the Effect of Dexmedetomidine and Magnesium Sulfate in Open Resection of Pheochromocytoma

The Perioperative Use of Dexmedetomidine and Magnesium Sulfate Compared With Traditional Anesthetic Technique for Open Resection of Pheochromocytoma.

Pheochromocytoma (pheo) is a catecholamine secreting tumor arising from chromaffin cells of the adrenal medulla in 90% of cases & in 10% is extra-adrenal arising from the sympathetic chain. It is malignant in 10% of cases, bilateral in 10% of patients & 10% of all pheo are inherited (Familial Pheo) as autosomal dominant either alone or as a part of multiple endocrine neoplasia (MEN) syndrome.In this prospective work, the investigators will try to compare the peri-operative hemodynamic course of Dexmedetomidine & magnesium sulphate (MgSo₄) infused patients with the traditional anesthetic technique (α₁ & β-adrenergic blockers plus vasodilators) during open surgical resection of Pheo. The investigators are aiming to check the safety & efficacy of the recommended technique on the peri-operative hemodynamic stability & controlling the hypertensive crisis during tumor manipulation.

Pheochromocytoma (pheo) is a catecholamine secreting tumor arising from chromaffin cells of the adrenal medulla in 90% of cases & in 10% is extra-adrenal arising from the sympathetic chain. It is malignant in 10% of cases, bilateral in 10% of patients & 10% of all pheo are inherited (Familial Pheo) as autosomal dominant either alone or as a part of multiple endocrine neoplasia (MEN) syndrome.The anesthetic management of Pheo during surgical resection is usually challenging & faces many cardiovascular risks as tachycardia, arrhythmias, severe hypertension & may be pulmonary edema & profound hypotension after surgical devascularization of the tumor. These dangerous events are sequelae of catecholamine excess and often are refractory to management . The proper anesthetic control is based on the use of α₁ & β-adrenergic blockers (phenoxy-benzamine, phentolamine, propranolol, labetalol) and vasodilators such as glycerine trinitrate (GTN) & sodium nitroprusside (SNP) .The rational of using magnesium sulphate MgSo₄ infusion to control catecholamine levels & catecholamine-related crisis has been established in several clinical emergencies such as severe tetanus & preoperative management of pre-eclampsia & eclampsia . MgSo₄ beneficial cardiovascular effects may be attributed to its ability to reduce catecholamine release from the adrenal medulla & to reduce α-adrenergic receptors sensitivity to catecholamines . MgSo₄ is also a direct vasodilator & a potent anti-arrhythmic drug particularly with high circulatory catecholamine level . The safety of MgSo₄ in the routine clinical range of 2-4 mmol/Liter is well settled in many clinical works. There is strong evidence that the sympathetic nervous system is intact in Pheo patients & neurons-released noradrenaline plays a fundamental role in blood pressure BP regulation. Dexmedetomidine is a short acting & highly selective central α₂-agonist that inhibits neuronal firing & thereby induces analgesia, anxiolysis, bradycardia & hypotension. It has been tried to attenuate the sympathetic pressor effect of tracheal intubation, cardiac surgeries & emergence from anesthesia .The unique adventitious anesthetic pharmacology induces preoperative sedation, intra-operative hemodynamic stability beside reducing the anesthetic requirements and adding to post-operative analgesia . Its peri-operative use has been suggested in both pediatric & adult patients of Pheo. In this prospective work,the investigators tried to compare the peri-operative hemodynamic course of Dexmedetomidine & MgSo₄ infused patients with the traditional anesthetic technique (α₁ & β-adrenergic blockers plus vasodilators) during open surgical resection of Pheo. The investigators are aiming to check the safety & efficacy of this recommended technique on the peri-operative hemodynamic stability & controlling the hypertensive crisis during tumor manipulation.

Traditional group in which the patients̕ hemodynamic adjustment will be conducted using orally or IV α₁ & β-adrenergic blockers [Prazosin (minipress): 0.5-20 mg/day, Propranolol (Inderal) :10-360 mg/day, Bisoprolol (Concor): 2.5-20 mg/day, Atenolol (Tenormin): 25-100 mg/day &/or Labetalol (Trandate)200-600 mg/day, Angiotensin Converting enzyme inhibitors ( ACE inhibitors ) & Angiotensin II receptor blockers ARBs e.g. Tritace 2.5-10 mg/day & Atacand 4-16 mg/day]

Dexmedetomidine-Magnesium Sulfate (Dex-MgSo₄) group: in which in addition to the orally prescribed drugs; on admission to the ICU, the Pheo-patient has serum-Mg level measurement & a bolus of 40 mg/kg MgSo₄ is given I.V. & may be repeated until the therapeutic level of MgSo₄ 2-4 mmol/Liter is reached. Dexmedetomidine sedation is started the evening prior to surgery by loading dose of 1µg/Kg followed by 0.2-0.7 µg/Kg/hour according to each patient

which in addition to the orally prescribed drugs; on admission to the ICU, the Pheo-patient has serum-Mg level measurement & a bolus of 40 mg/kg MgSo₄ is given I.V. & may be repeated until the therapeutic level of MgSo₄ 2-4 mmol/Liter is reached (7&10). Dexmedetomidine sedation is started the evening prior to surgery by loading dose of 1µg/Kg followed by 0.2-0.7 µg/Kg/hour according to each patient

1) Traditional group in which the patients̕ hemodynamic adjustment will be conducted using orally or IV α₁ & β-adrenergic blockers [Prazocin (minipress): 0.5-20 mg/day, Propranolol (Inderal) :10-360 mg/day, Bisoprolol (Concor): 2.5-20 mg/day, Atenolol (Tenormin): 25-100 mg/day &/or Labetalol (Trandate)200-600 mg/day, ACI & ACRB e.g. Tritace 2.5-10 mg/day & Atacand 4-16 mg/day]

Inclusion Criteria: Age 12-69 years ASA physical status I &II Surgically diagnosed pheochromocytoma, "unilateral or bilateral, adrenal or extra-adrenal". Diagnosis is confirmed radiologically with or without laboratory Vanillyl Mandelic Acid (VMA) level. Accepted Echo-heart data (EF ≥ 55%, no serious valve lesion) apart from hypertensive concentric ventricular hypertrophy & diastolic dysfunction grade I &II. Exclusion Criteria: Extremes of age ASA III & IV History of cardiac (MI & IHD) or cerebral (CVS) events History of major reaction to the used drugs History of major muscle, endocrinal or hematologic disorders Pregnant and lactating women Poor Echo-heart findings e.g. EF < 55%, severe valve lesions & severe pulmonary hypertension.