Safety and efficacy of combined orthotopic liver transplantation and coronary artery bypass grafting

Authors

  • David Axelrod,

    1. Division of Organ Transplantation, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
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  • Alan Koffron,

    Corresponding author
    1. Division of Organ Transplantation, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
    • Division of Organ Transplantation, Feinberg School of Medicine, Galter Pavillion Suite 17-200, 675 North St. Clair, Chicago, IL 60611
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    • Telephone: 312-695-8900; FAX: 312-695-9194

  • Andre DeWolf,

    1. Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, IL
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  • Alfred Baker,

    1. Division of Hepatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL
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  • John Fryer,

    1. Division of Organ Transplantation, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
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  • Talia Baker,

    1. Division of Organ Transplantation, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
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  • James Frederiksen,

    1. Division of Cardiothoracic Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
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  • Keith Horvath,

    1. Division of Cardiothoracic Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
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  • Micheal Abecassis

    1. Division of Organ Transplantation, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL
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Abstract

Advanced coronary artery disease (CAD) is increasingly common in patients awaiting orthotopic liver transplantation (OLT). Unfortunately, in patients whose coronary artery anatomy is not amenable to angioplasty, coronary artery bypass grafting (CABG) alone may precipitate hepatic decompensation. Thus, combined liver transplant and coronary artery bypass grafting (CABG-OLT) may be required to effectively treat both conditions. Clinical records were analyzed for 5 CABG-OLT procedures at a single institution. Operative indications, technical details, and postoperative course were determined for each patient. Patients undergoing CABG-OLT had a mean age of 57.8 years (range, 54-66) and were predominantly male (80%). All patients had significant 3-vessel coronary atherosclerotic disease with preserved left ventricular function. There were no intraoperative deaths. At mean 25 months of follow-up (range, 8.0-25) there was an 80% graft and patient survival. Overall average length of stay was 21 days (range, 7-59 days). In conclusion, CABG-OLT procedure appears to be safe and effective in the population of patients with advanced CAD and liver disease. In this series, patients appear to benefit from multidisciplinary preoperative evaluation, coordination between cardiac and transplant surgeons, careful graft selection, and use of sapheno-atrial veno-veno bypass. (Liver Transpl 2004;10:1386–1390.)

Improvements in surgical and anesthetic techniques have allowed orthotopic liver transplantation (OLT) to be performed in older patients with a higher incidence of advanced atherosclerotic coronary artery disease (CAD).1 The presence of CAD conveys a significant risk of perioperative morbidity and mortality following OLT and thus may preclude transplant.2 While percutaneous transluminal coronary angioplasty can often be used in the pretransplant setting, patients with lesions that are not amenable to percutaneous transluminal coronary angioplasty require coronary artery bypass grafting (CABG). Although CABG can be performed prior to OLT, patients with advanced but stable liver disease can rapidly progress to hepatic decompensation following general anesthesia and cardiopulmonary bypass (CPB), thus precluding operative repair of their CAD.3, 4 It is in this difficult population, that a combined coronary artery bypass graft and orthotopic liver transplant (CABG-OLT) may be required to treat both conditions.

Previous reports of combined CABG-OLT have been limited to a few case reports.58 We present a single institution's experience with 5 patients treated with this combined procedure to define the indications, operative technique, anesthetic management, and postoperative results.

Abbreviations:

OLT, orthotopic liver transplant; CABG, coronary artery bypass grafting; CABG-OLT, combined coronary artery bypass graft and orthotopic liver transplant; CAD, coronary artery disease; CPB, cardiopulmonary bypass; ESLD, end-stage liver disease; EF, ejection fraction; ACT, activated clotting time.

Patients and Methods

A total of 400 adult OLTs have been performed at our institution since 1994, including 5 patients who underwent a combined CABG-OLT. Medical and anesthetic records of these patients were retrospectively reviewed. This project was approved by the Northwestern University Medical School institutional review board.

Pretransplant Evaluation

Prior to OLT, a multidisciplinary team including surgery, hepatology, cardiology, and anesthesiology personnel evaluates patients. All patients routinely undergo a rigorous cardiac evaluation including myocardial perfusion scan or stress echocardiography. Patients with evidence of myocardial ischemia are evaluated with coronary angiography. Patients were considered for CABG-OLT if they had evidence of significant disease in 2 or more coronary arteries that was not amenable to percutaneous transluminal coronary angioplasty. Patients with significant left ventricular dysfunction or nonreconstructible coronary anatomy were excluded. Following medical and cardiac evaluation, patients were listed for OLT with the United Network for Organ Sharing.

Operative / Anesthetic Management

Once the patient was allocated an organ by the United Network for Organ Sharing and the onsite procurement team confirmed the quality of the organ, the patient was brought to the operating room. General anesthesia was induced and maintained using inhalation, narcotic, and paralytic agents. A pulmonary artery catheter allowing measurement of mixed-venous oxygen saturation was placed in all patients in addition to radial and femoral arterial catheters. A transesophageal echocardiography probe was placed for continuous monitoring of cardiac function.9

In patients without a diagnosis of cancer, the cardiac portion of the procedure was performed first, while in the case of known malignancy, the abdomen was entered first to exclude the presence of metastatic disease. After drainage of ascites fluid, if necessary, the chest was entered through a median sternotomy incision. If not previously opened, the peritoneal cavity was not entered to avoid contamination of the bypass circuit by ascitic fluid. After heparinization to achieve an activated clotting time (ACT) > 480 seconds, the patients were placed on CPB using right atrial and aortic cannulation. Aortocoronary bypass was performed using reversed saphenous vein grafts and internal mammary artery arteries as needed. Following construction of the proximal anastomoses, the patients were weaned from CPB and the heparinization was reversed with protamine. Finally, the aortic cannula was removed and the right atrial cannula was left in place as outflow for porto-systemic veno-venous bypass used during OLT. Aprotinin was administered to 2 patients (2,000,000 kallikrein inhibitory units over 30 minutes followed by 500,000 kallikrein inhibitory units per hour for the remainder of the procedure). The sternum and pericardial cradle were left open and protected with saline-soaked sponges to allow inspection for hemostasis during the OLT.

The abdomen was then entered using a bilateral subcostal incision with a midline extension. The liver was mobilized by dividing the ligamentous attachments. Next, the portal structures were dissected and the portal vein was mobilized to facilitate portal-sapheno-atrial bypass. The patients' left sapheno-femoral junction was identified and a heparin coated bypass cannula was inserted proximally. The portal vein was then cannulated using a heparin coated bypass cannula and portal-systemic veno-venous bypass was initiated using the atrial cannula for outflow. The remainder of the hepatectomy was completed, and the allograft was then anastomosed using either standard technique or side-to-side-venacavaplasty.10 The portal bypass cannula was then removed and the portal venous anastomosis was constructed. Portal-systemic veno-venous bypass was then terminated and the atrial and femoral cannulas were removed. Next, the arterial anastomosis was performed. At the conclusion of the arterial anastomosis, the patient's hepatic coagulopathy was reversed using protamine and fresh frozen plasma. Finally, the biliary anastomosis was completed using a choledochocholedochostomy without placement of a t-tube. At this point, the cardiac team returned to inspect for hemostasis and close the sternotomy using pleural and mediastinal drainage tubes. Next the abdominal incision was closed following the placement of Jackson-Pratt drains as needed and the patient was transferred to the surgical intensive care unit.

Protocols for the care of patients undergoing CABG-OLT were developed and implemented prior to the first procedure. The patient remained in the intensive care unit until extubated and hemodynamically stable. Once extubated, the patients were rapidly transferred to the general care floor and were discharged following the removal of all chest drains and the resumption of enteral nutrition. Postoperative immunosuppression consisted of tacrolimus and steroids.

Results

Patients undergoing combined CABG-OLT had a mean age of 57.8 years (range, 54-66 years) and were 80% male (Table 1). The patients' end-stage liver disease (ESLD) was a result of hepatitis C infection (60%), nonalcoholic steatohepatitis (20%), or polycystic liver disease (20%). Each had developed significant complications from their ESLD, including hepatocellular carcinoma in 60%.

Table 1. Patient Demographic Information
Patient NumberAge (yr)GenderUNOS/MELD StatusDiagnosisIndication for Transplant
  1. Abbreviation: SBP, spontaneous bacterial peritonitis.

148M2A (19)Hepatitis C, EtOH abuseAscites, variceal bleeding, SBP
266F2B (9)Hepatitic CHepatocellular carcinoma
363M29Nonalcoholic steatohepatitisHepatocellular carcinoma, ascites
454M31Hepatitis C, EtOH abuseHepatocellular carcinoma
558M26Polycystic liver diseaseAbdominal pain

Cardiac evaluation demonstrated preserved left ventricular function in all patients (mean ejection fraction, 59%) (Table 2). All patients had either significant 3-vessel CAD or left main coronary artery (LM) disease diagnosed by coronary angiography prior to transplant. No patient in this series underwent percutaneous treatment of his CAD.

Table 2. Cardiac Evaluation
Patient NumberEjection Fraction% Occlusion of Coronary Artery
Left MainLeft Anterior DescendingRight Circumflex ArteryCircumflex
160% 70%50%30%
260% 80%60%30%
360% 70%70%50%
455% 70%95%50%
560%50%90%50% 

CABG was performed to provide complete revascularization (Table 3). The mean time on coronary artery bypass was 99 minutes (range, 68-125 minutes). In the first 3 liver transplants, standard bicaval anastomoses were performed, while in the last 2 cases, a side-to-side venacavaplasty technique was utilized. The portal vein and hepatic artery reconstruction was performed in the standard fashion and a primary choledochocholedochostomy without t-tube was utilized for the biliary system. The mean overall case time was 834 minutes (range, 705-932 minutes).

Table 3. Operation Performed
Patient NumberBypassOLT
  1. Abbreviations: LAD, left anterior descending; RCA, right circumflex artery; CIRC, circumflex.

13 vessels: LAD, RCA, CIRCStandard bicaval anastomosis
23 vessels: LAD, RCA, CIRCStandard bicaval anastomosis
33 vessels: LAD, RCA, CIRCStandard bicaval anastomosis
42 vessels: LAD, RCASide to side venacavaplasty
52 vessels: LAD, RCASide to side venacavaplasty

There were no perioperative mortalities, although 1 patient died 5 months postoperatively from the complications of aggressive, severe recurrent hepatitis C infection with a cholestatic pattern and liver failure (Table 4). Postoperative morbidity included a pericardial effusion requiring reoperation (n = 1), a postoperative cardiac arrest requiring defibrillation (n = 1), acute rejection (n = 1), and an episode of nosocomial pneumonia (n = 1) in a patient requiring a prolonged intensive care unit stay. There were no incidences of sternal or abdominal wound infection, reoperation for intrathoracic or intraabdominal bleeding, or infection. One patient did require reoperation for persistent pericardial effusion treated with a pericardial window. The mean length of intensive care unit stay postoperatively was 10 days (range, 2-40 days) and the average overall length of hospital stay was 21 days (range, 7-59 days). The majority of patients (4 / 5) were discharged to home, while 1 patient required a brief inpatient rehabilitation stay. Cardiac function was well preserved except in the case of the patient who experienced the cardiac arrest (Table 5). Four of the 5 patients demonstrated an ejection fraction that was within normal limits. Troponin I values were elevated in 2 of the 5 patients, including the individual who was cardioverted. At a average follow up of 18 months (range, 10-43 months), 4 / 5 of the patients are alive with excellent allograft and cardiac function.

Table 4. Postoperative Course
Patient NumberLength of Follow-upStatusICU LOS (Days)Hospital LOS (Days)Complications
  1. Abbreviations: ICU, intensive care unit; LOS, length of stay.

143 monthsAlive29Pericardial effusion
22.5 monthsDead216Cardiac arrest 2.5 months post operatively
324 monthsAlive4059Postoperative cardiac arrest, pneumonia
410 monthsAlive414Acute rejection
510 monthsAlive27None
Table 5. Cardiac Results
Patient NumberPost CABG-EFECG ChangesPeak Troponin I
  1. Abbreviations: ECG, echocardiogram; CABG-EF, coronary artery bypass grafting-ejection fraction.

1>55%NoneNA
2>55%None12.5
335% with diffuse hypokinesisAnteroseptal ischemia97.2
4>55%NoneNA
5>55%NoneNA

Discussion

Coexisting cardiac and ESLD presents a formidable clinical challenge and is indicated in patients with advanced liver and cardiac disease. In this series, combined CABG-OLT appears to be a safe and effective approach to patients with severe CAD and ESLD. We have found that intensive care unit stays have been brief (mean, 2.5 days) and patients recovered sufficiently to be discharged to home (80%), excluding the single patient with a prolonged intensive care unit and rehabilitation stay resulting from postoperative cardiac dysfunction and pneumonia. Furthermore, in our series, there have been no deaths in the perioperative period and the 80% survival at 1 year is equivalent to other widely reported series following OLT alone.11

Combined liver and coronary disease is fairly common among older patients being evaluated for OLT. In patients greater than 50 years old being evaluated for OLT, there is a 16.2% incidence of severe CAD (coronary arterial stenosis > 70%).1 Furthermore, 13.3% of OLT candidates in this age group were asymptomatic despite angiographically evident severe CAD. Given the high incidence of asymptomatic disease, additional evaluation is needed. The results of dobutamine stress echocardiography have been mixed with some investigators reporting good results12 and others reporting in low-negative predictive values.13 Despite the overall utility of dobutamine stress echocardiography, patients at high risk, including those with clinical signs or symptoms or diabetes, may benefit from angiography to exclude the presence of clinically significant CAD.

CABG-OLT represents a very small percentage of the patients transplanted with significant CAD. In general, a staged procedure using percutaneous transluminal coronary angioplasty is best if the patient can tolerate this approach and has appropriate anatomy. In patients with moderate ESLD, who can survive CABG alone, this procedure should be carried out first. In the rare instance of rapid progression to liver failure, patients can be urgently transplanted. While there may be an increased risk of morbidity at the time of CABG, OLT following CABG can be safely performed.14 In patients with mild to moderate cardiac disease, it may be best to acceptable to proceed with OLT to reduce the risk of perioperative bleeding and liver decompensation. In this population, CABG after OLT was not associated with significantly increased mortality or morbidity, compared with CAGB alone.15, 16 CABG did result in a minor increase in transaminases, but did not result in rejection or allograft loss. The main indication for a combined procedure is the presence of significant, high-risk coronary lesions with preserved left ventricular function and very advanced liver disease. In this series, the majority of patients (4 / 5) had Childs-Turcotte-Pugh class C cirrhosis precluding CABG without transplant, while the remaining patient had compensated cirrhosis and hepatocellular carcinoma.

Several technical features of the combined procedure appear to be associated with the excellent results observed here. Donors were carefully selected to reduce the risk of primary nonfunction or primary dysfunction that would complicate the perioperative course. Early graft dysfunction could predispose the patient to significant hemorrhage, increasing the risk of perioperative cardiac tamponade. Next, all patients were managed with continuous transesophageal echocardiography (TEE) to facilitate their course on CPB and during the OLT.9 TEE facilitated careful monitoring of volume status and guided the use of intraoperative vasopressor agents.

During the operation, all patients were successfully weaned from CPB prior to the initiation of recipient hepatectomy. Prolonged use of CPB has been associated with significant intraoperative blood loss. In addition, the sternotomy wound was not closed during the performance of the OLT. Consequently, the mediastinum could be intermittently inspected to ensure hemostasis, the right atrial cannula was available for outflow from the veno-veno bypass circuit, and the surgical exposure was excellent even in the case of polycystic liver disease and massive hepatomegaly. Despite this prolonged period with an open sternotomy, including manipulation of the biliary tree, there were no postoperative sternal wound infections. Recently, we found that the use of side-to-side venacavaplasty resulted in reduced warm and cold ischemic times, easier hepatectomy, and markedly reduced operative times.10 All patients were placed on veno-veno bypass to provide maximum hemodynamic stability during the OLT. Finally, patients were carefully monitored in the postoperative period using ultrasonography within 12 hours to identify potentially correctable problems with the vascular or biliary anastomoses.

In conclusion, combined CABG-OLT appears to be a safe and effective procedure in patients with severe CAD and ESLD. The 1-year mortality rates are comparable with OLT alone and, in general, intensive care unit stay and length of hospital stay do not appear to be prolonged. CABG-OLT should be offered to patients with severe CAD who would otherwise be denied OLT due to their cardiac risk factors.

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