Is logistically motivated ex vivo lung perfusion a good idea? (original) (raw)
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The Journal of Heart and Lung Transplantation, 2012
BACKGROUND: Ex vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard International Society for Heart and Lung Transplantation criteria for transplantation. METHODS: We retrospectively evaluated 13 consecutive EVLP runs between January 2009 and December 2010. Lungs rejected for routine transplantation were implanted to the EVLP circuit and reperfused using acellular supplemented Steen Solution (Vitrolife, Göteborg, Sweden) up to a target flow rate of 40% of the donor's calculated flow at a cardiac index of 3.0 liters/min/m 2 ; target left atrial pressure Ͻ 5 mm Hg; and pulmonary artery pressure Ͻ 15 mm Hg. Mechanical ventilation was introduced after rewarming to 32°C: tidal volume, 6 to 8 ml/kg; respiratory rate, 7 to 8 breaths/min; duration of inspiration/expiration (I/E) ratio, 1:2; and positive end-expiratory pressure, 5 to 10 cm H 2 O. Hemodynamic and respiratory data monitoring with hourly clinical assessment were performed. Donor data, conversion rate to transplantation, and recipient outcome were analyzed. RESULTS: Donor data (n ϭ 13) were: age, 44.23 Ϯ 8.33 years; female/male, 8:5; cause of death: intracranial hemorrhage, 11 (85%), stroke, 1 (7.5%), hypoxic brain injury, 1 (7.5%); smoking history, 9 (69%), 17.44 Ϯ 8.92 pack-years; mechanical ventilation, 102.6 Ϯ 91.92 hours; chest x-ray imaging: abnormal, 12 (92.5%); normal, 1 (7.5%). EVLP: mean 141 Ϯ 28.83 minutes. Arterial partial pressure of oxygen/fraction of inspired oxygen 100% before termination of the circuit vs pre-retrieval value: 57.32 Ϯ 9.1 vs 42.36 Ϯ 14.13 kPa (p Ͻ 0.05). Six (46%) pairs of donor lungs were transplanted. Median follow-up was 297.5 days (range, 100-390 days), with 100% survival at 3 months. CONCLUSIONS: EVLP may facilitate assessment and/or reconditioning of borderline lungs, with a conversion rate of 46 % and good short-term survival.
European Journal of Cardio-Thoracic Surgery, 2014
OBJECTIVES: Only 15% of brain death donors are considered suitable for lung transplantation (LTx). The normothermic ex vivo lung perfusion technique is used to potentially increase the availability of high-risk lung donors. We report our experience of LTx with initially rejected donors after ex vivo lung reconditioning (EVLR). METHODS: From April 2011 to May 2013, we performed EVLR for 32 pairs of donor lungs deemed unsuitable for transplantation and rejected by the 11 French lung transplant teams. After EVLR, lungs with acceptable function were transplanted. During the same period, 81 double-lung transplantations (DLTx) were used as controls. RESULTS: During EVLR, 31 of 32 donor lungs recovered physiological function with a median PO 2 /FiO 2 ratio increasing from 274 (range 162-404) mmHg to 511 (378-668) mmHg at the end of EVLR (P < 0.0001). Thirty-one DLTx were performed. The incidence of primary graft dysfunction 72 h after LTx was 9.5% in the EVLR group and 8.5% in the control group (P = 1). The median time of extubation, intensive care unit and hospital lengths of stay were 1, 9 and 37 days in the EVLR group and 1 (P = 0.17), 6 (P = 0.06) and 28 days (P = 0.09) in the control group, respectively. Thirty-day mortality rates were 3.3% (n = 1) in the EVLR group and 3.7% (n = 3) in the control group (P = 0.69). One-year survival rates were 93% in the EVLR group and 91% in the control group. CONCLUSIONS: EVLR is a reliable and repeatable technique that offers a significant increase of available donors. The results of LTx with EVLR lungs are similar to those obtained with conventional donors.
Transplant International, 2014
This paper describes the initial clinical experience of ex-vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO 2 /FiO 2 was below 300 mmHg, or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia or sepsis were excluded. EVLP was run with a low flow, open atrium and low hematocrit technique. 35 lung transplants from brain death donors were performed, 7 of which after EVLP. EVLP donors were older (54±9 years vs. 40±15, EVLP vs. Standard, P<0.05), had lower PaO 2 /FiO 2 (264±78 mmHg vs. 453±119, P<0.05), and more chest X-ray abnormalities (P<0.05). EVLP recipients were more often admitted to Intensive Care Unit as urgent cases (57% vs. 18, P=0.05), Lung Allocation Score at transplantation was higher (79 vs. 39 [43][44][45][46], P<0.05). After transplantation, primary graft dysfunction (PGD 72 grade 3, 32% vs. 28, EVLP vs. Standard, P=1), mortality at 30 days (0% vs. 0%, P=1), and overall survival (71% vs. 86, EVLP vs. Standard, P=0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected.
Normothermic Ex Vivo Lung Perfusion in Clinical Lung Transplantation
New England Journal of Medicine, 2011
Background 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. Methods 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. Results 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. Conclusions 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.
Transplantation Proceedings, 2013
Background. Among the strategies to increase the number of lung transplants, ex vivo lung perfusion (EVLP) represents a novel technique to expand the donor pool. Methods. Data from donors referred to our center were retrospectively analyzed to identify grafts that could potentially be potentially reconditioned by EVLP and for comparison with those obtained by clinical application of EVLP program in our center. Results. Among 75 rejected lungs, 23 organs have been identified as potentially treatable with EVLP with a hypothetic increase of lung transplant activity of 53%. After the introduction of the EVLP program in our center, lung transplantation with reconditioned grafts was performed in 7 (23%) patients with a 30% increase in transplant procedures. Conclusion. Although less than expected, EVLP increased the number of lungs suitable for transplantation.
Transplantation of Initially Rejected Donor Lungs after Ex-Vivo Lung Perfusion
The Journal of Heart and Lung Transplantation, 2013
Objective: Ex vivo lung perfusion has the potential to increase the number of patients treated with lung transplantation. Our initial clinical experience with ex vivo lung perfusion is reviewed as well as early clinical outcome in patients transplanted with reconditioned lungs.
Background. Donation after circulatory death (DCD) has the potential to significantly alleviate the shortage of transplantable lungs. We report our initial experience with the use of portable ex vivo lung perfusion (EVLP) with the Organ Care System Lung device for evaluation of DCD lungs. Methods. We performed a retrospective review of the DCD lung transplantation (LTx) experience at a single institution through the use of a prospective database. Results. From 2011 to 2015, 208 LTx were performed at the University of Alberta, of which 11 were DCD LTx with 7 (64%) that underwent portable EVLP. DCD lungs preserved with portable EVLP had a significantly shorter cold ischemic time (161 � 44 vs 234 � 60 minutes, P = .045), lower grade of primary graft dysfunction at 72 hours after LTx (0.4 � +/- 0.5 vs 2.1 � +/- 0.7, P = .003), similar mechanical ventilation time (55 � +/- 44 vs 103 � +/- 97 hours, P = .281), and hospital length of stay (29 � +/- 11 vs 33 � +/- 10 days, P = .610). All patients were alive at 1-year follow-up after LTx with improved functional outcomes and acceptable quality of life compared with before LTx, although there were no intergroup differences. Conclusions. In our pilot cohort, portable EVLP was a feasible modality to increase confidence in the use of DCD lungs with validated objective evidence of lung function during EVLP that translates to acceptable clinical outcomes and quality of life after LTx. Further studies are needed to validate these initial findings in a larger cohort.
Histologic and functional evaluation of lungs reconditioned by ex vivo lung perfusion
The Journal of Heart and Lung Transplantation, 2012
BACKGROUND: Only about 15% of donor lungs are considered suitable for transplantation (LTx). Ex vivo lung perfusion (EVLP) has been developed as a method to reassess and repair damaged lungs. We report our experience with EVLP in non-acceptable donor lungs and evaluate its ability to recondition these lungs. METHODS: We studied lungs from 16 brain-dead donors rejected for LTx. After harvesting, the lungs were stored at 4°C for 10 hours and subjected to normothermic EVLP with Steen Solution (Vitrolife, Göteborg, Sweden) for 60 minutes. For functional evaluation, the following variables were assessed: partial pressure of arterial oxygen (PaO 2), pulmonary vascular resistance (PVR), and lung compliance (LC). For histologic assessment, lung biopsy was done before harvest and after EVLP. Tissue samples were examined under light microscopy. To detect and quantify apoptosis, terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling assay was used. RESULTS: Thirteen lung donors were refused for having impaired lung function. The mean PaO 2 obtained in the organ donor at the referring hospital was 193.7 mm Hg and rose to 489 mm Hg after EVLP. During EVLP, the mean PVR was 652.5 dynes/sec/cm 5 and the mean LC was 48 ml/cm H 2 O. There was no significant difference between the mean Lung Injury Score before harvest and after EVLP. There was a trend toward a reduction in the median number of apoptotic cells after EVLP. CONCLUSIONS: EVLP improved lung function (oxygenation capacity) of organs considered unsuitable for transplantation. Lung tissue structure did not deteriorate even after 1 hour of normothermic perfusion.
European Journal of Cardio-Thoracic Surgery, 2018
OBJECTIVES: Despite progress in lung transplantation (LTx) techniques, a shortage of donor lungs persists worldwide. Ex vivo lung perfusion (EVLP) is a technique that evaluates, optimizes and enables transplantation of the lungs that would otherwise have been discarded. Herein, we present our centre's first EVLP experiences between July 2012 and June 2016, when we performed 149 LTxs. METHODS: It was a single-centre, retrospective analysis of a prospectively collected database. The EVLP group (n = 9) consisted of recipients who initially received discarded donor lungs that were reconditioned using EVLP. The non-EVLP (N-EVLP) group (n = 18) consisted of data-matched patients receiving conventional quality lungs in the conventional way. Both groups were compared on primary graft dysfunction (PGD) grades 0-3, pulmonary function, chronic lung allograft dysfunction and survival. RESULTS: In the EVLP group, 33% (3/9) developed PGD1 at 72 h post-LTx. In the N-EVLP group, 11% (2/18) developed PGD1, 6% (1/18) PGD2 and 11% (2/18) PGD3 at 72 h post-LTx. At 3 and 24 months post-LTx, forced expiratory volume in 1 s as percentage of predicted was
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2017
Ex vivo lung perfusion (EVLP) was primarily developed for evaluation of impaired donor lungs. The good clinical results raise the question for its possible impact on lungs meeting standard criteria. Before application of EVLP on such lungs enters routine clinical practice, it must be demonstrated whether EVLP would affect or improve outcome when used in standard donor lungs. We performed a prospective randomized trial to investigate the role of EVLP in standard lung transplantation (Tx). This prospective randomized clinical trial compared patients who underwent Tx with ex vivo evaluated donor lungs with an equivalent patient population without previous EVLP. From October 2013 to May 2015, 193 lung Tx were performed at the Medical University of Vienna. During this period, 80 recipient/donor pairs that met the inclusion criteria were included in this trial, 41 pairs in the control group, and 39 in the EVLP group. In the EVLP group, 4 lungs (10.2%) ultimately did not qualify for Tx and...