detailed update on pheochromocytoma and anaesthesia

1. ANAESTHETIC
MANAGEMENT OF
PATIENT WITH
PHEOCHROMOCYTOMA
DR ASHISH NAIR
Department of anaesthesia

2. PHEOCHROMOCYTOMA
1. Catecholamine
Physiology/Pathophysiology
2. Clinical Presentation
1. Epidemiology
2. Signs & Symptoms
3. Diagnosis
1. Biochemical
2. Localization
4. Management
1. Preoperative
2. Operative
3. Postoperative
4. Pregnancy

3. CATECHOLAMINE PRODUCING
TUMORS
Neural Crest
Sympathoadrenal Progenitor Cell
(Neuroblasts)
Chromaffin Cell Sympathetic Ganglion Cell
Intra-adrenal Extra-adrenal
Pheochromocytoma
Ganglioneuroma
Neuroblastoma

4. CATECHOLAMINE PRODUCING
TUMORS
• Pheochromocytoma
• Paraganglioma (extra-adrenal pheo)
• Originate in extra-adrenal sympathetic chain/chromaffin tissue
• Ganglioneuroma
• Behave like paraganglioma biochemically
• Neuroblastoma
• Common malignancy in children, adrenal or sympathetic chain
• Catecholamine humoral effects usually minor
• Rapid growth & widespread metastasis
• Some differentiate and spontaneously regress
• Rx complex (surgery, XRT, chemotherapy)

5. CATECHOLAMINE PRODUCING
TUMORS
• Cheodectoma
• Carotid body, behave like paraganglioma
biochemically
• Glomus jugulare tumor
• Intracranial branch of CN IX and X
• Behave like paragangliomoa biochemically

6. PATHOPHYSIOLOGY

7. Tyrosine L-Dopa Dopamine
Norepinephrine
Epinephrine
Catecholamines
Normetanephrine
Metaneprine
PNMT
DBH
COMT
COMT
Metabolites
Homovanillic acid
(HVA)
MAO, COMT
Vanillymandelic Acid
(VMA)
MAO
MAOTumor Secretion:
• Large Pheo: more metabolites
(metabolized within tumor before release)
• Small Pheo: more catecholamines
• Sporadic Pheo: Norepi > Epi
• Familial Pheo: Epi > Norepi
• Paraganglioma: Norepi
• Cheodectoma, glomus jugulare: Norepi
• Gangioneuroma: Norepi
• Malignant Pheo: Dopamine, HVA
• Neuroblastoma: Dopamine, HVA
TH

8. ADRENERGIC RECEPTORS
• Alpha-Adrenergic Receptors
• 1: vasoconstriction, intestinal relaxation, uterine
contraction, pupillary dilation
• 2:  presynaptic NE (clonidine), platelet aggregation,
vasoconstriction,  insulin secretion
• Beta-Adrenergic Receptors
• 1:  HR/contractility,  lipolysis,  renin secretion
• 2: vasodilation, bronchodilation,  glycogenolysis
• 3:  lipolysis,  brown fat thermogenesis

9. PHEOCHROMOCYTOMA
• 0.1-1% of HTN population
• Found in 0.5% of those screened
• M = F
• 3rd to 5th decades of life
• Rare, investigate only if clinically suspicion:
• Signs or Symptoms
• Severe HTN, HTN crisis
• Refractory HTN (> 3 drugs)
• HTN present @ age < 20 or > 50 ?
• Adrenal lesion found on imaging (ex. Incidentaloma)

10. PHEO: ‘RULE OF 10’
• 10% extra-adrenal (closer to 15%)
• 10% occur in children
• 10% familial (closer to 20%)
• 10% bilateral or multiple (more if familial)
• 10% recur (more if extra-adrenal)
• 10% malignant
• 10% discovered incidentally

11. FAMILIAL PHEO
• MEN 2a(sipples syndrome)
P parathyroid adenoma
M medullary ca thyroid
P phaeochromocytoma
• 50% Pheo (usually bilateral), MTC, HPT
• MEN 2b (Gordins syndrome)
M medullary ca thyroid
M marfanoid habitus
P phaeochromocytoma
• 50% Pheo (usually bilatl), MTC, mucosal neuroma,
marfanoid habitus

12. • Von Hippel-Landau
• 50% Pheo (usually bilat), retinoblastoma, cerebellar
hemangioma, nephroma, renal/pancreas cysts
• NF-1 (Von Recklinghausen's)
• 2% Pheo (50% if NF-1 and HTN)
• Café-au-lait spots, neurofibroma, optic glioma
• Familial paraganglioma
• Familial pheo & islet cell tumor
• Other: Tuberous sclerosis, Sturge-Weber, ataxia-
telangectgasia, Carney’s Triad (Pheo, Gastric Leiomyoma,
Pulm chondroma)

13. PHEO: SIGNS & SYMPTOMS
• The five P’s:
• Pressure (HTN) 90%
• Pain (Headache) 80%
• Perspiration 71%
• Palpitation 64%
• Pallor 42%
• Paroxysms (the sixth P!)
• The Classical Triad:
• Headache(MC)
• Perspiration(SWEATING)
• Palpitations

14. HYPERADRENERGIC MANIFESTATIONS…
• HTN
• Palpitations
• Panic attacks(in pts with tumours which produce
an increase in epinephrine)
• inc BMR
• Weight loss
• Tacchyarrhythmias LIKE SVT,AF,ATRIAL
FLUTTER
• TREMORS
i. (β2 receptors in the muscle is responsible for
tremors)
ii. (only at peaks of catecholamines)

15. CONDITION WITH SIMILAR
SYMPTOMS…
• THYROTOXICOSIS..
• Sensitization of adrenergic receptors by T3
• Tremors always
• Proptosis
• No orthostatic Hypotension
OTHER DD’s
Malignant hyperthermia
Toxemia of pregnancy
Acute anxiety neurosis

16. CATECHOLAMINE CARDIOMYOPATHY
• Its a form of myocardial stunning from the toxic effects of catecholamine
on the myocardium.
• When severe, it can be associated with-:
• Pheochromocytoma can lead to pulmonary edema through different
pathways
- cardiogenic decompensation due to cardiomyopathy and increased
vascular resistance i.e. (d/t severe systolic and diastolic dysfunction)
- noncardiogenic edema due to increased hydrostatic pressure through
overfilling or constriction of the efferent pulmonary veins or via
increased permeability of the pulmonary capillaries due to high
catecholamine concentrations (synergistic effects of cell-secreted factors
on pulmonary vascular endothelium)
• Rule out primary cardiac PCC

17. PHEO: HYPOTENSION!
• Hypotension (orthostatic/paroxysmal) occurs in many patients
• Mechanisms:
• Loss of postural reflexes due to prolonged catecholamine
stimulation
• Tumor release of adrenomedullin (vasodilatory neuropeptide)
• fluctuation in vascular tone and subsequent suppression of baroceptor
signaling

18. PHEO CRISIS/ PAROXYSMS,
‘SPELLS’
• Triad - The Classical Triad:
• Headache(MC)
• Perspiration(SWEATING)
• Palpitations
• Catecholamines have t half(10-60 min),so episodic
hypertensive spikes
• Frequency: daily to monthly
• Spontaneous
• Precipitated:
• Diagnostic procedures,
• Drugs (opiods, unopposed -blockade, anesthesia induction,
histamine, ACTH, glucagon, metoclopramide)
• Strenuous exercise, movement that increases intra-abdo pressure
(lifting, straining)
• Micturition (bladder paraganlgioma)

19. PHEO: SIGNS & SYMPTOMS
• N/V, abdo pain, severe constipation (megacolon)
(alpha1 mediated intestinal relaxation)
• Chest-pains
• Anxiety
• Angina/MI with normal coronaries:
• Catecholamine induced:  myocardial oxygen consumption
or coronary vasospasm
• CHF
• HTN  hypertrophic cardiomyopathy  diastolic dysfn.
• Catechols induce dilated cardiomyopathy  systolic
dysfn.
• Cardiac dysrhythmia & conduction defects

20. PHEO: SIGNS (METABOLIC)
• Mild glucose intolerance(inc catecholamines)
• Lipolysis
• Weight-loss
• Ketosis > VLDL synthesis (TG)
• Hypercalcemia(least common)
• Associated MEN2 HPT
• PTHrP secretion by pheo

21. INDICATORS OF SUSPICION !!
• Family h/o MEN/ PHAEO
• Paroxysmal headache/sweating/palpitations
• <20yrs diagnosed HTN/resistant to therapy
• Unexplained grade 3 or 4 retinopathy
• Orthostatic hypotension in pt nt on rx
• Incidental adenoma on adrenal gland
• Carney’s triad
 Gastric srromal tr
 Pulm chondromas
 Extra-adrenal paragangliomas

22. • NON-SPECIFIC
• SPECIFIC
• Tumor localization test

23. NON-SPECIFIC INVESTIGATIONS
• CBC (RAISED HCt d/t hemoconc and reduced intravascular
volume)
• SE, creatinine, INR/PTT, blood sugar
• CXR
• 12 lead ECG (left ventricular strain, hypertrophy, bundle
branch blocks and ischemia.)
• 2D Echo (r/o dilated CMY 2º catechols) with cardiac
consultation
- to assess global systolic and valve function
- strain rate assessment (which essentially is an index of
myocardial deformation that correlates with severity of
diastolic dysfunction)

24. 24H URINE COLLECTION
• 24h urine collection:
• Creatinine, catecholamines, metanephrines, vanillymandelic acid
(VMA), +/-dopamine
• HPLC with electrochemical detection or mass spect
 IOC
METANEPHRINE AND CATECHOLAMINE ASSAY > VMA
(19TH HARRISON)
SPECIFIC
INVESTIGATIONS….

25. 24H URINE: FALSE POSITIVE
• Drugs: TCAs, MAO-i, levodopa, methyldopa, labetalol,
propanolol, clonidine (withdrawal), ilicit drugs (opiods,
amphetamines, cocaine), ethanol, sympathomimetics (cold
remedies)
• Hold these medications for 2 weeks!
• Major physical stress (hypoglycemia, stroke, raised ICP, etc.)
• OSA

26. VMA values
• Less than or equal to 2.3mg/24hr(3-8yrs age)
• Less than or equal to 3.9mg/24hr(13-17yrs age)

27. PLASMA CATECHOLAMINES
• Drawn with patient fasting, supine, with an
indwelling catheter in place > 30 min
• Plasma total catechols > 11.8 nM (2000 pg/mL)
• SEN 85% SPEC 80%
• False positives: same as for 24h urine testing,
also with diuretics, smoking
• CKD
• Oliguric to Anuric  24h Urines inaccurate
• Plasma epinephrine best test for pheo in CKD
• Plasma norepi and metanephrines falsely elevated in
CKD

28. MOST SPECIFIC TEST
• Total metanephrine (19TH HARRISON)
URINE
MOST SENSITIVE
- Fractional metanephrine (19TH HARRISON)
PLASMA
MOST SENSITIVE AND SPECIFIC
• - Free metanephrine + catecholamine + chromogranin A (19TH
HARRISON)

29. NORMAL PCC
CATECHOLAMINES <100-150 mcg/day >250 mcg/day
METANEPHRINE <1.3 mg/day >1.3mg/day
VMMA < 7mg/day >14mg/day
PLASMA
CATECHOLAMINE
<1 mcg/ml > 1 mcg/ml

30. SUPPRESSION/STIMULATION
TESTING
• Clonidine suppression / pentolinium suppression
• May precipitate hypotensive shock!
• Unlike normals, pheo patients won’t suppress their plasma norepi
with clonidine
• Glucagon / histamine / tyramine stimulation
• May precipitate hypertensive crisis!
• Pheo patients, but not normals, will have a > 3x increase in plasma
norepi with glucagon

31. Norad secreting tumor
• Severe HTN with brady cardia
Adrenaline secreting tumor
• HTN with tacchycardia

32. LOCALIZATION: IMAGING
• IOC for localization- MRI abdomen(sen-98%) (19TH HARRISON)
T2 weighted mri with contrast is best for abdominal
phaeochromocytoma and paraganglioma
• MIBG scan(sen-81%)
• 123I or 131I labelled metaiodobenzylguanidine
• MIBG catecholamine precurosr taken up by the tumor
• PET is most accurate but not IOC

33. • CT abdomen
• Adrenal pheo SEN 93-100%
• Extra-adrenal pheo SEN 90%
• Mc site- organ of zuckerkandl

34. PHEO MANAGEMENT
• Prior to 1951, reported mortality for excision of
pheochromoyctoma UPTO 45%
• HTN crisis, arrhythmia, LVF,MI, stroke
• Hypotensive shock
• Currently, mortality: 0 - 2.7 %
• Preoperative preperation, -blockade?
• New anesthetic techniques?
• Anesthetic agents
• Intraoperative monitoring: arterial line, EKG monitor,
CVP line, Swan-Ganz catheter
• Experienced & Coordinated team:
• Endocrinologist, Anesthesiologist and Surgeon

35. PREOPERATIVE PREPARATION
Arterial pressure control
Reversal of chronic circulating volume depletion
Heart rate and arrhythmia control
Reversal of glucose and electrolyte disturbances

36. ARTERIAL PRESSURE CONTROL
AND
VOLUME EXPANSION

37. • Management of hypotension
• Fluids + salt load
• Beta blocker
• Stop all alpha blocker
• Hematocrit fall is a sign of good fluid management
• If only beta blocked heart—pulmonary oedema and a/c cardiac
failure

38. PREOP PREPERATION
REGIMENS
• Combined  +  blockade(7-10 days prior to OT)
• Phenoxybenzamine
• Selective 1-blocker (ex. Prazosin,Doxazosin)
• Propanolol
• Metyrosine
• Calcium Channel Blocker (CCB)
• Nicardipine

39. 1) PREOP  BLOCKADE
• AIM - restore blood volume status by reversing vasoconstriction
• Start at least 10-14d preop
Allow sufficient time for ECF volume to restore
• If pt has ST-T changes on ECG
- Long term  blockade is required (1-6 months)
- This helps in clinical and ECG resolution of catecholamine cardiomyopathy

40. • Phenoxybenzamine
• Drug of choice
• Its an irreversible , long-acting , non-selective  blocker
• BUT, chances of postoperative refractory (catecholamine-resistant)
hypotension (STOP 24-48hrs before surgery due to its long T1/2)
• 24-48 hrs for new receptors to form
• Target BP- <120/80 (systolic bp < 90 on standing)
• Start 10 mg bid/ tid  increase by 10-20 mg every 3 days
(max dose 80-250mg/day)
• Increase dose till BP is under cntrl and no more paroxysms
• Maintenance 40-80 mg/d (some need > 200 mg/d)
• Salt load: NaCl 600 mg od-tid as tolerated
• Regulates norepinephrine release from cardiac sympathetic neurons
causing reflex tacchy via 1 stimulation ( blocker??)
• Central  2 blockade leads to- somnolence, headache, nasal congestion
• Side-effect: orthostasis with dosage required to normalized seated BP,
reflex tachycardia
• Drawback: periop hypotension/shock unlikely to respond to pressor
agent.

41. • Selective 1-blockers
• Prazosin, Terazosin, Doxazosin
• Competitive selective 1-blockers and reversible so
intraoperatively there might be instability
• Not routinely used as incomplete -blockade
• Less orthostasis(postop hypotension) & reflex tachycardia then
phenoxybenzamine
• Used more for long-term Rx (inoperable or malignant pheo)
• Prazosin ( 2-5 mg 2 or 3 times daily )
Usually started at 1mg q8h
Gradually increase dose till maximum of 8-12 mg/day
• Terazosin( 2-5 mg daily )
• Doxazosin (2-8 mg daily for, which can be increased to 32 mg/day)

42. CALCIUM CHANNEL BLOCKERS
• The dihydropyridine calcium channel blockers
• Inhibit nor-epinehrine induced calcium influx into vascular smooth muscle
• Not recommended for monotherapy unless patients have very mild hypertension or develop
severe orthostatic hypotension with  blockers
• Are particularly useful in the subset of patients with catecholamineinduced
myocarditis/vasospasm
• Beta blockade can ppt CCF in catecholamine cardiomyopathy
• Nicardipine (most commonly used)
• Started po 24h to few weeks preop to cntrl BP and allow ECF volume restoration
• most commonly used agent(30mg bd)
• After intubation  IV Nicardipine (start 2.5 ug/kg/min)
• IV Nicardipine adjusted to SBP
• Stopped prior to ligation of tumor venous drainage
• Tachycardia Rx with concurrent IV esmolol
• Advantage: periop hypotension may still respond to pressor agents as opposed to those
patients who are completely -blocked

43. RAPID IV  BLOCKADE
• Done over atleast 3 days
Day 1
Phenoxybenzamine 1mg/kg in 500ml 5%dex over 2 hours
With
Oral propanolo if HR>120/’
Day 2
Phenoxybenzamine 1-1.5mg/kg in 500ml 5%dex over 2 hours
With
Oral propanolo if HR>100/’
Day 3
Phenoxybenzamine 1.5-2 mg/kg in 500ml 5%dex over 2 hours
With
Oral propanolo if HR>100/’

44. HEART RATE
AND
ARRHYTHMIA CONTROL

45. PREOP:  BLOCKADE
• -blockade
• Used to control reflex tachycardia and prophylaxis against arrhythmia during
surgery
• Atenolo,metoprolol
• Start only after effective -blockade (may ppt HTN)
• If given alone will have un-opposed alpha action
• If suspect CHF/dilated CMY  start low dose
• Propanolol most studied in pheo prep
• Start 10 mg po bid  increase to cntrl HR

46. PREOP:  +  BLOCKADE
• If BP still not cntrl despite  +  blockade
• Add Prazosin to Phenoxybenzamine
• Add CCB, ACE-I
• Avoid diuretics as already ECFv contracted
• Metyrosine

47. PREOP:  +  BLOCKADE
• Meds given on day of surgery
• Periop HTN:
• IV phentolamine
• Short acting non-selective -blocker
• Test dose 1 mg, then 2-5 mg IV q1-2h PRN or as
continuous infusion (100 mg in 500cc D5W, titrate to
BP)
• IV Nitroprusside (NTP)
• Periop arrhythmia: IV esmolol
• Periop Hypothension: IV crystalloid +/-
colloid

48. ASSESSMENT AND OPTIMIZATION
OF
MYOCARDIAL FUNCTION

49. • ECG-Ventricular hypertrophy, tacchyarythmias or mycardial ischemia
• 2D echo-Possibility of diastolic dysfunction and systolic dysfunction
• Conc hypertrophy(c/c HTN),
• TAKASUBO CARDIOMYOPATHY

50. REVERSAL
OF
GLUCOSE
AND
ELECTROLYTE DISTURBANCES

51. HYPERGLYCEMIA
• Increased glycogenolysis(1 receptors)
• Impaired insulin release(2 receptor)
• Lipolysis(1 receptors)
• Increased glucagon release coupled with peripheral insulin
resistance(2 receptors)
ELECTROLYTE MEASUREMENT
Catecholamine induced renal impairment
Hypercalcemia(NET a/w parathyroid adenoma)MEN 2A

52. ASSESSMENT OF ADEQUATE
OPTIMIZATION

53. ROIZEN CRITERIA
(used for assessment of adequacy of preparation )
• No in-hospital blood pressure >160/90 mmHg for 24 h
prior to surgery;
• orthostatic hypotension with blood pressure >80/45 mmHg;
• No ST or T wave changes for 1-week prior to surgery;
• No more than 5 premature ventricular contractions per minute.
• Other indicators- serial HCt
- RBS control
- improved physiological status
1st sign of alpha blockade is orthostatic hypotension
1st symptom of alpha blockade is giddiness

54. METYROSINE/ ALPHA METHYL
TYROSINE
• Synthetic inhibitor of Tyrosine
Hydroxylase (TH)
• Special pharm access, no DIN
• Dose – 0.5-4 gm/day
• Start 250 mg qid  max 1 gm qid
• Severe S/E’s: sedation, extrapyramidal, diarrhea,
nausea/vomit, anxiety, renal/chole stones, galactorrhea
• Alone may insufficiently cntrl BP and reported HTN
crises during pheo operation
• Restrict use to inoperable/malignant pheo or as adjunct
to  +  blockade or other preop prep
Tyrosine L-Dopa Dopamine
Norepinephrine
Epinephrine
PNMT
DBH
TH

55. INTRAOPERATIVE MANAGEMENT
Choice of surgery
• Laproscopic surgery (<100gm, <6cm size)
• Transabdominal/retroperitoneal approach
advantages of laparoscopic approaches in general —
• less postoperative pain
• earlier mobilization
• recovery
• reduced incidence of postoperative pulmonary
• Less thromboembolic complications
• shorter hospital stays
• overall cost effectiveness

56. Risk factors for intraop haemodynamic instability
High pre induction nor epinephrine values
Large tumour size
Profound postural drop after commencement of  blockade
Pre induction MAP>100mmHg

57. ANAESTHETIC GOALS

58. • Primary goal being the delivery of an anesthetic which provides stable
hemodynamics in the face of catecholamine surges
• (especially at laryngoscopy, peritoneal insufflation, surgical
stimulation, and tumor handling)
• Careful planning and meticulous technique are essential, in addition to
close communication with the surgical team.

59. PREINDUCTION
• Admit night before for overnight IV saline
• NPO orders, consent
• phenoxybenzamine and doxazosin are traditionally withheld 12-24 h prior
to the operation
• A large-bore peripheral IV catheter is also inserted preinduction routinely
• Sedatives/anxiolytics - Relief from anxiety(a long-acting benzodiazepine
such as lorazepam or diazepam administered the night before the
operation), Tab restyl 0.5mg HS
• Steroid supplement – if bilateral adrenalectomy is planned
AVOID
- Morphine and pethidine – histamine release
- Reglan and droperidol – provoke HTNsive crisis
- Atropine – parasym block may cause unimposed symp activity
• For rapid volume expansion, colloids, plasma expanders, and blood
products are arranged as indicated

60. • vasoactive infusions prepared and kept ready
Traditional vasodilator set up includes nitroglycerin,
sodium nitroprusside, nicardipine, diltiazem as indicated
• Esmolol infusion for heart rate control
• Vasoconstrictors such as norepinephrine and vasopressin
• Inotropes to be added include epinephrine and
dobutamine
• Milrinone available in the setting of right ventricular
dysfunction

61. MONITORING
• Routine monitors
• Invasive arterial monitoring (continuous beat-to-beat monitoring
allows for close hemodynamic monitoring)
• Central venous cannulation is absolutely indicated for fluid
management as well as delivery of vasoactive agents
• Known CHF: consider Pulmonary artery catheters /Swan-Ganz
(indicated in patients with poor left ventricular function from a
catecholamine cardiomyopathy, pulmonary hypertension, or
significant myocardial disease.)
• intraoperative transoesophageal echocardiography to guide fluid
management and titration of vasodilators
• Oesophageal Doppler has been used in the paediatric population

62. Chosen anaesthetic technique should be:
Avoid drug induced catecholamine release
Avoid catecholamines release induced by anaesthetic or surgical
manoeuvers
Minimize haemodynamic responses to tumour handling
Treat episodes of hypotension particularly after tumor
devascularisation

63. AVOID DRUG INDUCED
CATECHOLAMINE RELEASE

64. Drugs which Inc catecholamine release-
a) Promote pre-synaptic release
b) Inhibit their reuptake
c) Raised catecholamine levels with histamine release
Desflurane
Ketamine
Morphine,pethidine
Atracurium,pancuronium
Ephedrine,droperidol
Metoclopramide
Cocaine

65. Attenuation of the pressor response
• most critical portion- laryngoscopy and endotracheal intubation.
• crucial aspect of anesthetic induction and adjuncts commonly used include
fentanyl in small doses
• IV lidocaine 1-1.5mg/kg,
• IV esmolol 0.5 mg/kg bolus
• nitroglycerin,
• nicardipine
• sodium nitroprusside
Induction agents
commonly used include propofol and etomidate.
• Propofol has been documented to be safe in these patients
• Etomidate has the advantage of conferring cardiovascular stability, especially in
volume-depleted patients and is associated with myoclonic jerks
• Ketamine is usually avoided due to its sympathomimetic effects
• Pento causes histamine release and also causes reflex tachycardia

66. NMBDs
• The choice of neuromuscular blocker prior to laryngoscopy
is critically important in the pheochromocytoma resection.
• The depolarizing agent, succinylcholine, has the potential
for causing catecholamine surges from the muscle
fasciculations that it produces which can mechanically
compress the tumor, in addition to stimulation of the
autonomic ganglia
• Pancuronium, a nondepolarizing agent, has a
sympathomimetic effect that can trigger a pressor
response in these patients
• vecuronium is the most widely used and preferred. It has
no autonomic effects, does not cause histamine release

67. MAINTENANCE
O2 + n2o + inhalational agent
Opioids (fent/remifent)
Vec intermittent doses
• Halothane (which is contraindicated in pheochromocytoma patients as it
is arrhythmogenic,sensitizing the myocardium to circulating
catecholamines.
• Desflurane, which is favored in ambulatory anesthesia for its low blood-
gas partition coefficient (and resultant rapid emergence) does cause
significant sympathetic stimulation
• Sevoflurane is widely used for pheochromocytoma excision. Given its
relatively favorable hemodynamic profile, it is less irritable to the airways
than desflurane and lacks arrhythmogenic potential.
• Enflurane and isoflurane have been extensively used without
complications.
• Nitrous oxide is benign in these patients.

68. AVOIDING CATECHOLAMINE
RELEASE INDUCED
BY
ANAESTHETIC
OR
SURGICAL MANOEUVRES
 Avoid hypoventilation – causes sympathetic nervous system stimulation

69. Haemodynamic responses( catecholamine release) is provoked by-
• tumour handling (most significant)
• tracheal intubation
• the raised intra-abdominal
• pressure associated with capnoperitoneum
(Capnoperitoneal pressures of up to 28mm Hg have been advocated
to both improve surgical access and reduce venous bleeding)
• coughing.
How to prevent??
MgSO4
OPIOIDS like Remifent
DEXMED

70. MAGNESIUM SULPHATE
• inhibits adrenal catecholamine release
• reduces α-adrenergic receptor sensitivity to catecholamines
• dilates predominantly arteriolar vessels, reducing left ventricular
afterload while maintaining preload
• exerts antiarrhythmic effects via antagonism of L-type calcium
channels
• Dose-
• 3–5 μg/kg fentanyl combined with 40–60 mg /kg of
magnesium sulphate before intubation followed by an
infusion of 1–2 g /h

71. REMIFENTANIL
• alternative to fentanyl as its pharmacokinetic profile
facilitates rapid titration to effect
• Blunts haemodynamic response to intubation or pain
• inadequate in preventing hypertension associated
with tumour manipulation
DEXMEDETOMIDINE
• centrally acting selective α2-receptor agonist with sedative
and analgesic properties.
• Slow onset
• LD-1 μg/kg(over 10 min) and then infused at around 0.5 μg
/kg/h central sympatholytic
• effects result in substantial reductions in plasma
norepinephrine levels

72. MINIMIZING HAEMODYNAMIC
RESPONSES TO TUMOUR
HANDLING

73. • Early surgical ligation of the adrenal vein was
traditionally recommended to attenuate
intraoperative haemodynamic instability
• Surgicl ligation of the adrenal vein was
recommended to attenuate intraoperative
haemodynamic instability
• Hypertensive crises are generally managed with a
vasodilator
• Tachyarrhythmias, including the reflex tachycardia
seen with the use of many vasodilators, are controlled
with β-blockers
• β-Blockers also minimizes the excessive inotropy seen
with epinephrine-secreting tumour

74. PHEO: RX OF HTN CRISIS
When??
Intubation
Tumor manipulation
Hypocalcemia/hypercarbia
Rx
• IV phentolamine
• IV NTP
• IV NTG
• IV NIVARDIPINE
• IV esmolol
• IV labetalol – combined  +  blocker

75. PHENTOLAMINE
• reversible non-selective α-receptor antagonist
• results in vasodilatation and can lead to reflex
tachycardia
• administered as a bolus of 2-5 mg, has a short duration
of action, but may demonstrate tachyphylaxis
• particularly useful to control surges in arterial pressure
while establishing desired infusion rates of other drugs.

76. SODIUM NITROPRUSSIDE
• Nitric oxide donors
• SNP causes predominantly arteriolar dilatation
• Preferential use as the first-line vasodilator for phaeochromocytoma
surgery(more rapid decrease in arterial pressure)
• SNP may reduce coronary perfusion through its greater effect on
diastolic arterial pressure and theoretical potential to induce
intracoronary steal
• SNP infusions should be started at 0.5–1.5 μg /kg/min and increased
up to 4 μg /kg/min as required.
• the risk of cyanide toxicity is very low for intraoperative infusions of
<12 h in patients with normal renal and hepatic function
• Tachyphylaxis commonly becomes an issue after a continuous
infusion lasting over 24 h.
• Cover with foil paper and keep 4hrly monitoring

77. GLYCERYL TRINITRATE(NTG)
• Nitric oxide donors-
• 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
• GTN infusions are usually adjusted according to response within the
range of 10–200 μg/min or 0.5-10mcg /kg /min

78. NICARDIPINE
• a dihydropyridine calcium channel antagonist
• potent arterial vasodilator
• It is initiated at a rate of 3–5 mg/h for 15 min and adjusted by
increments of 0.5 or 1 mg/h every 15 min.
• Once the target pressure is achieved, the infusion should be
gradually reduced to 2–4 mg/h
• Hypertensive crises can be treated with boluses of 1–2 mg.
• Cardiac output is maintained without the tachycardia seen with
SNP and GTN
• its elimination half-life of 40–60 min can result in persistent
hypotension
• Clevidipine -shorter half-life via plasma and tissue esterase
hydrolysis and has been successfully used

79. INTRAOP TACCHYARRYTHMIAS
• Beta blockers
Propanolo 1mg increments
Atenolol
Esmolol
• Amiodarone – SVT with CCF
• Lidocaine - VT

80. ESMOLOL
• selective β1 antagonist
• rapid action and short duration. (t1/2 9mins)
• These properties make it the ideal β-blocker
• The initial loading dose is 500 μg/kg over 1 min, followed by a 4
min maintenance infusion of 50 μg/kg/min

81. TREATING HYPOTENSION AFTER
TUMOUR DEVASCULARIZATION

82. • Can be managed with a combination of fluid boluses, titration of
vasodilators and administration of direct α-receptor agonists.
• hypotension seen after devascularization of the tumour is relatively
common and may be both profound and catecholamine-resistant.
CAUSES
• residual α-blockade(preoperative use of phenoxybenzamine)
• Abrupt catecholamine deficiency after tumour resection
• catecholamine receptor down-regulation caused by chronic elevation of
catecholamine levels
• Hypotensive agents should be stopped
• Fluid balance optimization
• Rule out ongoing postoperative haemorrhage and myocardial
dysfunction.

83. VASOPRESSIN
• systemic vasoconstriction and pulmonary vasodilatation by acting on
V1 receptors.
• increases circulatory volume by acting on V2 receptors in the DCT
and collecting ducts of the kidney, thus increasing water
reabsorption.
• Bolus doses of 0.4–20 units were administered and subsequently
followed by an infusion of 1–3 mU/kg/min

84. METHYLENE BLUE
• It appears to function through a cyclic guanosine
monophosphate inhibition mechanism that plays a key
role in vasoplegic syndromes.
• It has been reported to have been used in refractory
vasoplegic patients with hepatic and renal failure, as well
as in the cardiac arena
• has been used for treatment of malaria,
methemoglobinemia, neonatal hypotension, as well as in
the surgical setting to detect urinary tract leaks
• Also used for location parathyroid adenoma

85. POSTOPERATIVE CARE

86. • Most patients should be suitable for extubation at the end of
surgery.
• Invasive arterial pressure monitoring in a high dependency
environment for at least 24 h after the procedure
1)DELAYED HYPERTENSION
• Upto 3 days post-op
• pain (most commonly)
• co-existing essential hypertension
• urinary retention
• fluid overload
• Inadvertent ligation of the renal artery precipitates hyper-
reninism.
• Persistent hypertension(>2weeks) (incomplete tumour
resection or metastatic disease)

87. 2)Lifelong steroid replacement
• indicated if a bilateral adrenalectomy has been performed
• 100 mg of hydrocortisone administered every 8 h.
• In the first postoperative 72 h, the hydrocortisone dosage is
weaned to 25 mg twice daily before being converted to oral
prednisolone.
3)Hypoglycaemia
• due to rebound hyper-insulinism
• (the inhibitory effect of norepinephrine on insulin producing
cells is eliminated )
• Hypoglycemia is masked by concurrent β-receptor blockade
• Regular blood glucose monitoring

88. 4)HYPOTENSION
• The mechanisms and management of postoperative
hypotension have been discussed previously.
• Most cases can stop all BP meds postop
• Postop hypotension: IV crystalloid
• HTN free: 5 years 74% 10 years 45%
FOLLOW UP
• 24h urine collection 2 wk postop
• Follow-up at 6 weeks and 6 months followed by an annual
review for at least 10 yr.
• Surveillance:
• 24h urine collections q1y for at least 10y
• Lifelong f/up

89. PHEO: UNRESECTABLE,
MALIGNANT
• -blockade
• Selective 1-blockers (Prazosin, Terazosin, Doxazosin)
1st line as less side-effects
• Phenoxybenzamine: more complete -blockade
• -blocker
• CCB, ACE-I, etc.
• Nuclear Medicine Rx:
• Hi dose 131I-MIBG or 111indium-octreotide depending
on MIBG scan or octreoscan pick-up
• Sensitize tumor with Carboplatin + 5-FU

90. PHEO & PREGNANCY
• Diagnosis with 24h urine collections
• MRI is safest modality
• No stimulation tests, no MIBG if pregnant
• Risk of supine hypotension syndrome + release of catecholamine by uterine
compression
• 1st & 2nd trimester (< 24 weeks):
• Phenoxybenzamine + blocker prep
• Resect tumor ASAP laprascopically
• 3rd trimester:
• Phenoxybenzamine + blocker prep
• When fetus large enough: cesarian section followed by tumor resection
• Vaginal deliver is strictly CI
• EA > GA/SA
• ergometrine/PG is CI as may inc BP
• MgSO4 is safe for use
dose – 40-60mg/kg iv bolus F/b 2g/hr iv infusion