FRCA Notes

Management of Phaeochromocytoma in Pregnancy

So far past questions on this topic have been confined to the non-parturient, so getting to grips with the generic management of phaeochromocytoma first is propbably sensible.

Resources

  • Phaeochromocytoma is a rare cause of hypertension in pregnancy; incidence 1 in 15,000 to 1 in 300,000 pregnancies
  • Hypertension is the first presenting feature in 20% of cases
  • Outcomes remain poor compared with the non-pregnant population:
    • Maternal mortality 4 - 9%
    • Fetal mortality 7 - 14%

  • The general principles of managing phaeochromocytoma still apply (see phaeochromocytoma), with the added considerations of:
    • Maintaining uteroplacental perfusion; the uteroplacental circulation lacks autoregulation so both hypertension and hypotension can harm the fetus
    • Avoiding teratogenic or fetotoxic drugs

  • Management requires a multidisciplinary team including endocrinologists, maternal fetal medicine (MFM), endocrine surgeons and anaesthetists, ideally in a tertiary centre

  • Median gestation at diagnosis is around 24 - 26 weeks
  • 70 - 77% of patients have their tumour resected after delivery

Timing Considerations
First trimester Highest risk of spontaneous miscarriage with surgery
Second trimester Preferred window for resection if diagnosed early enough
Third trimester
(diagnosis >24 weeks)		 Highest risk of preterm labour with surgery
Medical management with resection after delivery

  • Where the tumour is found early enough, resection before delivery is associated with higher rates of term delivery and less neonatal distress

Medical management

  • α-blockade is recommended as maternal and fetal harm appears to be mediated by catecholamines
  • The aim is to avoid both excessive vasoconstriction from catecholamines and hypotension from excessive antihypertensive therapy

Surgical management

  • Laparoscopic adrenalectomy is usual and can be performed safely in pregnancy provided:
    • Left lateral tilt to minimise aortocaval compression
    • Insufflation pressures of 10 - 15mmHg to preserve venous return
    • Care with initial port placement to avoid injury to the gravid uterus
  • Conversion to open surgery may be needed if laparoscopic exposure is inadequate

Perioperative management of the pregnant patient undergoing phaeochromocytoma resection


  • The goal is tight blood pressure control with adequate α-blockade, combined with restoration of intravascular volume
  • This minimises haemodynamic swings and optimises uteroplacental perfusion during surgery

Blood pressure targets

  • No established targets exist in pregnancy due to the rarity of the condition
  • Non-pregnant targets:
    • Seated: 130/80mmHg; HR 60 - 70bpm
    • Standing: SBP >90mmHg; HR 70 - 80bpm
  • NICE recommends a target of <135/85mmHg for hypertension in pregnancy
  • The CHAP trial showed improved pregnancy outcomes when treating to <140/90mmHg

  • It is therefore reasonable to aim for similar targets to non-pregnant patients, with close attention to maternal and fetal wellbeing

α-blockade

  • The mainstay of optimisation; started at least 14 days before surgery

  • Phenoxybenzamine (non-selective, irreversible)
    • Traditional first line but use is declining
    • More orthostatic hypotension, sedation, reflex tachycardia and post-operative hypotension
    • Crosses the placenta; risk of neonatal respiratory depression and hypotension

  • Doxazosin (α1-selective)
    • Less sedation and orthostatic hypotension; cheaper
    • Not associated with neonatal distress
    • Phenoxybenzamine gives slightly more complete blockade, but there is no difference in cardiovascular outcomes

Adjuncts

  • Calcium channel blockers
    • Added if α-blockade alone gives inadequate control
    • Nifedipine has a known safety profile in pregnancy; its short half-life may benefit the neonate

  • β-blockers
    • Only once α-blockade is established, to avoid unopposed α-stimulation and hypertensive crisis
    • Used for reflex tachycardia and tachyarrhythmias
    • Labetalol is preferred; atenolol is associated with intrauterine growth restriction

Methyldopa

  • Although first line for hypertension in pregnancy, it is not recommended in phaeochromocytoma
  • May worsen hypertension and interferes with urinary catecholamine and metanephrine assays

Volume restoration

  • Excess catecholamines cause contraction of the circulating volume
    • Contributes to post-operative hypotension and impaired uteroplacental flow
  • High sodium diet and increased fluid intake are recommended alongside α-blockade

  • The general principles are unchanged: avoid triggers of catecholamine release, anticipate and treat surges, and anticipate hypotension after tumour devascularisation
  • Close communication with the surgical team throughout is essential

Monitoring and access

  • Arterial line prior to induction
  • CVC should be considered, particularly with difficult peripheral access
    • Not mandatory given evidence for safe peripheral vasopressor use
    • Required if using GTN or nitroprusside infusions
  • PA catheter and TOE are not routine; reserve for severe cardiopulmonary disease
  • Useful alternatives include urine output, lactate and base excess trends, and respiratory variation on the arterial trace

Drug choice


Preferred Use with caution Avoid
Rocuronium
Vecuronium
Remifentanil
Calcium channel blockers
Magnesium
GTN
Phenylephrine		 Atracurium
Suxamethonium
Esmolol
Benzodiazepines
Dexmedetomidine		 Pancuronium
Sodium nitroprusside
Ketamine
Morphine and tramadol
Desflurane
Ephedrine
Dexamethasone
Metoclopramide, haloperidol, chlorpromazine

Catecholamine surges

  • Triggered by anxiety, laryngoscopy and intubation, insufflation, and tumour manipulation
  • Hypertension risks uteroplacental insufficiency and fetal hypoxia

  • Before adrenal vein ligation, consider:
    • Calcium channel blockers
    • Magnesium
    • Remifentanil

Drug Considerations in pregnancy
Magnesium Vasodilates, reduces catecholamine release and protects against arrhythmia
Long history of safe obstetric use
Remifentanil Very effective at blunting sympathetic responses
Crosses the placenta but less neonatal effect than other opioids
Nicardipine Potent vasodilator with little reflex tachycardia; safe in pregnancy
Half-life of 20 - 40 mins risks hypotension after vein ligation
Clevidipine Ultra-short acting (half-life 15 mins), organ-independent elimination
Limited pregnancy data but no malformations in animal studies
GTN Preferred to nitroprusside; rapidly titratable and widely used in pregnancy
Tachyphylaxis in longer cases
Sodium nitroprusside Crosses the placenta; risk of fetal cyanide toxicity
Esmolol Titratable, but sparse safety data and some reports of fetal distress
Dexmedetomidine Sympatholytic and anxiolytic; no impact on neonatal outcome
Long context-sensitive half-time risks hypotension after devascularisation
Midazolam Anxiolysis reduces catecholamine release
Small absolute risk of malformation in first trimester; single dose on a case-by-case basis

Hypotension after adrenal vein ligation

  • Abrupt hypotension is common once the tumour is devascularised, due to:
    • Withdrawal of catecholamines
    • Adrenoreceptor down-regulation
    • Residual antihypertensive effect
  • Risks fetal malperfusion

  • After adrenal vein ligation, consider:
    • Fluid resuscitation to euvolaemia first
    • Noradrenaline
    • Vasopressin; useful in catecholamine-resistant hypotension

  • Close monitoring is required; ICU admission may be prudent
  • Post-operative fetal wellbeing assessment directed by the MFM team

Complications

  • Persistent hypotension; may need ongoing fluids and vasopressors to preserve maternal and fetal perfusion
  • Hypertension, tachyarrhythmias and other cardiovascular events
  • Hypoglycaemia from abrupt loss of catecholamine-mediated insulin resistance and suppression of insulin secretion
  • Adrenal insufficiency from inadequate glucocorticoid output by the remaining adrenal tissue

  • Most patients will deliver with the tumour in situ; an individualised multidisciplinary delivery plan is essential
  • Elective Caesarean section was previously recommended to avoid hypertensive crisis in labour
  • There is no clear consensus on neuraxial versus general anaesthesia; careful haemodynamic monitoring and management is key regardless of technique

Vaginal delivery

  • May be appropriate if sympathetic stimulation is minimised
  • Neuraxial analgesia helps to blunt the sympathetic response to labour
  • A prolonged second stage should be avoided

Drugs to avoid

  • All drugs that may trigger catecholamine release, as above
  • Oxytocin should be given with caution due to hypotension and tachycardia
  • Ergometrine (methylergometrine) should be avoided