DCD

Fact-Finding Questions Hospital Leadership Should Ask

1. How should our hospital care team and hospital OR team prepare for the use of normothermic regional perfusion (NRP)?
2. Is our DCD policy current and up-to-date and does it address NRP?
3. What are some of the ethical considerations in utilizing NRP?
4. What are the different types of machine perfusion technologies that we may see at our hospital, and what should our hospital OR team know about them?

Key Points Hospital Leadership Should Remember

1. NRP and machine perfusion are not the same.
2. NRP is a recovery process or technique utilized for an increasing number of DCD cases to increase organ utilization and improve post-transplant outcomes through the preservation of organs by restoring blood circulation to specific regions of the body using specialized machines.
3. NRP complements ex-vivo perfusion devices as novel and transformative changes in the donation and transplantation environment.
4. Machine perfusion technologies are particularly beneficial for medically complex donors, DCD donors, and in cases where logistical challenges are present. These technologies support organ preservation, assessment, and, in some instances, repair.
5. Perfusion technologies and techniques, such as NRP, present opportunities for donors and families to maximize their gift in situations that would have otherwise not been considered a possibility for donation.

Model Elements for DCD Practice Within the Hospital

Ongoing developments in technology and techniques aim to maximize organ utilization and preservation, can modify processes, and affect case durations. It is crucial that all stakeholders involved in the donation process remain informed about these changes.

Preservation and Perfusion Technologies and Techniques

Over the last decade, there has been an increased focus on utilizing machine perfusion as an alternative to static cold storage (e.g., organ transport cooler) for organ preservation. Machine perfusion involves dynamically reconditioning and repairing donor organs by restoring oxygen and nutrient delivery and enabling the administration of therapeutic agents via a pump system, both at the time of recovery (in-vivo) and during transport to the recipient facility (ex-vivo). In-vivo refers to limited circulation being re-established after death, with the perfusion circuit set up within a specific region of the body. Ex-vivo refers to circulation being maintained through a recovered organ outside the body, using a machine-based perfusion system. Beyond its potential to enhance organ quality through repair, machine perfusion offers the prospect of salvaging organs that previously would not have been able to be transplanted. Additionally, it allows for pre-transplant viability assessment of the donor organ ‘while on the pump,’ preventing unnecessary transplantation of organs that may not function properly in the recipient. Lastly, machine perfusion extends the time the organs remain viable for transplantation, facilitating daytime surgeries and ensuring smooth transfer of the donor organ to the recipient hospital.¹

Organs recovered from DCD donors are exposed to warm ischemia during the process of circulatory death. Warm ischemia creates organ injury at the cellular level as oxygen and nutrient delivery slows and stops during the dying process.² Warm ischemic injury can result in varying degrees of short- and long-term organ dysfunction after DCD organs are transplanted. Organs recovered from brain dead/death by neurologic criteria (BD/DNC) donors do not experience warm ischemia, and thus warm ischemia is the reason why transplants using DCD organs have historically had worse outcomes compared to those using organs from BD/DNC donors.³

Restoring oxygen and nutrient delivery to DCD organs affected by warm ischemia before transplanting them has the potential to repair cellular injury and improve organ quality. This is the concept behind machine perfusion, an important breakthrough that may narrow the quality gap between DCD and BD/DNC donor organs. Machine perfusion can be performed in two different ways:

1. Ex-Vivo (Outside the Body) – With ex-vivo perfusion, DCD organs are recovered following standard protocols. After recovery, organs are placed on an organ-specific perfusion device. Oxygenated fluid is pumped through the organ to reverse warm ischemic injury and improve organ quality prior to transplantation. To further assess function of the organ, organs can often be maintained on the ex-vivo perfusion device during transportation up to the time of transplant.⁴
2. In-Situ (Inside the Body) – With in-situ or in-vivo perfusion, commonly known as Normothermic Regional Perfusion (NRP), oxygenated blood is perfused through the organs with the help of a closed circuit connected to an extracorporeal membrane oxygenation (ECMO) machine, while the organs are still in the donor’s body. This restores oxygen to the warm ischemic organs as early as possible after declaration of death, minimizing the effect of the warm ischemic injury. After a period of NRP to improve organ quality, the organs are flushed, cooled, and recovered normally.⁵ The use of NRP on a donor case may increase standard DCD case time in the OR.

As the field of machine perfusion matures within the United States’ donation and transplantation system, hospitals should expect to see several different perfusion strategies employed in the coming years.

Ex-Vivo Machine Perfusion

The use of ex-vivo perfusion has minimal impact on organ recovery operations at the hospital. There are two strategies for ex-vivo perfusion:

1. “On-Site” Perfusion (also known as on-site normothermic machine perfusion “NMP”) –  With this strategy, a portable perfusion device is taken to the hospital with the transplant recovery team. After a DCD procurement, the organ is prepared on the back table and connected to the portable perfusion device.⁶ Sometimes the transplant recovery team may request that the hospital provide several units of packed red blood cells to prime the perfusion machine; other than that, there is minimal impact on the procedure from the hospital’s perspective.
2. “Back-to-Base” Perfusion – With this strategy, organs are packaged on ice at the hospital in the usual manner and are transported to the recipient hospital, where the organ is placed on the perfusion device and maintained until the time of transplantation.⁷

These two ex-vivo perfusion strategies have been increasingly implemented in North America and Europe. The use of ex-vivo perfusion for kidneys has been commonplace for decades. Recent advances have led to the ability to perfuse non-kidney organs such as livers, hearts, and lungs. DCD organs particularly benefit from ex-vivo perfusion to reverse the warm ischemia injury inherent in the DCD process, improving post-transplant outcomes as compared to conventional ice storage.⁷ Ex-vivo perfusion is an important example of how technological and clinical advances maximize the donor’s gift by improving the quality and number of transplantable organs recovered from DCD donors.

In-Situ Normothermic Regional Perfusion (NRP)

NRP is an organ recovery technique designed to minimize the impact of warm ischemia on DCD organs. The United Kingdom and some European countries have been utilizing NRP for several years. Since 2020, NRP has gained traction in the United States and has been increasingly offered throughout the country. Proponents contend that NRP is the most effective method for improving the quality and number of organs recovered from DCD donors, as it both increases the organ pool for transplant recipients and maximizes the gift of the DCD donor. Indeed, NRP has been repeatedly shown to improve post-transplant liver and kidney outcomes, increase the utilization of livers from DCD donors, and has directly contributed to increases in United States DCD heart utilization.^8,9,10,11,12

NRP utilizes the deceased donor’s vasculature as conduits to deliver blood and oxygen to the transplantable organs in the post-mortem state.⁸ Arterial and venous cannulas are placed within major blood vessels within the donor’s body, and these cannulas are connected to a portable circuit containing a pump to propel perfusion, heater, oxygenator, and fluid reservoir. Blood vessels leading to the newly deceased donor’s brain may be either, clamped, occluded with a balloon device, and/or vented to ensure that oxygenated blood does not perfuse the brain. Warm, oxygenated blood is then circulated through the organs intended for transplantation while the organs are still in the donor’s body, minimizing the time from warm ischemic injury to organ perfusion. Perfusion is maintained for typically one to two hours to allow recovery of organ injury as well as organ assessment, and then the organs are flushed with cold preservation solution, recovered, and packaged as in a typical donor operation.

Types of NRP

Abdominal NRP

Abdominal NRP (A-NRP) targets perfusion of the liver, kidneys, and pancreas and can be used in DCD donors when thoracic organs are not intended for transplantation. A-NRP is accomplished by canulating either the femoral artery/vein (peripheral cannulation) or the aorta/vena cava (central cannulation) for connection to an extracorporeal mechanical organ support.¹³ The descending thoracic aorta is occluded either by a balloon device or a vascular clamp, limiting perfusion to the abdominal organs alone for resuscitation and assessment. Oxygenated blood flow is reinitiated with the aid of extracorporeal mechanical organ support. A-NRP is typically performed by abdominal surgeons supported by a trained perfusionist who operates the extracorporeal device.

Thoracoabdominal NRP

Thoracoabdominal NRP (TA-NRP) targets perfusion of the heart and lungs in addition to the liver, kidneys, and pancreas, increasing the number of potentially transplantable organs recovered from a DCD donor. As with A-NRP, an extracorporeal mechanical device is utilized. TA-NRP is usually performed by placing cannulas in the heart and ascending aorta, with the aortic arch vessels clamped or divided to prevent cerebral perfusion.¹⁴ TA-NRP is typically initiated by thoracic surgeons supported by a trained perfusionist. Abdominal surgeons are on-site to recover the abdominal organs, and an anesthesia provider might be requested to re-intubate the donor after NRP is established. During TA-NRP the heart resumes beating, and the NRP flow can be weaned to allow the heart and lungs to support perfusion and oxygenation.

Central versus Peripheral Cannulation Strategies

Some interventions intended to facilitate a successful donation outcome are performed prior to the determination of death of the potential DCD donor. The scope of pre-mortem interventions that may be allowed vary according to hospital policy and OPO practice. Pre-mortem interventions require informed consent. The most common example of a pre-mortem intervention is the administration of heparin. When NRP is planned, the typical dosage is 50,000 units, which is permitted in most hospitals in the United States.

NRP can be performed without the need for pre-mortem intervention, evidenced by the experience in the United Kingdom where pre-mortem interventions including Heparin are not performed.¹⁵ Under these restrictions central cannulation by rapid post-mortem surgical access to the abdominal or thoracic great vessels is performed, similar to organ recovery from DCD donors when NRP is not utilized.

When more extensive pre-mortem interventions are possible and consent is obtained, surgeons may place the cannulas to be used for NRP through a small bedside procedure prior to initiation of the DCD process. Sheath access for a balloon occlusion device may also be placed at the bedside. This pre-mortem peripheral cannulation technique can facilitate the post-mortem initiation of NRP by connecting the cannulas to the device and inflating the occlusion balloon, simplifying the early NRP process. At this time there are no data available to directly compare the post-transplant outcomes of organs recovered via central post-mortem or peripheral pre-mortem cannulation for NRP.

Hospital Considerations

The goal of NRP is to increase the number of donors and maximize each donor’s gift (both in the number of organs and the quality of each organ). NRP may increase the length of the OR time due to a possible longer wait period for the patient to die, as well as added perfusion time. As in all organ donation cases, communication between the hospital patient care team, hospital OR personnel, transplant recovery teams, and OPO recovery team is critical for a smooth, successful NRP recovery process. There are a few NRP-specific considerations that require attention before and during an NRP recovery.

Review of Hospital Policy for Pre-Mortem Intervention

The emergence of NRP is a reminder that hospitals need an up-to-date review of their DCD-specific policies. Clear communication of policies specific to pre-mortem interventions are necessary so that transplant recovery teams can plan their cannulation strategy (i.e., central vs. peripheral).

OR Selection

NRP cases may require additional transplant recovery team members to be present. Operating rooms with ample space to accommodate larger surgical teams are preferred. The perfusionists setting up the NRP device will need access to electrical power as well as wall oxygen. A room should be selected to allow the device to be placed close to these resources without obstructing personnel flow in the room. Teams may request table space to set up and operate small point-of-care blood monitoring devices during NRP, which are used to measure values such as arterial blood gases (pH, pCO₂, pO₂), lactate, potassium, glucose, and hemoglobin to assess organ perfusion and viability.¹⁶ Surgical instrument selection is the same as for other organ donor operations; all NRP-specific equipment including tubing, cannulas, and the device itself will be provided by the transplant recovery teams. The team may request basic supplies such as IV fluids. Of note, an electrocautery device (Bovie) will be needed to obtain hemostasis after initiation of NRP.

Hospital Staff Needed

NRP should not require any additional hospital staff than a standard DCD case. It should be noted that NRP cases may take longer to set up and perform compared to standard DCD cases, with expected case length similar to a donation after BD/DNC of a multiorgan donor. As in all DCD cases with thoracic organ recovery, an anesthesia provider may be asked to be on standby to intubate the donor post-mortem for TA-NRP cases.

Blood Products

Maintaining volume in the NRP circuit is critical for successful perfusion. Teams may request that several units of typed-and-crossed packed red blood cells are available for transfusion into the NRP circuit in case they are needed.

Ethics

The ethical aspects of NRP have been well-established in many Western nations, including Spain, France, Italy, and the United Kingdom. In France, NRP is now mandatory for DCD donors due to the improvements in organ utilization and post-transplant outcomes.¹⁶

At the time of the authoring of this guide, NRP is still rather new to the United States’ donation and transplantation system, and the discussion of NRP ethics is ongoing and dynamic.^17,18 One such concern has been whether there is a possibility of brain reperfusion during NRP despite the application of preventative measures. Current and ongoing research supports the ethical compliance of NRP with the dead donor rule, affirming the absence of perfusion to the brain during the procedure.¹⁹ The Alliance provides resources for comprehensive information about different ethical considerations and will be updating these as changes occur. (See resource section.)