Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, ...determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.
Objective The study objective was to compare the outcomes of intraoperative extracorporeal membrane oxygenation versus cardiopulmonary bypass support in lung transplantation. Methods We performed a ...retrospective cohort study from a prospective database of adult lung transplantations performed at the University of Toronto from 2007 to 2013. Among 673 lung transplantations performed in the study period, 267 (39.7%) required cardiopulmonary support. There were 39 cases of extracorporeal membrane oxygenation (2012-2013) and 228 cases of cardiopulmonary bypass (2007-2013). Patients who were bridged with extracorporeal life support, underwent a concomitant cardiac procedure, received a combined liver or heart transplant, were colonized with Burkholderia cenocepacia , or required emergency cannulation for cardiopulmonary support were excluded. Finally, 33 extracorporeal membrane oxygenation cases were matched with 66 cases of cardiopulmonary bypass according to age (±10 years), lung transplantation indication, and procedure type (bilateral vs single lung transplantation). Results Recipient factors such as body mass index and gender were not different between extracorporeal membrane oxygenation and cardiopulmonary bypass groups. Furthermore, donor variables were similar, including age, body mass index, last PaO2/FiO2 ratio, smoking history, positive airway cultures, and donor type (brain death and donation after cardiac death). Early outcomes, such as mechanical ventilation requirement, length of intensive care unit stay, and length of hospital stay, significantly favored extracorporeal membrane oxygenation (median 3 vs 7.5 days, P = .005; 5 vs 9.5 days, P = .026; 19 vs 27 days, P = .029, respectively). Perioperative blood product transfusion requirement was lower in the extracorporeal membrane oxygenation group. The 90-day mortality for the extracorporeal membrane oxygenation group was 6% versus 15% for cardiopulmonary bypass ( P = .32). Conclusions Extracorporeal membrane oxygenation may be considered as the first choice of intraoperative cardiorespiratory support for lung transplantation.
Availability of organs is a limiting factor for lung transplantation, leading to substantial mortality rates on the wait list. Use of organs from donors with transmissible viral infections, such as ...hepatitis C virus (HCV), would increase organ donation, but these organs are generally not offered for transplantation due to a high risk of transmission. Here, we develop a method for treatment of HCV-infected human donor lungs that prevents HCV transmission. Physical viral clearance in combination with germicidal light-based therapies during normothermic ex-vivo Lung Perfusion (EVLP), a method for assessment and treatment of injured donor lungs, inactivates HCV virus in a short period of time. Such treatment is shown to be safe using a large animal EVLP-to-lung transplantation model. This strategy of treating viral infection in a donor organ during preservation could significantly increase the availability of organs for transplantation and encourages further clinical development.
Lung transplantation (LTx) is now a very established treatment for patients with end-stage lung diseases. However, shortage of suitable donors is still a major limitation for realizing the full ...success of this therapy. Donor lungs from both brain death donors (BDD) and circulatory death donors (DCD) are often injured as a result of brain injury-related cytokine storm, aspiration, infection, fluid overload, ventilator-associated lung injury, and warm ischemia, which prevents them safely being used for transplantation 1. Attempts to transplant injured donor lungs can lead to high incidence of severe primary graft dysfunction (PGD) and associated short- and long-term consequences to recipients 2. Therefore, utilization rates of lungs from multi-organ donors is low, ranging from 5% to 20%. One of the most attractive strategies to increase donor lung utilization is by improving assessment and treatment of the organ once it is removed from the hostile peri-procurement environment of the donor. In order to achieve this, normothermic ex vivo lung perfusion (EVLP) has been developed over the last 10 years.
Extracorporeal life support (ECLS) is increasingly used to bridge deteriorating patients awaiting lung transplantation (LTx), however, few systematic descriptions of this practice exist. We therefore ...aimed to review our institutional experience over the past 10 years.
In this case series, we included all adults who received ECLS with the intent to bridge to LTx. Data were retrieved from patient charts and our institutional ECLS and transplant databases.
Between January 2006 and September 2016, 1111 LTx were performed in our institution. ECLS was used in 71 adults with the intention to bridge to LTx; of these, 11 (16%) were bridged to retransplantation. The median duration of ECLS before LTx was 10 days (range, 0-95). We used a single dual-lumen venous cannula in 23 patients (32%). Nine of 13 patients (69%) with pulmonary hypertension were bridged by central pulmonary artery to left atrium Novalung. Twenty-five patients (35%) were extubated while on ECLS and 26 patients (37%) were mobilized. Sixty-three patients (89%) survived to LTx. Survival by intention to treat was 66% (1 year), 58% (3 years) and 48% (5 years). Survival was significantly shorter in patients undergoing ECLS bridge to retransplantation compared with first LTx (median survival, 15 months (95% CI, 0-31) versus 60 months (95% CI, 37-83); P = .041).
In our center experience, ECLS bridge to first lung transplant leads to good short-term and long-term outcomes in carefully selected patients. In contrast, our data suggest that ECLS as a bridge to retransplantation should be used with caution.
A 60-year-old previously healthy man was admitted to hospital with COVID-19 pneumonia that was treated initially with noninvasive ventilation, steroids and antibiotics. Six weeks after admission, the ...patient remained dependent on oxygen, using a high-flow nasal cannula combined with a nonrebreather mask. Physical examination found proximal muscle wasting due to the long hospital stay. Computed tomography of his chest showed bilateral dense consolidations with superimposed interstitial and fibrotic changes. Because we thought the fibrosis was unlikely to resolve, we discussed the option of lung transplantation with him and his family, both of whom were interested in the procedure. An acute clinical deterioration subsequently led to his intubation, transfer to our extracorporeal life support centre and placement on veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a bridge to transplantation. Seventeen days after ECMO cannulation, the patient underwent successful double lung transplantation with removal of the V-V ECMO immediately after transplant.
The objective of this study was to review the international experience in lung transplantation using lung donation after circulatory death (DCD).
In this retrospective study, data from the ...International Society for Heart and Lung Transplantation (ISHLT) DCD Registry were analyzed. The study cohort included DCD lung transplants performed between January 2003 and June 2013, and reported to the ISHLT DCD Registry as of April 2014. The participating institutions included 10 centers in North America, Europe and Australia. The control group was a cohort of lung recipients transplanted using brain-dead donors (DBDs) during the same study period. The primary end-point was survival after lung transplantation.
There were 306 transplants performed using DCD donors and 3,992 transplants using DBD donors during the study period. Of the DCD transplants, 94.8% were Maastricht Category III, whereas 4% were Category IV and 1.2% Category V (euthanasia). Heparin was given in 54% of the cases, donor extubation occurred in 90% of the cases, and normothermic ex vivo lung perfusion (EVLP) was used in 12%. The median time from withdrawal of life support therapy (WLST) to cardiac arrest was 15 minutes (5th to 95th percentiles of 5 to 55 minutes), and from WLST to cold flush was 33 minutes (5th to 95th percentiles of 19.5 to 79.5 minutes). Recipient age and medical diagnosis were similar in DCD and DBD groups (p = not significant NS). Median hospital length of stay was 18 days in DCD lung transplants and 16 days in DBD transplants (p = 0.016). Thirty-day survival was 96% in the DCD group and 97% in the DBD group. One-year survival was 89% in the DCD group and 88% in the DBD group (p = NS). Five-year survival was 61% in both groups (p = NS). The mechanism of donor death within the DCD group seemed to influence recipient early survival. The survival rates through 30 days were significantly different by donor mechanism of death (p = 0.0152). There was no significant correlation between the interval of WLST to pulmonary flush with survival (p = 0.11).
This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors. It should be further evaluated whether the mechanism of donor death influences survival after DCD transplant.
Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics ...to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU).
We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge.
The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time.
In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).
More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung ...can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP.
In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital.
During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP.
Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059.).
Ex-vivo lung perfusion (EVLP) can be used to extend overall lung preservation time by splitting one long cold ischaemic time into two shorter ones and interposing an additional EVLP time. We assessed ...the outcomes after clinical transplantation of lungs with more than 12 h of preservation time.
For this retrospective study, we searched the Toronto Lung Transplant Program database for patients who had received at least one lung transplant between Jan 1, 2006, and April 30, 2015, at a single hospital in Toronto, Canada. We split the identified patients into those with a total preservation time of more than 12 h and those with a total preservation time of less than 12 h to act as the control group. Total preservation time was defined as the sum of first cold ischaemic time, EVLP time, and second cold ischaemic time. We excluded patients if they had received a heart-lung transplant or were younger than 18 years. In bilateral lung transplantations, we used the longer preservation time of the two lungs for analysis. Lung preservation was done according to present standards of care and EVLP was done according to the Toronto EVLP technique. The primary outcomes were survival and International Society for Heart and Lung Transplantation Primary Graft Dysfunction (PGD) grade at 72 h post-transplantation. We compared outcomes with our control group using univariable and multivariable models.
We identified 906 patients who met eligibility criteria and had sufficient data for analysis (<12 h group n=809; mean lung preservation time 400·8 min SD 121·8 vs >12 h group n=97; 875·7 min 109·0). Median hospital and intensive-care unit length of stay were similar between the less than 12 h group and the more than 12 h group (hospital stay: 23 days 16-42 vs 25·5 days 17-50·25, p=0·60; intensive-care unit stay: 4 days 2-14 vs 4 days 2-16, p=0·53). PGD grade was also not different between the two groups at 72 h post-transplantation (p=0·85). There was also no difference in survival between the two groups as shown on Kaplan-Meier survival curves (p=0·61). Multivariable survival analysis using Cox's model showed increasing recipient age to be a significant variable affecting survival.
Extension of graft preservation time beyond 12 h with EVLP does not negatively affect early lung transplantation outcomes. Extension of clinical lung preservation times might allow for more transplantations to be done as a result of improved facilitation and increased flexibility around timing of lung transplantation operations.
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