Cerebral autoregulation (CA) is a physiological response to protect against a wide range of changing perfusion pressures to maintain a stable cerebral bloodflow. This is important in patients with intracranial space-occupying lesions where brain compliance may already be impaired. The use of dexmedetomidine is rapidly increasing in neuroanesthesia. Despite its widespread use, there are very few studies evaluating its effect on CA under the effect of anesthesia. This study will be done in patients with supratentorial tumors, who are possibly at critical autoregulatory threshold.

After getting approval from Institute’s Ethics Committee and obtaining written, informed consent from patients, a randomized double blind placebo-controlled trial will be conducted in American Society of Anesthesiologists (ASA) 1 patients, aged 18-60 years undergoing elective craniotomy and excision of supratentorial tumors. Patients with any history of neurological or vascular disease, syncope, dizziness, seizure or loss of consciousness, anticipated difficult airway, previous intracranial surgery and those unable or unwilling to give a written informed consent will be excluded from the study. Preoperative bilateral carotid Doppler will be performed to rule out carotid pathologies in all patients.

On the day of surgery, the patients will be pre-medicated with intramuscular glycopyrrolate 0.2 mg, thirty minutes before shifting to the operating theater (OT). Once the patient is shifted to the OT, routine monitors such as ECG, SpO2 and non-invasive blood pressure will be attached and an intravenous line will be secured. Bispectral Index (BIS) sensor will be placed to monitor and maintain the depth of anesthesia until the tests are completed. Invasive pressure monitoring by an arterial cannula will be secured under local anesthesia.

Anesthesia will be induced with fentanyl 2 µg/kg and propofol 1-2 mg/kg to achieve loss of response to verbal command. Tracheal intubation will be facilitated with rocuronium 1 mg/kg. Anesthesia will be maintained using oxygen with air and sevoflurane (2-3%) at a total fresh gas flow rate of 2 liters/minute to obtain a BIS value between 40 and 60. Analgesia and muscle relaxation will be maintained by a continuous infusion of fentanyl and rocuronium. Ventilation will be adjusted to maintain normocapnia. Hypotension will be treated with mephentermine 3 mg and bradycardia will be treated with atropine 0.4 mg to maintain these parameters within 20% of the baseline. After 5 minutes of constant BIS and EtCO2 values obtained within the pre-defined range, a TCD probe of 2 MHz frequency will be placed on the temporal bone window of the side with the tumor and the middle cerebral artery (MCA) will be insonated. The mean MCA flow velocity will be recorded as an average of three readings. The Transient Hyperemic Response (THR) Test will then be performed with the TCD probe in place while manually compressing the common carotid artery on the side of the tumor for 10 seconds. The Transient Hyperemic Response Ratio (THRR) will be calculated as the ratio of the peak hyperemic flow velocity recorded after carotid release and the pre-compression baseline MCA flow velocity. A ratio above 1.10 will be considered as intact autoregulation, while values lower than 1.10 will be taken as poor or absent autoregulation.

At the end of these baseline tests, patient randomization will be done based on computer-generated random numbers. Patient allocation will be done only after baseline tests have been conducted; patients with deranged intracranial compliance at baseline or in those with failure to obtain insonating window will be excluded from allocation. The patient will be allocated into one of the two groups using sequentially numbered, opaque sealed envelopes: drug or placebo. In the Study Group (Group D), the patient will receive infusion of dexmedetomidine (4 mg/ml dilution) 1mg/kg bolus over 10 minutes. Patients in the Control Group (Group C) will receive infusion of normal saline at identical rates through a similar syringe-infusion pump presuming that the syringe contains dexmedetomidine. An anesthesiologist who is not part of patient management will prepare the infusion of the test drug in a 50 ml syringe. At the completion of the infusion of the test drug, the Doppler tests will be repeated and the same measurements will be done in identical steps. Surgery will then be allowed to proceed and the infusion of the test drug will be stopped.

Based on a proforma that has already been made, records will be made of demographic parameters, intraoperative anesthesia-related details, hemodynamic parameters, as well as values derived from transcranial doppler such as MCA flow velocity at baseline (MCAFV1), during carotid compression (MCAFV2) and after release of compression (MCAFV3), pulsatility index, compression ratio and THRR.