Ketamine and Glutamate After Brain Injury : a Microdialysis Study

Phase 2

• Conditions: Head Trauma
• Interventions: Drug: Ketamine; Drug: Sufentanil

• Registration Number: NCT02232347
• Lead Sponsor: Pierre-Julien CUNGI

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.

Study Timeline

• Status Verified: 2014-09
• Study First Submitted: 2014-09-02
• Study First Submitted QC: 2014-09-02
• Last Update Submitted: 2014-09-02
• Study First Posted: 2014-09-05
• Last Update Posted: 2014-09-05
• Study Start: 2014-10
• Primary Completion: 2016-10
• Study Completion: 2017-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ketamine	Ketamine	ketamine 5 mg/kg/h, continuous infusion for 48 hours
sufentanil	Sufentanil	sufentanil 0,5 mcg/kg/h, continuous infusion for 48 hours

Primary Outcome Measures

Name	Time	Method
brain glutamate concentrations	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)

Secondary Outcome Measures

Name	Time	Method
metabolic profile	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.
Episodes of intracranial hypertension (ICHT) and brain ischemia	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
Therapeutic Intensity Level (TIL)	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.
Glasgow Outcome Scale (GOS) et extended Glasgow Outcome Scale (eGOS)	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.

Trial Locations

Locations (1)

Sainte Anne Military Teaching Hospital; 🇫🇷 Toulon, France