What is the recommended pre‑operative preparation, including α‑blockade, β‑blockade, and volume management, for a patient with pheochromocytoma undergoing adrenalectomy?

Preoperative Preparation for Pheochromocytoma Adrenalectomy

Initiate α-blockade 10–14 days before surgery with either phenoxybenzamine or selective α1-blockers (doxazosin, prazosin, terazosin), targeting supine blood pressure <130/80 mmHg and standing systolic >90 mmHg, followed by volume expansion with high-sodium diet and 1–2 L IV saline 24 hours preoperatively; add β-blockers only after adequate α-blockade if tachyarrhythmias develop. 12

Biochemical Confirmation First

• Measure plasma or urine metanephrines preoperatively to confirm catecholamine secretion and determine the need for α-blockade. 1
• Elevated normetanephrine ≥2-fold above the upper reference limit identifies norepinephrine-producing tumors and mandates α-blockade. 1
• Critical exception: Isolated elevation of methoxytyramine (dopamine-only tumors) does not require α-blockade and may cause harm; these patients are typically normotensive or hypotensive. 1

α-Blockade Protocol

Agent Selection

• Both phenoxybenzamine (non-selective) and selective α1-blockers (doxazosin, prazosin, terazosin) are acceptable, though recent evidence suggests important differences. 331
• The PRESCRIPT trial showed phenoxybenzamine produced less intraoperative hemodynamic instability than selective agents, though time outside target blood pressure range was similar. 1
• However, a 2025 study found doxazosin was associated with longer hypertensive crises (median 15 vs. 10 minutes), higher intraoperative vasopressor use (39.6% vs. 10.9%), and longer hospitalization compared to phenoxybenzamine. 4
• Terazosin offers once-daily dosing advantage over prazosin. 31

Timing and Titration

• Begin α-blockade 7–14 days before surgery with gradual dose escalation. 33125
• Target blood pressure: supine <130/80 mmHg and standing systolic >90 mmHg. 125
• Avoid prolonged α-blockade >30 days, as this is an independent risk factor for hypertensive crisis, longer crisis duration, and increased vasopressor requirements. 4
• The final titrated dose of α-blocker does not influence hypertensive outcomes. 4
• After final dose adjustment, 14 days is sufficient; longer duration provides no additional benefit. 6

Critical Sequencing Rule

• Never administer β-blockers before adequate α-blockade—this causes unopposed α-stimulation and severe hypertension. 125
• β-blockers (preferably β1-selective agents like esmolol) may be added only after α-blockade if tachycardia develops. 125

Volume Expansion and Adjunctive Measures

• Administer high-sodium diet plus 1–2 L IV saline 24 hours before surgery to prevent postoperative hypotension from peripheral hypovolemia. 125
• Use compression stockings to minimize orthostatic symptoms. 15
• Treat or prevent constipation during α-blockade. 33

Second-Line Agents

• Calcium channel blockers (e.g., nifedipine SR, amlodipine) can be added for refractory hypertension or used as monotherapy when α-blockers cause intolerable orthostatic hypotension. 125
• Metyrosine (tyrosine hydroxylase inhibitor) may be added when available but does not eliminate hypertensive crisis risk during tumor manipulation. 12

Intraoperative Preparedness

• Experienced anesthesiologist familiar with catecholamine-secreting tumors must provide continuous arterial blood pressure and ECG monitoring. 1
• Have immediately available: IV phentolamine (for hypertensive crises), magnesium sulfate, calcium channel blockers, nitroprusside, esmolol, and vasopressors for post-resection hypotension. 157
• Never biopsy a suspected pheochromocytoma—this can precipitate fatal hypertensive crisis. 125
• Despite optimal preoperative blockade, intraoperative hypertensive crises (≥180/90 mmHg) occur in approximately 23.5% of cases and require immediate pharmacologic intervention. 8

Postoperative Management

• Expect profound hypotension after tumor removal due to sudden catecholamine withdrawal despite preoperative volume expansion; aggressive fluid resuscitation and vasopressors may be required. 129
• Check blood glucose every 2–4 hours postoperatively, as hypoglycemia commonly follows abrupt catecholamine reduction. 15
• Patients receiving selective α-blockade (doxazosin) are more likely to require postoperative vasopressor support or ICU admission compared to phenoxybenzamine. 9
• Remeasure plasma or urine metanephrines 2–6 weeks after surgery to confirm complete tumor removal. 3315

Special Populations

• In head-and-neck paragangliomas, only 7.7% are clinically significant secretors (hyperadrenergic symptoms plus normetanephrine ≥2-fold upper limit); routine blockade may be unnecessary in biochemically insignificant cases. 1
• Bilateral carotid-body paragangliomas carry specific risk of post-operative baroreflex failure requiring vigilant hemodynamic monitoring. 1
• Pregnancy (first 24 weeks): Laparoscopic adrenalectomy after 10–14 days of α-blockade. 5
• Pregnancy (third trimester): Medical management until fetal viability, then combined cesarean delivery and tumor excision. 5

Common Pitfalls

• Diabetes, urinary metanephrines >10× upper limit of normal, and preoperative α-blockade >30 days are independent risk factors for intraoperative hypertensive crisis. 4
• Tumor size is an independent risk factor for intraoperative hemodynamic instability. 6
• Laparoscopic approach is standard for most cases but requires the same rigorous preoperative preparation as open surgery. 338