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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pheochromocytoma

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: General anesthetic


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: General Anesthesia<br>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] | Drug: Dexmedetomidine<br>* 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<br>* Other names: drug group;|
| Active Comparator: Dexmedetomidine<br>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 | Drug: General anesthetic<br>* 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]<br>* Other names: control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of Hypertensive crisis | rise of B.P. more than 20% of base line | 12 hours follow up |