Optimal Postoperative Pain Management After Lung Surgery (OPtriAL)

Optimal Postoperative Pain Management After Lung Surgery (OPtriAL): Multi-centre Randomised Trial

Adequate pain control after video-assisted thoracoscopic surgery (VATS) for lung resection is important to improve postoperative mobilisation, recovery, and to prevent pulmonary complications. So far, no consensus exists on optimal postoperative pain management after VATS anatomic lung resection.

Thoracic epidural analgesia (TEA) is the reference standard for postoperative pain management following VATS. Although the analgesic effect of TEA is clear, it is associated with patient immobilisation, bladder dysfunction and hypotension which may result in delayed recovery and longer hospitalisation. These disadvantages of TEA initiated the development of unilateral regional techniques for pain management. The most frequently used techniques are continuous paravertebral block (PVB) and single-shot intercostal nerve block (ICNB).

The investigators hypothesize that using either PVB or ICNB is non-inferior to TEA regarding postoperative pain and superior regarding quality of recovery (QoR). Signifying faster postoperative mobilisation, reduced morbidity and shorter hospitalisation, these techniques may therefore reduce health care costs and improve patient satisfaction.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative; Lung Cancer; VATS; Locoregional Anaesthesia; Thoracic Epidural
• Intervention / Treatment: Procedure: Thoracic epidural analgesia; Procedure: Continuous regional paravertebral block; Procedure: Single shot intercostal nerve block

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Veldhoven, Netherlands, 5504 DB
    • Máxima MC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (>18 years)
• Patients referred for anatomic lung resection (pneumonectomy, (bi)lobectomy or segmentectomy for either benign or malignant disease) with the intention of performing it by video-assisted thoracoscopic surgery (VATS) or robot-assisted thoracoscopic surgery (RATS)
• Patients should be able to provide informed consent and fill out questionnaires in Dutch language.

Exclusion Criteria:

• Patients with contra-indications for TEA or PVB (infection at skin site, increased intracranial pressure, non-correctable coagulopathy, bridging indication for therapeutic anticoagulation (CHADS-VASc ≥ 8), sepsis and mechanical spine obstruction) or allergic reactions to local anaesthetics will be excluded.
• Patients chronically using opioids for reasons not related to the operation will be excluded from the study since postoperative baseline opioid requirement will be higher and TEA remains the preferred technique for these patients.
• In case the lung surgeon estimates the operation to be performed through a thoracotomy instead of VATS/RATS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Thoracic epidural analgesia; See intervention description	Procedure: Thoracic epidural analgesia; After correct placement of the epidural catheter, a local anaesthetic (ropivacaine, levobupivacaine or bupivacaine) will be started and, according to in house protocols, an opioid will be added to the epidural solution. A provisional stop of the administration of the epidural infusion is planned after 48 hours (on the second postoperative day).
Experimental: Continuous regional paravertebral block; See intervention description	Procedure: Continuous regional paravertebral block; The PVB catheter is placed under general anaesthesia at the beginning of the VATS procedure under direct thoracoscopic vision. The level of the PVB catheter placement is chosen at the intercostal space of the largest incision (mostly thoracic level 4 or 5). Under direct thoracoscopic vision, the surgeon inserts a Touhy needle. The tip of the needle is observed beneath the pleural surface thoracoscopically. Injection of about 2 mL ropivacaine 7.5mg/mL will create subpleural hydrodissection to reach the adequate paravertebral plane for placement of the catheter. The PVB catheter is subsequently placed under direct thoracoscopic vision and left next to the sympathetic chain in the paravertebral space. Next, a bolus of ropivacaine (total amount 20 mL including the given amount for hydrodissection) is given through the catheter. Postoperatively, a ropivacaine 2 mg/mL pump for continuous infusion is given with an infusion rate of 8-14 ml/hour.
Experimental: Single shot intercostal nerve block; See intervention description	Procedure: Single shot intercostal nerve block; At the end of the surgery a single shot ICNB will be placed at 9 levels (thoracic level 2 to 10) with 2-3mL local anaesthetics per intercostal space under direct thoracoscopic vision. The injection site will be chosen just lateral from the sympathetic trunk. This group will have no analgesic catheters for continuous analgesia. No mobility restrictions are instructed in this group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scores	Proportion of pain scores ≥4 as assessed by the numerical rating scale (NRS) (measured from 0 until 10; lowest value signifying no pain and highest value signifying worst pain)	Postoperative day 0-2
Quality of Recovery (QoR)	QoR measured with the QoR-15 questionnaire on postoperative 1 and 2 (maximum score of 150, the higher the score the better the outcome)	Postoperative day 1-2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cumulative use of opioids and analgesics	total opioid and non-opioid consumption as supplementary analgesic requirement	Postoperative day 0 until 3 as well as the use and dosage of opioid use at the follow-up period 2-3 weeks after the operation
postoperative complications	according to the Clavien-Dindo classification;	until 2-3 weeks of follow-up
hospitalisation	defined as the total number of days in hospital after the surgical intervention (including readmissions within the first 30 postoperative days), the following standardised discharge criteria after surgery will be applied in all participating hospitals: normal intake of nutrition, independent mobility, absence of fever (<38 °C), and no presence of chest tube;	30 postoperative days
patient satisfaction	5-point Likert scale: not at all satisfied, slightly satisfied, neutral, very satisfied and extremely satisfied	Postoperative day 0 until 3
degree of mobility	4-point scale: on the bed (1), to the chair (2), to the toilet (3), outside the patient's hospital room(4)	Postoperative day 0 until 3

Collaborators and Investigators

• Sponsor: Maxima Medical Center
• Collaborators: Radboud University Medical Center; ZonMw: The Netherlands Organisation for Health Research and Development; Amsterdam UMC

Publications and helpful links

General Publications

• Spaans LN, Dijkgraaf MGW, Meijer P, Mourisse J, Bouwman RA, Verhagen AFTM, van den Broek FJC; OPtriAL study group. Optimal postoperative pain management after VATS lung resection by thoracic epidural analgesia, continuous paravertebral block or single-shot intercostal nerve block (OPtriAL): study protocol of a three-arm multicentre randomised controlled trial. BMC Surg. 2022 Sep 4;22(1):330. doi: 10.1186/s12893-022-01765-y.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): October 1, 2023
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): July 8, 2024
• Last Update Submitted That Met QC Criteria: July 4, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: NL75375.041.20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will become available for non-commercial scientific research (open access) after a period of 12 months after the last data collection. Data request can be done by contacting the PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No