Prognosis of Brain Reflexes (PRORETRO)

Evaluation of the Clinical and Electrophysiological Responses of the Brainstem in Patients With Alteration of Consciousness in Relation or Not With Sedation: Prognostic Study of Brain Reflexes

Severe diseases in intensive care unit (ICU) patients are associated with a high mortality rate which nevertheless remains difficult to predict. Recently, the abolition of some brainstem reflexes at clinical examination of ICU patients within the first 24 hours after has been shown of prognostic value in ICU patients requiring sedation. Early abolition of the cough reflex was associated with an increase in mortality and that of the oculocephalic reflex was predictive of coma or delirium after sedation has been stopped. A dysfunction of the brainstem may account for these results and be present in other patient subpopulations, particularly those who do not receive iv sedation or the brain injured patients, who were eluded from the previous study. This dysfunction could take place in the muti-organ failure characteristic of the severe ICU patient. On the other hand, a preliminary study performed on somatosensory evoked potentials has shown that a latency of the P14 wave greater than 16 ms between day 1 and day 3 after admission was associated with death at 28 days. The primary goal of this project is to confirm this hypothesis. By studying the clinical and electrophysiological responses of the brainstem in ICU patients, with or without brain injury, with alteration of consciousness in relation or not with sedation. The other objectives are to determine the correlations between neurophysiological clinical neurological, or neuroradiological data with delirium occurrence.

The main objective of this study is to determine, in ICU patients with or without brain injury and with alteration of consciousness in relation or not with sedation, if abolition of the cough reflex at Day 1 after admission is predictive of mortality at 28 days, independent from cause for admission and severity.

Study Overview

• Status: Unknown
• Conditions: Adult Patients With Alteration of Consciousness; Admitted Into the Intensive Care Unit (ICU)
• Intervention / Treatment: Other: neuro-electrophysiologic analyses

Detailed Description

Adult Medical or surgical, brain-injured or not, ICU patients requiring invasive mechanical ventilation for at least 48 hours and with alteration of consciousness induced or not by sedatives. Inclusion will take place at the 24th hour (± 12) after admission into the ICU will be enrolled. Those patients with either pregnancy, post anoxic coma, brain death, pre-existing neurologic disease disturbing the interpretation of the brainstem reflexes (Guillain-Barre, myasthenia, gravis, brain tumor, inflammatory or degenerating disease of the posterior fossa, acute peripheral neurologic disease), or declined participation will be excluded.

The measurements will be based on:

D1 : Demographic data, cause for admission, brainstem reflexes, Glasgow Coma Scale score, Confusion Assessment Method for the ICU (CAM-ICU) , Richmond Agitation Sedation Scale (RASS), Behavioral Pain Scale (BPS), simplified index of gravity (IGS 2) score, Sequential Organ Failure Assessment (SOFA) scores, cumulated sedative doses and Secondary Systemic Cerebral Aggressions (ACSOS) parameters D3 : parameters of D1, electrophysiologic analyses: Electroencephalogram (EEG), auditory evoked potentials (EAEP), Somatosensory Evoked Potential (SEP), recording of clinico-biological data, Cognitive evoked potentials (CEP) in patients with consciousness alteration still on mechanical ventilation at day 3.

D1-D28 : date of death, date of extubation, SOFA, CAM-ICU, cumulated doses of sedatives and analgesics, duration of sedation, occurrence of nosocomial pneumonia after Day 2, brain imaging data if available.

D28 : Glasgow Outcome Coma Scale and mini mental state

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Clichy la Garenne, France, 92
    • Recruiting
    • Beaujon Hospital
    • Contact: Jean Mantz, MD PhD

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:

• Adult Medical or surgical, brain-injured or not, patients
• Admitted to the intensive care Unit (ICU)
• Requiring invasive mechanical ventilation for at least 48 hours
• With alteration of consciousness induced by sedatives or not
• Within the 24 hours (± 12) after admission into the ICU

Exclusion Criteria:

• Pregnancy
• Post anoxic coma
• Brain death
• Pre-existing neurologic disease disturbing the interpretation of the brainstem reflexes (Guillain-Barre, myasthenia, gravis, brain tumor, inflammatory or degenerating disease of the posterior fossa, acute peripheral neurologic disease)
• Declined participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Electrophysiologic analyses	Other: neuro-electrophysiologic analyses; mismatch negativity (MMN) cognitive evoked potentials (CEP) auditory evoked potentials (AEP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality at Day 28	day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurophysiologic response (P14 latency value greater than 16 ms of the SEP of the median nerve)	P14 latency value greater than 16 ms of the SEP of the median nerve	day 1 and day 3

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (ANTICIPATED): May 1, 2019
• Study Completion (ANTICIPATED): May 1, 2019

Study Registration Dates

• First Submitted: March 6, 2015
• First Submitted That Met QC Criteria: March 17, 2015
• First Posted (ESTIMATE): March 24, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: P120915; 2014-A01102-45 (OTHER: RCB)