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

Effect of Preoperative Pregabalin on Optic Nerve Sheath Diameter as a Surrogate for Intracranial Pressure in Elective Craniotomy Patients.

When patients undergo brain tumor removal surgery (craniotomy), the pressure inside the skull may increase, which can lead to brain swelling and slower recovery. Currently, doctors measure this pressure using invasive monitors placed inside the brain, but these are not used for all patients.

This study investigates whether a medication called pregabalin, given before surgery, can help reduce pressure inside the skull. Pregabalin is already approved for treating pain, anxiety, and seizures. The study will measure pressure indirectly using a simple, painless ultrasound of the eye (optic nerve sheath diameter), which is a validated non-invasive method to estimate intracranial pressure.

Participants will be randomly assigned to receive either pregabalin 150 mg or a placebo (inactive pill) on the evening before surgery and again on the morning of surgery. The ultrasound measurement will be taken at four time points: before the first dose, before anesthesia induction, upon arrival to the intensive care unit, and 24 hours after surgery. Researchers will also measure pain levels, medication use, and recovery quality.

The goal is to determine if preoperative pregabalin can safely reduce intracranial pressure and improve recovery in craniotomy patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Pregabalin; Intracranial Pressure Changes; Optic Nerve Sheath Diameter Measurement
• Intervention / Treatment: Drug: Pregabalin; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Qalyubia Governorate
    • Banhā, Qalyubia Governorate, Egypt, 13511
      • Benha University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregabalin Group; Participants in this arm will receive pregabalin 150 mg orally on the evening before surgery (approximately 8:00 PM) and a second dose of pregabalin 150 mg orally 90 minutes before anesthesia induction on the day of surgery.	Drug: Pregabalin; Pregabalin 150 mg capsule administered orally. Participants receive one capsule on the evening before surgery (approximately 8:00 PM) and a second capsule 90 minutes before anesthesia induction on the day of surgery. Each capsule contains 150 mg of pregabalin as the active ingredient. The drug is given with 30 mL of water. Pregabalin is a gamma-aminobutyric acid (GABA) analogue that binds to the alpha2-delta subunit of voltage-gated calcium channels, reducing the release of excitatory neurotransmitters including glutamate, noradrenaline, and substance P. This intervention is being tested for its potential neuroprotective effect and ability to reduce intracranial pressure as measured by optic nerve sheath diameter.
Placebo Comparator: Placebo Group; Participants in this arm will receive matching placebo capsules (containing microcrystalline cellulose) orally on the evening before surgery (approximately 8:00 PM) and a second matching placebo capsule orally 90 minutes before anesthesia induction on the day of surgery. The placebo capsules are identical in appearance, size, color, and taste to the pregabalin capsules.	Drug: Placebo; Matching placebo capsule containing microcrystalline cellulose administered orally. Participants receive one capsule on the evening before surgery (approximately 8:00 PM) and a second capsule 90 minutes before anesthesia induction on the day of surgery. The placebo capsules are identical in appearance, size, color, and taste to the pregabalin 150 mg capsules to maintain blinding. The placebo contains no active pharmaceutical ingredient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optic Nerve Sheath Diameter (ONSD) at Pre-induction	Optic nerve sheath diameter measured by ultrasound. Measurements will be taken 3 mm posterior to the optic disc using a high-frequency linear probe (7.5-12 MHz) placed gently over the closed upper eyelid. Three measurements will be taken from each eye, and the mean value of both eyes will be calculated.	immediately before anesthesia induction on the day of surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain Scores	Pain intensity measured using the Numeric Rating Scale (NRS) from 0 (no pain) to 10 (worst imaginable pain). Assessed at rest.	2, 6, 12, and 24 hours after surgery.
Total Opioid Consumption in First 24 Hours		24 hours after surgery
Quality of Recovery Score		24 hours and 48 hours after surgery

Collaborators and Investigators

• Sponsor: Benha University

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2026
• Primary Completion (Estimated): December 10, 2026
• Study Completion (Estimated): January 10, 2027

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Ultrasound; Brain Tumor; Pregabalin; Perioperative Medicine; Craniotomy; Optic Nerve Sheath Diameter; Intracranial Pressure
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Amino Acids, Peptides, and Proteins; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amino Acids; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Pregabalin
• Other Study ID Numbers: RC.11.4.2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No