Comparing Sedatives for Intracranial Pressure Control in Traumatic Brain Injury (ICP-TBI)

Effect of Propofol, Midazolam, and Dexmedetomidine on Intracranial Pressure and Clinical Outcomes in Patients With Moderate-to-Severe Traumatic Brain Injury Undergoing Urgent Neurosurgical Intervention

The goal of this clinical trial is to compare the effects of propofol, midazolam, and dexmedetomidine on intracranial pressure control and clinical outcomes in adults with moderate-to-severe traumatic brain injury undergoing urgent neurosurgical intervention.

The main questions it aims to answer are:

• Which sedative agent provides better control of intracranial pressure, assessed by optic nerve sheath diameter (ONSD), during the first 24 hours after neurosurgical intervention?
• How do the three sedative agents compare in achieving target sedation depth, maintaining hemodynamic stability, and improving short-term clinical outcomes such as ICU mortality, duration of mechanical ventilation, and ICU length of stay?

Participants will be randomly assigned to receive propofol, midazolam, or dexmedetomidine for 24 hours of continuous sedation. Clinical, hemodynamic, and neurological outcomes will be assessed and compared among the three study groups.

Study Overview

• Status: Not yet recruiting
• Conditions: Moderate-to-Severe Traumatic Brain Injury
• Intervention / Treatment: Drug: propofol; Drug: midazolam; Drug: Dexmedetomidine

Detailed Description

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability worldwide. Prevention of secondary brain injury through optimal control of intracranial pressure (ICP) is a key component of intensive care management in patients with moderate-to-severe TBI. Sedative agents are routinely used to facilitate mechanical ventilation, reduce cerebral metabolic demand, and improve ICP control. However, uncertainty remains regarding the optimal sedative agent for this patient population.

Propofol, midazolam, and dexmedetomidine are among the most commonly used sedatives in neurocritical care. Each agent has distinct pharmacological characteristics that may influence intracranial pressure, hemodynamic stability, neurological assessment, and clinical outcomes. Despite widespread use, direct comparative evidence between these agents remains limited.

This prospective randomized clinical trial aims to compare the effects of propofol, midazolam, and dexmedetomidine on intracranial pressure control and clinical outcomes in adult patients with moderate-to-severe traumatic brain injury undergoing urgent neurosurgical intervention. Intracranial pressure will be assessed noninvasively using serial optic nerve sheath diameter (ONSD) measurements obtained by ocular ultrasonography during the first 24 hours of continuous sedation.

Participants will be randomly assigned to receive one of the three sedative regimens according to a standardized protocol targeting a Richmond Agitation-Sedation Scale (RASS) score of -3 to -4. Standard neurocritical care management and analgesia protocols will be applied to all study groups.

The study will evaluate the comparative effects of the three sedative agents on intracranial pressure control, sedation quality, hemodynamic stability, adverse events, secondary brain injury, and short-term clinical outcomes. The findings are expected to provide evidence to guide sedative selection in patients with moderate-to-severe traumatic brain injury, particularly in settings where invasive intracranial pressure monitoring is not routinely available.

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohamed Abdelhamed, M.Sc; Phone Number: +201061651065; Email: mohamed.said@med.aswu.edu.eg

Study Locations

• Egypt
  • Asyut Governorate
    • Asyut, Asyut Governorate, Egypt, 81528
      • Aswan University Hospital
      • Contact: Mohamed Abdelhamed, M.Sc.; Phone Number: 01061651065; Email: hamedo_2020@yahoo.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years

  • Moderate to severe traumatic brain injury with post-resuscitation Glasgow Coma Scale (GCS) ≤12
  • Undergone urgent neurosurgical intervention (craniotomy, craniectomy, or ICP monitor placement) within 24 hours of injury
  • Admitted to ICU and expected to require continuous sedation
  • Hemodynamically stable or stabilized (defined as MAP ≥65 mmHg with vasopressor requirement ≤0.1 mcg/kg/min norepinephrine equivalent)
  • Informed consent obtained from legally authorized representative

Exclusion Criteria:

• The Relative refusal to participate in the research.
• Known allergy or contraindication to propofol, midazolam, or dexmedetomidine
• Pre-existing neurological disorders (epilepsy, prior stroke, brain tumors, dementia) that may interfere with outcome assessment
• Severe hepatic dysfunction (Child-Pugh Class C) or acute liver failure
• Severe renal dysfunction (eGFR <30 mL/min/1.73m² or requiring renal replacement therapy)
• Pregnancy or breastfeeding
• Hemodynamic instability requiring norepinephrine >0.1 mcg/kg/min or equivalent vasopressor support
• Heart rate <50 bpm or second/third-degree AV block without pacemaker (relative contraindication for dexmedetomidine)
• Clinical determination of brain death or expected survival <24 hours
• Enrollment in another interventional trial
• Severe polytrauma requiring ongoing surgical interventions that would interfere with protocol adherence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propofol; Participants receive continuous intravenous propofol infusion initiated at 1 mg/kg/h and titrated to 1-4 mg/kg/h to maintain a target RASS score of -3 to -4 for 24 hours.	Drug: propofol; Continuous intravenous propofol infusion initiated at 1 mg/kg/h and titrated within a range of 1-4 mg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 during the 24-hour study intervention period.
Experimental: Midazolam; Participants receive continuous intravenous midazolam infusion initiated at 0.03 mg/kg/h and titrated to 0.02-0.1 mg/kg/h to maintain a target RASS score of -3 to -4 for 24 hours.	Drug: midazolam; Continuous intravenous midazolam infusion initiated at 0.03 mg/kg/h and titrated within a range of 0.02-0.1 mg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 during the 24-hour study intervention period. An initial bolus dose of 0.05 mg/kg may be administered if rapid sedation is required.
Experimental: dexmedetomidine; Participants receive continuous intravenous dexmedetomidine infusion initiated at 0.4 μg/kg/h and titrated to 0.2-0.7 μg/kg/h to maintain a target RASS score of -3 to -4 for 24 hours.	Drug: Dexmedetomidine; Continuous intravenous dexmedetomidine infusion initiated at 0.4 μg/kg/h and titrated within a range of 0.2-0.7 μg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 during the 24-hour study intervention period. No loading dose will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Pressure Control Assessed by Optic Nerve Sheath Diameter (ONSD)	Intracranial pressure control will be evaluated using serial optic nerve sheath diameter (ONSD) measurements obtained by ocular ultrasonography. The primary outcome will be the mean ONSD over the 24-hour intervention period, analyzed as a continuous measure of intracranial pressure control.	Baseline, 6 hours, 12 hours, and 24 hours after initiation of sedation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Time at Target Sedation Level	Percentage of assessment time during which patients maintained the target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4. The Richmond Agitation-Sedation Scale ranges from +4 (combative) to -5 (unarousable). Higher scores indicate greater agitation, whereas lower scores indicate deeper sedation. The target sedation level for this study is RASS -3 to -4.	24 hours after initiation of sedation
Mean Richmond Agitation-Sedation Scale (RASS) Score	Mean Richmond Agitation-Sedation Scale (RASS) score during the 24-hour intervention period. The RASS ranges from +4 (combative) to -5 (unarousable), with target sedation defined as -3 to -4.	24 hours after initiation of sedation
Need for Rescue Sedation	Proportion of patients requiring rescue sedation due to failure to achieve target sedation despite maximum protocol dose.	24 hours after initiation of sedation
Time to Achieve Target Sedation	Time from initiation of study sedative infusion until achievement of target Richmond Agitation-Sedation Scale (RASS) score (-3 to -4).The RASS ranges from +4 (combative) to -5 (unarousable)	24 hours after initiation of sedation
Incidence of Hypotension	Incidence of hypotension, defined as mean arterial pressure (MAP) <65 mmHg or cerebral perfusion pressure (CPP) <60 mmHg.	24 hours after initiation of study sedation
Vasopressor Requirements	Vasopressor requirements assessed by the proportion of patients requiring vasopressor support.	24 hours after initiation of study sedation.
Incidence of Bradycardia.	Percentage of participants who develop bradycardia, defined as a sustained heart rate <50 beats per minute (bpm).	24 hours after initiation of study sedation.
Percentage of Participants Who Developed Secondary Brain Injury ✅	Secondary brain injury will be assessed by the presence of new or progressive findings on brain computed tomography (CT) compared with baseline imaging, including new intracranial hemorrhage, progression of cerebral edema (defined as >25% increase in midline shift or worsening basal cistern effacement), new cerebral infarction, or transtentorial or uncal herniation. Brain CT scans will be reviewed by a blinded neuroradiologist.	Baseline and 24 hours after initiation of study sedation.
Duration of Mechanical Ventilation	Duration of invasive mechanical ventilation, measured as the number of days from initiation of mechanical ventilation until successful liberation from ventilatory support.	From initiation of mechanical ventilation until successful extubation, assessed for up to 30 days.
Time to Neurological Awakening	Time from discontinuation of study sedation to achievement of a Glasgow Coma Scale (GCS) motor score of ≥5. The Glasgow Coma Scale motor component ranges from 1 (no motor response) to 6 (obeys commands), with higher scores indicating better neurological function.	From discontinuation of study sedation until achievement of a Glasgow Coma Scale motor score of ≥5, assessed for up to 30 days.
ICU Mortality	Death from any cause during the ICU stay following urgent neurosurgical intervention for traumatic brain injury.	From ICU admission until ICU discharge, assessed for up to 30 days.

Collaborators and Investigators

• Sponsor: Aswan University
• Investigators: Study Chair: Ahmed Elsaied Aly, Ph.D., Sohag University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: June 20, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Imidazoles; Phenols; Benzene Derivatives; Benzazepines; Benzodiazepines; Midazolam; Dexmedetomidine; Propofol
• Other Study ID Numbers: 1230/3/26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared because the study contains sensitive clinical data, and sharing could compromise participant confidentiality. Data are subject to institutional policies and ethics committee restrictions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No