Predicting Outcome After Cardiac Surgery in Patients With Cirrhosis: A Comparison of Child Pugh and MELD Scores
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1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2004;2: Predicting Outcome After Cardiac Surgery in Patients With Cirrhosis: A Comparison of Child Pugh and MELD Scores AMITABH SUMAN,* DAVID S. BARNES,* NIZAR N. ZEIN,* GAVIN N. LEVINTHAL,* JASON T. CONNOR, and WILLIAM D. CAREY* Departments of *Gastroenterology and Hepatology and Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio Background & Aims: This study aims to quantify the risk of cardiac surgery in patients with cirrhosis. Methods: Records of all adult patients with cirrhosis undergoing cardiac surgery using cardiopulmonary bypass at the Cleveland Clinic (Cleveland, OH) from January 1992 to June 2002 were analyzed for any relationship of Child Pugh class and/or score and Model for End-Stage Liver Disease (MELD) score with outcome measures of hepatic decompensation and death during the first 3 months after surgery. Results: Forty-four patients underwent coronary artery bypass grafting (16 patients), valve surgery (16 patients), a combination of the 2 procedures (10 patients), or pericardiectomy (2 patients). Twelve patients (27%) developed hepatic decompensation, and 7 patients (16%) died. Proportions of hepatic decompensation were 3 of 31, 8 of 12, and 1 of 1 patients, and death, 1 of 31, 5 of 12, and 1 of 1 patients in Child Pugh classes A, B, and C, respectively. The association of hepatic decompensation and mortality with Child Pugh class, Child Pugh score, and MELD score was significant (P < 0.005). Areas under the receiver operating characteristic curves for mortality were similar for Child Pugh ( ) and MELD scores ( ). A cutoff Child Pugh score >7 was found to have a sensitivity and specificity of 86% and 92% for mortality, with a negative value of 97% (95% confidence interval [CI ], 83 99) and positive value of 67% (95% CI, 31 91), respectively. However, a similar cutoff value for MELD score could not be established. Conclusions: Child Pugh score and/or class and MELD score are significantly associated with hepatic decompensation and mortality after cardiac surgery using cardiopulmonary bypass in patients with cirrhosis. Such surgery can be conducted safely in patients with a Child Pugh score <7. Patients with a Child Pugh score >8 have a significant risk for mortality. Patients with cirrhosis are known to be at increased risk for hepatic decompensation after surgery and anesthesia. 1,2 This conclusion is based on retrospective studies involving patients undergoing mostly abdominal surgery. 2 4 There have been only a few reports with small numbers of patients regarding the risks involved in cardiac surgery in patients with cirrhosis, especially for cardiac surgery requiring cardiopulmonary bypass (CPB). 5 9 We therefore decided to analyze our data for cardiac surgery using CPB in patients with cirrhosis to determine the predictors and quantify the risk for hepatic decompensation and mortality. The risk has been estimated by means of the preoperative Child Pugh (CP) class and/or score, which was developed with a view to stratify risk after portosystemic shunt surgery in patients with cirrhosis, 10,11 and has been found over the years to be a reliable predictor of functional status of liver and survival. The Model for End-Stage Liver Disease (MELD) scoring system initially was developed for patients undergoing transjugular intrahepatic portosystemic shunt procedures. 12 It subsequently has been validated for predicting survival in patients with end-stage liver disease. 13 Recently, it was found to be superior to CP score and/or class in predicting 3-month mortality and survival 14 in patients with end-stage liver disease on the liver transplantation wait list. The MELD scoring system has not been used to evaluate surgical risk in patients with cirrhosis. It prompted us to compare it with CP score regarding ability to determine surgical risk and prediction of outcome. Methods The study was performed retrospectively with the approval of the institutional review board. Using computer coding, patients with cirrhosis who underwent cardiac surgery using CPB from January 1992 to June 2002 were identified. Their charts and computer records were studied. A diagnosis of cirrhosis was established from liver biopsy records or a combination of clinical findings and radiological imaging of the liver, including ultrasound, computed tomographic scan, or magnetic resonance imaging, suggestive of cirrhosis. The find- Abbreviations used in this paper: CP, Child Pugh; CI, confidence interval; CPB, cardiopulmonary bypass; INR, international normalized ratio; MELD, Model for End-Stage Liver Disease; PBC, primary biliary cirrhosis by the American Gastroenterological Association /04/$30.00 PII: /S (04)
2 720 SUMAN ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 8 ing of a cirrhotic liver on laparoscopy or laparotomy also was taken as evidence of cirrhosis. Cause of cirrhosis was determined by using the available records. Type of cardiac surgery performed was noted. Preoperative laboratory data and clinical findings and medical history were used to determine CP class and/or score and MELD score for each patient. Intubation time, CPB time, and anesthetic medications administered were obtained from records maintained by the Department of Anesthesiology. The course of events was followed up for up to 3 months after cardiac surgery. The occurrence of hepatic decompensation, evidenced by the new appearance of ascites, portosystemic encephalopathy, jaundice, coagulopathy, variceal bleed, and hepatorenal syndrome, was noted, as was the cause of death in relevant patients. The diagnosis of hepatic encephalopathy was made after ruling out hypoxemia or other metabolic factors, including drug effects responsible for a change in mental status. Patients who underwent liver or cardiac transplantation or had inadequate documentation to support a diagnosis of cirrhosis or inadequate data to calculate CP and/or MELD score were excluded from the study. Statistical Analysis The outcome measures of hepatic decompensation and death were compared with a variety of explanatory variables, including age, sex, cause of cirrhosis, type of cardiac surgery, CP score and/or class, MELD score, bilirubin level, albumin level, international normalization ratio (INR), creatinine level, intubation time, CPB time, and anesthetic medications administered. Relationships between explanatory variables and outcome measures of hepatic decompensation and mortality were assessed by using Fisher s exact tests for categorical variables and Wilcoxon s rank-sum test for continuous variables. The area under the empiric receiver operating characteristic curve for mortality was calculated and plotted for the purpose of comparison. Results Initially, 66 patients with possible cirrhosis undergoing cardiac surgery using CPB were identified. Twenty-two patients were excluded; 13 patients because the diagnosis of cirrhosis was not proven, and 9 patients because of unavailability of sufficient laboratory data. Forty-four patients with cirrhosis undergoing cardiac surgery using CPB were analyzed. Twenty-seven patients (61%) were men. Ages ranged from 15 to 74 years. Causes of cirrhosis were alcohol in 11 patients; hepatitis C, hepatitis B, or autoimmune hepatitis in 3 patients each; and cholestatic liver disease (primary biliary cirrhosis [PBC]/primary sclerosing cholangitis, and cardiac cirrhosis) in 2 patients each. In 20 patients, the cause was unknown. They were classified as cryptogenic. Types of cardiac surgery were coronary artery bypass graft in 16 patients, valve surgery in 16 patients, combined coronary artery bypass graft and valve surgery in 10 patients, and pericardiectomy in 2 patients. All except 1 patient underwent cardiac surgery electively. No patient had congestive heart failure at the time of surgery. The number of patients in CP classes A, B, and C were 31, 12, and 1 at the time of surgery, respectively. Preoperative MELD scores varied from 6 to 27. Twelve patients (27%; 95% confidence interval [CI ], 14 40) developed hepatic decompensation (inclusive of those who died), whereas 7 patients (16%; 95% CI, 5 27) died. Modes of hepatic decompensation were hepatic encephalopathy in 8 patients, ascites in 4 patients, and gastrointestinal bleed, hepatorenal syndrome, and jaundice in 1 patient each. All patients who died had hepatic decompensation; acute renal failure was noted in 6 patients, and sepsis was evident in 5 patients. No patient had cardiac complications contributing directly to death. Numbers of patients who had hepatic decompensation from CP classes A, B, and C were 3 (9.7%), 8 (66%), 1 (100%), and numbers of patients who died were 1 (3%), 5 (41%), and 1 (100%), respectively. Factors found to be significantly associated with hepatic decompensation and death were CP class, CP score, MELD score, bilirubin level, albumin level, and INR (Table 1). Cause of liver disease, type of cardiac surgery, serum creatinine level, CPB time, and intubation time were not found to be associated with either hepatic decompensation or death (Table 1). A cutoff CP score 7 was found to offer 86% sensitivity and 92% specificity for predicting mortality and 66% sensitivity and 97% specificity for hepatic decompensation. For MELD scores, a cutoff value 13 offered 71% sensitivity and 89% specificity for mortality and 67% sensitivity and 97% specificity for hepatic decompensation. Parameters of bilirubin, albumin, and INR did not provide a cutoff value, with sensitivity and specificity as high as CP score (Table 2). Areas under the receiver operating characteristic curve for mortality were similar for CP score and MELD score; and , respectively (P 0.72; Figure 1). A cutoff CP score 7 gave a positive value of 67% (95% CI, 31 91) and a negative value of 97% (95% CI, ) for mortality (Figure 2). No significant association was found between use of medications, including enflurane, isoflurane, fentanyl, midazolam, morphine, and sufentanil, and hepatic decompensation and mortality in 43 patients for whom data were available. Discussion Our report on the outcome of cardiac surgery in patients with cirrhosis is the largest series published to
3 August 2004 CARDIAC SURGERY IN CIRRHOTICS 721 Table 1. Relationship Between Variables and Outcome Measures Hepatic decompensation Death Factor Yes (n 12) No (n 32) P Yes (n 7) No (n 37) P Continuous variables (N 44) Age (yr) a a Bilirubin (mg/dl) a a Albumin (g/dl) a a INR a a Creatinine (mg/dl) a a MELD score a a CP score a a Operating room intubation time (hr) a a CPB time (min) a a Categorical variables Sex 0.99 b 0.40 b Men Women CP class b b A B C CP score a a Type of surgery 0.17 b 0.22 b CABG VS CABG VS Pericardiectomy Cause of cirrhosis 0.83 b 0.87 b Alcohol Cryptogenic Other NOTE. Continuous variables expressed as mean SD, categorical values expressed as number of patients. INR, international normalized ratio; MELD, Model for End-Stage Liver Disease; CP, Child Pugh; CPB; cardiopulmonary bypass; CABG, coronary artery bypass graft; VS, valve surgery. a Wilcoxon s rank-sum test. b Fisher exact test. date. Patients with well-compensated cirrhosis may safely undergo cardiac surgery using CPB. Our data show a similar and significant association of CP score and MELD score with hepatic decompensation and mortality. The best cutoff values of these scores for predicting mortality and hepatic decompensation were 7 for CP score and 13 for MELD score (Figure 3). Although both these cutoff values had high specificity, they lacked Table 2. Sensitivity, Specificity, and Positive and Negative Predictive Values of Different Parameters Mortality Hepatic decompensation Parameters Cutoff value Sensitivity Specificity Positive value Negative value Sensitivity Specificity Positive value Negative value CP score MELD score Bilirubin Albumin INR CP, Child Pugh; MELD, Model for End-Stage Liver Disease; INR, international normalized ratio.
4 722 SUMAN ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 2, No. 8 Figure 1. Receiver operating characteristic curve for mortality. Areas under the curve (AUCs) for Child Pugh (CP) score and Model for End-Stage Liver Disease (MELD) score are similar (P 0.72). sensitivity (Table 2). However, CP scores 7 had high sensitivity, as well, but only for mortality (Table 2) and therefore appear as the most acceptable cutoff value for predicting mortality. Although 1 patient with a CP score 7 died, the mortality rate of 1 of 35 patients (3%) is not different from that of overall mortality in large cardiac surgery databases. 15 Its low sensitivity for hepatic decompensation is consistent with the 4 patients with a Figure 2. Model for End-Stage Liver Disease (MELD) score versus Child Pugh (CP) score. Outcome is denoted as death (D) or survival (S). Figure 3. Model for End-Stage Liver Disease (MELD) score versus Child Pugh (CP) score. Decompensation is denoted as positive ( ) and negative (filled circle). CP score 7 who developed hepatic decompensation. Studies have used CP classification to compare risk among CP classes A, B, and C. None have used CP score as a continuous variable to assess the risk of cardiac surgery. The present study confirms the poor prognosis of patients with CP classes B and C reported elsewhere in much smaller studies. 5 8 At the same time, use of a CP numerical score further refines the conclusion. It aligns patients with CP class B with a score of 7 with patients with CP class A regarding the safety of cardiac surgery. The negative value of 97% for mortality in patients with a CP score 7 appears reassuring given the overall cardiac surgery mortality rate of 4.8% in a multinational database of 19,030 patients. 15 At the same time, risk for mortality increases substantially in those with a CP score 7. MELD score has not been used as a means of assessing surgical risk in patients with cirrhosis. In our study, it turns out to be as good a predictor of hepatic decompensation as CP score, but lacked sensitivity in predicting mortality. The individual parameters of bilirubin, albumin, and INR showed a significant relation with the outcome measures, but none was as strongly associated with mortality and hepatic decompensation as CP score and MELD score. There are few reports of cardiac surgery in patients with cirrhosis. In a retrospective review of 13 patients, Klemperer et al. 5 found an 80% mortality rate in patients with CP class B cirrhosis who underwent surgery, mostly urgently, compared with none in those with CP class A. Bizouarn et al. 6 studied 12 patients, most CP class A, who underwent surgery electively and reported
5 August 2004 CARDIAC SURGERY IN CIRRHOTICS 723 significant hepatic dysfunction in only 2 patients. The experience of elective cardiac surgery in 3 patients with CP class A cirrhosis reported in 2001 did not show postoperative decompensation. 7 In another retrospective study, 8 of 10 patients with cirrhosis undergoing cardiac surgery reported no deaths in 4 patients with CP class A and a 50% mortality rate in 6 patients with CP class B; CPB was used in half these patients. A common conclusion of these studies is that cardiac surgery is reasonably safe in patients with CP class A, whereas it may not be advisable in patients with CP class B. However, the number of patients is uniformly small, and some surgeries were performed on a beating heart. Hence, firm recommendations were difficult to make regarding advisability of cardiac surgery. Moreover, CP class (A, B, and C), rather than number (5 15), was reported; therefore, some patients who are good risks for cardiac surgery (CP class/score B7) might be excluded. In a large retrospective review, patients with PBC were suggested to fare better than those with cirrhosis of other causes, especially cryptogenic cirrhosis, after anesthesia and surgery. 2 However, only 12 patients in that series underwent cardiac surgery, and it is not known how many of them had PBC. We had only 2 patients with PBC and/or primary sclerosing cholangitis, and a valid comparison is not possible, However, a comparison of patients with alcoholic cirrhosis, cryptogenic cirrhosis, and all other causes grouped into one did not show a significant relationship between cause of cirrhosis and hepatic decompensation (P 0.83) or death (P 0.87). Although we found statistically significant results to suggest relationships between many variables and outcome, it was not possible to perform a multivariate analysis because of the small number of events (hepatic decompensation and/or death). It is a difficult problem to solve because most hepatic decompensations and/or deaths occurred in patients with advanced cirrhosis, and they do not undergo surgery frequently. The clinical findings of ascites and hepatic encephalopathy are thought to have some subjectivity involved, and that could mitigate the choice of a CP score cutoff value. However, notwithstanding these limitations, the present study comes to a categorical conclusion. Risks for postoperative mortality for patients with cirrhosis being considered for cardiac surgery using CPB can be assessed accurately by using the numerical CP score. A score 7 is associated with low mortality, whereas a score 7 is associated with a very high mortality rate. A prospective study using the cutoff CP score 7 and involving a large number of patients with CP class B is desirable, but probably not practical, to prove its clinical usefulness. References 1. Friedman LS. The risk of surgery in patients with liver disease. Hepatology 1999;29: Ziser A, Plevak DJ, Wiesner RH, Rakela J, Offord KP, Brown DL. Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery. Anesthesiology 1999;90: Poggio JL, Rowland CM, Gores GJ, Nagorney DM, Donohue JH. A comparison of laparoscopic and open cholecystectomy in patients with compensated cirrhosis and gallstone disease. Surgery 2000;127: Yeh CN, Chen MF, Jan YY. Laparoscopic cholecystectomy in 226 patients. Experience of a single center in Taiwan. Surg Endosc 2002;16: Klemperer JD, Ko W, Krieger KH, Connolly M, Rosengart TK, Altorki NK, Lang S, Isom OW. Cardiac operations on patients with cirrhosis. Ann Thorac Surg 1998;65: Bizouarn P, Ausseur A, Desseigne P, Le Teurnier Y, Nougarede B, Train M, Michaud JL. Early and late outcome after elective cardiac surgery in patients with cirrhosis. Ann Thorac Surg 1999;67: Nimomiya M, Takamoto S, Kotsuka Y, Ohtsuka T. Indication and perioperative management for cardiac surgery in patients with liver cirrhosis. Jpn J Thorac Cardiovasc Surg 2001;49: Kaplan M, Cimen S, Sinen M, Demirtas MM. Cardiac operations for patients with chronic liver disease. Heart Surg Forum 2002; 5: Watanbe Y, Kumon K. Assessment by pulse dye-densitometry indocyanine green (ICG) clearance test of hepatic function of patients before cardiac surgery: its value as a predictor of serious postoperative liver dysfunction. J Cardiothorac Vasc Anesth 1999;13: Child CG III, Turcotte JG. Surgery and portal hypertension. In: Child CG III, ed. The liver and portal hypertension. Philadelphia, PA: Saunders, 1964: Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. 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