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

NCT ID: NCT04527198

Last Updated: 2021-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-14
• Study Completion Date: 2020-12-31

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.

Conditions

COVID-19

Keywords

Brainstem dysfunction; Delirium; Awareness; Arousal; Dysautonomia; Autonomic system; SARS-COV-2; COVID-19; sedation; mechanical ventilation; EEG; EKG

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Brainstem Responses Assessment Sedation Score (BRASS)

Intervention Type: 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

Intervention Type: 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).

Interventions

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.

Intervention Type: 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).

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

EEG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bertrand HERMANN, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Cochin

Paris, , France

HEGP

Paris, , France

Countries

France

References

Rohaut B, Porcher R, Hissem T, Heming N, Chillet P, Djedaini K, Moneger G, Kandelman S, Allary J, Cariou A, Sonneville R, Polito A, Antona M, Azabou E, Annane D, Siami S, Chretien F, Mantz J, Sharshar T; Groupe d'Exploration Neurologique en Reanimation (GENER). Brainstem response patterns in deeply-sedated critically-ill patients predict 28-day mortality. PLoS One. 2017 Apr 25;12(4):e0176012. doi: 10.1371/journal.pone.0176012. eCollection 2017.

Reference Type: BACKGROUND

PMID: 28441453 (View on PubMed)

Benghanem S, Cariou A, Diehl JL, Marchi A, Charpentier J, Augy JL, Hauw-Berlemont C, Gavaret M, Pene F, Mira JP, Sharshar T, Hermann B. Early Clinical and Electrophysiological Brain Dysfunction Is Associated With ICU Outcomes in COVID-19 Critically Ill Patients With Acute Respiratory Distress Syndrome: A Prospective Bicentric Observational Study. Crit Care Med. 2022 Jul 1;50(7):1103-1115. doi: 10.1097/CCM.0000000000005491. Epub 2022 Feb 9.

Reference Type: DERIVED

PMID: 35135966 (View on PubMed)

Other Identifiers

2020-A01559-30

Identifier Type: REGISTRY

Identifier Source: secondary_id

APHP200644

Identifier Type: -

Identifier Source: org_study_id