Optimal Postoperative Chest Tube and Pain Management in Patients Surgically Treated for Primary Spontaneous Pneumothorax (Pneumotrial)

Optimal Postoperative Chest Tube and Pain Management in Patients Surgically Treated for Primary Spontaneous Pneumothorax (Pneumotrial); a Randomized Controlled Trial

Guidelines lack high quality evidence on optimal postoperative chest tube and pain management after surgery for primary spontaneous pneumothorax (PSP). This results in great variability in postoperative care and length of hospital stay (LOS). Chest tube and pain management are prominent factors regarding enhanced recovery after thoracic surgery, and in standardised care they are crucial to improve quality of recovery and decrease LOS.

Historically, postoperative chest tubes are left in place for at least a fixed number of 3-5 days, irrespective of absence of air leakage. This period was deemed necessary for adequate pleurodesis and prevention of recurrence. However, it is suggested that removal on the same day of surgery is safe and associated with a reduced LOS.

Regarding postoperative pain management, thoracic epidural analgesia (TEA) is the gold standard for postoperative pain management following video-assisted thoracic surgery (VATS). Although the analgesic effect of TEA is clear, it is associated with hypotension and urinary retention. Therefore, unilateral regional techniques, such as paravertebral blockade (PVB), are developed.

The investigators hypothesize that early chest tube removal accompanied by a single-shot paravertebral blockade (PVB) for analgesia is safe regarding pneumothorax recurrence and non-inferior regarding pain, but superior regarding LOS when compared to standard conservative treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain, Postoperative; VATS; Locoregional Anaesthesia; Thoracic Epidural; Pneumothorax, Primary Spontaneous; Chest Tube Drainage
• Intervention / Treatment: Procedure: Thoracic epidural analgesia; Procedure: Late chest tube removal; Procedure: Single-shot paravertebral block; Procedure: Early chest tube removal

• Study Type: Interventional
• Enrollment (Estimated): 366
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Quirine C.A. van Steenwijk, MD; Phone Number: +31-40888-8550; Email: quirine.van.steenwijk@mmc.nl
• Study Contact Backup: Name: Frank J.C. van den Broek, MD, PhD; Phone Number: +31-40888-8550; Email: frankvanden.broek@mmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients operated for PSP
• Age ≥ 16 years
• Able to read and understand the Dutch language
• Mentally able to provide informed consent
• Patients should have a preoperative chest CT scan in order to exclude evident secondary pneumothorax. Previously made CT scans, within a time range of maximum 5 years, are accepted. The identification of blebs or bullae on CT scan is not defined as secondary pneumothorax.

Exclusion Criteria:

• Previous ipsilateral thoracic surgery (except diagnostic thoracoscopy only) or ipsilateral thoracic radiotherapy
• Underlying lung disease that provoked the pneumothorax (secondary pneumothorax): genetically proven Birt-Hogg-Dubé syndrome, periodic pneumothorax in female patients in reproductive age with known endometriosis (or known catamenial pneumothorax), pulmonary cystic fibrosis, active pneumonia, lung fibrosis, chronic obstructive pulmonary disease (COPD), pulmonary ipsilateral malignancy
• Contra-indications for TEA (infection at skin site, increased intracranial pressure, non-correctable coagulopathy, sepsis and mechanical spine obstruction)
• Patients chronically (>3 months) using opioids will be excluded since postoperative baseline opioid requirement will be higher and TEA remains the preferred technique for these patients
• Allergic reactions to analgesics used in the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chest tube duration at least 3 days plus TEA	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).; Procedure: Late chest tube removal; Postoperatively, the chest tube is connected to a Thopaz+ system (Medela inc.) and installed to -2 or -5 cm H2O. The chest tube will be left in place during a fixed period of 3 postoperative days. The chest tube will be removed at the earliest at POD 3 in case the following criteria are met: The patient is lucid and capable of sitting up straight in bed on his/her own; No air leakage indicated by the Thopaz+ system during at least 4 hours, or <15 mL/min air leakage during at least 6 hours; Postoperative X ray (performed at least 4 hours after surgery or ultimately performed the morning of POD1) demonstrating complete lung expansion at the level of the hilum.; Absence of bloody drainage by the Thopaz+ system
Experimental: Chest tube duration at least 3 days plus single-shot PVB	Procedure: Late chest tube removal; Postoperatively, the chest tube is connected to a Thopaz+ system (Medela inc.) and installed to -2 or -5 cm H2O. The chest tube will be left in place during a fixed period of 3 postoperative days. The chest tube will be removed at the earliest at POD 3 in case the following criteria are met: The patient is lucid and capable of sitting up straight in bed on his/her own; No air leakage indicated by the Thopaz+ system during at least 4 hours, or <15 mL/min air leakage during at least 6 hours; Postoperative X ray (performed at least 4 hours after surgery or ultimately performed the morning of POD1) demonstrating complete lung expansion at the level of the hilum.; Absence of bloody drainage by the Thopaz+ system; Procedure: Single-shot paravertebral block; At the beginning of surgery, before pleurectomy, a single shot PVB will be placed at 10 levels (T2-T11) by the surgeon with Ropivacaine 7.5mg/mL and 2-3mL per site under direct thoracoscopic vision. The injection site will be chosen at the paravertebral space, just lateral adjacent to the sympathetic trunk.
Experimental: Early chest tube removal plus TEA	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).; Procedure: Early chest tube removal; Postoperatively, the chest tube is connected to a Thopaz+ system (Medela inc.) and installed to -2 or -5 cm H2O. The chest tube will be removed at the earliest at 4 hours postoperatively in case the following criteria are met: The patient is lucid and capable of sitting up straight in bed on his/her own; No air leakage indicated by the Thopaz+ system during at least 4 hours, or <15 mL/min air leakage during at least 6 hours; Postoperative X ray (performed at least 4 hours after surgery or ultimately performed the morning of POD1) demonstrating complete lung expansion at the level of the hilum.; Absence of pure blood drainage by the Thopaz+ system
Experimental: Early chest tube removal plus single-shot PVB	Procedure: Single-shot paravertebral block; At the beginning of surgery, before pleurectomy, a single shot PVB will be placed at 10 levels (T2-T11) by the surgeon with Ropivacaine 7.5mg/mL and 2-3mL per site under direct thoracoscopic vision. The injection site will be chosen at the paravertebral space, just lateral adjacent to the sympathetic trunk.; Procedure: Early chest tube removal; Postoperatively, the chest tube is connected to a Thopaz+ system (Medela inc.) and installed to -2 or -5 cm H2O. The chest tube will be removed at the earliest at 4 hours postoperatively in case the following criteria are met: The patient is lucid and capable of sitting up straight in bed on his/her own; No air leakage indicated by the Thopaz+ system during at least 4 hours, or <15 mL/min air leakage during at least 6 hours; Postoperative X ray (performed at least 4 hours after surgery or ultimately performed the morning of POD1) demonstrating complete lung expansion at the level of the hilum.; Absence of pure blood drainage by the Thopaz+ system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate	Safety outcome: absolute number of patients with recurrence (maximum allowable difference between early and late chest tube removal groups of 9 recurrences) defined as having an ipsilateral recurrent pneumothorax after chest tube removal, confirmed by X-ray or CT within 1-year, requiring reintervention (either tube thoracostomy or reoperation) or hospital readmission.	Until 1 year follow-up
Pain score	Proportion of pain scores ≥4 as assessed by the numerical rating scale (NRS), defined as the number of NRS scores ≥4 divided by the total number of NRS measurements. NRS score is measured from 0 until 10; lowest value signifying no pain and highest value signifying worst pain.	Postoperative day 0-3
Postoperative length of stay (LOS)	the total number of in-hospital days including readmissions due to complications or recurrence within 30 postoperative days (POD). The day of surgery will be POD 0.	30 postoperative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	until 4 weeks follow-up
Quality of Life (QoL)	QoL will be measured using the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30). This 33-item questionnaire incorporates functional scales, symptom scales and overall health status. The scale range from 0 to 100; a higher score represents a higher response level.	until 1 year follow-up
Postoperative complications	according to the Clavien-Dindo classification	until 4 weeks follow-up
Postoperative chest tube drainage during hospitalisation	Total number of postoperative days with a chest tube. The day of surgery is day 0.	30 postoperative days
Cumulative use of opioids and analgesics	total opioid and non-opioid consumption as supplementary analgesic requirement	postoperative day 0-4 and the use at 4 weeks follow-up
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 0-4
Health status	Health status will we measured using the EuroQol-5D (EQ-5D) tool. This tool incorporates 5 aspects regarding health. The scale range from 0 to 100; a higher score represents a higher health status.	until 1 year follow-up
patient satisfaction	5-point Likert scale: not at all satisfied, slightly satisfied, neutral, very satisfied and extremely satisfied	postoperative day 0-4

Collaborators and Investigators

• Sponsor: Maxima Medical Center
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Leiden University Medical Center; ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: September 22, 2023
• First Posted (Actual): September 25, 2023

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Pleural Diseases; Pain, Postoperative; Pneumothorax
• Other Study ID Numbers: NL84451.015.23

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