Clinical trial NCT01028339: Mannitol vs HS to Treat ICHT After Severe TBI : Comparison on PtiO2 and Microdialysis Values
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Traumatic Brain Injury
Keywords: traumatic brain injury
PtiO2
Cerebral microdialysis
Osmotherapy
hypertonic saline
mannitol
Lead sponsor: Direction Centrale du Service de Santé des Armées
Sponsor class: OTHER
First posted: 2009-12-09
Enrollment: 30
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 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.

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

Primary outcomes:
measure: Effects of HS versus mannitol on lactate/pyruvate ratio
timeFrame: 20 min, 40 min, H1, H2, H3 and H4
Secondary outcomes:
measure: Metabolic profile evaluated thanks to measure of lactate/pyruvate ratio and cerebral glucose
timeFrame: 20 min, 40 min, H1, H2, H3 and H4
measure: Duration of PtiO2 > 15 mm Hg if PtiO2 was < 15 mm Hg before osmotherapy
timeFrame: 20 min, 40 min, H1, H2, H3 et H4
measure: Duration of ICP<20 mm Hg after osmotherapy
timeFrame: 20 min, 40 min, H1, H2, H3 and H4
measure: Interstitial osmolarity
timeFrame: 20 min, 40 min and H1
measure: Necessity of a third line therapy (hypothermia, craniectomy, propofol/barbiturate coma
timeFrame: Day after osmotherapy
measure: Length of stay
timeFrame: After leaving the unit
measure: Mortality
timeFrame: 28th days
measure: Glasgow outcome scale
timeFrame: 6th month
Other outcomes:
Locations:
city: Toulon
country: France
facility: HIA Sainte Anne
Study officials:
affiliation: Direction Centrale du Service de Santé des Armées
name: Henry BORET, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vialet R, Albanese J, Thomachot L, Antonini F, Bourgouin A, Alliez B, Martin C. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Crit Care Med. 2003 Jun;31(6):1683-7. doi: 10.1097/01.CCM.0000063268.91710.DF.
citation: Sakowitz OW, Stover JF, Sarrafzadeh AS, Unterberg AW, Kiening KL. Effects of mannitol bolus administration on intracranial pressure, cerebral extracellular metabolites, and tissue oxygenation in severely head-injured patients. J Trauma. 2007 Feb;62(2):292-8. doi: 10.1097/01.ta.0000203560.03937.2d.
citation: Soustiel JF, Vlodavsky E, Zaaroor M. Relative effects of mannitol and hypertonic saline on calpain activity, apoptosis and polymorphonuclear infiltration in traumatic focal brain injury. Brain Res. 2006 Jul 26;1101(1):136-44. doi: 10.1016/j.brainres.2006.05.045. Epub 2006 Jun 19.