Impairment of exogenous lactate clearance in experimental hyperdynamic septic shock is not related to total liver hypoperfusion

Introduction: Although the prognostic value of persistent hyperlactatemia in septic shock is unequivocal, its physiological determinants are controversial. Particularly, the role of impaired hepatic clearance has been underestimated and is only considered relevant in patients with liver ischemia or cirrhosis. Our objectives were to establish whether endotoxemia impairs whole body net lactate clearance, and to explore a potential role for total liver hypoperfusion during the early phase of septic shock. Methods: After anesthesia, 12 sheep were subjected to hemodynamic/perfusion monitoring including hepatic and portal catheterization, and a hepatic ultrasound flow probe. After stabilization (point A), sheep were alternatively assigned to lipopolysaccharide (LPS) (5 mcg/kg bolus followed by 4 mcg/kg/h) or sham for a three-hour study period. After 60 minutes of shock, animals were fluid resuscitated to normalize mean arterial pressure. Repeated series of measurements were performed immediately after fluid resuscitation (point B), and one (point C) and two hours later (point D). Monitoring included systemic and regional hemodynamics, blood gases and lactate measurements, and ex-vivo hepatic mitochondrial respiration at point D. Parallel exogenous lactate and sorbitol clearances were performed at points B and D. Both groups included an intravenous bolus followed by serial blood sampling to draw a curve using the least squares method. Results: Significant hyperlactatemia was already present in LPS as compared to sham animals at point B (4.7 (3.1 to 6.7) versus 1.8 (1.5 to 3.7) mmol/L), increasing to 10.2 (7.8 to 12.3) mmol/L at point D. A significant increase in portal and hepatic lactate levels in LPS animals was also observed. No within-group difference in hepatic DO2, VO2 or O2 extraction, total hepatic blood flow (point D: 915 (773 to 1,046) versus 655 (593 to 1,175) ml/min), mitochondrial respiration, liver enzymes or sorbitol clearance was found. However, there was a highly significant decrease in lactate clearance in LPS animals (point B: 46 (30 to 180) versus 1,212 (743 to 2,116) ml/min, P <0.01; point D: 113 (65 to 322) versus 944 (363 to 1,235) ml/min, P <0.01). Conclusions: Endotoxemia induces an early and severe impairment in lactate clearance that is not related to total liver hypoperfusion

Gastrointestinal neuroendocrine tumor with unresectable liver metastases: an example of multimodal therapeutic approach

Gastrointestinal neuroendocrine tumors (NET) frequently present with unresectable hepatic metastases, which poses a barrier for curative treatment. Resection of the primary tumor and subsequent orthotopic liver transplantation (OLT) has been proposed as a treatment approach but available data in this regard is limited. We present a clinical case of an otherwise asymptomatic 44-yo man complaining of abdominal pain and dyspepsia that was diagnosed of a 10 cm duodenal tumor with multiple hepatic metastases. A CT-guided biopsy confirmed a NET. He underwent first a Whipple’s procedure, and then was listed for liver transplantation. During the waiting time a multimodal therapeutic approach was used including the use of radioactive 177lutetium-labeled somatostatin analogues, long-acting somastostatin analogues and antiangiogenic antibodies (bevacizumab) in order to keep neoplastic disease under control. Two years after Whipple’s procedure and given disease stability he underwent OLT with an uneventful postoperative evolution. Patient condition and graft function are optimal after a 4-year follow-up period with no evidence of recurrence. This case report underscores how a multimodal approach involving careful patient selection, resective surgery as well as use of somatostatin analogues and antiangiogenic biological therapy followed by liver transplantation can achieve excellent long-term results in this difficult patient population

Accuracy of the BAR score in the prediction of survival after liver transplantation

Introduction and aim: The Balance of Risk (BAR) Score, a simple scoring system that combines six independent donor and recipient variables to predict outcome after liver transplantation (LT), was validated in a large U.S./European cohort of patients. This study aims to assess the performance of the BAR score to predict survival after liver transplantation and determine the factors associated with short and long-term survival in Latin-American patients. Material and methods: A retrospective cohort study was performed in 194 patients [112 (55.4%) males; mean age 52 ± 14 years] who underwent 202 LT during the period 2003–2015. Demographic, clinical, pathological and surgical variables, as well as mortality and survival rates, were analyzed. The BAR score was investigated through a receiver operating characteristics (ROC) curve with the calculation of the area under the curve (AUC) to evaluate the predictive score power for 3-month, 1 and 5-year mortality in a matched donor–recipient cohort. Youden index was calculated to identify optimal cutoff points. Results: The AUC of BAR score in predicting 3-month, 1-year and 5-year mortality were 0.755 (CI95% 0.689–0.812), 0.702 (CI95% 0.634–0.764) and 0.610 (CI95% 0.539–0.678) respectively. The best cut-off point was a BAR score ≥15 points. In the multivariate analysis BAR score <15 was associated with higher survival rates at 3 months and 1 and 5-years. Conclusions: BAR score <15 points is an independent predictor of better short and long-term survival in Latin-American patients undergoing LT. The BAR scoring system has an adequate diagnostic capacity allowing to predict 3 and 12-month mortality

Successful treatment of severe hepatopulmonary syndrome with a sequential use of TIPS placement and liver transplantation

Hepatopulmonary syndrome (HPS) is a complication of portal hypertension (PH) defined by the presence of liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations (IPVD) producing a right to left intrapulmonary shunt. Liver transplantation (LT) is the treatment of choice; however, severe hypoxemia may contraindi-cate LT. The use of transjugular intrahepatic porto-systemic shunts (TIPS) could be effective in HPS, although available data is limited. Aim: To report a clinical case of severe HPS treated sequentially with TIPS and LT. Case report: A 46 year old female cir-rhotic patient presented with rapidly progressive dyspnea, hypoxemia (PaO2 60 mmHg, SaO2 92%) and increased alveolar-arterial oxygen gradient (A-a) (46 mmHg). She also had orthodeoxia (SaO2 87% in sitting position, but 91% in a prone position). A CT scan and pulmonary angiography were normal. Spirometric assessment showed a mild restrictive pattern and a desaturation was observed in a six-minute walking test. Contrast-enhanced echocardiography (CEE) showed intrapulmonary shunting. A HPS was diagnosed and liver transplantation was disregarded due to severe hypoxemia. The patient underwent TIPS placement. After four weeks, a significant improvement of dyspnea and a complete remission of orthodeoxia were seen. One year later, the patient was successfully transplanted. Interestingly, six months after LT, and in the absence of dyspnea, a new CEE showed persistent passing of bubbles to the left cavities. Comments/Conclusion: Persistent right-to-left shunt after TIPS placement and liver transplantation in spite of the improvement of pulmonary function tests suggests long-term persistence of structural changes in the pulmonary vascular tree after liver transplantation. Because of lack of data, it is not possible to recommend the routine use of TIPS as a part of the conventional management of HPS. However, in patients with severe hypoxemia TIPS placement can reasonably be used as a bridge towards transplantation

Effects of dexmedetomidine and esmolol on systemic hemodynamics and exogenous lactate clearance in early experimental septic shock

Persistent hyperlactatemia during septic shock is multifactorial. Hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation together with impaired lactate clearance have been implicated. An excessive adrenergic response could contribute to persistent hyperlactatemia and adrenergic modulation might be beneficial. We assessed the effects of dexmedetomidine and esmolol on hemodynamics, lactate generation, and exogenous lactate clearance during endotoxin-induced septic shock. Methods: Eighteen anesthetized and mechanically ventilated sheep were subjected to a multimodal hemodynamic/perfusion assessment including hepatic and portal vein catheterizations, total hepatic blood flow, and muscle microdialysis. After monitoring, all received a bolus and continuous infusion of endotoxin. After 1 h they were volume resuscitated, and then randomized to endotoxin-control, endotoxin-dexmedetomidine (sequential doses of 0.5 and 1.0 μg/k/h) or endotoxin-esmolol (titrated to decrease basal heart rate by 20 %) groups. Samples were taken at four time points, and exogenous lactate clearance using an intravenous administration of sodium L-lactate (1 mmol/kg) was performed at the end of the experiment