Clinical trial NCT04266665: Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome
Official title: Effect of Dexmedetomidine on Brain Homeostasis and Neurocognitive Outcome of Patients Undergoing Brain Tumor Exclusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Brain Tumor
Metabolic Disturbance
Inflammatory Response
Oxygen Deficiency
Keywords: dexmedetomidine
brain oxygenation
biomarkers
neuroinflammation
brain metabolism
neurocognitive outcome
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
First posted: 2020-02-12
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Eligibility criteria: Inclusion Criteria:

* ASA-PS 1-3 (American Society of Anesthesiologists Physical Status classification)
* Scheduled for elective or semi-elective craniotomy for brain tumor resection
* Signed informed consent

Exclusion Criteria:

* History of craniotomy at the same site
* Morbid obesity
* Delirious person before surgery
* Preoperative heart rate (HR) \<45 beats/min or second or third degree AV block
* Treatment with a-methyldopa, clonidine or other a2-adrenergic agonist
* Pregnancy
* Liver or renal failure

Primary outcomes:
measure: Changes in S-100b protein
timeFrame: End of surgical procedure and 24 hours postoperatively
measure: Changes in NSE
timeFrame: End of surgical procedure and 24 hours postoperatively
Secondary outcomes:
measure: Changes in serum cortisol
timeFrame: End of surgical procedure and 24 hours postoperatively
measure: Changes in serum TNF-a
timeFrame: End of surgical procedure and 24 hours postoperatively
measure: Changes in serum IL-6
timeFrame: End of surgical procedure and 24 hours postoperatively
measure: Changes in Mini-Mental State Exam (MMSE)
timeFrame: 1 week and 1 month after the end of surgical procedure
measure: Changes in Μontreal Cognitive Assessment (MoCA)
timeFrame: 1 week and 1 month after the end of surgical procedure
measure: Changes in Addenbrooke's Cognitive Exam (ACE III)
timeFrame: 1 week and 1 month after the end of surgical procedure
Other outcomes:
measure: Changes in jugular venous oxygen saturation
timeFrame: 10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure
measure: Changes in arterio-jugular oxygen difference (AjvDO2)
timeFrame: 10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure
measure: Changes in arterio-jugular carbon dioxide difference (AjvCO2)
timeFrame: 10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure
measure: Changes in brain oxygen extraction ratio (O2Erbr)
timeFrame: 10, 30, 60, 120, 240 minutes after commencing the infusion of the tested agent and end of surgical procedure
Locations:
city: Thessaloniki
country: Greece
facility: AHEPA University Hospital
Study officials:
affiliation: Aristotle University Of Thessaloniki
name: Georgia Tsaousi, Professor
role: PRINCIPAL_INVESTIGATOR
References: