By using advanced respiratory monitoring, we will aim to gain more understanding about the physiological effects and potential benefits of FCV in comparison to PCV in patients with moderate to severe ARDS. We hypothesize that FCV results in a lower…
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is the difference in Mechanical Power (Joules per minute)
after 90 minutes on FCV compared to after 90 minutes of PCV; obtained from the
Pressure-Volume loops.
Secondary outcome
These following secondary study parameters will be measured at baseline (PCV)
and thereafter every 30 minutes on FCV and PCV for a total of 180 minutes:
- Dissipated energy (Joules per tidal volume) derived from Pressure-Volume
Loops
- EELV assessed by EIT; an important secondary endpoint is the difference
in EELV after 30 minutes on FCV compared to after 30 minutes on PCV.
- Airway pressures (peak airway pressure, plateau pressure, mean airway
pressure, PEEP, intrinsic PEEP, driving pressure) as measured on the airway
pressure tracings
- Transpulmonary pressures (end-expiratory transpulmonary pressure,
end-inspiratory transpulmonary pressure, transpulmonary driving pressure) as
measured using esophageal manometry
- Minute volume as measured using flow tracings
- Ventilatory ratio as a measure of dead space ventilation
- Regional Ventilatory Delay Index (RVDI) assessed by EIT
- Global Inhomogenity Index (GI) assessed by EIT
- P/F ratio
- Hemodynamic parameters (e.g. mean arterial pressure, heart rate)
These following secondary study parameters will be measured at five points
during the study, namely at baseline (PCV), two times after a 90 minutes
ventilation study period (FCV/PCV) and 90 minutes and 24 hours after the end of
the study (PCV). Biomarkers in EBC (exhaled breath condensate) as a measurement
for pulmonary inflammation that will be measured are pro-inflammatory cytokines
IL-1β, IL-6, IL-12p70, TNF-α, anti-inflammatory cytokine IL-10 and chemokine
IL-8 and biomarkers CD14, CD163 and CD25 for monocyt, macrophage and T-cell
activation respectively.
Background summary
During controlled mechanical ventilation (CMV) only the inspiration is
controlled by either a set driving pressure (Pressure Controlled Ventilation,
PCV) or tidal volume (Volume Controlled Ventilation, VCV). The expiration
depends on the passive elastic recoil of the respiratory system and cannot be
controlled and lasts until the airway pressure is equal to the positive
end-expiratory pressure (PEEP). The exponential decrease in airway pressure
during expiration may result in alveolar collapse and hypoxemia. Flow
controlled ventilation (FCV) is a mechanical ventilation method that uses a
constant flow during both inspiration and expiration. FCV results in a gradual
decrease in airway pressure during expiration as flow is controlled. In both
animal and prospective crossover studies, controlled expiration resulted in
higher mean airway pressures with reduced alveolar collapse. Besides, FCV
resulted in a higher ventilation efficiency measured by a decrease in minute
volume at stable arterial partial pressures of carbon dioxide (PaCO2). Where a
reduction in alveolar collapse may lead to less atelectrauma, a higher
ventilation efficiency may lead to a lower mechanical power (MP), which is the
amount of energy that is transferred to the respiratory system by the
mechanical ventilator every minute. Both are important determinants of
Ventilator Induced Lung Injury (VILI). This makes FCV a very interesting
ventilation mode in patients with the Acute Respiratory Distress Syndrome
(ARDS) in which VILI is still a major contributor to overall morbidity and
mortality.
Two prior prospective cross-over studies have been performed in (COVID-19) ARDS
patients that did show a lower minute volume with FCV compared to PCV or VCV.
However, these studies did not take into account assessments of the MP or
end-expiratory lung volume (EELV), which is a measurement of lung aeration.
Study objective
By using advanced respiratory monitoring, we will aim to gain more
understanding about the physiological effects and potential benefits of FCV in
comparison to PCV in patients with moderate to severe ARDS. We hypothesize that
FCV results in a lower mechanical power and an increased EELV (lung aeration)
compared to PCV, thereby potentially reducing the risk of VILI. To explore
whether FCV could decrease pulmonary inflammation by providing ventilation at a
lower mechanical power compared to PCV we will measure inflammatory biomarker
levels in exhaled breath condensate. Insights from this study allow the
optimization of personalized lung protective mechanical ventilation.
Study design
Randomized crossover physiological pilot study comparing FCV and PCV.
Intervention
Patients are mechanically ventilated with PCV mode at baseline. Upon inclusion
the EIT-belt and an esophageal balloon are placed to assess the EELV and
transpulmonary pressures respectively. Besides, patients are randomized between
the sequence of ventilation mode, namely 90 minutes of PCV followed by 90
minutes of FCV or 90 minutes of FCV followed by 90 minutes of PCV. When PCV is
switched to FCV the same mechanical ventilator settings are used as in the PCV
mode. After half an hour on FCV the PEEP, drivingpressure and flow of FCV are
optimised based on the highest compliance and lowest flow matching with a
stable PaCO2 thereby not exceeding lung protective ventilation limits
(transpulmonary driving pressure <= 12cmH2O and tidal volumes <= 8 ml/kg ideal
body weight (IBW)). PCV is always set according to standard of care. Total time
of measurements / study time is 180 minutes.
Besides, exhaled breath condensate will be collected from the expiratory tubing
system from the ventilator by means of the TURBODECCS collecting system. A
total of 5 samples will be collected (PCV baseline, after 90 minutes of FCV and
after 90 minutes of PCV), 90 minutes and 24 hours after the end of the study
(on PCV).
Study burden and risks
All patients are sedated and on CMV, therefore there will be no discomfort for
the patient. FCV has been successfully applied during surgery and on the ICU
and the patient will be monitored continuously so the clinical team can act
directly in case of any adverse event. The mechanical power is calculated
afterwards using software on the obtained Pressure-Volume loops (derived from
the continuous flow- and pressure measurements). Lung volume is measured with
EIT, a non-invasive, radiation-free monitoring tool. Transpulmonary pressures
are measured with an esophageal balloon that is placed in a similar manor as a
nasogastric feeding tube. During optimisation of FCV no lung protective
ventilation limits will be exceeded. Therefore, overall the risks of this study
are limited.
Doctor Molewaterplein 40
Rotterdam 3015 GD
NL
Doctor Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- 18 years or older;
- Provided written informed consent;
- Undergoing controlled mechanical ventilation via an endotracheal tube;
- Meeting all criteria of the Berlin definition of ARDS:
o Hypoxic respiratory failure within 1 week of a known clinical insult or new
or worsening respiratory symptoms
o Bilateral opacities on X-ray or CT-scan not fully explained by effusions,
lobar/lung collapse (atelectasis), or nodules
o Respiratory failure not fully explained by cardiac failure or fluid overload.
o Oxygenation: moderate ARDS P/F ratio between 101-200 mmHg, severe ARDS PF
ratio <= 100mmHg, both with PEEP >= 5 cmH2O.
- Development of ARDS <= 72 uur
- Intubated
Exclusion criteria
- Severe sputum stasis or production requiring frequent bronchial suctioning
(more than 5 times per nurse shift) - Untreated pneumothorax (i.e. no pleural
drainage) - Hemodynamic instability defined as a mean arterial pressure below
60mmHg not responding to fluids and/or vasopressors or a noradrenalin dose >
0.5mcrg/kg/min - High (>15 mmHg) or instable (an increase in sedation or
osmotherapy is required) intracranial pressure - An inner tube diameter of 6mm
or less - Anticipating withdrawal of life support and/or shift to palliation as
the goal of care - Inability to perform adequate electrical impedance
tomography (EIT) measurements - Contra-indications for nasogastric tube or
inability to perform adequate transpulmonary pressure measurements
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| CCMO | NL83234.078.23 |