Clinical trial NCT02404779: Treatment of Intracranial Hypertension of Severe Tramatic Brain Injured Patients. Physiopathologic Effects of Neuromuscular Blocking Agents
Official title: Treatment of Intracranial Hypertension of Severe Tramatic Brain Injured Patients. Physiopathologic Effects of Neuromuscular Blocking Agents. A Controlled Randomized Study Versus Placebo
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Traumatic Brain Injury
Intracranial Hypertension
Keywords: ICU
Deep sedation
Mechanical ventilation
Traumatic brain injury
Intracranial hypertension
Cisatracurium
Neuromuscular Blocking Agent
Randomization versus placebo
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2015-04-01
Enrollment: 34
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: Severely brain injured patients are at high risk of intracranial hypertension. Among medical treatments (sedatives), neuromuscular blocking agents (NMBA) are recommended by french but not english speaking societies.

Effects of NMBA are unknown. The present study is designed to compare the effects of NMBA versus placebo in the treatment of intracranial hypertension, and the underlying physiopathologic effects.

Detailed description: In case of intracranial hypertension, french neurocritical care society argue for the use of neuromuscular blocking agents before osmotherapy, barbituric coma, hypothermia and craniectomy.

English speaking societies don't sustain this approach. Since then, the use of NMBA remains controversial in case of intracranial hypertension and no study is available.

We propose to study severely brain injured patients presenting with intracranial hypertension and treat them with cisatracurium besilate or placebo.

Our hypothesis is that neuromuscular blockade might act on several parameters:

* Hemodynamics
* respiratory parameters, mechanical ventilation and blood gaz analysis
* cerebral velocities
* diminished O2 peripheral consumption
* cerebrospinal diffusion and concentration of cisatracurium and a metabolite laudanosine We wish to assess changes in ICP according to the above parameters in a controlled randomized non blinded fashion against placebo (NaCl 0,9%).

Eligibility criteria: Inclusion Criteria:

* - Age over 18
* Mechanical ventilation and deep sedation
* Severe traumatic brain injury
* Intracranial hypertension (ICP \> 20 mmHg during \> 15 minutes)
* Intracranial pressure monitoring
* Hemodynamically stable

Exclusion Criteria:

* - History of anaphylaxia with neuromuscular agents
* Hemodynamic instability
* Pregnant and/or breast feeding women

Primary outcomes:
measure: area under the curve of the temporal evolution of intracranial pressure
timeFrame: at day 1
Secondary outcomes:
measure: Course of intracranial and cerebral perfusion pressures and various cerebral monitoring data if available (SvjO2, PtiO2)
timeFrame: at day 1
measure: Monitoring of the time spent by intracranial pressure above 20 mmHg using continuous recording
timeFrame: at day 1
measure: Course of intracranial pressure based on the type of brain injury
timeFrame: at day 1
measure: Monitoring of the curare effect
timeFrame: at day 1
measure: Course of ventilation parameters
timeFrame: at day 1
measure: Course of transcranial Doppler data
timeFrame: at day 1
measure: Course of arterial blood gas data
timeFrame: at day 1
measure: Course of plasma and cerebrospinal fluid concentrations of cistracurium and laudanosine
timeFrame: at day 1
measure: Cerebrospinal fluid concentrations of cisatracurium and laudanosin in case of cerebrospinal fluid derivation
timeFrame: at day 1
measure: Occurrence of cardiovascular complications
timeFrame: at day 1
measure: Occurrence of pulmonary complications
timeFrame: at day 1
measure: Occurrence of renal complications
timeFrame: at day 1
measure: Occurrence of infectious complications
timeFrame: at day 1
measure: Doses of vasopressors or catecholamines
timeFrame: at day 1
measure: Need to increase therapeutics
timeFrame: at day 1
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
Study officials:
References: