Lung transplantation from uncontrolled and controlled donation after circulatory death: similar outcomes to brain death donors

Controlled donation after circulatory death donors (cDCD) are becoming a frequent source of lungs grafts worldwide. Conversely, lung transplantations (LTx) from uncontrolled donors (uDCD) are sporadically reported. We aimed to review our institutional experience using both uDCD and cDCD and compare to LTx from brain death donors (DBD). This is a retrospective analysis of all LTx performed between January 2013 and December 2019 in our institution. Donor and recipient characteristics were collected and univariate, multivariate and survival analyses were carried out comparing the three cohorts of donors. A total of 239 (84.7%) LTx were performed from DBD, 29 (10.3%) from cDCD and 14 (5%) from uDCD. There were no statistically significant differences in primary graft dysfunction grade 3 at 72 h, 30- and 90-day mortality, need for extracorporeal membrane oxygenation after procedure, ICU and hospital length of stay, airway complications, CLAD incidence or survival at 1 and 3 years after transplant (DBD: 87.1% and 78.1%; cDCD: 89.7% and 89.7%; uDCD: 85.7% and 85.7% respectively; P = 0.42). Short- and mid-term outcomes are comparable between the three types of donors. These findings may encourage and reinforce all types of donation after circulatory death programmes as a valid and growing source of suitable organs for transplantation.     

Uncontrolled donation after circulatory death: European practices and recommendations for the development and optimization of an effective programme

The shortage of organs remains one of the biggest challenges in transplantation. To address this, we are increasingly turning to donation after circulatory death (DCD) donors and now in some countries to uncontrolled DCD donors. We consolidate the knowledge on uncontrolled DCD in Europe and provide recommendations and guidance for the development and optimization of effective uncontrolled DCD programmes.     

External validation of prediction models for time to death in potential donors after circulatory death

Predicting time to death in controlled donation after circulatory death (cDCD) donors following withdrawal of life‐sustaining treatment (WLST) is important but poses a major challenge. The aim of this study is to determine factors predicting time to circulatory death within 60 minutes after WSLT and validate previously developed prediction models. In a single‐center retrospective study, we used the data of 92 potential cDCD donors. Multivariable regression analysis demonstrated that absent cough‐, corneal reflex, lower morphine dosage, and midazolam use were significantly associated with death within 60 minutes (area under the curve [AUC] 0.89; 95% confidenence interval [CI] 0.87‐0.91). External validation of the logistic regression models of de Groot et al (AUC 0.86; 95% CI 0.77‐0.95), Wind et al (AUC 0.62; 95% CI 0.49‐0.76), Davila et al (AUC 0.80; 95% CI 0.708‐0.901) and the Cox regression model by Suntharalingam et al (Harrell's c‐index 0.63), exhibited good discrimination and could fairly identify which patients died within 60 minutes. Previous prediction models did not incorporate the process of WLST. We believe that future studies should also include the process of WLST as an important predictor.     

Kidney transplant from uncontrolled donation after circulatory death donors maintained by nECMO has long‐term outcomes comparable to standard criteria donation after brain death

Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplant (KT) with short‐term outcomes similar to those obtained from donation after brain death (DBD) donors. However, heterogeneous results in the long term have been reported. We compared 10‐year outcomes between 237 KT recipients from uDCD donors maintained by normothermic extracorporeal membrane oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD donors during the same period at our institution. We further analyzed risk factors for death‐censored graft survival in the uDCD group. Delayed graft function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P < .01), although glomerular filtration rates at the end of follow‐up were similar in the 2 groups. uDCD and DBD groups had similar rates for 10‐year death‐censored graft (82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454). Donor age >50 years was associated with graft loss in the uDCD group (hazard ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant effect. uDCD KT under nECMO support resulted in similar graft function and long‐term outcomes compared with KT from standard criteria DBD donors. Increased donor age could negatively affect graft survival after uDCD donation.     

An experimental study of the recovery of injured porcine lungs with prolonged normothermic cellular ex vivo lung perfusion following donation after circulatory death

Donation after circulatory death (DCD) is an underused source of donor lungs. Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving standard donor lungs but may also be useful in the preservation and assessment of DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm ischemia and postmortem ventilation on graft recovery were evaluated. Adult male swine underwent general anesthesia and heparinization. In the control group (n = 4), cardioplegic arrest was induced and the lungs were procured immediately. In the four treatment groups, a period of agonal hypoxia was followed by either 1 h of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on EVLP were worse in all DCD lungs compared with controls. Hemodynamics and compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated impaired oxygenation. Normothermic cellular EVLP is effective in preserving and monitoring of DCD lungs. Early donor postmortem ventilation and timely procurement lead to improved graft function.     

Transplantation of kidneys from uncontrolled donation after circulatory determination of death: comparison with brain death donors with or without extended criteria and impact of normothermic regional perfusion

The aim of this study was to compare the outcomes of kidney transplants from uncontrolled DCD (uDCD) with kidney transplants from extended (ECD) and standard criteria donors (SCD). In this multicenter study, we included recipients from uDCD (n = 50), and from ECD (n = 57) and SCD (n = 102) who could be eligible for a uDCD program. We compared patient and graft survival, and kidney function between groups. To address the impact of preservation procedures in uDCD, we compared in situ cold perfusion (ICP) with normothermic regional perfusion (NRP). Patient and graft survival rates were similar between the uDCD and ECD groups, but were lower than the SCD group (P < 0.01). Although delayed graft function (DGF) was more frequent in the uDCD group (66%) than in the ECD (40%) and SCD (27%) groups (P = 0.08 and P < 0.001), graft function was comparable between the uDCD and ECD groups at 3 months onwards post‐transplantation. The use of NRP in the uDCD group (n = 19) was associated with a lower risk of DGF, and with a better graft function at 2 years post‐transplantation, compared to ICP‐uDCD (n = 31) and ECD. In conclusion, the use of uDCD kidneys was associated with post‐transplantation results comparable to those of ECD kidneys. NRP preservation may improve the results of uDCD transplantation.     

Uncontrolled donation after circulatory death: A cohort study of data from a long‐standing deceased‐donor kidney transplantation program

Despite good long‐term outcomes of kidney transplants from controlled donation after circulatory death (DCD) donors, there are few uncontrolled DCD (uDCD) programs. This longitudinal study compares outcomes for all uDCD (N = 774) and all donation after brain death (DBD) (N = 613) kidney transplants performed from 1996 to 2015 at our center. DBD transplants were divided into those from standard‐criteria (SCD) (N = 366) and expanded‐criteria (N = 247) brain‐dead donors (ECD). One‐, 5‐, and 10‐year graft survival rates were 91.7%, 85.7%, and 80.6% for SCD; 86.0%, 75.8%, and 61.4% for ECD; and 85.1%, 78.1%, and 72.2% for uDCD, respectively. Graft survival was worse in recipients of uDCD kidneys than of SCD (P = .004) but better than in transplants from ECD (P = .021). The main cause of graft loss in the uDCD transplants was primary nonfunction. Through logistic regression, donor death due to pulmonary embolism (OR 4.31, 95% CI 1.65‐11.23), extrahospital CPR time ≥75 minutes (OR1.94, 95%CI 1.18‐3.22), and in‐hospital CPR time ≥50 minutes (OR 1.79, 95% CI 1.09‐2.93) emerged as predictive factors of primary nonunction. According to the outcomes of our long‐standing kidney transplantation program, uDCD could help expand the kidney donor pool.     

Procurement of lungs for transplantation following donation after circulatory death: the Alfred technique

Introduction

Donation after circulatory death (DCD) is an evolving method for lung transplantation (LTx) with results comparable to donation after brain death (DBD).

Materials and Methods

DCD lung transplant program requires a systematic approach for an efficient utilization of hospital resources. The surgical techniques have been developed to minimize the ischemic time during lung procurement. We have presented our management protocol and the surgical techniques as used at the Alfred Hospital in Melbourne, Australia.

Results

We have transplanted 92 recipients with lungs procured from 91 donors over an 8 year period from May 2006 to July 2014. This accounted for an extra 19% lung transplant operations performed during this time period. Operative mortality was 1% and 8 year survival was 71% in DCD lung recipients.

Conclusions

DCD lung transplantation provides an additional significant pool of lung donors with satisfactory short and long term outcomes.     

In situ lung perfusion is a valuable tool to assess lungs from donation after circulatory death donors category I–II

Donations after circulatory death (DCD) lung grafts are an alternative to extend the donor pool in lung transplantation. This study investigates the use of an in situ lung perfusion system (ISLP) in the donor to evaluate category I–II lungs. Pigs were sacrificed by ventricular fibrillation. All animals underwent 20 min of cardiopulmonary resuscitation and 5 min hands‐off period after which heparin was administered. In group [WI‐1], this was followed by 1 h of warm ischemia (WI) and 2 h of topical cooling (TC). In group [WI‐2], 2 h of WI was followed by 1 h of TC. In group [WI‐0], there was a minimal period of WI and no TC. In all three groups, the lungs were then evaluated during 60 min with ISLP. [WI‐0] lungs showed a significantly higher compliance and Δ PO₂/FiO₂ compared with [WI‐1] and [WI‐2]. PaCO₂ and lactate production were higher in [WI‐2] versus [WI‐0]. Wet/Dry weight ratio was significantly higher in [WI‐2] compared with [WI‐0] in two lung biopsy locations. A high W/D weight ratio was correlated with a lower compliance, higher lactate production, and a higher PaCO₂. ISLP is an effective way to assess the quality of lungs from category I–II DCD donors.     

Kidney donation after circulatory death in a country with a high number of brain dead donors: 10-year experience in Belgium

Worldwide shortage of standard brain dead donors (DBD) has revived the use of kidneys donated after circulatory death (DCD). We reviewed the Belgian DCD kidney transplant (KT) experience since its reintroduction in 2000. Risk factors for delayed graft function (DGF) were identified using multivariate analysis. Five-year patient/graft survival was assessed using Kaplan-Meier curves. The evolution of the kidney donor type and the impact of DCDs on the total KT activity in Belgium were compared with the Netherlands. Between 2000 and 2009, 287 DCD KT were performed. Primary nonfunction occurred in 1% and DGF in 31%. Five-year patient and death-censored graft survival were 93% and 95%, respectively. In multivariate analysis, cold storage (versus machine perfusion), cold ischemic time, and histidine-tryptophan-ketoglutarate solution were independent risk factors for the development of DGF. Despite an increased number of DCD donations and transplantations, the total number of deceased KT did not increase significantly. This could suggest a shift from DBDs to DCDs. To increase KT activity, Belgium should further expand controlled DCD programs while simultaneously improve the identification of all potential DBDs and avoid their referral for donation as DCDs before brain death occurs. Furthermore, living donation remains underused.     

The unique moral permissibility of uncontrolled lung donation after circulatory death

Implementing uncontrolled donation after circulatory determination of death (uDCDD) in the United States could markedly improve supply of donor lungs for patients in need of transplants. Evidence from US pilot programs suggests families support uDCDD, but only if they are asked permission for using invasive organ preservation procedures prior to initiation. However, non‐invasive strategies that confine oxygenation to lungs may be applicable to the overwhelming majority of potential uDCDD donors that have airway devices in place as part of standard resuscitation. We propose an ethical framework for lung uDCDD by: (a) initiating post mortem preservation without requiring prior permission to protect the opportunity for donation until an authorized party can be found; (b) using non‐invasive strategies that confine oxygenation to lungs; and (c) maintaining strict separation between the healthcare team and the organ preservation team. Attempting uDCDD in this way has great potential to obtain more transplantable lungs while respecting donor autonomy and family wishes, securing public support, and enabling authorized persons to affirm or cease preservation decisions without requiring evidence of prior organ donation intent. It ensures prioritization of life‐saving, the opportunity to allow willing donors to donate, and respect for bodily integrity while adhering to current ethical norms.     

Duration of delayed graft function and outcomes after kidney transplantation from controlled donation after circulatory death donors: a retrospective study

The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n = 9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2–11.75) days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1 year, and a higher rate of acute rejection. On Kaplan–Meier analysis, the presence of DGF was associated with lower graft survival (log‐rank test P = 0.034), though duration of DGF was not (P = 0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617–11.450); P = 0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor.