Brainstem Dysfunction in COVID-19 Critically Ill Patients: a Prospective Observational Study (BRAINSTEM-COV)

November 26, 2021 updated by: Assistance Publique - Hôpitaux de Paris

Brainstem Dysfunction in Ventilated and Deeply Sedated COVID-19 Critically Ill Patients: a Prospective Observational Study

The purpose of this study is to determine the prevalence of brainstem dysfunction in critically ill ventilated and deeply sedated patients hospitalized in the Intensive Care Unit (ICU) for a SARS-CoV-s2 infection.

Study Overview

Detailed Description

The recent development of the pandemic due to the SARS-CoV-2 virus has showed that a substantial proportion of patients developed a severe condition requiring critical care, notably because of acute respiratory distress syndrome requiring mechanical ventilation and deep sedation. Outside of this coronavirus infection, this situation is classically associated with a high prevalence of brainstem dysfunction, even in the absence of brain injury. This dysfunction, either structural or functional, can be detected using appropriate clinical tools such as the BRASS score and/or using the quantitative analysis of EKG and EEG. Crucially, brainstem dysfunction is associated not only with ICU complications such as delirium, but also with a poorer survival.

Moreover, some reports of encephalitis cases and the presence of anosmia/agueusia raised the question of whether the virus could directly invade the central nervous system.

For these two reasons, it is reasonable to assume that brainstem dysfunction is particularly prevalent in critically ill patients infected with SARS-CoV-2 and that this dysfunction could be one of the major determinant of patients outcome.

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Paris, France, 75014
        • Hopital Cochin
      • Paris, France, 75015
        • HEGP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • ICU hospitalization
  • Invasive mechanical ventilation
  • Deep sedation (RASS<-3) >12 hours
  • Positive SARS-COV-2 PCR

Exclusion Criteria:

  • History of neurologic disease (stroke, degenerative disease)
  • Pregnant women
  • Moribund patients
  • Minor patient
  • Major patient under guardianship or curatorship
  • Prior inclusion in the study
  • Patient not affiliated to a social security scheme
  • Limitations and cessation of active therapies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: group 1
Major patients, admitted in intensive care for a SARS-CoV-2 infection and requiring mechanical ventilation and deep sedation (with or without neuromuscular blockade)

It consists of a standardized evaluation of brainstem reflexes with a score of 1 attributed for absence of pupillary light reflex, cough reflex and the combined absence of grimace and oculocephalic reflex, a score of 2 for absent corneal reflex and a score of 3 for absent grimace in the presence of oculocephalic The resulting sum ranges from 0 to 7.

It will be performed at two times points: a first time under sedation and a second time 3 to 5 days after sedation weaning.

A 20 minutes clinical (12 electrodes) EEG with an EKG lead will be performed a first time under sedation and a second time 3 to 5 days after sedation weaning.

These EEG recordings will allow to measure the sympathic-parasympathetic ratio using spectral analysis of the EKG and also to measure quantitative markers of brain EEG activity (spectral power and connectivity in delta, theta, alpha, beta and gamma band; complexity).

Other Names:
  • EEG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brainstem dysfunction prevalence
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
Clinical cranial nerves anomalies using validated scale (BRASS score- ranges from 0 to 7 - ) in deeply sedated patient (RASS <-3)
At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brainstem dysfunction prevalence after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning
Clinical cranial nerves anomalies using validated scale (BRASS score)
Day 4 to day 7 after sedation weaning
Link between brainstem dysfunction and clinical dysautonomia
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessationn
Analysis of the sympathico-parasympathetic ratio (using spectral analysis of the EKG signal) according to the presence or absence of brainstem dysfunction and its severity
At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessationn
Link between brainstem dysfunction and clinical dysautonomia after sedation weaning
Time Frame: 4 to 7 days after sedation weaning
Analysis of the sympathico-parasympathetic ratio (using spectral analysis of the EKG signal) according to the presence or absence of brainstem dysfunction and its severity
4 to 7 days after sedation weaning
Characterization of brainstem dysfunction in COVID-19 patients: EEG power
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
EEG power in delta, theta, alpha, beta and gamma frequency bands according to the presence or absence of brainstem dysfunction and its severity
At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
Characterization of brainstem dysfunction in COVID-19 patients: EEG power after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning.
EEG power in delta, theta, alpha, beta and gamma frequency bands according to the presence or absence of brainstem dysfunction and its severity
Day 4 to day 7 after sedation weaning.
Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
EEG functional connectivity using weighted Symbolic Mutual Information and weighted Phase Lag Index according to the presence or absence of brainstem dysfunction and its severity
At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity, after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning.
EEG functional connectivity using weighted Symbolic Mutual Information and weighted Phase Lag Index according to the presence or absence of brainstem dysfunction and its severity
Day 4 to day 7 after sedation weaning.
Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
EEG complexity using Kolmogorov complexity and permutation entropy according to the presence or absence of brainstem dysfunction and its severity
At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning.
EEG complexity using Kolmogorov complexity and permutation entropy according to the presence or absence of brainstem dysfunction and its severity
Day 4 to day 7 after sedation weaning.
Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification
Time Frame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
Multivariate classification of the presence or absence of brainstem dysfunction using support vector machine and extra-trees algorithm based on the EEG derived quantitative features presented above
At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification after sedation weaning
Time Frame: Day 4 to day 7 after sedation weaning.
Multivariate classification of the presence or absence of brainstem dysfunction using support vector machine and extra-trees algorithm based on the EEG derived quantitative features presented above
Day 4 to day 7 after sedation weaning.
Duration of mechanical ventilation
Time Frame: at ICU discharge up to 28 days
at ICU discharge up to 28 days
Mortality
Time Frame: at ICU discharge up to 28 days
at ICU discharge up to 28 days
Duration of hospitalisation
Time Frame: at hospital discharge up to 90 days
at hospital discharge up to 90 days
Duration of coma, disturbance of consciousness, delirium
Time Frame: at ICU discharge up to 28 days
at ICU discharge up to 28 days
Neurological functional evolution with mRankin
Time Frame: 90 days after inclusion
Using validated functional scale modified Rankin (mRankin) for independence assessment (mRankin ranges from 0 to 6 with higher scores indicating more severe disability)
90 days after inclusion
Neurological functional evolution with GOSE
Time Frame: 90 days after inclusion
Using validated functional scale Glasgow Outcome Scale Extended (GOSE) for independence assessment (GOSE ranges from 1 to 8 with higher scores indicating less severe disability outcome)
90 days after inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Bertrand HERMANN, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 14, 2020

Primary Completion (ACTUAL)

December 31, 2020

Study Completion (ACTUAL)

December 31, 2020

Study Registration Dates

First Submitted

June 2, 2020

First Submitted That Met QC Criteria

August 24, 2020

First Posted (ACTUAL)

August 26, 2020

Study Record Updates

Last Update Posted (ACTUAL)

December 9, 2021

Last Update Submitted That Met QC Criteria

November 26, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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