Microembolic Signals and Cerebrospinal Fluid Markers of Neuronal Damage After Surgical Aortic Valve Replacement
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Surgical aortic valve replacement Single observational study. Count of microembolic signals during open heart surgery and measurement of properative vs postoperative levels of markers in cerebrospinal fluid of neuronal damge. |
Other: Open heart surgery
TCD count of microembolic signals during surgical aortic valve replacement
|
Outcome Measures
Primary Outcome Measures
- 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 advance]
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.
Secondary Outcome Measures
- Cerebrospinal Fluid(CSF) Levels of S-100B(Microgram/Liter) [24 Hours after Surgery]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Clinical diagnosis aortic stenosis eligible for surgical treatment
Exclusion Criteria:
-
Coagulopathy
-
Regular Anticoagulation therapy
-
Carotid stenosis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Thoracic Anaesthesia & Intensive Care,Sahlgrenska University Hospital | Gothenburg | Sweden | 41345 |
Sponsors and Collaborators
- Sahlgrenska University Hospital, Sweden
Investigators
- Study Director: Sven Erik Ricksten, Professor, Sahlgrenska University Hospital,Thoracic Anesthesia & Intensive Care
Study Documents (Full-Text)
None provided.More Information
Publications
- Abu-Omar Y, Balacumaraswami L, Pigott DW, Matthews PM, Taggart DP. Solid and gaseous cerebral microembolization during off-pump, on-pump, and open cardiac surgery procedures. J Thorac Cardiovasc Surg. 2004 Jun;127(6):1759-65.
- Anderson RE, Hansson LO, Nilsson O, Liska J, Settergren G, Vaage J. Increase in serum S100A1-B and S100BB during cardiac surgery arises from extracerebral sources. Ann Thorac Surg. 2001 May;71(5):1512-7.
- Kruis RW, Vlasveld FA, Van Dijk D. The (un)importance of cerebral microemboli. Semin Cardiothorac Vasc Anesth. 2010 Jun;14(2):111-8. doi: 10.1177/1089253210370903. Review.
- Martin KK, Wigginton JB, Babikian VL, Pochay VE, Crittenden MD, Rudolph JL. Intraoperative cerebral high-intensity transient signals and postoperative cognitive function: a systematic review. Am J Surg. 2009 Jan;197(1):55-63. doi: 10.1016/j.amjsurg.2007.12.060. Epub 2008 Aug 23. Review.
- Stolz E, Gerriets T, Kluge A, Klövekorn WP, Kaps M, Bachmann G. Diffusion-weighted magnetic resonance imaging and neurobiochemical markers after aortic valve replacement: implications for future neuroprotective trials? Stroke. 2004 Apr;35(4):888-92. Epub 2004 Feb 19.
- van Dijk D, Kalkman CJ. Why are cerebral microemboli not associated with cognitive decline? Anesth Analg. 2009 Oct;109(4):1006-8. doi: 10.1213/ANE.0b013e3181b5af06.
- Dnr112-09
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Surgical Aortic Valve Replacement |
|---|---|
| Arm/Group Description | Open heart surgery : TCD count of microembolic signals during surgical aortic valve replacement |
| Period Title: Overall Study | |
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Surgical Aortic Valve Replacement |
|---|---|
| Arm/Group Description | Open heart surgery : TCD count of microembolic signals during surgical aortic valve replacement |
| Overall Participants | 10 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
10
100%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
75
(5)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
2
20%
|
| Male |
8
80%
|
| Region of Enrollment (participants) [Number] | |
| Sweden |
10
100%
|
Outcome Measures
| Title | Transcranial Doppler(TCD) Microembolic Signals During Surgical Aortic Valve Replacement Surgery |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Surgical Aortic Valve Replacement |
|---|---|
| Arm/Group Description | Open heart surgery : TCD count of microembolic signals during surgical aortic valve replacement |
| Measure Participants | 10 |
| Mean (Standard Error) [units on a scale] |
354
(79)
|
| Title | Cerebrospinal Fluid(CSF) Levels of S-100B(Microgram/Liter) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Surgical Aortic Valve Replacement |
|---|---|
| Arm/Group Description | Open heart surgery : TCD count of microembolic signals during surgical aortic valve replacement |
| Measure Participants | 10 |
| Mean (Standard Error) [microgram/Liter] |
0.11
(0.02)
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Surgical Aortic Valve Replacement | |
| Arm/Group Description | Open heart surgery : TCD count of microembolic signals during surgical aortic valve replacement | |
All Cause Mortality |
||
| Surgical Aortic Valve Replacement | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Surgical Aortic Valve Replacement | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Surgical Aortic Valve Replacement | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr Bjorn Reinsfelt |
|---|---|
| Organization | Sahlgrenska University Hospital,Cardiothoracic Anesthesia, 41345 Gothenburg ,SWEDEN |
| Phone | 0046702954263 |
| bjorn.reinsfelt@gu.se |
- Dnr112-09