anesthesia for pheochromacytoma

1. ANAESTHESIA FOR
PHEOCHROMACYTOMA
MODERATOR-DR KISHAN SHETTY

2. INTRODUCTION
Phaeochromocytomas are catecholamine secreting neuroendocrine
tumours that arise from the chromaffin cells of the sympathoadrenal
system.
The morbidity and mortality
Unexpected emergency situation - 50%
Planned surgery- < 2%
The word phaeochromocytoma in Greek means “dusky coloured
tumour”

3. Phaeochromocytoma is often referred to as the ‘10% tumour’
because-
10% are extra adrenal,
10 % are malignant,
10% are inherited as an autosomal dominant trait and
10% present bilaterally

4. Usually found in the adrenal medulla, but these tumours can be
found anywhere in association with the sympathetic ganglia.
The organ of Zuckerkandl near the aortic bifurcation is the most
common extra adrenal site.
Phaeochromocytomas are highly active tumours secreting
adrenaline, noradrenaline and rarely dopamine.
Most tumours predominantly secrete noradrenaline.

5. Disease condition associated with
phechromacytoma
Patients with MEN2a (Sipples’s syndrome) –
phaeochromocytoma,
medullary carcinoma of the thyroid and
hyperparathyroidism.
Von Hippel-Lindau Syndrome and
Von Recklinghausen’s Disease.

6. Clinical Feature
1.Cardiovasucular system-
Hypertension
Tachyarrhythmia's
Cardiomyopathy(secondary to increase peripheral resistance)
Myocardial infraction, pulmonary oedema

7. Central nervous system-
Anxiety, Psychosis, Nervousness
Tremors headache
Cerebrovascular haemorrhage-
Mural thrombus and embolic episodes due to dilated
cardiomyopathy
Hypertensive encephalopathy-
altered mental status, focal neurologic signs, seizures

8. Other clinical feature-
sweating
Facial pallor
Nausea and vomiting
Impaired glucose metabolism
Weight loss etc.

9. Diagnosis
1.Clinical
2.Biochemical
3.Radiological

11. Biochemical tests
1. Free catecholamine level in a 24 hr urine sample:
best confirmatory test.
High performance liquid chromatography allows accurate
measurement of free adrenaline, noradrenaline and dopamine in
body fluids.
2.Plasma or urine catecholamine metabolites such as metanephrines

12. 3.Plasma free metanephrines: a sensitive test
4. Urine metanephrine- levels: the single best urine screening test
5.Urinary vanillylmandellic acid (VMA) levels: the oldest and least
expensive test, but nonspecific

13. 24h Urine Collection Positive results (> 2-3 fold elevation):
24h U catechol's > 2-fold elevation
24h U total metanephrines > 1.2 ug/d
24h UVMA > 3-fold elevation

14. Radiological localization
1.MRI
2. CT
3.MIBG scan-
1.Meta-iodobenzyl guanidine is a radiopharmaceutical agent which is an
analogue of guanethedine, similar in structure to noradrenaline and
hence taken up by adrenergic neurons and concentrated in catecholamine
secreting tumours
2.MIGB is detected by scintigraphy. and such scans can help to localise
recurrent tumours, metastases and tumours in unusual sites

15. Investigation
1.Complete blood count
2 Blood sugar- hyperglycaemia is common
3.serum electrolyte
4. ECG: ST and T changes secondary to myocardial ischemia, ventricular
hypertrophy, arrhythmias. Most changes are reversible on treatment.
5. 2D Echo: to estimate myocardial function if cardiomyopathy is suspected

16. Adrenergic Receptors
Alpha-Adrenergic Receptors
α1: vasoconstriction, intestinal relaxation, uterine contraction, pupillary dilation
α2: ↓ presynaptic NE (clonidine), platelet aggregation, vasoconstriction, ↓
insulin secretion
Beta-Adrenergic Receptors
β1: ↑ HR/contractility, ↑ lipolysis, ↑ renin secretion
β2: vasodilation, Broncho dilation↑ glycogenolysis
β3: ↑ lipolysis, ↑ brown fat thermogenesis

17. PREOPERATIVE MANAGEMENT
1.Early multidisciplinary involvement is recommended in order to
optimise the better outcome.
2. mortality of patients undergoing surgery has dropped from 50% to
less than 6% since α receptor blockade was introduced

18. Preoperative adrenergic blockade
advantages
1.Lowers blood pressure
2.Increases intravascular volume,
3.Reduces the chance of hypertensive crises during induction and
tumour manipulation,
4.Allows resensitisation of adrenergic receptors
5. Reduces myocardial dysfunction in the perioperative period

19. Criteria for optimal control include
Blood pressure readings consistently less than 160/90
Presence of orthostatic hypotension (not less than 80/45)
ECG should be free of ST-T changes
No more than one premature ventricular contraction every 5
minutes
Nasal congestion

20. Nonselective α blockers
Phenoxybenzamine
used for achieving adrenergic blockade
it is an irreversible non selective α blocker which alkylates α
receptors permanently
started at least 14 days (sometimes even months) before surgery to
increase the intravascular volume and restore myocardial
dysfunction.
Dose-starting dose is 10 mg twice daily slowly increased up to 60 -
250mg/day

21. Adverse effect
1.Tachycardia
2.Resistant hypotension-
persistent alpha blockade after tumour removal

22. Selective α 1 blockers
Selective α1 blockers, do not induce a tachycardia as a side effect.
They are competitive blockers they are not as efficient as
phenoxybenzamine in preventing surges in blood pressure during
tumour manipulation when a massive release of catecholamine's
displaces the drug from the receptors.
Drugs are prazosin doxazosin etc.

23. Beta blockers
A non selective β blocker should not be prescribed before α blockade
1. blockade of β 2 vasodilator receptors leads to unopposed
stimulation and worsening of hypertension
2. beta blockade lead increased after load with less ability to
contract and this can precipitate heart failure in patients with
myocardial dysfunction.
3. β blockade should only be started after appropriate arteriolar
dilatation has been achieved with α blockers

24. Premedication
Atropine or Glycopyrolate to be omitted- causes tachycardia
Anxiolytic sedative-
benzodiazepine helps decrease in catecholamines release
Opioids- morphine preferably avoided as causes histamine release
Fentanyl, sufentanyl safe

25. INTRAOPERATIVE MANAGEMENT
The choice of surgery can be either an open (retroperitoneal or trans
peritoneal) approach or laparoscopic.
In laparoscopic Hospital stay is reduced and postoperative pain
control is better
Incidence of catecholamine surges would appear to be the same
with both procedure
gas insufflation during laparoscopy can produce a hypertensive crisis
more due to the increased intra-abdominal pressure.

26. Intraoperative goals
1.Avoid drugs or manoeuvres which produce a catecholamine surge
2.Maintain cardiovascular stability with short acting drugs
3. Maintain normovolaemia and haemodynamics after tumour
resection

27. Periods of instability include:
1.Induction and intubation
2.Surgical incision
3.Pneumoperitoneum during laparoscopic approach
4.Abdominal exploration and tumour manipulation
5.Ligation of venous drainage

28. Monitoring and vascular access
ECG
Pulse oximeter
EtCO2
Temperature probe
Invasive blood pressure – Arterial line(inserted prior to induction of
anaesthesia) and CVP monitoring
Large bore peripheral venous access
Urinary catheter

29. ANAESTHETIC TECHNIQUE
1. General and epidural anaesthesia preferred
2. A low thoracic epidural blocks sensory and sympathetic discharge in
the area of the surgical field, but it cannot prevent the effect of the
catecholamines released during surgical manipulation of the tumour.
3. Endotracheal intubation done after adequate depth of anaesthesia

30. INDUCTION
Essentially imp to give induction agents slowly along with close
monitoring of HR and arterial pressure
Thiopentone / propofol widely used
Etomidate –causes pain/ involuntary movement
Ketamine – not recommended
Multimodal – benzodiazapines+ opoid+ induction agent

31. Attenuate pressor response
Important for laryngoscopy and tracheal intubation
2% lignocaine – 1-1.5mg/kg
Esmolol – 50- 100 µg/kg
During laryngoscopy catecholamine levels ↑
Normally- 200- 2000 pg/ml
In pheochromacytoma- 2000- 20,000 pg/ml

32. Maintenance
Inhalational agent- isoflurane Or sevoflurane
Halothane undesirable -arrhythmogenic properties,sensitize
myocardium
Sevoflurane used successfully (fast onset …..fast offset)

33. Neuromuscular blockade
Non depolarising neuromuscular blocking drugs
DOC-Vecuronium
Succinylcholine- avoided causes fasciculation and rise in intra
abdominal pressure
Atracurium/ mivacurium- best avoided to release of histamine
Cisatracurium/ rocuronium- safe cardio stable and least histamine
release

34. Factors which release catecholamines
should be avoided.
stress
anxiety
pain
hypoxia
hypercarbia etc.

35. Pharmacological options for
intraoperative haemodyanamic control
Predominant
Hypertensive response -in noradrenaline secreting tumours
Tachycardia in- adrenaline secreting tumours
Tumour manipulation can result in blood levels of catecholamines
up to 200,000 to 1,000,000pg/mL

36. Phentolamine:
A competitive α blocker and direct vasodilator, given as boluses of 1-5 mg for
controlling surges in blood pressure.
Tachyphylaxis and tachycardia are common.
Phentolamine can be used on its own or in combination with labetalol

37. DRUGS USED ARE
1.Phentolamine
2. sodium nitropruside
3. Nitro-glycerine(NTG)
4. Beta blocker
5.Magnesium sulphate

38. Sodium nitroprusside:
A direct potent, vasodilator with an immediate onset and short
duration of action .
Dosage- 0.5-10ug/kg/min
Adverse effect- Hypotension cyanide toxicity

39. Glyceryl TriNitrate:
A venodilator.
dosage- 5-20ug/min
Adverse effect- cause reflex tachycardia

40. Magnesium sulphate:
Direct vasodilator, inhibits catecholamines from the adrenal medulla
and nerve terminals, reduces sensitivity of α receptors and is a useful
antiarrythmic.
A loading dose of 40-60mg/kg followed by 1-2g/hr

41. Volatile anaesthetics:
Increasing the depth of anaesthesia using volatile agents works
cause persisting hypotension after tumour removal
Calcium channel blockers:
Calcium ion transfer is needed for the release of catecholamines from the
adrenal medulla.
Nicardipine is the drug of choice from this group..

42. β blockers
Esmolol:
selective B1 for rapid intra op BP control
Bolus IV 250-500 µ/kg/min
Infusion 25 to 250 µ/kg/min
Labetalol:
mixed + ɑ Ɓ
Dose- 50- 200 mg/d PO
IV 0.25 mg/kg
Not used as a sole drug due to unpredictable control of BP

43. Catecholamine withdrawal following
venous ligation
Cause sudden hypotension due to-
1.A sudden drop in the catecholamine concentration,
2.The residual α blockade from phenoxybenzamine,
3.Down regulation of adrenoceptors,
4.Suppression of the normal contralateral adrenal gland from excessive
catecholamines,
5.Catecholamine induced myocardial dysfunction and
6.Hypovolaemia from blood and fluid loss are all causative

44. Preventative measure
1.Volume loading before tumour ligation and fluid boluses.
2. vasoactive medications. When fluid therapy adrenaline,
noradrenaline and phenylephrine.
3. Vasopressin -is effective in refractory cases (0.04U/min increase
as required)

45. POST OPERATIVE MANAGEMENT
Anticipated problem-
1 HYPOTENSION- require large volumes of fluid and vasopressor
therapy.
2. HYPOGLYCEMIA-excess insulin release and inadequate
glycogenolysis.
Steroid supplementation if bilateral adrenalectomy.
Postoperative analgesia-epidural or morphine intravenously

46. The majority of patients are restored to norm tension
Sustained hypertension after surgery due to
1. residual tumour,
2. renal ischemia or
3. underlying essential hypertension

47. Pheochromacytoma & Pregnancy
1.Grave prognosis -mortality: maternal - 48%, fetal 55%
2.Diagnosis with 24h urine collections and MRI
3.No stimulation tests, no MIBG if pregnant
4.Never spontaneous labour

48. A:1st & 2nd trimester (< 24 weeks):
Phenoxybenzamine + βblocker prep
Resect tumour laprascopically
B:3rd trimester:
Phenoxybenzamine + βblocker prep…..2-3 wks.
When 37 weeks: caesarean section followed by tumour resection

49. SUMMARRY
1.Managed by an team of anaesthesiologist, surgeon, endocrinologist
&cardiologist
2.Principles of anaesthetic management
3.Good adrenergic blockade preoperative
4.Vigilent intraop monitoring and treatment of hyper/ hypotension
5.Post op ICU care
6.Antihypertensive for a prolonged period

50. THANK YOU