Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome
Condition: Brain Tumor; Metabolic Disturbance; Inflammatory Response; Oxygen Deficiency
MeSH terms: Brain Neoplasms; Hypoxia
Study type: Interventional
Phase: Phase 4

Summary: 
      Brain tumor surgery is commonly associated with different degrees of preoperative
      intracranial hypertension and surrounding tumor edema, elicited by tumor underlying
      pathophysiology. During craniotomy for brain tumor resection maintenance of hemodynamic
      stability and intracranial homoeostasis is of paramount importance. Disordered hemodynamics
      or adverse stress may activate the immune inflammation or neuroendocrine responses and lead
      to a surge of inflammatory mediators and stress hormones, which are implicated in secondary
      brain insults.

      Adverse physiological responses caused by intraoperative disordered hemodynamics or
      surgery-related damage, may lead to some secondary brain injury (such as cerebral edema or
      cerebral hemorrhage), aggravating damage to brain tissue and affecting the recovery from
      anesthesia, cognition and prognosis in patients.

      Prevention of secondary brain injury is a key-endpoint to improve clinical outcomes in glioma
      patients undergoing craniotomy.

      Alpha2-adrenoceptor agonists have been widely used for sedation, analgesia and
      anti-sympathetic actions for many years, but the definite evidence of their potential use as
      neuroprotectants has so far been confined to animal studies, yet the findings are
      inconsistent.

      Dexmedetomidine (DEX) has been demonstrated to be a new type a2 adrenergic receptor (a2-AR)
      agonist, which can selectively bind with the a1 and a2 adrenergic receptor, and playing a
      dual role by restraining the activity of sympathetic nervous and stimulating the vagus nerve.
      Dexmedetomidine (DEX) also plays an important role in in inhibiting inflammatory and
      neuroendocrine responses. Animal experiments showed that the right must have a
      dexmedetomidine neuro-protective effect. However, the brain-protective effect of
      dexmedetomidine in anesthesia of craniotomy resection of glioma has not been reported.

      Thus, the aim of this study was to explore the effect of dexmedetomidine on perioperative
      brain protection, as well as cerebral oxygenation and metabolic status aiming to provide a
      basis for clinical rational drug use in patients undergoing craniotomy resection of glioma.
    

Detailed description: 
      Each participant will receive standard monitoring (ECG, SpO2, SBP, BIS, urine output,
      temperature). More detailed hemodynamic monitoring will be obtained by Edwards Lifesciences
      ClearSight system (CO, CI, SV, SVI, SVV, SVR, SVRI).

      TCI Propofol and Remifentanil will be the agents of choice for induction and maintenance in
      anesthesia and cisatracurium will be used for neuromuscular blockade for intubation.

      Protective mechanical ventilation will be chosen (7ml/kg IBW) with a respiratory rate to
      obtain a PaCO2 of 35-40 mmHg. PEEP will be changed for the best PaO2/FiO2 ratio and FiO2 of
      choice will be 0.5.

      The radial artery catheterization will be applied for direct blood pressure measurement and
      arterial blood gas sampling (pH, PaO2, PaCO2, HCO3, BE, osmolality, lactic acid, Hb, glucose,
      Na and K will be measured).

      The jugular bulb ipsilateral to the craniotomy site will be catheterized for receiving blood
      samples for blood gas analysis. The following oxygenation and metabolic parameters /
      derivates will be measured or calculated: SjvO2, pH, PjvO2, PjvCO2, HCO3, BE, Osmolality,
      Lactic acid jv, Hb, Glucose, Na, K, AjvDO2, AjvCO2, O2ERbr, eRQbr, AjvDL, and LOI.

      Dexmedetomidine or normal saline (placebo) administration will start 10 minutes after
      anesthesia induction and maintained throughout the surgical procedure.

      Phases

        -  T0: 5 minutes before administration of either DEX or placebo

        -  T15: 10 minutes after administration of either DEX or placebo

        -  T30: 30 minutes after administration of either DEX or placebo

        -  T60: 60 minutes after administration of either DEX or placebo

        -  T120: 120 minutes after administration of either DEX or placebo

        -  T240: 240 minutes after administration of either DEX or placebo

        -  End of surgical procedure Blood samples for measuring S-100b, NSE, cortisol, TNF-a and
           IL-6 will be obtained at phases T0, end of surgery and 24 hours after administration of
           either DEX or placebo.

      Neurocognitive testing will be performed before surgery, 1 week and 1 month later using
      Karnofsky Performance Status (KFS), Mini Mental State Exam (MMSE), Μontreal Cognitive
      Assessment (MoCA) and Addenbrooke's Cognitive Exam (ACE III).

      Intraoperative consumption of propofol and remifentanil will also be recorded
    

Intervention name(s): Dexmedetomidine; Normal saline
Intervention type(s): Drug; Other
Intervention description(s): Dexmedetomidine 2 μg/ml will be given as bolus 1mg/kg for 10 minutes with a maintenance dose of 0.8μg/kg/h until surgery completion; Equivalent doses for a solution containing 2mcg/ml of the tested drug calculating for a bolus 1mg/kg for 10 minutes with a maintenance dose of 0.8μg/kg/h until surgery completion
Other intervention name(s): Dexdor; NaCl 0.9%
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: dexmedetomidine; brain oxygenation; biomarkers; neuroinflammation; brain metabolism; neurocognitive outcome