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

Phase 4

• Conditions: Traumatic Brain Injury; Intracranial Hypertension
• Interventions: Drug: cisatracurium besilate; Other: Placebo

• Registration Number: NCT02404779
• Lead Sponsor: University Hospital, Clermont-Ferrand

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%).

Study Timeline

• Study First Submitted: 2015-03-16
• Study Start: 2015-03-19
• Study First Submitted QC: 2015-03-31
• Study First Posted: 2015-04-01
• Status Verified: 2020-06
• Last Update Submitted: 2020-07-02
• Last Update Posted: 2020-07-07
• Primary Completion: 2022-03-19
• Study Completion: 2022-06-18

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 34

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CISATRACURIUM	cisatracurium besilate	To compare the evolution of intracranial pressure (ICP) of severely brain injured patients with intracranial hypertension after administration of cisatracurium versus placebo.
PLACEBO	Placebo	To compare the evolution of intracranial pressure (ICP) of severely brain injured patients with intracranial hypertension after administration of cisatracurium versus placebo.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 transcranial Doppler data	at day 1	velocities
Course of arterial blood gas data	at day 1	pH, paO2, paCO2, Excess Base, HCO3-
Occurrence of renal complications	at day 1	use of renal replacement therapy
Occurrence of infectious complications	at day 1
Need to increase therapeutics	at day 1	barbiturate coma, hypothermia, osmotherapy, decompressive craniectomy
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
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
Course of plasma and cerebrospinal fluid concentrations of cistracurium and laudanosine	at day 1
Doses of vasopressors or catecholamines	at day 1

Trial Locations

Locations (1)

CHU de Clermont-Ferrand; 🇫🇷 Clermont-Ferrand, France