Normothermic regional perfusion mobile teams in controlled donation after circulatory death pathway: Evidence and peculiarities

Abstract

To facilitate the implementation of controlled donation after circulatory death (cDCD) programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation (ECMO) team (Spokes), some countries and Italian Regions have launched a local cDCD network with a ECMO mobile team who move from Hub hospitals to Spokes for normothermic regional perfusion (NRP) implantation in the setting of a cDCD pathway. While ECMO teams have been clearly defined by the Extracorporeal Life Support Organization, regarding composition, responsibilities and training programs, no clear, widely accepted indications are to date available for NRP teams. Although existing NRP mobile networks were developed due to the urgent need to increase the number of cDCDs, there is now the necessity for transplantation medicine to identify the peculiarities and responsibility of a NRP team for all those centers launching a cDCD pathway. Thus, in the present manuscript we summarized the characteristics of an ECMO mobile team, highlighting similarities and differences with the NRP mobile team. We also assessed existing evidence on NRP teams with the goal of identifying the characteristic and essential features of an NRP mobile team for a cDCD program, especially for those centers who are starting the program. Differences were identified between the mobile ECMO team and NRP mobile team. The common essential feature for both mobile teams is high skills and experience to reduce complications and, in the case of cDCD, to reduce the total warm ischemic time. Dedicated training programs should be developed for the launch of de novo NRP teams.

Key Words: Controlled donation after circulatory death; Extracorporeal membrane oxygenation; Normothermic regional perfusion; Mobile teams; Warm ischemia time

Core Tip: To facilitate the implementation of controlled donation after circulatory death (cDCD) programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation (ECMO) team, normothermic regional perfusion (NRP) mobile teams have been developed, mainly by the “conversion” of existing mobile ECMO teams. We summarized existing evidence on NRP teams with the goal of identifying the characteristic and essential features of a NRP mobile team for a cDCD program, especially for those centers starting the program.

INTRODUCTION

Controlled donation after circulatory death (cDCD)[1] is an emerging program which has recently proved to increase the potential donor pool, thus counteracting the shortage of donors. The cDCD programs are growing in many countries worldwide[2]. In Italy, the National Transplant Center reported a significant increase in the number of Italian procurement centers with a cDCD program from 2017 (number of centers: 14) to 2023 (number of centers: 72)[3]. According to the Italian law regulating death declaration after cardiac arrest, a 20-minute no-touch period is needed, which is the longest in the world. Nevertheless, in 2023 the heart from a cDCD Italian donor was recovered and successfully transplanted[4]. A cDCD pathway is characterized by logistical, organizational, and clinical challenges and its potentialities are still to be completely highlighted and implemented within a country and/or a region.

The European Society for Organ Transplantation[5] recommends the use of normothermic regional perfusion (NRP) both in uncontrolled and in cDCD. In donation after circulatory death (DCD), NRP can re-establish oxygenated blood after circulatory arrest, thus allowing the restoration of depleted energy substrates and the induction of endogenous antioxidants. Thus, NRP may contribute to the repair of ischemic-reperfusion injury. NRP also allows assessment of organ function. Logistically, NRP permits retrieval surgical teams to reach the procurement center. In a systematic review and meta-analyses of regional perfusion in donation after circulatory death organ transplantation[6], NRP proved to reduce post-transplant complications, especially biliary complications in controlled DCD livers compared with in situ cold preservation. In a retrospective analysis of United Kingdom adult cDCD donors where at least one abdominal organ was accepted for transplantation (2011-2019), Oniscu et al[7] reported that NRP use during cDCD organ recovery was associated with increased organ utilization and improved transplant outcomes compared to conventional organ recovery. In Italy, a 20-minute no touch period is needed for death declaration according to Italian law. That is why, NRP is mandatory in controlled and uncontrolled DCD as stated by the National Transplant Center. To facilitate the implementation of cDCD programs even in hospitals not equipped with a local Extracorporeal Membrane Oxygenation (ECMO) team (Spokes), some countries and Italian Regions launched a local cDCD network with a ECMO mobile team who moves from Hub hospitals to Spokes for NRP implantation in the setting of a cDCD pathway. In most cases, the Regional Transplant Center “converted” the local ECMO mobile team [experienced in the implantation of veno-venous (VV) and/or veno-arterial (VA) ECMO in peripheral hospitals and in the retrieval of these patients] into a NRP mobile team. Although ECMO teams have been clearly defined by the Extracorporeal Life Support Organization (ELSO), regarding composition, responsibilities and training programs, no clear, widely accepted indications are to date available for NRP teams. While existing NRP mobile networks were developed to increase the number of cDCDs, there is now the necessity for transplantation medicine to identify the peculiarities and responsibility of a NRP team for all those centers launching a cDCD pathway.

To this purpose, we summarized the characteristics of an ECMO mobile team, highlighting similarities and differences with the NRP mobile team. We also assessed existing evidence on NRP teams with the goal of identifying the characteristic and essential features of a NRP mobile team for a cDCD program, especially for those centers starting the program.

NOMENCLATURE

There is so far no consensus of nomenclature, mainly because ECMO mobile teams were launched in different periods in different countries and Italian regions. Most papers have reported the term ECMO mobile team, simply translating ECMO mobile for refractory cardiorespiratory and respiratory failure into a cDCD pathway. In 2018, in a position paper of the ELSO an unambiguous nomenclature for extracorporeal life support (ECLS) was provided[8-11]. It was clarified that the term “ECMO” referred to a specific extracorporeal configuration and application for support of cardiopulmonary dysfunction, even if it became synonymous with any form of extracorporeal system. The term “ECLS” then emerged to describe the entire family of extracorporeal support modalities for long-term support, including VA ECMO. The VA ECMO family was defined as the extracorporeal interval support for organ recovery to provide perfusion of organs awaiting recovery after declaration of cardiac death (EISOR). In 2018, for the first time, the term “mobile ECMO team for cDCD” was reported by a Spanish group from Granada who had implemented this program (as stated for cDCD outside their center) since 2015. Circelli et al[12] defined their “ECMO mobile team for cDCD” as “EISOR delivery”. The latter term cannot be found in any other paper on this topic. In the United States[13], different to Europe, the use of NRP has been driven by cardiothoracic teams aiming to transplant cDCD hearts. Retrospective analyses documented that kidneys, livers, and pancreases (“bystander” organs from cDCD donors) had good outcomes following thoracoabdominal NRP. Croome et al[14] (Mayo Clinic Florida) described the implementation and results of their abdominally driven “NRP program”[14]. They reported on 14 cases of cDCD performed with A-NRP that resulted in transplantation of 11 livers, 21 kidneys, and 1 pancreas in 6 months. In 2020, Pérez Redondo et al[15] reported their experience in Madrid, and addressed, for the first time, their mobile ECMO team for cDCD as “NRP mobile team”.

ECMO MOBILE TEAM VS NRP TEAM

In the past years ECMO was restricted to treatment of refractory cardio-respiratory failure on site only in selected tertiary-care centers[8,16-24]. After the first successful implementation of in-hospital ECMO therapy in the 1970s, growing evidence emerged showing the benefits of this supportive option. In the last decades “mobile ECMO” has been increasingly and progressively implemented since the H1N1 pandemic[8-11,17-24]. The term “mobile ECMO” indicates cannulation by an experienced team outside the specialized center, usually in local hospitals not equipped with ECMO support, followed by patient transport to the tertiary-care center. The ELSO provided guidelines for Transport and Retrieval of Adult and Pediatric Patients with ECMO Support, including a practical reference for providing primary and secondary mobile ECMO services. Special considerations were also included regarding communication and documentation, equipment as well as mobile ECMO team structure and responsibilities[20]. The comparison between Mobile ECMO teams and NRP teams allows the identification of differences (Table 1) that may be of help for all centers who are in the phase of starting and launching a cDCD program with a de novo mobile NRP team. While ECMO mobile teams are skilled for two different types of cannulations (VV and VA), NRP teams performed only VA cannulation followed by the opt site arterial cannulation for aortic balloon inflation and cannulation (abdominal-NRP configuration). No patient retrieval is required to an NRP team, different to a mobile ECMO team and this may affect the equipment. Different to NRP teams, mobile ECMO members are required, before ECMO implantation, to clinically assess the patient in the peripheral hospital and eventually to change the type of ECMO configuration (VA vs VV ECMO) in the presence of an abrupt and unexpected change in clinical conditions. In other words, the mobile ECMO team should be experienced in prehospital emergency care, ECMO and critical care, and ECMO technology and physiology. For both mobile teams, high technical skills are mandatory to lower the risk of complications and to reduce the time of implantation. In the case of NRP, the lower the time of implantation, the lower the warm ischemic time which is known to affect graft outcomes[5-7]. This is particularly true in Italy, with the 20-minute no touch period for death declaration. Technical skills and number of extracorporeal support runs are intuitively related. According to the ELSO registry[8,18], the number of annual ECMO runs to correlate with patient survival and the lower limit for a positive learning curve and maintenance of competence is at least 20 treatments per annum. Regarding respiratory failure, Combes et al[19], proposed ECMONet to consolidate all respiratory ECMO patients to regional or national high-volume ECMO centers preferably at tertiary hospitals. An organizational model of “Hub and Spoke” was implemented by ECMONet and applied during the coronavirus disease 2019 pandemic for refractory respiratory failure. The Hub and Spoke model was “translated “to transplantation medicine for cDCD program implementation also in procurement centers not equipped with a “in loco ECMO team”. This allows the spread of cDCD procurement in peripheral centers, within a cDCD regional network.

Table 1 Differences and similarities between mobile extracorporeal membrane oxygenation teams and normothermic regional perfusion teams.

	Mobile ECMO team	NRP team
Type of cannulation	VV ECMO	NRP
	VA ECMO
Transport of ECMO patients	Always	Never
Equipment utilized	The same as the components used for in-house ECMO support	The same as the components used for in-house ECMO support
Clinical assessment - ECMO indications	Always	Never (technical feasibility)

ECMO: Extracorporeal membrane oxygenation; VV: Veno-venous; VA: Veno-arterial; NRP: Normothermic regional perfusion.

Medical equipment used for mobile service (both ECMO and NRP) is similar and a checklist must be completed before leaving to prevent incompleteness of the equipment needed. Regarding staffing, every member of a mobile service (ECMO and/or NRP) should be appropriately trained and accustomed with ECMO handling in general and with potential problems related to the system.

With regard to mobile ECMO teams, geographic discrepancies were reported in their composition. In the United States, anesthesiologists are not included, while European ECMO teams comprise anesthesiologists/intensivists[8-11]. Our Center in Florence is an ECMO referral center, equipped with an ECMO mobile team which includes an intensivist, a cardiologist, a cardiac surgeon, a perfusionist and an ECMO nurse. Transesophageal echocardiography is systematically used for ECMO implantation (both VV and VA)[9,11] and it has proved to be feasible and useful especially in refractory respiratory failure as it allows the assessment of heart function (particularly right ventricular function) before implantation and the safe implantation of the monocannula, most frequently used.

NRP MOBILE TEAM – AVAILABLE EVIDENCE

To date, few papers have reported data on NRP mobile teams involved in a cDCD pathway at a peripheral hospital (Table 2). Pérez-Villares et al[25] described, for the first time, their experience with a NRP mobile team (which they called “ECMO mobile”) at the Virgen de las Nieves Hospital, Granada (Spain). They launched a DCD program both for uncontrolled and controlled donors after circulatory death. The ECMO mobile team worked for cDCD outside their hospital since 2015. In 2018 they reported their experience: 5 donations in Granada, and 3 in other cities (Jaen at 92 km, Motril at 69 km, and Linares at 136 km). The Mobile Team (called “the transplant team”) included two transplant coordinators, one ECMO operator and one organ extractor supervisor. In the paper by Pérez-Villares et al[25], cDCD donations achieved by the mobile ECMO team resulted in 2 liver transplants and 15 renal transplants[25,26]. A few years later, Pérez Redondo et al[15] (Madrid, Spain) reported the implementation a cDCD program (launched in 2016) in peripheral hospitals thanks to the introduction of a NRP team. As reported by the group in Madrid, during the first 18 months, 33 controlled DCD donations were performed, which constituted the majority (88%) of all cDCDs in the Autonomous Community of Madrid. The mobile NRP team included three members: A surgeon with cannulation experience, a nurse trained in ECMO set-up and perfusion, an intensive care specialist responsible for the coordination of the entire procedure (team leader), assessment of ischemic times and able to correct electrolyte alterations and hemodynamic derangement. A strict collaboration between the NRP mobile team and the surgical procurement team is mandatory for the success of the entire procedure. According to the Spanish organization, the transplant coordinator at the procuring hospital is responsible for the donor’s assessment and for the organization all the logistics for organ recovery. Only after the donor is deemed eligible, the mobile NRP team and the retrieval teams are activated. The responsibilities of the mobile NRP team are the cannulation process and maintenance of an efficacious NRP. In March 2019[27], a Spoke hospital in Milan, not equipped with an ECMO facility, performed the first Italian cDCD which resulted in kidney and liver transplantation, thanks to a mobile ECMO team from the Hospital of Pavia (IRCCS Policlinico San Matteo). This mobile NRP team included the transplant coordinator, the organ donation nurse coordinator, one perfusion technician, and a cardiac surgeon. In 2023 Circelli et al[12] reported the results of their regionalized (Emilia Romagna, Italy) pathway for implementing NRP provision, which started in 2016. They managed to recruit cDCD donors in hospitals pertaining to a Local Health Authority (Azienda Unità Sanitaria Locale) in Romagna, Italy. The NRP team includes a group of intensivists, interventional radiologists, vascular surgeon, nurses and perfusionists experienced in extracorporeal support. The NRP mobile team of the Cesena group was described as “flexible”, ranging from a full team to a three-member team, including one intensivist, one nurse and one perfusionist. The total warm ischemic time as reported by Circelli et al[12,28] ranged from a minimum of 37 minutes to a maximum of 109 minutes, with a mean warm ischemic time of 51.5 minutes (13.8 SD, interquartile range 10). In the first case of heart retrieval from a cDCD in Italy, the mobile NRP consisted of cardiac surgeons, a cardiac anesthesiologist and transplant coordinator, as reported by Gerosa et al[4].

Table 2 Evidence of extracorporeal membrane oxygenation mobile teams.

	Spain, Granada	Spain, Madrid	Italy, Padua	Italy, Cesena	Italy, Padua (Heart retrieval)
Staff	Two transplant coordinators (ECMO operator and organ extraction supervisor), and a team of surgeons (cannulation and organ extraction		The TPM, the organ donation nurse coordinator, 1 perfusion technician, and a cardiac surgeon	Intensivists	Cardiac surgeon
				Interventional radiologist	Cardiac anesthesiologist
				Vascular surgeon	Transplant coordinator
				Nurses
				Perfusionists
Experience	8 cDCDs	33 cDCDs	1 cDCDs	45 cDCDs
	2 liver transplants	39 kidneys, 12 livers and 5 bilateral lungs were recovered and transplanted	1 liver transplant	25 liver transplants
	15 kidney transplants		1 kidney transplant	34 kidney transplants

ECMO: Extracorporeal membrane oxygenation, VV: Veno-venous, VA: Veno-arterial, NRP: Normothermic regional perfusion, cDCD: Controlled donation after circulatory death.

HOW TO LAUNCH A DE NOVO NRP MOBILE TEAM

According to available evidence, converting an existing well experienced mobile ECMO team to a NRP team is the most rapid and safest way to start a cDCD program in peripheral hospitals. Transplantation medicine should address the training procedures for enrolling new members for NRP teams. Scarce and non-homogeneous training programs have been reported in previous papers[13,25]. Pérez Redondo et al[15] reported three training courses, planned for all physicians and nurses interested in becoming a member of a NRP mobile team. These were simulation-based courses which addresses all aspects of a NRP run during the cDCD pathway. Circelli et al[12,28] reported a type of “field training program” as their team composition was flexible. They referred to this program as “a periprocedural theoretical and hands-on EISOR training” to “promote a progressive automatization of referring equipment”.

The indispensable mission of a NRP mobile team is to provide an NRP implantation with the lowest risk of complications and in the shortest possible time. A field training program might be associated with unwanted complications. There is a need for a structured, well-designed training program for all professionals who wish to become a member of a NRP mobile team.

CONCLUSION

The main responsibilities of an NRP team are as follows: The cannulation process (guaranteeing the lowest risk of complications and the shortest time) and the maintenance of an efficacious NRP.