Anesthesia and Pheochromocytoma

Izabela Jugovac, MD Mursel Antapli, MD Sandeep Markan, MD

Medical College of Wisconsin Milwaukee, Wisconsin

Case Report

A 33-year-old woman weighing 108 kg with obesity and neurobromatosis was presented with a 2-year history of poorly controlled hypertension, headaches, palpitations, and occasional chest pain. Her blood pressure was 170/100 mm Hg, and she was treated with daily oral dose of diltiazem (360 mg), hydrodiuril (12.5 mg), lisinopril (20 mg), and metoprolol XL (25 mg) tablets. Biochemical evaluation for pheochromocytoma showed elevated 24-hour urine metanephrine levels of 5496 mcg and normetanephrine level of 6415 mcg. A computed tomographic scan of the abdomen showed a 6 6-cm right adrenal mass. The remainder of her preoperative tests was otherwise normal. Three weeks before surgery, the patient was started on phenoxybenzamine of 10 mg per day orally, which was gradually increased to 30 mg 3 times a day. The day before the planned surgery, the patient was admitted to surgical oor, her average blood pressure and heart rate were 134/76 mm Hg and 65 bpm, respectively. At midnight, she was given an extra dose of 40 mg of phenoxybenzamine and also received 1 L of 5% dextrose with 0.45% normal saline. The following morning patient was taken to the operating room, standard monitors were
REPRINTS: IZABELA JUGOVAC, MD, DEPARTMENT OF ANESTHESIOLOGY, MEDICAL COLLEGE OF WISCONSIN, MILWAUKEE, WI, E-MAIL: IJUGOVAC@MCW.EDU
INTERNATIONAL ANESTHESIOLOGY CLINICS Volume 49, Number 2, 5761 r 2011, Lippincott Williams & Wilkins

www.anesthesiaclinics.com | 57

58

Jugovac et al

applied, and a radial arterial and central venous line was placed. Anesthesia was induced with intravenous propofol (200 mg), fentanyl (100 mcg), rocuronium (60 mg), and maintained with end-tidal sevourane 2.0% to 3.0% in 66% nitrous oxide and 34% oxygen. The patient was ventilated with 8 to 10 ml/kg tidal volume to maintain an end-tidal CO2 between 33 and 36 mm Hg. The patient was positioned in a left lateral decubitus position and a 4-port technique for laparoscopy was used. After induction, intubation, and insufation of the abdomen, the patients blood pressure and heart rate remained stable. During surgery, especially during manipulation of the tumor, we encountered episodes of arrhythmias and hypertension during which systolic and diastolic blood pressure would reach values close to 250/120 mm Hg with a heart rate ranging from 30 to 150 bpm. These were managed with infusions of nitroglycerin and nitroprusside and intermittent boluses of atropine and esmolol to control the heart rate. At the end of surgery, the patients hemodynamic indices remained stable at 120 to 130/60 to 70 mm Hg and 60 to 65 bpm. We did not encounter a period of hypotension after the tumor removal. A total of 2 L of crystalloid was administered during the 3-hour surgery. Blood loss was estimated to be 500 mL and urine output was 600 mL. The patient was transferred to the intensive care unit for overnight observation, and her recovery remained uneventful.

Discussion

Pheochromocytoma is a tumor arising from catecholamine-producing chromafn cells in the adrenal medullaan intra-adrenal paraganglioma.1 Closely related tumors of extra-adrenal sympathetic (catecholamine producing) and parasympathetic (rarely catecholamine producing) paraganglia are classied as extra-adrenal paragangliomas. Practically, all pheochromocytomas produce catecholamines with a considerable variation in their content, depending on the expression of biosynthetic enzymes. Most extra-adrenal pheochromocytomas produce predominantly norepinephrine (NE). Many adrenal tumors produce either NE and epinephrine (EPI), or few rarely produce predominantly EPI (eg, in patients with multiple endocrine neoplasia type 2 and neurobromatosis type 1). The concentrations of catecholamines in pheochromocytoma tissues are enormous. Signicant eruptions result in a catecholamine storm called attacks.2 The adrenoceptors are the nal targets for catecholamines that are found in excess in most patients with pheochromocytoma. Both EPI and NE have overlapping but different effects on a and b adrenoceptors on various organs and systems. Patients with EPI-secreting pheochromocytomas more frequently show episodic symptoms and signs with palpitations, light-headedness
www.anesthesiaclinics.com

Anesthesia and Pheochromocytoma

59

or syncope, anxiety, and hyperglycemia than patients with tumors that secrete mainly NE, who more often have continuous symptoms and signs including hypertension, sweating, and headache.3 These catecholamine-specic effects on adrenoceptors explain the wide range of clinical presentations of patients with pheochromocytomas and serve as the basis for the appropriate preoperative adrenergic blockade. The main objective in the preoperative optimization of these patients is to control blood pressure, heart rate, arrhythmias, and to allow the restoration of blood volume. At our institution, our goal is to achieve preoperative blood pressure of 130/80 mm Hg or less while sitting and about 100 mm Hg systolic while standing (not less than 80/ 45 mm Hg); and target heart rate of about 60 to 70 bpm while sitting and 70 to 80 bpm while standing. There is no consensus on the best pharmacologic agent or optimal duration of therapy for the preparation of these patients for the pheochromocytoma surgery. Traditionally, a 14day to 21-day course of phenoxybenzamine, a nonselective a antagonist, has been established as the mainstay of treatment despite its nonselective a-1 and a-2 antagonism, for its noncompetitive irreversible blockade. Phenoxybenzamine has a long-lasting effect that diminishes only after the de novo a-adrenoceptor synthesis. The initial dose of phenoxybenzamine is usually 10 mg twice a day and is increased until the clinical manifestations are controlled or side effects appear. If the initial dosage is too high, the patient will have signicant postural hypotension with reex tachycardia, dizziness, syncope, nasal congestion, and other side effects, and dose titration is warranted. As the correct dose is approached, paroxysmal hypertensive episodes are brought under control, and when the right dose is achieved the patient becomes normotensive or mildly hypotensive. In addition, the prolonged action of phenoxybenzamine can contribute to hypotension in the rst 24 hours after the tumor removal.4 Another option is to administer phenoxybenzamine by infusion (0.5 mg/kg/d) for 5 hours a day, 3 days before the operation.5 This approach, however, requires that the patient be admitted to the hospital and closely monitored; this period is usually too short to start catecholamine synthesis inhibitors to achieve maximum effect as discussed below. Two studies reported no correlation between the duration of treatment (<1 wk vs. a longer time period) with phenoxybenzamine and the cardiovascular intraoperative stability. Other a adrenoceptor-blocking agents of use are prazosin, terazosin, and doxazosin.6 All 3 drugs are specic, competitive, and therefore short-acting a-1-adrenergic antagonists. In addition, b adrenoceptorblocking agents are needed when catecholamine or a-blocker-induced tachyarrhythmia occurs. A b adrenoceptor blocker should never be used in the absence of an a adrenoceptor blocker because the former will exacerbate EPI-induced vasoconstriction by blocking its vasodilator component. This will make hypertensive episodes worse in the patients
www.anesthesiaclinics.com

60

Jugovac et al

who are on a b-adrenoceptor blocker alone. Perhaps less effective than a-adrenoceptor blockers, calcium channel blockers provide another option for preparing the patient preoperatively. These drugs block NEmediated calcium inux into vascular smooth muscle, thereby controlling hypertension and tachyarrhythmias. Calcium channel blockers do not cause hypotension or orthostatic hypotension during normotensive periods.7 These agents may also prevent catecholamine-associated coronary spasm; therefore, they may be useful when pheochromocytoma is associated with catecholamine-induced coronary vasospasm. The administration of drugs that block catecholamine synthesis, thereby decreasing the stimulation of various adrenoceptors by lowering circulating catecholamine levels, is an important component of preoperative management. Methyl-l-tyrosine or metyrosine is an analog of tyrosine that competitively inhibits tyrosine hydroxylase, the ratelimiting step in catecholamine biosynthesis.8 It signicantly, but not completely, depletes catecholamine stores. The drug is usually used to control high blood pressure in patients with pheochromocytoma, particularly those with extensive metastatic disease or preoperatively in patients with biochemically active tumors. As mentioned earlier, there is no consensus on the best pharmacologic agent or optimal duration of therapy for preparation of these patients for pheochromocytoma surgery. Although a 3-week course of phenoxybenzamine remains the mainstay of treatment, its side effects and need for a 3-week treatment make patients less compliant with the regimen. Tauzin-Fin et al9 reported an effective and easy control of hypertensive crises during the pheochromocytoma manipulation in the patients who were treated with urapidil, a selective short-acting a-1 blocker, for 72 hours before surgery. Jankovic et al10 showed that it is possible to prepare a patient for pheochromocytoma removal within a period of 72 hours by combining magnesium sulfate and urapidil infusions. Their case report describes a patient who was noncompliant with the 2-week to 3-week phenoxybenzamine regimen and was submitted to a 3-day rapid preparation regimen that consisted of a 72-hour long urapidil infusion (10 to 15 mg/h) and a 24-hour infusion of magnesium sulfate (1 g/h) before the day of surgery. Poopalalingam and Chin11 reported a case where they were able to prepare the patient for surgery within a 24-hour period. Their patient was also noncompliant with the 3-week a blockade regimen and insisted on immediate surgery. This patient was started on a labetalol infusion 24 hours before the procedure and a magnesium sulfate infusion in the morning of the surgery. In conclusion, it is noted that the traditional view of a long preoperative stabilization phase with phenoxybenzamine has stood the test of time. This study highlights the possibility of a more rapid perioperative control of hemodynamics in patients with pheochromocytoma presenting for pheochromocytoma removal.
www.anesthesiaclinics.com

Anesthesia and Pheochromocytoma

61

References

1. Ito Y, Fujimoto Y, Obara T. The role of epinephrine, norepinephrine, and dopamine in blood pressure disturbances in patients with pheochromocytoma. World J Surg. 1992;16:759763. 2. Huynh TT, Pacak K, Brouwers FM, et al. Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2. Eur J Endocrinol. 2005; 153:551563. 3. Ueda T, Oka N, Matsumoto A, et al. Pheochromocytoma presenting as recurrent hypotension and syncope. Intern Med. 2005;44:222227. 4. Boutros AR, Bravo EL, Zanettin G, et al. Perioperative management of 63 patients with pheochromocytoma. Cleve Clin J Med. 1990;57:613617. 5. Chew SL. Recent developments in the therapy of phaeochromocytoma. Expert Opin Investig Drugs. 2004;13:15791583. 6. Cubeddu LX, Zarate NA, Rosales CB, et al. Prazosin and propranolol in preoperative management of pheochromocytoma. Clin Pharmacol Ther. 1982;32:156160. 7. Proye C, Thevenin D, Cecat P, et al. Exclusive use of calcium channel blockers in preoperative and intraoperative control of pheochromocytomas: hemodynamics and free catecholamine assays in ten consecutive patients. Surgery. 1989;106:11491154. 8. Sjoerdsma A, Engelman K, Spector S, et al. Inhibition of catecholamine synthesis in man with methyl-tyrosine, an inhibitor of tyrosine hydroxylase. Lancet. 1965; 2:10921094. 9. Tauzin-Fin P, Krol-Houdelk MC, Gosse P, et al. Laparoscopic adrenalectomy for pheochromocytoma: perioperative blockade with urapidil. Ann Fr Anesth Reanim. 2002;21:464470. 10. Jankovic RJ, Konstantinovic SM, Milic DJ, et al. Can a patient be successfully prepared for pheochromocytoma surgery in three days? A case report. Minerva Anestesiol. 2007;73:245248. 11. Poopalalingam R, Chin EY. Rapid preparation of a patient with pheochromocytoma with labetolol and magnesium sulfate. Can J Anaesth. 2001;48:876880.

www.anesthesiaclinics.com