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

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

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.

Study Overview

• Status: Terminated
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: Mannitol; Drug: Hypertonic saline

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Toulon, France, 83130
    • HIA Sainte Anne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Mannitol	Drug: Mannitol; Mannitol
Experimental: Hypertonic saline	Drug: Hypertonic saline; 2 mL/kg of 7.5% hypertonic saline associated to hydroxyethyl starch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Direction Centrale du Service de Santé des Armées
• Investigators: Principal Investigator: Henry BORET, MD, Direction Centrale du Service de Santé des Armées

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): June 1, 2012
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: December 3, 2009
• First Submitted That Met QC Criteria: December 8, 2009
• First Posted (Estimate): December 9, 2009

Study Record Updates

• Last Update Posted (Estimate): August 8, 2012
• Last Update Submitted That Met QC Criteria: August 7, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: mannitol; traumatic brain injury; PtiO2; Cerebral microdialysis; Osmotherapy; hypertonic saline
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Physiological Effects of Drugs; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Mannitol
• Other Study ID Numbers: SSH versus mannitol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No