Physiological Effects of Lung Recruitment During General Anesthesia and Low-tidal Volume Ventilation

Study Overview
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Brief Summary
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Low-tidal volume ventilation is arising as a tool to optimize the ventilatory management and to improve clinical outcome in patients undergoing general anesthesia for abdominal surgery. A recent large randomized controlled trial failed to detect a significant difference between two different approaches for ensuring adequate lung recruitment (PEEP=12 cmH2O + scheduled recruiting maneuvers vs. PEEP 2 cmH2O) during protective ventilation. Thus, in patients undergoing open abdominal surgery and receiving low-tidal volumes, the effects of different positive end-expiratory pressure (PEEP) levels and recruiting maneuvers remain to be established. Design: prospective, cross-over, physiological trial. PURPOSE To assess the physiological effects of different PEEP levels with or without scheduled recruiting maneuvers in patients undergoing general anesthesia for open abdominal surgery and receiving low-tidal volume ventilation.

Official Title
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Physiological Effects of Positive End-expiratory Pressure With or Without Recruiting Maneuvers in Patients Receiving Low-tidal Volume Ventilation During General Anesthesia for Open Abdominal Surgery. A Randomized, Cross-over Study

Conditions
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Anesthesia, General, Surgery

Intervention / Treatment
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* Drug: Fluid resuscitation or amine administration
* Drug: General anesthetic
* Drug: Fluid administration
* Procedure: Low-tidal volume ventilation
* Procedure: Scheduled recruiting maneuvers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA physical status I-II patients scheduled for open abdominal surgery (major gastrointestinal surgery: duodeno-cephalo-pancreatectomy, gastrectomy, hemi-colectomy; gynecological surgery; oncologic surgery) Expected duration of surgery >= 150 minutes Exclusion Criteria: Pregnancy BMI>30 kg/m^2 hepatic surgery Cardiac failure NYHA>2 History of chronic respiratory failure

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Each patient will be randomized to receive or not scheduled recruiting maneuvers every hour. In each of the two groups, patients will receive mechanical ventilation with 3 different levels of PEEP in a sequential, randomized, cross-over manner: each period will last 40 minutes. A randomization sequence will be produced by a dedicated software and sealed envelopes will be used to allocate patients to study treatments.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEEP2 + RM<br>General anesthetic, 40 minutes of Low-tidal volume ventilation with PEEP=2 cmH2O and scheduled recruiting maneuvers at the beginning of each PEEP step, continuous fluid administration at a standard dose, fluid resuscitation or amine administration if deemed necessary by the attending physician blinded to the design of the study | Drug: Fluid resuscitation or amine administration<br>* Fluid administration or amine administration if deemed necessary by the attending physician. Haemodynamics will be monitored through noninvasive cardiac output assessment by arterial pulse contour analysis<br>Drug: General anesthetic<br>* Total intravenous anesthesia with a standard protocol<br>Drug: Fluid administration<br>* 3-5 ml/kg of balanced crystalloids will be administered throughout the whole surgical procedure<br>Procedure: Low-tidal volume ventilation<br>* Volume-control ventilation with tidal volume=7 ml/kg of predicted body weight for the entire surgical procedure. Respiratory rate will be set to maintain EtCO2 within a physiological range and kept unchanged for the entire duration of the study<br>Procedure: Scheduled recruiting maneuvers<br>* Pressure-control ventilation inspiratory pressure=10 cmH2O. Steplike 5-cmH2O-PEEP increase every 30 seconds to achieve a peep of 35 cmH2O, followed by 5-cmH2O-PEEP reduction every 30 seconds to set PEEP<br>|
| Experimental: PEEP7 + RM<br>General anesthetic, 40 minutes of Low-tidal volume ventilation with PEEP=7 cmH2O and scheduled recruiting maneuvers at the beginning of the PEEP step, continuous fluid administration at a standard dose, fluid resuscitation or amine administration if deemed necessary by the attending physician blinded to the design of the study | Drug: Fluid resuscitation or amine administration<br>* Fluid administration or amine administration if deemed necessary by the attending physician. Haemodynamics will be monitored through noninvasive cardiac output assessment by arterial pulse contour analysis<br>Drug: General anesthetic<br>* Total intravenous anesthesia with a standard protocol<br>Drug: Fluid administration<br>* 3-5 ml/kg of balanced crystalloids will be administered throughout the whole surgical procedure<br>Procedure: Low-tidal volume ventilation<br>* Volume-control ventilation with tidal volume=7 ml/kg of predicted body weight for the entire surgical procedure. Respiratory rate will be set to maintain EtCO2 within a physiological range and kept unchanged for the entire duration of the study<br>Procedure: Scheduled recruiting maneuvers<br>* Pressure-control ventilation inspiratory pressure=10 cmH2O. Steplike 5-cmH2O-PEEP increase every 30 seconds to achieve a peep of 35 cmH2O, followed by 5-cmH2O-PEEP reduction every 30 seconds to set PEEP<br>|
| Experimental: PEEP12 + RM<br>General anesthetic, 40 minutes of Low-tidal volume ventilation with PEEP=12 cmH2O and scheduled recruiting maneuvers at the beginning of the PEEP step, continuous fluid administration at a standard dose, fluid resuscitation or amine administration if deemed necessary by the attending physician blinded to the design of the study | Drug: Fluid resuscitation or amine administration<br>* Fluid administration or amine administration if deemed necessary by the attending physician. Haemodynamics will be monitored through noninvasive cardiac output assessment by arterial pulse contour analysis<br>Drug: General anesthetic<br>* Total intravenous anesthesia with a standard protocol<br>Drug: Fluid administration<br>* 3-5 ml/kg of balanced crystalloids will be administered throughout the whole surgical procedure<br>Procedure: Low-tidal volume ventilation<br>* Volume-control ventilation with tidal volume=7 ml/kg of predicted body weight for the entire surgical procedure. Respiratory rate will be set to maintain EtCO2 within a physiological range and kept unchanged for the entire duration of the study<br>Procedure: Scheduled recruiting maneuvers<br>* Pressure-control ventilation inspiratory pressure=10 cmH2O. Steplike 5-cmH2O-PEEP increase every 30 seconds to achieve a peep of 35 cmH2O, followed by 5-cmH2O-PEEP reduction every 30 seconds to set PEEP<br>|
| Experimental: PEEP2 - RM<br>General anesthetic, 40 minutes of Low-tidal volume ventilation with PEEP=2 cmH2O, continuous fluid administration at a standard dose, fluid resuscitation or amine administration if deemed necessary by the attending physician blinded to the design of the study | Drug: Fluid resuscitation or amine administration<br>* Fluid administration or amine administration if deemed necessary by the attending physician. Haemodynamics will be monitored through noninvasive cardiac output assessment by arterial pulse contour analysis<br>Drug: General anesthetic<br>* Total intravenous anesthesia with a standard protocol<br>Drug: Fluid administration<br>* 3-5 ml/kg of balanced crystalloids will be administered throughout the whole surgical procedure<br>Procedure: Low-tidal volume ventilation<br>* Volume-control ventilation with tidal volume=7 ml/kg of predicted body weight for the entire surgical procedure. Respiratory rate will be set to maintain EtCO2 within a physiological range and kept unchanged for the entire duration of the study<br>|
| Experimental: PEEP7 - RM<br>General anesthetic, 40 minutes of Low-tidal volume ventilation with PEEP=7 cmH2O, continuous fluid administration at a standard dose, fluid resuscitation or amine administration if deemed necessary by the attending physician blinded to the design of the study | Drug: Fluid resuscitation or amine administration<br>* Fluid administration or amine administration if deemed necessary by the attending physician. Haemodynamics will be monitored through noninvasive cardiac output assessment by arterial pulse contour analysis<br>Drug: General anesthetic<br>* Total intravenous anesthesia with a standard protocol<br>Drug: Fluid administration<br>* 3-5 ml/kg of balanced crystalloids will be administered throughout the whole surgical procedure<br>Procedure: Low-tidal volume ventilation<br>* Volume-control ventilation with tidal volume=7 ml/kg of predicted body weight for the entire surgical procedure. Respiratory rate will be set to maintain EtCO2 within a physiological range and kept unchanged for the entire duration of the study<br>|
| Experimental: PEEP12 - RM.<br>General anesthetic, 40 minutes of Low-tidal volume ventilation with PEEP=12 cmH2O, continuous fluid administration at a standard dose, fluid resuscitation or amine administration if deemed necessary by the attending physician blinded to the design of the study | Drug: Fluid resuscitation or amine administration<br>* Fluid administration or amine administration if deemed necessary by the attending physician. Haemodynamics will be monitored through noninvasive cardiac output assessment by arterial pulse contour analysis<br>Drug: General anesthetic<br>* Total intravenous anesthesia with a standard protocol<br>Drug: Fluid administration<br>* 3-5 ml/kg of balanced crystalloids will be administered throughout the whole surgical procedure<br>Procedure: Low-tidal volume ventilation<br>* Volume-control ventilation with tidal volume=7 ml/kg of predicted body weight for the entire surgical procedure. Respiratory rate will be set to maintain EtCO2 within a physiological range and kept unchanged for the entire duration of the study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Driving Pressure | Respiratory system elastic pressure (Plateau pressure-total PEEP) | At the end of each 40-minute step | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung strain | Lung static and dynamic strain | At the end of each 40-minute step | 
| Dead space | Approximated as the difference between End-tidal CO2 and PaCO2 divided by PaCO2 | At the end of each 40-minute step | 
| Oxygenation | PaO2/FiO2 | At the end of each 40-minute step | 
| Lung recruitment | % (lung recruitment/change in end-expiratory lung volume) | At the end of each 40-minute step | 
| Lung overdistension due to PEEP | % (lung overdistension/change in end-expiratory lung volume) | At the end of each 40-minute step | 
| Functional residual capacity | Change in functional residual capacity due to PEEP, measured with the Nitrogen washin-washout technique | At the end of each 40-minute step | 
| Heart rate | heart rate | At the end of each 40-minute step | 
| Blood pressure | Arterial blood pressure | At the end of each 40-minute step | 
| Stroke volume | Stroke volume, measured by pulse contour analysis | At the end of each 40-minute step | 
| Stroke volume variation | Stroke volume variation, measured by pulse contour analysis | At the end of each 40-minute step | 
| Cardiac Output | Stroke volume x heart rate | At the end of each 40-minute step | 
| Fluid requirements | Fluid bolus requirements, according to the decision of the attending physician blinded to the design of the study | At the end of each 40-minute step | 
| Vasoactive agents | Vasoactive agents requirements, according to the decision of the attending physician blinded to the design of the study | At the end of each 40-minute step | 
| Adverse events | Adverse events | At the end of each 40-minute step |