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.

Study Overview

• Status: Completed
• Conditions: Pheochromocytoma
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: General anesthetic

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11796
    • Department of Anesthesia and Pain medicine.National Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 69 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: General Anesthesia; 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; 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; Other Names: drug group
Active Comparator: Dexmedetomidine; 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; 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]; Other Names: control group

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute, Egypt
• Investigators: Principal Investigator: Ehab H Shaker, MD, National Cancer Institute- Cairo University

Publications and helpful links

Helpful Links

• Dexmedetomidine as intravenous sedating agent

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2019
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: March 22, 2020
• First Submitted That Met QC Criteria: March 22, 2020
• First Posted (Actual): March 25, 2020

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Paraganglioma; Pheochromocytoma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Anesthetics; Dexmedetomidine; Anesthetics, General
• Other Study ID Numbers: Ehab - Hegazy pheochromocytoma

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: After total completion of the study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No