Effect of Pregabalin on Optic Nerve Sheath Diameter in Craniotomy Patients.

This study is a prospective, randomized, double-blind, placebo-controlled trial. It will be conducted in the operating rooms and neurosurgical intensive care unit at the study hospital. The study population consists of adult patients aged eighteen to sixty-five years who are scheduled for elective supratentorial craniotomy to remove a brain tumor.

Participants will be randomly assigned in a one-to-one ratio to receive either pregabalin 150 mg or an identical placebo capsule. The study drug will be administered orally on the evening before surgery and again ninety minutes before anesthesia induction on the day of surgery. Neither the participants nor the treating physicians or outcome assessors will know which group the participant belongs to.

The primary outcome of the study is the optic nerve sheath diameter measured by ultrasound at the pre-induction time point, which is ninety minutes after the second dose of the study drug. An optic nerve sheath diameter greater than 5.5 millimeters is considered indicative of elevated intracranial pressure. Secondary outcomes include optic nerve sheath diameter at baseline, upon intensive care unit arrival, and twenty-four hours after surgery; the incidence of elevated optic nerve sheath diameter at each time point; postoperative pain scores; total opioid consumption in the first twenty-four hours; time to first pain medication request; the incidence of postoperative delirium; quality of recovery scores; preoperative anxiety levels; and any adverse events such as sedation, dizziness, nausea, or vomiting.

The sample size is one hundred participants, with fifty participants in each group. This calculation was based on an expected difference of 0.3 millimeters in optic nerve sheath diameter between groups, a standard deviation of 0.5 millimeters, an alpha level of 0.05, a power of eighty percent, and an anticipated ten percent dropout rate.

Anesthesia will be standardized for all participants using sevoflurane for maintenance. Fentanyl will be used for intraoperative pain control, and the total amount given will be recorded. Optic nerve sheath diameter measurements will be performed using a high-frequency linear ultrasound probe placed gently over the closed eyelid. Three measurements will be taken from each eye, and the average will be calculated.

Statistical analysis will follow the intention-to-treat principle, meaning participants will be analyzed according to the group they were originally assigned to regardless of whether they completed the study protocol. Continuous measurements will be compared using appropriate statistical tests, and a p-value less than 0.05 will be considered statistically significant.

Adverse events will be recorded throughout the hospital stay. Participants who develop severe sedation will be withdrawn from the study. The study protocol has been approved by the institutional review board, and written informed consent will be obtained from all participants. The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Recruitment is currently ongoing, and the study is expected to take approximately eighteen months to complete.

Inclusion criteria

• Age: 18-65 years
• ASA status: I-III
• Surgery Elective supratentorial craniotomy for tumor resection (meningioma, glioma, metastasis)
• Anesthesia: General anesthesia with sevoflurane
• Consent: Written informed consent obtained

Exclusion criteria

• Known hypersensitivity to pregabalin or gabapentinoids.
• Pre-existing optic nerve pathology or glaucoma that could cause ONSD measurement interference.
• Emergency surgery as No preoperative dosing window
• Preoperative ICP elevation (suspected or confirmed) to avoid Baseline ICP abnormality
• Severe renal impairment (CrCl < 30 mL/min).
• Preoperative use of gabapentinoids or benzodiazepines to avoid drug interaction/interference
• Pregnancy or breastfeeding for Safety
• Body mass index > 40 kg/m²
• History of substance abuse
• Inability to cooperate with ONSD measurement