Enhanced-contrast Brain Ultrasound in Cardiorespiratory Arrest

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

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.

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

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).