What is the recommended pre-operative management for a middle-aged adult with suspected pheochromocytoma presenting with paroxysmal hypertension, headache, sweating, and elevated metanephrines?

Pre-operative Management of Suspected Pheochromocytoma

Initiate alpha-adrenergic blockade immediately for at least 7-14 days before any surgical intervention, with phenoxybenzamine or doxazosin as first-line agents, targeting blood pressure <130/80 mmHg supine and systolic >90 mmHg standing. 1, 2, 3

Alpha-Adrenergic Blockade (Primary Treatment)

Start alpha-blockade as the foundation of preoperative management:

• Phenoxybenzamine (non-selective, non-competitive α1- and α2-blocker) or selective α1-blockers (doxazosin, prazosin, terazosin) should be initiated at least 7-14 days preoperatively with gradually increasing dosages until blood pressure targets are achieved 1

• Phenoxybenzamine may provide less intraoperative hemodynamic instability compared to doxazosin, based on the PRESCRIPT trial (the first randomized controlled trial in pheochromocytoma), though both drugs showed no difference in the primary endpoint of time outside predefined blood pressure range 1

• Target blood pressure goals: <130/80 mmHg when supine AND systolic blood pressure >90 mmHg when standing 2, 3

• Phenoxybenzamine is FDA-approved specifically for pheochromocytoma to control episodes of hypertension and sweating 4

Dosing Considerations

• Higher doses of phenoxybenzamine (mean 270 mg/day vs 140 mg/day) result in significantly less intraoperative vasodilator requirement (0.8 mg vs 8.7 mg nitroprusside, P<0.0005) and better hemodynamic stability 5

• Gradually titrate dosage upward based on blood pressure response and tolerability 1

Beta-Blockade (Secondary, Never First)

CRITICAL PITFALL: Never initiate beta-blockers before adequate alpha-blockade is established - this can precipitate severe hypertensive crisis from unopposed alpha-adrenergic stimulation 1, 2, 3

• Add beta-blockers (preferably β1-selective) ONLY after adequate alpha-blockade if tachycardia develops during alpha-blockade 1, 4

• Beta-blockers are used to control reflex tachycardia that commonly occurs with alpha-blockade 6

Adjunctive Medications

Calcium channel blockers can be used either:

• As adjuncts to alpha-blockers for refractory hypertension that persists despite adequate alpha-blockade 1
• As monotherapy in cases of normal to mildly elevated blood pressure or severe orthostatic hypotension when alpha-blockers are poorly tolerated 1

Metyrosine (tyrosine hydroxylase inhibitor) can be added where available:

• Inhibits catecholamine biosynthesis at the enzymatic level 1
• Combined phenoxybenzamine plus metyrosine results in better intraoperative blood pressure control, less blood loss, and reduced intraoperative fluid replacement compared to phenoxybenzamine alone 7
• Particularly useful in patients with more severe biochemical disease 7

Volume Expansion Protocol

Implement aggressive volume expansion 24 hours before surgery to prevent postoperative hypotension:

• High-sodium diet during the preoperative preparation period 1, 3
• Administer 1-2 liters of intravenous saline 24 hours prior to surgery 1, 2, 3
• Use compressive stockings to reduce risk of orthostatic hypotension 1, 3

This protocol addresses the contracted plasma volume that occurs with chronic catecholamine excess 5

Monitoring During Preoperative Preparation

Monitor for adequate alpha-blockade by assessing:

• Blood pressure control: supine BP <130/80 mmHg and standing systolic BP >90 mmHg 2, 3
• Resolution of paroxysmal symptoms (headache, sweating, palpitations) 8
• Development of mild orthostatic hypotension (indicates adequate blockade but monitor to prevent excessive hypotension) 1
• Side effects: nasal congestion, peripheral edema, reflex tachycardia 6

Common Pitfalls and Caveats

Never start beta-blockers first - this is the most critical error and can cause life-threatening hypertensive crisis from unopposed alpha-stimulation 1, 2, 3

Avoid fine needle biopsy of suspected pheochromocytoma as it can precipitate hypertensive crisis 9

Anticipate postoperative hypoglycemia due to sudden reduction in catecholamine levels after tumor removal 2

Expect more postoperative hypotension with phenoxybenzamine compared to selective alpha-blockers due to its irreversible binding and longer duration of action 6

Monitor closely for postoperative hypotension requiring aggressive fluid resuscitation, particularly in patients who received higher doses of phenoxybenzamine 5, 6

Duration of Preoperative Treatment

Minimum 7-14 days of alpha-blockade is mandatory before surgery to allow:

• Adequate blood pressure control 1, 2, 3
• Restoration of plasma volume 5
• Resolution of catecholamine-induced myocardial changes 8
• Reduction in perioperative cardiovascular complications 8

Algorithm Summary

1. Confirm diagnosis with elevated metanephrines (already done in this case) 1, 9
2. Initiate alpha-blockade immediately (phenoxybenzamine or doxazosin) 1, 2
3. Titrate to target BP (<130/80 supine, >90 systolic standing) over 7-14 days 2, 3
4. Add beta-blocker only if tachycardia develops after adequate alpha-blockade 1, 2
5. Consider metyrosine for severe disease or inadequate control 1, 7
6. Implement volume expansion (high sodium diet, 1-2L IV saline 24h pre-op, compression stockings) 1, 2, 3
7. Proceed to surgery only after achieving adequate blockade for minimum 7-14 days 1, 2