Rotation thromboelastometry velocity curve predicts blood loss during liver transplantation.

BACKGROUND: Patients undergoing liver transplantation (LT) have a high risk of bleeding. The goal of this study was to assess whether the first derivative of the velocity waveform (V-curve) generated by whole blood rotation thromboelastometry (ROTEM®) can predict blood loss during LT. METHODS: Preoperative V-curve parameters were retrospectively evaluated in 198 patients. Patients were divided into quartiles based on blood loss: low (LBL) in the first quartile and high (HBL) in the higher quartiles. A subgroup analysis was performed with patients stratified according to cirrhosis aetiology. A logistic regression model and receiver operator characteristics (ROC) curve were used to test the capacity of the V-curve, to discriminate between LBL and HBL. RESULTS: In the HBL group, the V-curve showed a lower maximum velocity of clot generation (MaxVel), a lower area under maximum velocity curve (AUC), and a higher time-to-maximum velocity (t-MaxVel) than in the LBL group. t-MaxVel was the only parameter showing a capacity to discriminate between the two groups, with a ROC area of 0.69 (95% CI; 0.62-0.74). The ROC area was 0.78 (95% CI; 0.75-0.83) for the 148 patients with cirrhosis, 0.73 (0.60-0.82) for patients with viral hepatitis and 0.83 (0.78-0.96) for patients with alcoholic hepatitis, the group that showed the best discriminative capacity. Moderate but significant correlations were found between all parameters of V-curve and BL. CONCLUSIONS: Pre-transplant V-curve obtained from ROTEM is a promising tool for predicting BL risk during LT, particularly in patients with cirrhosis.

Intraoperative Management of High-Risk Liver Transplant Recipients: Concerns and Challenges.

Liver transplantation (LT) offers patients with liver disease a real chance for long-term survival. In the past decade, successful survival after LT along with the Model for End-Stage Liver Disease-based allocation policy have increased willingness to accept patients with a higher risk profile and marginal organs and to prioritize the sickest patients on the waiting list. Therefore, the anesthesiologist now deals with very challenging patients. In the present review, we aimed to highlight key aspects of intraoperative LT management in high-risk patients and to place these aspects in the perspective of their impact on perioperative outcomes. Conservative standardized perioperative strategies mandate a switch toward accurate and tailored perioperative anesthetic care to maintain the steady improvement in recipient survival rates after LT. In our opinion, continuous assessment of fluid status and cardiac performance, strategies promoting graft decongestion, rational hemostatic management, and the identification of LT recipients with potential risk of vascular complications should constitute the cornerstone of intraoperative management.

Magnesium sulphate and 123I-MIBG in pheochromocytoma: two useful techniques for a complicated disease / Utilidad de la gammagrafia con 123 I-MIBG y del Sulfato de Magnesio en el diagnóstico y tratamiento del feocromocitoma

Pheochromocytoma is a tumour of the chromaffin tissue. It may, through catecholamine release, have deleterious effects on myocardial structure. A 48-year-old woman with a history of hypertension and type II diabetes mellitus (ASA II) was diagnosed of pheochromocytoma-induced myocarditis, which caused severe cardiogenic shock, with an ejection fraction of 20%. Extreme blood pressure swings required aggressive therapy with vasoactive drugs (norepinephrine and dopamine) and an intra-aortic balloon pump, despite which severe haemodynamic instability persisted. Finally, the use of magnesium sulphate allowed for cardiovascular stabilization and weaning off vasoactive drugs prior to surgery. 123I-metaiodobenzylguanidine scintigraphy helps not only to functionally confirm tumour tissue, but also to assess severity and prognosis of cardiac failure. Prognosis of pheochromocytoma-induced heart failure can be very poor. The use of these two well-known and relatively simple ‘tools’ for treatment and prognosis is a helpful option to keep in mind (AU)

Los feocromocitomas son tumores del tejido cromafín. Pueden, a través de la secreción de catecolaminas, causar efectos deletéreos sobre el miocardio. Una mujer de 48 años, con antecedentes de hipertensión arterial y diabetes mellitus tipo II (ASA II) fue diagnosticada de feocromocitoma, con miocardiopatía, y shock cardiogénico con fracción de eyección del 20%. Las extremas oscilaciones hemodinámicas requirieron tratamiento con fármacos vasoactivos (noradrenalina y dopamina) así como el uso de un balón de contrapulsación intra-aórtico, a pesar de lo cual persistía la inestabilidad. Finalmente, el uso de sulfato de magnesio permitió la estabilización de la paciente, pudiéndose retirar las drogas vasoactivas previo a la cirugía. El uso de la gammagrafía con 123-metayodobenzilguanidina sirve no sólo para la clasificación funcional del tejido tumoral, sino también para evaluar la severidad y pronóstico del fallo cardíaco. El pronóstico de la insuficiencia cardíaca inducida por feocromocitoma puede ser grave. El uso de estas conocidas y relativamente sencillas ‘herramientas’ para el tratamiento y el pronóstico son una opción útil a tener en cuenta (AU)

Coagulation profile after plasma exchange using albumin as a replacement solution measured by thromboelastometry.

BACKGROUND: Significant decrease in fibrinogen and other coagulation proteins is observed after plasma exchange when albumin is used as a replacement fluid. Little is known about how those changes impact on thromboelastometry (TEM). The aim of this study was to describe the changes in TEM after performing plasma exchange procedures using 5% albumin as a replacement fluid and its correlation with the standard coagulation tests. STUDY DESIGN AND METHODS: Consecutive patients treated with plasma exchange were prospectively recorded. We performed laboratory and TEM assays extrinsec patway [EXTEM and fibrin-based TEM (fibTEM)] from patient's blood sampled immediately before starting and immediately after finishing each procedure. Bleeding events during and after the procedure were monitored. Mann-Whitney U-test and Spearman's correlation test were used when needed. RESULTS: After plasma exchange, all TEM parameters decreased under normal limits, especially the clotting time (CT): 62% reduction (range: 35-84%) and the fibTEM: 50% (range: 62-27%); maximum clot firmness (MCF) decreased to a lesser extent, 23% (range: 29-21%). Main TEM parameters showed a strong correlation with fibrinogen values: CT, r = -0·81; MCF, r = 0·85; and fibTEM, r = 0·79. No bleeding complications were observed. CONCLUSION: A profound derangement of TEM parameters was observed after PE, evidenced by delay in the clot formation and reduction in the clot firmness. More studies are warranted to elucidate the clinical implications of derangement in TEM parameters in patients without concomitant coagulopathy.

Liver Transplant From Unexpected Donation After Circulatory Determination of Death Donors: A Challenge in Perioperative Management.

Unexpected donation after circulatory determination of death (uDCD) liver transplantation is a complex procedure, in particular when it comes to perioperative recipient management. However, very little has been published to date regarding intraoperative and immediate postoperative care in this setting. Herein, we compare perioperative events in uDCD liver recipients with those of a matched group of donation after brain death liver recipients. We demonstrate that the former group of recipients suffers significantly greater hemodynamic instability and derangements in coagulation following graft reperfusion. Based on our experience, we recommend a proactive recipient management strategy in uDCD liver transplantation that involves early use of vasopressor support; maintaining adequate intraoperative levels of red cells, platelets, and fibrinogen; and routinely administering tranexamic acid before graft reperfusion.

Magnesium sulphate and (123)I-MIBG in pheochromocytoma: Two useful techniques for a complicated disease.

Pheochromocytoma is a tumour of the chromaffin tissue. It may, through catecholamine release, have deleterious effects on myocardial structure. A 48-year-old woman with a history of hypertension and type II diabetes mellitus (ASA II) was diagnosed of pheochromocytoma-induced myocarditis, which caused severe cardiogenic shock, with an ejection fraction of 20%. Extreme blood pressure swings required aggressive therapy with vasoactive drugs (norepinephrine and dopamine) and an intra-aortic balloon pump, despite which severe haemodynamic instability persisted. Finally, the use of magnesium sulphate allowed for cardiovascular stabilization and weaning off vasoactive drugs prior to surgery. (123)I-metaiodobenzylguanidine scintigraphy helps not only to functionally confirm tumour tissue, but also to assess severity and prognosis of cardiac failure. Prognosis of pheochromocytoma-induced heart failure can be very poor. The use of these two well-known and relatively simple 'tools' for treatment and prognosis is a helpful option to keep in mind.

Coagulation profiles of unexpected DCDD donors do not indicate a role for exogenous fibrinolysis.

It has been suggested that vascular stasis during cardio-circulatory arrest leads to the formation of microvascular thrombi and the viability of organs arising from donation after circulatory determination of death (DCDD) donors may be improved through the application of fibrinolytic therapy. Our aim was to comprehensively study the coagulation profiles of Maastricht category II DCDD donors in order to determine the presence of coagulation abnormalities that could benefit from fibrinolytic therapy. Whole blood from potential DCDD donors suffering out-of-hospital cardiac arrest was sampled after declaration of death in the emergency department, and rotational thromboelastomeric analysis was performed. Between July 2012 and December 2013, samples from 33 potential DCDD donors were analyzed. All patients demonstrated hyperfibrinolysis (HF), as reflected by maximum clot lysis of 98-100% in all cases, indicating that there is no role for additional fibrinolytic therapy in this setting. As well, we observed correlations between thromboelastomeric lysis parameters and maximum hepatic transaminase levels measured in potential donors and renal artery flows measured during ex situ hypothermic oxygenated machine perfusion, indicating that further studies on the utility of thromboelastometry to evaluate organ injury and perhaps even viability in unexpected DCDD may be warranted.

Somatostatin therapy protects porcine livers in small-for-size liver transplantation.

Small-for-size (SFS) injury occurs in partial liver transplantation due to several factors, including excessive portal inflow and insufficient intragraft responses. We aim to determine the role somatostatin plays in reducing portal hyperperfusion and preventing the cascade of deleterious events produced in small grafts. A porcine model of 20% liver transplantation is performed. Perioperatively treated recipients receive somatostatin and untreated controls standard intravenous fluids. Recipients are followed for up to 5 days. In vitro studies are also performed to determine direct protective effects of somatostatin on hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). At reperfusion, portal vein flow (PVF) per gram of tissue increased fourfold in untreated animals versus approximately threefold among treated recipients (p = 0.033). Postoperatively, markers of hepatocellular, SEC and HSC injury were improved among treated animals. Hepatic regeneration occurred in a slower but more orderly fashion among treated grafts; functional recovery was also significantly better. In vitro studies revealed that somatostatin directly reduces HSC activation, though no direct effect on SEC was found. In SFS transplantation, somatostatin reduces PVF and protects SEC in the critical postreperfusion period. Somatostatin also exerts a direct cytoprotective effect on HSC, independent of changes in PVF.

Applicability and results of Maastricht type 2 donation after cardiac death liver transplantation.

Maastricht type 2 donation after cardiac death (DCD) donors suffer sudden and unexpected cardiac arrest, typically outside the hospital; they have significant potential to expand the donor pool. Herein, we analyze the results of transplanted livers and all potential donors treated under our type 2 DCD protocol. Cardiac arrest was witnessed; potential donors arrived at the hospital after attempts at resuscitation had failed. Death was declared based on the absence of cardiorespiratory activity during a 5-min no-touch period. Femoral vessels were cannulated to establish normothermic extracorporeal membrane oxygenation, which was maintained until organ recovery. From April 2002 to December 2010, there were 400 potential donors; 34 liver transplants were performed (9%). Among recipients, median age, model for end-stage liver disease and cold and reperfusion warm ischemic times were 55 years (49-60), 19 (14-21) and 380 (325-430) and 30 min (26-35), respectively. Overall, 236 (59%) and 130 (32%) livers were turned down due to absolute and relative contraindications to donate, respectively. One-year recipient and graft survivals were 82% and 70%, respectively (median follow-up 24 months). The applicability of type 2 DCD liver transplant was <10%; however, with better preservation technology and expanded transplant criteria, we may be able to improve this figure significantly.

Liver transplant using donors after unexpected cardiac death: novel preservation protocol and acceptance criteria.

Donors after cardiac death (DCD) suffer irreversible cardiac arrest prior to donation. We describe our liver transplant experience with DCD whose cardiac arrest is unexpected, not following the removal of ventilatory support, whom we maintain with normothermic extracorporeal membrane oxygenation (NECMO). A potential donor goes into cardiac arrest outside the hospital and is brought to the hospital under continuous cardiopulmonary resuscitation (CPR). The donor is declared dead and placed on a cardiocompressor. Femoral vessels are cannulated and connected to cardiopulmonary bypass (CPB) to establish NECMO. Blood parameters and CPB pump flow are monitored throughout NECMO, which is continued until cold preservation. From April 2002 to May 2006, 10 of 40 potential DCD livers were transplanted. Only one graft was lost to primary nonfunction (PNF) and another to hepatic artery thrombosis. Posttransplant hepatic function was good. Certain parameters, such as CPR and NECMO times, hepatic transaminases during NECMO, and donor age, determined the viability of DCD liver grafts and were used to establish criteria for their acceptance. Though considered marginal, unexpected DCD can represent an important source of viable livers for transplant if strict acceptance criteria are employed and they are maintained with NECMO prior to recovery.

Liver transplantation in high-risk patients: hepatopulmonary syndrome and portopulmonary hypertension.

Two pulmonary vascular disorders, considered mutually exclusive, may be present in candidates for orthotopic liver transplantation (OLT). On the one hand, hepatopulmonary syndrome (HPS), with a prevalence about 20% in end-stage liver disease, is characterized by pulmonary vascular dilatation and abnormal gas exchange. On the other hand, portopulmonary hypertension (POPH), a process defined by pulmonary hypertension associated with portal hypertension, is less common than HPS (4%). These entities have very distinct clinical implications; whereas HPS is clinically characterized by respiratory symptoms that evolve to severe hypoxemia, patients with POPH are commonly asymptomatic, frequently diagnosed in the setting of OLT, and the symptoms appear when there is hemodynamic compromise. The pathogenesis of both entities is a putative mechanism, the imbalance of vasoactive substances in pulmonary vessels. The role of OLT to reverse these vascular disorders is controversial, although complete resolution of HPS and, less frequently, POPH following OLT has been reported. The recognition that the presence of both HPS and POPH is an important cause of morbidity and mortality among recipients of OLT has resulted in a change in the policy to select OLT candidates. Accurate identification of patients with pulmonary vascular disorders associated with liver disease should be the first step in the management of OLT candidates. Because the determinants of the prognosis of OLT in the setting of these pulmonary vascular changes have not been well established, an accurate cardiopulmonary evaluation with careful assessment of pulmonary gas exchange (in HPS) and right ventricular function (in POPH) of potential OLT recipients is mandatory before the procedure.

Role of dopamine in renal dysfunction during laparoscopic surgery.

BACKGROUND: Sympathetic vascular insult and hemodynamic changes represent the most reliable explanation of renal impairment resulting from acute intraabdominal pressure. We evaluated the effects of low-dose dopamine administration during a long-lasting surgical laparoscopic procedure. METHODS: For this study 40, patients submitted to a colorectal laparoscopic procedure with 15 mmHg of intraabdominal pressure were randomly allocated to two groups: 20 receiving 2 mg/kg/min of dopamine and 20 receiving the same perfusion of saline. Hemodynamic parameters, renal function, urinary output, and creatinine clearance, were studied. RESULTS: The hemodynamic parameters were similar in both groups. The urinary output decreased during the intraoperative period only the saline group (p = 0.4). Then 2 h postoperatively, it increased in both groups, and no statistically significant differences were found between the groups. The creatinine clearance decreased in both groups during the intraoperative time, but it was worse in the saline group (-28 +/- 120 vs -194 +/- 106; p = 0.022). During the postoperative period, both groups showed improvement, but in control group the values remained lower than at baseline (p = 0.04), and significantly lower than in the dopamine group (230 +/- 337 vs 100 +/- 192; p = 0.012). CONCLUSIONS: An intrabdominal pressure of 15 mmHg induces a time-limited renal dysfunction, and low doses of dopamine could prevent this undesirable effect.

The effects of vasoactive drugs on hepatic blood flow changes induced by CO2 laparoscopy: an animal study.

UNLABELLED: Laparoscopic surgery is associated with systemic and splanchnic hemodynamic alterations. Recent data suggest that small-dose dobutamine may attenuate the reduction in splanchnic blood flow associated with increments in intraabdominal pressure. We conducted this study to analyze the effects of dopamine and dobutamine on the hepatic circulation in this setting. Twenty-one pigs were anesthetized and mechanically ventilated. A flow-directed pulmonary artery and carotid artery catheters were inserted. Perivascular flow probes were placed around the main hepatic artery and the portal vein. CO2 was insufflated into the peritoneal cavity to reach an intraabdominal pressure of 15 mm Hg. After 60 min, animals received dopamine (5 microg x kg(-1) x min(-1); n = 8), dobutamine (5 microg x kg(-1) x min(-1); n = 8), or saline (n = 5) for 30 min. Pneumoperitoneum induced significant increases in heart rate, mean arterial pressure, and systemic vascular resistance, with decreases in cardiac output and hepatic artery and portal vein blood flows. Dobutamine infusion, in contrast to dopamine, corrected, at least in part, cardiac output, systemic vascular resistance, and hepatic artery blood flow alterations, but neither drug restored total hepatic blood flow. IMPLICATIONS: Hepatic blood flow decreases during laparoscopic surgery. A small-dose infusion of neither dobutamine nor dopamine corrects the total hepatic blood flow impairment, but the former is able to restore the hepatic arterial blood supply in an animal model mimicking this condition.

Hepatic xanthine levels as viability predictor of livers procured from non-heart-beating donor pigs.

BACKGROUND: The aim of the present study was to evaluate hepatic content of adenine nucleotides and their degradation products in non-heart-beating donor (NHBD) pigs and its relationship with recipient survival. METHODS: Thirty animals were transplanted with an allograft from NHBDs. After warm ischemia (WI) time (20, 30, or 40 min), cardiopulmonary bypass and normothermic recirculation (NR) were run for 30 min. Afterward, the animals were cooled to 15 degrees C and liver procurement was performed. RESULTS: Survival rate was 100% in the 20WI, 70% in the 30WI, and 50% in the 40WI. Livers from non-surviving animals had higher levels of xanthine after NR than livers from surviving animals. Logistic regression analysis revealed that xanthine at the end of NR was the only variable able to predict survival with a calculated sensitivity of 80% and a specificity of 60%. Prolongation of warm ischemic period leaded to a greater xanthine accumulation as well as increased plasma alpha-glutathione S-transferase levels at reperfusion. Xanthine at NR and alpha-glutathione S-transferase at reperfusion significantly correlated, indicating that donor xanthine contributes to some extent to the severity of the lesion by ischemia-reperfusion. CONCLUSIONS: It is suggested that xanthine content in the donor is able to predict survival after transplantation. Xanthine is significantly involved in the hepatic lesion elicited by warm ischemia and subsequent ischemia-reperfusion associated to liver transplantation from a NHBD.

Bacterial translocation of enteric organisms in patients with cirrhosis.

BACKGROUND/AIMS: The aim of the study was to investigate the prevalence and associated risk factors for bacterial translocation in patients with cirrhosis, a mechanism involved in the pathogenesis of bacterial infections in experimental cirrhosis. METHODS: Mesenteric lymph nodes were obtained for microbiological culture from 101 patients with cirrhosis and from 35 non-cirrhotic patients. RESULTS: Enteric organisms were grown from mesenteric lymph nodes in 8.6% of non-cirrhotic patients. In the 79 cirrhotic patients without selective intestinal decontamination, the prevalence of bacterial translocation significantly increased according to the Child-Pugh classification: 3.4% in Child A, 8.1% in Child B and 30.8% in Child C patients (chi2 = 6.106, P < 0.05). However, translocation by Enterobacteriaceae, the organisms commonly responsible for spontaneous bacteremia and peritonitis in cirrhosis, was only observed in 25% of the cases. The prevalence of bacterial translocation in the 22 cirrhotic patients undergoing selective intestinal decontamination, all Child-Pugh class B and C, was 4.5%. The Child-Pugh score was the only independent predictive factor for bacterial translocation (odds ratio 2.22, P = 0.02). CONCLUSIONS: Translocation of enteric organisms to mesenteric lymph nodes is increased in patients with advanced cirrhosis and is reduced to the level found in non-cirrhotic patients by selective intestinal decontamination.

L-arginine reduces liver and biliary tract damage after liver transplantation from non-heart-beating donor pigs.

BACKGROUND: To evaluate whether L-arginine reduces liver and biliary tract damage after transplantation from non heart-beating donor pigs. METHODS: Twenty-five animals received an allograft from non-heart-beating donors. After 40 min of cardiac arrest, normothermic recirculation was run for 30 min. The animals were randomly treated with L-arginine (400 mg x kg(-1) during normothermic recirculation) or saline (control group). Then, the animals were cooled and their livers were transplanted after 6 hr of cold ischemia. The animals were killed on the 5th day, liver damage was assessed on wedged liver biopsies by a semiquantitative analysis and by morphometric analysis of the necrotic areas, and biliary tract damage by histological examination of the explanted liver. RESULTS: Seventeen animals survived the study period. The histological parameters assessed (sinusoidal congestion and dilatation, sinusoidal infiltration by polymorphonuclear cells and lymphocytes, endothelitis, dissociation of liver cell plates, and centrilobular necrosis) were significantly worse in the control group. The necrotic area affected 15.9 +/- 14.5% of the liver biopsies in the control group and 3.7 +/- 3.1% in the L-arginine group (P<0.05). Six of eight animal in the control group and only one of eight survivors in the L-arginine group developed ischemic cholangitis (P<0.01). L-Arginine administration was associated with higher portal blood flow (676.9 +/- 149.46 vs. 475.2 +/- 205.6 ml x min x m(-2); P<0.05), higher hepatic hialuronic acid extraction at normothermic recirculation (38.8 +/- 53.7% vs. -4.2 +/- 18.2%; P<0.05) and after reperfusion (28.6 +/- 55.5% vs. -10.9 +/- 15.5%; P<0.05) and lower levels of alpha-glutation-S-transferase at reperfusion (1325 +/- 1098% respect to baseline vs. 6488 +/- 5612%; P<0.02). CONCLUSIONS: L-Arginine administration during liver procurement from non heart beating donors prevents liver and biliary tract damage.

Dobutamine restores intestinal mucosal blood flow in a porcine model of intra-abdominal hyperpressure.

OBJECTIVE: To assess the effects of dopamine and dobutamine administration on the systemic and mesenteric (macro- and microvascular) circulatory disturbances induced by intra-abdominal hyperpressure. DESIGN: Prospective, randomized study. SETTING: Animal research laboratory in a university hospital. SUBJECTS: Twenty-five pigs of either gender, weighing 30-35 kg. INTERVENTIONS: Animals were anesthetized, and their lungs were mechanically ventilated. Pulmonary artery flotation and carotid artery catheters were inserted for hemodynamic monitoring and blood sampling. A perivascular flow probe was placed around the superior mesenteric artery, and a laser Doppler probe was positioned in the lumen of the ileum to measure arterial and intestinal mucosal blood flows, respectively. CO2 was insufflated into the peritoneal cavity to reach an intra-abdominal pressure of 15 mm Hg, and 60 mins later, animals received dopamine (5 microg/kg/min; n = 10), dobutamine (5 microg/kg/min; n = 10), or saline (n = 5) for 30 mins. MEASUREMENTS AND MAIN RESULTS: Peritoneal CO2 insufflation induced significant increases in heart rate, arterial pressure, and systemic vascular resistance with concomitant decreases in cardiac output and superior mesenteric arterial and intestinal mucosal blood flows. Although dobutamine infusion reversed the decrease in cardiac output, it failed to restore superior mesenteric artery blood flow; however, intestinal mucosal blood flow returned to baseline levels. Dopamine also attenuated the decrease in cardiac output, but it had no beneficial effect on splanchnic hemodynamic variables. CONCLUSIONS: Low-dose infusion of dobutamine, but not dopamine, corrects the intestinal mucosal perfusion impairment induced by moderate increases in intra-abdominal pressure.