Sedation of Ventilated Traumatic Brain Injury Patients With Midazolam Alone Versus Combination With Dexmedetomidine or Magnesium Sulfate; Monitored by Ultrasonograghic Optic Nerve Sheath Diameter

TBI (Traumatic Brain Injury) Clinical Trial

Official title:

Sedation of Ventilated Traumatic Brain Injury Patients With Midazolam Alone Versus Combination With Dexmedetomidine or Magnesium Sulfate; Monitored by Ultrasonograghic Optic Nerve Sheath Diameter

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05340803
• Other study ID #: ONSD for TBI patients
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: November 1, 2022
• Est. completion date: December 1, 2025

Study information

• Verified date: April 2022
• Source: Assiut University
• Contact: Alshymaa Hassan Mohammed, Master
• Phone: 01067555351
• Email: Alshimaa.hassan[@]medicine.luxor.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In TBI, there is a strong correlation between increased ICP and bad outcome. So, appropriate monitoring can be the gold standard in management of TBI. ICP can be measured by invasive and noninvasive methds. One of these noninvasive methods is bedside measurement of optic nerve sheath diameter (ONSD) by ocular ultrasonography

Description:

In the previous few years, agreat evidence has established for efficiency of dexmedetomidine (DEX) in management of TBI. Dexmedetomidine is a highly selective alpha-2 receptor agonist, its major sympatholytic and sedative actions are mediated primarily via reduced transmission in the locus coeruleus which is a part of the reticular activating system. It provides excellent sedation without respiratory depression, ease of arousability, and need not be stopped during weaning the patient from mechanical ventilation or for neurological assessment. It suits as an ideal sedative agent for patients with TBI. DEX has been shown to reduce cerebral ischemia/ reperfusion injury by suppressing inflammation, activating the anti-apoptotic signaling pathways, and inhibiting neuronal autophagy. Animal studies have shown that alpha-2 agonists are neuroprotective in craniocerebral and subarachnoid injuries but this has not been definitively shown in humans . The efficacy of DEX for sedation in intubated ICU patients is well established; however, its use in patients with TBI has not been comprehensively described .

Magnesium has shown great promise as a potential therapeutic agent in TBI during animal experiments . Magnesium is essential for the maintenance of cell membrane integrity, the stabilisation of genetic material and for a number of fundamental enzymatic reactions such as glycolysis, oxidative phosphorylation and protein synthesis, it is also known to act presynaptically to inhibit the release of excitatory amino acids, and be a non-competitive inhibitor of the voltage-gated N-methyl-D-aspartate (NMDA) receptor, an important link in the excitotoxic phase of secondary brain injury. As a consequence, magnesium's role in TBI has been of great interest to researchers.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 108
• Est. completion date: December 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Middle age patients ( 18- 45 years old).

2. Sever TBI (GCS < 8 and in need for mechanical ventilation).

3. Stable hemodynamics

Exclusion Criteria:

1. Age: younger than 18 or older than 45 years old.

2. Mild and moderate TBI (GCS > 8).

3. Shocked and hypoxic patients.

4. Contraindications to dexmedetomidine as sever hypotension (mean arterial blood pressure < 60 mmHg), sever bradycardia (heart rate < 45 beat/min), and AV block in the group that will be sedated by midazolam and dexmedetomidine (group B).

5. Adverse effects of dexmedetomidine in group B and need to stop it as sever hypotension (mean arterial blood pressure < 60 mmHg) , sever bradycardia (heart rate < 45 beat/min), and atrial fibrillation.

6. Contraindications to magnesium sulfate as heart block, myocardial damage, hypermagnesemia and renal failure in the group that will be sedated by midazolam and magnesium sulfate (group C).

7. Manifestations of magensium toxicity in group C and need to stop infusion if urine output < 80 mL in 4 hours, deep tendon reflexes are absent or serum magnesium level > 3.5 mmol/L .

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• TBI (Traumatic Brain Injury)
• Wounds and Injuries

Intervention

Radiation:
• Ultrasonograghic optic nerve sheath diameter US-ONSD
To compare effect of sedation in 3 groups by follow up of intracranial pressure by US-ONSD

Drug:
• midazolam
midazolam
• dexmedetomidine
dexmedetomidine
• magnesium sulfate
magnesium sulfate

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Optic nerve sheath diameter (ONSD) changes by using ultrasound	ONSD is an indicator for changes in intracranial pressure in response to sedation with midazolam alone versus combination with dexmedetomidine or magnesium sulfate which group will show better control of the increased intracranial pressure to prevent secondary brain insults. ONSD of 5.8mm was used as cutoff point for identifying ICP above 20 mmHg.	up to 24 hours