Effect of hypertonic saline in the pretreatment of lung donors with hemorrhagic shock.

BACKGROUND: Hemorrhagic shock-induced lung edema and inflammation are two of the main reasons for the rejection of lungs donated for transplantation. Hypertonic saline (HS) induces intravascular volume expansion and has considerable immunomodulating effects that might minimize edema. Our hypothesis is based on the use of a hypertonic solution for treatment of donors who are in shock in an attempt to increase the supply of lungs for transplantation. METHODS: A total of 80 rats were allocated to four groups: one group was given an infusion of normal saline (NS; n = 20), one group received HS; n = 20, a sham group (n = 20), and a Shock group (n = 20). Half of the lungs from each group were evaluated in an ex vivo perfusion system, and the other half was used for measurements of cytokine levels and neutrophil counts. RESULTS: In the ex vivo perfusion assessment, the pulmonary artery pressures of the animals in the NS and HS groups did not exhibit significant differences compared with those in the sham group (P > 0.05) but were lower than those in the Shock group (P < 0.01). Furthermore, the tumor necrosis factor-α levels and neutrophil counts were lower in the HS group than those in the Shock group (P < 0.01) and did not exhibit significant differences compared with those in either the NS and Sham groups (P > 0.05). CONCLUSIONS: We showed that HS was equivalent to isotonic saline and contributed to the treatment of lungs subjected to hemorrhagic shock.

Experience of Lung Transplantation in Patients with Lymphangioleiomyomatosis at a Brazilian Reference Centre.

INTRODUCTION: Lung transplantation (LT) is the standard of care for patients with advanced lung diseases, including lymphangioleiomyomatosis (LAM). LAM accounts for only 1% of all LTs performed in the international registry. As a result, the global experience, including the use of mechanistic target of rapamycin (mTOR) inhibitors before and after LT in LAM, is still limited. METHODS: We conducted a retrospective review of all LAM patients who underwent LT at our centre between 2003 and 2016. Pre- and post-transplant data were assessed. RESULTS: Eleven women with LAM underwent LT, representing 3.3% of all procedures. Ten (91%) patients underwent double-LT. The mean age at diagnosis was 39 ± 6 years and the mean FEV1 before LT was 28 ± 14%. Only one patient underwent pleurodesis for recurrent pneumothorax. Pulmonary hypertension was confirmed in 3 (27%) patients. Four (36%) patients received sirolimus preoperatively; three of them received it until the day of LT, and there was no occurrence of bronchial anastomotic dehiscence after the procedure. Four patients (36%) received mTOR inhibitors post-transplant. The median follow-up from LT was 44 months. There were 3 deaths (27%) during the study and survival probabilities at 1, 3, and 5 years after LT were, 90, 90, and 77%, respectively. CONCLUSIONS: This data reinforces the role of LT for LAM patients with end-stage disease. The use of sirolimus seems to be safe before LT and the occurrence of complications after LT, including those LAM-related, should be continuously monitored.

A Retrospective Cohort Study of Risk Factors for Surgical Site Infection Following Lung Transplant.

BACKGROUND: Surgical site infections (SSIs) are among the leading health care-associated infections as well as a major problem in the postoperative period of lung transplant recipients. Little is known about the risk factors in this specific population. The objective of this study was to identify the incidence, risk factors, and outcomes of SSI following lung transplant. METHODS: Digital medical records of adult recipients subjected to lung transplant from July 2011 and June 2016 in a large Brazilian referral teaching public center were analyzed in this retrospective cohort follow-up. RESULTS: Among the 121 recipients analyzed, 19 (15.7%) had SSI; of these, 11 (57.8%) had superficial incisional infections, 1 (5.2%) had a deep incisional infection, and 7 (36.8%) had organ/space infection. Recipient-related risk factors for SSI were high body mass index (P = .041), prolonged surgery time (P = .043), and prolonged duration of chest drain placement (P = .009). At the multiple logistic regression was found that each hour elapsed in the surgical time increased the odds of SSI by around 2 times (odds ratio 2.34; 95% CI, 1.46-4.53; P = .002). Donor-related risk factors included smoking status (P = .05) and positive bronchoalveolar lavage (P < .001). Having an SSI was associated with an increased length of stay in intensive care units (P = .003), reoperation (P = .014), and a higher 1-year mortality rate (P = .02). CONCLUSIONS: The identified incidence rate was higher to that observed in the previous studies. The risk factors duration of chest tube placement and donor smoking status are different from those reported in the scientific literature.

Technical Challenges in Lung Transplantation of Kartagener Syndrome Recipients: A Unique Team Experience With 12 Patients.

Kartagener syndrome (KS) is a rare congenital disorder related to bronchiectasis, chronic sinusitis, and situs inversus, predisposing patients to recurrent respiratory infections that can evolve to end-stage lung disease; lung transplantation (LTx) is one of the therapeutic options. This study highlights some concerns in this group of patients, mainly related to the difficulty of performing the transplantation in recipients with suppurative disease and situs inversus. We conducted a retrospective analysis of all KS patients who underwent LTx at 2 national reference centers by the same LTx team. During 29 years of analysis, we performed 12 cases of bilateral sequential LTx in KS patients, representing 2.4% of all Ltx that we performed. Special perioperative care is needed, including vascular access sites and lung isolation techniques; operative concerns include the arteriotomy and bronchotomy during the back table preparation of the graft and concern about the length of the arterial and bronchial anastomosis. We found a higher incidence of bronchial complications is this group that had not been previously reported. Bilateral sequential orthotopic LTx is feasible in this group of patients, and more studies are needed to understand possible reasons for the apparent higher incidence of bronchial complications.

Extracorporeal Membrane Oxygenation and Lung Transplantation: Initial Experience at a Single Brazilian Center.

OBJECTIVE: To report initial experience from the use of extracorporeal membrane oxygenation (ECMO) in patients who received lung transplantation. METHODS: Retrospective study of a single tertiary center in the Brazilian state of São Paulo, a national reference in lung transplantation, based on the prospective collection of data from electronic medical records. The period analyzed extended from January 2009 (beginning of the program) until December 2018. RESULTS: A total of 75 lung transplants were performed, with ECMO used in 8 (10.7%) cases. Of the patients, 4 (50%) were female. The mean age was 46.4±14.3 years. The causes of the end-stage lung disease that led to transplantation were pulmonary arterial hypertension in 3 (37.5%) patients, bronchiectasis in 2 (25%) patients, pulmonary fibrosis in 2 (25%) patients, and pulmonary emphysema in 1 (12.5%) patient. In our series, 7 (87.5%) cases were sequential bilateral transplantations. Prioritization was necessary in 4 (50%) patients, and in 1 patient, ECMO was used as a bridge to transplantation. The ECMO route was central in 4 (50%), peripheral venovenous in 2 (25%) and peripheral venoarterial in 2 (25%) patients. The mean length of the intensive care unit (ICU) stay was 14±7.5 days and of the hospital stay was 34.1±34.2 days. The mean ECMO duration was 9.3±6.6 days with a 50% decannulation rate. Three patients were discharged (37.5%). CONCLUSION: Lung transplantation requires complex treatment, and ECMO has allowed extending the indications for transplantation and provided adjuvant support in the clinical management of these patients.

Evaluation and reconditioning of donor organs for transplantation through ex vivo lung perfusion.

OBJECTIVE: To assess the feasibility and impact of ex vivo lung perfusion with hyperoncotic solution (Steen Solution™) in the utilization of these organs in Brazil. METHODS: In this prospective study, we subjected five lungs considered to be high risk for transplantation to 4 hours of ex vivo lung perfusion, with evaluation of oxygenation capacity. High-risk donor lungs were defined by specific criteria, including inflammatory infiltrates, pulmonary edema and partial pressure of arterial oxygen less than 300mmHg (inspired oxygen fraction of 100%). RESULTS: During reperfusion, the mean partial pressure of arterial oxygen (inspired oxygen fraction of 100%) of the lungs did not change significantly (p=0.315). In the first hour, the mean partial pressure of arterial oxygen was 302.7mmHg (±127.66mmHg); in the second hour, 214.2mmHg (±94.12mmHg); in the third hour, 214.4mmHg (±99.70mmHg); and in the fourth hour, 217.7mmHg (±73.93mmHg). Plasma levels of lactate and glucose remained stable during perfusion, with no statistical difference between the moments studied (p=0.216). CONCLUSION: Ex vivo lung perfusion was reproduced in our center and ensured the preservation of lungs during the study period, which was 4 hours. The technique did not provide enough improvement for indicating organs for transplantation; therefore, it did not impact on use of these organs.

Ex vivo lung perfusion in Brazil.

OBJECTIVE: To evaluate the use of ex vivo lung perfusion (EVLP) clinically to prepare donor lungs for transplantation. METHODS: A prospective study involving EVLP for the reconditioning of extended-criteria donor lungs, the criteria for which include aspects such as a PaO2/FiO2 ratio < 300 mmHg. Between February of 2013 and February of 2014, the lungs of five donors were submitted to EVLP for up to 4 h each. During EVLP, respiratory mechanics were continuously evaluated. Once every hour during the procedure, samples of the perfusate were collected and the function of the lungs was evaluated. RESULTS: The mean PaO2 of the recovered lungs was 262.9 ± 119.7 mmHg at baseline, compared with 357.0 ± 108.5 mmHg after 3 h of EVLP. The mean oxygenation capacity of the lungs improved slightly over the first 3 h of EVLP-246.1 ± 35.1, 257.9 ± 48.9, and 288.8 ± 120.5 mmHg after 1, 2, and 3 h, respectively-without significant differences among the time points (p = 0.508). The mean static compliance was 63.0 ± 18.7 mmHg, 75.6 ± 25.4 mmHg, and 70.4 ± 28.0 mmHg after 1, 2, and 3 h, respectively, with a significant improvement from hour 1 to hour 2 (p = 0.029) but not from hour 2 to hour 3 (p = 0.059). Pulmonary vascular resistance remained stable during EVLP, with no differences among time points (p = 0.284). CONCLUSIONS: Although the lungs evaluated remained under physiological conditions, the EVLP protocol did not effectively improve lung function, thus precluding transplantation.

Psychological criteria for contraindication in lung transplant candidates: a five-year study.

Lung transplantation presents a wide range of challenges for multidisciplinary teams that manage the care of the recipients. Transplant teams should perform a thorough evaluation of transplant candidates, in order to ensure the best possible post-transplant outcomes. That is especially true for the psychologist, because psychological issues can arise at any point during the perioperative period. The objective of our study was to evaluate the psychological causes of contraindication to waiting list inclusion in a referral program for lung transplantation. We retrospectively analyzed data on psychological issues presented by lung transplant candidates, in order to understand these matters in our population and to reflect upon ways to improve the selection process.

Lung transplantation.

Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life.

Alternative solution for ex vivo lung perfusion, experimental study on donated human lungs non-accepted for transplantation.

PURPOSE: To evaluate a new perfusate solution to be used for ex vivo lung perfusion. METHODS: Randomized experimental study using lungs from rejected brain-dead donors harvested and submitted to 1 hour of ex vivo lung perfusion (EVLP) using mainstream solution or the alternative. RESULTS: From 16 lungs blocs tested, we found no difference on weight after EVLP: Steen group (SG) = 1,097±526g; Alternative Perfusion Solution (APS) = 743±248g, p=0.163. Edema formation, assessed by Wet/dry weigh ratio, was statistically higher on the Alternative Perfusion Solution group (APS = 3.63 ± 1.26; SG = 2.06 ± 0.28; p = 0.009). No difference on PaO2 after EVLP (SG = 498±37.53mmHg; APS = 521±55.43mmHg, p=0.348, nor on histological analyses: pulmonary injury score: SG = 4.38±1.51; APS = 4.50±1.77, p=0.881; apoptotic cells count after perfusion: SG = 2.4 ± 2.0 cells/mm2; APS = 4.8 ± 6.9 cells/mm2; p = 0.361). CONCLUSION: The ex vivo lung perfusion using the alternative perfusion solution showed no functional or histological differences, except for a higher edema formation, from the EVLP using Steen Solution(r) on lungs from rejected brain-dead donors.

Lung transplantation: overall approach regarding its major aspects.

Lung transplantation is a well-established treatment for patients with advanced lung disease. The evaluation of a candidate for transplantation is a complex task and involves a multidisciplinary team that follows the patient beyond the postoperative period. Currently, the mean time on the waiting list for lung transplantation in the state of São Paulo, Brazil, is approximately 18 months. For Brazil as a whole, data from the Brazilian Organ Transplant Association show that, in 2014, there were 67 lung transplants and 204 patients on the waiting list for lung transplantation. Lung transplantation is most often indicated in cases of COPD, cystic fibrosis, interstitial lung disease, non-cystic fibrosis bronchiectasis, and pulmonary hypertension. This comprehensive review aimed to address the major aspects of lung transplantation: indications, contraindications, evaluation of transplant candidates, evaluation of donor candidates, management of transplant recipients, and major complications. To that end, we based our research on the International Society for Heart and Lung Transplantation guidelines and on the protocols used by our Lung Transplant Group in the city of São Paulo, Brazil.

Extracorporeal membrane oxygenation and lung transplantation: initial experience at a single brazilian center

OBJECTIVE: To report initial experience from the use of extracorporeal membrane oxygenation (ECMO) in patients who received lung transplantation. METHODS: Retrospective study of a single tertiary center in the Brazilian state of São Paulo, a national reference in lung transplantation, based on the prospective collection of data from electronic medical records. The period analyzed extended from January 2009 (beginning of the program) until December 2018. RESULTS: A total of 75 lung transplants were performed, with ECMO used in 8 (10.7%) cases. Of the patients, 4 (50%) were female. The mean age was 46.4±14.3 years. The causes of the end-stage lung disease that led to transplantation were pulmonary arterial hypertension in 3 (37.5%) patients, bronchiectasis in 2 (25%) patients, pulmonary fibrosis in 2 (25%) patients, and pulmonary emphysema in 1 (12.5%) patient. In our series, 7 (87.5%) cases were sequential bilateral transplantations. Prioritization was necessary in 4 (50%) patients, and in 1 patient, ECMO was used as a bridge to transplantation. The ECMO route was central in 4 (50%), peripheral venovenous in 2 (25%) and peripheral venoarterial in 2 (25%) patients. The mean length of the intensive care unit (ICU) stay was 14±7.5 days and of the hospital stay was 34.1±34.2 days. The mean ECMO duration was 9.3±6.6 days with a 50% decannulation rate. Three patients were discharged (37.5%). CONCLUSION: Lung transplantation requires complex treatment, and ECMO has allowed extending the indications for transplantation and provided adjuvant support in the clinical management of these patients.

Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation.

Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4). The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients.

Evaluation and reconditioning of donor organs for transplantation through ex vivo lung perfusion / Avaliação e recondicionamento de pulmões doados para transplante por meio da perfusão pulmonar ex vivo

ABSTRACT Objective: To assess the feasibility and impact of ex vivo lung perfusion with hyperoncotic solution (Steen Solution™) in the utilization of these organs in Brazil. Methods: In this prospective study, we subjected five lungs considered to be high risk for transplantation to 4 hours of ex vivo lung perfusion, with evaluation of oxygenation capacity. High-risk donor lungs were defined by specific criteria, including inflammatory infiltrates, pulmonary edema and partial pressure of arterial oxygen less than 300mmHg (inspired oxygen fraction of 100%). Results: During reperfusion, the mean partial pressure of arterial oxygen (inspired oxygen fraction of 100%) of the lungs did not change significantly (p=0.315). In the first hour, the mean partial pressure of arterial oxygen was 302.7mmHg (±127.66mmHg); in the second hour, 214.2mmHg (±94.12mmHg); in the third hour, 214.4mmHg (±99.70mmHg); and in the fourth hour, 217.7mmHg (±73.93mmHg). Plasma levels of lactate and glucose remained stable during perfusion, with no statistical difference between the moments studied (p=0.216). Conclusion: Ex vivo lung perfusion was reproduced in our center and ensured the preservation of lungs during the study period, which was 4 hours. The technique did not provide enough improvement for indicating organs for transplantation; therefore, it did not impact on use of these organs.

RESUMO Objetivo: Avaliar a exequibilidade e o impacto da perfusão pulmonar ex vivo com solução hiperoncótica (Steen Solution™) na taxa de utilização desses órgãos no Brasil. Métodos: Neste estudo prospectivo, submetemos cinco pulmões considerados de alto risco para o transplante a 4 horas de perfusão pulmonar ex vivo, com avaliação da capacidade de oxigenação pulmonar. Os pulmões de doadores de alto risco foram definidos por critérios específicos, incluindo infiltrado inflamatório, edema pulmonar e pressão parcial de oxigênio arterial inferior a 300mmHg (fração inspirada de oxigênio de 100%). Resultados: Durante a reperfusão, a pressão parcial de oxigênio arterial (fração inspirada de oxigênio de 100%) média dos pulmões não sofreu alteração significativa (p=0,315). Na primeira hora, a pressão parcial de oxigênio arterial média foi de 302,7mmHg (±127,66mmHg); na segunda, 214,2mmHg (±94,12mmHg); na terceira, 214,4mmHg (±99,70mmHg); e na quarta, 217,7mmHg (±73,93mmHg). Os níveis plasmáticos de lactato e glicose se mantiveram estáveis ao longo da perfusão, sem diferença estatística na comparação entre os momentos estudados (p=0,216). Conclusão: A perfusão pulmonar ex vivo foi reproduzida em nosso centro e garantiu a preservação de pulmões durante o período de estudo, que foi de 4 horas. A técnica não promoveu melhora suficiente para indicação do órgão para o transplante e, portanto, não impactou na taxa de utilização desses órgãos.