Ketamine and Glutamate After Brain Injury : a Microdialysis Study (KETABRAIN)

September 2, 2014 updated by: Pierre-Julien CUNGI

Effect of Ketamine Versus Sufentanil on Cerebral Glutamate After Traumatic Brain Injury : a Randomized, Double-blinded, Microdialysis Study

The objective of the study is to compare the effects of 48 hours ketamine infusion versus sufentanil infusion on brain glutamate concentrations measured with microdialysis after traumatic brain injury.

We hypothesize that ketamine infusion will decrease high glutamate values faster than sufentanil.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Inclusion of 20 consecutive head trauma patients. Randomization and double-blind to compare the effects of ketamine versus sufentanil on brain glutamate concentrations measured with microdialysis.

Ketamine is an anti-N-methyl-D-aspartate (NMDA) medication. It is supposed to limit excitotoxicity of amino-acids, especially glutamate. Glutamate is known to be elevated in more than 60% of the severe head trauma patients. It induces cortical spreading depression which can aggravate prognosis. It's a daily used medication in anesthesia and intensive care units for sedation and induction of anesthesia. It's the recommended medication for induction of unstable wounded soldiers on the field because of its neutrality on haemodynamic state.

Sufentanil is the reference opioid for sedation in ICU in Europe. It can induce hypotension which is deleterious for cerebral perfusion pressure after brain trauma.

In our unit, patients with severe head injury are monitored by a triple lumen access device including ICP (IntraCerebral Pressure), PtiO2 (oxygen pressure in the brain) and microdialysis. This last monitoring allows measurement of brain parenchymal concentrations of small molecules : glucose, lactate, pyruvate, glutamate, glycerol,.... It's a tool to evaluate the metabolic state of the brain divided into 4 categories : normal, hyperglycolysis, ischemia and metabolic crisis.

Then, we will detail the effects of ketamine on metabolic state of the brain, especially glutamate concentration. Normal values are below 10 micromol/ml. After head trauma it can dramatically increase to values up to 50 or even 100 micromol/ml, with normalization after 24 hours. Ketamine is expected to decrease these high values faster than described in observational studies.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Toulon, France, 83130
        • Sainte Anne Military Teaching Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • > 18 years old
  • Glasgow Coma Scale (GCS) < 9
  • > 3 days of sedation expected at the arrival

Exclusion Criteria:

  • pregnancy
  • < 18 years old
  • estimated survival < 48 hours post-trauma
  • expected sedation < 3 days
  • coagulation impairment (platelets<100.000/mm3 and prothrombin time (TP) <60%)
  • Cardiac arrest before ICU admission
  • Admission > 12 hours after trauma
  • Multimodal monitoring implanted > 24 hours post trauma
  • Participation to the study refused by the next of kind
  • No next of kind

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ketamine
ketamine 5 mg/kg/h, continuous infusion for 48 hours
Drug: Ketamine
Active Comparator: sufentanil
sufentanil 0,5 mcg/kg/h, continuous infusion for 48 hours
Drug: Sufentanil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
brain glutamate concentrations
Time Frame: H0-H12, H12-H24, H24-H36 and H36-H48
To compare the kinetic of brain glutamate concentration decrease during 4 periods of 12 hours between ketamine infusion group (KET) and sufentanil standard infusion group (STD)
H0-H12, H12-H24, H24-H36 and H36-H48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
metabolic profile
Time Frame: H0-H12, H12-H24, H24-H36 and H36-H48
To compare the brain metabolic profile (normal, ischemic, hyperglycolytic and metabolic crisis) of the patients related to their group of treatment : ketamine (KET) and sufentanil (STD) by measuring brain glucose, brain lactate, brain glycerol concentrations and brain lactate/pyruvate ratio.
H0-H12, H12-H24, H24-H36 and H36-H48
Episodes of intracranial hypertension (ICHT) and brain ischemia
Time Frame: H0-H12, H12-H24, H24-H36 and H36-H48
To compare the number of ICHT episodes (ICP>20 mm Hg more than 15 minutes) and to compare the number of ischemic episodes (PtiO2<20 mm Hg more than 15 minutes) between the 2 groups
H0-H12, H12-H24, H24-H36 and H36-H48
Therapeutic Intensity Level (TIL)
Time Frame: Days 1 and 2
To compare the TIL value between the 2 groups. TIL is a score developed to measure the intensity of cares for head trauma patients. Lower scores are meaning less intense cares. It is calculated for 24 hours periods.
Days 1 and 2
Glasgow Outcome Scale (GOS) et extended Glasgow Outcome Scale (eGOS)
Time Frame: 6 months and 1 year
To describe the prognosis of the patients of the KETAMINE group versus SUFENTANIL group. GOS is the international validated score for evaluation of the prognosis after head trauma.
6 months and 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pierre-Julien CUNGI

Investigators

  • Principal Investigator: Ambroise MONTCRIOL, MD, Direction Centrale du Service de Santé des Armées

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Anticipated)

October 1, 2016

Study Completion (Anticipated)

May 1, 2017

Study Registration Dates

First Submitted

September 2, 2014

First Submitted That Met QC Criteria

September 2, 2014

First Posted (Estimate)

September 5, 2014

Study Record Updates

Last Update Posted (Estimate)

September 5, 2014

Last Update Submitted That Met QC Criteria

September 2, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DCSSA KETABRAIN

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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