The Role of Periodic Alveolar Recruitment Maneuvers in Intraoperative Protective Ventilation (REMAIN-2)

Effects of Three Open-lung Strategies on Respiratory Function and Lung Injury in Protective Ventilation for Laparoscopic Anterior Resection: a Randomized Controlled Trial

The goal of this clinical trial is to compare three open-lung strategies on respiratory function and lung injury in protective ventilation for laparoscopic anterior resection. It aims to answer whether a periodic alveolar recruitment maneuvers (PARM) strategy alone was an appropriate open-lung strategy in intraoperative protective ventilation. Patients were randomly assigned (1:1:1) to receive one of three open-lung strategies in protective ventilation: PARM alone (alveolar recruitment maneuvers [ARM] repeated every 30 min), positive end-expiratory pressure (PEEP) alone (a PEEP of 6 to 8 cm H2O), or a combination of PEEP and PARM (a PEEP of 6 to 8 cm H2O combined with ARM repeated every 30 min). The primary outcome is the mechanical power before the end of intraoperative mechanical ventilation. Secondary outcomes included the accumulative intraoperative mechanical power, an arterial partial pressure of oxygen (PaO2) / inhaled oxygen concentration (FiO2) ratio (P/F ratio) before the end of intraoperative mechanical ventilation, the rates of respiratory failure at post-anesthesia care unit (PACU) and three postoperative days, the concentration of soluble advanced glycation end products receptor (sRAGE) and Clara cell protein 16 (CC16) at the end of surgery, postoperative pulmonary complications score, postoperative hospitalization days and so on.

Study Overview

• Status: Completed
• Conditions: Postoperative Pulmonary Complications; Mechanical Power; Protective Ventilation; Alveolar Recruitment Maneuvers
• Intervention / Treatment: Other: periodic alveolar recruitment maneuvers; Other: positive end-expiratory pressure

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • The Sixth Affiliated Hospital, Sun Yat-sen University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Undergoing elective laparoscopic anterior resection and expected duration of mechanical ventilation 2 to 5 h.
2. Had an intermediate risk of developing postoperative pulmonary complications.
3. Pulse oxygen saturation in room air ≥ 94%.
4. Aged 60 to 80 years.

Exclusion Criteria:

• 1. Had received invasive mechanical ventilation for longer than 1 h within the last 2 weeks prior to surgery.

  2. Had a history of pneumonia within 1 month prior to surgery. 3. Had severe chronic obstructive pulmonary disease or pulmonary bullae. 4. Had a progressive neuromuscular illness. 5. With an American Society of Anesthesiologists (ASA) physical status of IV or higher.

  6. Intracranial hypertension. 7. Body mass index (BMI) ≥30 kg/m2. 8. Were involved in other interventional studies.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: periodic alveolar recruitment maneuvers (PARM) alone; Alveolar recruitment maneuvers [ARM] repeated every 30 min after tracheal intubation and after any disconnection from the ventilator.	Other: periodic alveolar recruitment maneuvers; A stepwise increment of tidal volume was used for each ARM.
Active Comparator: positive end-expiratory pressure (PEEP) alone; PEEP was routinely set at 6 cm H2O. If it was in a state of Trendelenburg position or carbon dioxide pneumoperitoneum, PEEP was set to 8 cm H2O.	Other: positive end-expiratory pressure; a PEEP of 6 to 8 cm H2O
Active Comparator: a combination of PEEP and PARM; Alveolar recruitment maneuvers [ARM] repeated every 30 min after tracheal intubation and after any disconnection from the ventilator. PEEP was routinely set at 6 cm H2O. If it was in a state of Trendelenburg position or carbon dioxide pneumoperitoneum, PEEP was set at 8 cm H2O.	Other: periodic alveolar recruitment maneuvers; A stepwise increment of tidal volume was used for each ARM.; Other: positive end-expiratory pressure; a PEEP of 6 to 8 cm H2O

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative mechanical power	Intraoperative mechanical power, calculated from values of tidal volume (Vt ), respiratory rate (RR), positive end-expiratory pressure (PEEP), plateau pressure (Pplat), and peak inspiratory pressure (Ppeak), using the following formula: mechanical power (J/min) = 0.098 × RR × Vt × (PEEP + ½[Pplat - PEEP] + [Ppeak - Pplat])	Before the end of intraoperative mechanical ventilation, about 5 to 10 minutes before the end of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical power during capnoperitoneum	mechanical power, J/min	30 minutes after starting carbon dioxide pneumoperitoneum
Accumulative mechanical power (AMP)	Accumulative mechanical power (AMP) = AMP before capnoperitoneum + AMP during capnoperitoneum + AMP after capnoperitoneum. Accumulative mechanical power before capnoperitoneum = mechanical power before capnoperitoneum (10 min after mechanical ventilation) × the length of mechanical ventilation before capnoperitoneum. Accumulative mechanical power during capnoperitoneum = mechanical power during capnoperitoneum (30 min after mechanical ventilation) × the length of mechanical ventilation during capnoperitoneum. Accumulative mechanical power after capnoperitoneum (after the end of capnoperitoneum) = mechanical power after capnoperitoneum (10 min after the end of capnoperitoneum) × the length of mechanical ventilation after capnoperitoneum	During intraoperative mechanical ventilation, an average of 3 hours
An arterial partial pressure of oxygen (PaO2) / Inhaled oxygen concentration (FIO2) ratio (P/F ratio)	P/F ratio, mmHg	Before the end of intraoperative mechanical ventilation, about 5 to 10 minutes before the end of surgery
Shunt fraction	Shunt fraction, %	Before the end of intraoperative mechanical ventilation, about 5 to 10 minutes before the end of surgery
Dead space rate	Arterial carbon dioxide partial pressure (PaCO2); partial pressure of carbon dioxide in end expiratory gas (PetCO2); Dead space fraction = (PaCO2-PetCO2)/ PaCO2.	Before the end of intraoperative mechanical ventilation, about 5 to 10 minutes before the end of surgery
Rate of respiratory failure at post-anesthesia care unit (PACU)	Respiratory failure: PaO2 < 60 mmHg or pulse oxygen saturation (SpO2) < 90% on room air, or a P/F ratio < 300 mmHg and requiring oxygen therapy.	Stay in the PACU for at least 20 minutes and at most 3 hours; assessed at 5 to 10 minutes before leaving PACU
Soluble advanced glycation end products receptor (sRAGE)	The concentration of plasma sRAGE, pg/ml	20 minutes after entering PACU
Clara cell protein 16 (CC16)	The concentration of plasma CC16, ng/ml	20 minutes after entering PACU
Surfactant Protein D (SP-D)	The concentration of plasma SP-D, ug/ml	20 minutes after entering PACU
Interleukin 6 (IL-6)	The concentration of plasma IL-6, pg/ml	20 minutes after entering PACU
Rate of postoperative respiratory failure	Respiratory failure: PaO2 < 60 mmHg or SpO2 < 90% on room air, or a P/F ratio < 300 mmHg and requiring oxygen therapy.	Time Frame: Day 0 to 3 after surgery
Rate of sustained hypoxaemia	Sustained hypoxaemia, hypoxaemia at any two consecutive days; hypoxaemia: during a follow-up visit when the patient was awake and breathing room air, SpO2 ≤ 92% or the change of SpO2 (ΔSpO2, preoperative SpO2 minus postoperative SpO2) ≥ 5%.	Day 0 to 3 after surgery
Postoperative pulmonary complications score	Postoperative pulmonary complications score: Operational Definitions of Postoperative Pulmonary Complications (Doi: 10.1001/jama.296.15.1851), graded on a scale from 0 (no pulmonary complications) to 4 (the most severe complications).	Day 0 to 3 after surgery
Postoperative hospitalization days	The duration between the operation date and the actual discharge date.	Day 0 to 30 after surgery
Death from any cause	Intraoperative or postoperative death from any cause	Day 0 to 30 after surgery
Rate of intraoperative hypotension	Intraoperative hypotension, mean arterial pressure (MAP) < 60 mmHg lasting more than 3 minutes.	During intraoperative mechanical ventilation, an average of 3 hours
Rate of need for vasoconstrictors	MAP < 60 mmHg and using any vasoconstrictors.	During intraoperative mechanical ventilation, an average of 3 hours
Rate of intraoperative hypoxemia	Intraoperative hypoxemia, SpO2 ≤ 92% lasting more than 3 minutes.	During intraoperative mechanical ventilation, an average of 3 hours
Rate of intraoperative bradycardia	Intraoperative bradycardia, heart rate ≤ 50 bpm and the decrease of heart rate from the basic value ≥ 20% lasting more than 3 minutes.	During intraoperative mechanical ventilation, an average of 3 hours
Rate of pneumothorax	Pneumothorax, air in the pleural space with no vascular bed surrounding the visceral pleura.	During surgery or within 7 days after surgery
Rate of pleural effusion	Pleural effusion, diagnosed according to previous literature (Doi: 10.1097/EJA.0000000000000118).	within 7 days after surgery
Unexpected admission to ICU	It does not include the patients who enter ICU at the request of surgeons but have normal spontaneous breathing, stable circulation and no disturbance of consciousness.	within 30 days after surgery
Tumor Necrosis Factor alpha (TNF-α)	TNF-α, pg/ml.	20 minutes after entering PACU

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Investigators: Principal Investigator: Hong Li, MD, The Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2023
• Primary Completion (Actual): November 8, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: July 18, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 28, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: E2023069

Drug and device information, study documents

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