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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT04527198

Collaborator

(none)

Enrollment

Locations

Arm

3.5

Actual Duration (Months)

Patients Per Site

7.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Diagnostic Test: Brainstem Responses Assessment Sedation Score (BRASS) Diagnostic Test: Electroencephalogram with EKG lead	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Sep 14, 2020

Actual Primary Completion Date :

Dec 31, 2020

Actual Study Completion Date :

Dec 31, 2020

Arms and Interventions

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)	Diagnostic Test: Brainstem Responses Assessment Sedation Score (BRASS) 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. Diagnostic Test: Electroencephalogram with EKG lead 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

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)

Diagnostic Test: Brainstem Responses Assessment Sedation Score (BRASS)

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.

Diagnostic Test: Electroencephalogram with EKG lead

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

Outcome Measures

Primary Outcome Measures

Brainstem dysfunction prevalence [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 Outcome Measures

Brainstem dysfunction prevalence after sedation weaning [Day 4 to day 7 after sedation weaning]
Clinical cranial nerves anomalies using validated scale (BRASS score)
Link between brainstem dysfunction and clinical dysautonomia [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
Link between brainstem dysfunction and clinical dysautonomia after sedation weaning [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
Characterization of brainstem dysfunction in COVID-19 patients: EEG power [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
Characterization of brainstem dysfunction in COVID-19 patients: EEG power after sedation weaning [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
Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity [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
Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity, after sedation weaning [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
Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity [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
Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity after sedation weaning [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
Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification [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
Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification after sedation weaning [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
Duration of mechanical ventilation [at ICU discharge up to 28 days]
Mortality [at ICU discharge up to 28 days]
Duration of hospitalisation [at hospital discharge up to 90 days]
Duration of coma, disturbance of consciousness, delirium [at ICU discharge up to 28 days]
Neurological functional evolution with mRankin [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)
Neurological functional evolution with GOSE [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)