Clinical trial NCT01990456: Strategies for Optimal Lung Ventilation in ECMO for ARDS: The SOLVE ARDS Study
Official title: Strategies for Optimal Lung Ventilation in ECMO for ARDS: The SOLVE ARDS Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Respiratory Distress Syndrome, Adult
Keywords: Extracorporeal Membrane Oxygenation
Ventilator-Induced Lung Injury
Ventilators, Mechanical
Pulmonary Heart Disease
Ultrasonography
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
name: The Physicians' Services Incorporated Foundation
First posted: 2013-11-21
Enrollment: 20
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: Due to lack of studies on mechanical ventilation strategies in patients with severe Acute Respiratory Distress Syndrome (ARDS) supported with Veno-Venous Extra-Corporeal Membrane Oxygenation (VV ECMO), ventilator settings in this patient population are set arbitrarily.

In this two-phases prospective, interventional, pilot study we hope to gain physiologically relevant data on two aspects of mechanical ventilation in patients with severe ARDS supported with VV ECMO: (1) the use of tidal ventilation and (2) the level of Positive End-Expiratory Pressure (PEEP).

1. PHASE 1: impact of tidal ventilation on VILI (10 patients) We hypothesized that a CPAP strategy that minimizes end-tidal pulmonary stress and strain mitigates VILI compared to the current mechanical ventilation practice that employs tidal ventilation in patients with severe ARDS on ECMO.

   In this first phase we will test whether administering a distending inspiratory pressure to produce tidal ventilation is superior to a strategy where only continuous positive airway pressure (CPAP) is applied for ventilation induced lung injury (VILI) mitigation, as assessed by its impact on biotrauma (serum cytokines) and physiologic measurements.
2. PHASE 2: impact of PEEP on VILI (10 patients) We also hypothesized that adjusting PEEP to maximize respiratory system compliance reduces VILI in patients with severe ARDS on ECMO.

In the second phase we will therefore gain more insight as to whether a strategy that utilizes a PEEP level that correspond to best compliance is beneficial over Zero End-Expiratory Pressure (ZEEP). We will test the impact of both strategies on biotrauma (serum cytokines), physiologic parameters, and right ventricular function (transesophageal echocardiographic assessment).

Because ARDS patients supported with VV ECMO can be hemodynamically unstable, the use of imaging techniques that require transport, such as computed tomography, is limited. Therefore, bedside imaging techniques, such as pleural and lung ultrasound (PLUS) and focused bedside cardiac ultrasonography, are important tools for clinicians who care for these patients. This study will allow us to learn whether these techniques are feasible and valid in this patient population.

Furthermore, the knowledge gained from this study will allow us to assess the rationale and feasibility of performing a similar larger, randomized study in the future.


Eligibility criteria: Inclusion Criteria:

* Severe ARDS (Berlin Definition)
* VV ECMO \< 72 hours
* Endotracheal intubation or tracheostomy

Exclusion Criteria:

* Thoracic surgery/lung transplantation during the current hospitalization
* Contraindications to a RM (MAP \< 60 mmHg despite administration of fluids and vasopressors; Active air leak through a thoracostomy tube; Pneumothorax, or subcutaneous or mediastinal emphysema, (if chest tube has not been inserted))
* Contraindications to TEE
* Age \< 16 years

Primary outcomes:
measure: Ventilator-Induced Lung Injury (VILI) in patients with ARDS on ECMO ventilated with different strategies (tidal ventilation, CPAP, ZEEP), as measured by Serum Cytokines
timeFrame: 1 hour after initiation of each experimental ventilation strategy
Secondary outcomes:
measure: Impact of a CPAP strategy (PEEP set at best compliance and at ZEEP) in patients with severe ARDS on ECMO, as measured by transesophageal echocardiography (TEE)
timeFrame: 30 minutes after initiation of experimental CPAP/ZEEP strategy
measure: Feasibility and validity of focused cardiac ultrasound, as compared to TEE as gold standard, in the assessment of RV function in patients with ARDS on ECMO
timeFrame: 30 minutes after initiation of experimental CPAP/ZEEP strategy
measure: Feasibility of lung ultrasound in patients with severe ARDS on ECMO
timeFrame: 30 minutes after initiation of experimental CPAP/ZEEP strategy
measure: Feasibility (patient recruitment, protocol adherence, physiologic tolerability)
timeFrame: At overall study completion (i.e., 24 months from study start or after enrolment of last patient)
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Medical Surgical ICU - Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, University of Toronto
name: Eddy Fan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, University of Toronto
name: Niall D. Ferguson, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: