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* From the Departments of Medicine, Endocrine Division,
Anesthesiology, and
Surgery, Université de Sherbrooke, Centre Universitaire de Santé de l'Estrie, Sherbrooke, Québec, Canada.
Address correspondence to: Dr. Marie-France Langlois, Assistant Professor of Medicine, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, Qc, J1H 5N4 Canada. Phone: 819-564-5241; Fax: 819-564-5292; E-mail: mflanglo{at}courrier.usherb.ca
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Abstract |
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Clinical features: A 55-yr-old woman presented with poorly controlled hypertension and investigation revealed an active pheochromocytoma of her left adrenal gland. During medical preparation for adrenalectomy, she developed an acute myocardial infarct complicated with unstable angina. This required urgent CABG, and combined surgery for the triple vessels coronary artery disease and the pheochromocytoma was planned. We explain the details of medical preparation before surgery and the anesthetic considerations during the surgical procedure. Postoperative recovery was normal and no complication occurred. Even if the pheochromocytoma was malignant, her urinary catecholamines two months after the surgery were normal and remain normal after more than two years of follow-up.
Conclusion: We report a patient who underwent combined CABG and adrenalectomy for pheochromocytoma. The CABG was done first, followed by the adrenalectomy with invasive monitoring. The procedure was well tolerated with cure of the two underlying conditions. So we propose that combined procedure should be considered in this clinical setting.
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The dramatic consequences of a hypertensive crisis caused by an uncovered pheochromocytoma during open-heart surgery are well known.4–6 However, the management of a patient with both advanced CAD requiring coronary artery bypass grafting (CABG) and clinically active pheochromocytoma is challenging and not well established. One approach is to perform the adrenalectomy followed by the CABG a few days or weeks later.7–8 In a case with more severe coronary artery disease, the CABG was done first and the adrenalectomy, six weeks later.9 In this report, we describe a case of pheochromocytoma complicated by severe coronary artery disease and managed with simultaneous CABG and adrenalectomy.
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Case Report |
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Investigation revealed very high levels of urinary catecholamines (Table
). Computed tomography showed a solid, nodular mass of 4.1 by 2.8 cm of her left adrenal gland, without extra-adrenal involvement (Figure 1). The meta-iodobenzylguanidine (131I MIBG) scan was negative for any abnormal uptake. An echocardiogram showed the presence of concentric left ventricular hypertrophy with well preserved systolic function.
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-blockade and optimal hydratation prior to surgery. The patient was also receiving 150 mg hydralazine and 5 mg quinapril per day. Phenoxybenzamine was progressively increased over five days, up to 20 mg three times daily, to achieve good BP control without orthostatic hypotension. On the 6th day of phenoxybenzamine treatment, despite normal BP and heart rate, the patient presented an acute inferior and anterior myocardial infarct. Thrombolysis with rTPA was initiated and led to reperfusion with an increase in CPK levels. Metoprolol was added to the medication, and the usual post-infarct care was given. A few days later, the patient had recurrent angina, and cardiac catheterization showed severe triple-vessel disease: occlusion of the right and left anterior descending coronary arteries and severe stenosis of the circumflex artery. The post-infarct echocardiogram revealed akinesia of the septum and moderate hypokinesia of the anterior wall, LV ejection fraction was approximately 35%, and a septo-apical thrombus was found. Aggressive treatment for heart failure was instituted and phenoxybenzamine was reduced to 10 mg twice daily. Anticoagulation with intravenous heparin was started.
The cardiac condition of the patient required urgent CABG but we were concerned about the high risk of complications associated with an unresected pheochromocytoma during and after such surgery. So, we decided to perform combined surgery with adrenalectomy immediately following CABG. Two weeks before the surgery, we progressively resumed the phenoxybenzamine to 20 mg every eight hours and we weaned the diuretic to assure maximal -blockade and optimal hydration. The patient already had adequate ß-blockade with 100 mg metoprolol per day. At that time, the other anti-hypertensive medications were 75 mg hydralazine and 20 mg quinapril per day, which were given for her reduced cardiac performance.
The day before surgery, the ECG showed normal sinus rhythm at 80bpm with subacute anteroseptal infarct. The Hb was 100 g•L–1 and serum electrolytes and creatinine were normal. Heparin infusion was ceased four hours before surgery. On the day of surgery, the patient received her usual antihypertensive medication and was premedicated with 0.15 mg•kg–1 diazepam and 0.15 mg•kg–1 morphine. After insertion of two large bore iv cannulas and right radial artery catheterization, anesthesia was induced with 5 µg•kg–1 sufentanil, 4 mg midazolam and 0.9 mg•kg–1 rocuronium. Her blood pressure decreased from 150/80 to 120/60 while her pulse diminished from 70 to 60 bpm. Insertion of the pulmonary artery catheter via the right jugular vein was uneventful. Central venous pressure (CVP) was 7 mmHg and the PCWP 14 mmHg. Indexed cardiac output was in normal range at 2,70 L•min–1•m–2. Systemic vascular resistance (SVR) was slightly above normal at 1400 dynes•sec–1•cm–5. Maintenance of anesthesia consisted of isoflurane 0.5% together with an infusion of 1 µg•kg–1•hr–1 sufentanil, amnesic doses of midazolam and hourly boluses 2 mg doxacurium. Before CBP, she received a total of 1500 mL Lactate Ringer. To reduce preoperative bleeding, 20 mg•kg–1 tranexamic acid, an antifibrinolytic agent, were given before cardiopulmonary bypass (CPB).
The surgical procedure began with the CABG. Sternotomy, heart exposure and insertion of CPB cannulas were done without complication. However, during CPB, the patient needed 50 µg•min–1 neosynephrine and 5 µg•min–1 noradrenaline perfusions in order to maintain mean arterial blood pressure above 50 mmHg. Intermittent 10°C blood cardioplegia was given to achieve cardiac arrest during CPB and thereafter every 10 min during the 45 min of cross-clamp to perform the distal anastomosis. The left internal mammary artery was anastomosed to the left anterior descending artery and saphenous grafts were anastomosed to the first diagonal, the posterolateral and right coronary arteries. After a "warm shot" of blood, the aorta was unclamped. The proximal anastomoses were performed with a partial aortic clamp. The patient was weaned from CPB after 80 min with 10 µg•min–1 adrenaline, 7 µg•min–1 noradrenaline and 20 µg•kg–1•min–1 dopamine. These drugs were progressively withdrawn in the following hour. At that time, CVP was 12 mmHg, pulmonary artery pressure 36/14 mmHg, cardiac output 6.9 L•min–1•m–2 and SVR 765 dynes•sec–1•cm–5. After decannulation of the CPB cannulas, the cannulating tourniquets were snared without being tied to permit an easy resumption of the CPB in case of extreme increase of blood pressure. 250 mg of protamine was then given slowly to reverse anticoagulation.
The second team of surgeons performed a left sub-costal incision extending laterally. The inferior part of the pancreas was dissected and a voluminous vein draining the infero-medial aspect of the adrenal gland was found. The vein was suture-ligated without hemodynamic change. The pheochromocytoma was easily removed. Throughout the adrenalectomy, the patient experienced no major change in blood pressure: mean arterial blood pressure was maintained around 70 mmHg.
General anesthesia lasted for six hours and five minutes and there was no excessive bleeding during the procedure. A total of 3.8 L of Ringer's lactate, two albumin units and four packed red blood cell units were given. The patient was then admitted to the recovery room in a stable hemodynamic state and transferred to the surgical intensive care unit. Because her SVR was low (585 dynes•sec–1•cm–5), she received neosynephrine (an average of 0.4 µg•kg–1•min–1) and low doses of adrenaline for the next 12 hr (an average of 6 µg•kg–1•min–1). Otherwise she maintained normal and stable pressure throughout the postoperative course. The trachea was extubated on the first post-operative day and she was released from the intensive care unit on day three. Her subsequent recovery was similar to the usual post-CABG evolution, except for a brief ileus.
Macroscopic examination of the mass revealed a 3.5 x 2.5 cm tumour (Figure 2), well delimited and encapsulated, originating from the adrenal gland. Microscopic examination showed that the tumour infiltrated locally the capsule, the adrenal cortex and the surrounding fat tissue. The tissue removed from the kidney hilus contained two infiltrated lymph nodes. Immunohistochemical binding of the tumour and lymph nodes was intense for chromogranine and moderate for synaptophysine in many cells. Thus, the final diagnosis was malignant pheochromocytoma with metastases to regional lymph nodes.
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Discussion |
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There are few reports of the management of patients with both severe CAD and pheochromocytoma. Vacheron et al.7 presented such a case and proposed the pheochromocytoma be removed first and then investigation of CAD should be considered and may lead to CABG. However, although the outcome of their patient was good, she did not have severe CAD (only the anterior descending coronary artery was affected) and she was not subjected to a recent infarct. Another group9 reported the case of a man with severe CAD, but without recent infarct, and bilateral adrenal pheochromocytomas managed by CABG under thoracic epidural analgesia, followed by bilateral adrenalectomy six weeks later.
Our patient was more at risk of cardiac complication during and after adrenalectomy than previously published cases. She had triple vessel disease complicated by unstable angina following a recent myocardial infarct. According to the score of Detsky et al.,10 unstable angina associated with recent myocardial infarct implies a risk ratio of 4.1 for peri-operative cardiac events, compared with 1.1 in unstable angina alone. Furthermore, the risk of a cardiac event after an adrenalectomy is probably higher for a pheochromocytoma than for other adrenal lesions.1,2 This emphasizes the high risk of cardiac event or mortality if the adrenalectomy is planned before the CABG, in such cases.
Because of these risks, we were forced into doing the CABG before the adrenalectomy. We could have done the CABG under thoracic epidural analgesia as described in 1991 by Liem et al.,9 but we decided to perform the adrenalectomy during the same procedure as the CABG. There are only two other case-reports, published by two different groups in 1995,8,11 where CABG and adrenalectomy for a pheochromocytoma were combined in the same procedure. Each case was found to have triple vessels CAD and pheochromocytoma, but had no recent myocardial infarct. Surgeries were well tolerated, without perioperative adverse events. The good outcome of these two cases and the normal postoperative evolution of our patient with recent myocardial infarct and triple vessels CAD show that combined surgery is feasible, even in very high risk patients.
The patient must be well prepared with - and ß-blockade, optimal hydration, invasive monitoring and CPB. In order to prevent hemodynamic instability during anesthesia, maintenance drugs known for their lack of histaminoliberation and minimal cardiovascular effects should be used: sufentanil, amnesic dose of midazolam and doxacurium, with small concentration of isoflurane. Hemodynamic instability during certain phases of anesthesia and surgery may be expected. So, the anesthesiologist must be prepared with stand by solutions of vasodilatators (nitroglycerine and nitroprusside) and direct-acting catecholamines (adrenaline, noradrenaline and neosynephrine). Indirect catecholamines such as ephedrine are not recommended because of the unpredictable response that patients with pheochromocytoma may have. This response is caused by release of catecholamines from nerve endings that are loaded by the reuptake process.12 We were also concerned by the possible release of catecholamines from the pheochromocytoma on rewarming and CPB weaning, but this did not happen in our case. Unfortunately, we did not measure plasma catecholamine concentration during specific phases.
The CABG was performed first to avoid retroperitoneal bleeding at the site of a fresh adrenalectomy during the anti-coagulated state needed for CPB. Then, the adrenalectomy could be performed with an open sternotomy, untied cannulating sites for CPB and back up extra-corporal circulation equipment in case of any adverse event. Invasive blood pressure and hemodynamic monitoring helped to detect and correct rapidly any BP increase during manipulation of the pheochromocytoma or decrease that is often seen postoperatively. Any decrease of blood pressure during CPB is more refractory to catecholamines because of the preoperative - and ß-blockade. These patients have a better response to volume replacement. Another concern is the possible coagulopathy post-CPB that could make the fresh coronary bypass bleed or the dissection of the adrenal gland more difficult. The ACT, PT, PTT and platelets counts were all normal post-CPB and no abnormal bleeding was noticed.
With combined surgery, recovery may be more secure because the two conditions are treated. This alleviates considerably the risk of postoperative cardiovascular events due to CAD, or post-CABG hypertensive complications associated with secreting pheochromocytoma. When the patient is -blocked preoperatively with phenoxybenzamine, hypotension can be expected postoperatively. To ensure optimal perfusion of the coronary bypasses, hypotension should be aggressively managed with optimal volume replacement and, if needed, high dose catecholamines.
Another particularity of our case was the malignant nature of the tumour based on the finding of local invasion or metastases. The most common metastatic sites are lymph nodes, bone, lung, and liver. In general, these are slow growing tumours. The five years survival rate is about 44%, but some patients have survived for 20 yr or longer.13
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Accepted for publication April 2, 2000.
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2 Debache N, Bleinc D, Touboul A, Haquin G, Chouty F, Lardoux H. Pheochromocytoma and myocardial infarction. One case in a 34 years old man. (French) Rev Med Interne 1986; 7: 167–9.
3 St. John Sutton MG, Sheps SG, Lie JT. Prevalence of clinically unsuspected pheochromocytoma. Review of a 50-year autopsy series. Mayo Clin Proc 1981; 56: 354–60.[Medline]
4 Brown P, Caplan RA. Recognition of an unsuspected pheochromocytoma during elective coronary bypass surgery. Can Anaesth Soc J 1986; 33: 785–9.[Medline]
5 Dunn EJ, Wolff RK, Wright CB, Callard GM, Flege JB Jr. Presentation of undiagnosed pheochromocytoma during coronary artery bypass surgery. J Cardiovasc Surg 1989; 30: 284–7.[Medline]
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Fenje N, Lee LW, Jamieson WRE, Manning G. Phaechromocytoma and mitral valve replacement. Can J Anaesth 1989; 36: 198–9.
7 Vacheron A, Heulin A, Baubion N, et al. Pheochromocytoma and coronary artery disease (two operations). Ann Med Interne 1984; 135: 305–7.[Medline]
8 Nielson DH, Tomasello DN, Brennan EJ Jr, Chen C. Concomitant coronary artery bypass grafting and adrenalectomy for pheochromocytoma. J Card Surg 1995; 10: 179–83.[Medline]
9 Liem TH, Moll JE, Booij LHDJ. Thoracic epidural analgesia in a patient with bilateral phaeochromocytoma undergoing coronary artery bypass grafting. Anaesthesia 1991; 46: 654–8.[Medline]
10 Detsky AS, Abrams HB, Forbath N, Scott JG, Hilliard JR. Cardiac assessment for patients undergoing noncardiac surgery. A multifactorial clinical risk index. Arch Intern Med 1986; 146: 2131–4.[Abstract]
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Seah PW, Costa R, Wolfenden H. Combined coronary artery bypass grafting and excision of adrenal pheochromocytoma. J Thorac Cardiovasc Surg 1995; 110: 559–60.
12 Roizen MF. Anesthetic implications of concurrent diseases. In: Miller RD (Ed.). Anesthesia, 5th ed. New-York: Churchill Livingstone Inc., 2000: 903.
13 Sheps SG, Jiang N-S, Klee GG, van Heerden JA. Recent developments in the diagnosis and treatment of pheochromocytoma. Mayo Clin Proc 1990; 65: 88–95.[Medline]
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