Intertransverse Process Block to Improve Quality of Recovery and Pain Management in Adult Cardiac Surgical Patients

The Chinese University of Hong Kong

Status: Not yet enrolling

Conditions: Chronic Postsurgical Pain

Treatments: Procedure: Sham block; Procedure: Intertransverse process block

Study type: Interventional

Funder types: Other

Identifiers

NCT06946290

ITPB - chronic pain

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the efficacy of intertransverse process block (ITPB) in improving quality of recovery and potentially preventing chronic postsurgical pain (CPSP) 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 quality of recovery after cardiac surgery, and its analgesic efficacy in the immediate postoperative period
2. 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.
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

Full 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 efficacy of ITPB in quality of recovery after cardiac surgery, and the potential to mitigate both acute and chronic postsurgical pain in cardiac surgical patients.

Study Design:

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

Randomization and Concealment Randomisation will be performed in 1:1 ratio using the REDCap randomisation module in the study database, allocating participants to either the ITPB (intervention) or control group in randomly permuted blocks of size four. Sequentially numbered, coded, sealed, opaque envelopes, each containing the group assignment of either interventional or control are then prepared by a third party who takes no further part in the study. The ITPB syringes will be prepared under strict aseptic conditions by a nurse not involved in the study, with blind labelling. The surgical team, blinded to group allocation, will perform standardised surgical procedures. Anaesthetists and nurses responsible for data collection in both ICU and wards are also blinded to the treatment allocation.

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, 20 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.

Statistics and sample size calculation Sample size was calculated using G*Power software version 3.1.9.3 (Kiel University, Kiel, Germany), based on the QoR-15 score at 24 hours postoperatively the primary outcome. The minimum clinically important difference (MCID) for the QoR-15 score is eight points, and the typical standard deviation (SD) ranges from 10 to 16. Assuming a two-sided type I error of 0.05, type II error of 0.2, and a population variance of 144 (SD = 12), a sample size of 36 per group is required. Allowing for a 20% dropout rate, a total of 96 patients (48 patients per group) will provide 80% power to detect a mean difference of ≥8 points in the QoR-15 score at 24 hours between the two groups.

All outcomes will be analysed and reported on an intention-to-treat basis, with patients analysed according to their randomised group regardless of protocol adherence. A secondary per protocol analysis will be conducted for patients who do not adhere fully to the study protocol. Given the repeated measures of pain scores over time, which are correlated, Generalised Estimating Equation (GEE) models will be used to assess the time effects of postoperative analgesia. Categorical data will be reported as counts and percentages. Continuous variables will be presented as mean (standard deviation) or median (interquartile range), depending on normality assessed using the Shapiro-Wilk's test. Between-group comparison will be conducted using the independent sample t-test for parametric data and Mann-Whitney U test for nonparametric data. Categorical variables will be compared using the Chi-square test. Data analyses will be performed using SPSS 27.0 (IBM Corp, Armonk, NY), and GEE modelling will be conducted using Stata V.14 (Statam College Station, Texas, USA), with a Gaussian distribution, identify-link function, exchangeable correlation structure, and robust standard errors. A P-value of <0.05 will be considered statistically significant, without adjusting for multiple comparisons.

Enrollment: 96 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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96 participants in 2 patient groups

ITPB group

Experimental group

Description:

Intertransverse process block is performed on patients with injection of 20ml 0.25% levobupivacaine at the retro-SCTL space after a test bolus of 1-2ml 0.9% normal saline. The same procedure is repeated on the other side with same volume of study medication.

Treatment:

Procedure: Intertransverse process block

Sham block group

Sham Comparator group

Description:

Sham intertransverse process block is performed on patients with injection of 20ml placebo at the retro-SCTL space after a test bolus of 1-2ml 0.9% normal saline. The same procedure is repeated on the other side with same volume of study medication.

Treatment:

Procedure: Sham block