Mechanical Ventilation to Accelerate Recovery of Lung Function in Veno-venous Extracorporeal Membrane Oxygenation; Lung Rest Or Moderate Mechanical Ventilation in ECMO: Randomized Trial
Trial Snapshot
- Phase
- Not Applicable
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Number of patients receiving a ventilation strategy other than the assigned ventilation strategy over the 72 hour period following randomisation
Study Overview
Brief Summary
Feasibility trial to inform a future multicentre randomized control trial. The investigators aim to evaluate the feasibility of a trial of near apnoeic ventilation (two breaths per minute) compared with standard ventilation (respiratory rate between 10 and 30 breaths) for patients with acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO). Additionally, when a patient is determined as ready to wean from ECMO the investigators will explore the feasibility of two ECMO weaning strategies and explore the physiological effects on respiratory effort and gas exchange.
Detailed Description
Background
Acute respiratory distress syndrome (ARDS) is a common clinical syndrome characterised by life threatening respiratory failure requiring mechanical ventilation. Although lifesaving, mechanical ventilation can cause further injury to the lungs, known as ventilator-induced lung injury (VILI). Strategies to mitigate VILI in ARDS have proven to improve patient outcomes. ARDS patients that have severe lung failure, despite mechanical ventilation, often require veno-venous extracorporeal membrane oxygenation (ECMO). ECMO uses an artificial membrane lung to take over gas exchange. This allows reduction in injurious ventilator settings thereby also reducing VILI.
While the indications for ECMO initiation are standardised in the UK and ECMO utilisation is increasing,there remains uncertainty as to the best approach to mechanical ventilation whilst patients are receiving ECMO and what strategies are maximally attenuating VILI during its use. Importantly it is known that despite the reduction in ventilatory pressures and volumes facilitated by ECMO, these sickest and most fragile lungs continue to be susceptible to VILI. A reduction in respiratory rate (RR) to near apnoeic ventilation (2 breaths per minute) seems to be associated with the greatest physiological reduction in VILI components, whilst maintaining important physiological mechanisms such as surfactant production which rely on some lung inflation. Employing a near apnoeic ventilation strategy may be associated with faster resolution of ARDS resulting in reduced duration of ECMO, ventilation and ICU stay, and healthcare costs.
Rationale
Interventions which mitigate VILI lead to less lung inflammation/oedema and better outcomes in ARDS patients. However, the recent REST trial of extracorporeal carbon dioxide removal showed that the resultant modest reduction in volume and pressure had no clinical effect. Hence, a modest reduction in ventilation may not be as effective as an almost complete absence (near apnoeic) of ventilation. The latter can only be achieved alongside ECMO support. Reductions in respiratory rate to near apnoeic ventilation have multiple effects on VILI, including:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult patients aged 18 years or older on the date of screening
- •Acute and potentially reversible cause of ARDS
- •Receiving invasive mechanical ventilation
- •Requiring ECMO for severe ARDS
- •Tidal volume ≥ 2.5ml/kg predicted body weight
Exclusion Criteria
- •Patients who meet the one or more of the following will be excluded from the trial.
- •Declined consent
- •>12 hours following ECMO initiation
- •Patient likely to die or for withdrawal of life sustaining therapies within 24 hours
- •Use of V-A ECMO or hybrid ECMO modes
- •Current pregnancy
Arms & Interventions
Near Apnoeic Ventilation
Near Apnoeic ventilation (with a respiratory rate of 2 breaths per minute, plateau pressure of 30cmH20 and PEEP set according to the mean airway pressure being delivered during mechanical ventilation prior to randomisation) for a 72 hour period following randomisation
Intervention: Near Apnoeic ventilation (Other)
Near Apnoeic Ventilation
Near Apnoeic ventilation (with a respiratory rate of 2 breaths per minute, plateau pressure of 30cmH20 and PEEP set according to the mean airway pressure being delivered during mechanical ventilation prior to randomisation) for a 72 hour period following randomisation
Intervention: Crossover standardised ECMO weaning trials (Other)
Standard Care
Standard care for patient on ECMO as per consultant with respiratory rate of 15-30, PEEP of 10cmH20 or more and Plateau pressure of 25cmH20 or less for a 72 hour period following randomisation
Intervention: Crossover standardised ECMO weaning trials (Other)
Outcomes
Primary Outcomes
Number of patients receiving a ventilation strategy other than the assigned ventilation strategy over the 72 hour period following randomisation
Time Frame: During the 72 hours following randomisation
Number of patients receiving a ventilation strategy other than the assigned ventilation strategy over the 72 hour period following randomisation (excluding time off the ICU for imaging or surgical/interventional procedures)
Secondary Outcomes
- Time to achieving carbon dioxide output (VCO2) natural lung > 50% of total of CO2 output(Up to 6 months following date of randomisation)
- Number of patients with non-adherence to assigned ECMO weaning strategy(Up to 6 months following date of randomisation)
- Change in total compliance of the respiratory system during a low flow pressure volume loop after 72hrs of the assigned ventilation strategy(72 hours)
- Rate of successful ECMO weaning trial(Up to 6 months following date of randomisation)
- Time to achieve a PaO2 > 30 kPa with Cilley's test (arterial oxygenation achieved after an increase in FiO2 to 1.0 with no other changes to the ventilator or ECMO settings)(Up to 6 months following date of randomisation)