Severe and Moderate Primary Graft Dysfunction in Adult Heart Recipients.

INTRODUCTION: The aims of this study were to determine the incidence of severe and moderate primary graft dysfunction (PGD) in our center, to identify, retrospectively, donors' and recipients' risk factors for PGD development, and to evaluate the impact of PGD within 30 days after heart transplantation. METHODS: Donors' and recipients' medical records of 64 consecutive adult cardiac transplantations performed between January 2016 and June 2017 were reviewed. The International Society for Heart and Lung Transplantation (ISHLT) criteria were used to diagnose moderate and severe PGD. Associations of risk factors for combined moderate/severe PGD were assessed with appropriate statistical analyses. RESULTS: Sixty-four patients underwent heart transplantation in this period. Twelve recipients (18.7%) developed severe or moderate PGD. Development of PGD was associated with previous donor cardiopulmonary resuscitation and a history of prior heart surgery in the recipient (P=0.01 and P=0.02, respectively). The 30-day in hospital mortality was similar in both PGD and non-PGD patients. CONCLUSION: The use of the ISHLT criteria for PGD is important to identify potential risk factor. The development of PGD did not affect short-term survival in our study. More studies should be done to better understand the pathophysiology of PGD.

Severe and Moderate Primary Graft Dysfunction in Adult Heart Recipients

ABSTRACT Introduction: The aims of this study were to determine the incidence of severe and moderate primary graft dysfunction (PGD) in our center, to identify, retrospectively, donors' and recipients' risk factors for PGD development, and to evaluate the impact of PGD within 30 days after heart transplantation. Methods: Donors' and recipients' medical records of 64 consecutive adult cardiac transplantations performed between January 2016 and June 2017 were reviewed. The International Society for Heart and Lung Transplantation (ISHLT) criteria were used to diagnose moderate and severe PGD. Associations of risk factors for combined moderate/severe PGD were assessed with appropriate statistical analyses. Results: Sixty-four patients underwent heart transplantation in this period. Twelve recipients (18.7%) developed severe or moderate PGD. Development of PGD was associated with previous donor cardiopulmonary resuscitation and a history of prior heart surgery in the recipient (P=0.01 and P=0.02, respectively). The 30-day in hospital mortality was similar in both PGD and non-PGD patients. Conclusion: The use of the ISHLT criteria for PGD is important to identify potential risk factor. The development of PGD did not affect short-term survival in our study. More studies should be done to better understand the pathophysiology of PGD.

Dengue infection in kidney transplant recipients: clinical course and its impact on renal function / Infecção por dengue em receptores de transplante renal: curso clínico e seu impacto na função renal

Abstract Introduction: Kidney transplant recipients (KTR) are at increased risk for dengue virus (DENV) infection. The aim of this study was to outline the clinical presentation and laboratory profile of DENV infection in KTR and its impact on renal function. Methods: This was a retrospective study of KTR diagnosed with DENV infection. Adult patients who visited Santa Casa de Belo Horizonte Nephrology Center between April and September 2019 were included. Patients who did not sign the Informed Consent were excluded. Data were collected from the database and medical records. The study was approved by the local Institutional Ethics Committee and the Informed Consent was obtained. Results: Nineteen KTR were evaluated. The main signs and symptoms were myalgia, headache/retro-orbital pain, fever, and gastrointestinal symptoms. Two patients had acute cholecystitis without calculus, three experienced pleural and/or pericardial effusion, and one developed acute myocarditis. All patients were under immunosuppression with prednisone, tacrolimus, and mycophenolate, and most were not receiving induction therapy. Temporary suspension/reduction of immunosuppression was required in 58% of patients and leukopenia was the most common reason. Thrombocytopenia was common and 58% of patients developed acute kidney injury. All patients recovered renal function. Conclusions: DENV infection in KTR patients seems to follow a similar course as in the general population. Although there was no control group, we suspect that immunosuppression, preexisting kidney disease or type of donor was not a determining factor in most patients. Transient renal dysfunction was common but reversible. No patient experienced death or graft loss.

Resumo Introdução: Receptores de transplante renal (RTR) apresentam maior risco de infecção pelo vírus da dengue (DENV). O objetivo deste estudo foi delinear apresentação clínica e perfil laboratorial da infecção por DENV em RTR e seu impacto na função renal. Métodos: Este foi um estudo retrospectivo de RTR diagnosticados com infecção por DENV. Incluiu-se pacientes adultos que estiveram no Centro Nefrológico da Santa Casa de Belo Horizonte entre Abril/Setembro, 2019. Foram excluídos pacientes que não assinaram o Termo de Consentimento Livre e Esclarecido. Dados foram coletados do banco de dados e registros médicos. O estudo foi aprovado pelo Comitê de Ética Institucional local e obteve-se o Consentimento Livre e Esclarecido. Resultados: Avaliou-se dezenove RTR. Principais sinais e sintomas foram mialgia, cefaleia/dor retro-orbital, febre, sintomas gastrointestinais. Dois pacientes apresentaram colecistite aguda sem cálculo, três sofreram derrame pleural e/ou pericárdico, um desenvolveu miocardite aguda. Todos os pacientes estavam sob imunossupressão com prednisona, tacrolimus, micofenolato. A maioria não estava recebendo terapia de indução. Suspensão/redução temporária da imunossupressão foi necessária em 58% dos pacientes e leucopenia foi a razão mais comum. Trombocitopenia foi comum e 58% dos pacientes desenvolveram lesão renal aguda. Todos recuperaram a função renal. Conclusões: A infecção por DENV em pacientes RTR parece seguir um curso semelhante ao da população em geral. Embora não houvesse grupo controle, suspeitamos que imunossupressão, doença renal preexistente ou tipo de doador não foram fator determinante na maioria dos pacientes. Disfunção renal transitória foi comum, mas reversível. Nenhum paciente veio ao óbito ou sofreu perda do enxerto.

Experiencia en trasplante pulmonar pediátrico en Chile / Experience with pediatric lung transplantation in Chile

El trasplante de pulmón (TP) es una opción para pacientes pediátricos con enfermedades pulmonares terminales. OBJETIVO: Evaluar resultados y sobrevida de pacientes pediátricos trasplantados de pulmón. MÉTODOS: Análisis retrospectivo de registros clínicos de pacientes TP ≤ 15 años de Clínica Las Condes. Se analizaron datos demográficos, tipo de trasplante, función pulmonar basal y post trasplante, complicaciones precoces y tardías y sobrevida. RESULTADOS: Nueve pacientes < 15 años de edad se han trasplantado. La edad promedio fue 12,7 años. La principal indicación fue fibrosis quística (7 pacientes). El IMC promedio fue de 17,6 y todos estaban con oxígeno domiciliario. El 77% utilizó soporte extracorpóreo intraoperatorio. Las principales complicaciones precoces fueron hemorragia y la disfunción primaria de injerto mientras que las tardías fueron principalmente las infecciones y la disfunción crónica de injerto. Cuatro pacientes han fallecido y la sobrevida a dos años fue de 85%. El trasplante les permitió una reinserción escolar y 3 lograron completar estudios universitarios. CONCLUSIÓN: El trasplante pulmonar es una alternativa para niños con enfermedades pulmonares avanzadas mejorando su sobrevida y calidad de vida.

Lung transplantation (TP) is a treatment option in children with terminal lung diseases. OBJECTIVE: To evaluate the results and survival of pediatrics lung transplant patients. METHODS: Retrospective analysis of clinical records of lung transplantation of patients ≤ 15 years from Clínica Las Condes, Santiago, Chile. Demographic data, type of transplant, baseline and post transplant lung function, early and late complications and survival rate were analyzed. RESULTS: Nine patients ≤ 15 years-old were transplanted. The average age at transplant was 12.7 years. The main indication was cystic fibrosis (7 patients). The average BMI was 17.6 and all the patients were with home oxygen therapy. 77% used extracorporeal intraoperative support. Average baseline FEV1 was 25.2% with progressive improvement in FEV1 of 77% in the first year. The main early complications were hemorrhage and primary graft dysfunction, while late complications were infections and chronic graft dysfunction. Four patients have died and the estimated 2 years survival was 85%. They achieved school reinsertion and three managed to complete university studies. CONCLUSION: Lung transplantation is an alternative for children with advanced lung diseases improving their survival and quality of life.

Evaluation of the blood-oxygen-level-dependent (BOLD) sequence with 3 Tesla device in renal transplant patients in the assessment of early allograft disfunction, correlated with biopsy / Avaliação da sequência dependente do nível de oxigênio no sangue (BOLD) com dispositivo 3 Tesla em pacientes transplantados renais na avaliação da disfunção de enxerto precoce, correlacionada com biópsia

ABSTRACT Objective To evaluate the ability of blood-oxygen-level-dependent (BOLD) magnetic resonance imaging at 3 Tesla to measure tissue oxygen bioavailability based on R2* values, and to differentiate between acute tubular necrosis and acute rejection compared to renal biopsy (gold standard). Methods A prospective, single-center study, with patients submitted to renal transplantation between 2013 and 2014, who developed graft dysfunction less than 4 weeks after transplantation. All patients were submitted to abdominal magnetic resonance imaging at 3 Tesla using the same protocol, followed by two BOLD sequences and kidney biopsy. Results Twelve male (68.75%) and three female (31.25%) patients were included. A total of 19 percutaneous renal biopsies were performed (four patients required a second biopsy due to changes in clinical findings). Pathological findings revealed ten cases of acute tubular necrosis, four cases of acute rejection, and five cases with other (miscellaneous) diagnoses. Comparison between the four groups of interest failed to reveal significant differences (p=0.177) in cortical R2* values, whereas medullary R2* values differed significantly (p=0.033), with lower values in the miscellaneous diagnoses and the acute tubular necrosis group. Conclusion BOLD magnetic resonance imaging at 3 Tesla is a feasible technique that uses indirect tissue oxygen level measurements to differentiate between acute rejection and acute tubular necrosis in renal grafts.

RESUMO Objetivo Avaliar a sequência de ressonância magnética blood-oxygen-level-dependent (BOLD) realizada em um equipamento 3 Tesla para medir a biodisponibilidade do oxigênio do tecido pelo valor de R2* na diferenciação de necrose tubular aguda e rejeição aguda, comparando à biópsia renal (padrão-ouro). Métodos Estudo unicêntrico, prospectivo, com pacientes submetidos a transplante renal de 2013 a 2014, que desenvolveram disfunção do enxerto menos de 4 semanas após o transplante. Todos os pacientes foram submetidos à ressonância magnética abdominal 3 Tesla com o mesmo protocolo, seguida de duas sequências BOLD e biópsia renal. Resultados Foram incluídos 12 homens (68,75%) e três mulheres (31,25%). Foram realizadas 19 biópsias renais percutâneas (quatro pacientes necessitaram de segunda biópsia devido à alteração nos achados clínicos). Os resultados histopatológicos incluíram dez casos de necrose tubular aguda, quatro de rejeição aguda e cinco casos de outros diagnósticos (miscelânea). A comparação entre os quatro grupos de interesse não mostrou diferenças significativas em relação ao R2* no córtex (p=0,177). Quanto ao R2* da medula, observaram-se diferenças significativas (p=0,033), com miscelânea e necrose tubular aguda apresentando valores mais baixos quando comparados aos demais. Conclusão A ressonância magnética BOLD 3 Tesla é uma técnica viável que indiretamente utiliza a concentração de oxigênio no tecido em enxertos renais e pode ser usada para a diferenciação entre rejeição aguda e necrose tubular aguda.

Donor hypernatremia and smoking addiction contribute to primary graft failure in heart transplantation.

INTRODUCTION: Primary graft failure (PGF) is an important contributor to early mortality, accounting for 41% of deaths within the first 30 days after heart transplantation (HT). Donor hypernatremia has been associated with PGF development. However, controversial data exist regarding the impact of sodium deregulation in patient survival after HT. This study aimed to assess the influence of donor hypernatremia on PGF development and to determine the serum sodium level threshold to assist in decision-making for organ procurement. METHODS: The medical record from 200 HT patients and organ donors were retrospectively assessed and categorized by PGF occurrence. Donor sodium levels were compared and cut-off points obtained by receiver operating characteristic (ROC) curve. A multiple logistic regression model was applied to assess the effects of factors and covariates that influence PGF development. RESULTS: Sodium levels of donors were significantly higher in recipients who developed PGF than those who did not develop PGF (162 vs. 153 mmol/L, P = .001). The sodium cut-off value determined by the ROC curve was 159 mmol/L. The group who received organs from donors with a serum sodium concentration ≥159 mmol/L had a higher incidence of PGF (63.3% vs 32.4%, P < .001). Furthermore, donor sodium levels ≥159 mmol/L increased the likelihood of recipients developing PGF by 3.4 times. It is also observed that the incidence of donor smoking addiction was significantly higher in the PGF group (28.6% vs. 11.5%, P = .004) and donor smoking addiction increased the risk of developing PGF by 2.8 times. CONCLUSION: Smoking addiction and the application of suboptimal organs from donors with hypernatremia contribute to primary graft failure in heart transplantation.

A liberação de citocinas induzida pela morte cerebral não está associada à disfunção primária do enxerto: um estudo de coorte / Brain death-induced cytokine release is not associated with primary graft dysfunction: a cohort study

RESUMO Objetivo: Examinar a associação entre os níveis de citocinas no plasma do doador e o desenvolvimento de disfunção primária do enxerto de órgãos transplantados a partir de doadores falecidos. Métodos: Foram incluídos no estudo de forma prospectiva 17 doadores falecidos e os respectivos 47 pacientes receptores de transplante. Os receptores foram divididos em dois grupos: grupo 1, de pacientes que desenvolveram disfunção primária do enxerto, e grupo 2, de pacientes que não desenvolveram disfunção primária do enxerto. Os níveis de TNF, IL-6, IL-1β, e IFN-γ, avaliados por meio de ELISA, foram comparados entre os grupos. Resultados: Obtiveram-se 69 órgãos, sendo realizados 48 transplantes. Os níveis plasmáticos de citocinas nos doadores não diferiram entre os grupos (em pg/mL): TNF no grupo 1, com 10,8 (4,3 - 30,8) versus no grupo 2, com 8,7 (4,1 - 33,1), com valor de p = 0,63; IL-6 no grupo 1: 1.617,8 (106,7 - 5.361,7) versus no grupo 2: 922,9 (161,7 - 5.361,7), com p = 0,56; IL-1β, no grupo 1: 0,1 (0,1 - 126,1) versus no grupo 2: 0,1 (0,1 - 243,6), com p = 0,60; e IFN-γ, no grupo 1: 0,03 (0,02 - 0,2) versus no grupo 2: 0,03 (0,02 - 0,1), p = 0,93). Obtivemos resultados similares ao examinar separadamente os casos de transplante renal. Conclusão: Nesta amostra de receptores de transplante, os níveis plasmáticos das citocinas TNF, IL-6, IL-1β e IFN-γ nos doadores não se associaram com o desenvolvimento de disfunção primária do enxerto.

ABSTRACT Objective: To examine the association between donor plasma cytokine levels and the development of primary graft dysfunction of organs transplanted from deceased donors. Methods: Seventeen deceased donors and the respective 47 transplant recipients were prospectively included in the study. Recipients were divided into two groups: group 1, patients who developed primary graft dysfunction; and group 2, patients who did not develop primary graft dysfunction. Donor plasma levels of TNF, IL-6, IL-1β, and IFN-γ assessed by ELISA were compared between groups. Results: Sixty-nine organs were retrieved, and 48 transplants were performed. Donor plasma cytokine levels did not differ between groups (in pg/mL): TNF, group 1: 10.8 (4.3 - 30.8) versus group 2: 8.7 (4.1 - 33.1), p = 0.63; IL-6, group 1: 1617.8 (106.7 - 5361.7) versus group 2: 922.9 (161.7 - 5361.7), p = 0.56; IL-1β, group 1: 0.1 (0.1 - 126.1) versus group 2: 0.1 (0.1 - 243.6), p = 0.60; and IFN-γ, group 1: 0.03 (0.02 - 0.2) versus group 2: 0.03 (0.02 - 0.1), p = 0.93). Similar findings were obtained when kidney transplants were analyzed separately. Conclusion: In this sample of transplant recipients, deceased donor plasma cytokines TNF, IL-6, IL-1β, and IFN-γ were not associated with the development of primary graft dysfunction.

Disfunção e não função primária do enxerto hepático: revisão integrativa / Primary liver graft dysfunction and non-function: integrative literature review

RESUMO Evitar mortes na fila de espera por um órgão não é mais o único foco de atenção das equipes de transplantação. As pesquisas e cuidados na prática clínica têm sido cada vez mais voltados para o funcionamento do enxerto pós-implante. O objetivo desse estudo foi identificar a nomenclatura utilizada na literatura para disfunção e não função de um enxerto hepático, bem como, investigar as incidências e fatores de risco. Trata-se de uma revisão integrativa da literatura de publicações na íntegra em português, inglês e espanhol, entre 2012 e 2016, nas bases: CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE e Web of Science. Foram selecionados 14 estudos em que se identificou incidências variando entre 7% e 27% e a nomenclatura utilizada para descrever o evento foi mau funcionamento inicial, hipofunção do enxerto, função marginal ou retardo na função. Foram encontradas incidências de não função primária do enxerto hepático entre 1,4% e 8,4% dos pacientes e a nomenclatura usada para descrever o evento foi disfunção precoce ou perda do enxerto. Os fatores de risco encontrados são relacionados às variáveis do doador, receptor, enxerto e logística do transplante. Conclui-se que o conhecimento das diferentes nomenclaturas empregadas na literatura, das incidências da disfunção e não função primária e seus fatores de risco são fundamentais para qualificar as intervenções de controle dos eventos na perspectiva de melhorar a sobrevida do paciente pós-transplante hepático.

ABSTRACT Avoiding deaths in the waiting list for an organ is no longer the only focus of the transplant teams attention. Research and care in clinical practice has been increasingly focused on post transplant graft survival and functioning. In the present work, we performed an integrative literature review to identify the terminology used about liver graft dysfunction and non-function, as well as to investigate the incidence and risk factors of these clinical events. We chosen articles written in Portuguese, English and Spanish between 2012 and 2016, based on CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE and Web of Science. We selected 14 studies, in which we identified the incidence of hepatic graft dysfunction ranging from 7% to 27%. The terminology used to describe this clinical event was initial malfunction, graft hypofunction, marginal function or delay in function. The primary non-function of the liver graft was found in 1.4% to 8.4% of the patients, and the terminology used to describe the event was early dysfunction or graft loss. The risk factors found are related to donor, recipient, graft and transplant logistics variables. We conclude that knowledge of the different terminologies employed in the literature, related to dysfunction and primary non- function incidence, and of their risk factors are fundamental to qualify the control of the events, aiming to improve patients' survival after liver transplantation.

Primary graft dysfunction of the liver: definitions, diagnostic criteria and risk factors / Disfunção primária do enxerto hepático: definições, critérios diagnósticos e fatores de risco

ABSTRACT Primary graft dysfunction is a multifactorial syndrome with great impact on liver transplantation outcomes. This review article was based on studies published between January 1980 and June 2015 and retrieved from PubMed database using the following search terms: “primary graft dysfunction”, “early allograft dysfunction”, “primary non-function” and “liver transplantation”. Graft dysfunction describes different grades of graft ischemia-reperfusion injury and can manifest as early allograft dysfunction or primary graft non-function, its most severe form. Donor-, surgery- and recipient-related factors have been associated with this syndrome. Primary graft dysfunction definition, diagnostic criteria and risk factors differ between studies.

RESUMO A disfunção primária do enxerto hepático é uma síndrome multifatorial com grande impacto no resultado do transplante de fígado. Foi realizada uma ampla revisão da literatura, consultando a base de dados PubMed, em busca de estudos publicados entre janeiro de 1980 e junho de 2015. Os termos descritivos utilizados foram: “primary graft dysfunction”, “early allograft dysfunction”, “primary non-function” e “liver transplantation”. A disfunção traduz graus diferentes da lesão de isquemia e reperfusão do órgão, e pode se manifestar como disfunção precoce ou, na forma mais grave, pelo não funcionamento primário do enxerto. Fatores relacionados ao doador, ao transplante e ao receptor contribuem para essa síndrome. Existem definições diferentes na literatura quanto ao diagnóstico e aos fatores de risco associados à disfunção primária.

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.

Associated clinical and laboratory markers of donor on allograft function after heart transplant

Abstract Introduction: Primary graft dysfunction is a major cause of mortality after heart transplantation. Objective: To evaluate correlations between donor-related clinical/biochemical markers and the occurrence of primary graft dysfunction/clinical outcomes of recipients within 30 days of transplant. Methods: The prospective study involved 43 donor/recipient pairs. Data collected from donors included demographic and echocardiographic information, noradrenaline administration rates and concentrations of soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2), interleukins (IL-6 and IL-10), monocyte chemoattractant protein-1, C-reactive protein and cardiac troponin I. Data collected from recipients included operating, cardiopulmonary bypass, intensive care unit and hospitalization times, inotrope administration and left/right ventricular function through echocardiography. Results: Recipients who developed moderate/severe left ventricular dysfunction had received organs from significantly older donors (P =0.020). Recipients from donors who required moderate/high doses of noradrenaline (>0.23 µg/kg/min) around harvesting time exhibited lower post-transplant ventricular ejection fractions (P =0.002) and required longer CPB times (P =0.039). Significantly higher concentrations of sTNFR1 (P =0.014) and sTNFR2 (P =0.030) in donors were associated with reduced intensive care unit times (≤5 days) in recipients, while higher donor IL-6 (P =0.029) and IL-10 (P =0.037) levels were correlated with reduced hospitalization times (≤25 days) in recipients. Recipients who required moderate/high levels of noradrenaline for weaning off cardiopulmonary bypass were associated with lower donor concentrations of sTNFR2 (P =0.028) and IL-6 (P =0.001). Conclusion: High levels of sTNFR1, sTNFR2, IL-6 and IL-10 in donors were associated with enhanced evolution in recipients. Allografts from older donors, or from those treated with noradrenaline doses >0.23 µg/kg/min, were more frequently affected by primary graft dysfunction within 30 days of surgery.

The relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation is modified by donor smoking and reperfusion hyperoxia.

BACKGROUND: Donor smoking history and higher fraction of inspired oxygen (FIO2) at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion. METHODS: We performed a nested case-control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. Using mass spectroscopy, F2-isoprostanes and isofurans were measured in plasma collected after transplantation. Cases were defined in 2 ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD) or any grade 3 PGD (any PGD). RESULTS: There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (28.6 pg/ml vs 19.8 pg/ml, p = 0.03). Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (29.6 pg/ml vs 19.0 pg/ml, p = 0.03) among patients reperfused with FIO2 >40%. Among recipients of lungs from donors with smoke exposure, plasma F2-isoprostane (38.2 pg/ml vs 22.5 pg/ml, p = 0.046) and isofuran (66.9 pg/ml vs 34.6 pg/ml, p = 0.046) levels were higher in severe PGD compared with control subjects. CONCLUSIONS: Plasma levels of lipid peroxidation products are higher in patients with severe PGD, in recipients of lungs from donors with smoke exposure, and in recipients exposed to higher Fio2 at reperfusion. Oxidative injury is an important mechanism of PGD and may be magnified by donor exposure to cigarette smoke and hyperoxia at reperfusion.

Experience of ECMO in Primary Graft Dysfunction after Orthotopic Heart Transplantation / Experiência na Utilização de ECMO na Disfunção Primária de Enxerto Pós-Transplante Cardíaco Ortotópico

Background:Primary graft dysfunction is the main cause of early mortality after heart transplantation. Mechanical circulatory support has been used to treat this syndrome.Objective:Describe the experience with extracorporeal membrane oxygenation to treat post-transplant primary cardiac graft dysfunction.Methods:Between January 2007 and December 2013, a total of 71 orthotopic heart transplantations were performed in patients with advanced heart failure. Eleven (15.5%) of these patients who presented primary graft dysfunction constituted the population of this study. Primary graft dysfunction manifested in our population as failure to wean from cardiopulmonary bypass in six (54.5%) patients, severe hemodynamic instability in the immediate postoperative period with severe cardiac dysfunction in three (27.3%), and cardiac arrest (18.2%). The average ischemia time was 151 ± 82 minutes. Once the diagnosis of primary graft dysfunction was established, we installed a mechanical circulatory support to stabilize the severe hemodynamic condition of the patients and followed their progression longitudinally.Results:The average duration of extracorporeal membrane oxygenation support was 76 ± 47.4 hours (range 32 to 144 hours). Weaning with cardiac recovery was successful in nine (81.8%) patients. However, two patients who presented cardiac recovery did not survive to hospital discharge.Conclusion:Mechanical circulatory support with central extracorporeal membrane oxygenation promoted cardiac recovery within a few days in most patients.

Fundamento:A disfunção primária de enxerto é a principal causa de mortalidade precoce após o transplante cardíaco. O uso de assistência circulatória mecânica tem sido empregado no tratamento dessa síndrome.Objetivo:Descrever a experiência com o uso de oxigenação por membrana extracorpórea para tratamento de disfunção primária de enxerto pós-transplante cardíaco.Métodos:Entre janeiro de 2007 e dezembro de 2013, foram realizados 71 transplantes cardíacos ortotópicos em pacientes com insuficiência cardíaca avançada. Destes, 11 (15,5%) pacientes apresentaram disfunção primária de enxerto, os quais constituíram a população deste estudo. As manifestações da disfunção primária de enxerto na nossa população foram falência no desmame da circulação extracorpórea em seis (54,5%) pacientes, instabilidade hemodinâmica grave no pós-operatório imediato com disfunção cardíaca acentuada em três (27,3%) e pós-parada cardíaca em dois (18,2%). O tempo de isquemia médio foi 151 ± 82 minutos. Assim que o diagnóstico de disfunção primária de enxerto foi estabelecido, procedeu-se à instalação de suporte circulatório mecânico para estabilização de quadro hemodinâmico grave, e a evolução dos pacientes foi estudada temporalmente.Resultados:A duração média de assistência em oxigenação por membrana extracorpórea foi 76 ± 47,4 horas (variação de 32 a 144 horas). O desmame com recuperação cardíaca obteve sucesso em nove (81,8%) pacientes. No entanto, dois pacientes, que tiveram recuperação cardíaca, não sobreviveram à alta hospitalar.Conclusão:O uso de assistência circulatória mecânica por meio de oxigenação por membrana extracorpórea central promoveu recuperação cardíaca em poucos dias na maioria dos pacientes.

Implementación y resultados de un nuevo programa de ECMO para trasplante de pulmón y distrés respiratorio agudo / Implementation and results of a new ECMO program for lung transplantation and acute respiratory distress

RESUMEN Objetivo: El desarrollo de la membrana de oxigenación extracorpórea en América Latina representa un desafío para la especialidad. El objetivo de este artículo fue describir los resultados de un nuevo programa de membrana de oxigenación extracorpórea en una unidad de cuidados intensivos. Métodos: Estudio de cohorte retrospectivo. Incluye 22 pacientes que requirieron membrana de oxigenación extracorpórea desde Enero de 2011 hasta Junio de 2014. Se evaluaron características basales, indicaciones, duración de la corrida, días de ventilación mecánica, días de unidad de cuidados intensivos, complicaciones y mortalidad hospitalaria. Resultados: Quince pacientes requirieron membrana de oxigenación extracorpórea post-trasplante pulmonar y 7 pacientes por distrés respiratorio agudo. Todos los pacientes trasplantados fueron destetados de membrana de oxigenación extracorpórea, con una duración mediana de 3 días (Rango intercuantil - IQR: 2 - 5), de ventilación mecánica 15,5 días (IQR: 3 - 35), de estadía unidad de cuidados intensivos 31,5 días (IQR: 19 - 53) y de estadía hospitalaria 60 días (IQR: 36 - 89), con una mortalidad de 20%. Los pacientes con distrés respiratorio agudo tuvieron una mediana de duración de membrana de oxigenación extracorpórea de 9 días (IQR: 3 - 14), mediana de ventilación mecánica 25 días (IQR: 13 - 37), de estadía en terapia 31 días (IQR: 11 - 38), y hospitalaria 32 días (IQR: 11 - 41), y 57% de mortalidad. Las principales complicaciones fueron infecciones (80%), insuficiencia renal aguda (43%), sangrados en sitio quirúrgico y de inserción de cánulas (22%), plaquetopenia (60%) y coagulopatía (30%). Conclusión: A pesar de encontrarnos transitando una curva de aprendizaje, consideramos la experiencia satisfactoria, con resultados y complicaciones comparables a las reportadas en la literatura. .

ABSTRACT Objective: The development of the extracorporeal membrane oxygenation in Latin America represents a challenge in this specialty field. The objective of this article was to describe the results of a new extracorporeal membrane oxygenation program in an intensive care unit. Methods: This retrospective cohort study included 22 patients who required extracorporeal membrane oxygenation and were treated from January 2011 to June 2014. The baseline characteristics, indications, duration of the condition, days on mechanical ventilation, days in the intensive care unit, complications, and hospital mortality were evaluated. Results: Fifteen patients required extracorporeal membrane oxygenation after lung transplantation, and seven patients required oxygenation due to acute respiratory distress. All transplanted patients were weaned from extracorporeal membrane oxygenation with a median duration of 3 days (Interquartile range - IQR: 2 - 5), were on mechanical ventilation for a median of 15.5 days (IQR: 3 - 25), and had an intensive care unit stay of 31.5 days (IQR: 19 - 53) and a median hospital stay of 60 days (IQR: 36 - 89) with 20% mortality. Patients with acute respiratory distress had a median oxygenation membrane duration of 9 days (IQR: 3 - 14), median mechanical ventilation time of 25 days (IQR: 13 - 37), a 31 day stay in therapy (IQR: 11 - 38), a 32 day stay in the hospital (IQR: 11 - 41), and 57% mortality. The main complications were infections (80%), acute kidney failure (43%), bleeding at the surgical site and at the site of cannula placement (22%), plateletopenia (60%), and coagulopathy (30%). Conclusion: In spite of the steep learning curve, we considered this experience to be satisfactory, with results and complications comparable to those reported in the literature. .

Trasplante pulmonar: estado actual / Lung transplantation: current state

El trasplante pulmonar es considerado en la actualidad el tratamiento de elección para pacientes portadores de una patología pulmonar avanzada, sin compromiso de otro órgano vital y que tengan sobrevida esperada de menos de dos años. Ha presentado una evolución notable en los últimos años mejorando la sobrevida y calidad de vida de los pacientes, lo que ha sido asociado a la mejoría de drogas inmunosupresoras, mejor diagnóstico de situación inmunológica, técnicas de preservación del injerto, protocolos efectivos de profilaxis infecciosa y diagnóstico precoz de las complicaciones. Los desafíos en la actualidad son el déficit de órganos, que lleva aumento de lista de espera por lo que se han desarrollado técnicas de optimización de injertos, la extensión de la edad de los candidatos a trasplante y se mantiene sin grandes modificaciones la disfunción crónica de injerto.

Lung transplantation is currently considered the treatment of choice for patients with advanced lung disease, without involvement of other vital organ and have expected survival of less than two years. In recent years has presented a remarkable development improving survival and quality of life of patients, which has been associated with improvement of immunosuppressive drugs, better diagnosis of immunological state, techniques graft preservation, effective prophylaxis infectious protocols and early diagnosis of medical complications. The challenges today are the shortage of organs, which has increased waiting list so that optimization techniques have been developed graft, the extension of the age of transplant candidates and remains largely unchanged chronic dysfunction graft.

Causas que contribuyen a la pérdida del trasplante renal de donante cadavérico en la Fundación Surcolombiana de Trasplantes. Febrero 2007 a noviembre de 2012, Neiva, Colombia / Factors contributing to the loss of deceased donor kidney at Fundación Surcolombiana de Trasplantes. February 2007-November 2012, Neiva, Colombia

RESUMEN Introducción: La enfermedad renal crónica (ERC) es una patología prevalente, y el trasplante renal es la alternativa para mejorar la calidad de vida de estos pacientes. Buscamos identificar las causas que contribuyen a la pérdida del trasplante renal a fin de mejorar el protocolo de manejo en nuestra población. Metodología: Estudio de cohorte retrospectivo en pacientes con trasplante renal (donante cadavérico) del Hospital Universitario de Neiva, Colombia, seguimiento a un año. Los datos se procesaron en STATA 11.1, se aplicó un análisis univariado, odds ratio (OR), IC 95% y la prueba de Fisher con significación p < 0,05. Resultados: Un total de 160 pacientes, el 49,38% con hipertensión arterial (HTA) y diabetes mellitus (DM) como causa de ERC. Incidencia de fracaso del 20%. Probables causas de pérdida del trasplante: edad mayor de 60 años (OR: 2,3), tiempo de isquemia fría mayor de 13 h (OR: 2), edad del donante mayor a 50 años (OR: 2,8). Complicaciones al primer mes: urológicas (OR: 3,3), vasculares (OR: 4), rechazo agudo (OR: 3,3). Al sexto mes: vasculares (OR: 45), urológicas (OR: 3,3), infecciosas (OR: 2,8). Al año: rechazo agudo (OR: 11,3), nefropatía crónica del injerto (OR: 15,3) e infecciosas (OR: 9,4). Conclusiones: La HTA y la DM son las principales etiologías de ERC. Las causas de fracaso de trasplante renal fueron vasculares e infecciosas. Se sugirieron probables factores de riesgo de importancia estadística y clínica, pero es necesario un mayor tamaño de muestra para hacer más robusta la evidencia estadística. © 2013 Sociedad Colombiana de Anestesiología y Reanimación.

ABSTRACT Introduction: Chronic kidney disease (CKD) is a prevalent dysfunction and renal transplant is the alternative for improving the lives of these patients. We seek to identify the factors that contribute to the loss of renal transplant in order to improve the management protocol in our population. Methodology: Retrospective cohort study in patients with renal transplantation (deceased donor) at Hospital Universitario de Neiva, Colombia, with a year of follow-up period. Data were processed in STATA 11.1, using univariate analysis, odds ratio (OR), (95% CI) and Fisher test, with p < 0.05 significance. Results: In 160 patients, 49.38% with arterial hypertension (HTN) and diabetes mellitus (DM) as the cause for CKD, there was 20% failure incidence. Probable causes of transplant loss: age over 60 (OR: 2.3); time of cold ischemia greater than 13 h (OR: 2); donor age greater than 50(OR: 2.8). One-month complications: urologic (OR: 3.3), vascular (OR: 4), acute rejection (OR:3.3). Six-month complications: vascular (OR: 4.5), urologic (OR: 3.3), infectious (OR: 2.8). One-year complications: acute rejection (OR: 11.3), chronic graft nephropathy (OR: 15.3), infection (OR: 9.4). Conclusions: Arterial hypertension and DM are the main etiologies of CKD. The causes of renal transplant failure were mainly vascular and infectious. Probable risk factors of statistical and clinical importance were suggested but a larger sample size is required for more robust statistical evidence.

Preoperative plasma club (clara) cell secretory protein levels are associated with primary graft dysfunction after lung transplantation.

Inherent recipient factors, including pretransplant diagnosis, obesity and elevated pulmonary pressures, are established primary graft dysfunction (PGD) risks. We evaluated the relationship between preoperative lung injury biomarkers and PGD to gain further mechanistic insight in recipients. We performed a prospective cohort study of recipients in the Lung Transplant Outcomes Group enrolled between 2002 and 2010. Our primary outcome was Grade 3 PGD on Day 2 or 3. We measured preoperative plasma levels of five biomarkers (CC-16, sRAGE, ICAM-1, IL-8 and Protein C) that were previously associated with PGD when measured at the postoperative time point. We used multivariable logistic regression to adjust for potential confounders. Of 714 subjects, 130 (18%) developed PGD. Median CC-16 levels were elevated in subjects with PGD (10.1 vs. 6.0, p<0.001). CC-16 was associated with PGD in nonidiopathic pulmonary fibrosis (non-IPF) subjects (OR for highest quartile of CC-16: 2.87, 95% CI: 1.37, 6.00, p=0.005) but not in subjects with IPF (OR 1.38, 95% CI: 0.43, 4.45, p=0.59). After adjustment, preoperative CC-16 levels remained associated with PGD (OR: 3.03, 95% CI: 1.26, 7.30, p=0.013) in non-IPF subjects. Our study suggests the importance of preexisting airway epithelial injury in PGD. Markers of airway epithelial injury may be helpful in pretransplant risk stratification in specific recipients.

A hiponatremia como fator preditivo da perda precoce do transplante hepático na modalidade intervivos / Hyponatremia as a predictor factor of early loss after living donor liver transplantation

INTRODUÇÃO: O transplante hepático intervivos representa alternativa para reduzir a falta de doação de órgãos. OBJETIVO: Analisar a influência da natremia como fator preditivo da perda precoce do transplante hepático nos três primeiros meses na modalidade intervivos. MÉTODO: Estudo retrospectivo, observacional e analítico de 78 doentes adultos submetidos ao transplante de fígado com doador vivo. A média etária foi 50,7±6,8 anos (18 a 65 anos) e dividiu-se os doentes transplantados em grupo I, com 62 (79,5%) pacientes com sobrevivência do enxerto superior a três meses, e grupo II com 16 (20,5%), que faleceram e/ou apresentaram falha do enxerto no prazo de até três meses após a realização do transplante hepático. Foram analisadas as seguintes variáveis: sexo, idade, etiologia da doença hepática e o nível sérico de sódio no momento do transplante. Foi considerada "perda precoce" a sobrevivência do enxerto hepático menor que três meses após a realização do transplante. Na avaliação dos fatores de risco para perda precoce do enxerto hepático foram utilizados o teste do χ2, o teste t de Student e a análise uni e multivariada. A análise de sobrevivência do enxerto foi realizada pelo modelo de Kaplan-Meier. RESULTADOS: Sexo (p=0,4) e idade (p=0,67) não apresentaram diferença significante. O nível sérico de sódio foi significantemente (p=0,01) maior no grupo I do que no grupo II. CONCLUSÃO: Os valores da natremia estão associados à maior probabilidade de sucesso no transplante hepático na modalidade intervivos.

INTRODUCTION: Living donor liver transplantation has become an appreciable and effective alternative to reduce the problem resulting from the lack of organ donation. OBJECTIVE: To analyze the influence of serum sodium as a predictor of early loss of liver transplantation in the first three months in living donor modality. METHOD: In this analytical study, 78 adults submitted to living donor liver transplantation were studied retrospectively. The mean age was 50.7±6.8 years (18 to 65 years). The transplant recipients were divided into two groups: group I consisted of 62 (79.5%) patients with graft survival longer than three months, and group II consisted of 16 (20.5%) patients who died and/or showed graft failure within three months after liver transplantation. The following variables were analyzed: gender, age, etiology of liver disease and serum sodium concentration at the time of transplantation. Liver graft survival of less than three months after transplantation was defined as "early loss". The χ2 test, Student's t-test and uni and multivariate analysis were used for the evaluation of risk factors for early graft loss. Graft survival was analyzed using the Kaplan-Meier model. RESULTS: No significant difference in gender (p=0.4) and age (p=0.67) was observed between the two groups. Serum sodium concentration was significantly (p=0.01) higher in group I than in group II. CONCLUSION: Serum sodium concentration is associated with a higher probability of graft failure after living donor liver transplantation.

Predictive factors of early graft loss in living donor liver transplantation / Fatores preditivos da perda precoce do enxerto hepático em transplante hepático intervivos

CONTEXT: Living donor liver transplantation has become an alternative to reduce the lack of organ donation. OBJECTIVE: To identify factors predictive of early graft loss in the first 3 months after living donor liver transplantation. METHODS: Seventy-eight adults submitted to living donor liver transplantation were divided into group I with 62 (79.5%) patients with graft survival longer than 3 months, and group II with 16 (20.5%) patients who died and/or showed graft failure within 3 months after liver transplantation. The variables analyzed were gender, age, etiology of liver disease, Child-Pugh classification, model of end-stage liver disease (MELD score), pretransplantation serum sodium level, and graft weight-to-recipient body weight (GRBW) ratio. The GRBW ratio was categorized into < 0.8 and MELD score into >18. The chi-square test, Student t-test and uni- and multivariate analysis were used for the evaluation of risk factors for early graft loss. RESULTS: MELD score <18 (P<0.001) and serum sodium level > 135 mEq/L (P = 0.03) were higher in group II than in group I. In the multivariate analysis MELD scores > 18 (P<0.001) and GRBW ratios < 0.8 (P<0.04) were significant. CONCLUSIONS: MELD scores >18 and GRBW < 0.8 ratios are associated with higher probability of graft failure after living donor liver transplantation.

CONTEXTO: O transplante hepático intervivos constitui alternativa para amenizar a falta de doação de órgãos. OBJETIVO: Identificar os fatores preditivos da perda precoce do enxerto hepático nos 3 primeiros meses após transplante hepático intervivo. MÉTODOS: Setenta e oito adultos submetidos ao transplante de fígado intervivos foram divididos em grupo I com 62 (79,5%) doentes com sobrevivência do enxerto superior a 3 meses, e grupo II com 16 (20,5%) que faleceram e/ou apresentaram falha do enxerto até 3 meses após o transplante hepático. As variáveis analisadas foram: sexo, idade, origem da doença hepática, classificação de Child-Pugh, critério MELD, nível sérico de sódio pré-transplante e relação GRBW. O critério MELD foi categorizado em > 18 e a relação GRBW em < 0,8. Na avaliação dos fatores de risco para perda precoce do enxerto hepático foi utilizada a análise uni e multivariada. RESULTADOS: Critério MELD <18 (P = 0,001) e nível sérico de sódio >135 mEq/L (P = 0,03) foram maiores nos doentes do grupo II. A probabilidade de perda do enxerto no transplante hepático intervivos teve como variáveis independentes o índice MELD > 18 e a relação GRBW< 0,8. CONCLUSÃO: Os valores de MELD >18 e GRBW <0,8 estão associados com maior probabilidade de insucesso no transplante hepático intervivos.