates that TTMPB can extend analgesic duration by over 48 h [13–15]. Although several randomized controlled trials have investigated the application of TTMPB in cardiac surgery, the findings have been inconsistent [16–18]. Numerous studies have reported that TTMPB is effective in minimizing hemodynamic disturbances during median sternotomy, reducing the incidence of postoperative cognitive dysfunction, alleviating pain during postoperative rest and physical activity, decreasing opioid consumption, shortening ICU stays, and lowering the incidence of nausea and vomiting [19–21]. The TTMPB procedure involves the injection of local anesthetics into the fascial plane situated deeper between the internal intercostal muscles and the transverse thoracic muscles. It is important to note that the deep surface of the transverse thoracic muscles is adjacent to the pleura, while the superficial surface is associated with the internal thoracic arteries and veins. Furthermore, distinguishing the transverse thoracic muscles from the internal intercostal muscles can be challenging, leading to potential operational difficulties and risks. Incorrect procedures may result in complications such as hematoma, pneumothorax, and systemic local anesthetic toxicity. The deeper anatomical positioning, variability, and thinner structure of the transverse pectoralis muscle contribute to the increased technical complexity of performing a TTMPB. To mitigate these operational risks and challenges without compromising clinical efficacy, some researchers have proposed an enhanced technique known as the pecto-intercostal fascial plane block (PIFPB). This approach involves administering the anesthetic within the fascial plane adjacent to the sternum, beneath the pectoralis major muscle, and above the internal intercostal muscles. Previous studies have indicated that there is no significant difference in morphine consumption or pain scores within 24 h post-sternotomy in cardiac surgery patients when comparing the modified PIFPB to the TTMPB, thereby demonstrating that both methods provide comparable analgesic effects for managing acute pain [22].

Emerging evidence suggests that regional block techniques may reduce the incidence and severity of CPSP following thoracotomies, hysterectomies, cesarean sections, and mastectomies; however, these findings remain a subject of ongoing debate [23]. Notably, the prevalence of chronic pain after thoracotomy is substantial, with reported estimates ranging from 30 to 40% [8, 24, 25]. Given the clinical burden associated with post-thoracotomy pain, the implementation of a multimodal analgesic strategy incorporating nerve blockade warrants further investigation as a means to effectively alleviate both acute and CPSP, thereby promoting enhanced recovery trajectories in surgical patients. Accumulating data indicate that the PIFPB may serve as a valuable component of perioperative pain management in individuals undergoing median sternotomy for cardiac procedures. Nevertheless, the extent to which PIFPB may specifically contribute to the prevention of chronic pain following sternotomy remains inadequately elucidated. To address this critical knowledge gap, we conducted a single-center, double-blind, randomized controlled trial aimed at evaluating the effect of preoperative PIFPB on the incidence of CPSP in patients undergoing median sternotomy cardiac surgery.

Objectives {7}

The principal objective of this study is to assess the impact of preoperative single-shot PIFPB on the incidence of chronic pain three months following cardiac surgery performed via median thoracotomy, in comparison to a placebo.

Trial design {8}

To explore this issue, we designed a single-center, prospective, randomized, controlled, double-blind study, aiming to hypothesize that preoperative PIFPB could reduce the incidence of postoperative CPSP in patients undergoing cardiac surgery via median sternotomy.

Methods: participants, interventions and outcomes

Study setting {9}

The study is scheduled to be conducted on patients undergoing elective cardiac surgery via median sternotomy at Zhongda Hospital, Southeast University, Nanjing, China.

Eligibility criteria {10}

The criteria for participant inclusion and exclusion in this study are delineated as follows:

Inclusion criteria: 1. Patients scheduled for an initial median thoracotomy procedure. 2. Age 18 years or older. 3. Classified as American Society of Anesthesiologists (ASA) grade I-IV. 4. Patients who have received approval from the hospital's ethics committee and have provided informed consent, either personally or through a family member.

Exclusion criteria:

① Patients who have been evaluated as having relative or absolute contraindications for nerve block puncture: such as allergy to local anesthetic drugs, puncture site infection, hematoma, etc. ② Acute or chronic pain already existed before the operation; ③ Preoperative history of opioid abuse; ④ Patients with severe systemic diseases (kidney failure, liver failure, pneumonia); ⑤ Patients who have preoperative mental system problems or communication difficulties and refuse to participate; ⑥ Patients who have undergone secondary surgery or died after the operation.

Who will take informed consent? {26a}

The principal investigator will evaluate eligible patients for participation in this study according to the established inclusion and exclusion criteria. Members of the research team will present the study protocol to the participants. Should the patient express a willingness to participate, a written informed consent form will be provided for the patient's signature.

Additional consent provisions for collection and use of participant data and biological specimens {26b}

This is not applicable, as no biological specimens from the participants will be collected throughout the duration of the trial.

Interventions

Explanation for the choice of comparators {6b}

The novel PIFPB technique requires evaluation for its analgesic efficacy in cardiac surgery. The selection of appropriate interventions will yield significant insights into the effects of this regional technique on pain management. In the event that both subject groups report postoperative pain with a numeric rating scale (NRS) score of 4 or higher, clinicians are authorized to administer supplementary analgesic medications, such as non-steroidal anti-inflammatory drugs or opioids, to manage the pain.

Intervention description {11a}

The preoperative, intraoperative and postoperative management of the patients will all follow the institution's standardized cardiac anesthesia protocol. Anesthesia induction will be achieved with midazolam at a dosage of 0.05–0.1 mg/kg, fentanyl at 2–5 μg/kg, cyclopofol at 0.2–0.4 mg/kg, and rocuronium at 0.6 mg/kg. Following tracheal intubation, mechanical ventilation will be administered to maintain end-tidal carbon dioxide levels between 35–40 mmHg. For anesthesia maintenance, cycloprofol was administered at 0.4–2.4 mg/kg/h, cisatracurium at 0.1–0.2 mg/kg/h, and sevoflurane at 0.5 minimum alveolar concentration. Sevoflurane administration will be ceased during cardiopulmonary bypass. The patient's state index (PSI) will be maintained within the range of 25–50. Fentanyl was administered via continuous infusion at a rate of 2–5 μg/kg/h, with dosage adjustments made as necessary to maintain heart rate and mean arterial pressure within ± 20% of baseline values. Supplemental doses of fentanyl (0.01–0.02 μg/kg) were administered as needed to mitigate hemodynamic responses during thoracotomy. No local anesthetics were utilized during the procedure. Postoperatively, the administration of sevoflurane and fentanyl was discontinued, and cyclopofol along with necessary vasoactive agents were administered. All patients were subsequently transferred safely to the ICU for further management. Following the surgical procedure, both patient cohorts received sufentanil for patient-controlled intravenous analgesia (PCIA). A solution was prepared by combining 150 μg of sufentanil and 8 mg of tropisetron with normal saline to achieve a total volume of 100 ml. The background infusion rate for PCIA was set at 1 ml/h, with each patient-controlled analgesia (PCA) dose being 1.2 ml, and a lockout interval of 15 min was implemented. In instances where PCA proved ineffective, clinicians were permitted to administer alternative analgesic medications, including non-steroidal anti-inflammatory drugs or other opioids. The timing of the initial administration of supplementary analgesics and any opioid-related side effects were meticulously documented.

Following induction of general anesthesia and endotracheal intubation, patients will be positioned supine. The injection site will undergo standard aseptic preparation. In the PIFPB group, a linear ultrasound transducer will be positioned parasternal at the level of the 4th–5th intercostal spaces, approximately 2–3 cm lateral to the midline. The imaging depth will be optimized to 2–3 cm. Under real-time ultrasound guidance, 20 ml of 0.375% ropivacaine will be injected bilaterally into the fascial plane between the pectoralis major and internal intercostal muscles (total 40 ml).

The control group will receive bilateral injections of 40 ml 0.9% normal saline using identical technique and volume per side.

Criteria for discontinuing or modifying allocated interventions {11b}

Research interventions have been delineated. Upon implementation of an intervention, modifications are not permissible. The investigator will withdraw the participant from the study if any of the following conditions arise during the experiment:

1. Participants may request to terminate their involvement in the intervention during the course of the experiment.

2. Subjects may be voluntarily discharged due to exacerbated perioperative conditions or the necessity of a subsequent surgical procedure.

3. The presence of an unacceptable risk of a serious adverse event.

Strategies to improve adherence to interventions {11c}

Before the commencement of the study, the cardiac anesthesiologists responsible for the surgeries will be provided with detailed information regarding the study protocol and will undergo training in perioperative management to enhance adherence to the protocol. In addition to the intervention, participants will receive standard care during their hospital stay. The investigators will endeavor to maintain close follow-up and effective communication with the participants throughout the duration of the study. Prior to data collection, participants will receive a comprehensive study timeline and advance notice regarding forthcoming follow-up visits. Any inquiries or concerns from participants related to the study or clinical treatment will be addressed with patience and in detail.

Relevant concomitant care permitted or prohibited during the trial {11d}

During the procedure, the application of any additional regional blocks or local analgesics is strictly prohibited.

Provisions for post-trial care {30}

The study will observe a limited number of common adverse reactions. Potential complications include infection at the puncture site and damage to adjacent tissues. To date, no adverse events associated with this nerve block technique have been documented in the literature. We employ a modified version of the transverse thoracic muscle plane block, known as the thoracic intercostal fascia plane block. This technique involves the injection within the fascia plane adjacent to the sternum, beneath the pectoralis major muscle and above the internal intercostal muscles, enhancing the safety of the procedure. Participants are advised to promptly report any discomfort, changes in their condition, or unexpected events during the study period to their physician, regardless of whether these are related to the study. The physician will assess the situation and provide appropriate medical care.

Outcomes {12}

We will collect perioperative data on patients, including demographics, medical and lifestyle histories, medication use, ASA physical status classification, and details of surgery and anesthesia. The primary outcome is the incidence of chronic pain three months post-surgery, assessed using the NRS. A blinded researcher will conduct telephone follow-ups to record NRS scores, where 0 indicates no pain, 1–3 mild pain, 4–6 moderate pain, and 7–10 severe pain.

The secondary observation indicators encompass the following: (1) the intensity of acute postoperative pain, as measured by the NRS scores for surgical incision at intervals of 24, 48, 72, and 96 h, as well as 5 days post-surgery, both at rest and during coughing; (2) the incidence of chronic pain at 6 and 12 months postoperatively, assessed via telephone follow-up, employing the same methods and standards as those utilized at 3 months post-surgery; and (3) the impact of chronic pain on quality of life at 3, 6, and 12 months post-surgery. This included an evaluation of the nature of postoperative pain and the presence of anxiety and depression, conducted through telephone follow-up. The Chinese version of the Brief Pain Inventory (BPI) is employed to assess the impact of chronic pain on patients' quality of life. The nature of postoperative pain is evaluated using the Short-form McGill Pain Questionnaire-2 (SF-MPQ-2), which is designed to assess both chronic neuropathic and non-neuropathic pain. The Hospital Anxiety and Depression Scale (HADS) is employed to assess postoperative anxiety and depression. (4) Patient satisfaction with analgesia is evaluated using a numerical scoring scale ranging from 0 to 10, where 0 indicated extreme dissatisfaction and 10 indicated complete satisfaction, 48 h following surgery. (5) The quality of postoperative recovery is assessed using the Chinese version of the QoR-15 scale 48 h after the operation. (6) The total consumption of opioids within five days post-operation is recorded. (7) Adverse events associated with thoracic intercostal fascia plane block are monitored. (8) The occurrence of nausea, vomiting, dizziness, pruritus, and hypersomnia in patients within 48 h following surgery is recorded. (9) Data are collected on the time of the first administration of rescue analgesic, the time of tracheal tube removal, the length of stay in the ICU, the total length of hospital stay, number of compressions for PCA, and the duration of drainage tube placement. Prior to data collection, the meanings of the BPI Scale, HADS, the SF-MPQ-2, the QoR-15 scale, and the NRS score are thoroughly explained to the patients.

Participant timeline {13}

The timeline for enrollment, interventions, and assessments for the study participants is detailed in Table 1, while the study flowchart is depicted in Fig. 1.

Table 1.

Example template of recommended content for the schedule of enrolment, interventions, and assessments

Study period	Enrollment	Surgery		Post surgey
Time point	Day-1	Pre-anesth	Pre-op	24 h	48 h	72 h	96 h	D5	M3	M6	M12
Inclusion/exclusion criteria	X
Sign informed consent	X
Allocation		X
Intervention:
PIFPB			X
Control			X
Assessments:
Baseline characteristics			X
NRS for pain				X	X	X	X	X	X	X	X
BPI for the impact of chronic pain									X	X	X
SF-MPQ-2 for neuropathic pain									X	X	X
HADS for anxiety and depression									X	X	X
Satisfaction					X
QoR-15					X
Opioid drugs consumption								X
Adverse events								X
Nausea, vomiting, dizziness, pruritus and hypersomnia					X
Rescue analgesics				X	X	X	X	X
Extubation time				X
Length of stay in ICU					X
Total length of hospital stay
Number of compressions for PCA					X
Duration of drainage tube

Fig. 1.

PIFPB, Pecto-intercostal fascial plane block; PCA, Patient-controlled analgesia; NRS, Numeric rating scale; BPI, Brief Pain Inventory; SF-MPQ-2, Short-form McGill Pain Questionnaire-2; HADS, Hospital Anxiety and Depression Scale; QoR-15, Quality of Recovery-15 questionnaire

Sample size {14}

Based on previous literature reports, it has been observed that the incidence of chronic pain within 3 months after median sternotomy for cardiac surgery is approximately 30% to 40% [8, 24, 25]. We assume that the incidence of chronic pain in the patients of this study is approximately 35% 3 months after median thoracotomy, and the incidence of chronic pain in the PIFPB group will be reduced to 20%. We used the PASS software to calculate the required sample size, with an alpha error of 0.05 and a power of 80% (double proportional test, two-sided t-test). It was concluded that each group included 136 patients, totaling 272. Considering a 10% loss to follow-up rate, this study will recruit 152 patients in each group, totaling 304 patients.

Recruitment {15}

On the day preceding the surgical procedure, the researcher will visit the ward to present the patient with comprehensive details regarding the research protocol. This include an explanation of the benefits of participation, potential adverse reactions and risks, the rights of the patient to participate or withdraw from the study, and the guidelines concerning the use of personal information and data. Subsequently, the informed consent form will be signed.

Assignment of interventions: allocation

Sequence generation {16a}

The study will employ block randomization with randomly varying block sizes (4, or 6) to ensure balanced group allocation while minimizing predictability. A study statistician not involved in participant enrollment will generate the allocation sequence using the R statistical software (version 4.2.2, R Foundation for Statistical Computing, Vienna, Austria), ensuring reproducible randomization.The randomization will be stratified by key prognostic factors, including age (18 ~ 60 vs. ≥ 60 years) and surgical approach (on-pump vs off-pump procedure), to enhance between-group comparability. The allocation sequence will be concealed until assignment by using sequentially numbered, opaque, sealed envelopes (SNOSE).

After obtaining informed consent, research assistants (who are blinded to the block size and sequence generation) will open the next sequentially numbered envelope to reveal the participant’s group assignment (1:1 ratio: experimental group vs. control group). The allocation process will be documented to ensure transparency.

Concealment mechanism {16b}

The grouping situation will be sealed in sequentially numbered opaque envelopes and locked in the cabinet of the research office. Random information will not be published until the envelope is opened.

Implementation {16c}

On the day of the operation, a nurse anesthetist not involved in the study will open the envelopes sequentially according to the recruitment order to determine the allocation results. Based on the group assignment, either 40 ml of 0.375% ropivacaine or 40 ml of 0.9% normal saline will be prepared and placed into two syringes that are identical in appearance and labeling, marked only with the patient number. These will be handed over to the research assistant for delivery to the operating room. The nerve block will be administered by the same experienced anesthesiologist, who is blinded to the group assignments, to ensure the quality and consistency of the block. Consequently, the subjects, anesthesiologists, nurses, evaluators of observational indicators, and statistical analysts all remained blinded to the specific group allocations.

Assignment of interventions: blinding

Who will be blinded {17a}

All participants will remain blinded to group assignments. The anesthesiologists responsible for administering the block and those providing intraoperative care will also be blinded. Additionally, a blinded investigator will be tasked with collecting perioperative data. The cardiac surgeons, along with the medical staff in the cardiac ICU and the ward, will be kept unaware of the group allocations.

Procedure for unblinding if needed {17b}

In the event of a serious adverse event or emergency related to surgery, the principal investigator may unblind.

Data collection and management

Plans for assessment and collection of outcomes {18a}

On the day preceding the surgical procedure, the principal investigator will visit the ward to perform a pre-anesthesia evaluation of the patients to assess their eligibility for inclusion in the study. Baseline data will be documented on the Case Report Form (CRF), and informed consent will be obtained. The intraoperative management of patients will be carried out by anesthesiologists who are blinded to the group assignments and research hypotheses. Intraoperative data will be recorded by a designated researcher present in the operating room. Postoperative data collection and analysis will be conducted by a separate researcher who is also blinded to the group assignments. All data will be systematically entered into the CRF. Additionally, to mitigate assessment bias, all assessors participating in the trial will receive training prior to the commencement of the study.

Plans to promote participant retention and complete follow-up {18b}

Prior to data collection, researchers will furnish participants with comprehensive information about the study and the requirements for follow-up, ensuring effective communication throughout the process. We will address any questions or concerns the participants may have regarding the research and clinical treatment with patience and meticulous attention.

Data management {19}

The pertinent data from all participants will initially be documented on paper Case Report Forms (CRFs), with the stipulation that the original entries remain unaltered. These paper-based CRFs will be submitted to the data management team for transcription into electronic files in Excel format by a designated researcher not involved in the study. The accuracy and integrity of data entry will be reviewed by the Data Monitoring Committee (DMC) during periodic safety/efficacy assessments. The DMC, whose members have no conflicts of interest related to this study, will ensure compliance with “Clinical Operating Procedures” and regulatory requirements. All research data will be preserved for five years following the study’s conclusion.

Confidentiality {27}

All electronic data and paper documents will be securely retained within the hospital's information system and a locked file storage cabinet, respectively, for a minimum duration of five years following the study's conclusion. Access to the study dataset will be restricted exclusively to the investigators. To ensure confidentiality, participants' personal identifying information will be substituted with study identification codes.

Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}

This is not applicable, as there are no relevant plans due to the absence of biological specimens in the current trial.

Statistical methods

Statistical methods for primary and secondary outcomes {20a}

All the data of this experiment will be statistically described and analyzed using SPSS 25.0 software (SPSS, Chicago, Illinois, USA). The Kolmogorov–Smirnov test is used to determine whether continuous data follow a normal distribution. The measurement data conforming to the normal distribution are expressed as mean ± standard deviation (x ± s), and the two-independent sample t-test is used for comparison between groups. Measurement data with non-normal distribution will be expressed as median (M) and interquartile range (IQR), and the Mann–Whitney U test is used for comparison between groups. The confidence interval of the median difference between groups will be estimated using the Hodges-Lehmann method. Count data will be expressed as n (%), and comparisons between groups will be conducted using chi-square test or Fisher's exact probability method.

The primary outcome will be analyzed using intention-to-treat Analysis. For cases with missing primary outcomes, Complete Case Analysis (CC) will be used. At the same time, a sensitivity analysis will be conducted, and the worst-case interpolation method will be adopted to verify whether the main results were robust.

Interim analyses {21b}

This trial is anticipated to have a high safety profile, with no significant safety concerns expected to arise. Furthermore, the recruitment process is projected to be completed expeditiously. Consequently, there is no intention to perform an interim analysis. Nonetheless, should any safety issues be identified, we reserve the right to suspend the research prematurely.

Methods for additional analyses (e.g. subgroup analyses) {20b}

The pre-defined subgroups include gender (male or female), age (≤ 60 years old, > 60 years old), BMI (< 25, ≥ 25 kg/m²), educational level (below high school, above high school), operation duration (< 120 min, ≥ 120 min), and operation type (valve, bypass, valve combined with bypass). For repeated measurement data (such as NRS scores at different time points), the linear mixed-effects model (LMM) will be used for analysis. Test level: α = 0.05, P < 0.05 is considered statistically significant.

Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}

This study employs an intention-to-treat design. We will provide a detailed account of the intervention measures and highlight the critical aspects of collaboration with patients during the pre-anesthesia assessment and informed consent process. It is anticipated that only a limited number of participants may deviate from the research protocol. In instances of data loss, various imputation methods will be utilized to enhance the dataset, and the impact of these methods will be assessed through sensitivity analysis.

Plans to give access to the full protocol, participant level-data and statistical code {31c}

This trial is initiated by the principal investigator. Access to the complete protocol, participant-level data, and statistical code for research purposes will be considered upon submission of a reasonable written request and subsequent authorization from the principal investigator.

Oversight and monitoring

Composition of the coordinating centre and trial steering committee {5d}

This study is designed as a single-center trial, and as such, it will not involve a coordinating center or a trial steering committee. The principal investigator will convene weekly meetings with the study team to evaluate and discuss the study's progress and to report any serious incidents to the Ethics Committee. Additionally, there will be no involvement from stakeholders or the private sector.

Composition of the data monitoring committee, its role and reporting structure {21a}

The Data Monitoring Committee (DMC) will consist of clinical experts, ethicists, and statisticians who are independent of the research team. The committee operates autonomously from the sponsor and is free from any conflicts of interest. The DMC’s responsibilities encompass a thorough oversight of the trial’s safety, efficacy, and quality. Its primary activities include developing the charter, convening meetings, conducting evaluations, and ultimately presenting their recommendations to the trial sponsor or steering committee. The DMC’s fundamental mission is to safeguard the rights and safety of the participants and to ensure the trial data’s scientific integrity and reliability.

Adverse event reporting and harms {22}

We will evaluate each adverse event based on its nature (expected versus unexpected), severity (serious versus non-serious), and relevance to the intervention (relevant versus irrelevant). Serious, unexpected, and intervention-related adverse events will be promptly reported to the Ethics Committee. The principal investigator will conduct regular reviews of all adverse events and will convene meetings to discuss the assessment of adverse events as necessary. All adverse events occurring during this trial will be documented in the CRF and reported to the principal investigator. Participants will be monitored until they are deemed to have fully recovered or have overcome the adverse event.

Frequency and plans for auditing trial conduct {23}

An anesthesia nurse not involved in this trial will function as an independent reviewer throughout the trial period. Independent reviews are scheduled to occur biweekly or following the recruitment of every 10 new participants after their postoperative follow-up. Any errors identified will be documented and reported to the principal investigator. The review process will encompass the evaluation of CRF content, identification of missing or duplicate data, verification of data accuracy, and examination of informed consent documentation.

Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}

The Ethics Committee has evaluated and approved the study protocol. Any modifications to the protocol are prohibited without prior authorization from the Ethics Committee. Should an amendment be required, it must first be assessed by the principal investigator. Subsequently, a formal written request for the amendment should be submitted to the Ethics Committee for additional review and approval.

Dissemination plans {31a}

The findings of this study are slated for dissemination through presentations at academic conferences and publication in peer-reviewed journals. Upon the study's completion, the results and conclusions will be communicated to all participants. The principal investigator will serve as the lead author. Investigators who have participated in the study for a minimum of three months and have made substantial contributions to the manuscript drafting will be included as co-authors.

Discussion

Currently, median sternotomy is the predominant incision technique employed in cardiac surgery. Postoperative pain is a prevalent complication associated with cardiac surgical procedures, with approximately 10% to 50% of patients experiencing chronic pain, which significantly impairs their quality of life [2–4]. There is a well-documented correlation between acute postoperative pain and the subsequent development of chronic incision pain across various surgical modalities. Consequently, the implementation of regional anesthesia techniques, which can inhibit the transmission of nociceptive nerve impulses, may mitigate central sensitization and prevent the transition from acute to chronic pain. Despite the established association between the intensity of acute postoperative pain and the likelihood of chronic pain development, the precise causal relationship between these phenomena remains to be elucidated.

In prior research, PIFPB has been effectively utilized for acute pain management following median thoracotomy in cardiac surgery, with its safety thoroughly established [22]. Despite the confirmed efficacy of bilateral PIFPB in median thoracotomy during adult cardiac surgery, the influence of this technique on CPSP in patients undergoing median thoracotomy is not yet well understood. To investigate this matter, we have designed a single-center, prospective, randomized, controlled, double-blind study. This study aims to test the hypothesis that preoperative PIFPB could reduce the incidence of CPSP in patients undergoing median sternotomy for cardiac surgery. Furthermore, we monitored postoperative pain and opioids consumption in patients from one to five days following surgery, along with adverse reactions, satisfaction with postoperative analgesia, quality of postoperative recovery, the characteristics of chronic pain, and changes in anxiety and depression at three, six, and twelve months post-operation. We anticipate that our findings will elucidate the impact of PIFPB on CPSP following cardiac surgery and its potential mechanisms, thereby contributing to the optimization of analgesic strategies for this specific patient population.

In summary, this trial aims to elucidate the effect of preoperative ultrasound-guided intercostal fascial plane block on the development of CPSP following median sternotomy in patients undergoing cardiac surgery. The findings are expected to provide a robust scientific foundation for its application in postoperative pain management in this clinical context. A 12-month follow-up period constitutes a key innovative aspect of the study. Nevertheless, several limitations should be acknowledged. First, deeply sedated patients experiencing delayed extubation post-surgery may be unable to complete the NRS assessments at the designated time points, potentially introducing follow-up bias. Second, the block procedure is performed after anesthesia induction, and the sensory dermatomal spread following the block is not assessed. Lastly, the optimal concentration and volume of local anesthetics required for PIFPB were not investigated, highlighting the necessity for further research in this area.

Trial status

The trial has been officially registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn) under the registration number ChiCTR2500104378. It is slated to commence in January 1, 2025 and conclude in December 31, 2027. Patient recruitment is anticipated to begin in August 8, 2025 and is expected to be completed by December 31, 2026. The current protocol is version 02, dated March 8, 2025.

Abbreviations

PIFPB

Pecto-intercostal fascial plane block

TTMPB

Transversus Thoracic Muscle Plane Block

CPSP

Chronic post-surgical pain

ERAS

Enhanced Recovery After Surgery

ASA

American Society of Anesthesiology

PSI

The patient's state index

NRS

Numeric rating scale

BPI

Brief Pain Inventory

SF-MPQ-2

Short-form McGill Pain Questionnaire-2

HADS

The Hospital Anxiety and Depression Scale

QoR-15

Quality of Recovery-15 questionnaire

ICU

Intensive care unit

CRF

Case record form

PCA

Patient-controlled analgesia

PCIA

Patient-controlled intravenous analgesia

Authors’ contributions {31b}

Juan Yao and Jie Sun designed the study; Juan Yao authored the manuscript; data analysis was conducted by Fangming Shen and Yajing Chen; Jue Xie and Xiao-Xiang Tan contributed to the study execution; Wenlan Cai and Xinjian Lu gathered the data; and Zhen Wang and Bin Li edited the manuscript. The manuscript will be reviewed by all the authors.

Funding {4}

Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Construction Funds (Grant No.YKK24267). The funding organization did not exert any influence over the design, implementation, analysis, or publication of the trial.

Data availability {29}

The data collected throughout the study can be obtained from the corresponding author upon submission of a reasonable request. For inquiries, please email dgsunjie@hotmail.com.

Declarations

Ethics approval and consent to participate {24}

The Ethics Committee of Zhongda Hospital, affiliated with Southeast University, granted approval for this study on March 19, 2025, under approval number No.2025ZDSYLL053-P01. The research team will secure written informed consent from each participant prior to their involvement in the study.

Consent for publication {32}

All researchers participating in this trial provided their consent for publication.

Competing interests {28}

The authors disclose that they have no competing interest.