Ketamine and Glutamate After Brain Injury : a Microdialysis Study (KETABRAIN)
Primary Purpose
Head Trauma
Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Ketamine
Sufentanil
Sponsored by
About this trial
This is an interventional treatment trial for Head Trauma focused on measuring traumatic brain injury, ketamine, microdialysis, PtiO2, glutamate
Eligibility Criteria
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
Sites / Locations
- Sainte Anne Military Teaching Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ketamine
sufentanil
Arm Description
ketamine 5 mg/kg/h, continuous infusion for 48 hours
sufentanil 0,5 mcg/kg/h, continuous infusion for 48 hours
Outcomes
Primary Outcome Measures
brain glutamate concentrations
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)
Secondary Outcome Measures
metabolic profile
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.
Episodes of intracranial hypertension (ICHT) and brain ischemia
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
Therapeutic Intensity Level (TIL)
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.
Glasgow Outcome Scale (GOS) et extended Glasgow Outcome Scale (eGOS)
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.
Full Information
NCT ID
NCT02232347
First Posted
September 2, 2014
Last Updated
September 2, 2014
Sponsor
Pierre-Julien CUNGI
1. Study Identification
Unique Protocol Identification Number
NCT02232347
Brief Title
Ketamine and Glutamate After Brain Injury : a Microdialysis Study
Acronym
KETABRAIN
Official Title
Effect of Ketamine Versus Sufentanil on Cerebral Glutamate After Traumatic Brain Injury : a Randomized, Double-blinded, Microdialysis Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Unknown status
Study Start Date
October 2014 (undefined)
Primary Completion Date
October 2016 (Anticipated)
Study Completion Date
May 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Pierre-Julien CUNGI
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head Trauma
Keywords
traumatic brain injury, ketamine, microdialysis, PtiO2, glutamate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ketamine
Arm Type
Experimental
Arm Description
ketamine 5 mg/kg/h, continuous infusion for 48 hours
Arm Title
sufentanil
Arm Type
Active Comparator
Arm Description
sufentanil 0,5 mcg/kg/h, continuous infusion for 48 hours
Intervention Type
Drug
Intervention Name(s)
Ketamine
Intervention Type
Drug
Intervention Name(s)
Sufentanil
Primary Outcome Measure Information:
Title
brain glutamate concentrations
Description
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)
Time Frame
H0-H12, H12-H24, H24-H36 and H36-H48
Secondary Outcome Measure Information:
Title
metabolic profile
Description
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.
Time Frame
H0-H12, H12-H24, H24-H36 and H36-H48
Title
Episodes of intracranial hypertension (ICHT) and brain ischemia
Description
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
Time Frame
H0-H12, H12-H24, H24-H36 and H36-H48
Title
Therapeutic Intensity Level (TIL)
Description
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.
Time Frame
Days 1 and 2
Title
Glasgow Outcome Scale (GOS) et extended Glasgow Outcome Scale (eGOS)
Description
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.
Time Frame
6 months and 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ambroise MONTCRIOL, MD
Phone
0483162358
Ext
0033
Email
ambroise.montcriol@free.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ambroise MONTCRIOL, MD
Organizational Affiliation
Direction Centrale du Service de Santé des Armées
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sainte Anne Military Teaching Hospital
City
Toulon
ZIP/Postal Code
83130
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre Julien CUNGI, MD
First Name & Middle Initial & Last Name & Degree
Eric MEAUDRE, MD
First Name & Middle Initial & Last Name & Degree
Henry BORET, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
17511549
Citation
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Results Reference
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PubMed Identifier
22101599
Citation
Hughes S. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 3: is ketamine a viable induction agent for the trauma patient with potential brain injury. Emerg Med J. 2011 Dec;28(12):1076-7. doi: 10.1136/emermed-2011-200891.
Results Reference
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PubMed Identifier
20219164
Citation
Filanovsky Y, Miller P, Kao J. Myth: Ketamine should not be used as an induction agent for intubation in patients with head injury. CJEM. 2010 Mar;12(2):154-7. doi: 10.1017/s1481803500012197. No abstract available.
Results Reference
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PubMed Identifier
19640746
Citation
Hudetz JA, Pagel PS. Neuroprotection by ketamine: a review of the experimental and clinical evidence. J Cardiothorac Vasc Anesth. 2010 Feb;24(1):131-42. doi: 10.1053/j.jvca.2009.05.008. Epub 2009 Jul 29. No abstract available.
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Citation
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Citation
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Ketamine and Glutamate After Brain Injury : a Microdialysis Study
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