Use of Octopus™ Tissue Stabilizer for Minimal Manipulation Approach of Bronchial Anastomosis in Lung Transplant

ABSTRACT Bronchial anastomotic complications are a cause of grave concern for surgeons that perform lung transplantations. There are several risk factors that may lead to this complication, being inadequate surgical technique one of them, specifically regarding adequate exposure and manipulation of the bronchial stump and anastomosis. Here we report the use of Octopus™ Tissue Stabilizer as a mean to allow for a better exposure of the stump and facilitate a "no-touch" approach towards anastomosis. Systematic application of devices that facilitate the employment of the correct surgical techniques can have an effect in reducing the incidence of bronchial anastomotic complications.

Brazilian initial experience with lung transplantation due to irreversible lung fibrosis post-COVID-19 in a national reference center: a cohort study

ABSTRACT BACKGROUND: Lung transplantation (LTx) has been discussed as an option for treating irreversible lung fibrosis post-coronavirus disease 2019 (COVID-19), in selected cases. OBJECTIVES: To report on the initial experience and management of end-stage lung disease due to COVID-19 at a national center reference in Brazil. DESIGN AND SETTING: Cohort study conducted at a national reference center for lung transplantation. METHODS: Medical charts were reviewed regarding patients' demographics and pre-COVID-19 characteristics, post-LTx due to COVID-19. RESULTS: Between March 2020 and September 2021, there were 33 cases of LTx. During this period, we evaluated 11 cases of severe COVID-19-related acute respiratory distress syndrome (ARDS) that were potentially candidates for LTx. Among these, LTx was only indicated for three patients (9.1%). All of these patients were on venovenous extracorporeal membrane oxygenation (ECMO), and the procedure that they underwent was central venoarterial ECMO. All three patients were still alive after the first 30 postoperative days. However, patient #1 and patient #2 subsequently died due to fungal sepsis on the 47th and 52nd postoperative days, respectively. Patient #3 was discharged on the 30th postoperative day. CONCLUSIONS: LTx is feasible among these complex patients. Survival over the first 30 days was 100%, and this favors surgical feasibility. Nonetheless, these were critically ill patients.

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 / 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.

Ex vivo lung perfusion in Brazil / A experiência brasileira na perfusão pulmonar ex vivo

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.

Objetivo: Avaliar o emprego da técnica de perfusão pulmonar ex vivo (PPEV) clinicamente com a finalidade de transplante. Métodos: Estudo prospectivo envolvendo o recondicionamento de pulmões limítrofes, definidos por critérios específicos, tais como relação PaO2/FiO2 < 300 mmHg, com um sistema de PPEV. Entre fevereiro de 2013 e fevereiro de 2014, os pulmões de cinco doadores foram submetidos à PPEV por até 4 h. Durante a PPEV, a mecânica pulmonar foi avaliada continuamente. Amostras do perfusato foram colhidas a cada hora, assim como foi realizada a avaliação funcional dos órgãos. Resultados: A média de PaO2 dos pulmões captados foi de 262,9 ± 119,7 mmHg, sendo que, ao final da terceira hora de perfusão, essa foi de 357,0 ±108,5 mmHg. A capacidade de oxigenação dos pulmões apresentou discreta melhora durante a PPEV nas primeiras 3 h (246,1 ± 35,1; 257,9 ± 48,9; e 288,8 ± 120,5 mmHg, respectivamente), sem diferenças significativas entre os momentos (p = 0,508). As médias de complacência estática foram de, respectivamente, 63.0 ± 18,7; 75,6 ± 25,4; e 70,4 ± 28,0 mmHg após 1, 2 e 3 h, com melhora significativa entre a hora 1 e 2 (p = 0,029), mas não entre a hora 2 e 3 (p = 0,059). A resistência vascular pulmonar permaneceu estável durante a PPEV, sem diferenças entre os momentos (p = 0,284). Conclusões: Os pulmões avaliados permaneceram em condições fisiológicas de preservação; no entanto, o protocolo não foi efetivo para promover a melhora na função pulmonar, inviabilizando o transplante.

Lung transplantation: overall approach regarding its major aspects / Transplante pulmonar: abordagem geral sobre seus principais aspectos

ABSTRACT 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.

RESUMO O transplante pulmonar é uma terapia bem estabelecida para pacientes com doença pulmonar avançada.A avaliação do candidato para o transplante é uma tarefa complexa e envolve uma equipe multidisciplinar que acompanha o paciente para além do período pós-operatório.O tempo médio atual em lista de espera para transplante pulmonar é de aproximadamente 18 meses no estado de São Paulo. Em 2014, dados da Associação Brasileira de Transplante de Órgãos mostram que 67 transplantes pulmonares foram realizados no Brasil e que 204 pacientes estavam na lista de espera para transplante pulmonar.O transplante pulmonar é principalmente indicado no tratamento de DPOC, fibrose cística, doença intersticial pulmonar, bronquiectasia não fibrocística e hipertensão pulmonar.Esta revisão abrangente teve como objetivos abordar os aspectos principais relacionados ao transplante pulmonar: indicações, contraindicações, avaliação do candidato ao transplante, avaliação do candidato doador, gestão do paciente transplantado e complicações maiores. Para atingirmos tais objetivos, utilizamos como base as diretrizes da Sociedade Internacional de Transplante de Coração e Pulmão e nos protocolos de nosso Grupo de Transplante Pulmonar localizado na cidade de São Paulo.

Lung transplantation / Transplante pulmonar

ABSTRACT 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.

RESUMO O transplante pulmonar é um tratamento mundialmente aceito para alguma pneumopatias avançadas, conferindo aos receptores maior sobrevida e melhor qualidade de vida. Desde o primeiro transplante realizado com sucesso em 1983, mais de 40 mil transplantes foram feitos em todo mundo. Destes, cerca de 700 foram no Brasil. No entanto, a sobrevida do transplante é menor do que a desejada, com altos índices de mortalidade relacionados à disfunção primária do enxerto, infecções e disfunção crônica do enxerto, principalmente sob a forma da síndrome da bronquiolite obliterante. Novas tecnologias têm sido desenvolvidas para aprimoramento das diversas etapas do transplante pulmonar. Para aumentar a oferta de pulmões, o recondicionamento pulmonar ex vivo vem sendo utilizado em alguns países, inclusive no Brasil. Para suporte avançado de vida no período perioperatório, equipamentos de oxigenação extracorpórea e de suporte hemodinâmico vêm sendo utilizado como ponte para o transplante em pacientes gravemente doentes em lista de espera e para manter pacientes vivos até a resolução da disfunção primária do enxerto pós-transplante. Existe uma demanda reprimida de pacientes que necessitam de transplante pulmonar no Brasil e que nem sequer chegam a ser encaminhados a um centro transplantador, pois só existem sete deles ativos no país. É urgente a criação de novos centros capazes de realizar transplante pulmonar para oferecer a pacientes com algumas pneumopatias avançadas uma chance de viver mais e com melhor qualidade de vida.

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. .

Recondicionamento pulmonar ex vivo: uma nova era para o transplante pulmonar / Ex vivo lung reconditioning: a new era for lung transplantation

O transplante pulmonar consolidou-se como a melhor opção terapêutica para diversas pneumopatias terminais. O baixo número de doadores viáveis ainda persiste como uma grande limitação ao aumento do número de transplantes de pulmão, causando alta mortalidade na lista de espera. Diferentemente do transplante de outros órgãos sólidos, a maior limitação do transplante pulmonar não é o número absoluto de doadores e sim a viabilidade desses órgãos, que é reduzida devido às agressões ao pulmão ocasionadas pela morte encefálica e aos cuidados na UTI. Diversas são as propostas para o aumento do número de doadores: intensificação das campanhas de doação, o uso de doadores com coração parado, transplante pulmonar lobar intervivos e maior flexibilidade dos critérios para aceitação de doadores de pulmão. Todavia, a proposta que atrai a atenção de diversos grupos de transplante pulmonar é a perfusão pulmonar ex vivo, principalmente pela perspectiva de recuperação de pulmões inicialmente descartados. Esse sistema consiste na reperfusão e ventilação do bloco pulmonar isolado em um circuito de circulação extracorpórea modificado. Devido aos bons resultados apresentados e à perspectiva de aumento no número de órgãos aptos a transplante, diversos grupos têm estudado a técnica. Pesquisadores na Suécia, Canadá, Áustria, Inglaterra, Espanha e Brasil já possuem experiência sólida com o método e introduziram algumas variações. O objetivo deste artigo foi revisar o desenvolvimento, o estado da arte e as perspectivas futuras do modelo ex vivo de perfusão e recondicionamento pulmonar.

Lung transplantation has come to be viewed as the best treatment option for various end-stage lung diseases. The low number of viable donors continues to be a major obstacle to increasing the number of lung transplants, resulting in high mortality among patients on the waiting list. Unlike transplantation of other solid organs, lung transplantation is primarily limited not by the absolute number of donors but by the viability of the donor lungs, which can be damaged by brain death and by treatments given in the ICU. There are various proposals of ways to increase the number of lung donors: intensification of donation campaigns, use of non-heart-beating donors, living lobar lung transplantation, and adoption of more flexible criteria for donors. However, the proposal that has attracted the most attention from lung transplantation researchers is ex vivo lung perfusion, especially due to the prospect of reconditioning previously discarded lungs. This system consists of perfusion and ventilation of the isolated heart-lung block using a modified cardiopulmonary bypass circuit. Various authors have been studying this technique due to the satisfactory results obtained and the prospect of an increase in the number of organs suitable for transplantation. Researchers in Sweden, Canada, Austria, England, Spain, and Brazil have extensive experience with the method and have introduced modifications to it. The objective of this article was to review the development of, state of the art in, and future prospects for the ex vivo model of lung perfusion and reconditioning.