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

Aortic Stenosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01319799
• Other study ID #: Dnr112-09
• Status: Completed
• Phase: N/A
• First received: March 21, 2011
• Last updated: July 19, 2011
• Start date: November 2010
• Est. completion date: June 2011

Study information

• Verified date: November 2010
• Source: Sahlgrenska University Hospital, Sweden
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: The National Board of Health and Welfare
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Clinical diagnosis aortic stenosis eligible for surgical treatment

Exclusion Criteria:

• Coagulopathy

• Regular Anticoagulation therapy

• Carotid stenosis

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis

Intervention

Other:
• Open heart surgery
TCD count of microembolic signals during surgical aortic valve replacement

Locations

Country	Name	City	State
Sweden	Department of Thoracic Anaesthesia & Intensive Care,Sahlgrenska University Hospital	Gothenburg

Sponsors (1)

Lead Sponsor	Collaborator
Sahlgrenska University Hospital, Sweden

Country where clinical trial is conducted

Sweden, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.The exact time is not possible to estimate in advance, but usually approximates 2 hrs in duration	(day 1) TCD will be performed from start of surgery till end of surgery-exact time cannot be stated in advance	Yes
Secondary	Cerebrospinal fluid(CSF) levels of S-100B,NSE and Tau Time Frame: Description: Differences in preoperative vs postoperative CSF levels of S-100B/NSE/Tau Cerebrospinal fluid(CSF) levels of S-100B,NSE and Tau	Differences in preoperative vs postoperative CSF levels of S-100B/NSE/Tau	24 Hours after Surgery	Yes