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

Phase 2

Completed

• Conditions: Pheochromocytoma
• Interventions: Drug: General anesthetic; Drug: Dexmedetomidine

• Registration Number: NCT04320589
• Lead Sponsor: National Cancer Institute, Egypt

Brief Summary

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

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.

Study Timeline

• Study Start: 2019-06-30
• Study First Submitted: 2020-03-22
• Study First Submitted QC: 2020-03-22
• Study First Posted: 2020-03-25
• Status Verified: 2021-08
• Primary Completion: 2021-08-30
• Study Completion: 2021-08-30
• Last Update Submitted: 2021-08-30
• Last Update Posted: 2021-09-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
The rate of Hypertensive crisis	12 hours follow up	rise of B.P. more than 20% of base line

Trial Locations

Locations (1)

Department of Anesthesia and Pain medicine.National Cancer Institute; 🇪🇬 Cairo, Egypt