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

NCT ID: NCT04320589

Last Updated: 2021-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-30
• Study Completion Date: 2021-08-30

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.

Conditions

Pheochromocytoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

General Anesthesia

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

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

General anesthetic

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

General anesthetic

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

Intervention Type: DRUG

Other Intervention Names

drug group; control group

Eligibility Criteria

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, Egypt

OTHER

Sponsor Role: lead

Responsible Party

Ehab Hanafy Shaker

lecturer of anesthesia ,critical care and pain medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ehab H Shaker, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute- Cairo University

Locations

Department of Anesthesia and Pain medicine.National Cancer Institute

Cairo, , Egypt

Countries

Egypt

Related Links

https://anesthesiology.pubs.asahq.org/article.aspx?articleid=1942849

Dexmedetomidine as intravenous sedating agent

Other Identifiers

Ehab - Hegazy pheochromocytoma

Identifier Type: -

Identifier Source: org_study_id