What is the recommended pre‑operative management for a patient with a paraganglioma to prevent intra‑operative hypertensive crises and postoperative hypotension?

Preoperative Management of Paraganglioma

For norepinephrine-producing paragangliomas, initiate α-adrenergic blockade 7-14 days before surgery with either phenoxybenzamine or doxazosin, titrated to achieve blood pressure <130/80 mmHg supine and >90 mmHg standing, combined with high-sodium diet and 1-2 liters of IV saline 24 hours preoperatively to prevent both intraoperative hypertensive crises and postoperative hypotension. 1

Mandatory Preoperative Biochemical Assessment

• All patients require preoperative measurement of plasma or urine metanephrines to determine catecholamine secretion profile, as this dictates whether α-blockade is necessary. 1
• Norepinephrine production is identified by elevated plasma/urine normetanephrine (≥2-fold upper reference limit), which mandates preoperative α-blockade. 1
• Dopamine-only producing tumors (isolated elevation of plasma methoxytyramine) do not require α-blockade and may actually cause harm, as these patients are typically normotensive or hypotensive. 1

Alpha-Blockade Protocol for Norepinephrine-Producing Tumors

Choice of Agent

• Both phenoxybenzamine (non-selective α1/α2 blocker) and selective α1-blockers (doxazosin, prazosin, terazosin) are acceptable, though the PRESCRIPT trial showed phenoxybenzamine resulted in less intraoperative hemodynamic instability despite no difference in time outside target blood pressure range. 1, 2
• Meta-analysis confirms non-selective α-blockade (phenoxybenzamine) more effectively prevents intraoperative blood pressure fluctuations and reduces need for intraoperative vasodilators compared to selective blockade. 3
• Selective α1-blockers may result in more intraoperative hypotension (67% vs 35% with phenoxybenzamine) and greater need for postoperative vasopressor support. 4

Timing and Titration

• Start α-blockade at least 7-14 days preoperatively with gradually increasing doses until blood pressure targets are achieved. 1
• Target blood pressure: supine <130/80 mmHg and standing systolic >90 mmHg to balance hypertension control while avoiding excessive orthostatic hypotension. 5
• The European Society for Medical Oncology recommends terazosin as an α1-selective option with once-daily dosing advantage over prazosin. 5

Critical Sequencing Rule

• Never administer β-blockers before establishing adequate α-blockade, as this causes unopposed α-stimulation leading to severe hypertension. 1, 5
• β-blockers (preferably β1-selective like esmolol) should only be added after α-blockade if tachycardia develops during α-blockade. 1

Adjunctive Medications

When α-Blockade Alone is Insufficient

• Calcium channel blockers (nifedipine slow-release) can be added as second-line agents for refractory hypertension or used as monotherapy in cases of severe orthostatic hypotension when α-blockers are poorly tolerated. 1, 5
• Metyrosine (inhibits catecholamine synthesis via tyrosine hydroxylase inhibition) can be used as add-on therapy where available, though it does not eliminate the danger of hypertensive crises during tumor manipulation. 1, 6

Volume Expansion Strategy

• High-sodium diet and 1-2 liters of IV saline 24 hours before surgery are standard practice to reduce preoperative orthostatic hypotension and prevent postoperative hypotension. 1
• Compression stockings should be used to further minimize orthostatic symptoms. 1
• The FDA warns that adequate intravascular volume must be maintained intraoperatively and postoperatively to avoid hypotension and decreased perfusion of vital organs, as large volumes of plasma may be needed after tumor removal. 6

Special Considerations

Clinically Insignificant Catecholamine Elevation

• In a series of 182 head and neck paragangliomas, only 7.7% were deemed clinically significant secretors (hyperadrenergic symptoms plus normetanephrine ≥2-fold upper limit). 1
• Patients with clinically insignificant elevations had no perioperative hemodynamic instability without pretreatment, though whether they should receive prophylactic blockade remains debatable. 1

Bilateral Carotid Body Paragangliomas

• Postoperative baroreflex failure is a specific risk with bilateral carotid body tumors, requiring careful monitoring for severe hemodynamic complications during and after surgery or radiotherapy. 1, 7

Intraoperative Preparedness

• Experienced anesthesiologists familiar with catecholamine-secreting tumors are essential, with continuous arterial blood pressure and ECG monitoring. 8
• Have readily available: IV phentolamine for hypertensive crises, magnesium sulfate, calcium channel blockers, nitroprusside, esmolol for tachycardia, and aggressive fluid resuscitation/vasopressors for post-resection hypotension. 8, 6
• Never perform biopsy of suspected paraganglioma, as this can precipitate fatal hypertensive crisis. 8

Postoperative Management

• Anticipate profound hypotension after tumor removal due to sudden catecholamine withdrawal and pre-existing peripheral hypovolemia despite preoperative volume expansion. 7, 6
• Monitor blood glucose every 2-4 hours initially, as hypoglycemia commonly occurs after sudden reduction in catecholamine levels. 7
• Measure plasma/urine metanephrines at 2-8 weeks postoperatively to confirm complete tumor removal. 1, 7