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The aim of this study is to demonstrate that cerebral blood flow and brain function do not resume after death declaration in organ donors who undergo normothermic regional perfusion to restore organ function following death determination by circulatory criteria, when appropriate safeguards are applied.
To assess the absence of cerebral perfusion and function, investigators will use continuous and comprehensive multimodal neuromonitoring throughout the withdrawal of life-sustaining therapies, the dying process and the NRP procedure.
This will be a proof-of-concept study aimed at establishing the feasibility of multimodal neuromonitoring in patient undergoing abdominal (A-NRP) and thoraco-abdominal (TA-NRP) and to investigate whether resumption of CBF or function occurs in a cohort of DCD organ donors during A-NRP and TA-NRP. A central goal of this study is to demonstrate the absence of cerebral blood flow and function following normothermic regional perfusion, thereby improving clinical confidence to its safety and maintenance of adherence to death determination in organ donors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Consented Organ Donors | Consented for organ donation following withdrawal of life-sustaining measures and planned DCD within the next 96 hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neuromonitoring | Other | Neuromonitoring during withdrawal of life sustaining therapies, dying process and during normothermic regional perfusion after death. The neuromonitoring will include:
|
| Measure | Description | Time Frame |
|---|---|---|
| Aim 1: Assessment of brain reanimation (restoration of brain circulation and/or function) | To determine the presence or absence of the brain circulation and function during normothermic regional perfusion assessed by intra-parenchymal neuromonitoring, non-invasive neuromonitoring and clinical examination. Reperfusion or regain of brain function during normothermic regional perfusion will be expressed in proportion. Restoration of either cerebral perfusion or neurological function in a patient will be considered a single brain reanimation event. Clinical examination will consist of serial pupillary light reflex assessment and monitoring for respiratory efforts during normothermic regional perfusion. Evidence of brain function will be determined by the presence of rhythmic delta wave activity on electroencephalography, N20 response with somatosensory evoked potentials or presence of brainstem auditory evoked potentials. Restoration of brain circulation will be determined by the presence of cerebral blood flow (>10mls/100g/min) or brain tissue oxygen tension (>2mmHg). | One hour prior to withdrawal of life-sustaining therapies, during the dying duration and for 2 hours during normothermic regional perfusion |
| Aim 2: Feasibility of conducting multimodal monitoring | To assess the feasibility of implementing multimodal neuromonitoring in DCD organ donors undergoing normothermic regional perfusion. This will be a descriptive outcome in which investigators will calculate the duration of available data for each modality and compare it with the total observation period. The investigators hypothesized that feasibility will be strong and that > 80% data variables will be collected for the pre-specified duration in each case. | One hour prior to withdrawal of life-sustaining therapies, during the dying duration and for 2 hours during normothermic regional perfusion |
| Measure | Description | Time Frame |
|---|---|---|
| Aim 3: To assess the agreement between invasive and non-invasive neuromonitoring in determining the presence or absence of brain reanimation during normothermic regional perfusion. | To assess the agreement between invasive (intra-parenchymal cerebral blood flow, intra-parenchymal brain oxygenation, invasive EEG) and non invasive neuromonitoring (transcranial doppler, surface EEG, brainstem auditory evoked potentials, somatosensory evoked potentials) in determining the presence of brain circulation and function during normothermic regional perfusion |
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Inclusion Criteria:
Exclusion Criteria:
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Consented eligible organ donors
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rebecca Grey Clinical Research Coordinator | Contact | 604-875-4111 | 68336 | cerebri.research@ubc.ca |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vancouver General Hospital | Recruiting | Vancouver | British Columbia | V5Z1M9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36175093 | Background | Murphy N, Lingard L, Blackstock L, Ott M, Slessarev M, Basmaji J, Brahmania M, Healey A, Shemie S, Skaro A, Wilson L, Weijer C. Protocol for a qualitative pilot study to explore ethical issues and stakeholder trust in the use of normothermic regional perfusion in organ donation in Canada. BMJ Open. 2022 Sep 29;12(9):e067515. doi: 10.1136/bmjopen-2022-067515. | |
| 37131028 |
| Label | URL |
|---|---|
| Summary statistics on organ transplants, wait-lists and donors. 2022. | View source |
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Microdialysis Plasma/ serum to assess for brain biomarkers
|
| During normothermic regional perfusion |
| Murphy NB, Weijer C, Slessarev M, Chandler JA, Gofton T. Implications of the updated Canadian Death Determination Guidelines for organ donation interventions that restore circulation after determination of death by circulatory criteria. Can J Anaesth. 2023 Apr;70(4):591-595. doi: 10.1007/s12630-023-02413-6. Epub 2023 May 2. No abstract available. |
| 37131020 | Background | Shemie SD, Wilson LC, Hornby L, Basmaji J, Baker AJ, Bensimon CM, Chandler JA, Chasse M, Dawson R, Dhanani S, Mooney OT, Sarti AJ, Simpson C, Teitelbaum J, Torrance S, Boyd JG, Brennan J, Brewster H, Carignan R, Dawe KJ, Doig CJ, Elliott-Pohl K, Gofton TE, Hartwick M, Healey A, Honarmand K, Hornby K, Isac G, Kanji A, Kawchuk J, Klowak JA, Kramer AH, Kromm J, LeBlanc AE, Lee-Ameduri K, Lee LA, Leeies M, Lewis A, Manara A, Matheson S, McKinnon NKA, Murphy N, Briard JN, Pope TM, Sekhon MS, Shanker JJS, Singh G, Singh J, Slessarev M, Soliman K, Sutherland S, Weiss MJ, Shaul RZ, Zuckier LS, Zorko DJ, Rochwerg B. A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline. Can J Anaesth. 2023 Apr;70(4):483-557. doi: 10.1007/s12630-023-02431-4. Epub 2023 May 2. |
| 30667536 | Background | Shapey IM, Summers A, Augustine T, van Dellen D. Systematic review to assess the possibility of return of cerebral and cardiac activity after normothermic regional perfusion for donors after circulatory death. Br J Surg. 2019 Feb;106(3):174-180. doi: 10.1002/bjs.11046. Epub 2019 Jan 22. |
| 36227032 | Background | Peled H, Mathews S, Rhodes D, Bernat JL. Normothermic Regional Perfusion Requires Careful Ethical Analysis Before Adoption Into Donation After Circulatory Determination of Death. Crit Care Med. 2022 Nov 1;50(11):1644-1648. doi: 10.1097/CCM.0000000000005632. Epub 2022 Oct 13. No abstract available. |
| 31922653 | Background | Manara A, Shemie SD, Large S, Healey A, Baker A, Badiwala M, Berman M, Butler AJ, Chaudhury P, Dark J, Forsythe J, Freed DH, Gardiner D, Harvey D, Hornby L, MacLean J, Messer S, Oniscu GC, Simpson C, Teitelbaum J, Torrance S, Wilson LC, Watson CJE. Maintaining the permanence principle for death during in situ normothermic regional perfusion for donation after circulatory death organ recovery: A United Kingdom and Canadian proposal. Am J Transplant. 2020 Aug;20(8):2017-2025. doi: 10.1111/ajt.15775. Epub 2020 Jan 27. |
| 32541563 | Background | van de Leemkolk FEM, Schurink IJ, Dekkers OM, Oniscu GC, Alwayn IPJ, Ploeg RJ, de Jonge J, Huurman VAL. Abdominal Normothermic Regional Perfusion in Donation After Circulatory Death: A Systematic Review and Critical Appraisal. Transplantation. 2020 Sep;104(9):1776-1791. doi: 10.1097/TP.0000000000003345. |
| 24136827 | Background | Shapey IM, Muiesan P. Regional perfusion by extracorporeal membrane oxygenation of abdominal organs from donors after circulatory death: a systematic review. Liver Transpl. 2013 Dec;19(12):1292-303. doi: 10.1002/lt.23771. |
| 34856070 | Background | Hessheimer AJ, de la Rosa G, Gastaca M, Ruiz P, Otero A, Gomez M, Alconchel F, Ramirez P, Bosca A, Lopez-Andujar R, Atutxa L, Royo-Villanova M, Sanchez B, Santoyo J, Marin LM, Gomez-Bravo MA, Mosteiro F, Villegas Herrera MT, Villar Del Moral J, Gonzalez-Abos C, Vidal B, Lopez-Dominguez J, Llado L, Roldan J, Justo I, Jimenez C, Lopez-Monclus J, Sanchez-Turrion V, Rodriguez-Laiz G, Velasco Sanchez E, Lopez-Baena JA, Caralt M, Charco R, Tome S, Varo E, Marti-Cruchaga P, Rotellar F, Varona MA, Barrera M, Rodriguez-Sanjuan JC, Briceno J, Lopez D, Blanco G, Nuno J, Pacheco D, Coll E, Dominguez-Gil B, Fondevila C. Abdominal normothermic regional perfusion in controlled donation after circulatory determination of death liver transplantation: Outcomes and risk factors for graft loss. Am J Transplant. 2022 Apr;22(4):1169-1181. doi: 10.1111/ajt.16899. Epub 2021 Dec 21. |
| 34729491 | Background | Basmaji J, Weijer C, Skaro A, Healey A, Shemie SD, Slessarev M. Paving the Road for the Adoption of Normothermic Regional Perfusion in Canada. Crit Care Explor. 2021 Oct 28;3(11):e0553. doi: 10.1097/CCE.0000000000000553. eCollection 2021 Nov. |
| 33977568 | Background | Ivanics T, Shwaartz C, Claasen MPAW, Patel MS, Yoon P, Raschzok N, Wallace D, Muaddi H, Murillo Perez CF, Hansen BE, Selzner N, Sapisochin G. Trends in indications and outcomes of liver transplantation in Canada: A multicenter retrospective study. Transpl Int. 2021 Aug;34(8):1444-1454. doi: 10.1111/tri.13903. Epub 2021 Jul 7. |
| 31193600 | Background | Schaapherder A, Wijermars LGM, de Vries DK, de Vries APJ, Bemelman FJ, van de Wetering J, van Zuilen AD, Christiaans MHL, Hilbrands LH, Baas MC, Nurmohamed AS, Berger SP, Alwayn IP, Bastiaannet E, Lindeman JHN. Equivalent Long-term Transplantation Outcomes for Kidneys Donated After Brain Death and Cardiac Death: Conclusions From a Nationwide Evaluation. EClinicalMedicine. 2018 Oct 9;4-5:25-31. doi: 10.1016/j.eclinm.2018.09.007. eCollection 2018 Oct-Nov. |
| 38993888 | Background | Bleszynski MS, Parmentier C, Torres-Hernandez A, Ray S, Yousuf A, Norgate A, Schiff J, Shwaartz C, Sapisochin G, McGilvray I, Selzner M, Reichman TW. Pancreas transplantation with grafts obtained from donation after cardiac death or donation after brain death results in comparable outcomes. Front Transplant. 2023 Aug 9;2:1176398. doi: 10.3389/frtra.2023.1176398. eCollection 2023. |
| 31718887 | Background | Palleschi A, Rosso L, Musso V, Rimessi A, Bonitta G, Nosotti M. Lung transplantation from donation after controlled cardiocirculatory death. Systematic review and meta-analysis. Transplant Rev (Orlando). 2020 Jan;34(1):100513. doi: 10.1016/j.trre.2019.100513. Epub 2019 Oct 18. |
| 33875633 | Background | Haque OJ, Roth EM, Fleishman A, Eckhoff DE, Khwaja K. Long-Term Outcomes of Early Experience in Donation After Circulatory Death Liver Transplantation: Outcomes at 10 Years. Ann Transplant. 2021 Apr 20;26:e930243. doi: 10.12659/AOT.930243. |
| 29407328 | Background | Tang JX, Na N, Li JJ, Fan L, Weng RH, Jiang N. Outcomes of Controlled Donation After Cardiac Death Compared With Donation After Brain Death in Liver Transplantation: A Systematic Review and Meta-analysis. Transplant Proc. 2018 Jan-Feb;50(1):33-41. doi: 10.1016/j.transproceed.2017.11.034. |
| Organ Transplants in Canada: Donations and need. 2022. | View source |