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BACKGROUND: Acute kidney injury (AKI) is a common postoperative complication in bilateral orthotopic lung transplant (BOLTx) recipients, but the contribution of intraoperative variables is not well defined. The authors hypothesized that intraoperative hypotension as well as hypoxia and vasopressor use would be associated with the development of postoperative AKI after BOLTx in patients without pre-existing renal dysfunction. METHODS: The authors performed a retrospective analysis of patients undergoing BOLTx at a single center between 2013 and 2017. Intraoperative variables of hemodynamics included duration of mean arterial pressure <55, <60, and <65 mm Hg; duration of oxygen saturation <90%; and vasoactive-inotropic score (VIS). Associations between the occurrence of AKI and intraoperative hypotension, hypoxemia, and VIS were evaluated while controlling for significant confounding variables. RESULTS: AKI occurred in 177 (72%) of 245 patients in postoperative days 1-7. Notable significant differences in univariate analyses included cumulative mechanical support time, maximum VIS, peripheral oxygen saturation <90% for >15 min, total minutes oxygen saturation <90%, and surgery duration in minutes. There was no significant difference in intraoperative hypotension measured as a duration >15 min for mean arterial pressure <55, <60, or <65 mm Hg. Multivariate logistic regression revealed preoperative creatinine (Odds ratio [OR], 7.77; confidence interval [CI], 1.96-30.83; P = 0.004), surgery duration (OR, 1.004; CI, 1.002-1.007; P = 0.002), and oxygen saturation (OR, 2.06; CI, 1.01-4.24; P = 0.049) <90% for >15 min to be independently associated with AKI. CONCLUSIONS: This study revealed that >15 min of intraoperative hypoxia was independently associated with postoperative AKI after BOLTx.
Assuntos
Injúria Renal Aguda , Transplante de Pulmão , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Humanos , Hipóxia/diagnóstico , Hipóxia/etiologia , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: A wearable artificial lung could improve lung transplantation outcomes by easing implementation of physical rehabilitation during long-term pretransplant respiratory support. The Modular Extracorporeal Lung Assist System (ModELAS) is a compact pumping artificial lung currently under development. This study evaluated the long-term in vivo performance of the ModELAS during venovenous support in awake sheep. Feedback from early trials and computational fluid dynamic analysis guided device design optimization along the way. METHODS: The ModELAS was connected to healthy sheep via a dual-lumen cannula in the jugular vein. Sheep were housed in a fixed-tether pen while wearing the device in a holster during support. Targeted blood flow rate and support duration were 2-2.5 L/min and 28-30 days, respectively. Anticoagulation was maintained via systemic heparin. Device pumping and gas exchange performance and hematologic indicators of sheep physiology were measured throughout support. RESULTS: Computational fluid dynamic-guided design modifications successfully decreased pump thrombogenicity from initial designs. For the optimized design, 4 of 5 trials advancing past early perioperative and cannula-related complications lasted the full month of support. Blood flow rate and CO2 removal in these trials were 2.1 ± 0.3 L/min and 139 ± 15 mL/min, respectively, and were stable during support. One trial ended after 22 days of support due to intradevice thrombosis. Support was well tolerated by the sheep with no signs of hemolysis or device-related organ impairment. CONCLUSIONS: These results demonstrate the ability of the ModELAS to provide safe month-long support without consistent deterioration of pumping or gas exchange capabilities.
Assuntos
Órgãos Artificiais , Circulação Extracorpórea/instrumentação , Transplante de Pulmão , Pulmão/cirurgia , Troca Gasosa Pulmonar , Respiração , Animais , Desenho de Equipamento , Circulação Extracorpórea/efeitos adversos , Pulmão/fisiopatologia , Circulação Pulmonar , Carneiro Doméstico , Fatores de TempoRESUMO
OBJECTIVE: Ex vivo lung perfusion creates a proinflammatory environment leading to deterioration in graft quality that may contribute to post-transplant graft dysfunction. Triptolide has been shown to have a therapeutic potential in various disease states because of its anti-inflammatory properties. On this basis, we investigated the impact of triptolide on graft preservation during ex vivo lung perfusion and associated post-transplant outcomes in a rat transplant model. METHODS: We performed rat normothermic ex vivo lung perfusion with acellular Steen solution containing 100 nM triptolide for 4 hours and compared the data with untreated lungs. Orthotopic single lung transplantation after ex vivo lung perfusion was performed. RESULTS: Physiologic and functional parameters of lung grafts on ex vivo lung perfusion with triptolide were better than those without treatment. Graft glucose consumption was significantly attenuated on ex vivo lung perfusion with triptolide via inhibition of hypoxia signaling resulting in improved mitochondrial function and reduced oxidative stress. Also, intragraft inflammation was markedly lower in triptolide-treated lungs because of inhibition of nuclear factor-κB signaling. Furthermore, post-transplant graft function and inflammatory events were significantly improved in the triptolide group compared with the untreated group. CONCLUSIONS: Treatment of lung grafts with triptolide during ex vivo lung perfusion may serve to enhance graft preservation and improve graft protection resulting in better post-transplant outcomes.
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BACKGROUND: Deep vein thrombosis (DVT) remains a common complication following lung transplantation despite universal routine DVT screening. Moreover, many of the previously reported risk factors are incompletely defined. We sought to explore the influence of DVT screening and to more definitively assess predisposing risk factors. METHODS: A single-institution, retrospective, cohort study of 1141 patients undergoing lung transplantation from January 1, 2005, to December 31, 2014, was performed evaluating for the rate of DVT. Patients were given prophylactic subcutaneous heparin postoperatively. DVT events were noted if they occurred before 90 days after transplant. We compared DVT rates before and after 2008 when universal screening was implemented. We also evaluated the timing of DVT event and location (above the knee vs below the knee). DVTs were treated with standard anticoagulation therapy or an inferior cava filter when patients were unable to tolerate anticoagulation treatment. Univariable and multivariable models were used to identify risk factors for occurrence. A propensity match was performed to match groups across the eras, and a Cox regression was performed to identify differences in 1-year survival trajectory between cohorts. RESULTS: The rates of DVT before and after routine screening were 8.8% (36 DVT out of 412 transplants) and 17.3% (126 out of 729 transplants), respectively. These 2 rates were significantly different (P < .01); moreover, the observed DVT incidence per year was not significantly different across the 6 years after universal DVT screening was implemented (P > .90 for all comparisons). Observed DVT incidence at day 0 and day 14 were 3.8% and 3.8%, respectively, for the cohort before DVT protocols were established. Observed DVT incidence for the cohort after protocols were established at the same time points was 8.7% and 3.7%, respectively. Univariable analysis revealed that significant factors associated with a DVT include hypercholesterolemia (odds ratio [OR], 6.90; 95% confidence interval [CI], 1.82-26.13; P < .01), the number of days in the intensive care unit (OR, 1.03; 95% CI, 1.00-1.01; P < .01), and the length of stay in the hospital (OR, 1.01; 95% CI, 1.01-1.02; P < .01), whereas having quit smoking (vs never smoked) was associated with a decrease in DVT development (OR, 0.50; 95% CI, 0.33-0.75; P < .01). Multivariable analysis revealed 2 significant variables: hypercholesterolemia (OR, 8.13; 95% CI, 1.22-54.37; P = .03) and length of stay (OR, 1.03; 95% CI, 1.01-1.05; P < .01). There was a trend for better 1-year survival in the post-2008 era (Exp[ß], 1.49; P = .09). CONCLUSIONS: The rate of DVT diagnosis significantly increased after universal DVT screening was implemented. Furthermore, those patients undergoing lung transplantation with extended length of stay and hypercholesterolemia were prone to increased rates of DVT. There was a trend toward better 1-year survival in DVT-screened patients, suggesting DVT screening may result in beneficial outcomes.
Assuntos
Transplante de Pulmão/efeitos adversos , Programas de Rastreamento/métodos , Ultrassonografia Doppler Dupla , Trombose Venosa/diagnóstico por imagem , Adulto , Idoso , Anticoagulantes/administração & dosagem , Esquema de Medicação , Feminino , Heparina/administração & dosagem , Humanos , Hipercolesterolemia/epidemiologia , Incidência , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Filtros de Veia Cava , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controleAssuntos
Antivirais/uso terapêutico , Fibrose Cística/cirurgia , Seleção do Doador , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Transplante de Pulmão/métodos , RNA Viral/sangue , Doadores de Tecidos/provisão & distribuição , Adulto , Fibrose Cística/diagnóstico por imagem , Fibrose Cística/fisiopatologia , Usuários de Drogas , Feminino , Hepacivirus/genética , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Recuperação de Função Fisiológica , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Acute cellular rejection (ACR) is a major risk factor for chronic lung allograft dysfunction after lung transplantation. Acute cellular rejection can persist or recur despite augmentation of immunosuppression by conventional methods. There are limited therapeutic options in treating these recurrent and refractory ACRs. We describe our experience with cyclophosphamide therapy for recurrent and refractory ACR in lung transplant recipients. METHODS: Six consecutive patients who were treated with cyclophosphamide for recurrent or refractory ACR were included in the series. The primary outcome measures were improvement in ACR score and forced expiratory volume at 1 second. Secondary outcome measures included adverse drug events including bone marrow suppression, gastrointestinal side effects, and infections. RESULTS: Five of the 6 patients treated demonstrated complete resolution of ACR on follow-up biopsies. Acute cellular rejection score improved after cyclophosphamide treatment (P = 0.03). None of the patients had high grade (≥A3) ACR in the 3 months after cyclophosphamide administration. Cyclophosphamide had no effect on forced expiratory volume at 1 second trend or bronchiolitis obliterans score. All patients tolerated cyclophosphamide with minor gastrointestinal side effects, mild bone marrow suppression, and nonfatal infections that were amenable to treatment. CONCLUSIONS: Cyclophosphamide therapy is an option in treating recurrent and refractory ACR in patients who have failed conventional treatments. Cyclophosphamide is tolerated well without serious adverse drug events (ADE).
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BACKGROUND: The role of the circulating leukocytes in lungs and their relationship with circulating proinflammatory cytokines during ischemia-reperfusion injury is not well understood. Using ex vivo lung perfusion (EVLP) to investigate the pathophysiology of isolated lungs, we aimed to identify a therapeutic target to optimize lung preservation leading to successful lung transplantation. METHODS: Rat heart-lung blocks were placed on EVLP for 4 hours with or without a leukocyte-depleting filter (LF). After EVLP, lung grafts were transplanted, and posttransplant outcomes were compared. RESULTS: Lung function was significantly better in lung grafts on EVLP with a LF than in lungs on EVLP without a LF. The interleukin (IL)-6 levels in the lung grafts and EVLP perfusate were also significantly lower after EVLP with a LF. Interestingly, IL-6 levels in the perfusate did not increase after the lungs were removed from the EVLP circuit, indicating that the cells trapped by the LF were not secreting IL-6. The trapped cells were analyzed with flow cytometry to detect apoptosis and pyroptosis; 26% were pyroptotic (Caspase-1-positive). After transplantation, there was better graft function and less inflammatory response if a LF was used or a caspase-1 inhibitor was administered during EVLP. CONCLUSIONS: Our data demonstrated that circulating leukocytes derived from donor lungs, and not circulating proinflammatory cytokines substantially impaired the quality of lung grafts through caspase-1-induced pyroptotic cell death during EVLP. Removing these cells with a LF and/or inhibiting pyroptosis of the cells can be a new therapeutic approach leading to long-term success after lung transplantation.
Assuntos
Leucócitos/citologia , Transplante de Pulmão/métodos , Pulmão/patologia , Pulmão/fisiologia , Preservação de Órgãos/métodos , Piroptose , Animais , Ponte Cardiopulmonar , Caspase 1/metabolismo , Citocinas/metabolismo , Humanos , Inflamação , Interleucina-6/metabolismo , Leucócitos/metabolismo , Masculino , Microcirculação , Perfusão , Ratos , Ratos Endogâmicos Lew , Testes de Função Respiratória , Resultado do TratamentoRESUMO
OBJECTIVE: To identify preoperative predictors of extracorporeal support in patients with pulmonary hypertension (PH) undergoing bilateral sequential lung transplantation (LTx), and to examine outcomes associated with the use of extracorporeal support. DESIGN: Retrospective, observational study. SETTING: Single organ transplantation and tertiary care university medical center. PARTICIPANTS: Adults with PH (preoperative mean pulmonary artery pressure (mPAP)≥25 mmHg) who underwent primary bilateral sequential LTx during 2007 to 2013. MEASUREMENTS AND MAIN RESULTS: Of 262 patients with PH undergoing LTx, extracorporeal support was initiated intraoperatively in 149 (57%). Preoperative severe right ventricle (RV) dysfunction and moderate or severe tricuspid regurgitation (TR) were associated with extracorporeal support. In the remaining 208 patients without those factors, increasing preoperative oxygen requirement (odds ratio [OR] 1.30 per 1 L/min, 95% confidence intervals [CI] 1.11-1.52, p = 0.001), presence of RV dilation (OR 2.77, 95% CI 1.28-6.02, p = 0.010), and mPAP (OR 1.33 per 5-mmHg increase in mPAP, 95% CI 1.04-1.70, p = 0.021) were associated independently with extracorporeal support in the multivariable model. Analysis of 49 propensity-matched pairs showed longer intensive care unit (5 v 14 days, p = 0.006) and hospital stays (27 v 39 days, p = 0.016) and increased need for tracheostomy (16% v 41%, p = 0.017) in patients exposed to extracorporeal support but no differences in 30-day mortality, stroke, myocardial infarction, or dialysis. CONCLUSIONS: Severity of RV dysfunction, TR, RV dilatation, increasing oxygen requirement, and increasing mPAP showed significant associations with the need for extracorporeal support during LTX in patients with PH. Extracorporeal support was associated with increased length of stay and tracheostomy but not with mortality or other complications. © 2016 Elsevier Inc. All rights reserved.
Assuntos
Hipertensão Pulmonar/cirurgia , Tempo de Internação/tendências , Transplante de Pulmão/tendências , Diálise Renal/tendências , Idoso , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/epidemiologia , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Diálise Renal/métodos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/epidemiologia , Disfunção Ventricular Direita/cirurgiaRESUMO
OBJECTIVES: Atrial arrhythmia (AA) after lung transplantation (LTx) is a potentially morbid event often associated with increased length of hospital stay. Predictors of postsurgical AA, however, are incompletely understood. We characterized the incidence and predisposing risk factors for AA in patients undergoing LTx. METHODS: A retrospective analysis of prospectively collected data was conducted to identify LTx recipients between January 2008 and October 2013. Patients were divided into 2 groups on the basis of postoperative AA development. Univariable and multivariable analyses were performed to define differences between groups and identify factors associated with AA. Survival differences were assessed by the use of competing risks methodology. RESULTS: A total of 198 of 652 (30.4%) patients developed AA at a median onset of 5 days after transplant. Increasing age (hazard ratio [HR] 1.03 per additional year, P < .001) and previous coronary artery bypass grafting (HR 2.77, P = .002) were found to be independent risk factors. Counterintuitively, patients with a medical history of AA before LTx had a lower incidence of postoperative AA. Preoperative beta-blocker usage was not a significant predictor of postoperative AA. Postoperative AA was a significant predictor of long-term mortality (HR 1.63, P = .007) when we adjusted for other risk factors. CONCLUSIONS: AA is a common occurrence after LTx, occurring with greatest frequency in the first postoperative week, and results in a significant reduction in long-term survival. Increasing age and before coronary artery bypass grafting were identified as independent risk factors for AA development. Better understanding of these risk factors may improve identification of patients at heightened risk after transplantation.
Assuntos
Fibrilação Atrial/epidemiologia , Flutter Atrial/epidemiologia , Transplante de Pulmão , Idoso , Feminino , Humanos , Incidência , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pennsylvania/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: Lung transplantation is a life-saving procedure for patients who have end-stage lung disease. The frequency and severity of complications have not been fully characterized. We hypothesized that early in-hospital, postoperative complications decrease long-term survival. METHODS: We retrospectively identified in-hospital complications in lung transplant recipients, from the period January 2007 to October 2013. Complications were graded using the extended Accordion Severity Grading System (ASGS). Complications were categorized by event and organ system. Survival analysis was performed (P < .05) using a time-dependent model. RESULTS: Among 748 eligible patients, 3381 independent in-hospital, postoperative complications occurred in 92.78% of patients. Median follow-up was 5.4 years. Complications associated with significant decrease in 5-year survival were: renal (hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.40-4.48); hepatic (HR 4.08, 95% CI 2.86-5.82); cardiac (HR 1.95, 95% CI 1.56-2.45). The maximum ASGS of ≥5 (18.5% vs 73.8%), and the weighted ASGS sum >10 (2.5% vs 73.8%), were found to be significant predictors of long-term survival. Multivariate analysis identified a weighted ASGS sum of >10, and renal, cardiac, and vascular complications as predictors of decreased long-term survival. CONCLUSIONS: Rigorous delineation of complications after lung transplantation showed that grade 5 ASGS in-hospital postoperative complications, and a weighted ASGS sum >10, were independent predictors of decreased long-term survival well beyond the initial perioperative period. These results may identify important targets for best practice guidelines and quality-of-care measures after lung transplantation.
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Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Comorbidade , Feminino , Humanos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pennsylvania , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Adult lung transplant recipients with small chests have traditionally received lungs from pediatric donors, placing an additional strain on the already restricted pediatric donor pool. Performing lobar lung transplantation (LLT) can circumvent issues with donor-recipient size mismatch; however, LLT imparts additional risks. Here, we review our experience using LLT and standard lung transplantation using a pediatric donor (PDLT) for adults with small chests. METHODS: We retrospectively reviewed consecutive patients with end-stage lung disease and a height of 65 inches or less who underwent LLT (n = 15) or PDLT (n = 15) between 2006 and 2012 at our institution, a high-volume lung transplant center. RESULTS: Lobar lung transplantation recipients were older (54 ± 10 vs 48 ± 8 years) and had higher pulmonary pressure (57 ± 11 vs 52 ± 27 mmHg) and higher lung allocation scores (70 ± 9 vs 51 ± 8) than PDLT recipients (all P < 0.05). Mean waiting time was 62 days for PDLT and 9 days for LLT. Postoperatively, the incidence of severe primary graft dysfunction and the incidence of acute renal insufficiency were higher, and the mean intensive care unit stay was longer in the LLT group, but the incidence of bronchial anastomotic complications was higher in the PDLT group because of significant size discrepancy in the main bronchus (P < 0.05). Interestingly, long-term functional outcomes and survival rates were similar between the groups. CONCLUSIONS: Both LLT and PDLT are viable surgical options for adult patients with small chests. Because of the potential impact on posttransplant outcomes, the technical complexity of transplantation, decisions regarding the best surgical approach should be made by experienced surgeons.