Combined aortic valve replacement and orthotopic liver transplantation

CASE REPORTS

Combined Aortic Valve Replacement and Orthotopic Liver Transplantation Brian M. Parker, MD, James T. Mayes, MD, J. Michael Henderson, MD, and Robert M. Savage, MD

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ULTIPLE ORGAN transplantation including combined procedures involving the liver and the heart have been reported previously,1-7 but the number of these cases in the literature is small. Severe valvular heart disease not requiring orthotopic heart transplantation may occasionally be encountered in patients with end-stage liver disease (ESLD). Several cases of valvular heart disease requiring either valve repair or replacement secondary to bacterial endocarditis performed subsequent to orthotopic liver transplantation (OLT) have been reported.8-11 Two instances of aortic valve replacement (AVR) for aortic stenosis after liver transplantation have been presented in the literature.12,13 The authors now report the first case of combined AVR and OLT. CASE REPORT

A 56-year-old man with Laennec’s cirrhosis was evaluated at this institution for OLT in 1996. Presenting symptoms of ESLD included fatigue, easy bruising, mild encephalopathy, and ascites. Past medical history was significant for insulin-dependent diabetes mellitus, mild emphysema with a 40-pack year history of tobacco abuse, mild renal insufficiency, childhood polio without significant neurologic deficit, and rheumatic fever. Laboratory values were significant for the following: albumin, 2.9 mg/dL; blood urea nitrogen, 29 mg/dL; creatinine, 1.5 mg/dL; hemoglobin, 11.9 g/dL; and platelets, 106,000/␮L. A transthoracic echocardiogram (TTE) revealed normal right and left ventricular function, an ejection fraction of 60%, and a right ventricular systolic pressure of 46 mmHg, indicating mild-to-moderate pulmonary hypertension. Mild aortic stenosis was noted with an aortic valve area of 1.4 cm2 and a peak valvular gradient of 26 mmHg. Right and left cardiac catheterizations were performed, which revealed neither pulmonary hypertension nor coronary artery disease. The patient was subsequently approved by this institution’s Liver Transplantation Selection Committee and listed for OLT based on United Network for Organ Sharing criteria.

From the Departments of General Anesthesiology, General Surgery, and Cardiothoracic Anesthesiology, The Cleveland Clinic Foundation, Cleveland, Ohio. Address reprint requests to Brian M. Parker, MD, Section of Anesthesia for General Surgery and Liver Transplantation, Department of General Anesthesiology/E31, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail: [email protected] Copyright © 2001 by W.B. Saunders Company 1053-0770/01/1504-0014$35.00/0 doi:10.1053/jcan.2001.24993 Key words: liver transplantation, aortic valve replacement 474

A follow-up TTE was performed 16 months later and showed normal biventricular function, an aortic valve area of 1.3 cm2, and a peak gradient of 33 mmHg across the aortic valve. The patient’s interim medical condition was otherwise unchanged. A third TTE 32 months after initial evaluation showed normal right ventricular function and moderate concentric left ventricular hypertrophy with an ejection fraction of 55%. The aortic valve area was now 0.9 cm2, however, with a peak valvular gradient of 64 mmHg, consistent with moderateto-severe aortic stenosis. The patient denied chest pain, paroxysmal nocturnal dyspnea, or orthopnea. The patient did complain of dyspnea on ambulating 1 flight of stairs and increasing edema of the lower extremities. Based on these new findings, the patient was no longer considered an optimal candidate for OLT. After determining aortic valvuloplasty was not possible, a combined AVR and OLT was considered pending further cardiac evaluation. A dobutamine stress echocardiogram was negative for myocardial ischemia. A repeat left-sided cardiac catheterization again revealed no evidence of coronary artery disease and confirmed the reduced aortic valve area observed by TTE. In June 1999, the patient was admitted to the hospital with new-onset orthopnea, paroxysmal nocturnal dyspnea, dyspnea at rest, severe bilateral wheezing, and jugular venous distention. A TTE showed preserved right ventricular function, severe concentric left ventricular hypertrophy, an unchanged aortic valve area, and an increased gradient across the aortic valve of 84 mmHg with 1⫹ aortic insufficiency. The patient was noted to have worsening renal dysfunction (blood urea nitrogen, 34 mg/dL; creatinine, 2.2 mg/dL). After a 7-day hospital course, the patient was discharged home, only to be readmitted that same evening for combined AVR and OLT when a donor organ became available. On readmission, pertinent preoperative laboratory values included hemoglobin, 10.0 g/dL; platelets, 77,000/␮L; and prothrombin time, 15.1 seconds. Preinduction invasive hemodynamic monitor placement included a 20G right brachial arterial catheter and a 7.5F thermodilution pulmonary artery catheter inserted through an 8.5F introducer sheath into the right internal jugular vein. Preinduction baseline hemodynamic parameters included heart rate, 110 beats/min; arterial blood pressure, 140/60 mmHg; central venous pressure, 8 mmHg; pulmonary artery pressure, 38/14 mmHg, systemic vascular resistance, 594 dyne 䡠 sec 䡠 cm⫺5; and cardiac output, 12.4 L/min (cardiac index 6.7 L min/m). An 8.5F Rapid Infusion Catheter (Arrow International, Inc. Reading, PA) was placed in each upper extremity for the administration of fluids and blood products through the Rapid Infusion System (Haemonetics Corp, Braintree, MA). Anesthesia was induced by rapid se-

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COMBINED AVR AND OLT

quence using etomidate, 0.2 mg/kg; succinylcholine, 1.5 mg/ kg; and fentanyl, 14.5 ␮g/kg, with isoflurane, midazolam, fentanyl, pancuronium, and air/oxygen (FIO2 ⫽ 0.4) used for maintenance. The patient’s coagulation status was monitored by a Thrombelastograph Coagulation Analyzer (Haemoscope Corp, Skokie, IL) throughout surgery. Aprotinin was started before surgical incision using a bolus dose of 1 million KIU followed by a maintenance infusion of 3650 KIU/kg/h for the duration of the combined procedure. After median sternotomy, systemic heparinization, and aortic and right atrial cannulation, the patient was placed on cardiopulmonary bypass (CPB), and the diseased aortic valve (actual measured valve area, 0.9 cm2 after excision) was replaced with a Carpentier-Edwards 21-mm pericardial bioprosthetic valve (Edwards Lifesciences Corporation, Irvine, CA). Total aortic cross-clamp time was 33 minutes, whereas total CPB time was 41 minutes. Sinus rhythm was restored spontaneously, and valvular function was evaluated by an epicardial echocardiography probe before uneventful patient separation from CPB. Systemic heparinization was reversed, and bypass cannulae were removed. The chest was left open to facilitate OLT and as a precautionary measure in case of intraoperative cardiac complications. The post-CPB serum potassium was 5.9 mEq/dL (pre-CPB value, 4.8 mEq/dL), requiring treatment with an insulin and glucose infusion for normalization to avoid potential cardiovascular complications during and immediately after reperfusion of the allograft secondary to hyperkalemia. After abduction of the patient’s right arm (⬍90°) to facilitate exposure for the venovenous bypass axillary return, OLT was begun, with the dissection and anhepatic stages proceeding without incident. Reperfusion of the donor organ was also uneventful. Total venovenous bypass time was 80 minutes. Total blood products administered during the combined procedure included 14 units of packed red blood cells, 5 units of fresh frozen plasma, 8 6-packs of pooled donor platelets, and 1050 mL of cell-salvaged autologous blood. The chest and abdominal incisions were closed after placement of temporary pacer wires, and the patient was taken to the intensive care unit in stable condition. In the immediate postoperative period and throughout postoperative day (POD) 1, the allograft produced minimal bile. Elevated liver function tests revealed significant hepatic injury (aspartate aminotransferase, 7013 U/L; alanine aminotransferase, 3634 U/L). The patient awakened on POD 1 but was confused and remained intubated. On POD 2, the patient’s mental status was greatly improved. The patient’s right hand and arm strength were greatly diminished compared with his left, with slightly increased muscle tone. Significant edema was noted in the right upper extremity as well. A left hemispheric thromboembolic event in the middle cerebral artery distribution was suspected; however, head tomographic images revealed no evidence of neurologic insult. A TTE revealed no evidence of a cardiac source for embolization. Allograft function improved on POD 2. The patient developed acute oliguric renal failure, however, and a dopamine infusion was started. The patient was subsequently weaned from mechanical ventilation and extubated on POD 5. Gradual daily improvement of the patient’s right upper extremity weakness and edema resulted in a return to normal preoperative

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function on POD 8. On POD 12, the patient was transferred out of the intensive care unit to the ward with significant improvement in renal function. The patient was subsequently discharged from the hospital on POD 30. DISCUSSION

Surgical procedures involving the heart and the liver are rare and have been confined to either combined orthotopic heart transplantation and OLT1-7 or coronary artery bypass graft surgery and OLT.14-18 AVR and pulmonic valve vegetectomy for bacterial endocarditis after OLT have also been reported.8-11 A single OLT recipient as well as a living donor liver transplant recipient both underwent AVR for aortic stenosis remotely after liver transplantation procedures.12,13 Until now, no case of combined AVR and OLT has been reported in either the cardiac or liver transplantation literature. In this patient, left ventricular function was well preserved during progression of aortic stenosis until just before surgery, when the patient presented in congestive heart failure. During AVR for stenosis alone, hemodynamic goals include intraoperative maintenance of sinus rhythm and left ventricular preload as well as adequate afterload. Tachycardia, hypotension, or both, can result in reduced coronary perfusion pressure, leading to ischemia, ventricular dysfunction, and lethal arrhythmias in this setting. In patients with ESLD alone, an adaptive hyperdynamic circulatory state exists, which is heralded by an increased cardiac output that can be 15 to 20 L/min in some individuals. Over time, a progressive decrease in systemic vascular resistance is seen that may be due to (1) systemic vasodilation secondary to either altered production or impaired hepatic clearance of vasoactive substances in the circulation and (2) portal-systemic and peripheral arteriovenous shunting that arises as portal hypertension develops secondary to the increased resistance to blood flow through the cirrhotic liver. ESLD patients may be hypovolemic because of significant ascites formation and aggressive diuretic therapy in conjunction with ongoing paracentesis. During OLT, maintaining normovolemia and the adaptive hyperdynamic state are the main hemodynamic goals, whereas tachycardia in these patients is usually pre-existing and well tolerated. The evaluation and anesthetic management of patients affected by concurrent ESLD and significant aortic stenosis present numerous challenges. If AVR is undertaken before OLT, potential complications of CPB and surgery may result in further deterioration of liver function, necessitating urgent or emergent OLT when a donor organ may not be readily available. Undertaking OLT before AVR can result in the inability to restore timely and adequate cardiac output through the stenotic valve if severe hypotension and tachycardia are encountered secondary to massive bleeding from either surgery or severe coagulopathy. The management of this patient presented several significant challenges. First, the degree of aortic stenosis present on initial evaluation was not thought to be prohibitive for undergoing OLT. The progression of aortic stenosis during 32 months resulted in removing the patient from the donor organ waiting list, however, while re-evaluating the treatment options available. Aortic valvuloplasty was not thought to be feasible be-

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cause of the potential for complications requiring further definitive surgical intervention on an emergent basis or the possibility of failure secondary to restenosis of the valve before performing OLT. A combined procedure was chosen after additional testing showed preserved cardiac function without evidence of coronary artery disease. Because this was not a scheduled procedure, significant preoperative planning was required so that all members of the participating anesthesia, surgical, and nursing teams were aware of the logistical issues involved. Aprotinin was used throughout this combined procedure for several reasons. First, aprotinin was used to reduce intraoperative transfusion requirements, which was previously shown in the redo cardiac surgery and liver transplantation literature.19,20 Second, aprotinin was used to help prevent the occurrence of fibrinolysis as a result of the patient’s pre-existing coagulopathy as well as from the 2 instances of extracorporeal circulation needed to perform the AVR and the OLT. Finally, a low-dose aprotinin regimen was used during surgery because this technique was previously found to be as efficacious as high-dose aprotinin during OLT21 and because this was not a reoperative cardiac procedure. Initially, postoperative liver function was poor and was accompanied by the onset of acute oliguric renal failure. It is

possible that increased donor organ ischemic time resulting from the combined procedure may have contributed to the delayed function of the allograft. It also appeared that the patient had experienced a thromboembolic event, resulting in the observed weakness of the right upper extremity. This event most likely would have occurred during aortic cannulation for CPB. It appears more likely, however, that the patient’s weakness was due to a reversible brachial plexus injury. The most plausible mechanism of injury for the observed arm and hand weakness is brachial plexus injury secondary to median sternotomy and retraction to expose the mediastinum,22-24 combined with subsequent right arm abduction to facilitate venovenous bypass. In this patient, total resolution of upper extremity symptoms occurred in 8 days with no long-term sequelae noted. In summary, combined operative cases, such as the procedure presented here are extremely rare. In patients with significant aortic stenosis and ESLD, combined AVR and OLT may be considered and performed with careful patient selection and appropriate planning in conjunction with the necessary preoperative and postoperative follow-up. Nevertheless, complications may still arise and should be anticipated, as was seen in this patient in the immediate postoperative period.

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donor liver transplantation in a patient with severe aortic stenosis. Br J Anaesth 83:488-490, 1999 14. Morris JJ, Hellman CL, Gawey BJ, et al: Case 3-1995: Three patients requiring both coronary artery bypass surgery and orthotopic liver transplantation. J Cardiothorac Vasc Anesth 9:322-332, 1995 15. Manas DM, Roberts DR, Heaviside DW, et al: Sequential coronary artery bypass grafting and orthotopic liver transplantation: A case report. Clin Transplant 10:320-322, 1996 16. Pelosi F Jr, Klintmalm GB, Simon WB, Roberts WC: Liver transplantation and coronary artery bypass grafting. Am J Cardiol 79:1405-1407, 1997 17. Massad MG, Benedetti E, Pollak R, et al: Combined coronary bypass and liver transplantation: Technical considerations. Ann Thorac Surg 65:1130-1132, 1998 18. Benedetti E, Massad MG, Chami Y, et al: Is the presence of surgically treatable coronary artery disease a contraindication to liver transplantation? Clin Transplant 13:59-61, 1999 19. Royston D, Bidstrup BP, Taylor KM, Sapsford RN: Effect of aprotinin on need for blood transfusion after repeat open-heart surgery. Lancet 2:1289-1291, 1987 20. Scudamore CH, Randall TE, Jewesson PJ, et al: Aprotinin reduces the need for blood products during liver transplantation. Am J Surg 169:546-549, 1995 21. Soilleux H, Gillon MC, Mirand A, et al: Comparative effects of small and large aprotinin doses on bleeding during orthotopic liver transplantation. Anesth Analg 80:349-352, 1995 22. Kirsh MM, Magee KR, Gago O, et al: Brachial plexus injury following median sternotomy incision. Ann Thorac Surg 11:315-319, 1971 23. Stangl R, Altendorf-Hofmann A, von der Emde J: Brachial plexus lesions following median sternotomy in cardiac surgery. Thorac Cardiovasc Surg 39:360-364, 1991 24. Vahl CF, Carl I, Muller-Vahl H, Struck E: Brachial plexus injury after cardiac surgery: The role of internal mammary artery preparation. A prospective study on 1000 consecutive patients. J Thorac Cardiovasc Surg 102:724-729, 1991