Comparing Sedatives for Intracranial Pressure Control in Traumatic Brain Injury

Official title

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

Overview

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.

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.

Interventions

• 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.
• 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.
• 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.

Primary outcome measures

• Intracranial Pressure Control Assessed by Optic Nerve Sheath Diameter (ONSD) [Time frame: Baseline, 6 hours, 12 hours, and 24 hours after initiation of sedation]

Secondary outcome measures (11)

• Proportion of Time at Target Sedation Level [Time frame: 24 hours after initiation of sedation]
• Mean Richmond Agitation-Sedation Scale (RASS) Score [Time frame: 24 hours after initiation of sedation]
• Need for Rescue Sedation [Time frame: 24 hours after initiation of sedation]
• Time to Achieve Target Sedation [Time frame: 24 hours after initiation of sedation]
• Incidence of Hypotension [Time frame: 24 hours after initiation of study sedation]
• Vasopressor Requirements [Time frame: 24 hours after initiation of study sedation.]
• Incidence of Bradycardia. [Time frame: 24 hours after initiation of study sedation.]
• Percentage of Participants Who Developed Secondary Brain Injury ✅ [Time frame: Baseline and 24 hours after initiation of study sedation.]
• Duration of Mechanical Ventilation [Time frame: From initiation of mechanical ventilation until successful extubation, assessed for up to 30 days.]
• Time to Neurological Awakening [Time frame: From discontinuation of study sedation until achievement of a Glasgow Coma Scale motor score of ≥5, assessed for up to 30 days.]
• ICU Mortality [Time frame: From ICU admission until ICU discharge, assessed for up to 30 days.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Aswan University Hospital — Asyut

Identifiers

NCT: NCT07678216 · 1230/3/26

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗