BJA Education

1. PERIOPERATIVE CARE OF
PHAEOCHROMOCYTOMA
BY DR. CHAMIKA HURUGGAMUWA
REGISTRAR IN ANAESTHESIOLOGY
TH KANDY

3. CLASSIFICATION
• Phaeochromocytomas are catecholamine-secreting tumours of
the adrenal medulla.
• Arise from the chromaffin cells of the sympathoadrenal system.

4. AETIOLOGY
• The majority develop sporadically,
• one-third of cases have specific gene mutations which are
usually inherited in an autosomal-dominant fashion.
• These may be associated with other tumours,
• multiple endocrine neoplasia 2A and 2B,
• Von Hippel–Lindau disease,
• succinate dehydrogenase enzyme mutations, and
• neurofibromatosis.

5. • Almost 100% of patients with MEN2a have or will develop
phaeochromocytoma and they are frequently bilateral.
• MEN2b is characterised by medullary carcinoma thyroid,
phaeochromocytoma

6. INCIDENCE
• European incidence 0.2 per 100 000 people.
• The traditional ‘Rule of 10s’
• 10% of phaeochromocytomas are ‘extra-adrenal’ ,
• 10% are malignant,
• 10% are bilateral,
• 10% are found in normotensive patients, and
• 10% are familial.
• significantly higher proportion of tumours that are malignant (29%), extra-adrenal
(24%),2 and/or familial (32%).
• Equal in both males and females,
• Most prevalent between the third and fifth decades of life.

7. • Phaeochromocytomas are highly active tumours secreting
adrenaline, noradrenaline and rarely dopamine.
• Most tumours predominantly secrete noradrenaline. (Normal
adrenal secretion is 85% adrenaline).
• Familial phaeochromocytomas are an exception because they
secrete large amounts of adrenaline

8. SYMPTOMS
classic symptom triad
• of headache, palpitations, and sweating.
• Hypertension is present in around 90% of cases, although it is paroxysmal in 35–50%
• Other non-specific presentations include
• anxiety, lethargy, nausea,
weight loss, hyperglycaemia, tremor.
• Abdominal pain may result from bowel ischaemia due to excessive vasoconstriction.
• Visual disturbance may develop from papilloedema induced by malignant hypertension.
• Half of phaeochromocytomas are diagnosed incidentally on abdominal imaging for an
unrelated indication.

9. BIOCHEMICAL TESTS
• Mixture of norepinephrine, epinephrine, or, more rarely, dopamine
• Traditional biochemical diagnosis of phaeochromocytomas relied
upon 24 h collections of urinary catecholamines and
vanillylmandelic acid.
• Blood sampling for plasma catecholamines.
• The short half-life of plasma catecholamines makes it difficult to
differentiate pathological over-production from a transient stress
response to venesection

11. • Modern techniques measure levels of metanephrine and
normetanephrine.
• Dopamine-secreting tumours can be identified by measuring plasma
or urinary dopamine and homovanillic acid levels.

12. • Both modern and traditional methods have numerous potential causes of
false-positive results,
• Recent exercise,
• Venous sampling in the sitting position,
• Dietary factors,
• Renal impairment,
• Common medications:
• • norepinephrine re-uptake inhibitors (amitriptyline, olanzapine, venlafaxine),
• • adrenergic receptor blockers (atenolol, phenoxybenzamine),
• • monoamine oxidase inhibitors (moclobemide, phenelzine),
• • recreational drugs (cocaine, amphetamine, caffeine),
• • sympathomimetics (salbutamol, terbutaline),
• • others (paracetamol).

13. LOCALISATION
• MRI and CT both provide accurate and consistent identification
of the majority of phaeochromocytomas.
• MIBG scan. Meta-iodobenzyl guanidine is a
radiopharmaceutical agent which is an analogue of
guanethedine, similar in structure to noradrenaline

14. PREOPERATIVE PREPARATION
• The objectives of preoperative care include:
• • Arterial pressure control,
• • Reversal of chronic circulating volume depletion,
• • Heart rate and arrhythmia control,
• • Assessment and optimization of myocardial function,
• • Reversal of glucose and electrolyte disturbances

15. ARTERIAL PRESSURE CONTROL AND VOLUME
EXPANSION
• Early phaeochromocytoma surgery saw mortality rates of up to 45%
• Severe intraoperative hypertension,
• Strokes,
• Arrhythmias,
• Myocardial ischaemia,
• Left ventricular failure, and
• Refractory hypotension after tumour resection.

16. PREOPERATIVE ADRENERGIC BLOCKADE
ACHIEVES THE FOLLOWING OBJECTIVES:
• • Lowers blood pressure,
• • Increases intravascular volume,
• • Reduces the chance of hypertensive crises during induction and
tumour manipulation,
• • Allows resensitisation of adrenergic receptors
• • Reduces myocardial dysfunction in the perioperative period

17. • Commonly used α-blockers include
• Phenoxybenzamine and
• Doxazosin.

18. NON SELECTIVE -PHENOXYBENZAMINE
• Non-selective, non-competitive, Long acting α-blocker
Twice daily dosage ----- 10 mg twice daily slowly increased up to 60 -
250mg/day.
Disadvantages,
undesirable α 2 receptor blockade --------- inhibition of presynaptic NA
reuptake ===========tachycardia,
===========persistent α blockade which can be
responsible for resistant hypotension after tumour removal
• Central α2-blockade results in somnolence, headache, and nasal
congestion

19. SELECTIVE - DOXAZOSIN
• competitive, selective α1-blocker.
• It does not cause tachycardia or sedation and some studies
suggest a reduced incidence of postoperative hypotension,
• Its efficacy is currently being investigated by the PRESCRIPT
trial, which randomizes patients to receive either
phenoxybenzamine or doxazosin.

20. CALCIUM CHANNEL BLOCKERS
• Calcium channel blockers inhibit norepinephrine-induced calcium
influx and have been utilized for haemodynamic control before
surgery.
• Sustained-release nicardipine 30 mg twice daily
• A high sodium diet and fluid intake are also recommended to help
restore blood volume

21. HEART RATE AND ARRHYTHMIA CONTROL
• Tachyarrhythmias - Epinephrine/Dopamine secreting tumours
Secondary to α-blockade
Selective β1 antagonists (Atenolol or Metoprolol ) after complete α-
blockade.
unopposed α-mediated vasoconstriction that could occur after antagonism
of β2-mediated vasodilatation,
precipitate a hypertensive crisis
while the negative inotropic effect of β-blockade further
compromises myocardial function)

22. ASSESSMENT AND OPTIMIZATION OF
MYOCARDIAL FUNCTION
• ECG
• Ventricular hypertrophy, Tachyarrhythmias, Myocardial ischaemia.
• Various forms of cardiomyopathy
• Hypertrophic cardiomyopathy
• 2D ECHO IS MANDATORY.

23. REVERSAL OF GLUCOSE AND ELECTROLYTE
DISTURBANCES
• Hyperglycaemia
• Increased glycogenolysis (α1 receptors),
• Impaired insulin release (α2 receptors),
• lipolysis (β1 receptors),
• Increased glucagon release coupled with peripheral
Insulin resistance (β2 receptors)

24. • Electrolyte measurements will identify catecholamine induced
renal impairment.
• Hypercalcaemia occurs when a neuroendocrine tumour is
associated with a parathyroid adenoma (e.g. as occurs in MEN
2A).

25. ASSESSMENT OF ADEQUATE OPTIMIZATION
• 1982 Roizen criteria for optimal preoperative control have been
cited:
• • Arterial pressure readings consistently <160/90,
• • The Presence of orthostatic hypotension with a decrease in
systolic arterial pressure of at least 15% but not <80 mm Hg,
• • An ECG which is free of ST or T wave changes for 2 weeks.

26. • contemporary arterial pressure targets are tighter (seated
arterial pressure of <130/80mmHg) and orthostatic
hypotension is not a necessity.
• ST or Twave changes may reflect inverted Takotsubo
cardiomyopathy rather than ischaemia

27. INTRAOPERATIVE MANAGEMENT
• Open surgery - large or invasive adrenal masses and most
paragangliomas.
• Laparoscopic surgery – Transabdominal or Retroperitoneal
approach

28. RISK FACTORS FOR INTRAOPERATIVE
HAEMODYNAMIC INSTABILITY
• High pre-induction plasma norepinephrine levels,
• Large tumour size,
• Profound postural drop after commencement of α-blockade,
• Pre-induction mean arterial pressure (MAP) above 100 mm Hg

29. THE CHOSEN ANAESTHETIC TECHNIQUE
SHOULD:
• • Avoid drug-induced catecholamine release,
• • Avoid catecholamine release induced by anaesthetic or surgical
manoeuvres,
• • minimize haemodynamic responses to tumour handling,
• • treat episodes of hypotension, particularly after tumour
devascularization.

30. AVOIDING DRUG-INDUCED
CATECHOLAMINE RELEASE
• desflurane ketamine morphine
pethidine atracurium pancuronium ephedrine
droperidol metoclopramide cocaine
• succinylcholine

31. AVOIDING CATECHOLAMINE RELEASE INDUCED BY
ANAESTHETIC
OR SURGICAL MANOEUVRES
• Tumour handling
• Tracheal intubation and the raised intra-abdominal pressure
associated with capnoperitoneum or coughing

32. Magnesium sulphate
• Inhibits adrenal catecholamine release
• Reduces α-adrenergic receptor sensitivity to catecholamines
• Dilates arteriolar vessels,
• Antiarrhythmic effects via antagonism of L-type calcium channels
Remifentanil
Blunt Haemodynamic responses to intubation or pain

33. Dexmedetomidine
• Centrally acting selective α2-receptor agonist with sedative and
analgesic properties.
• Adjuvant to volatile or propofol anaesthesia
• Central sympatholytic effects result in substantial reductions in
plasma norepinephrine levels

34. MINIMIZING HAEMODYNAMIC RESPONSES TO
TUMOUR
HANDLING
• Profound hypertension, bradycardia (with norepinephrine),
• Tachyarrhythmias (with epinephrine)
• Hypertensive crises are generally managed with a vasodilator,
while tachyarrhythmias, including the reflex tachycardia seen
with the use of many vasodilators, are controlled with β-
blockers

35. • Phentolamine
• Sodium nitroprusside and Glyceryl trinitrate
• Nicardipine
• Esmolol

36. TREATING HYPOTENSION AFTER TUMOUR
DEVASCULARIZATION
• Final ligation of the tumour’s venous supply is associated with a
sudden drop in plasma catecholamine concentrations, often
precipitating rapid refractory hypotension.
• Down-regulation of α-receptors,
• Suppression of the contralateral adrenal medulla,
• persistence of pre-operative adrenergic-receptor blockade,
• Relative hypovolaemia and
• catecholamine-induced cardiomyopathy.

37. • In the first instance, hypotensive agents should be stopped and fluid
balance optimized taking into account the possibility of ongoing
postoperative haemorrhage, myocardial dysfunction, or both.
• Norepinephrine can initially be used to increase peripheral vascular
resistance and vasopressin should be considered if hypotension is
refractory.
• Vasopressin

38. MONITORING
• Standard AAGBI monitoring
• Invasive arterial monitoring
• CVP
• Cardiac output monitoring

39. POSTOPERATIVE CARE
• Managed post operatively in an ITU/HDU
• Extubation at the end of surgery if uncomplicated intraop.
• All patients should receive invasive arterial pressure monitoring in a high
dependency environment for at least 24 h after the procedure
• steroid supplementation if bilateral adrenalectomy is carried out or if
hypoadrenalism is suspected
• Post operative pain control depends on the type of incision. Epidural
analgesia provides good post operative pain relief and may be
supplemented by regular oral medications

40. Hypertension
• pain,
• co-existing essential hypertension,
• urinary retention, or
• fluid overload.
• Inadvertent ligation of the renal artery precipitates hyper-reninism,
which may lead to delayed hypertension.
• Incomplete tumour resection

41. • Hypoglycaemia

42. INCIDENTAL PRESENTATION DURING
SURGERY
• Presenting features include hypertension (by far the most
• common presentation during incidental surgery),
• Tachyarrhythmias,
• and cardiac failure associated with hypotension and pulmonary oedema
• Surgery should be terminated as soon as is feasible and thus, unlike
planned phaeochromocytoma surgery, continued catecholamine surges may
persist after operation.
• Excessive intra- and postoperative vascular spasm may result in myocardial
or cerebral infarction, acute kidney injury, and/or mesenteric ischaemia.