The protocol combines a lung cooling rapid recovery technique with abdominal normothermic regional perfusion for abdominal graft procurement in controlled asystole donors, which is a safe and useful method to expand the donor pool.
Controlled donation after circulatory death (cDCD) has contributed to increasing donor numbers all over the world. Experiences published in the last years confirm that the outcomes after lung transplantation from cDCD are similar to those from brain death donors; however, the utilization of lungs from asystole donors remains low. Several reasons may be involved: different legal frameworks among countries and centers with different premortem interventions, inadequate lung donor care before procurement, or even poor experience with cDCD procedures and protocols.
Initially, the rapid recovery technique was commonly employed for the procurement of thoracic and abdominal organs in cDCD, but, in the last decade, abdominal normothermic regional perfusion (ANRP) with extracorporeal membrane oxygenation devices has become a useful method to restore blood flow to abdominal organs, allowing their quality improvement and their functional assessment prior to transplantation. This makes the donation procedure more complex and generates doubts about injury to the grafts due to dual temperature.
The aim of this article is to describe a protocol based on a single center experience with Maastricht III donors combining lung cooling rapid recovery in the thorax and abdominal normothermic regional perfusion. Tips and tricks focused on premortem interventions and lung procurement procedure techniques are explained. This may help to minimize the reluctance among professionals to use this combined technique and encourage other donor centers to use it, despite the increased complexity of the procedure.
Donation after circulatory death (DCD) started in Spain with uncontrolled donors. In 1996, the first national consensus document on DCD was published as a guide for the practice of uncontrolled donation after circulatory death1 (uDCD), also setting a moratorium on controlled donation after circulatory death (cDCD). In 2012, a new consensus emerged establishing the basis and the legislative framework for the practice of both uDCD and cDCD2. Currently, Spain is one of the most active countries in DCD, reaching the highest rate of donors after circulatory death in the world3. This type of donor represented nearly 35% of the total donors in 2021 in the country, with a marked decrease in uDCD and donors being exclusively cDCD4.
Organ procurement in cDCD is commonly performed using the super-rapid recovery technique5. After the declaration of death and when the non-touch period has elapsed, a rapid sternotomy and laparotomy is performed. The abdominal aorta and pulmonary artery are cannulated and flushed with cold perfusion solutions to preserve the abdominal and thoracic organs, plus topical cooling is conducted before retrieval6. In this situation, cDCD is characterized by the unpredictable consequences of warm ischemia, after the withdrawal of life-sustaining therapy. The ischemic damage during this period of agonic hypotension and progressive hypoxia, followed by the non-touch period after cardiac arrest, is further exacerbated by the later period of cold ischemia7. This combination of warm and cold ischemia seems to be detrimental, especially to abdominal grafts8,9,10, generating more reluctance among professionals in the use of these organs from cDCD donors.
To minimize these risks, an in situ preservation model, based on previous experiences from Spanish teams working in uCDC11, has been developed with growing interest. The use of extracorporeal membrane oxygenation (ECMO) systems to restore blood flow after death and before graft recovery can reverse the metabolic deviations resulting from ischemia and restore cellular physiology12. Abdominal normothermic regional perfusion (ANRP) can improve the quality of ischemic-damaged organs in cDCD13. Organ function can be assessed and improved, allowing a better selection of abdominal grafts for transplantation.
Recent international multicenter experiences provide evidence that ANRP versus the rapid recovery (RR) technique helps overcome traditional limitations in cDCD, reducing rates of post-transplant biliary complications, facilitating successful transplantation of older livers, and improving liver graft survival14,15. In kidneys, it seems to improve short-term outcomes with a lower delayed graft function and higher 1 year graft survival rates16. With this evidence, ANRP in cDCD has gained advantages over the rapid recovery technique for abdominal graft procurement and is now applied in several European countries and other parts of the world17,18.
The use of lungs from cDCD donors, however, was promptly adopted worldwide. A lung functional warm ischemic time of up to 60 min does not seem to affect survival19. In the last decade, several centers and multi-institutional experiences have reported outcomes after lung transplant from cDCD comparable to those from DBD20,21. The RR technique is the routine method for lung procurement: lungs are cooled topically and removed after being flushed with cold preservation solution22.
The first experiences combining ANRP and RR of lungs in cDCD were reported by two United Kingdom groups23,24. Years later, a variation of this technique adding premortem interventions was published25. Results present this dual procurement technique as safe and effective for both abdominal and thoracic grafts26. Obviously, the donation procedure becomes more complex. It requires technological and human resources, sufficient organizational capabilities, and has a higher economic cost. All of this may discourage professionals from starting a program. The aim of this study is to present a protocol especially focused on premortem interventions, cannulation, and aortic occlusion balloon placement, with tips and tricks learned from experience, and comment the different technical details to consider during lung retrieval when ARNP is used. At present, in the Center, cDCD donors have become the main source of grafts for thoracic and abdominal transplantation.
These interventions are undertaken at the bedside in the intensive care unit (ICU). This protocol follows the guidelines of the University Hospital Marqués de Valdecilla ethics committee and is in accordance with the Spanish legal framework regarding donation procedures. Informed consent was obtained from next of kin for video recording of the procedures for research. cDCD is considered in patients with catastrophic brain damage or a terminal heart or a neurodegenerative disease for whom the decision to withdraw life-sustaining therapy (WSLT) has been made. Exclusion criteria and lung evaluation are the same as with brain death donors (Table 1).
1. Premortem interventions in the donor
2. Withdrawal of life-sustaining therapy (WLST) and declaration of death
3. Lung recovery and procurement technique
NOTE: Lung recovery and procurement techniques are performed by the thoracic surgeon and the transplant coordinator (Figure 4).
4. Abdominal normothermic regional perfusion
5. Liver and renal recovery
NOTE: Liver and renal recovery are performed by the hepatic surgeon and kidney surgeon, respectively.
We performed a descriptive analysis of 30 lung transplants performed at University Hospital Marqués de Valdecilla with lungs obtained from cDCD donors in the last 2 years, 2020 and 2021. Donor and recipient demographic characteristics, technical data, postoperative outcomes, and short-term results are presented here. These results are presented as absolute numbers and percentages for categorical variables and as measures of central tendency and dispersion for continuous variables. The Kolmogorov-Smirnov test was used to test for normal distribution of the data.
Donor characteristics and technical data
Table 2 shows donors' demographic characteristics and technical data. Half of the donors were males, and the median age was 56.5 years. Only 16.7% had a smoking history. Brain injury was caused in most cases by hemorrhage (53.3%), followed by anoxia (23.3%), and trauma (3.35%). Other causes included the withdrawal of life-sustaining therapy in patients with amyotrophic lateral sclerosis. The median time of donor ICU stay and mechanical ventilation was 6 days. The mean value of final donor partial oxygen pressure in arterial blood over fractional inspired oxygen concentration (PaO2/FiO2) was 427 mmHg. In two cases, ex vivo lung perfusion was necessary for reconditioning the lungs due to the macroscopic appearance of edema.
Lung recipient and transplant-related characteristics
Table 3 shows the lung recipient and transplant-related characteristics. The percentage of patients with interstitial lung disease (ILD) was the highest (50%), followed by chronic obstructive pulmonary disease (COPD; 40%) and bronchiectasis (10%). Most recipients had a smoking history (83.3%), only 16.7% had systemic hypertension, and 10% had diabetes mellitus (DM). Pulmonary hypertension was present in 14 recipients (46.7%). All procedures were bilateral lung transplants, and none were performed in an urgent situation. One recipient needed intraoperative extracorporeal life support during surgery with ECMO. The median cold ischemic time was 292.5 min for the first graft and 405 min for the second.
Post-transplant complications and short-term outcomes
There were no intraoperative deaths. The incidence of primary graft dysfunction (PGD) grades is presented in Table 4. Two recipients (6.6%) needed postoperative ECMO support due to PGD3. There was no need for re-thoracotomy due to bleeding or other causes in the postoperative period. The median time for postoperative intubation was 24 h, for ICU stay was 3.1 days, and for hospital stay was 18.9 days. Acute cellular rejection in the first 3 weeks was present in 12 recipients (40%). There was no hospital mortality, and 30 day survival was 100%.
Figure 1: Assembly of arterial cannula connections. The figure shows the materials used for arterial cannula connection with ECMO and pressure lines. A 10 cm piece of the ECMO line is cut and used as a bridge between the arterial cannula and a straight connector with Luer lock with a three-way stopcock assembled. The three-way stopcock relates to the pressure line, and the other end of the straight connector is inserted into the ECMO line. Please click here to view a larger version of this figure.
Figure 2: Cannulation. (A) The figure shows the double lumen cannula used for femoral artery cannulation. (B) The femoral artery and venous cannulation are performed in one groin by open access. Cannulas are purged, clamped, and connected to the ECMO device. The wound incision is closed, and cannulas are fixed to the skin with silk sutures to avoid displacement. (C) The aortic occlusion balloon is introduced by the free lumen of the femoral artery cannula. Please click here to view a larger version of this figure.
Figure 3: Aortic occlusion balloon. Checking position and function. (A) The aortic occlusion catheter in the correct position checked by chest X-ray (see radiopaque marks above the diaphragm). The femoral pulse in the arterial cannula disappears when the balloon is filled, while the radial pulse is maintained (wave pulse and O2 saturation). The complete disappearance of the femoral pulse indicates the minimum balloon filling volume. (B) If the balloon is not completely full or is too advanced, pressure will be detected in both the femoral and radial arteries. This figure has been modified from Tanaka et al.29. Please click here to view a larger version of this figure.
Figure 4: Scheme of RR lung procurement with ARNP. The figure shows a summary of the procedure. Abbreviations: ECMO = extracorporeal membrane oxygenation; PEEP = positive end-expiratory pressure; ANRP = abdominal normothermic regional perfusion, RR = rapid recovery. This figure has been modified and adapted from Miñambres et al.36. Please click here to view a larger version of this figure.
Table 1: Criteria selection for lung donation in cDCD. This table shows the general criteria for lung donor selection in cDCD. Abbreviations: cDCD = controlled donation after cardiac death; WLST = withdrawal of life-sustaining therapy; FWIT = functional warm ischemic time. Please click here to download this Table.
Table 2: Donor characteristics and technical data. This table shows the main donor characteristics and technical data registered. Abbreviations: cDCD = controlled donation after circulatory death; MV = mechanical ventilation; ICU = intensive care unit; WLST = withdrawal of life-sustaining therapy; CA = cardiac arrest; WIT = warm ischemic time; PaO2/FiO2 = partial pressure of oxygen in arterial blood/fraction of inspired oxygen; EVLP = ex vivo lung perfusion; IQR = interquartile range; SD = standard deviation. Please click here to download this Table.
Table 3: Lung recipient and transplant-related characteristics. This table shows the main lung recipient characteristics and data registered during transplant surgery. Abbreviations: COPD = chronic obstructive pulmonary disease; ILD = interstitial lung disease; DM = diabetes mellitus; BMI = body mass index; CMV = cytomegalovirus; ECMO = extracorporeal membrane oxygenation; ICU = intensive care unit; MV = mechanical ventilation; PaO2/FiO2 = partial pressure of oxygen in arterial blood/fraction of inspired oxygen; IQR = interquartile range; SD = standard deviation. Please click here to download this Table.
Table 4: Post-transplant complications and short-term outcomes. This table shows data registered during the hospital stay and short-term results. Abbreviations: PGD = primary graft dysfunction, ECMO = extracorporeal membrane oxygenation; ICU = intensive care unit. Please click here to download this Table.
Though the use of simultaneous lung cold perfusion with ARNP in cDCD was first published in 2014, very few experiences have been described for this25,26,29. Moreover, the utilization of cDCD lungs, regardless of the technique used, remains low in most countries.
The critical steps within this protocol are the use of premortem interventions; a specific methodology to ensure coronary and cerebral perfusion is not restored with ANRP; the minimization of injury to the grafts due to dual temperature; and the goal of maintaining an adequate flow in the ECMO device to ensure abdominal organ perfusion.
The premortem interventions are contemplated in Spanish protocols. Although they are not essential, premortem heparinization and cannulation can not only reduce the functional warm ischemic time of abdominal organs but also avoid the need for access to the aorta for cannulation after the declaration of death. If there is premortem manipulation, it must be properly explained, and explicit informed consent must be obtained always being respectful of the wishes and values of the patients and their relatives. Initially, both groins were used: one for cannulation and another for aortic occlusion balloon insertion. The use of a double lumen arterial cannula provides both an ECMO entry line and an access port for the occlusion balloon, leaving the contralateral groin free in case of need.
The main ethical concern surrounding the use of ANRP is the possibility of resuscitation. It is mandatory to ensure an adequate lack of flow to aortic arch vessels and avoid any possibility of restoring cerebral and coronary circulation once death has been declared and ANRP is started. To achieve this, aorta clamping (thoracic or abdominal) is performed23,24,30. Aortic occlusion with a balloon was first reported by our group25 and validated31. This methodology ensures an appropriate blockage of the aorta, guaranteeing the absence of perfusion during all the procedure by continuous monitorization of balloon volume and left radial artery pressure. It also avoids the need for prompt access to the aorta, turning a rushed procedure into a calmer one, which could potentially reduce organ damage and losses due to surgical events generated by the hurry32,33.
Initially, the abdomen was simultaneously opened with the thorax. This, added to topical cooling of the lungs with cold saline, favored heat loss. To minimize graft injury due to dual temperature, the thoracic team starts the procedure while the abdomen is left closed during lung procurement. This contributes to maintaining abdominal normothermia and makes the surgical field more comfortable. In addition, only 1 L of cold saline is delivered to each hemithorax for topical lung cooling. With experience, we have noticed this is not mandatory, as ventilated lungs have good tolerance to warm ischemia19,34.
One reason for the low recovery of lungs in cDCD with combined ANRP is the fear of the abdominal teams regarding the poor flow in the pump during lung preservation and procurement. Maintaining pump flow and avoiding volume loss to ensure abdominal organ perfusion are two main goals during the procedure. With the use of the non-touch cava vein technique35, the inferior cava vein is not clamped during lung preservation, improving the blood return to the ECMO circuit. Additionally, a fluid overload is administered to the donor before the cava is clamped to prevent the absence of thoracic venous return. Despite the isolation of the inferior vena cava and descending aorta in the chest, continuous oozing from the intrathoracic blood vessels, especially the azygous vein, during and after lung procurement can lead to volume loss. Ligation of the azygous vein is mandatory, and hemostasis must be careful during lung block removal. The thoracic cavity must be checked for any bleeding points before the thoracic surgeon leaves the surgical field.
Limitations of the method include the following. Premortem interventions are not ethically or legally accepted in many countries. There is wide variability in protocols on cDCD around the world17. Although not essential, these maneuvers have important advantages such as the reduction of FWIT.
This combined procedure increases the complexity of the whole organ procurement process and demands logistical needs. Protocols must be supported by competent authorities and the experience of all the individuals involved is important. Intensive care professionals qualified in cDCD donor management, as well as thoracic and abdominal teams familiar with ECMO systems, are usually concentrated in reference centers, discouraging other small centers to start a program in cDCD. Many hospitals in the national territory of Spain are attached to donation programs but lack the necessary means to put cDCD with ANRP into practice. For this reason, mobile ECMO teams have been set up in several communities to travel and support the preservation and procurement of abdominal organs36,37,38.
Recently, as an evolution of ANRP, in situ thoracoabdominal normothermic regional perfusion has emerged as a novel technique to recover hearts from cDCD donors39,40.
At University Hospital Marqués de Valdecilla, located in Cantabria, the region with the highest rate of donation in the Spanish territory, the cDCD program was implemented in 2014. Prior experience with uDCD41 helped us to face this rapid transition to cDCD and embrace this new scenario. As the number of cDCD donors increased, the protocol and technique evolved and were refined. In the last 2 years, 38.4% of lung transplants were performed with cDCD donors (30 of 78), and cDCD lung donation has greatly reduced the time spent on the waiting list (median of 67 days in 2020, 94 days in 2019, 129 days in 2018, and 206 days in 2017), as published in the Spanish National Registry42.
Despite the increased complexity of donor management and organ procurement, this combined retrieval method is feasible, and it is safe for both thoracic and abdominal grafts.
The authors have nothing to disclose.
The authors acknowledge all the members involved in the Lung Transplant Program at University Hospital Marqués de Valdecilla.
Vial 5 mL Heparin 1000 UI/mL | ROVI | For donor heparinization | |
ECMO KIT (MATERIALS FOR CANNULATION) | |||
Artery pressure lines | BEXEN MEDICAL | 137.15 | Artery pressure line por radial artery and femoral cannula |
Bandage scissors | SURGIMEDIC | BC-881R | Shear to cut ECMO lines |
Bio-medicus Venous cannula 21 Fr (7.0 mm) x 27.5 in (69.9 cm) | MEDTRONIC | 96670-121 | Venous cannula |
Clhorhexidine solution 2% | Disinfectant solution | ||
ECMO device Maquet Rotaflow | Maquet, Rasttat, Germany | ECMO system | |
Electrocautery handle | DEXTRO | SW12200 | |
EndoReturn Arterial Cannula Kit 21-23F | Edwards Lifesciences | ER21B, ER23B | Arterial cannula with a doble lumen to ECMO connection and to introduce aortic oclussion balloon |
Ethicon LigaClip med/short 20 titanium medium | ETHICON | MCS30 | Ligaclips for control bleeding during groin dissection |
Ethicon LigaClip med/short 20 titanium small | ETHICON | MCS20 | Ligaclips for control bleeding during groin dissection |
Insertion Kit Bio-medicus 180cm | MEDTRONIC | 96551 | Insertion Kit for ECMO cannulas, with catheter, metal wire guide and dilators |
Irrigation pear | MEDLINE | DYNDE 20125 | Pear to be filled with saline and purge ECMO lines at the site of connection with cannulas |
Luer cone syringe 50cc | CARDIONATUR | 60ML | Syringe filled with saline to fill occlusion balloon |
Mersilk no 1, LR-60 CONV , 75 cm | ETHICON | W562H | Silk curved suture for ECMO cannulas fixation |
Prolene 4/0 | ETHICON | W8355 | polypropylene suture for purse string in femoral vessels or vascular suture |
Prolene 5/0 , 60 cm | ETHICON | 8325 | polypropylene suture for vascular suture |
Prolene 5/0, 90 cm | ETHICON | 8720 | polypropylene suture for vascular suture |
Reliant Stent Graft Balloon Catheter 12F | Medtronic, Ireland | AB46 | Aortic occlusion balloon introduced through femoral artery. It is used as an endoclamp |
Scalpel blade no 11 | INTRAVEN | 150011 | |
Scapel blade no 23 | INTRAVEN | 150023 | |
Silicone tube | IBERHOSPITEX | 0027224-P | Silicone tube to connect suction system |
Sofsilk braided silk no 1 strands | COVIDIEN | L-12 | Silk strand for ligation or bleeding control |
Sofsilk braided silk no 3 strands | COVIDIEN | L-115 | Silk strand for ligation or bleeding control |
straight connector 3/8"x3/8" with Luer lock | ANDOCOR | 04CS0022 | Piece to connect arterial cannula with ECMO line and the three way stop-cock for pressure line and blood sampling |
Surgical pads pack | TEXPOL | 146500 | |
Surgical stapler | COVIDIEN | 8886803712 | Stapler to close surgical wound |
Three-way stopcock | BD CONNECTA | 394501 | Three way stop-cock to connect farterial cannula with pressure line |
Vessel loop large | MEDLINE | VLMAXR | Vascular loop to embrace femoral artery and vein for bleeding control. |
Vessel loop small | MEDLINE | VLMINR | Vascular loop to embrace femoral artery and vein for bleeding control. |
Yankauer suction terminal 50 V | DEXTROMEDICA | 349701 | Suction terminal for suction while surgical dissection |
SURGICAL TOOLS FOR CANNULATION | |||
Adson retractor 20 cm adn 33 cm | |||
Aortic clamp | |||
Boyd Scissors 18 cm | |||
Dissection forceps without jaws 21 cm | |||
Farabeuf retractor small | |||
Mayo scissors straight 14 cm and 16 cm | |||
Metzembaum scissors 18 cm, 20 cm and 23 cm | |||
Mosquito forceps straigth and curved | |||
Needle holder 18 cm and 23 cm | |||
Russ dissection forceps 15 cm | |||
Scalpel handle no 23 and no 21, 21 cm | |||
Surgical Dissector 23 cm | |||
MATERIALS FOR LUNG PROCUREMENT | |||
10 cc syringe | BD DISCARDIT | 309110 | |
Alprostadil 500 mcgs injectable solution | PFIZER | Prostaglandin injected with lung preservation solution | |
Disposable GIA cartridge Steril 6/Ca | MEDTRONIC | 1141634 | |
Disposable GIA stapler 60/3.8 3/Ca | MEDTRONIC | 2802122 | Stapler for trachea and bronquial division |
Foley catheter 18 Ch Folysil | Folysil, Coloplast | AA6118 | urinary catheter employed to canulated pulmonary veins for retrograde perfusion |
Lung preservation solution Perfadex 1000 mL | Medisan, Uppsala, Sweeden | 19811 ( box of 10 units) | Lung preservation solution |
Mersilk no 1, LR-60 CONV , 75 cm | ETHICON | W562H | Silk curved suture for pericardium sutures |
Paediatric Venous cannula | SORIN GROUP | V132-12 | Cannula used for pulmonary artery cannulation |
Prolene 4/0 | ETHICON | W8355 | polypropylene suture for purse string in pulmonary artery |
Scalpel blade no 11 | INTRAVEN | 150011 | |
Sofsilk braided silk no 1 strands | COVIDIEN | L-12 | Silk strand to fix arterial cannula with the tourniquet |
Sofsilk braided silk no 3 strands | COVIDIEN | L-115 | Silk strand for vessel ligation |
Sterile bags | To keep and store lungs. | ||
Straigth connector 1,4"/1,4" with luer lock | ANDOCOR | 04CS0032 | Piece to connect pulmonary artery arterial cannula with preservation line and the three way stop-cock for prostaglandin |
Three-way stopcock | BD CONNECTA | 394501 | Three way stop-cock to connect farterial cannula with pressure line |
Uromatic set for irrigation double lead | MEDISAVE | TRC4007N | Irrigation system for lung preservation solution |
Uromatic set for irrigation single lead | MEDISAVE | TRC4002 | Irrigation system for lung preservation solution |
SURGICAL TOOLS FOR LUNG PROCUREMENT | |||
Aortic cross- clamp | |||
Battery-powered surgical saw | |||
Cooley vascular clamp | |||
Dissecting forceps 18 cm and 27,9 cm | |||
Finochietto sternal retractor | |||
Metzembaum scissors 20 cm and 23 cm | |||
Mosquito forceps curved 12,5 cm | |||
Vascular clamps | |||
SURGICAL TOOLS FOR ABDOMINAL ORGAN PROCUREMENT | |||
Adson articulated retractors | |||
Allis forceps 16 cm | |||
Aortic cross-clamps | |||
Boyd scissors 17 cm | |||
Castroviejo needle holder | |||
Cooley Vascular clamps | |||
Crile forceps curved 18 cm | |||
Davis retractor 24.5 cm | |||
DeBakey dissecting forceps 19.7 cm adn 24.1 cm | |||
DeBakey vascular clamps | |||
Dissecting forceps 18 cm and 27.9 cm | |||
Duval forceps 23 cm | |||
Farabeuf retractors | |||
Kidney Trays 300 cc and 500 cc | |||
Kocher forceps straigth 18 cm | |||
Langenbeck retractors 21 cm and 23 cm | |||
Mayo scissors straigth and curved , 17 cm | |||
Mosquito forceps straigth and curved, 12.5 cm | |||
Needle holders 15 cm, 18 cm, 23 cm and 23 cm. | |||
Pean forceps 16 cm | |||
Potts scissors 19cm | |||
Rochester forceps curved 24 cm | |||
Rochester forceps straigth 24 cm | |||
Russ dissection forceps 15 cm and 20 cm | |||
Scalpel handles | |||
Senn-mueller retractor 16 cm |