Eur J Cardiothorac Surg 2007;31:1094-1098. doi:10.1016/j.ejcts.2007.01.042
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved
Open-heart surgery in patients with liver cirrhosis
Yong An,
Ying-Bin Xiao*,
Qian-Jin Zhong
Department of Cardiovascular Surgery, Xin-Qiao Hospital, Third Military Medical University, ChongQing 400037, China
Received 11 September 2006;
received in revised form 22 January 2007;
accepted 23 January 2007.
* Corresponding author. Tel.: +86 23 68755607; fax: +86 23 68755607. (Email: anyongsmcvs{at}163.com).
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Abstract
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Background: This retrospective study was designed to examine morbidity and mortality rates and to find predictors of outcome in patients with liver cirrhosis (LC) undergoing open-heart surgery. Methods: Between May 1996 and June 2005, 24 patients with LC underwent an open-heart surgery in our institution. Results: There were 14 females and 10 males. Their age ranged from 36 to 72 (average 53 ± 13) years. Seventeen cases were classified as having Child-Pugh class A cirrhosis, six as having class B cirrhosis, and one as having class C cirrhosis. The mean cardiopulmonary bypass (CPB) time and the cross-clamp time were 160 ± 53 and 90 ± 42 min, respectively. In the first 24 h after operation, the mean chest tube output was 1080 ± 320 ml. Mean duration of mechanical ventilation was 32 ± 22 h and mean intensive care unit stay time was 11 ± 8 days. Sixty-six percent of the patients experienced significant morbidity. Fifty-three percent of patients with class A cirrhosis and 100% of those with class B and C cirrhosis suffered postoperative complications. The overall mortality rate was 25%. Postoperative mortality of patients with Child-Pugh class A cirrhosis, class B cirrhosis, and C cirrhosis were 6, 67, and 100%, respectively. Preoperative serum total bilirubin (TB), cholinesterase (ChE), and CPB time were defined as predictors to differentiate survivors and nonsurvivors. Conclusion: Child-Pugh class is related to morbidity and mortality after open-heart surgery in patients with LC. But CPB surgery is associated with higher morbidity and mortality in patients with advanced LC. The increased serum level of TB and the low serum concentration of ChE preoperatively, and the prolonged CPB time were found to be predictors of outcome in patients with LC undergoing open heart surgery.
Key Words: Open-heart surgery • Cardiopulmonary bypass • Liver cirrhosis • Child-Pugh classification • Postoperative complications • Postoperative mortality
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1. Background
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It is well known that liver disease is still a major health problem in Asia [1]. As techniques of open-heart surgery and postoperative patient care improve, the number of patients with preoperative comorbidities who undergo major surgery is increasing. However, clinical outcome after major surgery in patients with more advanced liver dysfunction, i.e., cirrhosis, are still unsatisfactory. Due to the systemic and hepatic effects of cardiopulmonary bypass (CPB), the risk of further hepatic damage during CPB to an already compromised liver must also be a particular concern [2]. In recent studies, open-heart surgery for patients with chronic liver disease was associated with high mortality and morbidity [3–10]. Because the number of patients was small, few reports were definitive. This retrospective study was designed to examine morbidity and mortality rates and to find predictors of outcome in patients with liver cirrhosis (LC) undergoing open-heart surgery.
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2. Patients and methods
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From May 1996 to June 2005, 24 patients with LC underwent open-heart surgery in our institution. Their preoperative status and postoperative clinical results were assessed. The study was performed according to the principles of the Helsinki Declaration of Human Rights and was approved by the Ethics and Research Committee of Human Investigation at Xin-Qiao Hospital. When LC was not confirmed by biopsy, cirrhosis was established from signs of portal hypertension with characteristic morphologic changes of liver and spleen confirmed by ultrasound, computer tomography, and magnetic resonance imaging. Other criteria, such as history of ascites, thrombocytopenia, esophageal varices, typical gastric lesions, and nonspecific biological abnormalities (hyperbilirubinemia, cold agglutinins), were also obtained. The patients were then classified according to the classification of Child-Pugh [11]. Ceftazidime (50 mg/kg) was administrated in 24 cirrhotic patients for antibiotic prophylaxis 24 h before and just before the initiation of CPB. Anesthesia was induced with fentanyl (40–100 µg/kg), etodimate (0.3–0.4 mg/kg) and vecuronium (0.1–0.15 mg/kg). All patients underwent CPB with isovolaemic haemodilution, moderate hypothermia (28 ± 5 °C), roller pump and membrane oxygenator. The perfusion flow was kept over 2.8 l/min/m2 during northemia and over 2.2 l/min/m2 during hypothermia in every patient. The mean arterial pressure (MAP) was kept between 50 and 80 mmHg with dopamine, nitroglycerin, nitroprusside. Arterial blood gas was monitored routinely every half hour or on any occasion when considered necessary. The priming solution contained 1.5–2.0 l of lactated Ringer's solution, heparin (2000 U/l), aprotinin (a loading dose of 2 million KIU, then 500,000 KIU/h), and 0.5–1 unit of packed red cells if blood cardioplegic solution was indicated or predicted hematocrit level during CPB was below 20%. Systemic heparin was given through the right atrium at a dose of 300 U/kg just before cannulation. For valvular replacements operations, either a Carbomedics (Carbomedics, inc) or a St, Jude Medical (St, Jude Medical, inc) Mechanical prosthesis was used. After weaning from CPB and heparin neutralization with 10 mg protamine for each 1000 units of heparin. Packed red blood cells and platelets were infused when necessary. Their clinical data, postoperative complications, and mortality were recorded. Mortality is death during the hospitalization after operation or within 30 days of hospital discharge.
Values of continuous variables were expressed as mean ± standard deviation. Nonparametric tests (Mann–Whitney test and Fisher's exact test) were used for comparison between survivors and nonsurvivors. Values of p less than 0.05 were considered significant. Statistical analyses were performed with computerized statistical packages (SPSS 10.0 software, SPSS, Chicago, IL, USA).
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3. Results
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Perioperative data were summarized in Tables 1 and 2
. There were 14 females and 10 males. Their age ranged from 36 to 72 (average 53 ± 13) years. Of the 24 patients identified with a preoperative history of cirrhosis, 17 cases were classified as having Child-Pugh class A cirrhosis, 6 as having Child-Pugh class B cirrhosis, and 1 as having Child-Pugh class C cirrhosis. The causes of cirrhosis were posthepatitic cirrhosis in 15 patients, cardiac in 7, and alcohol related in 1, and unknown in 1. A variety of cardiac procedures were performed (Table 1). The mean CPB time and the cross-clamp time were 160 ± 53 and 90 ± 42 min, respectively. In the first 24 h after operation, the mean chest tube output was 1080 ± 320 ml (range 350–1800 ml), mean duration of mechanical ventilation was 32 ± 22 h (range 12–120 h), and mean intensive care unit stay time was 11 ± 8 days (range 3–20 days). In the first 48 h after operation, mean transfusion requirements were 5.6 ± 2.4 units. Three of six patients with Child-Pugh class B cirrhosis versus 3 of 17 with class A cirrhosis were returned to the operating room for re-exploration because of excessive mediastinal bleeding or cardiac tamponade.
Postoperative morbidity and mortality were summarized in Table 2, Figs. 1 and 2
. Sixty-six percent of the patients (16 of 24) experienced significant morbidity. Fifty-three percent of patients with Child-Pugh class A cirrhosis and 100% of those with Child-Pugh class B and C cirrhosis suffered postoperative complications. Postoperative major complications, such as infection (42%), re-exploration for mediastinal bleeding (25%), cardiac tamponade (17%), further hepatic dysfunction (25%), renal failure (29%), respiratory failure (31%), heart failure (13%), gastrointestinal disorder (25%), excessive pleural effusion requiring an additional drainage (33%). The overall mortality rate was 25% (6/24). Postoperative mortality of patients with Child-Pugh class A cirrhosis, Child-Pugh class B cirrhosis, and C cirrhosis were 6% (1/17), 67% (4/6), and 100% (1/1), respectively. One patient with Child-Pugh class A cirrhosis died of serious pneumonia because of Fungal infection. The cause of death in patients with Child-Pugh class B cirrhosis were characterized by progressive clinical deterioration associated with major infectious or hemorrhagic complications culminating in hepatic failure (two patients) and multisystem organ failure (two patients). The nonsurvivor with Child-Pugh class C cirrhosis was weaned from CPB with difficulty and died of sepsis and multisystem organ failure.
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Fig. 1. Morbidity and mortality according to Child-Pugh Classification in patients with liver cirrhosis.
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Analysis of possible risk factors for mortality for cirrhotic patients undergoing open-heart surgery was shown in Table 3
. Preoperative serum total bilirubin (TB) concentration (nonsurvivor vs survivor: 26.8 ± 2.6 vs 14.5 ± 2.3 µmol/l, p
= 0.004) was significantly higher only in nonsurvivor group. Serum cholinesterase (ChE) concentration (nonsurvivor vs survivor: 1765 ± 789 vs 3313 ± 1221 IU/l, p
= 0.02) was significantly lower in nonsurvivor group. The CPB time (nonsurvivor vs survivor: 200 ± 53 vs 140 ± 41 min, p
= 0.03) was significantly prolonged in the nonsurvivor group. Preoperative serum TB, ChE, and CPB time were identified as the predictors to difference between survivors and nonsurvivors.
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4. Discussion
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Liver disease is a major source of morbidity and mortality in the intensive care unit (ICU). Cirrhotic patients admitted to the ICU have increased mortality (40–90%) and a poor prognosis [12]. Patients with cirrhosis are known to have high complication and mortality rates after major abdominal operations [13]. Also, patients with cardiac cirrhosis who undergo valve operations are known to have a high operative mortality rate [14,15]. Due to the systemic and hepatic effects of CPB, open-heart surgery for patients with chronic liver disease is associated with high mortality and morbidity. The risk of further hepatic damage during CPB to an already compromised liver must be a concern.
Our data suggest that in patients with LC who undergo open-heart surgery, substantial morbidity and mortality can be expected. The overall morbidity and mortality rate was 66 and 25%, respectively. Postoperative mortality of patients with Child-Pugh class A cirrhosis, Child-Pugh class B cirrhosis, and C cirrhosis were 6, 67, and 100%, respectively, which is similar to that reported early [3,4,8,9]. Recent studies showed that patients with mild cirrhosis tolerated open-heart surgery well. However, It was empirically agreed that cardiac operations using cardiopulmonary bypass are contraindicated in patients with advanced cirrhosis [3,4]. It has been well documented that CPB triggers the production and release of numerous vasoactive substances and cytotoxic mediators that affect coagulopathy, immune system, vascular resistance, vascular permeability, fluid balance, and major organ function [16]. Other contributing factors, such as hypothermia, hemodilution, and hypoperfusion during CPB, also may be responsible for the morbidity and mortality after operation. Previous reports have shown that the higher mortality was not attributable to impaired cardiac function, but to an increased susceptibility to infections, gastrointestinal complications, and bleeding [8]. For patients with hepatic dysfunction, problems with hemostasis can be expected because of thrombocytopenia, platelet dysfunction, decreased hepatic production of coagulation factors, fibrinolysis, and portal hypertension [17]. Similar to these reports, the present study also demonstrated the higher prevalence of infections, such as mediastinitis and septicemia, probably related to poor nutritional state and excessive mediastinal bleeding requiring re-exploration. Also similar to earlier reports [3], the incidence of postoperative fluid retention, characterized by ascite, pericardial effusion, and pleural effusion, was considerably high and management was troublesome in most cases. Poor nutritional status, sodium retention, and portopulmonary hypertension in cirrhotic patients may be responsible for the abnormalities [12,18].
To our knowledge, there are few reports dealing with cardiac surgery in patients with preoperative liver dysfunction, especially posthepatitic cirrhosis. Hill et al. reported two patients with fulminant hepatic failure after cardiac surgery [19]. They mentioned that prolonged CPB time during operation caused postoperative liver dysfunction. However, as reported by Matsuda, hepatic hypoperfusion with subsequent hypoxia also occurs as a result of postoperative low cardiac out states [20]. Study showed that total hepatic blood flow is reduced, but is better maintained by high pump flow than by low pump flow rate [21]. Hypothermic CPB may increase the hepatic circulation, although the additional advantages usually gained by the use of pulsatile perfusion may be partly lost when hypothermia is combined with a high pump flow rate [22]. Moreover, cirrhotic patients have many distinctive anatomical and physiological features that influence postoperative course considerably. For patients with portal hypertension, an increased proportion of the total hepatic blood flow is supplied by the hepatic artery. Therefore, a decrease in arterial pressure or arterial oxygenation is more likely to produce further hepatic damage in these patients as compared with normal patients [19]. In the present study, further hepatic dysfunction was observed in six patients after long CPB time. We believe that prolonged CPB time can be the result of technical difficulties during the operation. Although a prolonged CPB time is not the primary cause of morbidity and mortality, it can influence their prognosis, especially causing further hepatic damage. However, to select the most suitable procedure, preoperative risk analysis must include an assessment of the degree of liver dysfunction. Further studies including more patients are necessary to identify the cirrhotic patients with portal hypertension at risk of developing ascites or severe hepatic dysfunction after cardiac surgery.
Our study also showed that preoperative serum TB, ChE were identified as the predictors to difference between survivors and nonsurvivors. Nonsurvivors presented with significantly higher preoperative bilirubin levels. Patients with hepatic dysfunction, defined as the presence of preoperative jaundice associated with an elevated serum bilirubin above 3 mg/l, experienced a much higher mortality rate compared with the control group [23,24]. In patients with end-stage cardiac failure requiring ventricular assist device, a low preoperative bilirubin level has been shown to be the only significant predictor for survival [25]. Markedly lower value of cholinesterase observed in nonsurvivors would represent bad nutritional status and reduced hepatic reserve [2]. Assessment and optimization of perioperative nutritional status thus are essential for an improvement of postoperative clinical outcomes in such patients.
Besides the Child-Pugh score and CPB time, cardiac surgeon must take preoperative TB and ChE into consideration for patient selection and perioperative management. However, it is difficult to completely evaluate hepatic function with one or two tests because the liver has many functions, accordingly, to estimate hepatic functional reserve. It is necessary to evaluate the overall results of various liver function tests. The results of these different tests do not all indicate the same degree of dysfunction among all patients. Moreover, although these parameters are clinically easy to use for estimating operability, they are not sufficient to select the most suitable operative procedure.
In conclusion, Child-Pugh class is associated with hepatic decompensation and mortality after open-heart surgery using cardiopulmonary bypass in patients with cirrhosis. Such surgery can be performed safely in patients with a Child-Pugh A. But cardiac interventions undergoing CPB for patients with more advanced liver cirrhosis are associated with high mortality and morbidity. The high value of preoperative serum TB, the low value of ChE, and long CPB time are thought to be the predictors of prognosis after open-heart surgery in patients with severe liver cirrhosis. Our findings indicate that open-heart surgery for patients with chronic liver disease should be selected carefully before operation and carried out with a short duration of CPB.
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Abstract
1. Background
