Flow Cytometry Based Platelet Reactivity Testing to Predict the Occurrence of Per-operative Solid Microemboli During Carotid Endarterectomy.

OBJECTIVE: Peri-operative antiplatelet therapy (APT) aims to prevent thrombotic events such as stroke. High platelet reactivity ,despite the use use of APT, increases the risk of thrombotic events. Transcranial Doppler imaging (TCD) is used to detect peri-operative microembolic signals (MES) during carotid endarterectomy (CEA). Peri-operative MES are associated with an increased risk of procedural stroke and new silent lesions on diffusion weighted magnetic resonance imaging following surgery. The main components of TCD detected MES are platelet aggregates, and therefore patients displaying multiple MES during surgery could have benefited from more stringent APT. This study investigated whether the use of flow cytometry based platelet reactivity measurements were correlated with the incidence of pre-operative MES and thereby in the future suitable to predict patients at increased risk of peri-operative thrombotic events. METHODS: Bilateral TCD with MES detection was performed in 197 patients undergoing CEA. Platelet reactivity was assessed with a flow cytometry based platelet reactivity assay measuring platelet response in whole blood. High on treatment platelet reactivity status was assessed for all patients. The secondary outcome was major adverse cardiovascular events (MACE) within one year. RESULTS: In total, 197 patients were included, 49 had peri-operative MES. The platelet response to adenosine diphosphate (ADP) correlated with MES (p = .021), and high on treatment platelet reactivity after adenosine diphosphate stimulation was associated with MACE (OR 2.34, 95% confidence interval 1.126 - 4.890, p = .023). CONCLUSION: Pre-operative platelet reactivity determined by flow cytometry after ADP stimulation correlated with the occurrence of intra-operative MES and post-operative MACE. Clopidogrel treatment showed the most substantial effect on reducing MES frequency and platelet reactivity measured by flow cytometry.

Transcranial Doppler 24 Hours after Carotid Endarterectomy Accurately Identifies Patients Not at Risk of Cerebral Hyperperfusion Syndrome.

OBJECTIVES: Intra-operative transcranial Doppler (TCD) is the gold standard for prediction of cerebral hyperperfusion syndrome (CHS) in patients after carotid endarterectomy (CEA) under general anaesthesia. However, post-operative cerebral perfusion patterns may result in a shift in risk assessment for CHS. This is a study of the predictive value of additional post-operative TCD measurements for prediction of CHS after CEA. METHODS: This was a retrospective analysis of prospectively collected data in patients undergoing CEA with available intra- and post-operative TCD measurements between 2011 and 2016. The mean blood flow velocity in the middle cerebral artery (MCAVmean) was measured pre-operatively, intra-operatively, and post-operatively at two and 24 h. Intra-operative MCAVmean increase was compared with MCAVmean increase two and 24 h post-operatively in relation to CHS. Cerebral hyperperfusion (CH) was defined as MCAVmean increase ≥ 100%, and CHS as CH with the presence of headache or neurological symptoms. Positive (PPV) and negative predictive values (NPV) of TCD measurements were calculated to predict CHS. RESULTS: Of 257 CEA patients, 25 (9.7%) had CH intra-operatively, 45 (17.5%) 2 h post-operatively, and 34 (13.2%) 24 h post-operatively. Of nine patients (3.5%) who developed CHS, intra-operative CH was diagnosed in two and post-operative CH in eight (after 2 h [n = 5] or after 24 h [n = 6]). This resulted in a PPV of 8%, 11%, and 18%, and a NPV of 97%, 98%, and 99% for intra-operative, 2 h and 24 h post-operative TCD, respectively. CONCLUSIONS: TCD measurement of the MCAVmean 24 h after CEA under general anaesthesia is most accurate to identify patients who are not at risk of CHS.

Validation of the Automated Electronic Microemboli Detection System in Patients Undergoing Carotid Endarterectomy.

PURPOSE: To assess the diagnostic value of automatic embolus detection software (AEDS) in transcranial Doppler (TCD) monitoring for the detection of solid microemboli in patients at risk for perioperative stroke during carotid endarterectomy (CEA). MATERIALS AND METHODS: In 50 patients undergoing CEA, perioperative TCD registration was recorded. All recorded events, identified and saved by the AEDS, were analyzed off-line doubly by two human experts (HEs) within a time frame of > 4 months. The inter- and intraobserver variability was assessed. The overall agreement with the HEs, the sensitivity, specificity, negative and positive predictive values (NPV and PPV) of the AEDS were computed for different cut-offs (patient displaying perioperative 5, 10, 20, 25, or 50 microemboli). RESULTS: 77 233 events were analyzed. The inter- and intraobserver variability was good (min κ = 0.72, max κ = 0.79). AEDS and the HEs identified 760 and 470 solid emboli, respectively. The agreement between AEDS and the HEs for solid emboli detection was poor (κ = 0.24, SE = 0.016). The specificity and NPV were high (99.2 % and 99.6 %) but the sensitivity and PPV were low (30.6 % and 19.8 %). Applying a threshold of > 20 microemboli resulted in the best sensitivity (100.0 %), specificity (84.4 %), PPV (42.7 %), NPV (100.0 %) and area under the curve (0.898). However, 58.3 % of the patients were false positive as classified by AEDS. CONCLUSION: In this validation cohort, AEDS has insufficient agreement with HEs in the identification of solid emboli. AEDS and HEs disagree with respect to the identification of specific patients at risk. Therefore, AEDS cannot be used as a standalone system to identify patients at risk for perioperative stroke during CEA.