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Microembolic Signals and Cerebrospinal Fluid Markers of Neuronal Damage After Surgical Aortic Valve Replacement

Microembolic Signals and Cerebrospinal Fluid Markers of Neuronal Damage After Surgical Aortic Valve

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT01319799
Enrollment
10
Registered
2011-03-22
Start date
2010-11-30
Completion date
2011-06-30
Last updated
2017-03-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Aortic Stenosis

Keywords

Embolism, Nervous system, Aorta, Valves, Ultrasonics

Brief summary

The use of MRI have shown that the incidence of postoperative cerebral lesions due to cerebral embolization is high (1). Nonetheless the extent of postoperative neurological dysfunction is only a fraction of the actual amount of new postoperative changes detected on MRI. Transcranial Doppler (TCD) has shown the occurrence of extensive microembolic signals in intracerebral arteries during open heart procedures (2). The clinical significance of cerebral microemboli is not clear (3-5). The use of serological markers to assess cerebral injury after open cardiac surgery is difficult to interpret. The levels of markers seems to be contaminated from extracerebral sources (6). In order assess the release of markers of neuronal damage after open aortic valve surgery the investigators intend to examine the levels of S-100B, NSE and Tau in cerebrospinal fluid (CSF) by comparing the levels preoperative with the levels one day after surgery. Furthermore the investigators will determine the total amount of cerebral microembolic signals during the surgical procedure by means of TCD. The investigators will statistically test if there is any correlation between the increase in cerebrospinal fluid levels of S-100B,NSE and Tau and the cerebral embolic load.

Detailed description

Patients and clinical procedures 10 patients scheduled for open aortic valve surgery at our institution will be included into this prospective, observational study. The Human Ethics Committee of the University of Gothenburg, approved the study protocol. The day before surgery a lumbar puncture at level L3-4 will be performed using a 27G Whitacre needle. A sample of 2.5 ml of cerebrospinal fluid will be taken for analysis of S-100B, NSE, Tau and albumin. On arrival at OR, standard perioperative monitoring will be established, including an Auditory Evoked Potential (AEP) monitor for anaesthetic depth measurements (AEP Monitor/2, Danmeter, Odense, Denmark) and radial arterial and central venous lines. General anaesthesia is induced with propofol 0.5-1 mg/kg and fentanyl 10 μg/kg. Tracheal intubation will be facilitated using atracurium 0,5 mg/kg. Sevoflurane is used to maintain an anaesthetic depth adjusted to an AAI index of 15-30 as recorded by the AEP monitor. Hemodynamic stability will be obtained by the use of colloidal solution administration, guided by the use of intra-operative transesophageal echocardiography, and norephineprine to maintain a mean arterial pressure above 75 mmHg-Also during CPB. A lumbar puncture will be repeated the first postoperative day repeating the measurement of markers in CSF A certified cardiologist or anaesthesiologist assess focal neurological impairment before and within 24 hours after the procedure. Transcranial Doppler (TCD) By TCD the right medial cerebral artery (RMCA) will be insonated by the transtemporal approach at a depth of approximately 50 mm using standard criteria. The investigators use a 2 MHz power M-mode TCD monitor (ST3 ©, Spencer Technologies Seattle, WA), with the probe fixed in position using a head frame. The Doppler signals will be continuously monitored and saved to monitor hard drive. Two physicians independently evaluate the TCD data files offline, and identify microembolic signals (MES) using criteria for counting emboli signals on spectral and PMD TCD. Statistical Analysis: Descriptive statistics and tests of normality for continuos data Correlation analysis; Total cerebral embolic load vs. increase of CSF level S-100B/ NSE/Tau.

Interventions

OTHEROpen heart surgery

TCD count of microembolic signals during surgical aortic valve replacement

Sponsors

Sahlgrenska University Hospital
Lead SponsorOTHER

Study design

Observational model
CASE_ONLY
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Healthy volunteers
No

Inclusion criteria

* Clinical diagnosis aortic stenosis eligible for surgical treatment

Exclusion criteria

* Coagulopathy * Regular Anticoagulation therapy * Carotid stenosis

Design outcomes

Primary

MeasureTime frameDescription
Transcranial Doppler(TCD) Microembolic Signals During Surgical Aortic Valve Replacement Surgery(day 1) TCD will be performed from start of surgery till end of surgery-exact time cannot be stated in advanceTranscranial Doppler measurement of microembolic signals will be measured during the surgical procedure.Microembolic signals are detected by offline analysis of the Dopplerspectral analysis of the blood flow in the medial cerebral artery. Different intensities (dB),flow direction and time frame appearances in the Doppler spectral envelope is distinguishable for a neurosonolgist according to predefined criteria for an embolic signal-defined in previous litterature.The total amount of signals during one surgical procedure is counted. The appearance of microembolic signals related to specific procedures performed during cardiac surgery with cardiopulmonary bypass is noted. The exact time range is not possible to estimate in advance,due to the fact that each surgical procedure varies in time.The range of values for each individual patient, based on pilos, will vary from 50 to approximately 1500 embolic counts for one surgical procedure. A high value is negative for the patient.

Secondary

MeasureTime frameDescription
Cerebrospinal Fluid(CSF) Levels of S-100B(Microgram/Liter)24 Hours after SurgeryDifferences in preoperative vs postoperative CSF levels of S-100B in microgram/Liter The assumption is that a cardiac open heart surgical procedure with cardiopulmonary bypass will influence the postoperative level of marker of neuronal cell damage in the central nerve system. An increase in the levels, compared to the preoperative values, indicates neuronal cell damage detectable in the CSF, namely the brains own extracellular fluid.

Countries

Sweden

Participant flow

Participants by arm

ArmCount
Surgical Aortic Valve Replacement
Open heart surgery : TCD count of microembolic signals during surgical aortic valve replacement
10
Total10

Baseline characteristics

CharacteristicSurgical Aortic Valve Replacement
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
10 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
Age, Continuous75 years
STANDARD_DEVIATION 5
Region of Enrollment
Sweden
10 participants
Sex: Female, Male
Female
2 Participants
Sex: Female, Male
Male
8 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
0 / 10
serious
Total, serious adverse events
0 / 10

Outcome results

Primary

Transcranial Doppler(TCD) Microembolic Signals During Surgical Aortic Valve Replacement Surgery

Transcranial Doppler measurement of microembolic signals will be measured during the surgical procedure.Microembolic signals are detected by offline analysis of the Dopplerspectral analysis of the blood flow in the medial cerebral artery. Different intensities (dB),flow direction and time frame appearances in the Doppler spectral envelope is distinguishable for a neurosonolgist according to predefined criteria for an embolic signal-defined in previous litterature.The total amount of signals during one surgical procedure is counted. The appearance of microembolic signals related to specific procedures performed during cardiac surgery with cardiopulmonary bypass is noted. The exact time range is not possible to estimate in advance,due to the fact that each surgical procedure varies in time.The range of values for each individual patient, based on pilos, will vary from 50 to approximately 1500 embolic counts for one surgical procedure. A high value is negative for the patient.

Time frame: (day 1) TCD will be performed from start of surgery till end of surgery-exact time cannot be stated in advance

ArmMeasureValue (MEAN)Dispersion
Surgical Aortic Valve ReplacementTranscranial Doppler(TCD) Microembolic Signals During Surgical Aortic Valve Replacement Surgery354 units on a scaleStandard Error 79
Secondary

Cerebrospinal Fluid(CSF) Levels of S-100B(Microgram/Liter)

Differences in preoperative vs postoperative CSF levels of S-100B in microgram/Liter The assumption is that a cardiac open heart surgical procedure with cardiopulmonary bypass will influence the postoperative level of marker of neuronal cell damage in the central nerve system. An increase in the levels, compared to the preoperative values, indicates neuronal cell damage detectable in the CSF, namely the brains own extracellular fluid.

Time frame: 24 Hours after Surgery

ArmMeasureValue (MEAN)Dispersion
Surgical Aortic Valve ReplacementCerebrospinal Fluid(CSF) Levels of S-100B(Microgram/Liter)0.11 microgram/LiterStandard Error 0.02

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026