Clinical trial NCT02232347: Ketamine and Glutamate After Brain Injury : a Microdialysis Study
Official title: Effect of Ketamine Versus Sufentanil on Cerebral Glutamate After Traumatic Brain Injury : a Randomized, Double-blinded, Microdialysis Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Head Trauma
Keywords: traumatic brain injury
ketamine
microdialysis
PtiO2
glutamate
Lead sponsor: Direction Centrale du Service de Santé des Armées
Sponsor class: OTHER
First posted: 2014-09-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: brain glutamate concentrations
timeFrame: H0-H12, H12-H24, H24-H36 and H36-H48
Secondary outcomes:
measure: metabolic profile
timeFrame: H0-H12, H12-H24, H24-H36 and H36-H48
measure: Episodes of intracranial hypertension (ICHT) and brain ischemia
timeFrame: H0-H12, H12-H24, H24-H36 and H36-H48
measure: Therapeutic Intensity Level (TIL)
timeFrame: Days 1 and 2
measure: Glasgow Outcome Scale (GOS) et extended Glasgow Outcome Scale (eGOS)
timeFrame: 6 months and 1 year
Other outcomes:
Locations:
city: Toulon
country: France
facility: Sainte Anne Military Teaching Hospital
Study officials:
affiliation: Direction Centrale du Service de Santé des Armées
name: Ambroise MONTCRIOL, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS; Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. I. Blood pressure and oxygenation. J Neurotrauma. 2007;24 Suppl 1:S7-13. doi: 10.1089/neu.2007.9995. No abstract available.
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.
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citation: Ward JL, Harting MT, Cox CS Jr, Mercer DW. Effects of ketamine on endotoxin and traumatic brain injury induced cytokine production in the rat. J Trauma. 2011 Jun;70(6):1471-9. doi: 10.1097/TA.0b013e31821c38bd.
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citation: Bourgoin A, Albanese J, Wereszczynski N, Charbit M, Vialet R, Martin C. Safety of sedation with ketamine in severe head injury patients: comparison with sufentanil. Crit Care Med. 2003 Mar;31(3):711-7. doi: 10.1097/01.CCM.0000044505.24727.16.
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