Pheochromocytoma and Anaesthesia Management

1. Overview and Relevance to Anaesthesia

1. Pre-vein ligation - paroxysmal catecholamine surges causing severe hypertension, tachycardia, and arrhythmias
2. Post-vein ligation - sudden catecholamine withdrawal causing profound hypotension
3. Postoperative - hypoglycaemia, delayed hypotension, residual hypertension

2. Preoperative Assessment

Symptoms to evaluate

• Classic triad: paroxysmal hypertension, headache, sweating (plus palpitations)
• Spells triggered by positional change, anxiety, medications (especially opioids, metoclopramide)
• Catecholamine-induced cardiomyopathy (may be severe and reversible)
• Chronic hypovolaemia (vasoconstricted vascular bed, contracted plasma volume)

Investigations

• 24-hour urinary fractionated metanephrines/catecholamines (>98% sensitivity/specificity for low-suspicion patients)
• Plasma fractionated metanephrines (sensitivity 96-100%, preferred in high-suspicion or familial cases)
• ECG - ST-T changes, arrhythmias
• Echocardiogram if cardiomyopathy suspected (longstanding, high catecholamine burden)
• Localisation: MRI/CT; MIBG scan

Roizen Criteria for preoperative readiness (1980s, still referenced)

1. BP < 165/90 mmHg
2. Orthostatic hypotension present (SBP still > 80/45 mmHg)
3. No new ST-T changes on ECG
4. < 1 PVC per 5 minutes

3. Preoperative Medical Preparation

Alpha-blockers (first-line)

Key rule: Alpha blockade MUST precede beta blockade. Starting a beta-blocker first causes unopposed alpha stimulation (no vasodilation, only reduced cardiac output) - this precipitates a hypertensive crisis.

Beta-blockers (second-line, only after alpha is established)

• Added only if persistent tachycardia or arrhythmias develop after alpha blockade
• Atenolol 12.5-25 mg BD/TDS or Metoprolol 25-50 mg TDS/QDS
• Propranolol (traditional) - can cause profound bradycardia, myocardial depression; use cautiously

Calcium Channel Blockers (alternative to or adjunct with alpha blockade)

• Option 2 in the algorithm above (especially if patient cannot tolerate orthostasis from alpha blockers)
• Nicardipine, amlodipine (10-20 mg/day), nifedipine, verapamil
• Amlodipine shown to be an efficacious alternative to alpha blockade for preventing intraoperative haemodynamic instability

Metyrosine (catecholamine synthesis inhibitor)

• Tyrosine hydroxylase inhibitor; reduces catecholamine production 50-80%
• Dose: 250 mg BD/TDS, titrate by 250-500 mg every 2-3 days; 500 mg the night before surgery
• Reserved for refractory cases (severe hypertension not controlled by blockade), metastatic disease, or perioperative catecholamine storms
• Causes profound sedation; not routinely stocked

Volume Restoration

• High sodium diet (3-5 g/day) + liberal fluid intake during alpha blockade reverses catecholamine-induced volume contraction
• 1-2 L IV fluid bolus the night before surgery (inpatient)
• A falling haematocrit during alpha blockade confirms appropriate volume expansion

4. Intraoperative Management

Monitoring

• Arterial line (mandatory) - placed before induction for beat-to-beat BP monitoring
• Large-bore IV access (x2 minimum)
• Central venous access - when postoperative vasoactive infusions anticipated (not routine)
• Transesophageal echocardiography (TOE) or pulmonary artery catheter - in patients with ventricular dysfunction or significant cardiac disease
• Urinary catheter, temperature, glucose monitoring

Premedication

• Benzodiazepines or dexmedetomidine for anxiolysis - reduces catecholamine surges on arrival/transfer

Induction

• Slow, controlled induction; intubation only after deep anaesthetic level achieved
• Propofol or etomidate - both safe
• Ketamine - AVOID (stimulates sympathetic nervous system, triggers catecholamine release)
• Adequate depth before laryngoscopy; consider topical lidocaine to the airway to blunt the intubation response

Maintenance

• All inhalational agents acceptable except desflurane (can cause transient tachycardia) - best avoided
• Halothane - AVOID (sensitises myocardium to catecholamine-induced arrhythmias)
• Isoflurane, sevoflurane commonly used
• Neuromuscular blockers: Most acceptable; pancuronium - AVOID (vagolytic, causes tachycardia and can cause hypertension)
• Opioids: Most are safe; avoid large doses of morphine (histamine release) and atracurium at large bolus doses (histamine release)
• Epidural analgesia: Can supplement for postoperative pain control, but does not reliably attenuate intraoperative hypertensive crises and risks postoperative hypotension

Drugs to AVOID Summary

5. Intraoperative Haemodynamic Crises

Pre-vein ligation: Hypertensive crises

Magnesium deserves special mention - it is now commonly used as it both vasodilates and directly reduces catecholamine release from the tumour.

Post-vein ligation: Hypotension

• Residual alpha blockade
• Hypovolaemia
• Loss of catecholamine-mediated vascular tone ...produces profound hypotension.

1. Aggressive IV fluid loading begins before vein ligation (anticipate the drop)
2. Phenylephrine - first-line vasopressor (alpha-1 agonist, easy to use)
3. Norepinephrine or epinephrine infusions if phenylephrine insufficient
4. Choice of vasopressor can be guided by the tumour's dominant catecholamine secretion (e.g., norepinephrine if elevated normetanephrines preoperatively)
5. Vasopressin and methylene blue - for vasopressor-refractory cases

Glucose management

• Intraoperative hyperglycaemia: catecholamine excess causes insulin resistance and decreased secretion - correct judiciously (residual insulin effect causes postop hypoglycaemia)
• Post-vein ligation: rebound hypoglycaemia risk (especially with epinephrine-secreting tumours)

6. Postoperative Management

7. Special Scenarios

Undiagnosed pheochromocytoma discovered intraoperatively

• Unexpected severe hypertension + tachycardia during abdominal manipulation
• Treat with nitroprusside + esmolol; convert to controlled resection if feasible
• Abort surgery if haemodynamic control unachievable; prepare formally and reschedule

Bilateral pheochromocytoma / MEN 2

• Risk of postoperative adrenal insufficiency - steroid cover required
• Consider cortisol-sparing approach; partial adrenalectomy may be appropriate in hereditary cases

Pregnancy

• Rare but life-threatening; maternal and foetal mortality high if undiagnosed
• Alpha blockade (phenoxybenzamine) after 1st trimester; surgical resection before 24 weeks if possible; otherwise deliver then resect
• 2025 BJA Education review highlights evolving management (Management of phaeochromocytoma in pregnancy)

Catecholamine-induced cardiomyopathy

• May be severe but is reversible after resection
• Preoperative echocardiogram mandatory when suspected
• Cautious fluid management; TOE intraoperatively
• Heart failure may improve markedly within weeks after tumour removal

8. Key Messages - Quick Reference

• Miller's Anesthesia, 10th Edition, pp. 4240-4246 (Chapter on Pheochromocytoma - preoperative, intraoperative, postoperative management)
• Morgan & Mikhail's Clinical Anesthesiology, 7th Edition, pp. 1431-1432 (Catecholamine Excess - Anesthetic Considerations)
• Campbell Walsh Wein Urology, 3-Volume Set (Fig. 106.20 - Preoperative medical management pathways)
• Fischer's Mastery of Surgery, 8th Edition, pp. 1338 (Pheochromocytoma preoperative preparation)
• Mulholland & Greenfield's Surgery, 7th Edition, p. 4182-4183 (Treatment and intraoperative management)
• 2025 European Clinical Guidance: European guidance on adrenal management - confirms alpha blockade ≥7-14 days before surgery as cornerstone

Recent evidence note (2025): A Frontiers in Endocrinology study found that prolonged alpha-blockade >30 days and doxazosin use were associated with more hypertensive crises intraoperatively and greater vasopressor requirements postoperatively compared to phenoxybenzamine and shorter preparation - suggesting the timing and agent choice matters more than simply "longer is better." This aligns with the Miller's note (PMID data) that >30-day preoperative blockade correlates with intraoperative bradycardia and postoperative hypotension.