Goal of Open Lung Ventilation in Donors

Study Overview
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Brief Summary
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The primary goal of this study is to assess whether ventilation of deceased organ donors with an open lung protective ventilatory strategy will improve donor lung utilization rates and donor oxygenation compared to a conventional ventilatory strategy.

Detailed Description
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Deceased organ donors are maintained on life support including mechanical ventilation during the time between brain death and organ procurement. The optimal mode of mechanical ventilation for deceased organ donors has not been definitively established. Since deceased organ donors may develop atelectasis leading to impaired oxygenation, an open lung protective ventilatory strategy with higher positive end expiratory pressure (PEEP), lower tidal volume and recruitment maneuvers has been hypothesized to be beneficial. Favorable outcomes were observed in a European clinical trial comparing open lung protective ventilation (OLPV) to a conventional ventilatory strategy in terms of donor oxygenation and lung utilization for transplantation (Mascia L et al, Journal of the American Medical Association 2010). However, donor management procedures in Europe are much shorter in duration compared to the US and it is not clear that these findings are generalizable to the US donor management environment. The GOLD trial will test the effect of an OLPV strategy compared to conventional ventilation (CV) in the US donor management environment. This multi center trial will enroll 400 brain dead organ donors randomized into 1 of 2 treatment arms. After randomization, mechanical ventilation will be protocolized according to treatment arm with one arm receiving control ventilation (CV) utilizing standard Donor Network West (DNW) protocols and the other arm receiving the OLPV strategy with higher positive end expiratory pressure (PEEP) and lower tidal volume compared to CV. The primary outcomes is donor lung utilization for transplantation.

Official Title
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Goal of Open Lung Ventilation in Donors

Conditions
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Brain Death, Organ Donation, Organ Transplant Failure or Rejection

Intervention / Treatment
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* Other: Open lung protective ventilation
* Other: Conventional ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Brain death Authorization for research ≥13 years of age Exclusion Criteria: Arterial/Inspired oxygen ratio (PaO2/FiO2) ≤ 150 mmHg PaO2/FiO2 ≥ 400 mmHg BMI > 40 Hepatitis B surface antigen positive Hepatitis C positive Failure to complete donation process Hemodynamic instability

Ages Eligible for Study
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Minimum Age: 13 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: Parallel Assignment
Interventional Model Description: Enrolled donors will be randomly assigned to two different modes of mechanical ventilation for the duration of donor management
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Lung Protective Ventilation<br>Volume cycled assist control ventilation with tidal volume 8 cc/kg predicted body weight, PEEP 10 cm water (H2O), recruitment maneuvers every 8 hours and after any ventilator disconnect | Other: Open lung protective ventilation<br>* Higher PEEP, lower tidal volume mechanical ventilation<br>|
| Active Comparator: Conventional Ventilation<br>Volume cycled assist control ventilation with tidal volume 10 cc/kg predicted body weight, PEEP 5 cm H2O, recruitment maneuvers after any ventilator disconnect | Other: Conventional ventilation<br>* Lower PEEP, standard tidal volume mechanical ventilation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Donor lung utilization rate | Percent of donor lungs procured and transplanted into recipient | during donor management period (usually 12-48 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Donor lung utilization in likely donors | Percent of donor lungs used from donors with < 50 pack year smoking, age < 65, negative serologies, and no underlying chronic lung disease | during donor management period (usually 12-48 hours) | 
| Donor oxygenation | Change in donor arterial oxygen (PaO2) from enrollment to procurement | during donor management period (usually 12-48 hours) | 
| Donor static compliance of the respiratory system | Change in compliance of the respiratory system (in ml/cm H2O) from enrollment to procurement. Static compliance (Cstat) is calculated as Cstat = ΔV / Pplat - PEEP where V is the volume delivered by the ventilator, Pplat is the end-inspiratory plateau pressure and PEEP is the level of positive end expiratory pressure. | during donor management period (usually 12-48 hours) | 
| Donor radiographic atelectasis scoring | Change in chest radiograph atelectasis score from enrollment to procurement | during donor management period (usually 12-48 hours) | 
| Recipient primary graft dysfunction | International Society of Heart and Lung Transplantation grade 2 or 3 primary graft dysfunction in lung transplant recipient | 72 hours after transplant | 
| Recipient mortality | Lung transplant recipient death | 30 days after transplant |