Clinical trial NCT06946290: Intertransverse Process Block for Chronic Postsurgical Pain in Adult Cardiac Surgical Patients
Official title: Intertransverse Process Block for Chronic Postsurgical Pain in Adult Cardiac Surgical Patients: a Prospective Double-Blinded Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Chronic Postsurgical Pain
Keywords: ITPB
Intertransverse process block
Chronic postsurgical pain
Cardiac surgery
quality of recovery
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2025-04-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate the efficacy of intertransverse process block (ITPB) in preventing chronic postsurgical pain (CPSP) and improving pain control in adult patients undergoing elective cardiac surgery (e.g., coronary artery bypass graft \[CABG\], valve repair/replacement, or combined CABG/valve procedures).

The main questions it aims to answer are:

1. To investigate the efficacy of intertransverse process block (ITPB) on CPSP after cardiac surgery by determining the incidence of CPSP at 3 month, defined as persistent pain that was not present before surgery or that had different characteristics, and other possible causes of pain are excluded.
2. To investigate the quality of recovery after cardiac surgery, and its analgesic efficacy in the immediate postoperative period
3. To investigate the efficacy of ITPB on the incidence of CPSP at 6 month, 12 month, and the pain interference (sensory and affective components, physical activities) at 3 month, 6 month and 12 month after surgery

Detailed description: Introduction:

The cornerstone of modern pain management in cardiac surgery lies in proactively preventing the development of chronic postsurgical pain (CPSP). This paradigm shift emphasizes pre-emptive interventions to disrupt the cascade of events and central sensitization that transform acute postoperative pain into a persistent, debilitating condition. CPSP, a significant and often underestimated consequence of cardiac surgery, affects a substantial proportion of patients, with prevalence rates ranging from 28% to 56% in the years following surgery. Its impact extends beyond mere discomfort, significantly impairing daily function, reducing quality of life, and imposing a substantial economic burden on the healthcare system.

The pathophysiology of CPSP involves a complex interplay of factors, with central sensitization playing a pivotal role. This process, characterized by heightened neuronal excitability within the central nervous system, amplifies pain signals and can lead to persistent pain even after the initial injury has healed. Therefore, a crucial aspect of CPSP prevention lies in disrupting the afferent nociceptive signals transmitted from the injured tissues to the spinal cord and brain, thereby preventing the establishment and perpetuation of central sensitization.

While opioids have traditionally been the mainstay of postoperative pain management, their use is not without significant drawbacks. Opioids can have dose-dependent side effects, including respiratory depression, nausea, and constipation. Furthermore, prolonged opioid use can lead to tolerance, opioid-induced hyperalgesia, and an increased risk of chronic opioid use. Recognizing these limitations, the current emphasis in pain management is on multimodal analgesia strategies that incorporate non-opioid medications and regional anaesthesia techniques to optimize pain control while minimizing the risks associated with opioid use.

Non-steroidal anti-inflammatory drugs (NSAIDs) offer a valuable adjunct in pain management, but their use in cardiac surgery is often limited due to concerns regarding bleeding complications and potential renal impairment. Other non-opioid analgesics, such as paracetamol and gabapentinoids, have shown limited efficacy in managing the intense pain associated with sternotomy. Regional anaesthesia techniques have emerged as promising strategies for both acute pain management and potential CPSP prevention in various surgical settings. Techniques such as epidural anaesthesia and paravertebral blocks have demonstrated efficacy in reducing postoperative pain intensity and opioid requirements. However, their application in cardiac surgery presents unique challenges. Epidural anaesthesia carries the risk of neuraxial hematoma due to systemic anticoagulation and heparinization, while paravertebral blocks may be associated with complications such as pneumothorax and pleural puncture. Erector spinae plane block (ESPB) has shown inconsistent results in reducing postoperative pain and morphine consumption in cardiac surgery. Parasternal plane blocks offer advantages over neuraxial techniques but may not adequately address visceral pain.

While regional anaesthesia is crucial for managing acute postoperative pain, its impact on CPSP remains largely unknown. The potential for regional anaesthesia to reduce CPSP has been identified as one of the top research priorities in anaesthesia and perioperative care. Intertransverse process block (ITPB) is a novel and promising alternative, targeting the paravertebral space through extra- paravertebral injection within the intertransverse tissue complex, posterior to the superior costotransverse ligament (SCTL). Recent MRI studies have demonstrated consistent spread of local anaesthetic to the ipsilateral intercostal, paravertebral spaces, neural foramina, and epidural space following ITPB, suggesting potential for both somatic and visceral analgesia. It demonstrated preferential spread of LA to the epidural space and neural foramina over the ESPB, and into the thoracic paravertebral space with effective analgesia after breast and video-assisted thoracoscopic surgeries. Compared to other regional techniques in cardiac surgery, ITPB may offer a simpler and safer approach with reduced risk of pleural puncture and bleeding. Therefore, this trial will assess the analgesic efficacy of ITPB aimed at mitigating both acute and chronic postsurgical pain in cardiac surgical patients.

Study Design:

Single-centre, prospective, randomized, placebo-controlled, double-blinded trial

Randomization and Concealment Patients are randomly allocated to interventional or control group by drawing sequentially numbered, coded, sealed, opaque envelopes, each containing the group assignment of either interventional or control. The sealed envelopes for randomization will be prepared by a third party who takes no further part in the study. The ITPB syringes are prepared under strict asepsis by a nurse not involved in the study. ITPB is performed by a single anaesthesiologist who is blinded to group allocation. The primary care team, blinded to group allocation, performs surgeries using standardized technique. Anaesthesiologists and nurses blinded to group allocation recorded data intraoperatively, in the ICU, and at regular intervals in cardiac wards. Data will be recorded at 2-hour, 4-hour, 8-hour, 12-hour, 24-hour, 48-hour and 72-hour after extubation and at 1-month, 3-month, 6-month and 12 months after surgery by blinded personnel.

Anaesthesia and Interventions All patients receive standard cardiac surgery monitoring. General anaesthesia is induced with midazolam 0.01-0.05 mg/kg, fentanyl 2-5 mcg/kg, and rocuronium 0.5-1 mg/kg to facilitate intubation. Anaesthesia is maintained with sevoflurane and propofol infusion, targeting a Bispectral Index of 40-60. ITPB is performed after anaesthesia induction with the patient in lateral decubitus positioning. Intraoperative opioids (fentanyl and morphine) will be administered at the discretion of the anaesthesiologist. The postoperative analgesia protocol was identical in both study groups, including patient-controlled analgesia (PCA) morphine protocol for 72 hours after surgery, oral analgesics (paracetamol 1g every 6 hours, dihydrocodeine 30mg three times a day), and on-demand antiemetics (intravenous ondansetron 4mg every 8 hours). Rescue analgesics on top of the protocol regimen can be prescribed as needed. Upon ICU admission, propofol infusion is stopped to facilitate weaning from ventilator using Adaptive Support Ventilation (ASV), which adjusts the ventilation parameters depending on the patent's lung mechanics and effort. Pain will be assessed regularly in ICU and on the ward. Upon extubation, pain scores are assessed at 2-hour, 4-hour, 8-hour, 12-hour, 24-hour, 48-hour and 72-hour. Patients receive PCA morphine for moderate to severe pain. Nausea, vomiting and rescue antiemetics are documented.

Ultrasound Block Placement The intervention group received bilateral ITPB after GA induction, whilst sham blocks are performed in the control group. All blocks are performed by an anaesthesiologist who had previously performed ≥50 successful ITPB blocks, using Philips EPIQ ultrasound system, with a curved array transducer (C5-1), and 80mm echogenic nerve block needle (SonoTAP; PAJUNK, Germany). ITPB is performed with the patients positioned in a lateral decubitus position. The target intervertebral level (T4-5) is identified and marked in the preview ultrasound scan. The transducer is placed 2-3 cm lateral to the spinous process. Under strict asepsis, a single-level (T4-5) ultrasound-guided ITPB is performed with the in-plane insertion of the block needle from lateral to medial direction until its tip is at the medial aspect of the retro-SCTL space. After confirming the needle position by distension of the retro-SCTL space after a test bolus injection of 1-2 ml 0.9% normal saline, 25 ml 0.25% levobupivacaine or placebo is injected via the nerve block needle in small aliquots. The same procedure is repeated on the other side with the same volume of study medication. The time required to perform the block will be recorded as the time from insertion of block needle to removal from the patient after injection.

Data Collection All data is collected by research team members blinded to group assignment. Patient demographics and body mass index are recorded. Cumulated opioid consumption data and time to first morphine rescue are extracted from PCA pump. At 2-hour, 4-hour, 8-hour, 12-hour, 24-hour, 48-hour and 72-hour post-extubation, pain scores at rest and on coughing are quantified using NRS from 0 to 10. Zero represents no pain at all while 10 points represents the worst pain ever. The patients are asked to rate the overall satisfaction to pain management on a verbal analogue scale (0=worst possible, 100=best possible) at the predefined points. Any nausea and vomiting, and use of rescue antiemetics are documented. The Chinese validated QoR-15 will be completed at baseline (preoperatively) and postoperatively at 24-hour and 72-hour after extubation. The SF-MPQ- 2 and BPI will be used to evaluate the CPSP at 3-month, 6-month and 12-month after surgery.

Subjects Sample size is calculated using G\*Power software version 3.1.9.3 (Kiel University, Kiel, Germany) and based on the QoR-15 score at 24 hours after surgery, which is the primary outcome variable. The minimum clinically important difference (MCID) for the QoR-15 score at 24 hours is 8 and the typical standard deviation (SD) of QoR-15 in the postoperative period ranges between 10-16. Based on these data, for a two-sided test, assuming a type I error of 0.05 and type II error of 0.2, population variance of 144 (SD was assumed to be 12), we calculate a sample size of 36 in each group. Considering a 10% dropout rate, a total of 100 patients (50 patients in each group) will provide 90% power to detect a difference in the mean QoR-15 score ≥8 at 24 hours.

Data processing and analysis The primary analyses are performed on a modified intention-to-treat basis. Patients are analysed according to their randomized allocated groups but are excluded from the analysis if they do not adhere to the protocol after randomisation. Categorical data is reported as numbers and percentages. Continuous variables are reported as mean (standard deviation) or median (interquartile range) as appropriate after checking for normality using the Shapiro- Wilk's test. Comparison of continuous data is performed by Student's t test and by Mann- Whitney U test for non-normally distributed data. Chi-square test is used to compare groups with categorical variables. Level of significance is set at P\<0.05. SPSS 27.0 software (IBM Corp, Armonk, NY) is used for data analysis.

Numerical rating scale (NRS) pain scores measured at rest and during movement at 2-hour, 4-hour, 8-hour, 12-hour, 24-hour, 48-hour and 72-hour after extubation will be analysed using Generalized Estimating Equation (GEE) models to evaluate the analgesia time effects between groups, pain scores at rest and movement, and their interactions.

Eligibility criteria: Inclusion Criteria:

* adult patients aged 18 or older
* undergoing elective CABG, valve repair/replacement, or combined CABG/valve procedure via sternotomy

Exclusion Criteria:

* Emergency surgery
* redo surgery
* history of chronic pain or being on chronic opioids/sedatives
* renal failure with an estimated glomerular filtration rate ≤30 ml/min (calculated by Cockcroft-Gault formula)
* re-operation within 24 hours after surgery
* intraoperative use of remifentanil
* inability to provide informed consent.

Primary outcomes:
measure: Quality of recovery at 24 hours after extubation
timeFrame: 24 hours after extubation
Secondary outcomes:
measure: Numerical rating scale
timeFrame: 2-hour, 4-hour, 8-hour, 12-hour, 24-hour, 48-hour and 72-hour after extubation
measure: Patient satisfaction with pain management
timeFrame: 2-hour, 4-hour, 8-hour, 12-hour, 24-hour, 48-hour and 72-hour after extubation
measure: Postoperative morphine consumption
timeFrame: 2-hour, 4-hour, 8-hour, 12-hour, 24-hour, 48-hour and 72-hour after extubation
measure: Time for first morphine rescue
timeFrame: Up to postoperative day 3, with time of first morphine required recorded
measure: Intraoperative opioid consumption
timeFrame: Intraoperative record
measure: Duration of mechanical ventilation
timeFrame: Up to postoperative day 1, ventilation requirement will be observed with duration of ventilation required after operation recorded.
measure: Length of stay in ICU and hospital
timeFrame: Up to 1 month after surgery, length of stay in intensive care unit and hospital will be recorded
measure: Number of episodes of postoperative nausea and vomiting
timeFrame: Perioperative up to 7 days
measure: Percentage and number of patients having chronic post-surgical pain
timeFrame: 3 month, 6 month and 12 month after surgery
measure: Pain interference with SF-MPQ-2
timeFrame: 3 month after surgery
measure: Pain interference with SF-MPQ-2
timeFrame: 6 month after surgery
measure: Pain interference with SF-MPQ-2
timeFrame: 12 month after surgery
measure: Pain interference with BPI
timeFrame: 3 month after surgery
measure: Pain interference with BPI
timeFrame: 6 month after surgery
measure: Pain interference with BPI
timeFrame: 12 month after surgery
measure: Number of episodes requested antiemetics after surgery
timeFrame: Up to postoperative day 7
Other outcomes:
Locations:
Study officials:
affiliation: Hospital Authority
name: Henry Wong
role: PRINCIPAL_INVESTIGATOR
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