Confirming Permanent Lack of Blood Flow to the Brain During A-NRP DCC Organ Transplant

Study Overview
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Brief Summary
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This study aims to evaluate the surgical technique used in Abdominal Normothermic Regional Perfusion (A-NRP) in death determination by circulatory criteria (DCC) organ donors. The proposed study will demonstrate that there is no resumption of brain blood flow or activity during the A-NRP procedure. This will be assessed using multimodal neuromonitoring protocol that enables continuous focused monitoring of brain blood flow and activity during A-NRP. This will provide evidence that brain blood flow and activity does not resume during NRP and ensure donor safety in using this technique in standard of care practice.

Detailed Description
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This will be a multi-centre prospective observational cohort study that will enroll eligible DCC donors at participating donation hospitals. Participating programs will implement the A-NRP processes and organ recovery at the donation sites. Neurocritical care teams and donation physicians at the donation site and independent of transplant teams will implement neuromonitoring using the following modalities: Transcranial colour-coded Doppler (TCCD) as a measure of brain blood flow, Electroencephalography (EEG), as a measure of cortical brain electrophysiologic activity, and Somatosensory evoked potentials (SSEP) or brainstem auditory evoked potentials (BAEP), as a measure of brainstem electrophysiologic activity. The neuromonitoring team will interpret observed signals in real-time during the A-NRP process. This study will confirm whether current A-NRP surgical safeguards ensure maintenance of permanent cessation of brain blood flow and/or activity during A-NRP and will guide the adoption of A-NRP in Ontario.

Official Title
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Confirming the Permanent Cessation of Intracranial Circulation During Abdominal Normothermic Regional Perfusion After the Determination of Death by Circulatory Criteria

Conditions
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Organ Transplant

Intervention / Treatment
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* Other: Neuromonitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≤ 18 years of age Potential DCC donors whose families/surrogate decision makers have consented to DCC organ donation according to current criteria of the participating transplant programs. These may include patients donating a liver, kidneys, pancreas, and/or lungs; please see Appendix A for organ specific donor inclusion criteria. Exclusion Criteria: < 18 years of age DCC donors who proceed to donation following medical assistance in dying or those who are able to provide first-person consent at the time of donation Injuries that anatomically preclude the use of neurological monitoring

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DCC Donors<br>Standard criteria DCC donors will be undergoing the A-NRP perfusion process to recondition organs prior to procurement. Multimodal neuromonitors will be placed on the donor prior to withdrawal of life support and readings will be recorded during the withdrawal process and for the duration of the A-NRP perfusion process. The neuromonitoring team will be looking for evidence of brain blood flow or activity. | Other: Neuromonitoring<br>* Multimodal neuromonitoring will include: Transcranial colour-coded Doppler (TCCD), Electroencephalography (EEG), and Somatosensory evoked potentials (SSEP) or brainstem auditory evoked potentials (BAEP)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Donor resumption of brain blood flow and/or activity | Proportion of enrolled patients who have resumption of brain blood flow and/or activity during A-NRP on any neuromonitor and that is confirmed by neurocritical care physician and that results in termination of A-NRP | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Donor accrual rate | Number of eligible donors who are enrolled in the study and complete study procedures | Through study completion, an average of 1 year | 
| Consent rate | Number of donors who consent to study procedures divided by the number of donors approached for study consent (target ≥ 80%) | Through study completion, an average of 1 year | 
| Neuromonitoring modalities | Number of neuromonitoring modalities used per patient and reasons for excluding specific modalities | Through study completion, an average of 1 year | 
| Duration and proportion of neuromonitoring signal | Duration of continuous neuromonitoring and proportion of total recording time with adequate signal per patient (velocity waveforms for TCCD, uv/mm for EEG, brainstem auditory evoked potentials (BAEP) signal, and somatosensory evoked potentials (SSEP) signal) | Through study completion, an average of 1 year | 
| Neuromonitoring failure | Proportion of enrolled patients who had failure of neuromonitoring equipment during recording | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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A-NRP, neuromonitoring, brain activity, transplant