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Completed

NCT Number: NCT04527198

Brainstem Dysfunction in 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.

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Brainstem Responses Assessment Sedation Score (BRASS)

Diagnostic Test

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.

Electroencephalogram with EKG lead

Diagnostic Test

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

Primary outcomes

  1. 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)

Secondary outcomes

  1. 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)

  2. 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

  3. 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. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Duration of mechanical ventilation

    Time frame: at ICU discharge up to 28 days

  13. Mortality

    Time frame: at ICU discharge up to 28 days

  14. Duration of hospitalisation

    Time frame: at hospital discharge up to 90 days

  15. Duration of coma, disturbance of consciousness, delirium

    Time frame: at ICU discharge up to 28 days

  16. 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)

  17. 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)

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • URC-CIC Paris Descartes Necker Cochin

Registry information

Official study title

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

Acronym: BRAINSTEM-COV

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Aug 26, 2020
Registry last updated
Mar 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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