After obtaining approval from our Ethical Committee (no: 17100267), we conducted this prospective, randomized, double-blind placebo controlled clinical study at the Department of Anesthesia and Intensive Care Unit during the period between April 2018 and March 2020. A written informed consent from all participants was obtained. The study was registered at ClinicalTrial.gov and the number is NCT03204006. The study was conducted and adherent to the CONSORT guidelines and to the regulations and amendments of Helsinki Declaration.

Seventy patients with controlled hypertension undergoing general anesthesia were enrolled in the study with the ages ranging from 20 to 60 years old with American Society of Anesthesiologists (ASA) class II. Based on join national committee on hypertension (JNC-8), hypertension was defined as systolic blood pressure >140 mmHg and or diastolic blood pressure > 90 mmHg.

The exclusion criteria included (1) failure to obtain patient’s consent or patient’s refusal; (2) history of myocardial infarction or abnormal electrocardiogram at the time of anesthesia; (3) cardiovascular, pulmonary, renal, or hepatic diseases; (4) patients on beta blockers; and (5) patient with difficult airway; laryngoscopy and intubation exceeded 20 s or requiring > 2 attempts.

Enrolled patients were randomly assigned into two equal groups: control which received 20 ml sodium chloride 0.9% and dexmed group which received intravenous dexmedetomidine 0.5 mcg/kg diluted to 20 ml with sodium chloride 0.9% as infusion over 10 min (Basar et al. 2008). Each group had 35 patients. Randomization was based on computer-generated codes maintained in sequentially numbered opaque envelopes. The infusions were prepared by an independent anesthesiologist not involved in this study.

Preoperative assessment, including history taking, physical examination, and review of the results of routine investigations, was done for all patients. Patients’ demographics and clinical data, such as age, weight, and gender, were recorded.

Standard monitors were connected to all patients which included 5-lead electrocardiogram, pulse oximetry, non-invasive blood pressure, and capnography. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) were measured before induction of anesthesia as a baseline reading. A standard protocol of anesthetic management was used for all patients. Pre-oxygenation by O2 100% for 3 min after intravenous access. Sodium chloride 0.9% was infused at rate of 4 ml/kg/h. The study drug (dexmedetomidine 0.5 mcg/kg or sodium chloride 0.9%) was administered intravenously using a syringe pump over 10 min. It started and finished just before induction of anesthesia.

General anesthesia was induced by fentanyl 1μg /kg, propofol 1.5–2 mg/kg, intravenous lignocaine 1 mg/kg, and cisatracurium 0.15 mg/kg for endotracheal intubation. Trachea was intubated after 3 min of mask ventilation with oral endotracheal tube of appropriate size under direct laryngoscopy. Isoflurane inhalational anesthetic with 50% oxygen in air and cisatracurium 0.03 mg/kg was used for maintenance of anesthesia. The lungs were mechanically ventilated to keep intra-operative end-tidal carbon dioxide (EtCO2) between 35 and 40 mmHg. At the end of surgery and discontinuing isoflurane inhalation, neostigmine 2.5 mg and atropine 1 mg were used for muscle relaxant reversal.

Hemodynamic variables (HR, SBP, DBP, MBP) were recorded at baseline, after 5 min of study drug infusion, 3 min after induction and prior to intubation, 1 min after intubation, 3 min after intubation, and 5 min after intubation. Frequency of hypotension, bradycardia, and change in electrocardiogram were recorded. Bradycardia (heart rate<60 beat\min) was managed with intravenous atropine 0.5 mg while hypotension (mean arterial blood pressure <20% of baseline) was treated with intravenous ephedrine 5 mg. The primary outcomes of this study were the changes in the heart rate pre- and post-induction of anesthesia. Secondary outcomes included systolic blood pressure, diastolic blood pressure, mean arterial pressure, and occurrence of hypotension or bradycardia.

Data was collected and analyzed using SPSS (Statistical Package for the Social Science, version 20, IBM, Armonk, NY). Continuous data was expressed in the form of mean ± SD or median (range) while nominal data was expressed in the form of frequency (percentage).

Chi-square test was used to compare the nominal data while Student’s t-test was used to compare means of two groups. P value was significant if < 0.05.

The primary outcome of this study was the change in the heart rate. The sample size was selected by using estimates of the sample size proportions (α=0.05) and a power of 80%. If dexmedetomidine reduces the heart rate by 20%, the estimated sample size would be 32 patients in each group. We enrolled 35 patients in each group to compensate for possible drop out.