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Abstract
Introduction This study aims to determine whether paravertebral block (PVB) provides better postoperative analgesia, lower incidence of complications and faster recovery compared with local anaesthetic wound infiltration for school-aged children undergoing cardiac surgery with cardiopulmonary bypass via thoracotomy.
Method and analysis This is a single-centre, randomised controlled trial. We will enrol 100 children aged 6–14 years with atrial or ventricular septal defects scheduled for thoracotomy cardiac surgery with cardiopulmonary bypass. The patients will be randomly assigned to the PVB group and the control group in a ratio of 1:1. After the surgery, we will conduct unilateral PVB with ropivacaine for patients in the PVB group, and local anaesthetic wound infiltration for patients in the control group. We will use the double-dummy design to ensure blinding. The patients will not be administered analgesics after returning to the PICU(paediatric intensive care unit). Their bedside nurse will monitor their pain condition. When the Faces Pain Scale-Revised (FPS-R) Pain Score is ≥4, sufentanil infusion will be started. The primary outcome will be total opioid consumption within 24 hours after surgery. Secondary outcomes will be (1) FPS-R Scores at 6 hours, 12 hours, 18 hours and 24 hours after surgery; (2) The rate of opioid treatment for remedial analgesia; (3) The first time of FPS-R Score is ≥4 postoperatively. Exploratory outcomes will be: (1) Length of postoperative mechanical ventilation, ICU stay and hospital stay; (2) The rate of postoperative nausea and vomiting and respiratory depression 24 hours after surgery.
Ethics and dissemination This study was approved by the Ethics Committee of the Chinese Academy of Medical Sciences, Fuwai Hospital (No 2023–2135) and PUMC. Written informed consent will be obtained from each patient or their legal representatives before enrolment. The results of this trial will be published in an international peer-reviewed scientific journal.
Trial registration number Chinese Clinical Trial Registry (ChiCTR2400081773) Clinical Trial（NCT06312904）
- Anaesthesia in cardiology
- Paediatric anaesthesia
- Pain management
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STRENGTHS AND LIMITATIONS OF THIS STUDY
This is a randomised controlled trial that aims to determine whether postoperative paravertebral block provides better postoperative analgesia and leads to a lower incidence of complications and a faster recovery process compared with local anaesthetic wound infiltration in school-aged children undergoing thoracotomy cardiac surgery with cardiopulmonary bypass.
This trial will use a double-dummy design to enable the anaesthesiologist to be blinded.
We will use the Faces Pain Scale-Revised Score to evaluate postoperative pain, which is the most appropriate and accurate tool to evaluate pain for school-aged children.
The patient population and surgical types studied in this trial have not been studied before and are most suitable for enhanced recovery after surgery in cardiac surgery.
This is a single-centre study; therefore, the generalisability may be limited.
Introduction
Postoperative pain after cardiac surgery is severe, and adequate postoperative analgesia is important for fast recovery.1 2 The traditional postoperative analgesia for cardiac surgery is mainly based on opioids.3 4 However, the use of large doses of opioids can lead to delayed postoperative recovery.5 6 In recent years, the promotion and application of enhanced recovery after surgery (ERAS) have led to an overall improvement in the quality of care.7 8 ERAS emphasises postoperative multimodal analgesia to reduce opioid use. Regional anaesthesia including neuraxial techniques, fascial plane blocks and paravertebral block (PVB) are essential components of postoperative multimodal analgesia.
However, there are risks associated with analgesia after cardiac surgery. Cardiac surgery requires systemic blood heparinisation, which despite neutralisation with protamine, can leave patients susceptible to serious complications such as epidural haematoma than other types of surgeries. Therefore, regional nerve block techniques such as PVB have gradually gained popularity in recent years. PVB is also associated with complications such as vascular puncture (3.8%), pleural puncture (1.1%) and pneumothorax (0.5%).9 However, compared with epidural block, PVB may be technically easier to perform than thoracic epidural, and may be associated with a lower risk of epidural haematoma, hypotension and urinary retention.10–12 PVB involves injecting anaesthetics into the paravertebral space. Injection of local anaesthetics near the intervertebral foramina, where the spinal nerves emerge, produces a segmental, ipsilateral blockade of the somatic and sympathetic nerves in the thorax or abdomen, depending on the block levels. PVB has been widely used in thoracic and breast surgery for perioperative analgesia and has been shown to be both safe and effective.13 14
There are several prospective studies on the application of PVB in adult cardiac surgery.15–17 These studies have shown that PVB has the same postoperative analgesia effect as an epidural anaesthesia has, but is associated with lower complication rates.16–18
To date, the evidence of using PVB in paediatric cardiac surgery is scarce, and we found only two published prospective trials on this topic. El-Morsy et al conducted a randomised trial that enrolled 60 paediatric patients aged 1–24 months undergoing thoracotomy cardiac surgery. The authors concluded that both thoracic PVB and thoracic epidural block resulted in comparable postoperative pain scores and pulmonary function and that PVB was associated with a significantly lower failure rate and fewer side effects.19 A recently published randomised controlled trial compared PVB with parent-and/or-nurse-controlled intravenous analgesia (PNCA) in paediatric patients undergoing median sternotomy cardiac surgery. They enrolled 180 patients aged 1 month to 3 years and found that a combination of bilateral single-dose PVB and PNCA pain management was superior to PNCA pain management alone and contributed to a rapid recovery process.20
Crucial elements of the ERAS strategy in paediatric patients undergoing cardiac surgery include: fast-track cardiac anaesthesia, minimally invasive cardiac surgery (MICS) and multimodal analgesia.21 Even though MICS has smaller incisions, they may still result in significant pain due to muscle separation and intercostal nerve damage.22 It is important to combine MICS with multimodal anaesthesia to facilitate recovery process in these children. Therefore, we decided to investigate the effect of PVB on thoracotomy repair of atrial/ventricular septal defect surgery for paediatric patients, which has not been studied previously. Since PVB has been repeatedly compared with epidural anaesthesia and has been shown to be equally effective in providing analgesia, for safety issues, we decided not to compare PVB with epidural anaesthesia in our trial. Instead, we hope to compare PVB with local anaesthetic wound infiltration at the incision area and drainage site, which is a common practice in our hospital and at many other institutions. Most previous studies have focused on infants and children younger than 3 years of age, and there are currently no prospective studies on school-aged children or adolescents. Thus, we chose to focus on this population, who can express their sense of pain more clearly.23
The main hypothesis of this study is that postoperative unilateral PVB provides better analgesic effect compared with that provided by local anaesthetic wound infiltration in school-aged paediatric patients undergoing thoracotomy cardiac surgery with cardiopulmonary bypass.
Method and analysis
Trial status
This study has been registered in the Chinese Clinical Trial Registry and at ClinicalTrials.gov. Recruitment started on 11 March 2024. We expect the study to be completed by December 2024.
Study design and setting
This is a single-centre, randomised controlled trial that aims to determine whether postoperative PVB provides better postoperative analgesia, leads to a lower incidence of complications, and has a faster recovery process compared with local anaesthetic wound infiltration for children undergoing thoracotomy cardiac surgery with cardiopulmonary bypass (CPB). We will conduct this trial at Fuwai Hospital, National Centre for Cardiovascular Diseases, Beijing, China. Figure 1 shows the flow chart of this study. We wrote this protocol according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist and included all the 33 items required in the checklist (online supplemental material 1).
Supplemental material
Study flow chart. CRF, case report form; ERAS, enhanced recovery after surgery; FPS-R, Faces Pain Scale–Revised; PVB, paravertebral block; PONV, postoperative nausea and vomiting.
Eligibility criteria
Inclusion criteria
Children 6–14 years of age;
Children who have atrial septal defect or ventricular septal defect scheduled for thoracotomy cardiac surgery with cardiopulmonary bypass;
Informed consent signed by the parent or legal guardian.
Exclusion criteria
Patients who are intubated, on mechanical circulatory support or administered intravenous inotropes before surgery;
Emergency surgery or redo cardiac surgery;
Body weight more than 50 kg;
Diagnosed with severe pulmonary hypertension;
Left ventricular ejection fraction (LVEF) less than 45% in most recent echocardiography before surgery;
Allergic to ropivacaine or other regular anaesthetics, analgesics or other medications regularly used in the study;
Preoperative platelet counts less than 100 × 109 /L, coagulopathy or bleeding tendency;
Preoperative use of antiplatelets or anticoagulants;
Diagnosed with scoliosis or other contraindications for PVB.
Randomisation and blinding
Patients enrolled in the study will be randomly assigned to one of the two groups in a 1:1 allocation (control group and PVB group). In order to ensure group comparability, a block randomisation will be used. After the random numbers are generated by the computer, all the random numbers will be coded and sealed into sequentially numbered, opaque envelopes.
Before surgery, a pharmacist who is not involved in the follow-up process will open the envelope and prepare medications based on the grouping results. The pharmacist will prepare two medications, A and B, for each patient. For patients in the PVB group, drug A will be 3 mg/kg of 0.375% ropivacaine, and drug B will be the same volume of normal saline. For patients in the control group, drug B will be 3 mg/kg of 0.375% ropivacaine, and drug A will be the same volume of normal saline. The anaesthesiologists will use drug A to perform PVB and drug B to perform local anaesthetic wound infiltration on the patients (figure 1). This double-dummy design enables the blinding of the anaesthesiologist. The patients, guardians, surgeons, ICU physicians and nurses, data collectors, and data analysts will not be aware of the trial grouping during the whole process. If patients are seriously ill or clinicians have any concerns about the treatment, blinding will be removed. After unblinding, the patients will remain in the trial and be followed up. Any intraoperative event or deviation from the protocol will be recorded on the case report form (CRF).
Intervention
Paravertebral block
PVB was performed in the operation room immediately after the surgery before extubation. Patients in both the experimental group and the control group will be treated with drug A for PVB at the T4-T5 level and drug B for local anaesthetic wound infiltration at the incision area and the drainage site.
The sagittal inplane method under ultrasound guidance will be used to perform the PVB. Patients will be placed in a left lateral decubitus position and the lower edge of the T4 spinous process on the right side will be selected as the punction point. The ultrasonic probe will be placed about 2.5 cm away from the spine on the operation side in a direction that is parallel to the spinal column and perpendicular to the skin. The position of the probe will be adjusted until the pleura and the superior costotransverse ligament can be distinguished, thus confirming the paravertebral space. After determining the position, the needle will be injected under ultrasound guidance to make it pass through the skin, external intercostal muscle and superior transverse costal ligament until it reaches the paravertebral space. After pumping back without fluid/blood and gas, drug A will be injected into the paravertebral space. Pleural depression will be observed after injection.
Local anaesthetic wound infiltration will be performed on the incision and the drainage site. The needle will be inserted into the subdermal layer of the wound edge, with one injection at each side of the wound. After aspiration to exclude intravascular placement, the anaesthetic will be slowly injected while withdrawing the needle.
Intraoperative management
On arrival at the operation theatre, sevoflurane (6%–8%) inhalation will be initiated to sedate the patient, and a peripheral venous cannula will be inserted. Intravenous induction will be performed using midazolam (0.1 mg/kg), cisatracurium (0.2 mg/kg), sufentanil (0.5 µg/kg), dexamethasone (0.2 mg/kg) and phencyclidine hydrochloride (0.01 mg/kg).
Mechanical ventilation will be started after endotracheal intubation to achieve an end-tidal carbon dioxide tension of 35–45 mm Hg, with a limited inhaled oxygen concentration of 30%–60% and a tidal volume of no more than 10 mL/kg during surgery. Anaesthesia will be maintained with continuous infusion of propofol 0.2–5 mg/kg/hour, dexmedetomidine 0.5–1 µg/kg/hour and cisatracurium 0.2 mg/kg/hour and combined with sevoflurane 1%–2% inhalation. Sufentanil will be added as required according to the vital signs, usually no more than 2 µg/kg throughout the operation process. Vasopressors, inotropes or vasodilators will be administered as required to maintain haemodynamic stability.
Standard monitoring will include a 5-lead ECG, pulse oximeter, arterial blood pressure, central venous pressure, nasopharyngeal temperature, rectal/bladder temperature and urine output.
The patient will be placed on the left side. The surgeons will make an incision on their right midaxillary line and enter the chest through the fourth intercostal space. Heparinisation for cardiopulmonary bypass will be based on a bolus dose of heparin 400 U/kg and maintenance of an activated clotting time >410 s during CPB. After systemic heparinisation, the ascending aorta, and the superior and inferior vena cavas will be cannulated. After aortic cross-clamping, cardioplegia will be perfused. Surgery will be performed under mild hypothermia (32–34°C), with haemoglobin >70 g/L (7 g/dL) during CPB. After weaning from CPB, modified ultrafiltration may be used accordingly and the haemoglobin target will be around 100 g/L (10 g/dL), and protamine will be titrated to reverse heparin.
Postoperative management
After returning to the paediatric intensive care unit (PICU), the patient will undergo a standardised fast-track recovery process in our hospital. We will induce the patient to breathe spontaneously while continuing the infusion of dexmedetomidine. Extubation will be performed when patients wake up and start to breathe spontaneously at a normal respiratory rate with a tidal volume ≥5 mL/kg. Other criteria for extubation will include normal pulse oxygen saturation, normal arterial blood gas values, stable haemodynamics, absence of significant bleeding, minimal inotropic support and normothermia.
The patients will not be administered any analgesic after returning to the PICU. Their bedside nurse will closely monitor their pain condition. If the patients show any signs of pain, they will be asked to rate their Faces Pain Scale-Revised (FPS-R) Pain Score. When the FPS-R Pain Score is ≥4, continuous infusion of sufentanil (0.05 µg/kg/hour) will be started. When 0＜FPS-R Pain Score＜4, non-opioid analgesics will be administered. First, we will start dexmedetomidine infusion at a rate of 0.5 µg/kg/hour (with no loading dose). If the patient still feels pain (0＜FRS＜4), then we will administer 0.5 mg/kg of ketorolac to the patient (single dose not exceeding 20 mg).
Outcome assessment
Primary outcome: Total opioid consumption within 24 hours after surgery (mg/kg morphine equivalent dose (MED)). A MED is the amount of opioids converted to a common unit (milligrams of morphine) that a patient requires in 24 hours.
Secondary outcomes: (1) FPS-R Scores at 6 hours, 12 hours, 18 hours and 24 hours after surgery; (2) The rate of opioid treatment for remedial analgesia; which means the percentage of patients who need opioids, (3) The first time of FPS-R Score is ≥4 postoperatively.
Exploratory outcomes: (1) Length of postoperative mechanical ventilation, length of ICU stay and hospital stay; (2) The rate of postoperative nausea and vomiting 24 hours after surgery; (3) The incidence of respiratory depression 24 hours after surgery.
The FPS-R Pain Score24 is a self-report measure of pain intensity developed for children. It was adapted from FPS25 to make it possible to score the sensation of pain on the widely accepted 0–10 metric. The scale shows a close linear relationship with Visual Analogue Pain Scale Scores across the age range of 4–16 years. It is easy to administer and requires no equipment except for the photocopied faces. The bedside nurse will show the patients a picture of six faces, and score 0, 2, 4, 6, 8 and 10 from left to right. ‘0’ equals ‘no pain’ and ‘10’ equals ‘very much pain’. They will ask the patient to choose a face that represents their current pain condition and record the pain score.
Data collection and monitoring
We will gather preoperative information including demographic data (age, gender, height, weight), major diagnosis, comorbidity, surgical history, allergy history, laboratory test results (platelet, haemoglobin, PT Prothrombin Time, APTT Activated Partial Thromboplastin Time), echocardiography information (LVEF, pulmonary artery pressure), and preoperative medication (inotropes, vasoactive agents, diuretics, anti-infective drugs). We will also record intraoperative parameters including type of surgery, time of surgery, time of anaesthesia, time of cardiopulmonary bypass, blood loss and transfusion. As is described in the outcome section, postoperative information concerning pain, analgesics, the recovery process and adverse events will all be documented in detail until the patient’s discharge.
The original data will be recorded in the CRFs and remain confidential. All data and its collection process will be completed under the supervision of the trial management centre. After the trial is completed, all data and CRF forms will be provided to the principal investigator for long-term follow-up.
Sample size estimation
Sample size calculation was based on the primary outcome, the total opioid consumption within 24 hours after surgery. Based on our preliminary test results, the average total opioid consumption within 24 hours after surgery in the control group was 0.85±0.18 mg/kg MED. Based on previously published literature12 13 26 and the experience of clinical experts, we assumed that in the PVB group, total opioid consumption within 24 hours after surgery will be reduced by an average of 30%, that is, 0.255 mg/kg MED. The combined SD was conservatively estimated to be 0.425 mg/kg MED. With a one-side significance level of 0.025, and a power level of 80%, 90 participants need to be enrolled (45 participants for each group). Sample size calculation was performed using the Power Analysis and Sample Size (PASS) software. Taking into account the maximum possible dropout rate of 10% in the study, this trial will eventually enrol 100 children, 50 children in each group.
Data analysis
This trial will be analysed according to the intention-to-treat principle, and any participant who completes randomisation will be followed up until the end of the trial (unless the participant withdraws the informed consent). Quantitative data will be expressed as mean±SD or median (IQR) depending on whether the data conforms to a normal distribution. Categorical data will be expressed as frequency (percentage). For normally distributed quantitative data, comparisons between groups will be performed using the two independent sample t-tests. For non-normally distributed quantitative data, comparisons between groups will be performed using the Mann-Whitney U test. For categorical data, comparisons between groups will be performed using the χ2 or Fisher’s exact test. Sensitivity analyses will be used to examine missing data after imputation using the worst-case imputation scenarios. All tests will be two-sided and a value of p<0.05 will be considered statistically significant. This study will use SPSS V.26.0 software (IBM, New York, USA) for data analysis.
Harms
A serious adverse event (SAE) for this study will be defined as any adverse medical event or unintended symptom associated with the study intervention that results in any of the following complications: life-threatening condition or mortality, disability, or serious cardiovascular or respiratory events. All related adverse events that meet the criteria for SAE will be recorded and reported to the ethics committee as part of the annual report. Adverse events will be the responsibility of the principal investigator. If there is clinical suspicion that the intervention is harmful, the study will be suspended. We will provide free clinical treatment as compensation.
Patient and public involvement
None.
Ethics and dissemination
The final version (V.2.2) of the study protocol was approved by the Ethics Committee of Fuwai Hospital, Chinese Academy of Medical Sciences, on 26 February 2024 (No 2023–2135). We have registered this trial at ClinicalTrials.gov (NCT06312904) and the Chinese Clinical Trial Registry (ChiCTR2400081773). Written informed consent will be obtained from each participant or their legal representatives before enrolment. For patients less than 8 years of age, the informed consent form will be signed by their legal guardians. For patients more than 8 years of age, both the patients and their legal guardians will sign the informed consent form. The informed consent forms for legal representatives and the patient themselves are provided in online supplement materials 2 and 3. The results of this trial will be published in an international peer-reviewed scientific journal.
Supplemental material
Supplemental material
Ethics statements
Patient consent for publication
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors JG, YJ and SY contributed substantially to the design of the work and drafting of the manuscript. JG, WK and LT conducted the study. All authors were involved in drafting and revising the intellectual content in the manuscript and approved the final version to be published. SY is the guarantor.
Funding Supported by National High-Level Hospital Clinical Research Funding (2023 GSP-QN-6).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.