Routine Versus Selective Intraoperative ECMO in Lung Transplant

Study Overview
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Brief Summary
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Intraoperative hemodynamic management is vital in the success of lung transplantation. Significant intraoperative hemodynamic compromise and hypoxic episodes may contribute to an increase in severe postoperative complications related to hypoperfusion, including cerebrovascular accidents, acute kidney injury, and mesenteric ischemia. In certain lung transplant recipients, intraoperative cardiopulmonary support is mandatory because certain factors would make off-pump transplants unsafe. These include severe pulmonary hypertension or severe ventricular dysfunction. In such patients, routine intraoperative support should be employed. However, it is possible to conduct the lung transplant without cardiopulmonary support in the remainder of patients who do not have severe pulmonary hypertension or right heart dysfunction. In such patients, the lung transplant may be started without cardiopulmonary support. However, cardiopulmonary support may be initiated on-demand if there is development or impending hemodynamic embarrassment or hypoxia. Conversely, the opposite approach would be to routinely conduct all lung transplant operations using cardiopulmonary support, which may also lead to specific ECMO-related complications. The investigators question whether on demand intraoperative ECMO in patients with significant risk factors will produce severe postoperative complications in a rate similar to routine ECMO.

Detailed Description
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Hypothesis: In patients where cardiopulmonary bypass (CPB) / ECMO is not mandatory, on-demand use of intra-operative ECMO is equivalent to routine use for patients undergoing lung transplant. The study will be a prospective, randomized controlled trial. The investigators seek to compare outcomes of two different strategies of cardiopulmonary support during lung transplantation; routine support with ECMO versus selective (on-demand), indication- based support with ECMO. The allocation ratio will be 1:1. A multi-center trial is necessary to allow for a sufficient sample size. However, the investigators believe a pilot study is essential to determine feasibility before embarking on such a significant undertaking. In this preliminary pilot study, recruitment will be limited to lung transplant patients at the Centre hospitalier de l'Universite de Montreal (CHUM). The primary purpose of the pilot study will be to define recruitment ability and assess the feasibility of conducting the study. Depending on the results of this pilot study, the next step would be to expand the study to multiple lung transplant centers to achieve an adequate sample size and power, allowing the investigators to answer the question of interest.

Official Title
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Randomized Trial of Routine Versus Selective Use of Intraoperative Extracorporeal Mechanical Support During Lung Transplantation : a Pilot Study

Conditions
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Lung Transplant; Complications, Extracorporeal Circulation; Complications, Postoperative Complications

Intervention / Treatment
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* Device: Routine ECMO
* Device: On demand ECMO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing lung transplant surgery during the study period (6 months) Exclusion Criteria: Inability to provide consent for the study or patient refusal Retransplantation Multi-organ transplantation Lung transplant recipients where intraoperative support is mandatory and off- pump transplant would be unsafe: a. Severe pulmonary hypertension (PH): i. Systolic pulmonary artery pressure (PAP) ≥ 80 mm Hg on echocardiography, right heart catheterization, or pulmonary artery catheter measurement ii. Mean PAP ≥ 55 mm Hg on echocardiography, right heart catheterization, or pulmonary artery catheter measurement iii. The ratio of mean pulmonary to systemic artery pressure of more than 0.66 b. Moderate to severe right ventricular (RV) hypokinesis or dysfunction c. Left ventricular dysfunction: Defined as ejection fraction (LVEF) < 50% on echocardiography, ventriculography, computed tomography (CT), or magnetic resonance imaging (MRI) d. Significant coronary artery disease (CAD)requiring stenting or surgical grafting

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: On demand ECMO (study group)<br> | Device: On demand ECMO<br>* Selective, indication-based intraoperative cardiopulmonary support. In this group, the transplant will be planned without cardiopulmonary support. intraoperative ECMO will be used selectively based on hemodynamic and/or gas exchange abnormalities : Inability to maintain adequate hemodynamics and stable perfusion or oxygenation during surgery Prolonged high dose pressor required to maintain adequate perfusion A sustained drop in cerebral saturation > 25% of baseline despite initial attempts at optimization Inability to tolerate pulmonary artery clamping Inadequate gas exchange despite attempts at the optimization of ventilator parameters and treatments related to respiratory mechanics and ventilation/perfusion matching Inadequate exposure to the surgical field<br>|
| Active Comparator: Routine ECMO (control group)<br> | Device: Routine ECMO<br>* Routine ECMO during lung tansplant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study recruitment rate |  | 6 months after the onset of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients loss to follow-up |  | 1 year | 
| The composite incidence of death, disabling stroke, grade 2 or 3 primary graft dysfunction at 72 hours, major bleeding (BARC grade 3a, 3b or 5), vascular complications, or stage II or III acute kidney injury at 14 days. |  | 14 days | 
| Incidence of all-cause mortality at 30 days, 90 days, and one year |  | 1 year | 
| Incidence of postoperative stroke / cerebrovascular accident |  | 14 days | 
| Incidence of an Early major postoperative neurologic complication (EMPNC): This includes stroke, severe encephalopathy, and severe seizures diagnosed within 14 days after surgery. |  | 14 days | 
| Incidence of severe postoperative complications. This is defined as Clavien-Dindo grade III complication or greater |  | 14 days |