This study is a prospective, randomized, single-blinded controlled trial conducted at AIIMS, Raipur, comparing opioid-free and opioid-based anaesthesia in patients undergoing elective supratentorial craniotomy. The study includes adult patients aged 18–65 years with a BMI of 18.5–29.9 kg/m², ASA grade 1 and 2, and a GCS of 15. Exclusion criteria include patients with hepatic, renal, or cardiac insufficiency, uncontrolled hypertension, prior opioid use, raised ICP, or those requiring postoperative ventilation. A total of 70 patients (35 per group) are enrolled based on a sample size calculation derived from previous studies, ensuring 80% power and a 5% significance level.

Patients are randomized into two groups using a computer-generated block randomization method, with allocation concealed in sequentially numbered opaque envelopes. Group A (opioid-free anaesthesia) receives dexmedetomidine (bolus: 0.5 mcg/kg; maintenance: 0.4 mcg/kg/hr) and ketamine (maintenance: 0.25 mg/kg/hr), while Group B (opioid-based anaesthesia) receives fentanyl (bolus: 2 mcg/kg; maintenance: 0.5 mcg/kg/hr). All patients also receive a scalp block with bupivacaine, sevoflurane-based anaesthesia, intravenous acetaminophen infusion, and ondansetron for PONV prophylaxis.

Intraoperative monitoring includes continuous assessment of heart rate, mean arterial pressure, and blood pressure at various surgical stages. Postoperative evaluations include pain scores (NRS/VAS), PONV incidence, and the use of rescue analgesics and anti-emetics at specific intervals: immediate post-op, 30 minutes, 1, 2, 3, 6, 12, and 24 hours. Data are analyzed using unpaired t-tests or Mann-Whitney U tests for quantitative variables and Chi-square or Fisher’s exact tests for qualitative data, with a p-value of <0.05 considered statistically significant. The study aims to evaluate the effectiveness of opioid-free anaesthesia as a potential alternative to opioid-based regimens while minimizing associated side effects.