A Clinical Trial of the Effect of Midazolam on the Cerebral Metabolism and Inflammatory Response in Patients With Moderate and Severe Traumatic Brain Injury

To explore the cerebral protective effect of midazolam in patients with traumatic brain injury, we will collect blood samples from patients treated with or without midazolam when the patient is admitted to ICU, 24 h, 48 h and 72 h after the admission before the use of midazolam for patients in group N1, and before the patient is treated with midazolam, 24 h， 48 h, 72 h after the use of midazolam for patients in group N2. Parameters of cerebral metabolism and inflammatory response will be obtained from the blood samples or the cerebrospinal fluid. With the aforementioned parameters, the relationship between clinical outcome and cerebral metabolism and inflammatory response will be detected with statistical method.

Study Overview

• Status: Unknown
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: Placebo; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Yangzhou, Jiangsu, China, 225001
      • Recruiting
      • Subei People's Hospital of Jiangsu province
      • Contact: Ruiqiang Zheng, Doctor; Phone Number: 18051060411; Email: rqzh7@yahoo.com.cn
      • Principal Investigator: Ruiqiang Zheng, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 or older;
• Hospitalized in ICU within 6 hours after the injury or after the operation;
• Traumatic brain injury is confirmed by computed tomography scan or magnetic resonance imaging, Glasgow Coma Scale is 3 to 12, and the patient should meet the diagnostic standard of severe traumatic brain injury;
• Informed consent is obtained.

Exclusion Criteria:

• Aged less than 18;
• Death is expected in 24 hours;
• History of neurological disease or history of drug abuse which may affect the outcome of the study;
• Failed to obtain Informed consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: N1(traditional treatment group); Patients in group N1 are treated with basic therapeutic measures which include reducing intracranial pressure with mannitol, hemostasis, acid inhibition, anti-infection, nutrition support and control of blood glucose, blood pressure and body temprature.	Drug: Placebo
Experimental: N2(midazolam group); Patients in group N2 was treated with intravenous infusion of midazolam on the basis of basic treatment measures which include reducing intracranial pressure with mannitol, hemostasis, acid inhibition, anti-infection, nutrition support and control of blood glucose, blood pressure and body temprature.	Drug: Midazolam; For patients allocated into group N2, 2 mg midazolam will be injected intravenously, and then it will be given at 0.05-0.1 mg/(kg·h) by intravenous infusion. If a surgery is needed, infusion of midazolam will begin 3 hours after the operation and continue for at least 72 hours. During the sedation with midazolam, BIS should be kept at 60 to 80. Morphine can be used to supply adequate analgesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral metabolic parameters	N1 group: blood samples will be collected when the patient is admitted to ICU, 24 h, 48 h and 72 h after the admission N2 group: blood samples will be collected before the use of midazolam, 24 h, 48 h and 72 h after the use Blood sample will be collected every time from the radial artery and the jugular bulb separately. The blood sample will be used for blood gas analysis Detail parameters by blood test: levels of lactic acid, oxygen saturation(SaO2), partial pressure of oxygen(Pa02), jugular bulb venous oxygen saturation(SjvO2), jugular bulb oxygen partial pressure(PjvO2), hemoglobin(Hb) Calculated parameters: arterial oxygen content(Ca02), jugular venous oxygen saturation (SjvO2), arterial venous oxygen content difference(Da-jvO2), cerebral extraction of oxygen(CERO2), Lactate differences between jugular and arterial blood(AVDL) and Cerebral lactate acid production(CLP)	from the admission to ICU to 72 h after the admission for Group N1 and before the use of midazolam to 72 h after the use for group N2
Parameters of intracranial inflammatory response	N1: blood samples and cerebrospinal fluid are collected when the patient is admitted to ICU, 24 h, 48 h and 72 h after the admission N2: blood samples and cerebrospinal fluid are collected before the use of midazolam, 24 h, 48 h and 72 h after the use every time, 3 ml blood sample will be collected from the jugular bulb and 2 ml cerebrospinal fluid will be collected at the corresponding time The blood sample will be anticoagulated by EDTA and then it will be centrifuged at 3000 r/min for 10 minutes within 30 minutes from the collection. The supernatant liquid will be stored in the freezer at -70℃. The cerebrospinal fluid centrifuged at 3000 r/min for 10 minutes, and then the supernatant liquid will be stored in the freezer at -80℃. Detail parameters: sFkn and IL-6 levels of the blood sample and CSF will be tested 2 times by ELISA and then take the average.	from the admission to ICU to 72 h after the admission for Group N1 and before the use of midazolam to 72 h after the use for group N2

Secondary Outcome Measures

Outcome Measure	Time Frame
Ramsay score	from the use of midazolam to 72 h after the use for group N2
seizure	from the admission to ICU to 72 h after the admission
one-week mortality	from the admission to ICU to one week after the admission

Collaborators and Investigators

• Sponsor: Subei People's Hospital of Jiangsu Province

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): March 1, 2015

Study Registration Dates

• First Submitted: February 21, 2014
• First Submitted That Met QC Criteria: February 24, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Estimate): February 25, 2014
• Last Update Submitted That Met QC Criteria: February 24, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: midazolam; traumatic brain injury; sedation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 2014021801