Dead Space in Mechanical Ventilation With Constant Expiratory Flow

Study Overview
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Brief Summary
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Conventional continuous mandatory mechanical ventilation relies on the passive recoil of the chest wall for expiration. This results in an exponentially decreasing expiratory flow. Flow controlled ventilation (FCV), a new ventilation mode with constant, continuous, controlled expiratory flow, has recently become clinically available and is increasingly being adopted for complex mechanical ventilation during surgery. In both clinical and pre-clinical settings, an improvement in ventilation (CO2 clearance) has been observed during FCV compared to conventional ventilation. Recently, Schranc et al. compared flow-controlled ventilation with pressure-regulated volume control in both double lung ventilation and one-lung ventilation in pigs. They report differences in dead space ventilation that may explain the improved CO2 clearance, although their study was not designed to compare dead space ventilation within the group of double lung ventilation. Dead space ventilation, or wasted ventilation, is the ventilation of hypoperfused lung zones, and is clinically relevant, as it is a strong predictor of mortality in patients with the acute respiratory distress syndrome (ARDS) and is correlated with higher airway driving pressures which are thought to be injurious to the lung (lung stress). This trial aims to study the difference in dead space ventilation between conventional mechanical ventilation in volume-controlled mode and flow controlled-ventilation.

Official Title
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Dead Space in Mechanical Ventilation With Constant Expiratory Flow

Conditions
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Mechanical Ventilation, Artificial Respiration

Intervention / Treatment
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* Device: Flow-controlled ventilation (FCV)
* Device: Conventional volume-controlled ventilation (VCV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults [18-70] yrs General anaesthesia for elective surgery Arterial line, central venous line and endotracheal tube as part of standard of care Expected duration of controlled mechanical ventilation ≥ 60 minutes Supine position (0±10°) Exclusion Criteria: One lung ventilation Known pregnancy Increased abdominal pressure (laparoscopy or BMI > 30kg/m2) COPD GOLD IV or home oxygen dependence Clinical signs of raised intracranial pressure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover volume-controlled ventilation and flow-controlled ventilation
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FCV-VCV<br>After titration of ventilation in baseline VCV (all arms), participants will first receive 30 min of baseline-matched FCV and subsequently 30 min of baseline-matched VCV. | Device: Flow-controlled ventilation (FCV)<br>* 30 minutes of FCV, delivered with the CE-marked Evone ventilator (Ventinova medical, the Netherlands)<br>Device: Conventional volume-controlled ventilation (VCV)<br>* 30 minutes of conventional VCV, delivered with the CE-marked Aisys CS3 (GE Healthcare, USA) or Flow-i (Getinge, Sweden) ventilators.<br>|
| Experimental: VCV-FCV<br>After titration of ventilation in baseline VCV (all arms), participants will first receive 30 min of baseline-matched VCV and subsequently 30 min of baseline-matched FCV. | Device: Flow-controlled ventilation (FCV)<br>* 30 minutes of FCV, delivered with the CE-marked Evone ventilator (Ventinova medical, the Netherlands)<br>Device: Conventional volume-controlled ventilation (VCV)<br>* 30 minutes of conventional VCV, delivered with the CE-marked Aisys CS3 (GE Healthcare, USA) or Flow-i (Getinge, Sweden) ventilators.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bohr dead space ventilation (VDBr/VT) | Quantified by the Bohr approach with volumetric capnography | During FCV and VCV measurements (30 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Enghoff dead space ventilation (VDEng/VT) | Quantified by the Enghoff approach with volumetric capnography | During FCV and VCV measurements (30 minutes) | 
| Change in physiological dead space volume (Vdfys) | Measured with volumetric capnography and Enghoff's approach | During FCV and VCV measurements (30 minutes) | 
| Change in airway dead space volume (Vdaw) | Measured with volumetric capnography and Fletcher's approach | During FCV and VCV measurements (30 minutes) | 
| Change in alveolar dead space volume (Vdalv) | As measured with volumetric capnography and Fletcher's approach | During FCV and VCV measurements (30 minutes) | 
| Ventilatory efficiency (VE/VCO2) | Ratio of minute ventilation to carbon dioxide output | During FCV and VCV measurements (30 minutes) | 
| Change in airway driving pressure (∆Paw) | Calculated as the difference between the plateau pressure (Pplat) during an inspiratory pause and the dynamic positive end-expiratory pressure (PEEP), as no expiratory hold is possible on the Evone. | During FCV and VCV measurements (30 minutes) | 
| Change in transpulmonary shunt fraction (Qs/Qt) | calculated with the modified Berggren equation | During FCV and VCV measurements (30 minutes) | 
| Change in global lung hyperdistention (hyperdistentionEIT) | Calculated from electric impedance tomography | During FCV and VCV measurements (30 minutes) | 
| Change in anterio-posterior distribution of ventilation on EIT (AP) | % anterior / % posterior | During FCV and VCV measurements (30 minutes) | 
| Change in right-left distribution of ventilation on EIT (RL) | % right / % left | During FCV and VCV measurements (30 minutes) | 
| Change in 4-layered distribution of ventilation on EIT |  | During FCV and VCV measurements (30 minutes) | 
| Change in centre of ventilation on EIT |  | During FCV and VCV measurements (30 minutes) | 
| Change in cardiac index (CI) | Calculated from the arterial waveform (pulse contour analysis) by the HemoSphere monitor | During FCV and VCV measurements (30 minutes) | 
| Change in mean arterial pressure (MAP) | Measured on a radial artery line | During FCV and VCV measurements (30 minutes) | 
| Change in partial pressure of arterial CO2 (PaCO2) | Measured on an arterial blood gas | During FCV and VCV measurements (30 minutes) | 
| Change in peak expiratory flow (PEF) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in peak inspiratory flow (PIF) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in mean airway pressure (MPaw) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in tidal volume (TV) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in respiratory rate (RR) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in minute ventilation (MV) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in inspiratory time (Ti) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in expiratory time (Te) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in ratio of inspiratory time to total breath time (Ti / Tt) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in positive end-expiratory pressure (PEEP) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in peak inspiratory pressure (PIP) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in plateau pressure (Pplat) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in static airway compliance (Caw) | Calculated as tidal volume / airway driving pressure | During FCV and VCV measurements (30 minutes) | 
| Change in end-tidal CO2 (ETCO2) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in global airway resistance (Raw) | As measured by the citrex respiratory monitor | During FCV and VCV measurements (30 minutes) | 
| Change in global airway time constant (TAUaw) | Calculated as global airway resistance x global airway compliance | During FCV and VCV measurements (30 minutes) | 
| Change in total energy | As calculated from monitoring data | During FCV and VCV measurements (30 minutes) | 
| Change in dissipated energy | As calculated from monitoring data | During FCV and VCV measurements (30 minutes) | 
| Change in P/F ratio | Calculated as partial pressure of arterial oxygen divided by inspiratory fraction of oxygen | During FCV and VCV measurements (30 minutes) |