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Jan 8, 2013

Preoperative Management of Pheochromocytoma


Pheochromocytomas arise from chromaffin cells mainly from adrenal medulla; can also arise from sympathetic ganglia, vagus nerve, carotid arteries, chromaffin tissue of bladder wall, rectum, gonads, renal, prostate and hepatic hili.

Symptoms are of excessive secretion of catecholamines (norepinephrine, epinephrine, or dopamine) into the circulation. Severe hypertension, often refractory to conventional treatment.

Response of receptors to catecholamines
·        Alpha 1 receptors cause vascular constriction
·        Alpha 2 receptors mediate the presynaptic feedback inhibition of norepinephrine.
·        Beta 1 receptors increase cardiac rate and contractility
·        Beta 2 receptors lead to arteriolar and venous dilation and relaxation of tracheobronchial smooth muscle

Alpha blockers

Patients of Pheochromocytoma are hypertensive and volume depleted

To control blood pressure in patients of Pheochromocytoma alpha blocker are drug of choice.  Some institutions use Phenoxybenzamine, which is long acting drug so need to be stopped at least one day before surgery and replaced with short acting alpha -1 blockers prazosin, terazosin, and doxazosin

Some advice to give alpha blockers for at least for 15 days before the surgery, so blood pressure stabilizes.

Intravenous Phenoxybenzamine can be given for 5days before surgery and replaced with short acting alpha-1 blockers a day before surgery.

Phenoxybenzamine is expensive drug, so many continue to use short acting alpha-1 blockers instead of Phenoxybenzamine.

In volume depleted patients alpa-1 blockers should be used with caution, because of hypotension during intra-operative and postoperative stage, managed with fluid and norepinephrine infusion.

Beta blockers

Beta blockers should never be given alone in patients of Pheochromocytoma. Beta blockers are to be given after adequately stabilizing with alpha blockers (unchecked alpha stimulation can lead to severe hypertension). Beta blockers are useful for controlling tachycardia.

Beta blockers are avoided in patients with LV dysfunction in patients of Pheochromocytoma.

Combined alpha and beta blockers

Labetalol a combined alpha and beta blocker is not a primary drug for preoperative management of Pheochromocytoma.

Needed alpha and beta block is 4:1 but with Labetalol it is 1:7, which may result in paradoxical episodes of hypertension or even hypertensive crisis

Calcium channel blockers.

These drugs are less effective than alpha blockers but are still useful to control blood pressure and heart rate.

These drugs block Norepinephrine mediated calcium influx into vascular smooth muscle, thereby controlling hypertension and tachyarrhythmias.

Role of calcium channel blockers in pheochrocytoma
·        These drug are can be used to supplement alpha blockers
·        Replace alpha blockers in patients with severe side effects
·        To prevent catecholamine induced arrhythmia
·        To prevent adrenoceptor blocker-induced sustained hypotension in patients with only intermittent hypertension
·        Useful when Pheochromocytoma is associated with catecholamine-induced coronary vasospasm.
·        Primary drug in Pheochromocytoma patients with normal blood pressure.

Catecholamine Synthesis Inhibition

Alpha -Methyl-L-tyrosine or Metyrosine (Demser) is an analog of tyrosine that competitively inhibits tyrosine hydroxylase, the rate-limiting step in catecholamine biosynthesis

Metyrosine significantly depletes catecholamine stores but not completely so it needs to be combined with catecholamine antagonists.

Metyrosine is useful in patients with extensive mets and uncontrolled hypertension
Some centers use Metyrosine routinely see algorithm

Metyrosine controls blood pressure both pre and intra operative stages, especially during surgical manipulation of tumor.

Side effects sedation, often sleepiness, depression, anxiety, galactorrhea, and rarely causes extrapyramidal signs (e.g. Parkinsonism in elderly patients)
Algorithm of Preoperative Management of Pheochromocytoma


Drugs and food to be avoided

Norepinephrine and Epinephrine release can be provoked  by glucagon, steroids, histamine, angiotensin II, and vasopressin so avoided

Tyramine in cheese, bananas, wine, soy sauce, avocados, and any fermented, smoked, or aged meat and fish are avoided.

Anti –obesity drugs, ephedrine, pseudoephedrine, or phenylpropanolamine tricyclic and other antidepressants, amitriptyline , nortriptyline , edronax , duloxetine , venlafaxine, cocaine are also avoided.