ESTELA REGINA RAMOS FIGUEIRA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/37 - Laboratório de Transplante e Cirurgia de Fígado, Hospital das Clínicas, Faculdade de Medicina
LIM/37 - Laboratório de Transplante e Cirurgia de Fígado, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Elastography for the Diagnosis and Graduation of Liver Disease in Patients with Long Term Parenteral Nutrition(2021) GALVAO, F.; VEZOZZO, D.; LEE, A.; WAISBERG, D.; ROCHA, M.; NACIF, L.; PINHEIRO, R.; FIGUEIRA, E.; CASSENOTE, A.; CARRILHO, F.; WAITZBERG, D.; CARNEIRO-D'ALBUQUERQUE, L.- Anesthetic Conditioning in Liver Transplantation: Results of a Multicenter Randomized Controlled Trial(2013) BONVINI, John M.; SCHADDE, Erik; CLAVIEN, Pierre-Alain; LESURTEL, Mickael; FIGUEIRA, Estela R. R.; FILHO, Joel A. Rocha; REYNTJENS, Koen; BREITENSTEIN, Stefan; BECK-SCHIMMER, BeatriceBackground data: In the age of organ scarcity and the increased use of older and steatotic organ grafts, protective strategies during transplantation are gaining importance. Volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury in liver resection and lead to improved clinical outcome. Whether volatile anesthetics change clinical outcome in liver transplantation is unknown. Methods: Cadaveric liver recipients were randomized from 03/2009 to 08/2012 at three University Centers (Zurich, Sao Paulo, Ghent). Standard liver transplant patients were randomly assigned to propofol anesthesia (control group) or conditioning with sevoflurane (sevoflurane group). Postoperative peak of the aspartate transaminase (AST) was defined as primary endpoint. Secondary endpoints were in-hospital complications, hospital- and ICU stay. Results: Ninety-eight patients, who underwent liver transplantation, were randomized to propofol (n=48) or sevoflurane (n=50). Peak AST after transplantation was 925 U/l (512-3274) in the propofol group (p=0.73) and 1097 U/l (interquartile range 540-2633) in the sevofluorane one. While the overall complication rate was not different, there was a trend towards less severe complications in the sevoflurane group: median complication score was grade IIIa (IQR II-IVb) for the propofol and grade II (IQR 0-IIIb) for the sevoflurane group (Odds ratio 0.51, 0.24 to 1.09, p=0.08). Conclusions: This first multicenter trial with different anesthesia regimens in liver transplantation showed comparable surrogate markers postoperatively, but a trend towards less severe complications in the sevoflurane group. Future trials should be adequately powered to assess complications and identify subgroups, which might benefit from anesthetic conditioning.
conferenceObject Elastography for the Diagnosis and Graduation of Liver Disease in Patients with Long Term Parenteral Nutrition(2021) GALVAO, F.; VEZOZZO, D.; LEE, A.; WAISBERG, D.; ROCHA, M.; NACIF, L.; PINHEIRO, R.; FIGUEIRA, E.; CASSENOTE, A.; CARRILHO, F.; WAITZBERG, D.; CARNEIRO-D'ALBUQUERQUE, L.conferenceObject EFFECTS OF ANAESTHETIC PRECONDITIONING PLUS POSTCONDITIONING WITH SEVOFLURANE IN WARM LIVER ISCHEMIA/REPERFUSION INJURY IN RATS(2012) FILHO, J. A. R.; FIGUEIRA, E. R. R.; SCHIMMER, B. B.; ANDRE, V. O.; BUTO, M. F. de Souza; NAKATANI, M.; PRADO, F. J. G.; CARMONA, M. J. C.; CLAVIEN, P. A.; D'ALBUQUERQUE, L. A. C.Background: Preconditioning is a therapeutic strategy aimed to increase ischemic tissue tolerance against ischemia/reperfusion (IR) injury. Recent studies demonstrated that volatile anaesthetics may improve postischemic recovery by an ischemic preconditioning-like mechanism. Postconditioning is a new concept that may have hepatoprotective effect. We hypothesized that sevoflurane preconditioning combined with postconditioning may reduce the hepatocellular damage in a rat model of warm liver IR. Methods: Ten Wistar rats under mechanical ventilation were divided into 2 groups of 5; 1) IR: rats subjected to 45 min of warm liver ischemia of left and median lobes, followed by resection of non-ischemic lobes at early reperfusion; and 2) SEVO + IR: rats were exposed to sevoflurane 2.5% for 15 min, followed by 5 min washout, before ischemia, plus sevoflurane 2.5% for 15 minat reperfusion. Carotid artery was cannulated for mean arterial pressure(MAP). Mean portal flow (MPF) was assessed by perivascular flowprobe. MAP and MPF were recorded at baseline, pre-repefusion and 4 h postreperfusion. Liver transaminases, creatinine, pH, bicarbonate (BIC) and base excess (BE), potassium (K), glucose and lactate were measured at 4 h postreperfusion. Results: AST and ALT were decreased in SEVO + IR group (12.118 ± 3.611 and 7.870 ± 1.586 U/L) compared to IR group (16.890 ± 1.630 and13.418 ± 1.088 U/L), P < 0.05. BIC, and K were increased in SEVO + IR group (11.20 ± .86 mmol/l and 6.1 ± 1.3 mEq/dl) compared to IR (6.70 ± 3.32 mmol/l and 4.7 ± 0.7 mEq/dl),P < 0.05. There were no differ- ences in MAP, MPF, creatinine, glucose, lactate, pH and BE; however glucose tended to be higher in SEVO + IR group (50.8 ± 26.0 mg/dl) compared to IR (35.0 ± 18.4 mg/dl). Conclusions: In experimental warm liver ischemia/reperfusion, sevoflurane preconditioning plus postconditioning reduced the hepatocellular injury demonstrated by lower levels of transaminases with a better behaviour of acid base variables and good hemodynamic recovery. These preliminary results are encouraging because postconditioning may have the advantage of being implemented at the moment of reperfusion, what is more feasible to be applied during liver transplantation surgery.- Surgical site infections in liver transplant recipients in the model for end-stage liver disease era: An analysis of the epidemiology, risk factors, and outcomes(2013) FREIRE, Maristela Pinheiro; OSHIRO, Isabel C. V. Soares; BONAZZI, Patricia Rodrigues; GUIMARAES, Thais; FIGUEIRA, Estela Regina Ramos; BACCHELLA, Telesforo; COSTA, Silvia Figueiredo; D'ALBUQUERQUE, Luiz Augusto Carneiro; ABDALA, EdsonIn recipients of liver transplantation (LT), surgical site infection (SSIs) are among the most common types of infection occurring in the first 60 days after LT. In 2007, the Model for End-Stage Liver Disease (MELD) scoring system was adopted as the basis for prioritizing organ allocation. Patients with higher MELD scores are at higher risk for developing SSIs as well as other health care-associated infections. However, there have been no studies comparing the incidence of SSIs in the pre-MELD era with the incidence in the period since its adoption. Therefore, the objectives of this study were to evaluate the incidence, etiology, epidemiology, and outcomes of post-LT SSIs in those 2 periods and to identify risk factors for SSIs. We evaluated all patients who underwent LT over a 10-year period (2002-2011). SSI cases were identified through active surveillance. The primary outcome measure was an SSI during the first 60 days after LT. Risk factors were analyzed via logistic regression, and 60-day survival rates were evaluated via Cox regression. We evaluated 543 patients who underwent LT 597 times. The SSI rates in the 2002-2006 and 2007-2011 periods were 30% and 24%, respectively (P=0.21). We identified the following risk factors for SSIs: retransplantation, the transfusion of more than 2 U of blood during LT, dialysis, cold ischemia for >400 minutes, and a cytomegalovirus infection. The overall 60-day survival rate was 79%. Risk factors for 60-day mortality were retransplantation, dialysis, and a longer surgical time. The use of the MELD score modified the incidence and epidemiology of SSIs only during the first year after its adoption. Risks for SSIs were related more to intraoperative conditions and intercurrences after LT than to a patient's status before LT. Liver Transpl 19:1011-1019, 2013. (c) 2013 AASLD.
- Immunoglobulin G profile in hyperacute rejection after multivisceral xenotransplantation(2012) GALVAO, Flavio H. F.; SOLER, Wangles; POMPEU, Eduardo; WAISBERG, Daniel R.; MELLO, Evandro S. D.; COSTA, Anderson C. L.; TEODORO, Walcy; VELOSA, Ana P.; CAPELOZZI, Vera L.; ANTONANGELO, Leila; CATANOZI, Sergio; MARTINS, Alessandro; MALBOUISSON, Luiz M. S.; CRUZ JR., Ruy J.; FIGUEIRA, Estela R.; FILHO, Joel A. R.; CHAIB, Eleazar; D'ALBUQUERQUE, Luiz A. C.Galvao FHF, Soler W, Pompeu E, Waisberg DR, Mello ES, Costa ACL, Teodoro W, Velosa AP, Capelozzi VL, Antonangelo L, Catanozi S, Martins A, Malbouisson LMS, Cruz RJ, Figueira ER, Filho JAR, Chaib E, D'Albuquerque LAC. Immunoglobulin G profile in hyperacute rejection after multivisceral xenotransplantation. Xenotransplantation 2012; 19: 298304. (c) 2012 John Wiley & Sons A/S. Abstract: Introduction: Xenotransplantation is a potential solution for the high mortality of patients on the waiting list for multivisceral transplantation; nevertheless, hyperacute rejection (HAR) hampers this practice and motivates innovative research. In this report, we describe a model of multivisceral xenotransplantation in which we observed immunoglobulin G (IgG) involvement in HAR. Methods: We recovered en bloc multivisceral grafts (distal esophagus, stomach, small intestine, colon, liver, pancreas, and kidneys) from rabbits (n = 20) and implanted them in the swine (n = 15) or rabbits (n = 5, control). Three hours after graft reperfusion, we collected samples from all graft organs for histological study and to assess IgG fixation by immunofluorescence. Histopathologic findings were graded according to previously described methods. Results: No histopathological features of rejection were seen in the rabbit allografts. In the swine-to-rabbit grafts, features of HAR were moderate in the liver and severe in esophagus, stomach, intestines, spleen, pancreas, and kidney. Xenograft vessels were the central target of HAR. The main lesions included edema, hemorrhage, thrombosis, myosites, fibrinoid degeneration, and necrosis. IgG deposition was intense on cell membranes, mainly in the vascular endothelium. Conclusions: Rabbit-to-swine multivisceral xenotransplants undergo moderate HAR in the liver and severe HAR in the other organs. Moderate HAR in the liver suggests a degree of resistance to the humoral immune response in this organ. Strong IgG fixation in cell membranes, including vascular endothelium, confirms HAR characterized by a primary humoral immune response. This model allows appraisal of HAR in multiple organs and investigation of the livers relative resistance to this immune response.
conferenceObject EFFECTS OF ANAESTHETIC PRECONDITIONING WITH SEVOFLURANE IN WARM LIVER ISCHEMIA/REPERFUSION INJURY IN RATS(2012) FIGUEIRA, E. R. R.; FILHO, J. A. R.; SCHIMMER, B. B.; NAKATANI, M.; TATEBE, E. R.; ANDRE, V. O.; PRADO, F. J. G.; CARMONA, M. J. C.; D'ALBUQUERQUE, L. A. C.Background: Preconditioning is a therapeutic strategy aimed to increase ischemic tissue tolerance against ischemia/reperfusion (IR) injury. Recentstudies demonstrated that volatile anaesthetics may improve postischemic recovery by an ischemic preconditioning-like mechanism. We hypothesized that pharmacological preconditioning with sevoflurane may reduce the hepatocellular damage in a rat model of warm liver IR. Methods: Ten Wistar rats under mechanical ventilation were divided into 2 groups of 5 animals: I) IR: rats subjected to 45 min of warm liver ischemia of the left and median lobes, followed by resection of the non-ischemic lobes at early reperfusion; and II) SEVO+IR: rats were exposed to sevoflurane 2.5% for 15 min, followed by washout during 5 min, before IR. The carotid artery was cannulated for mean arterial pressure (MAP) monitoring. The mean portal venous flow (MPF) was assessed by perivascular flowprobe. MAP and MPF were recorded at baseline, pre reperfusion and 4 hours post-reperfusion. Liver transaminases, creatinine, pH, bicarbonate (BIC) and base excess (BE), potassium (K), glucose and lactate were measured at 4 hours post-reperfusion. Results: AST and ALT were decreased in SEVO+IR group (10.056 ± 5.830 and 8.586 ± 5.296 U/L) compared to IR group (16.890 ± 1.630 and 13.418 ± 1.088 U/L), P < 0.05. BIC, BE and K were increased in SEVO+IR group (12.42 ± 4.39, -14.72 ± 4.46 mmol/l and 6.3 ± 0.9 mEq/dl) compared to IR (6.70 ± 3.32, -20.48 ± 4.22 mmol/l and 4.7 ± 0.7 mEq/dl), P< 0.05. MAP at 4 hours post-reperfusion was decreased in SEVO+IR group (65 ± 24 mmHg) compared to IR (93 ± 14 mmHg), P < 0.05. There were no differences in MPF, creatinine, glucose and lactate. Glucose tended to be higher and lactate lower in SEVO+IR group (54.0 ± 22.7 and 42.8 ± 18.6 mg/dl) compared to IR (35.0 ± 18.4 and 66.8 ± 25.9 mg/dl). Conclusions: In liver IR, sevoflurane preconditioning reduced hepatocellular injury demonstrated by lower levels of transaminases. Despite the lower mean arterial pressure presented in sevoflurane treated animals, no detrimental effect was observed in portal venous flow, hepatic metabolism and renal function. This study highlight the need for clarifying the mechanisms of sevoflurane preconditioning, and if there is additional hepatoprotection against cold IR injury.conferenceObject HEMODYNAMIC STUDY OF THE PORTAL VENOUS SYSTEM IN A MODEL OF WARM LIVER ISCHEMIA/REPERFUSION INJURY IN RATS(2012) BUTO, M. F. de Souza; FIGUEIRA, E. R. R.; FILHO, J. A. R.; NAKATANI, M.; TATEBE, E. R.; ANDRE, V. O.; MARTINS, A. R. de Carvalho; JUREIDINI, R.; CARMONA, M. J. C.; BACCHELLA, T.; CHAIB, E.; CECCONELLO, I.; ALBUQUERQUE, L. A. C. D.Background: Liver transplantation and resections require temporary interruption of the hepatic blood flow resulting in ischemia/reperfusion (IR) injury. The hepatic microcirculatory impairment is related to the severity of the IR injury and may be reflected in the liver macro hemodynamic. There is aninverse correlation between hepatic blood flow and the postoperative transaminases. The aim of the study was to evaluate the hemodynamic of the portal venous system after warm liver IR injury. Methods: Eighteen Wistar rats were divided into 3 groups: I) Control; II) sham: rats submitted to resection of right and caudate liver lobes; III) Ischemia (IR): rats subjected to 60 min of partial warm liver ischemia of left and median lobes, followed by resection of non-ischemic lobes at reperfusion. Four hours after reperfusion rats were anesthetized and submitted to mechanical ventilation. Carotid artery was cannulated for mean arterial pressure (MAP). Mean portal venous flow (MPF) was assessed by a perivascular flowprobe. A micropressure probe was introduced into portal vein to assess the mean portal venous pressure (MPP). At the end blood was collected for AST and ALT analysis. Results: The mean weigh of rats was 229 ± 18 g. AST and ALT were increased in IR group (6.675 ± 1.687 and 5.793 ± 1.119 U/L) compared to sham (897 ± 303 and 815 ± 433 U/L) and control groups (99 ± 28 and 64 ± 27 U/L), P < 0.05. MAP was decreased in IR group (90 ± 17 mmHg) compared to control group (114 ± 9 mmHg), P < 0.05; but there is no difference when compared to sham group (106 ± 16 mmHg). MPP was increased in sham group (9.3 ± 1.8 mmHg) compared to control (6.2 ± 1.7 mmHg) and IR (4.5 ± 1.7 mmHg) groups, P< 0.05. MPF was decreased in IR group (5.0 ± 2.2 ml/min) compared to sham (12.3 ± 2.1 ml/min) and control (12.2 ± 1.9 ml/min) groups, P< 0.05. Conclusions: This study showed that four hours after warm liver ischemia/reperfusion, the total hepatic blood flow is reduced, demonstrated by the decrease of 60% in mean portal flow and 21% in mean arterial pressure. These changes in the hepatic hemodynamics may be correlated with the severity of the liver ischemia/reperfusion injury. This model can be a tool to evaluate protective strategies against liver IR that impact hepatic macro hemodynamics.- Conditioning With Sevoflurane in Liver Transplantation: Results of a Multicenter Randomized Controlled Trial(2015) BECK-SCHIMMER, Beatrice; BONVINI, John M.; SCHADDE, Erik; DUTKOWSKI, Philipp; OBERKOFLER, Christian E.; LESURTEL, Mickael; DEOLIVEIRA, Michelle L.; FIGUEIRA, Estela R. R.; ROCHA FILHO, Joel A.; AULER JR., Jose Otavio Costa; D'ALBUQUERQUE, Luiz A. C.; REYNTJENS, Koen; WOUTERS, Patrick; ROGIERS, Xavier; DEBAERDEMAEKER, Luc; GANTER, Michael T.; WEBER, Achim; PUHAN, Milo A.; CLAVIEN, Pierre-Alain; BREITENSTEIN, StefanBackground. 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.
conferenceObject METABOLIC CHANGES IN A MODEL OF WARM LIVER ISCHEMIA/REPERFUSION INJURY IN RATS(2012) TATEBE, E. R.; FIGUEIRA, E. R. R.; FILHO, J. A. R.; ANDRE, V. O.; NAKATANI, M.; BUTO, Marcelo Felipe de Souza; JUREIDINI, R.; ANDRAUS, W.; BACCHELLA, T.; CHAIB, E.; CECCONELLO, I.; ALBUQUERQUE, L. A. C. D.Background: Liver ischemia/reperfusion (IR) is characterized by tissue injury associated with metabolic derangements as occurs in Liver transplantation (LT) and hepatic surgery. We hypothesized that a model reproducing whole liver ischemia may allow studying with more accuracy the metabolic derangements that follows particular clinical scenarios like LT. Methods: Eighteen Wistar rats were divided into 3 groups of 6 animals: I) Control: normal rats not subjected to liver resection or IR; II) sham: rats submitted to resection of right and caudate liver lobes; III) Ischemia (IR): rats subjected to 60 min of partial warm liver ischemia of the left lateral and median lobes, followed by resection of non-ischemic lobes at beginning of reperfusion. Four hours after reperfusion rats were anesthetized and submitted to mechanical ventilation. The carotid artery was cannulated and arterial blood was collected for analysis of lactate, potassium, glucose, hemoglobin and liver transaminases. Then animals were killed by exsanguination. Results: The mean weigh of the rats was 229 ± 18 g. AST and ALT were increased in the IR group (6.675 ± 1.687 and 5.793 ± 1.119 U/L) compared to the sham (897 ± 304 and 815 ± 433 U/L) and control groups (99 ± 28 and 64 ± 27 U/L), P< 0.05. Glucose was decreased in the IR group (115 ± 30 mg/dl) compared to the sham (224 ± 101 mg/dL) and control (298 ± 115 mg/dl) groups, P< 0.05. Lactate was increased in the IR group (24.7 ± 10.2 mg/dl) compared to the sham group (14.8 ± 6.3 mg/dL), P< 0.05. There were no differences in potassium and hemoglobin between groups. However the potassium in the IR group tended to be higher than control and sham groups. Conclusions: This experimental model of warm liver I/R showed that after 60 min of ischemia the hepatic metabolism is reduced. There was a decrease of 40% in the glucose and an increase of 60% in lactate serum levels. This impairment of these metabolic variables was associated with an increase in liver transaminases indicating a correlation with the I/R injury. This model may be useful to study the metabolic hepatic disorders that accompanies liver ischemia/reperfusion.