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

Sponsor

Assiut University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05340803

Collaborator

(none)

108

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
TBI (Traumatic Brain Injury)	Radiation: Ultrasonograghic optic nerve sheath diameter US-ONSD Drug: midazolam Drug: dexmedetomidine Drug: magnesium sulfate	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

To compare use of midazolam alone versus combination of midazolam with dexmedetomidine or magnesium sulfate in patients with sever TBI ( Glasgow Coma Scale < 8 and in need for mechanical ventilation) as regards effect on ICP monitored by US-ONSD as the primary outcome and anti-inflammatory effect (neuroprotective effect) by measurement of serum IL-6 as a secondary outcome.To compare use of midazolam alone versus combination of midazolam with dexmedetomidine or magnesium sulfate in patients with sever TBI ( Glasgow Coma Scale < 8 and in need for mechanical ventilation) as regards effect on ICP monitored by US-ONSD as the primary outcome and anti-inflammatory effect (neuroprotective effect) by measurement of serum IL-6 as a secondary outcome.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Each group will contain 36 patients by double-blind manner using numbered sealed envelopes and the main investigator responsible for measurement ONSD will not be informed about the drug or drugs used for each patient

Primary Purpose:

Supportive Care

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

Anticipated Study Start Date :

Nov 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A Sedation by midazolam alone	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
Active Comparator: Group B Sedation by midazolam and dexmedetomidine during the first 24 hours	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 Drug: dexmedetomidine dexmedetomidine
Active Comparator: Group C Sedation by midazolam and magnesium sulfate during the first 24 hours	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 Drug: magnesium sulfate magnesium sulfate

Arm

Intervention/Treatment

Active Comparator: Group A

Sedation by midazolam alone

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

Active Comparator: Group B

Sedation by midazolam and dexmedetomidine during the first 24 hours

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

Drug: dexmedetomidine

dexmedetomidine

Active Comparator: Group C

Sedation by midazolam and magnesium sulfate during the first 24 hours

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

Drug: magnesium sulfate

magnesium sulfate

Outcome Measures

Primary Outcome Measures

Optic nerve sheath diameter (ONSD) changes by using ultrasound [up to 24 hours]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Middle age patients ( 18- 45 years old).
Sever TBI (GCS < 8 and in need for mechanical ventilation).
Stable hemodynamics

Exclusion Criteria:

Age: younger than 18 or older than 45 years old.
Mild and moderate TBI (GCS > 8).
Shocked and hypoxic patients.
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).
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.
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).
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 .