Enhanced-contrast Brain Ultrasound in Cardiorespiratory Arrest

Study Overview
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Brief Summary
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Brain microcirculation alterations may be involved in comatose patients and non-survivors after cardiorespiratory arrest. For a three day-period, we investigate brain microcirculation using contrast-enhanced ultrasound with contrast Sonovue injection in patients with successful resuscitation after out-hospital or in-hospital cardiorespiratory arrest.

Detailed Description
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Brain ultrasound, extracranial echo-color duplex and ocular ultrasound (IE 33, Philips Medical System, the Netherlands) are performed in the first 24 hours, at 48 hours, and at 72-96 hours after successful resuscitation after out-hospital or in-hospital cardiorespiratory arrest. Ultrasound examinations are performed in four steps to 1) evaluate the global cerebral blood volume, 2) to estimate the presence or absence of cerebral autoregulation, and 3) to qualitatively evaluate the cerebral perfusion and microcirculation by enhanced microbubbles contrast injection 4) to qualitatively evaluate the intracranial pressure. Before performing brain ultrasound, echocardiography (IE 33, Philips medical System, the Netherlands) is performed to evaluate the cardiac output (L/min). First, the global cerebral blood volume (L/min) is evaluated as the sum of flow volumes of the internal carotid (ICA) and vertebral arteries (VA) extracranial arteries of both sides.The following measurements of flow velocities are taken in each artery: Peak systolic and end-diastolic velocity, time-averaged velocity (TAV), Pulsatility Index (PI). Flow volume (Q) of each artery is determined as Q = TAV x Area ((diameter of the artery /2)² x PI). Brain ultrasound is performed via temporal windows to measure the mean flow velocities (cm/sec) of the middle cerebral arteries. Second, the presence or absence of cerebral autoregulation is tested with the Transient hyperemic response by an ipsilateral common carotid compression one side and another during 5 seconds. Absence of cerebral autoregulation is considered if the flow velocity of the middle cerebral artery do not increase more than 10% after the compression. Third, the brain regional microcirculation is evaluated by the microbubbles contrast injection of Sonovue. The brain parenchyma is insonated via the temporal bone windows at the depth of 10cm with the ultrasound S5 multifrequency transducer 2-5 Megahertz (MHz) probe. After optimizing the acoustic bone window, Sonovue is injected intravenously as a bolus 2.4ml followed by 10ml saline flushed. The contralateral brain is evaluated 5 minutes after the first injection of Sonovue to allow a complete evacuation of contrast microbubbles. All real-time images are stored digitally on the hard disk as DICOM (Digital Image Communications in Medicine) images. Offline imaging analysis using a specific quantification software named QLAB10 (Philips Medical System, the Netherlands) to convert brain perfusion images into time-intensity curves (TIC) corresponding to the five different regions of interest (ROI) of brain parenchyma: anterior and posterior thalamus, lentiform nucleus, parieto-temporal and posterior white matter. Four variables were extracted from these TIC curves to qualitatively evaluate the brain microcirculation: peak intensity in dB, time to peak intensity in seconds, mean transit time in seconds (MTT), and area under the curve in percentage (AUC). To qualitatively evaluate the intracranial pressure, ocular ultrasound is performed to measure the change of the optic nerve sheath diameter(mm). Elevation of intracranial pressure is considered if this diameter is above 0.55 mm

Official Title
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Evaluation of Cerebral Microcirculation Using Non-invasive Contrast-enhanced Ultrasound and Microbubbles Sonovue Administration After Clinical Cardiorespiratory Arrest

Conditions
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Cardiorespiratory Arrest, Microcirculation

Intervention / Treatment
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* Diagnostic Test: Sonovue


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ICU patients with successful resuscitation after out-hospital or in-hospital cardiorespiratory arrest Exclusion Criteria: Younger than 18 years old Pregnancy Acute or history of neurological disorder: stroke, bleeding, trauma, post-neurosurgery, tumor, meningitis. Severe dementia, psychiatric or neuromuscular disability Untreated Acute coronary syndrome Acute Respiratory Distress Syndrome (ARDS) with the ratio of arterial oxygen partial pressure (mmHg) to fractional inspired oxygen (PaO2/ FiO2) less than 150 Severe systolic pulmonary hypertension above 90 mmHg Advanced liver cirrhosis with hyperammonemia Uremia > 200mmol/L Acute drug intoxications with coma Acute alcohol intoxication or withdrawal syndrome. Advanced malign diseases. History of allergy to the microbubble contrast SONOVUE. Insufficient echogenicity to ultrasound and incomplete insonation of the intracerebral arteries and brain parenchyma. Significant intracerebral and extracerebral arteries stenosis (≥ 70%) or vertebral artery hypoplasia (3mm).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: ICU patients with successful resuscitation after out-hospital or in-hospital cardiorespiratory arrest who are eligible for enhanced-contrast brain ultrasound with sulphur hexafluoride microbubbles contrast Sonovue examination
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sonovue group<br>ICU patients with successful resuscitation after out-hospital or in-hospital cardiorespiratory arrest who are eligible for enhanced-contrast brain ultrasound, extracranial echo-color duplex, and ocular ultrasound. | Diagnostic Test: Sonovue<br>* Twice dose of 2.4ml of Sulphur hexafluoride microbubbles contrast Sonovue administration to evaluate brain microcirculation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change of the Mean transit time from baseline (seconds) | Qualitative evaluation of brain microcirculation using the variables of the time-intensity curve after Sonovue administration: a prolonged of Mean transit time is expected in comatose patients or non-survivors. | Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 hours and at 72 or 96 hours | 
| Mean change of the Peak intensity from baseline (dB). | Qualitative evaluation of brain microcirculation using the variables of the time-intensity curve after Sonovue administration: a reduction of Peak intensity is expected in comatose patients or non-survivors. | Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 hours and at 72 or 96 hours | 
| Mean change of the time to Peak intensity from baseline (seconds). | Qualitative evaluation of brain microcirculation using the variables of the time-intensity curve after Sonovue administration: a reduction of the time to peak intensity is expected in comatose patients or non-survivors. | Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 hours and at 72 or 96 hours | 
| Mean change of the Area under the curve from baseline (percentage). | Qualitative evaluation of brain microcirculation using the variables of the time-intensity curve after Sonovue administration: a reduction of the area under the curve is expected in comatose patients or non-survivors. | Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 hours and at 72 or 96 hours | 
| Testing cerebral autoregulation: Transient Hyperemic test- Absence or presence from baseline | Absence of cerebral autoregulation is considered if there is no change in flow velocities of the middle cerebral arteries after short compression of the common carotid arteries occur comparing with the value prior to compression. | Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 hours and at 72 or 96 hours | 
| Mean change of the optic nerve sheath diameter from baseline (mm) | Qualitative estimation of intracranial pressure using ocular ultrasound to measure the optic nerve sheath diameter. Elevation of intracranial pressure with increase of this diameter above 0.55 mm is expected in comatose patients or non-survivors. | Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 hours and at 72 or 96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change of the mean velocities of the middle cerebral arteries from baseline (cm/second) | Qualitative evaluation of brain macrocirculation using brain ultrasound to measure the velocities of the middle cerebral arteries. Unchanged or elevation of these velocities are expected in comatose patients or non-survivors. | Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 hours and at 72 or 96 hours | 
| Mean change of global cerebral blood flow from baseline (L/minute) | Qualitative evaluation of brain macrocirculation: using extracranial echo-color duplex to measure the velocities of both carotid and vertebral arteries to estimate global cerebral blood flow. Unchanged or elevation of cerebral blood flow is expected in comatose patients or non-survivors. | Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 hours and at 72 or 96 hours | 
| Mean change of cardiac output from baseline (L/minute) | Qualitative evaluation of brain macrocirculation: using transthoracic echocardiography to estimate cardiac output. Unchanged or elevation of cardiac output is expected in comatose patients or non-survivors. | Comparison to baseline (24 hours after ICU admission) to the two other time points: at 48 hours and at 72 or 96 hours |