Improved Organ Utilization and Better Transplant Outcomes With In Situ Normothermic Regional Perfusion in Controlled Donation After Circulatory Death

Transplantation, Journal Year: 2022, Volume and Issue: 107(2), P. 438 - 448

Published: Aug. 22, 2022

Background . We evaluated whether the use of normothermic regional perfusion (NRP) was associated with increased organ recovery and improved transplant outcomes from controlled donation after circulatory death (cDCD). Methods This is a retrospective analysis UK adult cDCD donors‚ where at least 1 abdominal accepted for transplantation between January 1, 2011, December 31, 2019. Results A mean 3.3 organs transplanted when NRP used compared 2.6 per donor not used. When adjusting organ-specific risk profiles, odds all being by 3-fold liver ( P < 0.0001; 95% confidence interval [CI], 2.20-4.29), 1.5-fold kidney = 0.12; CI, 0.87-2.58), 1.6-fold pancreas 0.0611; 0.98-2.64). Twelve-mo survival superior recipients graft 51% lower risk-adjusted hazard failure (HR 0.494). In analyses, kidneys had 35% chance developing delayed function than non-NRP (odds ratio, 0.65; 0.465-0.901)‚ expected 12-mo estimated glomerular filtration rate 6.3 mL/min/1.73 m 2 better if 0.0001). Conclusions The during DCD leads to utilization conventional recovery.

Language: Английский

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The international experience of in-situ recovery of the DCD heart: a multicentre retrospective observational study

EClinicalMedicine, Journal Year: 2023, Volume and Issue: 58, P. 101887 - 101887

Published: March 2, 2023

BackgroundHeart transplantation is an effective treatment offering the best recovery in both quality and quantity of life those affected by refractory, severe heart failure. However, limited donor organ availability. The reintroduction donation after circulatory determination death (DCD) 2014 offered uplift transplant activity 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion DCD heart. objective this paper to assess clinical outcomes hearts recovered transplanted from donors undergoing taNRP.MethodThis was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use mechanical support immediately following transplantation, perioperative long-term actuarial survival incidence acute rejection requiring treatment. 157 taNRP transplants, performed between February 2, 2015, July 29, 2022, have been 15 major centres worldwide including UK, Spain, USA Belgium. 673 donations neurological (DBD) transplantations same were used as comparison group for survival.FindingstaNRP resulted 23% increase activity. Survival similar when compared DBD. 30-day 96.8% ([92.5%–98.6%] 95% CI, n = 156), 1-year 93.2% ([87.7%–96.3%] 72) 5-year 84.3% ([69.6%–92.2%] 13).InterpretationOur study suggests that provides significant boost rates are comparable obtained DBD may part be related short time or through possible selection bias younger donors, being uncontrolled Therefore, our offers method preservation procurement. This early success technique warrants further investigation use.FundingNone authors financial relationship with commercial entity has interest subject.

Language: Английский

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Maintaining the permanence principle of death during normothermic regional perfusion in controlled donation after the circulatory determination of death: Results of a prospective clinical study

American Journal of Transplantation, Journal Year: 2023, Volume and Issue: 24(2), P. 213 - 221

Published: Sept. 21, 2023

Language: Английский

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The Unified Brain-Based Determination of Death Conceptually Justifies Death Determination in DCDD and NRP Protocols

The American Journal of Bioethics, Journal Year: 2024, Volume and Issue: 24(6), P. 4 - 15

Published: June 2, 2024

Organ donation after the circulatory determination of death requires permanent cessation circulation while organ brain irreversible functions. The unified brain-based connects and criteria for in as follows: systemic causes which perfusion function. relevant that must cease is to brain. Eliminating from donor ECMO circuit thoracoabdominal NRP protocols satisfies but only if complete can be proved. Despite its medical physiologic rationale, remains inconsistent with Uniform Determination Death Act.

Language: Английский

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Consensus statement on normothermic regional perfusion in donation after circulatory death: Report from the European Society for Organ Transplantation’s Transplant Learning Journey

Transplant International, Journal Year: 2021, Volume and Issue: 34(11), P. 2019 - 2030

Published: June 19, 2021

Language: Английский

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Improved short-term outcomes of kidney transplants in controlled donation after the circulatory determination of death with the use of normothermic regional perfusion

American Journal of Transplantation, Journal Year: 2021, Volume and Issue: 21(11), P. 3618 - 3628

Published: April 23, 2021

Language: Английский

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Normothermic regional perfusion and US legal standards for determining death are not aligned

American Journal of Transplantation, Journal Year: 2022, Volume and Issue: 22(5), P. 1289 - 1290

Published: Feb. 16, 2022

The claim that Normothermic Regional Perfusion is compatible with circulatory determination of death because physicians do not intend to resuscitate the donor ignores fact laws on determining in all states define a condition and include element physician or patient intent. See Parent et (Page 1307) Wall al. (page 1311) US Department Health Human Services currently using regulations collaborative projects encourage organ procurement organizations obtain more organs from donation after (DCDD).1Centers for Medicare & Medicaid Services. CMS finalizes policy will increase number available lifesavings by holding accountable through transparency competition. Accessed February 20, 2022. https://www.cms.gov/newsroom/press-releases/cms-finalizes-policy-will-increase-number-available-lifesavings-organs-holding-organ-procurementGoogle Scholar,2Organ Procurement Transplantation Network. Second phase national DCD project ready launch. https://optn.transplant.hrsa.gov/news/second-phase-of-national-dcd-procurement-collaborative-project-ready-to-launch/Google Scholar One barrier transplant programs such has been concern loss circulation DCDD renders less desirable transplantation.3Domínguez-Gil B Ascher N Capron AM al.Expanding controlled death: statement an international collaborative.Intens Care Med. 2021; 47: 265-281Crossref PubMed Scopus (0) Google Programs other countries have responded developing protocol—Normothermic (NRP)—to improve quality quantity transplantable organs. Under NRP protocols, declared, restored means as extracorporeal membrane oxygenation (ECMO), while steps intravascular balloons ligation arteries are also taken concentrate support be transplanted avoid reaching brain. Although proponents protocols urged adoption United States,4Parent Moazami S al.Ethical logistical concerns establishing NRP-cDCD heart transplantation States.Am J Transplant. 2020; 20: 1508-1512Crossref (22) last April American College Physicians issued critical assessment ethics NRP—which it termed "a protocol accurately described retrieval cardiopulmonary arrest induction brain death"—and pause allow further study before wide adoption.5Ethics, death, normothermic regional perfusion (NRP) (cDCD): Statement Concern. Published 17, 2021. January 11, https://www.acponline.org/acp_policy/policies/ethics_determination_of_death_and_organ_transplantation_in_nrp_2021.pdfGoogle In this issue Journal, al.6Parent B, Caplan A, N, Response Physician's perfusion. Am doi:10.1111/ajt.16947Google al.7Wall AE, Fiedler Karp S, Applying ethical framework thoracic procedures. doi:10.1111/ajt.16959Google take argue ethically acceptable. Unfortunately, both groups rely at several points concept "intent," which absent legal standards determination. Their arguments thus fail address must resolved ensure compliance existing law. All follow established Uniform Determination Death Act (UDDA). these laws, individual died when either functions entire function ceased irreversibly. For years term "irreversible" (cannot changed) interpreted "permanent" (will change). Accordingly, dead under law return auto-resuscitation medical intervention. al declared "in strict accordance declaration requirements,"6Parent point out same standard cases.7Wall With NRP, however, resumes artificial support. This consequential legally contradicts requirement depends having permanently ceased. try escape conclusion claiming can nonetheless classified team accepted patient's instruction make any efforts resuscitation. authors assert "there no intention attempt doing so would medically ineffective."6Parent Whatever intention, remains restores and, indeed, restore heartbeat. similar argument but switch patient. They since aims only maintain viability prior retrieval, therefore "an act preservation, surrogate intended."7Wall intentions may important evaluating acceptability physicians' actions, bare intent: neither nor resume. That state where meaningful existence possible, trying induce spontaneous resumption futile, even consistent donor's wishes, irrelevant whether deceased law, turns person's physical anyone's intention. Furthermore, occlude carotids they indeed true preventing oxygen removes risk some patients restoration bloodflow could prompt least temporary inconsistent neurological circulatory-respiratory death. An ambitious district attorney might convincingly following intended render irreversible had ceased, ensuring Several ways conundrum possible. First, perfusate rather than oxygenated blood mean what being done does constitute "circulation." Alternatively, attorneys general willing opinion complies UDDA; though unlikely, option remove about liability. Or, ventilator withdrawal asystole, if were diagnosed based functions, then contradicting relevant. However, time needed neurologically body without heartbeat impair viability. Fourth, Law Commissioners considering revising UDDA, presents opportunity misalignment between emerging practices "redefinition" solely benefit undermine public trust determinations, adverse consequences donation. Finally, scientists develop methods ex vivo organs, thereby obviating need situ negates basis declaring death.3Domínguez-Gil manuscript conflicts interest disclose Journal Transplantation.

Language: Английский

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Understanding the Brain-based Determination of Death When Organ Recovery Is Performed With DCDD In Situ Normothermic Regional Perfusion

Transplantation, Journal Year: 2023, Volume and Issue: 107(8), P. 1650 - 1654

Published: May 12, 2023

The brain-based determination of death ("brain death") is now widely accepted throughout the world. It states that irreversible cessation brain functions fundamental criterion for human death. recent World Brain Death Project provided a comprehensive cataloguing all aspects including its medical and legal acceptance world.1 Organ donation after (DBDD) currently accounts majority multiorgan donations internationally. circulatory (DCDD) has grown worldwide since Institute Medicine United States endorsed practice controlled DCDD in 20002 US national conference on 2005 standardized practice.3 are expanding but remain fewer than number DBDD donations. donor requires permanent absence systemic circulation. When circulation absent, ceases. essential feature unified concept produces neuronal perfusion resulting functions. Thus, by criteria consistent with neurologic criteria. In situ normothermic regional (NRP) emerging as component organ recovery procedures DCDD. Controlled practiced hospitalized patients planned withdrawal life-sustaining therapy (WLST). NRP uses extracorporeal membrane oxygenation to reestablish specific regions body following determination. reestablished may be restricted abdominal cavity (A-NRP) or also include thoracic (TA-NRP). reportedly improves utilization recipient outcomes comparable those organs from donors,4,5 it raises complex medical, ethical, questions must resolved.6-8 protocols This situation principal question NRP: if resumption contradicts conditions declaration, how can declared dead circulation? use resolves dilemma clarifying relevant cease brain.9,10 If effectively ensure no brain, thereby preventing function, fulfills requirements respects rule. Ensuring ceased permanently will not restarted allows donors based despite restoration abdomen thorax. DEATH DETERMINATION IN DONATION AFTER CIRCULATORY OF Under current protocols, declaration determining potential donor's permanently. Three establish circulation: (1) completely, evidenced intra-arterial pressure monitoring, electrocardiography, echocardiography; (2) persists beyond time interval during which autoresuscitation been reported occur; (3) intervention made restore declared.11 these met, permanence fulfilled, validly dead, subsequent donated does violate rule.11 Although standards differ among jurisdictions, physicians who follow confident they acting accordance around world have long equated circulation.8 minimum 5 min absent establishes heart restart spontaneously permanent. standard was recommended Medicine2 common most European countries.12 5-min confirmed large prospective observational study autoresuscitation, determined WLST, longest between asystole 4 24 s.13 THE UNIFIED BRAIN-BASED There widespread basis functions, defined loss capacity consciousness, breathe, stem reflexes.1,14 caused primary pathology, such traumatic head injury, stroke, meningitis, hypoxic–ischemic damage secondary arrest. provides when function results arrest, applying DCDD, initially causes cease. Permanent perfusion, that, leads functions.9,10 Physiologic studies dying WLST show activity closely correlates electroencephalogram becomes isoelectric within 30 s cardiac arrest brain15 occur even sooner followed severe hypotension hypoxemia before arrest.16,17 Cessation triggers physiologic cascade: leading function. After complete circulation, grounds and, therefore, Permanence established elapsed resuscitative attempted. A ceases irreversibly means cannot restored. restored.18 From inception, testing enables formal retrospective assessment had previously (they restored). (real time) only According unifying death, valid because (see Figure 1). true endpoint consequence brain.FIGURE 1.: dependent brain.After permanently, direct would ideal method prove absence. But technical reasons, electrophysiological feasible donor, particularly Therefore, used surrogate justified strict causal relationship exists ceases: continue However, mere presence measurable necessarily imply detected blood flow achieve necessary threshold allow Yet, indicates possible. These precise thresholds unknown. GOAL TA-NRP IS TO RESTORE CIRCULATION THORACIC AND ABDOMINAL ORGANS added an preservation strategy reperfuse organs, reduce warm ischemic damage, better assessed being recovered transplantation. A-NRP, aorta clamped blocked restrict whereas stapling aortic arch vessels. purpose vessel clamping exclude initiated, mechanical ventilation restarted. transplantation suitability sinus rhythm contractions. perfuse opportunity assess heart's functional do techniques succeed totally excluding POTENTIAL INADEQUACIES CLAMPING AORTIC ARCH VESSELS completely excluded collateral arterial dynamics autoregulation. robust system arteries distributed aorta. Blood proceeds through carotid vertebral ultimately form Circle Willis. At level medulla, give off branches merge anterior spinal artery. artery distributes cord supply derived cervical (C1–T3), (T4–T8), lumbar (T9 conus medullaris) via Adamkiewicz. That cephalad toward along impaired major routes flow. Clamping brain's main stimulate cerebral autoregulation generated NRP.19 Current data insufficient assure zero NRP, although animal models reassuring.20 experiment small sample pigs found vessels prevented electroencephalogram, evoked potentials, flow, oxygen uptake.21 uncertainty vessels, Kingdom Spain step severing distal clamps draining aspirating ends severed while exposed atmospheric pressure.22 maneuver intended divert any possible away brain. For restored other means. Animal performed reassure eliminated incorporated into protocols. could inform best methods clinical monitoring TA-NRP. To resolve over restoring studies, Spain, should conducted TA-NRP, example, contrast angiography. Given sufficiently sensitive detect functioning, areas difficult examine, like stem, one assume functioning. RECOMMENDATIONS DEVELOP AN INTERNATIONAL CONSENSUS ON CONCEPT WHEN IMPLEMENTED International Professional Societies Develop Medical Standards Should Work Achieve Consensus Unified Brain-based Concept applicable both distinct. achieved brain.23 Determining outside context donation.1 continue. Establishing international professional consensus provide framework policy practice, promoting public trust addressing barriers opportunities Such accomplished expert collaboratives solid scientific evidence.1,14,24 Future laboratory research determine residual exceeds restrictive vascular blocking implemented. Protocols Recovery, Especially With Situ Preservation Using Must Ensure Absence Circulation validated assurance stop experimentally proven clinically effective. Programs using validation available consider implementing reassurance continued TA-NRP–assisted recovery.25 Surgical Recovery Maneuvers Used Prevent During Be Legally, Ethically, Socially Acceptable Discussions qualified professionals families information about aims, methods, maneuvers sufficient family members surrogates make informed decisions authorizing donation. Transparency conversations ensures Some commentators emphasized desirability pursuing ex avoids ethical issues providing many benefits.26 this alternative associated substantially higher costs own limits countries where legislation observation period longer support development practices communicating families, hospital personnel explore their attitudes understanding We encouraged efforts Canadian panel adopted guideline functions.27 Their rationale recommendations serve model worldwide, Alignment prevailing clinical, remains necessary.7,8

Language: Английский

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Normothermic regional perfusion: Ethical issues in thoracic organ donation

Journal of Thoracic and Cardiovascular Surgery, Journal Year: 2022, Volume and Issue: 164(1), P. 147 - 154

Published: March 31, 2022

Language: Английский

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Critical warm ischemia time point for cardiac donation after circulatory death

American Journal of Transplantation, Journal Year: 2022, Volume and Issue: 22(5), P. 1321 - 1328

Published: Feb. 3, 2022

Donation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, necessary period warm ischemia is concern. This study aims determine critical time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal life-sustaining therapy (WLST), at arrest (CA) and every 2 min thereafter. Samples were processed into representative pools assess calcium homeostasis, mitochondrial function cellular viability. Compared baseline, no significant deterioration was observed any studied parameter CA (median: 9 min; IQR: 7-13 range: 4-19 min). Ten CA, phosphorylation cAMP-dependent protein kinase-A Thr197 SERCA2 decreased markedly; parallelly, complex II IV activities decreased, caspase 3/7 activity raised significantly. These results did not differ when with higher WLST times (≥9 min) analyzed separately. In human cardiomyocytes, from first 10 associated compromise or findings may help incorporate transplant programs.

Language: Английский

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