Protocol for a randomised controlled trial: optimisation of perioperative analgesia protocol for uniportal video-assisted thoracoscopic surgery


Despite advancements in minimally invasive surgeries and multimodal analgesic techniques, perioperative pain management during thoracic surgery remains inadequate. Thoracic surgery continues to present one of the most challenging perioperative pain scenarios.1 Postoperative thoracic pain can affect active coughing and early mobilisation, which can impair sputum clearance and increase the risk of atelectasis and thrombotic events. Optimal perioperative pain management in thoracic surgery includes a minimally invasive incision, multimodal analgesia, regional analgesia, minimal opioid utilisation, and effective chest drainage.2–4

Based on the strategy for multimodal analgesia, recent research has explored various methods to alleviate pain after thoracic surgery. In 2022, the PROSPECT guidelines proved that among several alternative nerve block methods, single-shot erector spinae plane block (ESPB) and single-shot paravertebral block (PVB) offer superior analgesic effect on video-assisted thoracoscopic surgery (VATS), supported by robust clinical evidence.5 Conversely, the efficacy of serratus anterior and intercostal nerve blocks varies significantly among individuals; both carry the risk of incomplete blockade. Epidural analgesia is no longer the first-line analgesic regimen due to its adverse effects on the circulation and respiration. Paracetamol or non-steroidal anti-inflammatory drugs/COX-2 can be administered before and after surgery. Additionally, postoperative patient-controlled intravenous analgesic (PCIA) and opioid rescue are included in routine analgesic regimens.

The primary objective of uniportal video-assisted thoracoscopic surgery (uVATS) is to minimise surgical trauma, which may be beneficial for both postoperative pain and oncology. In our centre, surgical incision is made at the fourth or fifth (the widest) intercostal space and drainage tube is placed at the incision site, significantly reducing the risk of intercostal nerve injury. Regarding multiportal VATS, surgical operation and drainage tube placement are performed through the seventh intercostal space, a narrower area often associated with postoperative pain. Nachira et al reported that chest tube removal was an obvious cause of pain relief in 93% of the patients, regardless of the analgesic regimen.6 Several studies have affirmed the value of alleviating postoperative pain using uniportal instead of multiportal VATS7 and the optimal type and location of the thoracic drainage tube.8 By optimising incision and drainage tube stimulation using uVATS, further optimisation of our analgesic protocol could be possible.

Despite the existing guidelines and recent recommendations for multimodal analgesic strategies for thoracic surgery, little is known about the optimal analgesic regimen for uVATS. Postoperative pain usually peaks at 14–72 hours after uVATS. Since the recommended nerve block for VATS is mostly a single-shot PVB or ESPB, the effective time spans 18–48 hours. The patients’ ambulation time ranges between 10 and 30 hours after surgery, while chest tube removal time could be 30–50 hours after surgery. Does the nerve block protocol influence postoperative pain? Due to the substantial heterogeneity of multicentre data, an accepted standard analgesic protocol has not been established.9–12 Although single-shot PVB presents a steep learning curve and may cover sputum excretion and initial ambulation time after surgery,13 it may not consistently reveal deep blood vessels under ultrasound guidance. In addition, PVB presents a risk of block failure and haemothorax, which outweigh the benefits of analgesia for minithoracotomy. In contrast, ESPB is relatively simple and superficial, with clear identification of muscle layers using ultrasonography and a lower risk of bleeding. A major drawback of ESPB is the limited individual variation in the diffusion of local anaesthetics to the ventral branch of the spinal nerves and intercostal spaces; thus, the analgesic effect may be weaker than that of PVB. PVB is good for visceral pain relief. However, it covers a smaller area compared with ESPB. In addition, although ESPB has convenience and safety advantages, it may be less effective than PVB. Compared with the published data on pain assessment for total intravenous and oral analgesia as the only postoperative analgesia for uVATS, nerve blocks may not be an absolute advantage for relieving postoperative pain.10 12 14 15

When striving to minimise surgical trauma using uVATS, the surgical team aims to expedite anaesthesia and operation time while reducing patient costs. Compared with these surgical changes, the risk of nerve block failure, difficult puncture visualisation or bleeding limits our hospital’s practical implementation of nerve blocks during short uVATS. Therefore, we compared the most accepted nerve block strategies combined with intravenous analgesia or PCIA alone for uVATS alongside optimised drainage tube strategies. This study discusses the impact of nerve block, clinical characteristics of postoperative pain over time, and potential risk factors for acute and chronic pain following uVATS.

The major mechanisms underlying pain after thoracic surgery include intercostal nerve injury and trauma to the muscles and tissues of the chest wall. Based on the existing guidelines, we assume that the current analgesic combination can be optimised. We also hypothesise that a minimal incision, chest tube insertion into a wider intercostal space and optimal perioperative analgesia would achieve a better postoperative analgesic effect.

In this study, we aim to determine the most effective and feasible perioperative analgesic regimen for short-term uVATS. This will be a single-centre, prospective, single-blind, randomised trial. The effects of postoperative analgesia will be tested in PVB combined with PCIA and in ESPB combined with PCIA or PCIA alone.

Methods and analysis

Trial design

Our reporting plan will follow the CONSORT reporting protocol and the Guidelines for Reporting Outcomes in Trial Reports The CONSORT-Outcomes 2022: Extension.16 17 This study will involve adult participants scheduled for resection of early-stage lung cancer or pulmonary nodules under uVATS at the China-Japan Friendship Hospital (online supplemental file 1).

Supplemental material

Participants: eligibility criteria and data collection

A minimum of 102 patients (34 per group) will be enrolled in the study (Sample size). Patients’ baseline information will be collected within 1 month after admission. Patients who meet the inclusion criteria will be selected from the thoracic surgery clinic. The detailed inclusion and exclusion criteria are listed in box 1. After obtaining informed consent (online supplemental file 2), a physician at the clinic will collect the patients’ baseline information. Preoperative records include age, sex, height, weight, primary disease, comorbidities, surgical history, medication use, anaesthesia history and the proposed operation. The patients will undergo physical examinations focused on cardiopulmonary function, airway condition and surgical design. After hospital admission, all patients will undergo routine preoperative analyses, including lung function, chest imaging, ECG, complete blood count, blood biochemistry and coagulation tests.

Supplemental material

Box 1

The inclusion and exclusion criteria

Inclusion criteria

  1. 18–85 years.

  2. ASA I-II*.

  3. Participants who are suitable for wedge resection, segmentectomy or lobectomy under uVATS evaluated by thoracic surgeons.

  4. Participants diagnosed with early-stage (0-IIA) lung cancer and those with incidental lung nodules that require surgical resection.

  5. Estimated operation time ≤3 hours.

  6. Informed consent obtained.

Exclusion criteria

  1. ASA ≥III.

  2. History of intrathoracic or chest wall surgery.

  3. Existence of ‘the doornail lymph node’, possible massive adhesions in the resected area.

  4. Pleural adhesions or other causes of difficulty in uVATS operation, determined from medical history or chest CT.

  5. Chronic pain.

  6. Preoperative analgesic medication use.

  7. NSAIDs contraindications: aspirin, asthma, allergy to NSAIDs, peptic ulcer, liver and kidney insufficiency, high risk of thrombotic events.

  8. Active autoimmune disease.

  9. Allergic to local anaesthetics.

  10. Severe coagulation dysfunction, contraindicated for nerve block.

  11. Soft tissue infections of the chest wall.

  • *American Society of Anaesthesiologists (ASA) physical status classification system.

  • Single-portal video-assisted thoracoscopic surgery.

  • NSAIDs, non-steroidal anti-inflammatory drugs.

Grouping, randomisation and allocation concealment

We will conduct a single-blind, randomised controlled trial. All participants are expected to be enrolled in the trial within 8 months. Enrolment will follow the eligibility criteria, and informed consent will be obtained during preoperative outpatient consultation. On admission, the participants will be assigned to groups using the block randomisation method (allocation ratio 1:1:1) by a researcher who is unaware of the meaning of the group code (Meng Tao Zheng). The participants will be stratified based on sequential ID numbers with a permuted block of six. Within each block, random sequences between 0 and 1 will be generated using EXCEL (Office V.2021, Microsoft). The group code (A, B or C) is defined as the remainder of the serial number divided by three. The researcher will place the group code in a light-proof envelope and put it in a medical record folder. A flowchart of the enrolled participants is shown in figure 1.

Figure 1
Figure 1

Flow diagram. ESPB, erector spinae plane block; PCIA, patient-controlled intravenous analgesia; PVB, paravertebral block; uVATS, uniportal video-assisted thoracoscopic surgery.


Preoperative preparations will be routinely performed in all participants. On the day of surgery, the participants will be transferred to the operating room alongside the medical record folder containing a light-proof envelope. The participants will remain unaware of their group assignments throughout the study. After induction of anaesthesia, the anaesthesiologist will open the light-proof envelope, obtain the group code and dispose of the group code cards and envelopes. The group codes will be recorded in the case report form (CRF). Only the principal investigator and anaesthesiologists will be privy to the intervention indicated by the group code. The anaesthesiologists will not be involved in the postoperative follow-up or data collection. Neither the physicians in charge of postoperative follow-ups nor statisticians will be informed of the specific interventions regarding each grouping code (A, B, or C).

Surgical management

All participants will undergo uVATS. In the lateral position, a 5 cm cotton chest pad will be placed below the shoulder and above the waist to optimise the intercostal space. A 3–5 cm incision will be made in the fourth or fifth intercostal space at the anterior to mid-axillary line.18 The precise location of surgical incision depends on the position of the widest intercostal space palpated after positioning. Before sterilisation, the linear probe of the ultrasound machine will be positioned at the surgeon’s incision mark along the intercostal space, perpendicular to the midpoint of the incision. The distance from the upper rib’s lower edge to the lower rib’s upper edge, parallel to the pleural line, will be measured19 and recorded as the width of the intercostal space.

A wound protector will also be used. In accordance with the conventional surgical protocol for uVATS,12 the surgeons will try to avoid cutting or continuously compressing the intercostal nerve or stretching the intercostal space. At the end of surgery, a 24F chest tube will be placed at the surgical incision, which corresponds to the widest intercostal space evaluated before making incision, with a depth of approximately 5 cm. Thoracoscopy will be performed to check that the chest tube would not impact or compress the pleura. After completely inflating the lungs, the chest tube will be connected to a water-sealed bottle. The indications for chest drainage tube removal include daily drainage volume of pleural fluid less than 30 mL, patient’s respiratory function and no sign of air leakage or bleeding in the drainage bottle. The patients will be asked to cough before extubation, and the chest tube will be removed if there is no sign of gas leakage in the drainage bottle.

Anaesthesia and intraoperative analgesic protocol

Anaesthesia will be performed according to the standard multimodal analgesia protocol for VATS.5 An intravenous injection of propofol, cis-atracurium and sufentanil 0.3–0.6 µg/kg will be used for induction. Additional sufentanil will be added during intubation, skin cutting or as needed to prevent postoperative flare-ups (≤1 µg/kg in total). Maintenance of anaesthesia will be performed using sevoflurane, propofol and remifentanil (0.2–0.5 µg/kg/min), with targeted bispectral index 40–60. Airway management, ventilator parameters and circulation maintenance will be according to the standard principles. Lidocaine cream will be locally applied before chest tube removal.20

After induction, the anaesthesiologist will read the grouping code and perform one of the following interventions: (1) The PVB+PCIA group: the patients in this group will receive ultrasound-guided paravertebral nerve block with ropivacaine (0.33%) and 5 mg of dexamethasone in a total of 30 mL of saline at the T4 or T5 level on the operative side in combination with PCIA. (2) The ESPB+PCIA group: the patients in this group will receive an ultrasound-guided erector spinae block with ropivacaine (0.25%) and 5 mg of dexamethasone in a total of 40 mL of saline at the T4 or T5 level on the operative side (depending on the location of incision) in combination with PCIA. (3) The PCIA group: The patients in the PCIA group will not receive a regional block.

PCIA with sufentanil (1.8–3.2 µg/h) and PCA (0.8–1 µg) will be administered to all participants immediately after surgery. The minimum interval doses will be 15–20 min. All participants will receive postoperative analgesia education before surgery. PCA will be administered prophylactically before ambulation, and chest tube removal will be enacted as needed when cough and pain are aggravated. The principle of postoperative analgesia is that pain of >3 points (moderate pain which makes the patient unable to rest or sleep) should be treated as soon as possible. Based on the analgesic effect or adverse reactions, the thoracic surgeons will contact the anaesthesiologist whenever necessary to adjust the analgesic regimen within the above range. There will also be a routine daily follow-up by the anaesthesiologists after surgery.

The standard postoperative rescue opioid regimen for uVATS in our thoracic ward includes pethidine hydrochloride (25–100 mg) intramuscular injection, administered up to three times daily as needed. Its analgesic effect peaks within 1–2 hours. Oral paracetamol and dihydrocodeine tartrate, each tablet containing 500 mg of acetaminophen and 10 mg of dihydrocodeine tartrate, is also used. Considering persistent pain, 1–2 tablets are taken orally (o.p.), and its analgesic effect peaks in 0.5–1 hours, with an overall action time within 3–4 hours. At each follow-up visit, opioid consumption will be calculated as the total opioid dose between the end of the follow-up visit and the time of the last follow-up visit, and the opioid dose will be converted to oral morphine equivalent (OME). The formula for conversion of morphine equivalents is referred to in the literature, and the usage and dosage are indicated in the drug label.21 The conversion formula is as follows: OME (strength per unit)×(number of units)×OME conversion factor=OME. Morphine 1 mg intravenous injection=morphine 3 mg o.p.=3 OME. Sufentanil 1 µg intravenous injection=morphine 1 mg intravenous injection=3 OME. Dihydrocodeine 10 mg o.p.=0.1 (conversion factor) ×10=1 OME. Meperidine 50 mg intramuscular injection=0.4 (conversion factor)×50=20 OME.

Non-opioids at our medical centre include intravenous and oral medications such as flurbiprofen, loxoprofen, acetaminophen, ketorolac and indomethacin. When the analgesic effect of opioids is not satisfactory, non-opioids are administered at regular intervals of 6, 8 or 12 hours, 3, 4, or 6 times per day. The initial dose is selected based on the patient’s postopioid treatment pain level. If the effect is poor, the dose will be increased each time and will not exceed the maximum dose. The overlapping use of non-opioid drugs is prohibited.


The patients will participate in the trial from the preoperative consultation period in the chest clinic until 6 months after surgery. After obtaining informed consent and enrolment in the trial, the participants’ basic information and pre-operative tests will be collected 1 day before surgery.

On the day of surgery, operation-related data, including the duration of anaesthesia, duration of surgery, intake and output volume (I/O), dosage of anaesthetics and vasoactive agents, the width of the intercostal space, and special events will all be recorded.

Postoperative follow-ups will cover 1, 4, 12 and 18 hours, and 1, 2, 3, 4 and 7 days after surgery, focusing on rest and cough pain using the visual analogue scale (VAS) (1–10) or numeric rating scale (NRS) (1–10), and dosage of opioid and non-opioid drugs. Adverse reactions, such as dizziness; nausea and vomiting; asthenia; urinary retention; hypotension; pneumothorax; and haemothorax, will be recorded in detail.

The time from the end of the procedure to chest drainage tube removal will be recorded. Ambulation time, hospitalisation time, and total hospital costs will also be recorded. Tactile and cold sensations will be measured at four points (<3 cm near the incision, on the other side of the symmetrical chest wall, and at the bilateral mid-clavicular-costal arch) using an alcohol-stained cotton swab.

Postdischarge follow-ups will be performed via postoperative clinic consultations or telephone follow-ups at 1, 2, 3, 4 and 6 months after surgery. Follow-up after discharge includes rest and cough pain, bilateral chest wall sensory differences, analgesic drug use and adverse reactions. Follow-up interviewers will be blinded to the group allocation. The participants’ variables and timelines are listed in table 1 and in online supplemental file 3.

Supplemental material

Table 1

Variables and study timeline

Outcome measurements

An estimate of 102 participants will be needed. The primary outcome will be total opioid consumption, calculated as the total opioid dose between the last and previous follow-ups. All opioid doses will be converted into OMEs.

The secondary outcomes are categorised as follows: (1) postoperative pain score: including resting and coughing pain assessed using VAS or NRS at each time point; (2) use of non-opioids and long-term postoperative analgesia (pain treatment for >3 months); (3) other parameters such as ambulation time, chest tube duration, length of stay and total hospitalisation cost; (4) adverse events (AEs) associated with analgesic regimens, such as dizziness, nausea and vomiting, asthenia, urinary retention, hypotension, pneumothorax and haemothorax, will also be recorded and compared within the groups.

Sample size

The sample size was estimated using the PASS V.2021 software. We referred to data of the participants who received PVB with PCIA,22 ESPB with PCIA,23 or a sufentanil PCIA pump only.24 The required opioids were converted into morphine equivalents. Data were subjected to one-way analysis of variance (ANOVA) and F-tests using effect size. Variables are determined as follows: two-sided hypothesis, power=0.8, α=0.05, G(group)=3, allocation ratio 1:1:1. Effect size is calculated as cumulative opioids (morphine equivalents) after VATS14–18; f=σm/σ, σm=√[Σ(μi-μ)²/G)=7.14 (μ is the mean of the group means, and μi is the mean of the ith group), σ (1.9, 7.4, 18.0). The results are as follows: power=0.907, ni=28, N=84. Considering that the permissible drop-out rate was no higher than 20%, the total sample size is 102 (n=34 in each group). We will conduct a power analysis after the study using the results collected from our participants. Power >0.8 is defined as meaningful to detect the effect size. In addition to the statistical significance of the study results, the clinical significance of the actual pain score, pain degree and dosage will also be considered, which will be discussed in the study results.

Modifications and potential harms

Other narcotic analgesics, sedatives, hypnotic drugs and analgesic measurements will not be included in this study. If the patient insists on other treatment options or is judged from a medical perspective, detailed reasons will be recorded, and the patient will drop out of the study (see Drop-out Records in CRF, online supplemental file 3).

Interim analyses will be performed when the number of enrolled patients reaches 50% of the sample size. Primary and secondary outcomes will be observed, and AEs will be reviewed. If necessary, the principal investigator will change the study procedure, and any reason will be documented and clarified.

AEs (eg, neural blockade failure, local anaesthetic intoxication, hypotension, postoperative nausea and vomiting, skin itching and prolonged hospitalisation due to complications) and their clinical treatments will be recorded. Severe AEs (SAEs) (eg, severe allergic reaction, total spinal anaesthesia, extensive intrathoracic bleeding, tension pneumothorax, severe infection, peptic ulcer, respiratory inhibition, thrombotic events, postoperative delirium, severe liver and kidney function and nerve injury) will be immediately treated and reported to the principal investigator and all relevant departments in the hospital. The patients will be unblinded to the study. After SAEs, investigators will review the protocol and terminate the trial if necessary (see online supplemental file 4).

Supplemental material


Statisticians will be blinded to the group allocation. Continuous data (normal distribution) will be represented by mean±SD, and non-normal distribution data will be represented by median value and quartiles. Categorical data will be expressed as percentages. Continuous data will be compared using one-way ANOVA for differences among the means of the three groups. Pain scores among the three groups will be compared using the Kruskal-Wallis test. Multiple χ2 tests will be used to test categorical variables among groups. Statistical significance will be set to a p<0.05.

Missing data

Patients with significant missing data will be excluded; their characteristics will be compared with assess the impact on the research validity. The study’s validity will be discussed with respect to missing data.

Limitations of this study

The surgical procedure used in the present study is restricted to uVATS. After confirming the optimal perioperative analgesic management scheme of uVATS, the effects of different surgical methods can be compared with maximise each factor’s potential to relieve postoperative pain after thoracic surgery and minimise analgesic-related complications in future studies. Given the single-centre nature of this study, its applicability may be limited to our centre for informing analgesic protocols, thus reducing its generalisability. We will continuously enrol all patients who meet the indications for uVATS under different chest surgeon admissions to minimise sampling bias. Considering the limitations of a single-centre study, a multicentre study on this topic should be considered in the future.

Data statement

Patient enrolment and baseline information will be recorded using the GOODWILL Electronic Medical Record System (V.6.0). CRFs, including informed consent forms with patient signatures, will be securely stored in a clinical trial filing cabinet. Electronic information will be stored on an authorised computer while maintaining clinical trial confidentiality. Anonymised trial documents and data results will be uploaded within 1 week to

Security cameras will be installed next to the computer and the filing cabinet for data storage. Surveillance video access will be restricted to medical staff and the principal investigator. Access to data will be limited to authorised personnel, including the Ethics Committee directors and principal investigators. All access to paper documents and electronic data will be logged, including the operator’s name and detailed reasons for access.

To prevent performance bias, postoperative analgesia regimens and follow-up will be provided by physicians who are unaware of the patient group or analgesic regimens during the surgery. To prevent detection bias, all follow-up physicians will be trained prior to the experiment. Evaluators will be blinded to the group assignments. Quantitative pain scores will be adopted, and chest pain and sensation examinations will be standardised. Missing data will be recorded and reported to the public to avoid attrition and reporting bias, and drop-outs will be compared among the three groups.

Patient and public involvement

Patients and the public are not involved in this study.

Ethics and dissemination

This study was approved by the Ethics Committee of China-Japan Friendship Hospital on 16 June 2023 (ethical approval ID: 2022-KY-127–1, online supplemental file 5). Informed consent will be obtained by the anaesthesiologist during preadmission assessment in the thoracic outpatient clinic before intervention. Participants will receive detailed information on perioperative analgesic regimens in all three groups, other surgical or anaesthetic treatment options, possible AEs and their right to withdraw from the study. This information is included in the informed consent form of the CRF and can be reviewed by the participants on request (online supplemental file 1).

Supplemental material

The interventions in our trial are optimised analgesia plans based on the existing guidelines for perioperative analgesia in thoracic surgery. We consider that our treatments align with the currently accepted standards without potential harm to the participants. Other possible special events related to this trial, such as changes in the operative approach, additional analgesic therapies that exceed the clinical trial protocol, failure of the regional block or patient disagreement with the current treatment, will all be included in the adverse-event report form (CRF form). Patients experiencing such events will withdraw from the trial and receive prompt clinical interventions, and the events will be reported promptly to the principal investigator, clinical team and ethics committee. The patients will be treated and followed up until they are stable. If necessary, the entire study will be terminated, and a report will be submitted to the responsible departments.

The results and conclusions of our research will be reported to all participants, research teams and the public through peer-reviewed journals. We aim to contribute to the optimisation of perioperative anaesthesia and analgesia protocols for small-incision thoracic surgery and an optimised drainage tube strategy based on the existing guidelines.

This post was originally published on