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Intraoperative Management of High-Risk Liver Transplant Recipients: Concerns and Challenges
Intraoperative Management of High-Risk Liver Transplant Recipients: Concerns and Challenges P. Tauraa,*, G. Martinez-Pallia,b, A. Blasia,b, E. Rivasa, J. Beltrana, and J. Balusta a Department of Anesthesiology, Hospital Clinic, University of Barcelona, Barcelona, Spain; and bInstituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain
ABSTRACT 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 EndStage Liver Diseaseebased 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.
L
IVER transplantation (LT) has revolutionized the approach to liver failure, altering the natural history of end-stage liver disease (ESLD), and is now the only definitive treatment for patients in whom conventional medical therapy has failed. The gradual development of the surgical procedure, patient selection, and immunosuppressive therapy have resulted in an overall 1-year survival rate of >80% in patients who would, otherwise, have little or no hope of survival [1]. The morbidity and mortality associated with this complex procedure have steadily declined in recent years. As success with LT has increased, the criteria for selection of recipients and donors have also changed to be less restrictive: Potential recipients excluded because of severe cardiovascular or respiratory disease in the early era of LT are currently accepted in the LT waiting list. The increasing willingness to accept patients with a higher risk profile and suboptimal organs reflects the increased experience and good results in large centers, but it creates a new challenge for intraoperative management. The intraoperative anesthetic approach has been increasingly identified as a driver of perioperative outcomes. In the present paper, we review 3 topics that are currently of significant interest in the setting of the intraoperative management of high-risk LT recipients: 1) the underlying ª 2016 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 48, 2491e2494 (2016)
hemodynamic and cardiac status; 2) management of blood loss and coagulopathy; and 3) prophylaxis and treatment of vascular thrombotic events. HEMODYNAMIC AND CARDIAC STATUS OF LT RECIPIENTS
Cardiac events occur in 25%e70% of patients during and after LT, affecting the graft and patient prognosis. Cardiovascular events remain one of the leading causes of nongraft-related death in LT. The recent interest in cardiac diseases in LT recipients stems from 2 facts. First, LT recipients today are older and have more comorbidities than 30 years ago. At present, the prevalence of coronary artery disease in these patients is at least similar to, if not greater than, that of most other surgical candidates. Second, the hemodynamic stress associated with LT can exacerbate an underlying cardiomyopathy.
*Address correspondence to Pilar Taura, MD, Department of Anesthesiology, Hospital Clinic, University of Barcelona, C/Villarroel 170, 08036 Barcelona, Spain. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.08.020
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TAURA, MARTINEZ-PALLI, BLASI ET AL
A hyperdynamic circulatory state, myocardial dysfunction, and abnormalities in autoregulation vascular tone are the most significant features of ESLD. The recently described cirrhotic cardiomyopathy (CCMP) defines a chronic cardiac dysfunction that is evident under stress conditions and affects >40% of patients with ESLD regardless of the etiology of the liver disease [2e4]. Chronic high cardiac output characteristic of ESLD patients has been invoked as the cause of the constellation of cardiovascular abnormalities that arise in some of these patients. Although the clinical presentation can be variable, all patients have common features: an increase in cardiac output and electrophysiologic abnormalities at early stages of the disease, progressive left ventricular diastolic dysfunction development with attenuated systolic contractile response to stress, and finally cardiac output decrease and cardiac failure. Indeed, the combination of impaired cardiac function and splanchnic arterial vasodilation is the most likely mechanism of hepatorenal syndrome [5]. Although, CCMP is rarely a contraindication to LT, it is considered to be a high-risk condition for intra- and postoperative complications. In fact, the impaired systolic response to stress after reperfusion of the liver graft has been identified as an etiologic factor in the incidence of pulmonary edema and cardiac events after LT [6], and it has also been recognized as a risk factor for post-reperfusion syndrome. Additionally, this hemodynamic derangement makes these patients especially prone to dynamic left ventricular outflow tract obstruction (LVOTO) even with systolic anterior motion (SAM) of the mitral valve. In LT candidates, the prevalence of inducible LVOTO is high (45%) and a preoperative outflow gradient of >36 mm Hg leads to severe intraoperative hypotension, though without a significant impact on outcome [7]. These findings highlight the clinical importance of close monitoring during surgery especially in high-risk recipients.
fluid restriction, whereas others adopt a more liberal strategy. Both excessive vasoconstriction and fluid restriction or aggressive fluid administration can precipitate acute cardiac failure in receptors with a poor cardiac reserve. The need to provide adequate tissue perfusion to distant organs makes it mandatory to match stroke volume and fluid management. Renewed interest in intraoperative hemodynamic monitoring has arisen as a consequence of the progressively increased severity of candidates prioritized by the Model for End-Stage Liver Disease score for graft allocation. Although the use of the pulmonary artery catheter (PAC) has declined owing to its invasive nature and known limitations in measuring preload, most academic centers still use it, particularly in recipients with diagnosed or suspected portopulmonary hypertension (PPHP). The role of nonPACederived parameters that measure pulse pressure and stroke volume variations, as well as extravascular lung water, sounds promising but remains to be determined in complicated LT recipients [8]. In contrast, transesophageal echocardiography (TEE) is becoming an increasingly popular imaging tool in the LT setting because it offers visual information of cardiac structure, filling, and changes in dynamic function and is a relatively noninvasive procedure. Likewise, TEE allows quick assessment of changes in global and regional contractility and rapid diagnosis of ventricular dilation and failure, especially of the right ventricle, which is of particular pathologic importance in patients with PPHP during the liver graft reperfusion [9]. Moreover, with TEE we are able to detect dynamic LVOTO, which is often misdiagnosed. The drawback to the use of TEE is that it requires experience in its use and equipment that may not be available at all centers at all times. Therefore, in the absence of scientific evidence indicating significant differences in patient outcome, the use of both PAC and TEE is advisable in high-risk patients.
Intraoperative Hemodynamic Monitoring
CONTROL OF BLOOD LOSS IN LT AND COAGULATION MANAGEMENT
The surgical procedure in LT characteristically involves challenging intraoperative hemodynamic management for the anesthesiologist. Numerous maneuvers during liver retrieval, portal clamping, and partial or total vena cava cross-clamping and unclamping induce significant hemodynamic fluctuations, leading to dramatic changes in cardiac preload and afterload. To diminish these changes, fluids and vasoconstrictive drugs may be necessary. It is now well known that static cardiac pressure measurements such as central venous pressure (CVP) give only limited information of preload, but they provide continuous information of the backpressure of the inferior vena cava into the new graft and may guide fluid management or the need for vasodilators to prevent injury to the new liver. The use of caval preservation (piggyback) technique or the addition of a venovenous bypass when caval cross-clamp is used may also minimize the large variations in preload. The fluid management of cirrhotic patients undergoing LT remains controversial. Some centers have advocated
LT has traditionally been associated with massive blood loss. Though there has been a great decline in blood product transfusion in the past few years, controlling blood loss remains a significant problem, especially in LT recipients of marginal organs or who are sicker. There is relatively solid evidence that low CVP during hepatic resection and LT surgery can reduce blood loss and allows the surgery to be performed with no requirement for blood transfusion [10]. The maintenance of low CVP by means of restrictive volume reposition avoids venous congestion in the splanchnic area and dilution of coagulation factors, and increases oxygen extraction for the new graft. Although the general tendency is to avoid excessively liberal reposition regimens, the use of lower CVP, particulary in patients with higher thrombotic or renal failure risk, is still debated. Likewise, the routine use of prophylactic antifibrinolytic and/or other prohemostatic agents (rFVIIa and prothrombin complex) is not recommended in the sickest recipients, because these
MANAGEMENT OF HIGH-RISK LT RECEIPIENTS
patients are prone to hypercoagulability status and thrombotic complications. Coagulation homeostasis in patients with cirrhosis has proven to be complex, because it affects pro- and anticoagulant factors as well as thrombocytopenia. Routine coagulation tests are aimed at assessing the patient’s procoagulant capacity and do not reveal possible compensatory effects within the system. Indeed, there is some evidence demonstrating the absence of a link between these tests and bleeding or transfusional needs during LT. Although prolonged prothrombin time/international normalized ratio and low platelet counts suggest a bleeding risk, cirrhotic patients have a “rebalanced” hemostatic system [11] with normal or even higher thrombin generation when measured with global tests such as thrombin generation assays, showing a delicate balance between tendency to bleeding and thrombosis. Importantly, Tripody et al [12] showed that procoagulant imbalance increases with the severity of liver disease (higher levels of von Willebrand factor with lower levels of C protein). Considering that the hemostatic procoagulant imbalance of patients classified as Child C is greater than that of those classified as Child A and B, coagulation parameters should not be corrected before or during surgery in Child C patients unless there is uncontrollable bleeding. Point-of-care coagulation monitoring with the use of whole blood viscoelastic testing (TEG/ROTEM) provides a picture of the complete coagulation process, giving information on the dynamics of clot formation: initiation, propagation, and firmness. In addition, it provides valuable information on the presence and severity of fibrinolysis and hypercoagulability and the presence of endogenous heparinoids related to vascular endothelial damage. It may also accurately guide transfusion needs, reducing the number of blood products transfused. Therefore, the use of viscoelastic testing during LT facilitates the management of 2 important clinical concerns: First, it guides transfusion by administering specific hemostatic agents, thus avoiding empirical administration of blood components; and second, it diagnoses hypercoagulable state and thromboembolic risk, thus allowing prophylactic measures to be started. We could therefore infer that, in very sick patients, the use of the thromboelastogram to manage coagulation is mandatory during LT. EARLY VASCULAR GRAFT COMPLICATIONS: ASSOCIATED COMPLICATIONS OF COMPLEX VASCULAR RECONSTRUCTION
Early vascular graft thrombosis is an important cause of graft failure and is mainly considered to be a surgical complication (small vessels, mismatches, possible intimal dissection, complex vascular anastomosis, and graft interposition). However, recent literature suggests that other nonsurgical factors might also be involved: the use of marginal grafts, overtransfusion, the use of hemostatic agents (rFVIIa, prothrombin complex, and antifibrinolytics), a low artery blood
2493
flow, and thrombophilic donor/recipient conditions may predispose patients to vascular thrombosis. The procoagulant imbalance developed in cirrhotic patients following LT (ie, persistent increase in factor VIII) also should be taken into account [13]. All of this supports the rationale of considering intraoperative or early postoperative prophylactic treatment, particularly in patients with a high risk of thrombosis. However, because of the lack of studies, there is no common consensus about when and how thromboprophylaxis should be given. Hepatic artery thrombosis (HAT) is a life-threatening complication of LT with an incidence of 2%e8% in brain-death-donor and cardiac-death-donor adult recipients, and w10% in living-donor liver transplant recipients. Mortality after HAT is high (50%) and the need for retransplantation is as high as 80%. Thromboprophylaxis Policy
Because flow and pressure are the main determinants of thrombosis, in receptors at high risk of vascular thrombosis the hemodynamic recipient status (euvolemia vs fluid restriction policy) and factors that may decrease hepatic arterial and portal blood flow should be considered. According to the most recent series, heparin seems to be the method of choice to reduce vascular complication in LT. Both unfractionated heparin (UFH) and low-molecular-weight heparin are used for this purpose [14,15]. The efficacy of antiaggregation after arterial reperfusion by aspirin administration reduces the incidence of immediate and early HAT. In our institution, we consider 2 scenarios: First, in patients with arterial blood flow <100 mL/min (after graft inflow modulation) or complex arterial reconstruction (multiple anastomoses, back-table reconstruction of accessory right or left hepatic arteries) 0.5 mg/kg UFH is administered and thereafter (after there is no evidence of bleeding) 100 mg aspirin daily for 6 months; and second, in patients with intraoperative HAT, 0.5 mg/kg UHF plus 325 mg aspirin is administered. At the end of LT, continuous perfusion of UFH is started together with 100 mg aspirin daily if the platelet count is higher than 50 109. Although antithrombotic regimens inevitably involve the risk of bleeding complications, these may be justified by the severity of prothrombotic status in some patients. Close surveillance of all vascular anastomoses with the use of Doppler ultrasonography facilitates early detection and treatment of these complications before irreversible graft failure. CONCLUSION
As success with LT has increased, increasing willingness to accept patients with a higher risk profile and suboptimal organs results in new challenges for intraoperative management. Accurate and tailored perioperative anesthetic care of high-risk LT recipients is required to maintain the steady improvement in recipient survival rates after LT. Continuous assessment of cardiac performance is mandatory during LT to preserve adequate organ perfusion during surgery and to prevent postoperative cardiac and respiratory
2494
complications. The anesthesiologist may be able to assist in decreasing blood loss and transfusion requirements and in promoting graft decongestion by means of reducing CVP. Likewise, intraoperative coagulation monitoring results in rational hemostatic management and guides pharmacologic intervention to treat intraoperative bleeding due to a coagulation defect. LT recipients with potential risk of vascular complications should be identified, and further investigations should confirm the efficacy of prophylactic antithrombotic measures in avoiding early anastomotic thrombosis. REFERENCES [1] Cardenas A, Gines P. Management of complications of cirrhosis in patients awaiting liver transplantation. J Hepatol 2005;1:S124e33. [2] Møller S, Hove JD, Dixen U, Bendtsen F. New insights into cirrhotic cardiomyopathy. Int J Cardiol 2013;167:1101e8. [3] Zardi EM, Abbate A, Zardi DM, Dobrina A, Margiotta D, van Tassell BW, et al. Cirrhotic cardiomyopathy. J Am Coll Cardiol 2010;56:539e49. [4] Nazar A, Guevara M, Sitges M, Terra C, Solà E, Guigou C, et al. Left ventricular function assessed by echocardiography in cirrhosis: relationship to systemic hemodynamics and renal dysfunction. J Hepatol 2013;58:51e7. [5] Krag A, Bendtsen F, Henriksen JH, Moller S. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites. Gut 2010;59:105e10. [6] Escobar B, Taura P, Martinez-Palli G, Fondevila C, Balust J, Beltran J, et al. Stroke volume response to liver graft reperfusion stress in cirrhotic patients. World J Surg 2014;38:927e35.
TAURA, MARTINEZ-PALLI, BLASI ET AL [7] Maraj S, Jacobs LE, Maraj R, Contreras R, Rerkpattanapipat P, Malik TA, et al. Inducible left ventricular outflow tract gradient during dobutamine stress echocardiography: an association with intraoperative hypotension but not a contraindication to liver transplantation. Echocardiography 2004;21: 681e5. [8] Feltracco P, Biancofiori G, Ori C, Saner FH, Della Rocca G. Limits and pitfalls of haemodynamic monitoring systems in liver transplantation surgery. Minerva Anestesiol 2012;78: 1372e84. [9] Burtenshaw AJ, Isaac JL. The role of trans-oesophageal echocardiography for perioperative cardiovascular monitoring during orthotopic liver transplantation. Liver Transpl 2006;12: 1577e83. [10] Massicotte L, Lenis S, Thibeault L, Sassine MP, Seal FR, Roy A. Effect of low central venous pressure and phlebotomy on blood product transfusion requirements during liver transplantations. Liver Transpl 2006;12:117e23. [11] Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010;116: 878e85. [12] Tripodi A, Primignani M, Chantarangkul V, Dell’era A, Clerici M, Franchis R, et al. An imbalance of pro- vs anticoagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009;137:2105e11. [13] Arshad F, Lisman T, Porte RJ. Hypercoagulability as a contributor to thrombotic complications in the liver transplant recipient. Liver Int 2013;33:820e7. [14] Algarni AA, Mourad MM, Bramhall SR. Anticogulation and antiplatelets as prophylaxis for hepatic artery thrombosis after liver transplantation. World J Hepatol 2015;7:1238e43. [15] Vivarelli M, la Barba G, Cuchetti A, Lauro A, del Gaudio M, Ravaioli M, et al. Can antiplatelet prophylaxis reduce the incidence of hepatic artery thrombosis after liver transplantation? Liver Transpl 2007;13:651e4.
ABSTRACT 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 EndStage Liver Diseaseebased 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.
L
IVER transplantation (LT) has revolutionized the approach to liver failure, altering the natural history of end-stage liver disease (ESLD), and is now the only definitive treatment for patients in whom conventional medical therapy has failed. The gradual development of the surgical procedure, patient selection, and immunosuppressive therapy have resulted in an overall 1-year survival rate of >80% in patients who would, otherwise, have little or no hope of survival [1]. The morbidity and mortality associated with this complex procedure have steadily declined in recent years. As success with LT has increased, the criteria for selection of recipients and donors have also changed to be less restrictive: Potential recipients excluded because of severe cardiovascular or respiratory disease in the early era of LT are currently accepted in the LT waiting list. The increasing willingness to accept patients with a higher risk profile and suboptimal organs reflects the increased experience and good results in large centers, but it creates a new challenge for intraoperative management. The intraoperative anesthetic approach has been increasingly identified as a driver of perioperative outcomes. In the present paper, we review 3 topics that are currently of significant interest in the setting of the intraoperative management of high-risk LT recipients: 1) the underlying ª 2016 Elsevier Inc. All rights reserved. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 48, 2491e2494 (2016)
hemodynamic and cardiac status; 2) management of blood loss and coagulopathy; and 3) prophylaxis and treatment of vascular thrombotic events. HEMODYNAMIC AND CARDIAC STATUS OF LT RECIPIENTS
Cardiac events occur in 25%e70% of patients during and after LT, affecting the graft and patient prognosis. Cardiovascular events remain one of the leading causes of nongraft-related death in LT. The recent interest in cardiac diseases in LT recipients stems from 2 facts. First, LT recipients today are older and have more comorbidities than 30 years ago. At present, the prevalence of coronary artery disease in these patients is at least similar to, if not greater than, that of most other surgical candidates. Second, the hemodynamic stress associated with LT can exacerbate an underlying cardiomyopathy.
*Address correspondence to Pilar Taura, MD, Department of Anesthesiology, Hospital Clinic, University of Barcelona, C/Villarroel 170, 08036 Barcelona, Spain. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.08.020
2491
2492
TAURA, MARTINEZ-PALLI, BLASI ET AL
A hyperdynamic circulatory state, myocardial dysfunction, and abnormalities in autoregulation vascular tone are the most significant features of ESLD. The recently described cirrhotic cardiomyopathy (CCMP) defines a chronic cardiac dysfunction that is evident under stress conditions and affects >40% of patients with ESLD regardless of the etiology of the liver disease [2e4]. Chronic high cardiac output characteristic of ESLD patients has been invoked as the cause of the constellation of cardiovascular abnormalities that arise in some of these patients. Although the clinical presentation can be variable, all patients have common features: an increase in cardiac output and electrophysiologic abnormalities at early stages of the disease, progressive left ventricular diastolic dysfunction development with attenuated systolic contractile response to stress, and finally cardiac output decrease and cardiac failure. Indeed, the combination of impaired cardiac function and splanchnic arterial vasodilation is the most likely mechanism of hepatorenal syndrome [5]. Although, CCMP is rarely a contraindication to LT, it is considered to be a high-risk condition for intra- and postoperative complications. In fact, the impaired systolic response to stress after reperfusion of the liver graft has been identified as an etiologic factor in the incidence of pulmonary edema and cardiac events after LT [6], and it has also been recognized as a risk factor for post-reperfusion syndrome. Additionally, this hemodynamic derangement makes these patients especially prone to dynamic left ventricular outflow tract obstruction (LVOTO) even with systolic anterior motion (SAM) of the mitral valve. In LT candidates, the prevalence of inducible LVOTO is high (45%) and a preoperative outflow gradient of >36 mm Hg leads to severe intraoperative hypotension, though without a significant impact on outcome [7]. These findings highlight the clinical importance of close monitoring during surgery especially in high-risk recipients.
fluid restriction, whereas others adopt a more liberal strategy. Both excessive vasoconstriction and fluid restriction or aggressive fluid administration can precipitate acute cardiac failure in receptors with a poor cardiac reserve. The need to provide adequate tissue perfusion to distant organs makes it mandatory to match stroke volume and fluid management. Renewed interest in intraoperative hemodynamic monitoring has arisen as a consequence of the progressively increased severity of candidates prioritized by the Model for End-Stage Liver Disease score for graft allocation. Although the use of the pulmonary artery catheter (PAC) has declined owing to its invasive nature and known limitations in measuring preload, most academic centers still use it, particularly in recipients with diagnosed or suspected portopulmonary hypertension (PPHP). The role of nonPACederived parameters that measure pulse pressure and stroke volume variations, as well as extravascular lung water, sounds promising but remains to be determined in complicated LT recipients [8]. In contrast, transesophageal echocardiography (TEE) is becoming an increasingly popular imaging tool in the LT setting because it offers visual information of cardiac structure, filling, and changes in dynamic function and is a relatively noninvasive procedure. Likewise, TEE allows quick assessment of changes in global and regional contractility and rapid diagnosis of ventricular dilation and failure, especially of the right ventricle, which is of particular pathologic importance in patients with PPHP during the liver graft reperfusion [9]. Moreover, with TEE we are able to detect dynamic LVOTO, which is often misdiagnosed. The drawback to the use of TEE is that it requires experience in its use and equipment that may not be available at all centers at all times. Therefore, in the absence of scientific evidence indicating significant differences in patient outcome, the use of both PAC and TEE is advisable in high-risk patients.
Intraoperative Hemodynamic Monitoring
CONTROL OF BLOOD LOSS IN LT AND COAGULATION MANAGEMENT
The surgical procedure in LT characteristically involves challenging intraoperative hemodynamic management for the anesthesiologist. Numerous maneuvers during liver retrieval, portal clamping, and partial or total vena cava cross-clamping and unclamping induce significant hemodynamic fluctuations, leading to dramatic changes in cardiac preload and afterload. To diminish these changes, fluids and vasoconstrictive drugs may be necessary. It is now well known that static cardiac pressure measurements such as central venous pressure (CVP) give only limited information of preload, but they provide continuous information of the backpressure of the inferior vena cava into the new graft and may guide fluid management or the need for vasodilators to prevent injury to the new liver. The use of caval preservation (piggyback) technique or the addition of a venovenous bypass when caval cross-clamp is used may also minimize the large variations in preload. The fluid management of cirrhotic patients undergoing LT remains controversial. Some centers have advocated
LT has traditionally been associated with massive blood loss. Though there has been a great decline in blood product transfusion in the past few years, controlling blood loss remains a significant problem, especially in LT recipients of marginal organs or who are sicker. There is relatively solid evidence that low CVP during hepatic resection and LT surgery can reduce blood loss and allows the surgery to be performed with no requirement for blood transfusion [10]. The maintenance of low CVP by means of restrictive volume reposition avoids venous congestion in the splanchnic area and dilution of coagulation factors, and increases oxygen extraction for the new graft. Although the general tendency is to avoid excessively liberal reposition regimens, the use of lower CVP, particulary in patients with higher thrombotic or renal failure risk, is still debated. Likewise, the routine use of prophylactic antifibrinolytic and/or other prohemostatic agents (rFVIIa and prothrombin complex) is not recommended in the sickest recipients, because these
MANAGEMENT OF HIGH-RISK LT RECEIPIENTS
patients are prone to hypercoagulability status and thrombotic complications. Coagulation homeostasis in patients with cirrhosis has proven to be complex, because it affects pro- and anticoagulant factors as well as thrombocytopenia. Routine coagulation tests are aimed at assessing the patient’s procoagulant capacity and do not reveal possible compensatory effects within the system. Indeed, there is some evidence demonstrating the absence of a link between these tests and bleeding or transfusional needs during LT. Although prolonged prothrombin time/international normalized ratio and low platelet counts suggest a bleeding risk, cirrhotic patients have a “rebalanced” hemostatic system [11] with normal or even higher thrombin generation when measured with global tests such as thrombin generation assays, showing a delicate balance between tendency to bleeding and thrombosis. Importantly, Tripody et al [12] showed that procoagulant imbalance increases with the severity of liver disease (higher levels of von Willebrand factor with lower levels of C protein). Considering that the hemostatic procoagulant imbalance of patients classified as Child C is greater than that of those classified as Child A and B, coagulation parameters should not be corrected before or during surgery in Child C patients unless there is uncontrollable bleeding. Point-of-care coagulation monitoring with the use of whole blood viscoelastic testing (TEG/ROTEM) provides a picture of the complete coagulation process, giving information on the dynamics of clot formation: initiation, propagation, and firmness. In addition, it provides valuable information on the presence and severity of fibrinolysis and hypercoagulability and the presence of endogenous heparinoids related to vascular endothelial damage. It may also accurately guide transfusion needs, reducing the number of blood products transfused. Therefore, the use of viscoelastic testing during LT facilitates the management of 2 important clinical concerns: First, it guides transfusion by administering specific hemostatic agents, thus avoiding empirical administration of blood components; and second, it diagnoses hypercoagulable state and thromboembolic risk, thus allowing prophylactic measures to be started. We could therefore infer that, in very sick patients, the use of the thromboelastogram to manage coagulation is mandatory during LT. EARLY VASCULAR GRAFT COMPLICATIONS: ASSOCIATED COMPLICATIONS OF COMPLEX VASCULAR RECONSTRUCTION
Early vascular graft thrombosis is an important cause of graft failure and is mainly considered to be a surgical complication (small vessels, mismatches, possible intimal dissection, complex vascular anastomosis, and graft interposition). However, recent literature suggests that other nonsurgical factors might also be involved: the use of marginal grafts, overtransfusion, the use of hemostatic agents (rFVIIa, prothrombin complex, and antifibrinolytics), a low artery blood
2493
flow, and thrombophilic donor/recipient conditions may predispose patients to vascular thrombosis. The procoagulant imbalance developed in cirrhotic patients following LT (ie, persistent increase in factor VIII) also should be taken into account [13]. All of this supports the rationale of considering intraoperative or early postoperative prophylactic treatment, particularly in patients with a high risk of thrombosis. However, because of the lack of studies, there is no common consensus about when and how thromboprophylaxis should be given. Hepatic artery thrombosis (HAT) is a life-threatening complication of LT with an incidence of 2%e8% in brain-death-donor and cardiac-death-donor adult recipients, and w10% in living-donor liver transplant recipients. Mortality after HAT is high (50%) and the need for retransplantation is as high as 80%. Thromboprophylaxis Policy
Because flow and pressure are the main determinants of thrombosis, in receptors at high risk of vascular thrombosis the hemodynamic recipient status (euvolemia vs fluid restriction policy) and factors that may decrease hepatic arterial and portal blood flow should be considered. According to the most recent series, heparin seems to be the method of choice to reduce vascular complication in LT. Both unfractionated heparin (UFH) and low-molecular-weight heparin are used for this purpose [14,15]. The efficacy of antiaggregation after arterial reperfusion by aspirin administration reduces the incidence of immediate and early HAT. In our institution, we consider 2 scenarios: First, in patients with arterial blood flow <100 mL/min (after graft inflow modulation) or complex arterial reconstruction (multiple anastomoses, back-table reconstruction of accessory right or left hepatic arteries) 0.5 mg/kg UFH is administered and thereafter (after there is no evidence of bleeding) 100 mg aspirin daily for 6 months; and second, in patients with intraoperative HAT, 0.5 mg/kg UHF plus 325 mg aspirin is administered. At the end of LT, continuous perfusion of UFH is started together with 100 mg aspirin daily if the platelet count is higher than 50 109. Although antithrombotic regimens inevitably involve the risk of bleeding complications, these may be justified by the severity of prothrombotic status in some patients. Close surveillance of all vascular anastomoses with the use of Doppler ultrasonography facilitates early detection and treatment of these complications before irreversible graft failure. CONCLUSION
As success with LT has increased, increasing willingness to accept patients with a higher risk profile and suboptimal organs results in new challenges for intraoperative management. Accurate and tailored perioperative anesthetic care of high-risk LT recipients is required to maintain the steady improvement in recipient survival rates after LT. Continuous assessment of cardiac performance is mandatory during LT to preserve adequate organ perfusion during surgery and to prevent postoperative cardiac and respiratory
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complications. The anesthesiologist may be able to assist in decreasing blood loss and transfusion requirements and in promoting graft decongestion by means of reducing CVP. Likewise, intraoperative coagulation monitoring results in rational hemostatic management and guides pharmacologic intervention to treat intraoperative bleeding due to a coagulation defect. LT recipients with potential risk of vascular complications should be identified, and further investigations should confirm the efficacy of prophylactic antithrombotic measures in avoiding early anastomotic thrombosis. REFERENCES [1] Cardenas A, Gines P. Management of complications of cirrhosis in patients awaiting liver transplantation. J Hepatol 2005;1:S124e33. [2] Møller S, Hove JD, Dixen U, Bendtsen F. New insights into cirrhotic cardiomyopathy. Int J Cardiol 2013;167:1101e8. [3] Zardi EM, Abbate A, Zardi DM, Dobrina A, Margiotta D, van Tassell BW, et al. Cirrhotic cardiomyopathy. J Am Coll Cardiol 2010;56:539e49. [4] Nazar A, Guevara M, Sitges M, Terra C, Solà E, Guigou C, et al. Left ventricular function assessed by echocardiography in cirrhosis: relationship to systemic hemodynamics and renal dysfunction. J Hepatol 2013;58:51e7. [5] Krag A, Bendtsen F, Henriksen JH, Moller S. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites. Gut 2010;59:105e10. [6] Escobar B, Taura P, Martinez-Palli G, Fondevila C, Balust J, Beltran J, et al. Stroke volume response to liver graft reperfusion stress in cirrhotic patients. World J Surg 2014;38:927e35.
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