Preoperative Treatment Of Patients With Pheochromocytomas

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It is ideal for patients to be hemodynamically stable on oral antihypertensives (see below) prior to surgery. During outpatient titration of antihyperten-sive doses, patients should have daily orthostatic measurements of blood pressure and pulse. Additionally, patients should measure their blood pressure at the time of paroxysmal symptoms. However, prolonged preoperative preparation of greater than

7 days is no more effective at preventing intraoperative hypertension than are shorter preparation times of 4 to 7 days.54 In fact, some hypertensive patients can be admitted emergently for hypertension control and hydration, stabilized, and taken directly to surgery with an intravenous infusion of a vasodilator drug, for example, nicardipine, nitroprusside, and nitroglycerin (see below).55

Calcium channel blockers are effective antihy-pertensive agents for patients with pheochromocy-toma and are preferred in many centers. Patients generally better tolerate calcium channel blockers than a-blockers. Perioperative fluid requirements are lower among patients pretreated with calcium channel blockers than with a-blockers.56 In a French series, 70 patients with pheochromocytoma were safely prepared for surgery using oral calcium channel blockers (usually nicardipine).57 Nicardipine may be given in doses of 20 to 40 mg orally every

8 hours. Nifedipine may be given as a slow-release preparation (eg, Adalat CC) in doses of 30 to 60 mg orally once daily. For hypertensive paroxysms, nifedipine 10 mg (chewed pierced capsule) is usually a quick and effective treatment. Chewed nifedipine is generally safe for use by patients with pheochromocytoma, who may self-administer it at home during paroxysms, but only with close blood pressure monitoring. Nifedipine carries an advantage of having been demonstrated to cause a reduction in the mitotic index of pheochromocytoma cells in vitro57 and to improve uptake of MIBG into some tumors.57,58 Another option is to use verapamil sustained release 120 to 240 mg orally once daily.

Alpha-adrenergic blockade has traditionally been used for most patients with pheochromocytoma in preparation for surgery. Patients who are normoten-

sive are also usually treated (carefully) preopera-tively. Phenoxybenzamine (Dibenzyline, 10 mg capsules), an oral nonselective a-blocker, is the most commonly used a-blocker; it is given orally in a starting dose of 10 mg daily and increased by 10 mg every 3 to 5 days until the blood pressure is < 140/90 mm Hg. Hydration should be encouraged. Patients must be monitored for worsening orthostatic hypotension. Other adverse effects are common, including dry mouth, headache, diplopia, inhibition of ejaculation, and nasal congestion. (Patients are cautioned not to use nasal decongestants if urinary catecholamines or 123I-MIBG scanning is planned, but antihistamines are acceptable.) Phenoxybenza-mine crosses the placenta and can cause hypotension and respiratory depression in the newborn for several days following birth.60 Most patients require 30 to 60 mg/day, but the dosage is sometimes escalated to as high as 120 mg/day. Excessive alpha-blockade with phenoxybenzamine is undesirable because it worsens postoperative hypotension. Furthermore, excessive alpha-blockade may deny a critical surgical indicator: a drop in blood pressure after complete resection of the tumor and aggravation of hypertension during palpation of the abdomen in case of multiple tumors or metastases. Alternatively, a short-acting selective a-blocker (eg, prazosin) appears to cause less reflex tachycardia and less postoperative hypotension.61 The starting dose of prazosin is 0.5 mg/day, increasing up to 10 mg twice daily if necessary.

Angiotensin-converting enzyme (ACE) inhibitors have been used successfully to treat hypertension in patients with pheochromocytoma. Catecholamines stimulate renin, thereby stimulating the production of angiotensin II. ACE inhibitors counteract this aspect of catecholamine hypertension.62

Metyrosine (Demser, a-methylparatyrosine) inhibits tyrosine hydroxylase, the first step in cate-cholamine biosynthesis. Owing to its potential side effects, it is usually used only to treat hypertension in patients with metastatic pheochromocytoma. However, it may be used in hypertensive patients with pheochromocytoma for preoperative preparation. Metyrosine is administered orally as 250 mg capsules, beginning with one every 6 hours; the dose is titrated upward every 3 to 4 days according to blood pressure response and side effects. The maxi mum dosage is 4 g/day. Catecholamine excretion is usually reduced by 35 to 80%. Preoperative treatment with metyrosine tends to reduce intraoperative hypertension and arrhythmias; however, postoperative hypotension is likely to be more severe for several days. Side effects of metyrosine include sedation, psychiatric disturbance, extrapyramidal symptoms, and potentiation of sedatives and phe-nothiazines. Crystalluria and urolithiasis can occur, so adequate hydration is mandatory.63 Metyrosine does not inhibit MIBG uptake by the tumor, allowing concurrent 123I-MIBG scanning or high-dose 131I-MIBG treatment.

Beta-adrenergic blockade may be considered for P-adrenergic symptoms such as flushing or tachycardia once there is adequate alpha-blockade. It is important to institute alpha-blockade first because blocking vasodilating P-adrenergic receptors without also blocking vasoconstricting ai-adrenergic receptors can lead to hypertensive crisis if serum norepinephrine levels are high. Even labetalol, a mixed a/p-blocker, has been reported to cause an unexpected exacerbation of hypertension. Propranolol 10 to 40 mg orally four times daily is occasionally required. Propranolol crosses the placenta and can cause intrauterine growth retardation. Newborns of mothers taking propra-nolol at delivery exhibit bradycardia, respiratory depression, and hypoglycemia.

Octreotide (SMS 201-995) 300 |g/day has been reported to reduce hypertensive episodes and cate-cholamine excretion in a man with pheochromocy-toma whose hypertensive episodes were uncontrolled using other means.64

Nonsteroidal anti-inflammatory drugs, such as naproxen, can be used to treat fevers caused by the release of IL-6 by the tumor.

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