Mannitol vs HS to Treat ICHT After Severe TBI : Comparison on PtiO2 and Microdialysis Values

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether hypertonic saline is as much effective as mannitol to treat intracranial hypertension after traumatic brain injury and has at least the same effects on PtiO2 and cerebral metabolism studied through microdialysis.

Detailed Description
-----------------
Mannitol is frequently used to treat intracranial hypertension after TBI. However, it can be deleterious, particularly through hyperdiuresis and risks of hypovolemia. It also needs volume compensation and induces logistical problem because of needs of high infused volume to achieve osmolar load and avoid hypotension. Finally, some recent studies tend to prove superiority of hypertonic saline versus mannitol on the prognosis of TBI. especially through modulation of inflammatory reactions mechanisms and apoptosis. We would like to prove non inferiority of hypertonic saline versus mannitol after TBI to allow its large utilization, especially by field military doctors with specific logistical problems. For that, more than the single Intracranial Pressure, we want to study effects of HS vs mannitol not only on PtiO2 but also on cerebral microdialysis which gives informations on focal metabolism with profiles of ischemia, metabolic crisis, hyperglycolysis (possible reflect of neuronal restoration) and normality.

Official Title
-----------------
Mannitol Versus Hypertonic Saline to Treat Intracranial Hypertension After Severe Traumatic Brain Injury : a Comparative Study on the Effects on PtiO2 and Microdialysis Values

Conditions
-----------------
Traumatic Brain Injury

Intervention / Treatment
-----------------
* Drug: Hypertonic saline
* Drug: Mannitol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Severe Traumatic brain injury monitored with ICP, PtiO2 and cerebral microdialysis And ICP> 20 mm Hg needing osmotherapy And approval of the next of kind Exclusion Criteria: Bilateral fixed dilated pupils Contra-indication to multimodal neuromonitoring Previous CNS disease Contra-indication to HS (cardiac insufficiency,...) Natremia > 155 mmol/L or osmolarity > 320 mOsm/L

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mannitol<br> | Drug: Mannitol<br>* Mannitol<br>|
| Experimental: Hypertonic saline<br> | Drug: Hypertonic saline<br>* 2 mL/kg of 7.5% hypertonic saline associated to hydroxyethyl starch<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of HS versus mannitol on lactate/pyruvate ratio |  | 20 min, 40 min, H1, H2, H3 and H4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolic profile evaluated thanks to measure of lactate/pyruvate ratio and cerebral glucose |  | 20 min, 40 min, H1, H2, H3 and H4 | 
| Duration of PtiO2 > 15 mm Hg if PtiO2 was < 15 mm Hg before osmotherapy |  | 20 min, 40 min, H1, H2, H3 et H4 | 
| Duration of ICP<20 mm Hg after osmotherapy |  | 20 min, 40 min, H1, H2, H3 and H4 | 
| Interstitial osmolarity |  | 20 min, 40 min and H1 | 
| Necessity of a third line therapy (hypothermia, craniectomy, propofol/barbiturate coma |  | Day after osmotherapy | 
| Length of stay |  | After leaving the unit | 
| Mortality |  | 28th days | 
| Glasgow outcome scale |  | 6th month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
traumatic brain injury, PtiO2, Cerebral microdialysis, Osmotherapy, hypertonic saline, mannitol