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

COVID-19 Clinical Trial

— BRAINSTEM-COV  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04527198
• Other study ID #: APHP200644
• Secondary ID: 2020-A01559-30
• Status: Completed
• Phase: N/A
• Start date: September 14, 2020
• Est. completion date: December 31, 2020

Study information

• Verified date: November 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

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.
• 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).

Locations

Country	Name	City	State
France	HEGP	Paris
France	Hôpital Cochin	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (1)

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, Chrétien F, Mantz J, Sharshar T; Groupe d'Exploration Neurologique en Réanimation (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. — View Citation

Outcome

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