Anaesthetic management of pheochromocytoma Dr. S. Parthasarathy MD., DA., DNB, MD (Acu), Dip. Diab.DCA, Dip. Software statistics- Phd Mahatma Gandhi Medical college and research institute , puducherry , India
What is it ?? • Pheochromocytomais a rare catecholamine secreting tumor arising commonly from adrenal medulla and to some extent from other paraganglia of the sympathetic chain but can arise from any part of the body • Intra adrenal – pheo ( WHO – 2004) • Others – extra adrenal paragangliomas • with an incidence of 1.55-2.1 per million population per year.
Why is it so called ?? • Pheo --- dusk • Chromo – colored • Cytoma -- tumour • Roux and Mayo performed succesful surgery in 1926 • Still we are discussing
the “rule of 10” • 10% of the tumors are bilateral, • 10% are extra-adrenal, • 10% of the tumors undergo malignant change 10% of the patients, pheochromocytoma exist with various familial disorders such as multiple endocrine neoplasia (MEN) syndromes [MEN 2A and 2B], von Recklinghausen disease, and von Hippel Landau syndrome.
MEN type IIA or IIB. • Type IIA includes medullary carcinoma of the thyroid, parathyroid hyperplasia, and pheochromocytoma; • Type IIB consists of medullary carcinoma of the thyroid, pheochromocytoma, and neuromas of the oral mucosa. • Pheochromocytomas may also arise in association with von Recklinghausen neurofibromatosis or von Hippel-Lindau disease (retinal and cerebellarangiomatosis
Systolic blood pressure changes – fluctuations present Epinephrine • More consistent high BP – norepinephrine
Subtle signs • Paroxysmal hypertension associated with a normal blood pressure between crises occurs in 50% of patients. • 30% of patients will have sustained hypertension. • Twenty-four–hour ambulatory blood pressure monitoring. • Orthostatic hypotension is also a common finding and considered to be secondary to hypovolemia and impaired venous and arterial vasoconstrictor reflex responses.
Feeling of doom • “ I thought I was going to die “ • Mimicking • Pregnancy ?? Toxemia
Adult pheochromocytomas are solid, highly vascular tumors usually 3 to 5 cm in diameter and average 100 g in weight (range, 1.0–4000 g). The average-size adult pheochromocytoma contains 100 to 800 mg of norepinephrine. • Rt adrenal more common
How to diagnose ?? • Secretions • Degradation products Intratumour degradation !! • Imaging
Adrenal CT and MRI have comparable sensitivity and specificity. Metaiodobenzylguanidine (MIBG) scanning offers superior specificity to MRI and CT, and is particularly helpful in localizing extra adrenal masses
Normal plasma level of catecholamines… - free epinephrine= 30 pg/ml (0.16 n mol/L) - free norepinephrine= [200 – 1700 mcg/ml] 300 pg/ml (1.8 n mol/L) - free dopamine= [<30 mcg/ml] 35 pg/ml (0.23 n mol/L) • T 1/2 ~ 2 minutes • Plasma Metanephrines • May be interfered by drugs ?? Paroxysms
Plasma free normetanephrine greater than 400 pg/mL and/or metanephrine greater than 220 pg/mL is diagnostic of a pheochromocytoma. • If normetanephrine is 112 to 400 pg/mL or metanephrine is 61 to 220 pg/mL, the diagnosis is equivocal. • A pheochromocytoma is excluded if normetanephrine is less than 112 pg/mL and metanephrine is less than 61 pg/mL.
24 hour urine… - Normetanephrine= 50 – 840 mcg/ml - Metanephrine= 0 – 370 mcg/ml - Vanillylmandelic acid (VMA) = <7.2 mcg/ml - Norepinephrine = 13 – 107 mcg/ml - Epinephrine = 0 – 15 mcg/ml
Clonidine suppression • 50 % suppression will not be there • Glucagon stimulation test • –increase plasma catecholamine but bp better with Pre admin with nifidepine
Hyperglycemia • Hypercholesterolemia • Hyperenninemia • Hypercalcemia • Steroids • Glucagon • Anaemia or polycythemia • ECG • ECHO • Chest Xray
Preoperative preparation • Rate • Blood pressure • Arrhythmias • End organ damage • WHY ??
The perioperative mortality associated with phaeochromocytoma is around 2% - unprepared may go upto 50 % • Induction without preparation may be hazardous • Venodilation and
Alpha blockers • Phenoxybenzamine • oral phenoxybenzamine 20 mg tds • with a maximum dose of 250 mg. • a long duration of alpha blockade and non-competitive blockade as a result of covalent binding to drug receptors prevents the frequent surges of catecholamine releases during pre-op period. • it blocks alpha-2 receptors also thereby inhibiting the feedback loop for release of nor-epinephrine and as a result huge amount of nor-epinephrine is released causing undesirable chronotropic and inotropic effects
Phenoxybenzamine • Increased post-op somnolence, headache, stuffy nose, and postural hypotension are some of the major side effects of phenoxybenzamine. • Insensitive to postop agonists • Can result in excess fluid administration and edema. • Tachycardia – beta blockers to be added – aten, metoprolol
So what do we need ?? • Prazosin 1 mg tdsupto 12 mg/ day – selective alpha 1 blocker • Doxazocin 2 – 4 mg/ day – long life • May not need beta blockers • Terazocin – similar but shorter half life • Proved doxazocin + labetolol 100 mg / day – effective
Do we need beta blockers ?? • Symptom free • Rate • Arrhythmias • Epinephrine and dopamine secreting tumours • Beta blockers only after sufficient arteriolar dilation – 2 weeks of Alpha blockers
Atenolol 100 mg/ day • Bisoprolol 10 – 20 mg / day • Labetolol 100 mg – 400 mg / day • Carvidolol 3. 25 mg • But propronolol – COPD and PAD • Celiprolol – newer – 200 mg / day – beta 1 antagonist but beta 2 agonist
Other drugs • SNP • 0.5–1.5 µg/kg/min initially, increased to maximum of 8 µg/kg/min; titrate to effect. Powerful vasodilator; short acting. • Nicardipine1–2 µg/kg/min increased to 7.5 µg/kg/min; titrate to effect. • Octreotide • magsulf
Adequate control achieved ?? • BP 160/ 90 or less • Mild orthostatic hypotension > 80/45 • No arrhythmias • ECG should be free of ST-T changes • Nasal congestion Roizen’s criteria
Goals • Intraoperative goals include avoiding drugs or maneuvers that may provoke catecholamine release or potentiate catecholamine actions and maintaining cardiovascular stability, preferably with short-acting drugs.
Intra op problems • hypertension and/or arrhythmias • anesthetic induction, • intubation, surgical incision, • abdominal exploration and particularly during tumor manipulation, • secondary to hypotension following ligation of the tumor’s venous drainage.
During laparoscopic surgery, creation of the pneumoperitoneum may cause release of catecholamines and large changes in hemodynamics that can be controlled with a vasodilator • Acute pulmonary edema can complicate the picture • Shorter post op stay !!!
Monitors • Routine + • CVP – • pressure change of more than 10 with IPPV- hypovolumia • Arterial catheter • PAC when dysfunction • Urinary output • TEE • Depth • Glucose , electrolytes
Iv fluids • RL or physiologic saline are the recommended fluids for use prior to tumor removal and a dextrose-containing solution should be added after tumor removal. A large positive fluid balance is usually required to keep intravascular volumes within a normal range.
Anaesthetic concerns – technique does not matter Prevent catecholamine surge Decrease ANS involvement
Factors that stimulate catecholamine release such as fear, stress, pain, shivering, hypoxia, and hypercarbia must be minimized or avoided in the perioperative period. • GA or RA + GA – OK • Midthoracic epidural with GA • Can epidural block surges ??
Anesthetic drugs that appear safe include thiopental, etomidate, benzodiazepines, fentanyl, sufentanil, alfentanil, enflurane, isoflurane, nitrous oxide, vecuronium, and rocuronium. • Despite these recommendations, the choice of anesthetic is not as crucial as the understanding with which the agents are used.
Say no to drugs !! • Scoline • Atracurium • Morphine • Ephedrine • Metoclopramide • Ketamine • Desflurane . Halothane
Intra op hypertension • Usually surges of 200 mmHg • SNP • Phentolamine • Labetolol • dexmed • Isoflurane • Epidural
Intra op arrythmias • Lignocaine • Esmolol
Blood loss ?? • No blood salvage • Inotropes ready – phenylephrine – better for hypo if volume status corrected • Vasopressin after clamps – better if down regulation suspected • Antiemetics – droperidol 0.625 mg IV with dexa
Postoperative Management • Patients usually remain in the ICU for at least 24 hours. Adequate pain control is essential, although somnolence and an increased sensitivity to narcotic analgesics have been observed. • The need for controlled ventilation is dictated by the extent of surgery, the site of surgery, and the patient’s medical condition.
The majority of patients become normotensive following complete tumor resection. • Plasma catecholamine levels do not return to normal until 7 to 10 days after surgery due to a slow release of stored catecholamines from peripheral nerves. • Fifty percent of patients are hypertensive for several days following surgery, • 25% to 30% of patients remain hypertensive indefinitely • Post op hypoglycemia ??
Hypertension post op ?? • Is there a metastasis ?? • Is it incomplete ?? • Is there a renal ischemia ?? • Steroid supplementation is necessary for patients who had bilateral adrenalectomies or if hypoadrenalism is suspected.