Anesthesia for

pheochromocytoma
Moderator: Dr. Aanchal
Presenter: Dr. Kavya
 TOPICS TO DISCUSS
• Introduction
• Aetiology
• Symptoms
• Preoperative optimisation
• Intraoperative management
• Postoperative care
 Introduction and classification
• Pheochromocytomas are catecholamine –secreting tumors of
adrenal medulla that arise from chromaffin cells of the
sympathoadrenal system.
• Paragangliomas closely related to neuroendocrine tumors
arising from extra-adrenal paraganglia, some of which
produce catecholamines.
 Aetiology
• Precise cause is unknown
• Isolated finding(90%); 10% inherited as AD
• Familial : bilateral adrenal / extra adrenal
• Incidental detection
• Both sexes equally affected
• Peak incidence 3rd -5th decades
• Can also be a part of MEN syndromes and
associated with several neuroectodermal dysplasias
 Rule of 10s’
• 10% are extra-
adrenal
• 10% malignant
• 10% bilateral
• 10% normotensive
patients
• 10% familial
 Symptoms
• Hypertension – continuous or paroxysmal (35-50 %)
• Headache
• Sweating
• Pallor
• Palpitations
• Non-specific symptoms :
• Anxiety, lethargy, nausea and tremor.
ECG:
Elevation or depression of ST segment
Flattening or inversion of T wave
Prolongation of QT interval, Arrhythmias
• Hyperglycemia
Excessive glycogenolysis
Impaired insulin release
• Hypermetabolic state- weight loss
• Visual disturbances
• Abdominal pain
 Biochemical tests
• Traditional biochemical diagnosis of phaeochromocytomas relied
upon
• 24 hr collections of urinary catecholamines and metanephrines
• vanillylmandelic acid (24 h due to diurnal variation in levels), and
also blood sampling for plasma catecholamines
• Most Sensitive test for high risk group is plasma free
metanephrines.
• Plasma free normetanephrine >400pg/ml
• Metanephrine >220pg/ml confirms the diagnosis
• Excluded if normetanephrine <112pg/ml
• Metanephrine <61pg/ml
• Plasma concentrations of total catecholamines

>2000pg/ml Diagnostic

500-2000pg/ml Equivocal

</= 500pg/ml Rules out

• In equivocal cases will use clonidine suppression test
• Glucagon stimulation test
• CT detects >95% of adrenal masses >1cm diameter
• MRI more advantage than CT in detecting small tumor
• Positron emission scanning
• Meta-iodobenzylguanidine (MIBG-123) is a radioactive
analogue of norepinephrine and is thus concentrated in
adrenergic tissue after ingestion.
• It can be used to identify both phaeochromocytomas and
paragangliomas
 Tumor location
• Tumor location can be predicted by the pattern of
catecholamine production by site of pheochromocytoma

Adrenal Extra-adrenal Adrenal+

extraadrenal
Norepinephrine 61% 31% 8%

Epinephrine 100% - -

NE+Epinephrine 95% - 5%
 Preoperative preperation
• 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
 Arterial pressure control and volume
expansion
• Early pheochromocytoma surgery has mortality rates of up to
45%
• Preoperative alpha block is standard practice and aims to
provide preoperative arterial pressure control with restoration
of blood volume, allow re-sensitization of adrenergic
receptors and decrease myocardial dysfunction.
• Commonly used alpha blockers include phenoxybenzamine
and doxazosin
 Phenoxybenzamine
• Phenoxybenzamine is a non-selective, non-competitive,
longacting α-blocker.
• Its non-competitive antagonism may reduce the effects of
catecholamine surges, but may be implicated in postoperative
refractory (catecholamine-resistant) hypotension.
• It should therefore be stopped 24–48 h before surgery due to
its long half-life.
• Reflex tachycardia via β1 stimulation
Prazosin:
• Selective, competitive α1 antagonist
• High first pass metabolism, increased elimination
and clearance
• First dose hypotension
• Spares α2 receptors and minimizes β agonist
action
• 1mg TID increased upto 12mg daily
• Doxazosin is a competitive, selective α1-blocker.
• It does not cause tachycardia or sedation and some studies
suggest a reduced incidence of postoperative hypotension,
making it a good alternative to phenoxybenzamine
• Prazosin and doxazosin pure alpha 1 competitive blockers,
shorter acting, less tachycardia easier to titrate.
 Calcium channel blockers
• Calcium channel blockers inhibit norepinephrine-induced
calcium influx and have been utilized for haemodynamic
control before surgery, mainly as an additional drug class to
further improve control in those already α-blocked
• Sustained-release nicardipine 30 mg twice daily is a
commonly used preparation
• An α1 blocker plus a CCB is an effective combination in
treatment of resistant cases
Heart rate and arrhythmia control
• Selective β1 antagonists (such as atenolol or metoprolol) are
preferred to manage these and must be started after
complete α-blockade.
• A non-selective β-blocker never be administered before α-
blockade, because blockade of vasodilatory β2 receptors
results in unopposed α-agonism, leading to vasoconstriction
and hypertensive crisis.
• Alpha methyl para-tyrosine (metyrosine) inhibits the rate
limiting enzyme tyrosine hydroxylase of catecholamine
synthetic pathway and decrease production by 50-80%
• In combination with phenoxybenzamine it facilitate
intraoperative hemodynamics .
• Side effects incude extrapyramidal reactions and crystalluria
have limited its application
• Metyrosine also decreases HTN caused by tumor
manipulation intraoperatively.
 Assessment and optimization of myocardial
function
• A degree of diastolic dysfunction appears to occur in the
majority of patients, while left ventricular systolic dysfunction
occurs in around 10%.
• Echocardiography is therefore considered mandatory
• Hypertrophic cardiomyopathy, as a result of chronic
hypertension, being the most frequent.
• There are also many case reports of inverted (atypical)
Takotsubo cardiomyopathy.
• The impaired cardiac function associated may improve once
catecholamine levels return to normal.
 Reversal of glucose and electrolyte
disturbances

• Hyperglycaemia can occur due to increased glycogenolysis (α1

receptors), impaired insulin release (α2 receptors), lipolysis (β1
receptors), and increased glucagon release coupled with peripheral
insulin resistance (β2 receptors) and is treated with standard
therapies.
• 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).
 Assessment of adequate optimisation
• α-Blockade is commenced at least 7–14 days before surgery, may
be longer in patients with cardiomyopathy or refractory
hypertension.
• Roizen criteria
• Until recently, the 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.
 Intraoperative management
• Surgery is increasingly laparoscopic, reducing postoperative
recovery times, but not haemodynamic instability.
• Open surgery is likely to be required for large or invasive
adrenal masses and most paragangliomas.
• Risk factors for intraoperative haemodynamic instability
include
• high pre-induction plasma norepinephrine levels,
• large tumour size,
• profound postural drop after commencement of α-blockade,
• and a pre-induction mean arterial pressure (MAP) above 100
mm Hg
 Intraoperative goals
• Avoidance of drugs or maneuvers that may provoke
catecholamine release or potentiate actions
• Maintenance of cardiovascular stability preferably with
short acting drugs
• Intraoperative monitoring with standard and invasive
methods
• Minimize haemodynamic responses to tumour handling,
• Treat episodes of hypotension, particularly after tumour
devascularization.
 Avoiding drug-induced catecholamine
release
• Drugs to consider avoiding on this basis include desflurane,
ketamine, morphine, pethidine, atracurium, pancuronium,
ephedrine, droperidol, metoclopramide, and cocaine.

• In addition to stimulating sympathetic ganglia, succinylcholine

may theoretically provoke tumour catecholamine release via
raised abdominal pressure from muscle fasciculation
 Avoiding catecholamine release induced by
anaesthetic or surgical manoeuvres
• Magnesium sulphate:
• It inhibits adrenal catecholamine release and reduces
α-adrenergic receptor sensitivity to catecholamines.
• Antiarrhythmic effects via antagonism of L-type calcium
channels.
• In a case series by James, 3–5 μg kg−1 fentanyl
combined with 40–60 mg kg−1 of magnesium sulphate
before intubation followed by an infusion of 1–2gh−1
(with further boluses if required) provided good control
of systolic arterial pressure before tumour handling.
 Remifentanyl
• It is very effective in blunting haemodynamic responses to
intubation or pain, although it is inadequate in preventing
hypertension associated with tumour manipulation when
used as a single agent.
• If remifentanil is used, alternative postoperative analgesics
are required
 Dexmedetomidine
• centrally acting selective α2-receptor agonist with sedative
and analgesic properties.
• It has a slow onset and is usually loaded at a dose of around 1
μg kg−1 (over 10 min) and then infused at around 0.5 μg kg−1
h−1 as an adjuvant to volatile or propofol anaesthesia.
• Its central sympatholytic effects result in substantial
reductions in plasma norepinephrine levels, making it a
potentially very attractive agent for phaeochromocytoma
surgery
 Minimizing haemodynamic responses to
tumour handling
• A recent randomized control trial found no difference in
plasma catecholamine levels or episodes of haemodynamic
instability between the early or late adrenal vein ligation
groups.
 Sodium nitroprusside(SNP) and glyceryl trinitrate(GTN)

• SNP causes predominantly arteriolar dilatation while GTN is

principally a venodilator
• GTN may have a greater role in patients with ischaemic heart
disease since it increases coronary blood flow by dilating
collateral vessels and suppressing coronary vasospasm
• SNP infusions should be started at 0.5–1.5 μg kg−1 min−1 and
increased up to 4 μg kg−1 min−1 as required.
• GTN infusions are usually adjusted according to response
within the range of 10–200 μgmin−1
• Tachyphylaxis commonly becomes an issue after a continuous
infusion lasting over 24 h and may cause tachycardia
 Nicardipine
• Nicardipine, a dihydropyridine calcium channel antagonist, is
a potent arterial vasodilator and can be administered by
infusion intraoperatively.
• It is initiated at a rate of 3–5 mg /hr for 15 min and adjusted
by increments of 0.5 or 1 mg /hr every 15 min.
• Once the target pressure is achieved, the infusion should be
gradually reduced to 2–4 mg/hr
• Hypertensive crises can be treated with boluses of 1–2 mg.
 Esmolol
• Esmolol is a selective β1 antagonist with a rapid action and
short duration.
• These properties make it the ideal β-blocker for these cases.
• The initial loading dose is 500 μg/kg over 1 min, followed by a
4 min maintenance infusion of 50 μg /kg/min , which is
subsequently titrated to clinical effect.
 Treating hypotension after tumour
devascularization
• Relatively common and may be both profound and
catecholamine-resistant
• combination of fluid boluses, titration of vasodilators, and
administration of direct α-receptor agonists.
• Norepinephrine can initially be used to increase peripheral
vascular resistance and vasopressin should be considered if
hypotension is refractory.
 Monitoring
• Invasive arterial monitoring should be obtained before induction
of anaesthesia.
• Central venous access
• There is no evidence base to support the use of cardiac output
monitoring.
• The use of intraoperative transoesophageal echocardiography to
guide fluid management and titration of vasodilators.
• Intraoperative ultrasonography to localize small functional
tumors and can perform adrenal sparing surgery when bilateral
tumors present.
• Arterial catheter for monitoring blood pressure on a beat-beat
basis
 Postoperative care
• Majority of the patients become normotensive following
complete tumor resection.
• Plasma catecholamines do not return to normal until 7-10days
postop because of slow release of stored catecholamines.
• Persistent hypertension
• Follow -up at 6 weeks and 6 months followed by an annual
review for at least 10 yr.
• Lifelong steroid replacement is indicated if a bilateral
adrenalectomy has been performed
• Dextrose containing solutions should be included as part of
fluid therapy and plasma glucose levels should be monitored
for 24hrs
 Incidental presentation during surgery
• Mortality rates are high upto 40%
• Presenting features include hypertension (common
presentation during incidental surgery), tachyarrhythmias, and
cardiac failure associated with hypotension and pulmonary
oedema.
• If phaeochromocytoma is suspected, intraoperative
management follows the same principles as in elective cases.
Factors triggering release of catecholamines should be
eliminated, including tumour manipulation, and invasive arterial
monitoring should be instigated urgently.
• Hypertension may be controlled by the use of an α-blocker,
such as phentolamine, or nitrates.
• Surgery should be terminated as soon as is feasible
• Postoperative management should be provided on a high
dependency unit until haemodynamic control is achieved with
definitive surgery generally waiting until optimal adrenergic
blockade
 Take home message
• Perioperative mortality associated with phaeochromocytoma
is around 2%.
• Good preoperative preparation and the judicial use of a
combination of vasodilatory and vasoactive medications help
in reducing the mortality and morbidity associated with
surgery.
• Good communication between the surgeon, endocrinologist
and anaesthetist is crucial for the safe management of these
patients
 References
• James MF. Use of magnesium sulphate in the anaesthetic management of
phaeochromocytoma: a review of 17 anaesthetics. Br J Anaesth 1989; 62:
616–23
• Groeben H, Nottebaum BJ, Alesina PF, Traut A, Neumann HP, Walz MK.
Perioperative α-receptor blockade in phaeochromocytoma surgery: an
observational case series. Br J Anaesth. 2017 Feb;118(2):182-189. doi:
10.1093/bja/aew392. PMID: 28100521.
• Stoelting’s anesthesia and co-existing disease 3rd edition
• Perioperative care of phaeochromocytoma David Connor BMedSci BMBS
FRCA1 and Stephen Boumphrey MBBS FRCA2 BJA Education, 16 (5): 153–158
(2016)