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.

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.

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

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.

This is an open-label randomized trial. Treating clinicians and investigators are aware of treatment allocation. Outcome assessment is blinded; optic nerve sheath diameter (ONSD) measurements are performed by a blinded ultrasonographer, and radiological outcomes are evaluated by a blinded neuroradiologist who is unaware of treatment assignment.