Single- and Double-Lung Transplantation: Results of an Initial Experience of 39 Cases in Ceará (Northeast Brazil).

INTRODUCTION: The lung transplantation (LTx) program began in Ceará in 2011 and the first LTx was performed on June 11, 2011. The aim of this study was to present the initial results of the 6-year experience of our program. METHODS: We retrospectively reviewed our experience on LTx from June 2011 to August 2017. Data on recipients and transoperative and postoperative outcomes were recorded in a database. RESULTS: Twenty-two (56.4%) were single LTx, 15 (38.5%) were double, and 2 (5.1%) bilateral lobar. The mean age was 47.5 ± 15 years, and 26 (66.7%) were men. Twenty-eight (71.8%) had pulmonary fibrosis; 5 (12.8%) had pulmonary emphysema, 3 (7.7%) had bronchiectasis; 2 (5.1%) had pulmonary hypertension, and 1 (2.6%) had lymphangioleiomyomatosis. Complications occurred in 82% (32/39) and in-hospital mortality was 30.8% (single LTx = 27.8% and double LTx = 33.3%). The main complications were infection in 17 (43.5%) cases and primary graft dysfunction in 7 (17.9%). There was a significant improvement in pulmonary function in the first year of follow-up (forced expiratory volume pre-LTx = 37% ± 16% and 12 months post-LTx = 72% ± 22%, P = .001); and overall survival at 36 months was 59.0%, with no difference between single- and double-lung transplants. CONCLUSIONS: Idiopathic pulmonary fibrosis was the most common underlying disease and single LTx was the most commonly performed operation. There was a high incidence of postoperative complications and in-hospital mortality, but the 36-month follow-up showed a marked improvement in lung function and a global survival similar to the literature.

Massive donor transfusion potentially increases recipient mortality after lung transplantation.

OBJECTIVE: Donor blood transfusion has been identified as a potential risk factor for primary graft dysfunction and by extension early mortality. We sought to define the contributing risk of donor transfusion on early mortality for lung transplant. METHODS: Donor and recipient data were abstracted from the Organ Procurement and Transplantation Network database updated through June 30, 2014, which included 86,398 potential donors and 16,255 transplants. Using the United Network for Organ Sharing 4-level designation of transfusion (no blood, 1-5 units, 6-10 units, and >10 units, massive), we analyzed all-cause mortality at 30-days with the use of logistic regression adjusted for confounders (ischemic time, donor age, recipient diagnosis, lung allocation score and recipient age, and recipient body mass index). Secondary analyses assessed 90-day and 1-year mortality and hospital length of stay. RESULTS: Of the 16,255 recipients transplanted, 8835 (54.35%) donors received at least one transfusion. Among those transfused, 1016 (6.25%) received a massive transfusion, defined as >10 units. Those donors with massive transfusion were most commonly young trauma patients. After adjustment for confounding variables, donor massive transfusion was associated significantly with an increased risk in 30-day (P = .03) and 90-day recipient mortality (P = .01) but not 1-year mortality (P = .09). There was no significant difference in recipient length of stay or hospital-free days with respect to donor transfusion. CONCLUSIONS: Massive donor blood transfusion (>10 units) was associated with early recipient mortality after lung transplantation. Conversely, submassive donor transfusion was not associated with increased recipient mortality. The mechanism of increased early mortality in recipients of lungs from massively transfused donors is unclear and needs further study but is consistent with excess mortality seen with primary graft dysfunction in the first 90 days posttransplant.

POST-REPERFUSION LIVER BIOPSY AND ITS VALUE IN PREDICTING MORTALITY AND GRAFT DYSFUNCTION AFTER LIVER TRANSPLANTATION.

Background: The outcome of the patients after liver transplant is complex and to characterize the risk for complications is not always easy. In this context, the hepatic post-reperfusion biopsy is capable of portraying alterations of prognostic importance. Aim: To compare the results of liver transplantation, correlating the different histologic features of the hepatic post-reperfusion biopsy with graft dysfunction, primary non-function and patient survival in the first year after transplantation. Method: From the 377 transplants performed from 1996 to 2008, 164 patients were selected. Medical records were reviewed and the following clinical outcomes were registered: mortality in 1, 3, 6 and 12 months, graft dysfunction in varied degrees and primary graft non-function. The post-reperfusion biopsies had been examined by a blinded pathologist for the outcomes. The following histological variables had been evaluated: ischemic alterations, congestion, steatosis, neutrophilic exudate, monomorphonuclear infiltrate and necrosis. Results: The variables associated with increased mortality were: steatosis (p=0.02209), monomorphonuclear infiltrate (p=0.03935) and necrosis (p<0.00001). The neutrophilic exudate reduced mortality in this study (p=0.00659). The primary non-function showed significant association (p<0.05) with the necrosis, steatosis and the monomorphonuclear infiltrate. Conclusion: Post-reperfusion biopsy is useful tool to foresee complications after liver transplant.

Racional: A evolução dos pacientes após transplante hepático é complexa e caracterizar o risco para complicações nem sempre é fácil. Nesse contexto, a biópsia hepática pós-reperfusão é capaz de retratar alterações de importância prognóstica. Objetivo: Avaliar os resultados no primeiro ano após transplante hepático, correlacionando as alterações histológicas à biópsia hepática pós-reperfusão com a sobrevida, a disfunção e o não-funcionamento primário do enxerto. Método: Dos 377 transplantes ocorridos de 1996 a 2008, 164 pacientes foram selecionados para estudo. Os seguintes desfechos clínicos foram registrados: mortalidade em 1, 3, 6 e 12 meses, disfunção do enxerto em graus variados e o não-funcionamento primário do enxerto. As biópsias pós-reperfusão foram examinadas por um patologista sem conhecimento dos resultados. As seguintes variáveis histológicas foram avaliadas: alterações isquêmicas, congestão, esteatose, exsudato neutrofílico, infiltrado monomorfonuclear e necrose. Resultados: As variáveis associadas com aumento da mortalidade foram: esteatose (p=0.02209), infiltrado monomorfonuclear (p=0.03935) e necrose (p<0.00001). O infiltrado neutrofílico reduziu a mortalidade neste estudo (p=0.00659). O não-funcionamento primário do enxerto mostrou associação significativa (p<0.05) com a necrose, a esteatose e com o infiltrado monomorfonuclear. Conclusão: A biópsia hepática pós-reperfusão é ferramenta útil em prever complicações após o transplante hepático.

Post-reperfusion liver biopsy and its value in predicting mortality and graft dysfunction after liver transplantation / Biópsia hepática pós-reperfusão e sua utilização na predição da mortalidade e da disfunção hepática pós-transplante

ABSTRACT Background: The outcome of the patients after liver transplant is complex and to characterize the risk for complications is not always easy. In this context, the hepatic post-reperfusion biopsy is capable of portraying alterations of prognostic importance. Aim: To compare the results of liver transplantation, correlating the different histologic features of the hepatic post-reperfusion biopsy with graft dysfunction, primary non-function and patient survival in the first year after transplantation. Method: From the 377 transplants performed from 1996 to 2008, 164 patients were selected. Medical records were reviewed and the following clinical outcomes were registered: mortality in 1, 3, 6 and 12 months, graft dysfunction in varied degrees and primary graft non-function. The post-reperfusion biopsies had been examined by a blinded pathologist for the outcomes. The following histological variables had been evaluated: ischemic alterations, congestion, steatosis, neutrophilic exudate, monomorphonuclear infiltrate and necrosis. Results: The variables associated with increased mortality were: steatosis (p=0.02209), monomorphonuclear infiltrate (p=0.03935) and necrosis (p<0.00001). The neutrophilic exudate reduced mortality in this study (p=0.00659). The primary non-function showed significant association (p<0.05) with the necrosis, steatosis and the monomorphonuclear infiltrate. Conclusion: Post-reperfusion biopsy is useful tool to foresee complications after liver transplant.

RESUMO Racional: A evolução dos pacientes após transplante hepático é complexa e caracterizar o risco para complicações nem sempre é fácil. Nesse contexto, a biópsia hepática pós-reperfusão é capaz de retratar alterações de importância prognóstica. Objetivo: Avaliar os resultados no primeiro ano após transplante hepático, correlacionando as alterações histológicas à biópsia hepática pós-reperfusão com a sobrevida, a disfunção e o não-funcionamento primário do enxerto. Método: Dos 377 transplantes ocorridos de 1996 a 2008, 164 pacientes foram selecionados para estudo. Os seguintes desfechos clínicos foram registrados: mortalidade em 1, 3, 6 e 12 meses, disfunção do enxerto em graus variados e o não-funcionamento primário do enxerto. As biópsias pós-reperfusão foram examinadas por um patologista sem conhecimento dos resultados. As seguintes variáveis histológicas foram avaliadas: alterações isquêmicas, congestão, esteatose, exsudato neutrofílico, infiltrado monomorfonuclear e necrose. Resultados: As variáveis associadas com aumento da mortalidade foram: esteatose (p=0.02209), infiltrado monomorfonuclear (p=0.03935) e necrose (p<0.00001). O infiltrado neutrofílico reduziu a mortalidade neste estudo (p=0.00659). O não-funcionamento primário do enxerto mostrou associação significativa (p<0.05) com a necrose, a esteatose e com o infiltrado monomorfonuclear. Conclusão: A biópsia hepática pós-reperfusão é ferramenta útil em prever complicações após o transplante hepático.

Early allograft dysfunction after liver transplantation: an intermediate outcome measure for targeted improvements.

BACKGROUND: The term early allograft dysfunction (EAD) identifies liver transplant (LT) allografts with initial poor function and portends poor allograft and patient survival. Aims of this study are to use EAD as an intermediate outcome measure in a large single center cohort and identify donor, recipient and peri-operative risk factors. MATERIAL AND METHODS: In 1950 consecutive primary LT, donor, recipient and peri-operative data were collected. EAD was defined by the presence of one or more of the following: total bilirubin ≥ 10 mg/dL (171 µmol/L) or, INR ≥ 1.6 on day 7, and ALT/AST > 2,000 IU/L within the first 7 days. RESULTS: The incidence of EAD was 26.5%. 1-, 3-, and 5-year allograft and patient survival for patients who developed EAD were significantly inferior to those who did not (P < 0.01 at all time points). Multivariate analysis demonstrated associations in the development of EAD with recipient pre-operative ventilator status, donation after cardiac death allografts, donor age, allograft size, degree of steatosis, operative time and intra-operative transfusion requirements (all P < 0.01). Patients with EAD had a significantly longer hospitalization at 20.9 ± 38.9 days (median: 9; range: 4-446) compared with 10.7 ± 13.5 days (median: 7; range: 3-231) in patients with no EAD (P < 0.01). CONCLUSIONS: This is the largest single center experience demonstrating incidence of EAD and identifying factors associated with development of EAD. EAD is a useful intermediate outcome measure for allograft and patient survival. Balancing recipient pretransplant conditions, donor risk factors and intra-operative conditions are necessary for avoiding EAD.

Conditioning With Sevoflurane in Liver Transplantation: Results of a Multicenter Randomized Controlled Trial.

BACKGROUND: During times of organ scarcity and extended use of liver grafts, protective strategies in transplantation are gaining importance. We demonstrated in the past that volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury during liver resection. In this randomized study, we examined if volatile anesthetics have an effect on acute graft injury and clinical outcomes after liver transplantation. METHODS: Cadaveric liver transplant recipients were enrolled from January 2009 to September 2012 at 3 University Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol (control group) or sevoflurane anesthesia. Postoperative peak of aspartate transaminase was defined as primary endpoint, secondary endpoints were early allograft dysfunction, in-hospital complications, intensive care unit, and hospital stay. RESULTS: Ninety-eight recipients were randomized to propofol (n = 48) or sevoflurane (n = 50). Median peak aspartate transaminase after transplantation was 925 (interquartile range, 512-3274) in the propofol and 1097 (interquartile range, 540-2633) in the sevoflurane group. In the propofol arm, 11 patients (23%) experienced early allograft dysfunction, 7 (14%) in the sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4 mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall and major complication rates were not different. An effect on clinical outcomes was observed favoring the sevoflurane group (less severe complications), but without significance. CONCLUSIONS: This first multicenter trial comparing propofol with sevoflurane anesthesia in liver transplantation shows no difference in biochemical markers of acute organ injury and clinical outcomes between the 2 regimens. Sevoflurane has no significant added beneficial effect on ischemia-reperfusion injury compared to propofol.

Liver retransplantation in adults: a 20-year experience of one center in southern Brazil.

INTRODUCTION: Liver retransplantation (LReTx) is the therapeutic option for hepatic graft failure. Survival after LReTx is poorer than after primary liver transplantation. Given the organ shortage, it is essential to optimize the use of this resource. OBJECTIVE: To evaluate rates, indications and patient survival after LReTx and identify factors associated with mortality following LReTx. MATERIAL AND METHODS: We conducted a retrospective cohort study of all adults undergoing LReTx based on registry data from the Liver Transplantation Group (Complexo Hospitalar Santa Casa de Porto Alegre), southern Brazil. RESULTS: Between June 16, 1991 and July 19, 2011, 824 patients underwent 866 liver transplants. Forty-two procedures corresponded to LReTx (4.8% of all liver transplants performed). Thirty-eight patients who underwent a single LReTx procedure were included in this study. The leading indication for LReTx was hepatic artery thrombosis (HAT) (31.6%), followed by primary nonfunction (PNF) (18.4%). The main indication for early LReTx was PNF (58.3%) and for late LReTx was HAT (38.5%). During the follow-up period, 26 patients (68.4%) died after LReTx. Patient survival at 1 and 3 years after LReTx was 44.7% and 44.7%, respectively. Patients infected with hepatitis C virus, serum albumin < 2.5 g/dL and receiving mechanical ventilation immediately before LReTx had a significantly lower survival rate than the other patients. CONCLUSION: Considering the increased mortality when the graft loss is delayed, it is necessary to define the minimum acceptable results to indicate LReTx and identify the patients who would most benefit from this treatment.

Early allograft dysfunction and liver transplant outcomes: a single center retrospective study.

BACKGROUND: Early allograft dysfunction (EAD) had been related to poor transplant outcomes during the early years of liver transplantation. We sought to determine the incidence of EAD at our unit and to evaluate its impact on posttransplant outcomes. METHODS: This single-center retrospective study included primary deceased donor liver grafts transplanted under the model for end-stage liver disease system. EAD was defined as a peak values of aminotransferase >2000 IU/mL during the first week or an international normalized ratio of ≥1.6 and/or bilirubin ≥10 mg/dL at day 7. The main endpoints were patient and graft survivals. RESULTS: Patients with versus without EAD showed similar recipient characteristics. Donors who experienced EAD who comprises 56% of recipients were heavier with larger body mass indices. EAD was an independent risk factor for allograft loss. Most retransplants were performed early due to nonfunction. The primary nonfunction rate among subjects with versus without EAD were 7% and 12% respectively (P < .05). Patient survival among those with EAD was 87.4%, while without EAD it was 90% (P = NS) with graft survivals of 81.4% and 88.7% respectively (P < .05). CONCLUSION: Patients with EAD show a significantly higher risk for allograft loss, but with a comparable survival after transplantation. Despite their worse outcomes, it seems that not all of these recipients behave equally.

Risk factors and survival impact of primary graft dysfunction after lung transplantation in a single institution.

BACKGROUND: Lung transplantation has become a standard procedure for some end-stage lung diseases, but primary graft dysfunction (PGD) is an inherent problem that impacts early and late outcomes. The aim of this study was to define the incidence, risk factors, and impact of mechanical ventilation time on mortality rates among a retrospective cohort of lung transplantations performed in a single institution. METHODS: We performed a retrospective study of 118 lung transplantations performed between January 2003 and July 2010. The most severe form of PGD (grade III) as defined at 48 and 72 hours was examined for risk factors by multivariable logistic regression models using donor, recipient, and transplant variables. RESULTS: The overall incidence of PGD at 48 hours was 19.8%, and 15.4% at 72 hours. According multivariate analysis, risk factors associated with PGD were donor smoking history for 48 hours (adjusted odds ratio [OR], 4.83; 95% confidence interval [CI], 1.236-18.896; P = .022) and older donors for 72 hours (adjusted OR, 1.046; 95% CI, 0.997-1.098; P = .022). The operative mortality was 52.9% among patients with PGD versus 20.3% at 48 hours (P = .012). At 72 hours, the mortality rate was 58.3% versus 21.2% (P = .013). The 90-days mortality was also higher among patients with PGD. The mechanical ventilation time was longer in patients with PGD III at 48 hours namely, a mean time of 72 versus 24 hours (P = .001). When PGD was defined at 72 hours, the mean ventilation time was even longer, namely 151 versus 24 hours (P < .001). The mean overall survival for patients who developed PGD at 48 hours was 490.9 versus 1665.5 days for subjects without PGD (P = .001). Considering PGD only at 72 hours, the mean survival was 177.7 days for the PGD group and 1628.9 days for the other patients (P < .001). CONCLUSION: PGD showed an important impacts on operative and 90-day mortality rates, mechanical ventilation time, and overall survival among lung transplant patients. PGD at 72 hours was a better predictor of lung transplant outcomes than at 48 hours. The use of donors with a smoking history or of advanced age were risk factors for the development of PGD.