The Role of Periodic Alveolar Recruitment Maneuvers in Intraoperative Protective Ventilation

Study Overview
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Brief Summary
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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.

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

Conditions
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Protective Ventilation, Mechanical Power, Alveolar Recruitment Maneuvers, Postoperative Pulmonary Complications

Intervention / Treatment
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* Other: periodic alveolar recruitment maneuvers
* Other: positive end-expiratory pressure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing elective laparoscopic anterior resection and expected duration of mechanical ventilation 2 to 5 h. Had an intermediate risk of developing postoperative pulmonary complications. Pulse oxygen saturation in room air ≥ 94%. 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.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: periodic alveolar recruitment maneuvers (PARM) alone<br>Alveolar recruitment maneuvers [ARM] repeated every 30 min after tracheal intubation and after any disconnection from the ventilator. | Other: periodic alveolar recruitment maneuvers<br>* A stepwise increment of tidal volume was used for each ARM.<br>|
| Active Comparator: positive end-expiratory pressure (PEEP) alone<br>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<br>* a PEEP of 6 to 8 cm H2O<br>|
| Active Comparator: a combination of PEEP and PARM<br>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<br>* A stepwise increment of tidal volume was used for each ARM.<br>Other: positive end-expiratory pressure<br>* a PEEP of 6 to 8 cm H2O<br>|

What is the study measuring?
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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 |