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

Not Applicable

Completed

• Conditions: COVID-19
• Interventions: Diagnostic Test: Brainstem Responses Assessment Sedation Score (BRASS); Diagnostic Test: Electroencephalogram with EKG lead

• Registration Number: NCT04527198
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

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 Timeline

• Study First Submitted: 2020-06-02
• Study First Submitted QC: 2020-08-24
• Study First Posted: 2020-08-26
• Study Start: 2020-09-14
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-26
• Last Update Posted: 2021-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
group 1	Electroencephalogram with EKG lead	Major patients, admitted in intensive care for a SARS-CoV-2 infection and requiring mechanical ventilation and deep sedation (with or without neuromuscular blockade)
group 1	Brainstem Responses Assessment Sedation Score (BRASS)	Major patients, admitted in intensive care for a SARS-CoV-2 infection and requiring mechanical ventilation and deep sedation (with or without neuromuscular blockade)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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 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: 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 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 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
Duration of mechanical ventilation	at ICU discharge up to 28 days
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: 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 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)
Mortality	at ICU discharge up to 28 days
Duration of hospitalisation	at hospital discharge up to 90 days

Trial Locations

Locations (2)

Hôpital Cochin; 🇫🇷 Paris, France

HEGP; 🇫🇷 Paris, France