Clinical trial NCT01319799: Microembolic Signals and Cerebrospinal Fluid Markers of Neuronal Damage After Surgical Aortic Valve Replacement
Official title: Microembolic Signals and Cerebrospinal Fluid Markers of Neuronal Damage After Surgical Aortic Valve
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Aortic Stenosis
Keywords: Embolism
Nervous system
Aorta
Valves
Ultrasonics
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
First posted: 2011-03-22
Enrollment: 10
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Elective surgical aortic valve replacement

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.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis aortic stenosis eligible for surgical treatment

Exclusion Criteria:

* Coagulopathy
* Regular Anticoagulation therapy
* Carotid stenosis

Primary outcomes:
measure: Transcranial Doppler(TCD) Microembolic Signals During Surgical Aortic Valve Replacement Surgery
timeFrame: (day 1) TCD will be performed from start of surgery till end of surgery-exact time cannot be stated in advance
Secondary outcomes:
measure: Cerebrospinal Fluid(CSF) Levels of S-100B(Microgram/Liter)
timeFrame: 24 Hours after Surgery
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Department of Thoracic Anaesthesia & Intensive Care,Sahlgrenska University Hospital
Study officials:
affiliation: Sahlgrenska University Hospital,Thoracic Anesthesia & Intensive Care
name: Sven Erik Ricksten, Professor
role: STUDY_DIRECTOR
References:
citation: Stolz E, Gerriets T, Kluge A, Klovekorn 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. doi: 10.1161/01.STR.0000120306.82787.5A. Epub 2004 Feb 19.
citation: 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. doi: 10.1016/j.jtcvs.2003.09.048.
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.
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. No abstract available.
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.
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. doi: 10.1016/s0003-4975(01)02399-2.