the Effect of Dexmedetomidine and Magnesium Sulfate in Open Resection of Pheochromocytoma
Condition: Pheochromocytoma
MeSH terms: Pheochromocytoma
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Dexmedetomidine; General anesthetic
Intervention type(s): Drug; Drug
Intervention description(s): 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]
Other intervention name(s): drug group; control group
Intervention MeSH terms: Dexmedetomidine; Anesthetics; Anesthetics, General
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention