Multimodal Neuromonitoring: an Explorative Study in Neurocritical Care Patients
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Medical University of Vienna
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Count of SD during electrocorticography
Study Overview
Brief Summary
Theoretical Framework & Background
Cortical spreading depressions (CSD) and seizures, are crucial in the development of delayed cerebral ischemia and poor functional outcome in patients suffering from acute brain injuries such as subarachnoid hemorrhage. Multimodal neuromonitoring (MMNM) provides the unique possibility in the sedated and mechanically ventilated patients to record these electrophysiological phenomena and relate them to measures of cerebral ischemia and malperfusion. MMNM combines invasive (e.g. electrocorticography, cerebral microdialysis, brain tissue oxygenation) and noninvasive (e.g. neuroimaging, continuous EEG) techniques. Additionally, cerebral microdialysis can measure the unbound extracellular drug concentrations of sedatives, which potentially inhibit CSD and seizures in various degrees, beyond the blood-brain barrier without further interventions.
Hypotheses
- Online multimodal neuromonitoring can accurately detect changes in neuronal metabolic demand and pathological neuronal bioelectrical changes in highly vulnerable brain tissue.
- Online multimodal neuromonitoring can accurately detect the impact of pathological neuronal bioelectrical changes on metabolic demand in highly vulnerable brain tissue.
- The occurrence and duration of pathological neuronal bioelectrical changes are dependent on sedatives and antiepileptic drug concentrations
- The occurrence and duration of pathological neuronal bioelectrical changes have a negative impact on functional and neurological long-term patient outcome.
- Simultaneous invasive and non-invasive multimodal neuromonitoring can identify a clear relationship of both methods regarding pathological neuronal bioelectrical changes and metabolic brain status.
Methods
Systematic analysis of MMNM measurements following standardized criteria and correlation of electrophysiological phenomena with cerebral metabolic changes in all included patients. In a second step neuroimaging, cerebral extracellular sedative drug concentrations and neurological functional outcome, will be correlated with both electrophysiologic and metabolic changes. Due to numerous high-resolution parameters, machine learning algorithms will be used to correlate comprehensive data on group and individual levels following a holistic approach.
Level of originality
Extensive, cutting edge diagnostic methods are used to get a better insight into the pathophysiology of electrophysiological and metabolic changes during the development of secondary brain damage. Due to the immense amount of high-resolution data, a computer-assisted evaluation will be applied to identify relationships in the development of secondary brain injury. For the first time systematic testing of several drug concentrations beyond the blood-brain barrier will be performed. With these combined methods, we will be able to develop new cerebroprotective treatment concepts on an individual basis.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Individuals between 18-80 years with poor grade aneurysmal SAH (World Federation Neurosurgical Societies >3), severe ICH (ICH Score >3) or severe TBI (Glasgow Coma Scale < 9). The diagnosis of SAH, ICH and TBI will be established by computed tomography (CT).
- •Individuals that are unlikely to regain consciousness within the following 48 hours.
- •Individuals that are expected to survive for the next 48 hours.
Exclusion Criteria
- •Individuals younger than 18 years old and older than 80 years.
- •Pregnant women (documented via positive ß-HCG test).
- •Patients, who do not want to participate in the study. As the patient is not able to consent prior to the study, information about the study details will be given to the patient in case of clinical improvement. The patient information sheet will be handed out.
- •Thereafter, the patient has the possibility to withdraw permission of study-participation.
Outcomes
Primary Outcomes
Count of SD during electrocorticography
Time Frame: up to 21 days
Count of cortical spreading depolarization (SD) during continuous electrocorticography
Daily pattern duration of CSD during electrocorticography
Time Frame: up to 21 days
Duration of cortical spreading depression (CSD) per hour during continuous electrocorticography
Daily pattern duration of NCSE during electrocorticography
Time Frame: up to 21 days
Duration of nonconvulsive status epilepticus (NCSE) per hour during continuous electrocorticography
Daily pattern duration of RPPIIC during electrocorticography
Time Frame: up to 21 days
Duration of rhythmic or periodic EEG patterns on the ictal-interictal continuum (RPPIIC) per hour during continuous electrocorticography
Daily duration of metabolic crisis
Time Frame: up to 21 days
Duration of metabolic crisis (defined as Lactate Pyruvate ratio \[LPR\] \> 40 and lactate higher than 4 mmol/l) during continuous electrocorticography
Neuropharmacology (AUC)
Time Frame: up to 21 days
AUC of routinely used sedative drug concentrations in blood and brain (Esketamine, Midazolam and Propofol)
Daily duration of mitochondrial dysfunction
Time Frame: up to 21 days
Duration of mitochondrial dysfunction (defined as LPR \> 40, Pyruvate \> 70 μmol/l and partial brain tissue oxygenation \[PbtO2\] \> 20 mmHg) during continuous electrocorticography
Neuroimaging
Time Frame: up to 28 days
Absence or presence of hypoperfusion or ischemic infarctions in neuroimaging
Daily duration of ischemia
Time Frame: up to 21 days
Duration of ischemia (defined as PbtO2 \< 15 mmHg and cerebral perfusion pressure \[CPP\] \< 60 mmHg) during continuous electrocorticography
Daily duration of elevated intracranial pressure (ICP)
Time Frame: up to 21 days
Duration of elevated intracranial pressure (defined as ICP \> 22 mmHg) during continuous electrocorticography
Neuropharmacology Cmax)
Time Frame: up to 21 days
Cmax of routinely used sedative drug concentrations in blood and brain (Esketamine, Midazolam and Propofol)
Functional patient outcome
Time Frame: up to 6 months
modified Rankin Scale
Neuropharmacology (t1/2)
Time Frame: up to 21 days
t1/2 of routinely used sedative drug concentrations in blood and brain (Esketamine, Midazolam and Propofol)
Secondary Outcomes
No secondary outcomes reported
Investigators
Johannes Herta
Principle Investigator, Co-Head of the Neurosurgical ICU
Medical University of Vienna