Opioid-Free Combined Anesthesia With Spontaneous Breathing for VATS

Opioid-Free Combined Anesthesia Under Spontaneous Breathing for Video-Assisted Thoracoscopic Surgery of Pulmonary Nodules: A Multicenter, Open-Label, Randomized Controlled, 2x2 Factorial Design Clinical Study

Non-tracheal intubated combined anesthesia with preserved spontaneous breathing significantly enhances the quality and speed of recovery post-VATS for patients undergoing lung nodule surgery. The "opioid-sparing strategy," which substitutes ketamine for opioids during surgery, not only provides effective analgesia but also protects perioperative lung function and reasonably prevents the occurrence of opioid-related adverse reactions; it also reduces medical costs and shortens the average hospital stay. However, the degree of benefit to patients lacks high-level clinical evidence. This study aims to comprehensively assess the effect of opioid-free combined anesthesia with preserved spontaneous breathing for VATS lung nodule surgery on postoperative rapid recovery from multiple aspects including postoperative lung function and pulmonary complications, pain, gastrointestinal function, nausea/vomiting, cognitive function, and depression/anxiety, intending to expand the dataset and application prospects in this field, and increase feasibility experience.

Study Overview

• Status: Recruiting
• Conditions: Video-assisted Thoracoscopic Lung Surgery；Anesthesia
• Intervention / Treatment: Drug: opioid based strategy; Procedure: Laryngeal mask airway; Preserved spontaneous breathing; Drug: opioid-free strategy; Procedure: Double lumen tracheal tube; Mechanical ventilation

Detailed Description

This study is a prospective, multicenter, randomized controlled, open-label, 2x2 factorial design trial involving two types of interventions: ventilation methods (2 levels: preserved spontaneous breathing, mechanical ventilation) and combined anesthesia methods (2 levels: opioid-free combined anesthesia, opioid-based combined anesthesia). To evaluate the clinical efficacy and safety of these two types of interventions, four parallel groups of patients undergoing video-assisted thoracoscopic surgery for pulmonary nodules under different anesthesia strategies were established: preserved spontaneous breathing and opioid-based combined anesthesia (OSB group), preserved spontaneous breathing and opioid-free combined anesthesia (KSB group), double-lumen endotracheal tube mechanical ventilation and opioid-based combined anesthesia (OMV group), and double-lumen endotracheal tube mechanical ventilation and opioid-free combined anesthesia (KMV group). This study will be conducted in the thoracic surgical centers of six hospitals in China, carried out by experienced senior anesthetists and thoracic surgeons. Patients undergoing anesthesia in this study will experience three observation phases. Phase 1 (perioperative phase, day 0 to day 2): Observing the lung function status and the occurrence of adverse events under different anesthesia plans during the perioperative period; Phase 2 (postoperative hospital stay, day 3 to day 7): Observing the lung function status and the occurrence of adverse events under different anesthesia plans during the hospital stay; Phase 3 (short-term follow-up, day 8 to day 30): Observing the lung function status and the occurrence of adverse events under different anesthesia plans during the short-term follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 480
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui Xu, Professor; Phone Number: (86)-13971001596; Email: huixu@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Tongji Hospital
      • Contact: Hui Xu; Phone Number: +8613971001596; Email: huixu@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ASA grades 1-2
2. Age > 18 years and < 70 years
3. Male or female patients
4. VATS pulmonary nodule operation is planned under general anesthesia
5. Voluntarily participate in the study and sign the informed consent

Exclusion Criteria:

1. Subject's operation is aborted
2. Serious adverse events, complications or special physiological changes during the perioperative period should not be continued
3. Expansion of surgical scope: resection of complex lung segment or complex lung lobectomy, thoracoscopic assisted small-incision surgery with enlarged incision, requiring pulmonary blood Tracheoplasty or bronchoplasty, partial pericardiectomy or conversion to thoracotomy
4. Those who need a second operation within a month
5. The patient or his/her guardian requests to withdraw on his/her own
6. Reasons why other researchers think the study needs to be discontinued

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OSB; Anesthesia was induced by intravenous injection of Sufentanil 0.1 µg/kg and propofol 2 mg /kg. The patient was placed with a laryngeal mask airway, connected to an anesthetic ventilator with spontaneous breathing mode. Anesthesia was maintained with propofol (5 mg/kg/h) and remifentanil (0.01 µg/kg/min) first, and then adjusted according to the depth of anesthesia. Paravertebral nerve blocks were performed at T4 and T6 levels with ropivacaine (0.5%, 10 ml) under ultrasound guidance. A mixture of 5 ml of 2% lidocaine and 5 ml of 0.5% ropivacaine was sprayed on the surface of the visceral pleura after thoracic cavity opening. The vagal and phrenic nerve trunks were blocked with 2 ml of the mixture.	Drug: opioid based strategy; Induction and maintenance of anesthesia with opioids; Procedure: Laryngeal mask airway; Preserved spontaneous breathing; The patient used a laryngeal mask to maintain spontaneous breathing
Experimental: KSB; Anesthesia was induced by intravenous injection of Sufentanil 0.1 µg/kg and propofol 2 mg /kg. The patient was placed with a laryngeal mask airway, connected to an anesthetic ventilator with spontaneous breathing mode. Anesthesia was maintained with propofol (5 mg/kg/h) and remifentanil (0.01 µg/kg/min) first, and then adjusted according to the depth of anesthesia. Paravertebral nerve blocks were performed at T4 and T6 levels with ropivacaine (0.5%, 10 ml) under ultrasound guidance. A mixture of 5 ml of 2% lidocaine and 5 ml of 0.5% ropivacaine was sprayed on the surface of the visceral pleura after thoracic cavity opening. The vagal and phrenic nerve trunks were blocked with 2 ml of the mixture.	Procedure: Laryngeal mask airway; Preserved spontaneous breathing; The patient used a laryngeal mask to maintain spontaneous breathing; Drug: opioid-free strategy; Esketamine was used for induction and maintenance of anesthesia
Experimental: OMV; Anesthesia was induced by intravenous sufentanil injection of 0.5 μg/kg. Propofol 2 mg/kg and rocuronium 0.9 mg/kg were subsequently administered intravenously. After rocuronium took effect, double-lumen bronchial tube intubation was performed under the guidance of video laryngoscope, and fixed after the bronchoscopic examination, anesthesia ventilator was connected for mechanical ventilation, tidal volume was 6 mL/kg (ideal body weight), respiratory rate was 12-16 times /min, and end-expiratory partial pressure of carbon dioxide was maintained at 35-45 mmHg. Intraoperative anesthesia was maintained with initial intravenous pump of propofol (5 mg/kg/h) and remifentanil (0.1 μg/kg/min) first , and then adjusted according to the depth of anesthesia. Paravertebral nerve blocks were performed at T4 and T6 levels with ropivacaine (0.5%, 10 ml) under ultrasound guidance.	Drug: opioid based strategy; Induction and maintenance of anesthesia with opioids; Procedure: Double lumen tracheal tube; Mechanical ventilation; The patient was mechanically ventilated using a double-lumen tracheal catheter
Experimental: KMV; Anesthesia was induced by intravenous injection of esketamine 0.5 mg/kg. Propofol 2 mg/kg and rocuronium 0.9 mg/kg were subsequently administered intravenously. After rocuronium took effect, double-chamber tracheal tube intubation was performed under the guidance of video laryngoscope, and fixed after the bronchoscopic examination, anesthesia ventilator was connected for mechanical ventilation, tidal volume was 6 mL/kg (ideal body weight), respiratory rate was 12-16 times /min, and end-expiratory partial pressure of carbon dioxide was maintained at 35-45 mmHg. Intraoperative anesthesia was maintained with the initial intravenous pump of propofol (5 mg/kg/h) and esketamine (0.5 mg/kg/h) first , and then adjusted according to the depth of anesthesia. Paravertebral nerve blocks were performed at T4 and T6 levels with ropivacaine (0.5%, 10 ml) under ultrasound guidance.	Drug: opioid-free strategy; Esketamine was used for induction and maintenance of anesthesia; Procedure: Double lumen tracheal tube; Mechanical ventilation; The patient was mechanically ventilated using a double-lumen tracheal catheter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung function 30 days after surgery	FEV1(% pred) at 30 days after thoracoscopic pulmonary nodule surgery.	30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative respiratory parameters	Airway peak pressure	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Intraoperative respiratory parameters	oxygenation index (OI=PaO2/FiO2)	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Intraoperative respiratory parameters	alveolar arterial oxygen partial pressure difference (P(A-a)DO2)	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Intraoperative respiratory parameters	respiratory index (RI=P(A-a)DO2 /PaO2)	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Intraoperative respiratory parameters	dynamic lung compliance	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Perioperative stage indicators	Blood loss, intraoperative transfusion	At the end of the operation
Perioperative stage indicators	operation time, anesthesia time, recovery time	At the end of the operation
Postoperative pain	Postoperative pain (numerical rating scale (NRS))	Six hours, 24 hours, 48 hours after surgery
Postoperative Lung function	FVC, FEV1, FEV1 (% pred)	1, 3, 5 days after surgery
Postoperative Lung function	Copd Patient Self-Assessment Test (CAT)，Scores range from 0 to 40, with ≥10 indicating the need for medical intervention.	1, 3, 5 days after surgery
Postoperative pulmonary complications	european perioperative clinical outcome (EPCO)	1, 3, 5 days after surgery
Postoperative gastrointestinal function	Intake, Feeling nauseated, Emesis, Exam, and Duration of symptoms scoring system, I-FEED，0 ~ 2 points, normal; 3 ~ 5 scores, postoperative gastrointestinal functional intolerance; ≥6 points, POGD.	Six hours, 24 hours, 48 hours after surgery
Postoperative depression/anxiety	(hospital anxiety and depression scale, HADS) scale score，Anxiety and depression were divided into two subscales: 0-7 was negative; 8-10 is mild; 11-14 divided into moderate; 15 to 21 is classified as severe	Before surgery, 2 days after surgery
Postoperative cognitive function	(mini-mental state examination, MMSE) scale score，The maximum score is 30 points. The classification of dementia is related to the level of education, so if the elderly are illiterate and less than 17 points, primary school and less than 20 points, secondary school and above less than 24 points, then dementia.	Before surgery, 1 day after surgery, 3 days after surgery
Time of first exercise after surgery	objective parameters included stable vital signs, no obvious bleeding tendency, NRS score less than 5 points	From the end of surgery，Until the first time of off-bed activity
The 6-minute walking experiment	Measure the distance covered by an individual walking for 6 minutes at the highest speed	30 days after surgery.
Length of stay	The number of days spent in the hospital from the end of surgery until discharge or death	From date of surgery Until the date of discharge or death
Quality of life measurement	Use a WHOQOL-BREF scale rating to evaluate quality of life	the date of discharge，and Thirty days after surgery
Intraoperative circulation parameters	Blood pressure	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Intraoperative circulation parameters	heart rate	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Intraoperative circulation parameters	pulse oxygen saturation	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Intraoperative circulation parameters	anesthesia depth index	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Intraoperative circulation parameters	body temperature	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation
Intraoperative circulation parameters	urine volume	At the beginning of the operation, 30 minutes after the operation began, 1 hour, 2 hours, at the end of the operation

Collaborators and Investigators

• Sponsor: Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 7, 2024
• First Submitted That Met QC Criteria: April 11, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 2, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Narcotics; Analgesics, Opioid
• Other Study ID Numbers: S036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No