THIC Cu: Treatment of Intracranial Hypertension of Severe Tramatic Brain Injured Patients. Physiopathologic Effects of Neuromuscular Blocking Agents

Sponsor

University Hospital, Clermont-Ferrand (Other)

Overall Status

Unknown status

CT.gov ID

NCT02404779

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury Intracranial Hypertension	Drug: cisatracurium besilate Other: Placebo	Phase 4

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%).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Treatment of Intracranial Hypertension of Severe Tramatic Brain Injured Patients. Physiopathologic Effects of Neuromuscular Blocking Agents. A Controlled Randomized Study Versus Placebo

Actual Study Start Date :

Mar 19, 2015

Anticipated Primary Completion Date :

Mar 19, 2022

Anticipated Study Completion Date :

Jun 18, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CISATRACURIUM To compare the evolution of intracranial pressure (ICP) of severely brain injured patients with intracranial hypertension after administration of cisatracurium versus placebo.	Drug: cisatracurium besilate
Placebo Comparator: PLACEBO To compare the evolution of intracranial pressure (ICP) of severely brain injured patients with intracranial hypertension after administration of cisatracurium versus placebo.	Other: Placebo

Arm

Intervention/Treatment

Experimental: CISATRACURIUM

To compare the evolution of intracranial pressure (ICP) of severely brain injured patients with intracranial hypertension after administration of cisatracurium versus placebo.

Drug: cisatracurium besilate

Placebo Comparator: PLACEBO

To compare the evolution of intracranial pressure (ICP) of severely brain injured patients with intracranial hypertension after administration of cisatracurium versus placebo.

Other: Placebo

Outcome Measures

Primary Outcome Measures

area under the curve of the temporal evolution of intracranial pressure [at day 1]
The primary outcome is the area under the curve of the temporal evolution of intracranial pressure, over a period of 30 minutes after the administration of neuromuscular blocking agent or placebo.

Secondary Outcome Measures

Course of intracranial and cerebral perfusion pressures and various cerebral monitoring data if available (SvjO2, PtiO2) [at day 1]
Monitoring of the time spent by intracranial pressure above 20 mmHg using continuous recording [at day 1]
Course of intracranial pressure based on the type of brain injury [at day 1]
diffuse axonal injury, subarachnoid hemorrhage, intracerebral hematoma)
Monitoring of the curare effect [at day 1]
train of four and PTC
Course of ventilation parameters [at day 1]
tidal volume, FiO2, PEEP
Course of transcranial Doppler data [at day 1]
velocities
Course of arterial blood gas data [at day 1]
pH, paO2, paCO2, Excess Base, HCO3-
Course of plasma and cerebrospinal fluid concentrations of cistracurium and laudanosine [at day 1]
Cerebrospinal fluid concentrations of cisatracurium and laudanosin in case of cerebrospinal fluid derivation [at day 1]
Occurrence of cardiovascular complications [at day 1]
hypotension, myocardial ischemia
Occurrence of pulmonary complications [at day 1]
acute respiratory distress syndrome, pneumonia acquired under mechanical ventilation
Occurrence of renal complications [at day 1]
use of renal replacement therapy
Occurrence of infectious complications [at day 1]
Doses of vasopressors or catecholamines [at day 1]
Need to increase therapeutics [at day 1]
barbiturate coma, hypothermia, osmotherapy, decompressive craniectomy