The major bottleneck in the field of transplantation remains the limited availability of donor organs. This constraint has existed since the very beginning of transplant medicine: it was already recognized by the first surgeons and continues to be endured by patients on waiting lists today. The concept of organ shortage is almost ritualistically repeated in scientific publications, at conferences, and in public awareness campaigns promoting organ donation. This problem is particularly pronounced in the pediatric setting and, more specifically, in pediatric heart donation.
To illustrate the magnitude of this issue, during the last 5 years (2020–2024), more than 1500 heart transplants were performed in Spain. Of these, only 19 corresponded to infants aged 1–12 months, and merely 3 were neonatal transplants (<28 days of life).
The challenge is twofold. On one hand, there is a limited donor supply; on the other, there is significant mortality among patients on the waiting list. In the United States, critically ill pediatric patients experience a median waiting time of 108 days. Up to 15% of these children die while awaiting a suitable organ. In Spain, a more developed healthcare–cultural framework, combined with a geographically compact territory, allows waiting times to be reduced to approximately 1–3 weeks.
To maximize survival during this period, short- and long-term mechanical circulatory support strategies are frequently employed. When feasible, ABO-compatible protocols are implemented, and in recent years, increasing reliance has been placed on controlled donation after circulatory death (DCD).
The recent article by Kucera et al., published in Seminars in Thoracic & Cardiovascular Surgery: Pediatric Cardiac Surgery Annual, provides a timely and comprehensive review of the currently available strategies for pediatric cardiac donation after circulatory death:
1. Rapid procurement and static cold storage
From a technical standpoint, the most straightforward strategy consists of rapid cardiac procurement following withdrawal of life-sustaining treatment, formal declaration of death based on circulatory criteria, and completion of the legally mandated no-touch period. The heart is then preserved using static cold storage with cardioplegic solutions.
The main advantage of this approach lies in its simplicity. It does not require additional technology or specialized equipment, which facilitates implementation in virtually any center experienced in DCD protocols. Moreover, its economic cost is substantially lower when compared with more advanced preservation strategies.
However, this modality carries a major limitation. The absence of any form of myocardial reanimation or functional assessment obliges transplant teams to base organ acceptance exclusively on warm and cold ischemic times. These parameters are particularly difficult to define accurately in pediatric donors, especially in small-sized patients. Myocardial tolerance to warm ischemia is limited, and the risk of primary graft dysfunction increases significantly. In addition, the maximum acceptable duration of cold ischemia severely restricts the allowable transport distance. For these reasons, this strategy has very limited applicability in contemporary heart transplantation and is virtually negligible in the pediatric population.
2. Ex vivo normothermic perfusion using cardiac preservation systems
Ex vivo normothermic perfusion, using devices such as the Organ Care System (OCS), has addressed several of the inherent limitations associated with static cold storage. Based on the Langendorff principle, these platforms allow the heart to be reanimated outside the body, perfused with oxygenated blood, and metabolically and functionally assessed during transport.
The principal advantage of this approach is the ability to perform an objective evaluation of graft viability prior to implantation, thereby reducing the uncertainty traditionally associated with DCD. In addition, it significantly expands the geographic radius for organ procurement. In recipients with prior cardiac operations or mechanical circulatory support, ex vivo perfusion facilitates a controlled explant and implantation without the added burden of prolonged cold ischemia.
Nevertheless, important limitations persist. First, the financial cost is substantial, approximately $80000 per case, driven both by the device itself and the associated disposable components. This restricts widespread adoption, particularly within publicly funded healthcare systems. Second, currently available systems are designed for larger donors and present clear technical constraints in pediatric patients, particularly those weighing less than 40 kg. This limitation excludes a significant proportion of potential pediatric donors and substantially reduces the overall impact of this technology in this population
3. Normothermic regional perfusion (NRP)
Thoracoabdominal normothermic regional perfusion has emerged as one of the most promising strategies for cardiac donation after circulatory death in Spain. Following formal declaration of death and completion of the legally required no-touch period, circulation is re-established using extracorporeal support, typically ECMO or cardiopulmonary bypass, while strictly excluding cerebral circulation through clamping of the supra-aortic vessels.
From a technical perspective, NRP enables in situ myocardial resuscitation under near-physiological conditions, allowing comprehensive echocardiographic and hemodynamic assessment under load. Unlike ex vivo perfusion platforms, NRP is not constrained by donor size, making it particularly suitable for pediatric patients and low-weight donors. In addition, its cost is significantly lower than that of ex vivo perfusion systems, as the required equipment is routinely available in most tertiary hospitals. Importantly, NRP also facilitates simultaneous multiorgan donation. At present, it represents the most cost-efficient strategy, as a single ECMO circuit allows recovery of all transplantable organs.
Despite these advantages, NRP is a technically demanding procedure that requires highly specialized coordination among surgical, anesthetic, and perfusion teams. In the European context, its main limitation is not technical but ethical and regulatory. Ensuring absolute absence of cerebral perfusion has led to strict protocols and considerable variability between countries and even between regions. In Spain, the three supra-aortic trunks are transected and actively drained using suction to guarantee cerebral isolation.
4. On-table reanimation (OTR)
On-table reanimation represents an emerging strategy designed to overcome some of the ethical and technical challenges associated with NRP. After declaration of death, the heart is rapidly procured and reanimated ex vivo in the operating room using a simplified circuit, allowing direct functional assessment prior to static cold storage and subsequent implantation.
This technique completely eliminates any possibility of cerebral reperfusion, thereby substantially simplifying the ethical debate and potentially facilitating implementation in more restrictive regulatory environments. Furthermore, it is applicable to donors of any size, including neonates and infants, and avoids reliance on costly commercial perfusion devices.
Its limitations are primarily related to its early stage of clinical development. Overall experience remains limited, functional assessment criteria are not yet fully standardized, and the duration of reanimation is shorter and less physiological than that achieved with NRP.
COMMENTARY:
One of the major barriers to the implementation of cardiac DCD has been bioethical in nature. Some have expressed concerns regarding organ perfusion with ECMO, fearing inadvertent cerebral reperfusion. Others have been uneasy with the duration of the mandatory no-touch period following declaration of death, due to concerns about autoresuscitation. Additional objections have arisen from an incomplete understanding of the concept of therapeutic proportionality prior to donation. Ultimately, these controversies converge on a single issue: the definition of death. Although the end of life has become increasingly medicalized, its acceptance is not solely scientific, but also deeply social.
Before the introduction of the Harvard criteria for brain death in 1968, death was declared exclusively on cardiorespiratory grounds, and the earliest transplants were performed under this definition. This was not because the heart was considered more important than other organs, but rather for practical reasons: death could be certified without specialized equipment or expertise, based simply on the absence of pulse and respiration. With technological advances, however, vital functions could be artificially sustained through mechanical ventilation, necessitating a new definition of death—brain death. This shift generated substantial controversy, as many struggled to accept that a warm, ventilated body with a beating heart could be considered dead.
Now that transplantation medicine has, in a sense, “returned to its origins” by re-adopting circulatory criteria for death, controversy has resurfaced. Questions regarding irreversibility persist. In Spain, a 5-minute no-touch period is observed; in the state of Pennsylvania, 2 minutes are required; in Italy, 20 minutes; and in Russia, up to 30 minutes. There is no clear consensus regarding the optimal duration, although no cases of autoresuscitation have been reported beyond 5 minutes. The lack of international consensus on the required duration of the no-touch period reflects not so much physiological uncertainty as a collective difficulty in accepting that death is a process rather than a precisely timed event. This raises an unavoidable question: can a person be dead, but not dead enough to donate?
The issue of restoring circulation after declaration of death is largely theoretical and conceptual. With supra-aortic vessels clamped or drained, and with adjunctive cerebral Doppler monitoring, absence of cerebral blood flow can be reliably confirmed. Although regional circulation is restored, death may not be “permanent” in a strictly hemodynamic sense, yet it remains irreversible at the cerebral level, which is the morally and clinically relevant criterion. In this context, opposition to regional normothermic perfusion appears to be driven less by evidence-based concerns than by conceptual unease with the idea of restoring regional circulation after having already accepted brain irreversibility as the ultimate moral and clinical criterion of death. This leads to a fundamental question: is death a discrete event recorded at a specific time, or a physiological process? The central challenge of pediatric cardiac donation after circulatory death is therefore not a technical one, but a semantic and conceptual one: accepting that death, like many biological phenomena, does not occur at a single, administratively precise moment, but unfolds as an irreversible physiological sequence.
In conclusion, ethical debate is inherently valuable and constitutes an essential component of medical progress. However, such reflection must not overshadow a non-negotiable principle: patient autonomy. The capacity to decide over one’s own body does not cease with death, and the expressed will to donate organs should be recognized as a fundamental right. Disregarding this will, under any pretext, not only undermines the process but also compromises its ethical legitimacy.
REFERENCE:
Comprehensive Options for Pediatric Donation After Circulatory Death Donors. Kucera, John A. et al. Seminars in Thoracic & Cardiovascular Surgery: Pediatric Cardiac Surgery Annual, (ahead of print)
