Clinical trial NCT04527198: Brainstem Dysfunction in COVID-19 Critically Ill Patients: a Prospective Observational Study
Official title: Brainstem Dysfunction in Ventilated and Deeply Sedated COVID-19 Critically Ill Patients: a Prospective Observational Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID-19
Keywords: Brainstem dysfunction
Delirium
Awareness
Arousal
Dysautonomia
Autonomic system
SARS-COV-2
COVID-19
sedation
mechanical ventilation
EEG
EKG
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-08-26
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Brainstem dysfunction prevalence
timeFrame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
Secondary outcomes:
measure: Brainstem dysfunction prevalence after sedation weaning
timeFrame: Day 4 to day 7 after sedation weaning
measure: Link between brainstem dysfunction and clinical dysautonomia
timeFrame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessationn
measure: Link between brainstem dysfunction and clinical dysautonomia after sedation weaning
timeFrame: 4 to 7 days after sedation weaning
measure: Characterization of brainstem dysfunction in COVID-19 patients: EEG power
timeFrame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
measure: Characterization of brainstem dysfunction in COVID-19 patients: EEG power after sedation weaning
timeFrame: Day 4 to day 7 after sedation weaning.
measure: Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity
timeFrame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
measure: Characterization of brainstem dysfunction in COVID-19 patients: EEG functional connectivity, after sedation weaning
timeFrame: Day 4 to day 7 after sedation weaning.
measure: Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity
timeFrame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
measure: Characterization of brainstem dysfunction in COVID-19 patients: EEG complexity after sedation weaning
timeFrame: Day 4 to day 7 after sedation weaning.
measure: Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification
timeFrame: At inclusion or in patients with neuromuscular blockade 12h-72h following neuromuscular blocking agent cessation
measure: Characterization of brainstem dysfunction in COVID-19 patients: multivariate classification after sedation weaning
timeFrame: Day 4 to day 7 after sedation weaning.
measure: Duration of mechanical ventilation
timeFrame: at ICU discharge up to 28 days
measure: Mortality
timeFrame: at ICU discharge up to 28 days
measure: Duration of hospitalisation
timeFrame: at hospital discharge up to 90 days
measure: Duration of coma, disturbance of consciousness, delirium
timeFrame: at ICU discharge up to 28 days
measure: Neurological functional evolution with mRankin
timeFrame: 90 days after inclusion
measure: Neurological functional evolution with GOSE
timeFrame: 90 days after inclusion
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: HEGP
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Bertrand HERMANN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.