Nitrous Oxide for Identifying the Intersegmental Plane in Segmentectomy: A Randomized Controlled Trial

Lung cancer is currently one of the most common malignant tumors in the world. In recent years, with the popularity of high-resolution CT, more and more early-stage lung cancers have been found. Anatomic pneumonectomy is gradually popular because it can completely remove lung nodules and preserve lung function to the greatest extent. During the surgery, the precise and rapid determination of intersegmental border is one of the key technologies. Improved inflation-deflation method is currently the most widely used method in clinical practice. Previous studies demonstrated that increasing the concentration of nitrous oxide in mixtures of N2O/O2 will lead to a faster rate of collapse. The rapid diffusion properties of N2O would be expected to speed lung collapse and so facilitate surgery. This study was designed to explore three types of inspired gas mixture used during two-lung anesthesia had an effect on the intersegmental border appearance time during pneumonectomy and its feasibility and safety: 75% N2O (O2: N2O = 1: 3), 50% N2O (O2: N2O = 1: 1), 100% oxygen.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Pulmonary Nodule, Solitary; Pulmonary Nodule, Multiple
• Intervention / Treatment: Procedure: nitrous oxide

Detailed Description

This randomized parallel group trial enrolled lung cancer patients scheduled to receive thoracoscopic anatomic segmentectomy at The First Affiliated Hospital of Nanjing Medical University. When anesthesia induction was completed, intubation was carried out using an appropriate-size double-lumen endobronchial tube (DLT) and the position of the DLT was confirmed with fiberoptic bronchoscopy and adjusted as needed. OLV of the dependent lung with FiO2=1.0 was begun in the lateral position, by clamping the DLT to the nonventilated lung proximally and opening the distal port of the DLT lumen to the atmosphere. Tidal volumes were 5 mL/kg ideal bodyweight (male: height -100, and female: height - 105) without positive end expiratory pressure (PEEP). In order to avoid possible confounding effects of inhalation of volatile anesthetics on oxygenation, all subjects received total intravenous anesthesia.

According to preoperative 3D-CTBA evaluation of bronchial and vascular structure of pulmonary nodules and pulmonary segments, the target segmental bronchus, arteries and intra-segment veins were accurately identi-fied and dissected by ligation or stapler cutting. After that, the anesthesiologist began to make preparations for the lung inflation. The portable nitrous oxide concentration detector (TD600-SH-B-N2O) was installed to detect N2O concentration (vol%), and then adjusted the anesthesia machine to the manual control mode. The flow of the selected gas mixture was set to 8L/min (Group75 set to N2O:O2=6:2, Group50 set to N2O:O2=4:4, Group0 set to O2=8), avoiding the interference of the total gas flow. When the N2O concentration detector reached the predetermined gas concentration, and then the collapsed lung was re-expanded completely with controlled airway pressure under 20 cmH2O (1cm H2O=0.098 kPa) by the anesthesiologist. This procedure took approximately 1 min, and then FiO2=1.0 was performed after the initiation of the OLV.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • The First Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210029
      • The First Affiliated Hospital with Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1、20 to 70 years of age; 2、early stage lung cancer（diameter of tumor consolidation ≤ 2cm, none evidence of lymph node or distant metas-tasis, c-stage ⅠA1 or ⅠA2）（active limited resection）； 3、 patients at high risk due to poor general condition who cannot undergo lobectomy (c-stage IA1 to IA3) (passive limited resection)

Exclusion Criteria:

1. a history of severe asthma or pneumothorax；
2. pulmonary bullae on chest CT；
3. patient refusal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group75; According to preoperative 3D-CTBA evaluation of bronchial and vascular structure of pulmonary nodules and pulmonary segments, the target segmental bronchus, arteries and intra-segment veins were accurately identified and dissected by ligation or stapler cutting. After that, the anesthesiologist began to make preparations for the lung inflation. The portable nitrous oxide concentration detector (TD600-SH-B-N2O) was installed to detect N2O concentration (vol%), and then adjusted the anesthesia machine to the manual control mode. The flow of the selected gas mixture was set to 8L/min (Group75 set to N2O:O2=6:2). When the N2O concentration detector reached the predetermined gas concentration, and then the collapsed lung was re-expanded completely with controlled airway pressure under 20 cmH2O (1cm H2O=0.098 kPa) by the anesthesiologist. This procedure took approximately 1 min, and then FiO2=1.0 was performed after the initiation of the OLV.	Procedure: nitrous oxide; During one-lung ventilation with an open chest, the nonventilated lung collapses initially due to elastic recoil, which quickly brings the lung down to its closing capacity. Remaining gas in the lung is then removed by absorption into the pulmonary capillary blood. The rapid diffusion properties of N2O（Blood gas distribution coefficient is 0.47）would be expected to speed lung collapse and so facilitate surgery. The previous study suggested that increasing the concentration of N2O in mixtures of N2O/O2 will lead to a faster rate of collapse. When using nitrous oxide in oxygen during lung ventilation, ongoing oxygen uptake by blood shunting will serve to increase the partial pressure of nitrous oxide in parts of the lung that are still expanded. This will soon result in a partial pressure gradient for nitrous oxide uptake also, with a consequent faster rate of lung collapse than would occur in a patient being ventilated with 100% oxygen.; Other Names: oxygen
Experimental: Group50; According to preoperative 3D-CTBA evaluation of bronchial and vascular structure of pulmonary nodules and pulmonary segments, the target segmental bronchus, arteries and intra-segment veins were accurately identified and dissected by ligation or stapler cutting. After that, the anesthesiologist began to make preparations for the lung inflation. The portable nitrous oxide concentration detector (TD600-SH-B-N2O) was installed to detect N2O concentration (vol%), and then adjusted the anesthesia machine to the manual control mode. The flow of the selected gas mixture was set to 8L/min (Group50 set to N2O:O2=4:4). When the N2O concentration detector reached the predetermined gas concentration, and then the collapsed lung was re-expanded completely with controlled airway pressure under 20 cmH2O (1cm H2O=0.098 kPa) by the anesthesiologist. This procedure took approximately 1 min, and then FiO2=1.0 was performed after the initiation of the OLV.	Procedure: nitrous oxide; During one-lung ventilation with an open chest, the nonventilated lung collapses initially due to elastic recoil, which quickly brings the lung down to its closing capacity. Remaining gas in the lung is then removed by absorption into the pulmonary capillary blood. The rapid diffusion properties of N2O（Blood gas distribution coefficient is 0.47）would be expected to speed lung collapse and so facilitate surgery. The previous study suggested that increasing the concentration of N2O in mixtures of N2O/O2 will lead to a faster rate of collapse. When using nitrous oxide in oxygen during lung ventilation, ongoing oxygen uptake by blood shunting will serve to increase the partial pressure of nitrous oxide in parts of the lung that are still expanded. This will soon result in a partial pressure gradient for nitrous oxide uptake also, with a consequent faster rate of lung collapse than would occur in a patient being ventilated with 100% oxygen.; Other Names: oxygen
Active Comparator: Group0; According to preoperative 3D-CTBA evaluation of bronchial and vascular structure of pulmonary nodules and pulmonary segments, the target segmental bronchus, arteries and intra-segment veins were accurately identified and dissected by ligation or stapler cutting. After that, the anesthesiologist began to make preparations for the lung inflation. The portable nitrous oxide concentration detector (TD600-SH-B-N2O) was installed to detect N2O concentration (vol%), and then adjusted the anesthesia machine to the manual control mode. The flow of the selected gas mixture was set to 8L/min (Group0 set to O2=8). When the N2O concentration detector reached the predetermined gas concentration, and then the collapsed lung was re-expanded completely with controlled airway pressure under 20 cmH2O (1cm H2O=0.098 kPa) by the anesthesiologist. This procedure took approximately 1 min, and then FiO2=1.0 was performed after the initiation of the OLV.	Procedure: nitrous oxide; During one-lung ventilation with an open chest, the nonventilated lung collapses initially due to elastic recoil, which quickly brings the lung down to its closing capacity. Remaining gas in the lung is then removed by absorption into the pulmonary capillary blood. The rapid diffusion properties of N2O（Blood gas distribution coefficient is 0.47）would be expected to speed lung collapse and so facilitate surgery. The previous study suggested that increasing the concentration of N2O in mixtures of N2O/O2 will lead to a faster rate of collapse. When using nitrous oxide in oxygen during lung ventilation, ongoing oxygen uptake by blood shunting will serve to increase the partial pressure of nitrous oxide in parts of the lung that are still expanded. This will soon result in a partial pressure gradient for nitrous oxide uptake also, with a consequent faster rate of lung collapse than would occur in a patient being ventilated with 100% oxygen.; Other Names: oxygen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Intersegmental Border Appearance Time During the Surgery	The starting point of intraoperative expansion and collapse observation is the time when the lung tissue is completely expanded after blocking the relevant structure of the target segment; the end point is when a clear demarcation is formed between the target segment and the immediately-reserved lung segment, and this boundary does not follow significant changes over time), and the time was recorded in seconds (S).	The time of appearance of the intersegmental plane that can be performed satisfactorily by surgeons

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The arterial blood gas results during perioperative period	Extracting arterial blood gas	Immediately after the radial arterial catheterization when inhaling the air, pre-intervention, 5minutes, 15minnutes during the single lung ventilation after the intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Postoperative Complications and the Length of Hospital Stay	Recording duration of surgery, the incidence of postoperative complications (including air leak, chylothorax, atelectasis, pulmonary embolism, pulmonary infection), total thoracic drainage, duration of drainage and postoperative hospital stay.	2 weeks after surgery.

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Study Chair: cunming liu, Master, The First Affiliated Hospital with Nanjing Medical University; Principal Investigator: zicheng liu, Doctorate, The First Affiliated Hospital with Nanjing Medical University; Principal Investigator: Wei Wen, Master, The First Affiliated Hospital with Nanjing Medical University; Principal Investigator: Jun Wang, Master, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Actual): July 15, 2020
• Study Completion (Actual): July 15, 2020

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: March 7, 2020
• First Posted (Actual): March 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: lung cancer; nitrous oxide; pulmonary nodule; thoracoscopic anatomic segmentectomy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Multiple Pulmonary Nodules; Solitary Pulmonary Nodule; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Anesthetics, Inhalation; Nitrous Oxide
• Other Study ID Numbers: 2019-SR-449

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
• product manufactured in and exported from the U.S.: No