Cardiac Surgery in Patients With End-Stage Liver Disease
2012; Elsevier BV; Volume: 28; Issue: 1 Linguagem: Inglês
10.1053/j.jvca.2012.09.018
ISSN1532-8422
AutoresGeraldine C. Diaz, John F. Renz,
Tópico(s)Abdominal vascular conditions and treatments
ResumoANESTHETIC MANAGEMENT of a patient with end-stage liver disease (ESLD) undergoing major cardiac surgery remains a significant clinical challenge. Morbidity typically results from sepsis, multisystem organ failure, or hepatic insufficiency. Previous limitations to only emergency indications have been relaxed, resulting in an increase in the incidence of major cardiac surgery in patients with ESLD.1Kaplan M. Cimen S. Kut M.S. et al.Cardiac operations for patients with chronic liver disease.Heart Surg Forum. 2002; 5: 60-65PubMed Google Scholar, 2Shaheen A.A. Kaplan G.G. Hubbard J.N. et al.Morbidity and mortality following coronary artery bypass graft surgery in patients with cirrhosis: A population-based study.Liver Int. 2009; 29: 1141-1151Crossref PubMed Scopus (52) Google Scholar A review of the New York State Department of Health Cardiac Surgery Registry from 1998 through 2006 showed a 22% increase in the performance of cardiac surgical procedures in patients with known liver disease.3New York State Department of Health Cardiac Surgery: Registryhttp://www.health.ny.gov/statistics/diseases/cardiovascular/Google Scholar This occurred despite liver disease being identified within this registry as a highly significant, independent predictor of poor outcome.3New York State Department of Health Cardiac Surgery: Registryhttp://www.health.ny.gov/statistics/diseases/cardiovascular/Google Scholar Several factors have increased the eligibility of the cirrhotic patient for major cardiac surgery. Foremost, the past 2 decades have witnessed a dramatic advancement in the medical management and life expectancy of patients with cirrhosis.4Sørensen H.T. Thulstrup A.M. Mellemkjar L. et al.Long-term survival and cause-specific mortality in patients with cirrhosis of the liver: A nationwide cohort study in Denmark.J Clin Epidemiol. 2003; 56: 88-93Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar, 5Schuppan D. Afdhal N.H. Liver cirrhosis.Lancet. 2008; 371: 838-851Abstract Full Text Full Text PDF PubMed Scopus (1492) Google Scholar The introduction of prophylactic β-blockers to decrease portal hypertension, the widespread application of endoscopic modalities to treat esophageal varices, the availability of the transjugular intrahepatic portosystemic shunt (TIPS), spontaneous bacterial peritonitis prophylaxis, and effective medications to suppress hepatitis viral replication have increased the life expectancy of patients with ESLD.5Schuppan D. Afdhal N.H. Liver cirrhosis.Lancet. 2008; 371: 838-851Abstract Full Text Full Text PDF PubMed Scopus (1492) Google Scholar Increased longevity has contributed to the increased incidence of hepatocellular carcinoma,6El-Serag H.B. Mason A.C. Rising incidence of hepatocellular carcinoma in the United States.N Engl J Med. 1999; 340: 745-750Crossref PubMed Scopus (2713) Google Scholar, 7El-Serag H.B. Davila J.A. Petersen N.J. et al.The continuing increase in the incidence of hepatocellular carcinoma in the United States: An update.Ann Intern Med. 2003; 139: 817-823Crossref PubMed Scopus (837) Google Scholar a complication of cirrhosis, and coronary artery disease in cirrhotic patients.2Shaheen A.A. Kaplan G.G. Hubbard J.N. et al.Morbidity and mortality following coronary artery bypass graft surgery in patients with cirrhosis: A population-based study.Liver Int. 2009; 29: 1141-1151Crossref PubMed Scopus (52) Google Scholar, 8Kalaitzakis E. Rosengren A. Skommevik T. et al.Coronary artery disease in patients with liver cirrhosis.Dig Dis Sci. 2010; 55: 467-475Crossref PubMed Scopus (73) Google Scholar, 9Morisaki A. Hosono M. Sasaki Y. et al.Risk factor analysis in patients with liver cirrhosis undergoing cardiovascular operations.Ann Thorac Surg. 2010; 89: 811-817Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar The refinement of cardiac and hepatic transplantation subspecialties has improved dramatically the treatment of patients with isolated organ failure. The natural progression of these accomplishments is the extension of expertise to dual-organ failure. Indeed, the annual incidence of combined heart-liver transplantation (CHLT) has more than doubled since 2000 (Fig 1)10United Network for Organ Sharing: Scientific registry of transplant recipientshttp://www.srtr.orgGoogle Scholar and all North American centers that have published on cardiac surgery in the setting of ESLD enjoy robust cardiac and hepatic transplantation programs. Cardiac surgery in patients with ESLD is associated with significant morbidity and mortality.1Kaplan M. Cimen S. Kut M.S. et al.Cardiac operations for patients with chronic liver disease.Heart Surg Forum. 2002; 5: 60-65PubMed Google Scholar, 11Bizouarn P. Ausseur A. Desseigne P. et al.Early and late outcome after elective cardiac surgery in patients with cirrhosis.Ann Thorac Surg. 1999; 67: 1334-1338Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar The principal source of morbidity is the gastrointestinal (GI) tract; cardiovascular complications are less common.2Shaheen A.A. Kaplan G.G. Hubbard J.N. et al.Morbidity and mortality following coronary artery bypass graft surgery in patients with cirrhosis: A population-based study.Liver Int. 2009; 29: 1141-1151Crossref PubMed Scopus (52) Google Scholar The most frequently reported GI complications after cardiac surgery include cholestasis (65%), hemorrhage (25%), and mesenteric ischemia (14%).12Zacharias A. Schwann T.A. Parenteau G.L. et al.Predictors of gastrointestinal complications in cardiac surgery.Tex Heart Inst J. 2000; 27: 93-99PubMed Google Scholar, 13D'Ancona G. Baillot R. Poirier B. et al.Determinants of gastrointestinal complications in cardiac surgery.Tex Heart Inst J. 2003; 30: 280-285PubMed Google Scholar, 14McSweeney M.E. Garwood S. Levin J. et al.Adverse gastrointestinal complications after cardiopulmonary bypass: Can outcome be predicted from preoperative risk factors?.Anesth Analg. 2004; 98: 1610-1617Crossref PubMed Scopus (50) Google Scholar, 15Hessel E.A. Abdominal organ injury after cardiac surgery.Semin Cardiothorac Vasc Anesth. 2004; 8: 243-263Crossref PubMed Scopus (54) Google Scholar Hepatic failure accounts for approximately 4% of observed GI complications but is associated with a mortality >70%.15Hessel E.A. Abdominal organ injury after cardiac surgery.Semin Cardiothorac Vasc Anesth. 2004; 8: 243-263Crossref PubMed Scopus (54) Google Scholar Estimating operative morbidity is difficult. Although liver disease is a recognized risk factor for mortality and complications after cardiac surgery, the widely recognized disease severity scores for cardiac surgery, including the New York Heart Association Functional Classification16Criteria Committee of the New York Heart AssociationNomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels ed 9.in: Little, Brown, Boston, MA1994: 253-256Google Scholar and the European System for Cardiac Operative Risk Evaluation (EuroSCORE),17Roques F. Nashef S.A. Michel P. Risk factors and outcome in European cardiac surgery: Analysis of the EuroSCORE multinational database of 19030 patients.Eur J Cardiothorac Surg. 1999; 15: 816-822Crossref PubMed Scopus (1459) Google Scholar do not adjust for liver disease. Thus, one must derive a prognosis by considering cardiac and hepatic diseases independently. Morbidity and mortality from cardiac surgery in cirrhotic patients correlate to the severity of liver disease.18Klemperer J.D. Ko W. Krieger K.H. et al.Cardiac operations in patients with cirrhosis.Ann Thorac Surg. 1998; 65: 85-87Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 19Hayashida N. Shoujima T. Teshima H. et al.Clinical outcome after cardiac operations in patients with cirrhosis.Ann Thorac Surg. 2004; 77: 500-505Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar, 20Lin C.H. Lin F.Y. Wang S.S. et al.Cardiac surgery in patients with liver cirrhosis.Ann Thorac Surg. 2005; 79: 1551-1554Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 21An Y. Xiao Y.B. Zhong Q.J. Open-heart surgery in patients with liver cirrhosis.Eur J Cardiothorac Surg. 2007; 31: 1094-1098Crossref PubMed Scopus (34) Google Scholar The Child-Turcotte-Pugh (CTP) classification has been the traditional standard for the evaluation of patients with cirrhosis (Table 1).22Child C. Turcotte J. Surgery and portal hypertension.in: The Liver and Portal Hypertension. WB Saunders, Philadelphia, PA1964: 49-50Google Scholar Initially developed to predict surgical mortality after portocaval shunting, the CTP classification is a disease severity index that assigns points to 5 different parameters of hepatic function, creating 3 functional classes of cirrhosis: A, B, and C.22Child C. Turcotte J. Surgery and portal hypertension.in: The Liver and Portal Hypertension. WB Saunders, Philadelphia, PA1964: 49-50Google Scholar The Model for ESLD (MELD) score is a more powerful predictor of ESLD mortality23Wiesner R.H. McDiarmid S.V. Kamath P.S. et al.MELD and PELD: Application of survival models to liver allocation.Liver Transpl. 2001; 7: 567-580Crossref PubMed Scopus (728) Google Scholar that largely has superseded the CTP classification; however, the association of MELD with morbidity and mortality from cardiac surgery has not been validated prospectively.Table 1Child-Turcotte-Pugh Classification22Child C. Turcotte J. Surgery and portal hypertension.in: The Liver and Portal Hypertension. WB Saunders, Philadelphia, PA1964: 49-50Google ScholarMeasurement1 Point2 Points3 PointsBilirubin (mg/dL) 3.0Albumin (g/dL)>3.52.8-3.5 6.0AscitesnoneSlightModerateEncephalopathy (grade)noneI-IIIII-IGradeTotal PointsSurgical RiskA5-6GoodB7-9ModerateC10-15Poor Open table in a new tab The initial comparison of the CTP classification with the MELD as a predictor of outcome after cardiac surgery using cardiopulmonary bypass (CPB) in cirrhotic patients was a retrospective study by Suman et al.24Suman A. Barnes D.S. Zein N.N. et al.Predicting outcome after cardiac surgery in patients with cirrhosis: A comparison of Child-Pugh and MELD scores.Clin Gastroenterol Hepatol. 2004; 2: 719-723Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar The outcome measurements were hepatic decompensation and death within 3 months of surgery. In their analysis, hepatic decompensation and mortality significantly correlated to CTP class, CTP score, and MELD score. A CTP threshold score >7 emerged as the most sensitive predictor of postoperative mortality, with a sensitivity of 86%, specificity of 92%, negative predictive value of 97%, and positive predictive value of 67%, respectively.24Suman A. Barnes D.S. Zein N.N. et al.Predicting outcome after cardiac surgery in patients with cirrhosis: A comparison of Child-Pugh and MELD scores.Clin Gastroenterol Hepatol. 2004; 2: 719-723Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar A significant threshold value for MELD could not be established, perhaps because the MELD is not as sensitive as the CTP class in evaluating portal hypertension and ascites, 2 complications that frequently antagonize postoperative recovery. Filsoufi et al25Filsoufi F. Salzberg S.P. Rahmanian P.B. et al.Early and late outcome of cardiac surgery in patients with liver cirrhosis.Liver Transpl. 2007; 13: 990-995Crossref PubMed Scopus (141) Google Scholar performed a retrospective study of cirrhotic patients undergoing major cardiac surgery at the Mt Sinai Medical Center from 1998 through 2004. This study identified a significant correlation among CTP class, preoperative thrombocytopenia, and hospital mortality that did not exist for the MELD. In addition, CTP class correlated with 1-year survival and the incidence of a major postoperative complication. These data led Filsoufi et al25Filsoufi F. Salzberg S.P. Rahmanian P.B. et al.Early and late outcome of cardiac surgery in patients with liver cirrhosis.Liver Transpl. 2007; 13: 990-995Crossref PubMed Scopus (141) Google Scholar to conclude that CTP class remains the best means of predicting mortality from cardiac surgery. Additional retrospective studies have verified thrombocytopenia as a poor prognostic indicator.9Morisaki A. Hosono M. Sasaki Y. et al.Risk factor analysis in patients with liver cirrhosis undergoing cardiovascular operations.Ann Thorac Surg. 2010; 89: 811-817Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 26Murashita T. Tamura N. Kobayashi T. et al.Preoperative evaluation of patients with liver cirrhosis undergoing open heart surgery.Gen. J Thorac Cardiovasc Surg. 2009; 57: 293-297Crossref PubMed Scopus (21) Google Scholar The identification of thrombocytopenia as an outcomes predictor highlights the sensitivity of CTP class for portal hypertension versus the MELD. Preoperative platelet count varies inversely to CTP class, with thrombocytopenia secondary to splenic sequestration a surrogate for the degree of portal hypertension.25Filsoufi F. Salzberg S.P. Rahmanian P.B. et al.Early and late outcome of cardiac surgery in patients with liver cirrhosis.Liver Transpl. 2007; 13: 990-995Crossref PubMed Scopus (141) Google Scholar This has been supported by additional studies linking thrombocytopenia with the extent of fibrosis and the presence of esophageal varices.27Pohl A. Behling C. Oliver D. et al.Serum aminotransferase levels and platelet counts as predictors of degree of fibrosis in chronic hepatitis C virus infection.Am J Gastroenterol. 2001; 96: 3142-3146Crossref PubMed Google Scholar, 28Sanyal A.J. Fontana R.J. Di Bisceglie A.M. et al.The prevalence and risk factors associated with esophageal varices in subjects with hepatitis C and advanced fibrosis.Gastrointest Endosc. 2006; 64: 855-864Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar Recent data from the United States,29Ailawadi G. LaPar D.J. Swenson B.R. et al.Model for end-stage liver disease predicts mortality for tricuspid valve surgery.Ann Thorac Surg. 2009; 87: 1460-1468Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Europe,30Thielmann M. Mechmet A. Neuhäuser M. et al.Risk prediction and outcomes in patients with liver cirrhosis undergoing open-heart surgery.Eur J Cardiothorac Surg. 2010; 38: 592-599Crossref PubMed Scopus (64) Google Scholar, 31Vanhuyse F. Maureira P. Portocarrero E. et al.Cardiac surgery in cirrhotic patients: Results and evaluation of risk factors.Eur J Cardiothorac Surg. 2012; 42: 293-299Crossref PubMed Scopus (29) Google Scholar and Japan9Morisaki A. Hosono M. Sasaki Y. et al.Risk factor analysis in patients with liver cirrhosis undergoing cardiovascular operations.Ann Thorac Surg. 2010; 89: 811-817Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar have suggested an increasing power of the MELD to predict outcomes in cardiac surgery in cirrhotic patients. Thielmann et al30Thielmann M. Mechmet A. Neuhäuser M. et al.Risk prediction and outcomes in patients with liver cirrhosis undergoing open-heart surgery.Eur J Cardiothorac Surg. 2010; 38: 592-599Crossref PubMed Scopus (64) Google Scholar retrospectively evaluated 57 patients with noncardiac ESLD who underwent cardiac surgery using CPB and compared the MELD, CTP class, and EuroSCORE for predicting mortality. Their analysis showed the MELD to be superior to the CPT class and EuroSCORE. Ailawadi et al29Ailawadi G. LaPar D.J. Swenson B.R. et al.Model for end-stage liver disease predicts mortality for tricuspid valve surgery.Ann Thorac Surg. 2009; 87: 1460-1468Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar determined the MELD was an effective method for risk stratification across patients with ESLD and that a MELD score >15 strongly predicted mortality in patients undergoing tricuspid valve surgery. Although other studies have not validated a linear correlation between the MELD and mortality, several investigators have suggested a potential "threshold" MELD score of 13-15 beyond which mortality noticeably increases.29Ailawadi G. LaPar D.J. Swenson B.R. et al.Model for end-stage liver disease predicts mortality for tricuspid valve surgery.Ann Thorac Surg. 2009; 87: 1460-1468Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 31Vanhuyse F. Maureira P. Portocarrero E. et al.Cardiac surgery in cirrhotic patients: Results and evaluation of risk factors.Eur J Cardiothorac Surg. 2012; 42: 293-299Crossref PubMed Scopus (29) Google Scholar, 32Modi A. Vohra H. Barlow C. Do patients with liver cirrhosis undergoing cardiac surgery have acceptable outcomes?.Interact Cardiovasc Thorac Surg. 2010; 11: 630-634Crossref PubMed Scopus (81) Google Scholar This approximates a borderline CPT classification of B/C.9Morisaki A. Hosono M. Sasaki Y. et al.Risk factor analysis in patients with liver cirrhosis undergoing cardiovascular operations.Ann Thorac Surg. 2010; 89: 811-817Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar A definitive comparison of CTP class with the MELD score will require a large, prospective, randomized trial that is unlikely to occur soon. Currently, all available data have suggested cardiac surgery can be performed safely in patients with CTP class A (Table 2). Significantly higher morbidity and mortality should be anticipated in patients with CTP classes B and C; however, the actual risk in these groups likely has been underestimated in reported series owing to careful patient selection.Table 2Cardiac Surgical Morbidity and Mortality Correlate With Severity of Liver Disease by Child-Pugh ClassStudyYearnA (%)B (%)C (%)Morbidity Klemperer et al18Klemperer J.D. Ko W. Krieger K.H. et al.Cardiac operations in patients with cirrhosis.Ann Thorac Surg. 1998; 65: 85-87Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar19981325100— Bizouarn et al11Bizouarn P. Ausseur A. Desseigne P. et al.Early and late outcome after elective cardiac surgery in patients with cirrhosis.Ann Thorac Surg. 1999; 67: 1334-1338Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar19991250100— Hayashida et al19Hayashida N. Shoujima T. Teshima H. et al.Clinical outcome after cardiac operations in patients with cirrhosis.Ann Thorac Surg. 2004; 77: 500-505Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar20041860100100 Suman et al24Suman A. Barnes D.S. Zein N.N. et al.Predicting outcome after cardiac surgery in patients with cirrhosis: A comparison of Child-Pugh and MELD scores.Clin Gastroenterol Hepatol. 2004; 2: 719-723Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar2004441066100 Lin et al20Lin C.H. Lin F.Y. Wang S.S. et al.Cardiac surgery in patients with liver cirrhosis.Ann Thorac Surg. 2005; 79: 1551-1554Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar200518398080 An et al21An Y. Xiao Y.B. Zhong Q.J. Open-heart surgery in patients with liver cirrhosis.Eur J Cardiothorac Surg. 2007; 31: 1094-1098Crossref PubMed Scopus (34) Google Scholar20072453100100 Filsoufi et al25Filsoufi F. Salzberg S.P. Rahmanian P.B. et al.Early and late outcome of cardiac surgery in patients with liver cirrhosis.Liver Transpl. 2007; 13: 990-995Crossref PubMed Scopus (141) Google Scholar2007272256100Mortality Klemperer et al18Klemperer J.D. Ko W. Krieger K.H. et al.Cardiac operations in patients with cirrhosis.Ann Thorac Surg. 1998; 65: 85-87Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar199813080— Bizouarn et al11Bizouarn P. Ausseur A. Desseigne P. et al.Early and late outcome after elective cardiac surgery in patients with cirrhosis.Ann Thorac Surg. 1999; 67: 1334-1338Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar1999122050— Hayashida et al19Hayashida N. Shoujima T. Teshima H. et al.Clinical outcome after cardiac operations in patients with cirrhosis.Ann Thorac Surg. 2004; 77: 500-505Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar200418050100 Suman et al24Suman A. Barnes D.S. Zein N.N. et al.Predicting outcome after cardiac surgery in patients with cirrhosis: A comparison of Child-Pugh and MELD scores.Clin Gastroenterol Hepatol. 2004; 2: 719-723Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar200444342100 Lin et al20Lin C.H. Lin F.Y. Wang S.S. et al.Cardiac surgery in patients with liver cirrhosis.Ann Thorac Surg. 2005; 79: 1551-1554Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar20051800 An et al21An Y. Xiao Y.B. Zhong Q.J. Open-heart surgery in patients with liver cirrhosis.Eur J Cardiothorac Surg. 2007; 31: 1094-1098Crossref PubMed Scopus (34) Google Scholar200724667100 Filsoufi et al25Filsoufi F. Salzberg S.P. Rahmanian P.B. et al.Early and late outcome of cardiac surgery in patients with liver cirrhosis.Liver Transpl. 2007; 13: 990-995Crossref PubMed Scopus (141) Google Scholar200727111867 Vanhuyse et al31Vanhuyse F. Maureira P. Portocarrero E. et al.Cardiac surgery in cirrhotic patients: Results and evaluation of risk factors.Eur J Cardiothorac Surg. 2012; 42: 293-299Crossref PubMed Scopus (29) Google Scholar2012341840100 Open table in a new tab Additional retrospective studies have suggested increased serum total bilirubin and low serum cholinesterase concentration as potential preoperative indicators18Klemperer J.D. Ko W. Krieger K.H. et al.Cardiac operations in patients with cirrhosis.Ann Thorac Surg. 1998; 65: 85-87Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar, 33Hirata N. Sawa Y. Matsuda H. Predictive value of preoperative serum cholinesterase concentration in patients with liver dysfunction undergoing cardiac surgery.J Card Surg. 1999; 14: 172-177Crossref PubMed Scopus (24) Google Scholar; however, these have not been validated prospectively and serum cholinesterase is not immediately available in North America. The physiologic challenge of cardiac surgery is tolerated poorly in the setting of cirrhosis. Risks associated with all major cardiac surgical procedures, including anesthesia, large-volume transfusion, coagulopathy, and disseminated intravascular coagulation, are amplified in the presence of liver disease. However, the physiologic stress of hypotension, hypoperfusion, and ischemia-reperfusion are the principal elements of hepatic injury. CPB imposes physiologic, immunologic, and metabolic demands on the liver. The hemodynamics of CPB is nonphysiologic, specifically nonpulsatile flow, low cardiac output, and hypotension. Significantly increased levels of circulating endogenous catecholamines released at the initiation of CPB decrease hepatic perfusion by approximately 20% and hepatic arterial blood flow by 20%-45% through vasoconstriction.34Reves J.G. Karp R.B. Buttner E.E. et al.Neuronal and adrenomedullary catecholamine release in response to cardiopulmonary bypass in man.Circulation. 1982; 66: 49-55Crossref PubMed Scopus (194) Google Scholar Decreased arterial flow disrupts circulatory distribution within the liver, resulting in an imbalanced oxygen supply. Decreased hepatic venous oxygen saturation and increased hepatosplanchnic oxygen extraction have been observed.34Reves J.G. Karp R.B. Buttner E.E. et al.Neuronal and adrenomedullary catecholamine release in response to cardiopulmonary bypass in man.Circulation. 1982; 66: 49-55Crossref PubMed Scopus (194) Google Scholar Gårdebäck et al35Gårdebäck M. Settergren G. Brodin L.A. et al.Splanchnic blood flow and oxygen uptake during cardiopulmonary bypass.J Cardiothorac Vasc Anesth. 2002; 16: 308-315Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar observed a 21% decrease in oxygen delivery to the liver and a 46% decrease in oxygen consumption by the liver during 32°F CPB. Decreased oxygen delivery potentiates further catecholamine release, free radical formation, and the generation of vasoactive small molecules within the circulation. Visceral ischemia-reperfusion injury is exacerbated by arterial atherosclerosis, stenosis or occlusion of visceral vessels, and aneurysms that are common in patients with cardiac disease. Poor hepatosplanchnic perfusion antagonizes intestinal mucosal injury, predisposing to endotoxemia, proinflammatory cytokine release, and the systemic inflammatory response syndrome (SIRS). Vasoactive small molecules generated by intestinal anaerobic metabolism, necrotic cellular debris, and translocated bacteria are transported to the liver through the portal vein. This compounds the SIRS response within the liver, increasing the hepatic reserve necessary to facilitate recovery. Thus, hepatic ischemia and necrosis are not solely the result of inadequate arterial supply, but an ischemia-induced loss of the intestinal barrier, resulting in small bowel injury, bacterial translocation, absorption of endotoxin, and an acceleration of SIRS. When the hepatic reserve is exceeded, sepsis, hemorrhage, or multisystem organ failure ensues.36Diaz G.C. Moitra V. Sladen R.N. Hepatic and renal protection during cardiac surgery.Anesthesiol Clin. 2008; 26: 565-590Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar The biliary system is the most metabolically active component of the liver and the principal recipient of the hepatic arterial supply. Active transport is required for biliary epithelia to pump conjugated bilirubin against a concentration gradient from hepatocytes into biliary canaliculi. Thus, the biliary system is exquisitely sensitive to arterial ischemia and biliary dysfunction, the earliest indicator of ischemic liver injury.36Diaz G.C. Moitra V. Sladen R.N. Hepatic and renal protection during cardiac surgery.Anesthesiol Clin. 2008; 26: 565-590Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Ischemia-induced biliary dysfunction is the etiology of the frequently observed cardiac surgical complications of "post-pump jaundice" and acalculous cholecystitis described >20 years ago.37Collins J. Ferner R. Murray A. et al.Incidence and prognostic importance of jaundice after cardiopulmonary bypass surgery.Lancet. 1983; 321: 1119-1123Abstract Scopus (0) Google Scholar Increased hepatic transaminases do not indicate hepatic arterial insufficiency reliably because liver-specific alanine and aspartate aminotransferases are released from hepatocytes that have significant potential for anaerobic metabolism. Furthermore, alanine and aspartate aminotransferases are not distributed uniformly throughout the liver but are most concentrated in the periportal zones, whereas the centrilobular zones are the most susceptible to early ischemic injury.36Diaz G.C. Moitra V. Sladen R.N. Hepatic and renal protection during cardiac surgery.Anesthesiol Clin. 2008; 26: 565-590Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 38Rao P.N. Bronsther O.L. Pinna A.D. et al.Hyaluronate levels in donor organ washout effluents: A simple and predictive parameter of graft viability.Liver. 1996; 16: 48-54Crossref PubMed Scopus (17) Google Scholar Increased alkaline phosphatase and γ-glutamyl transpeptidase are more sensitive predictors of acute biliary ischemia than transaminases but do not correlate linearly to the extent of hepatic injury.38Rao P.N. Bronsther O.L. Pinna A.D. et al.Hyaluronate levels in donor organ washout effluents: A simple and predictive parameter of graft viability.Liver. 1996; 16: 48-54Crossref PubMed Scopus (17) Google Scholar Hypotension, hypoperfusion, coagulopathy, hemorrhage, and transfusion are routine elements of cardiac surgery that impair hepatic metabolism. Contact activation of factor XII by the extracorporeal circuit stimulates inflammation by the activation of the intrinsic coagulation pathway, kallikrein, and complement. This is cascaded through platelet aggregation, debris, and microemboli formed within the bypass tubing.39Pearson D.T. Holden M.P. Poslad S.J. et al.A clinical evaluation of the gas transfer characteristics and gaseous microemboli production of two bubble oxygenators.Life Support Syst. 1984; 2: 252-266PubMed Google Scholar, 40Blauth C.I. Cosgrove D.M. Webb B.W. et al.Atheroembolism from the ascending aorta An emerging problem in cardiac surgery.J Thorac Cardiovasc Surg. 1992; 103: 1104-1112Abstract Full Text PDF PubMed Google Scholar, 41Doty J.R. Wilentz R.E. Salazar J.D. et al.Atheroembolism in cardiac surgery.Ann Thorac Surg. 2003; 75: 1221-1226Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar An emerging hypothesis is the potential of improved outcomes through CPB avoidance. In patients with normal hepatic function, prospective, randomized trials have shown CPB does not affect significantly the development of GI complications.42Velissaris T. Tang A. Murray M. et al.A prospective randomized study to evaluate splanchnic hypoxia during beating-heart and conventional coronary revascularization.Eur J Cardiothorac Surg. 2003; 23: 917-924Crossref PubMed Scopus (52) Google Scholar, 43Musleh G.S. Patel N.C. Grayson A.D. et al.Off-pump coronary artery bypass surgery does not reduce gastrointestinal complications.Eur J Cardiothorac Surg. 2003; 23: 170-174Crossref PubMed Scopus (56) Google Scholar, 44Ascione R. Talpahewa S. Rajakaruna C. et al.Splanchnic organ injury during coronary surgery with or without cardiopulmonary bypass: A randomized, controlled trial.Ann Thorac Surg. 2006; 81: 97-103Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar However, limited observational data from patients with known liver disease have suggested an advantage to avoiding CPB. Gaudino et al45Gaudino M. Santarelli P. 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