The ClearSight System for Postoperative Arterial Blood Pressure Monitoring After Carotid Endarterectomy: A Validation Study.

BACKGROUND: The majority of postoperative events in patients undergoing carotid endarterectomy (CEA) are of hemodynamic origin, requiring preventive strict postoperative arterial blood pressure (BP) control. This study aimed to assess whether BP monitoring with noninvasive beat-to-beat ClearSight finger BP (BPCS) can replace invasive beat-to-beat radial artery BP (BPRAD) in the postoperative phase. METHODS: This study was a single-center clinical validation study using a prespecified study protocol. In 48 patients with symptomatic carotid artery stenosis, BPCS and BPRAD were monitored ipsilateral in a simultaneous manner during a 6-hour period on the recovery unit following CEA. Primary endpoints were accuracy and precision of BP derived by ClearSight (Edward Lifesciences, Irvine, CA) vs. the reference standard (Arbocath 20 G, Hospira, Lake Forest, IL) to investigate if BPCS is a reliable noninvasive alternative for BP monitoring postoperatively in CEA patients. Validation was guided by the standard set by the Association for Advancement of Medical Instrumentation (AAMI), considering a BP-monitor adequate when bias (precision) is <5 (8) mm Hg. Secondary endpoint was percentage under- and overtreatment, defined as exceedance of individual postoperative systolic BP threshold by BPRAD or BPCS in contrast to BPCS or BPRAD, respectively. RESULTS: The bias (precision) of BPCS compared to BPRAD was -10 (13.6), 8 (7.2) and 4 (7.8) mm Hg for systolic, diastolic and mean arterial pressure (MAP), respectively. Based on BPCS, undertreatment was 5.6% and overtreatment was 2.4%; however, percentages of undertreatment quadrupled for lower systolic BP thresholds. CONCLUSIONS: Noninvasive MAP, but not systolic and diastolic BP, was similar to invasive BPRAD during postoperative observation following CEA, based on AAMI criteria. However, as systolic BP is currently leading in postoperative monitoring to adjust BP therapy on, BPCS is not a reliable alternative for BPRAD.

Defining the awake baseline blood pressure in patients undergoing carotid endarterectomy.

BACKGROUND: To minimize the incidence of intraoperative stroke following carotid endarterectomy (CEA) under general anesthesia, blood pressure (BP) is suggested to be maintained between "awake baseline" BP and 20% above. However, there is neither a widely accepted protocol nor a definition to determine this awake BP. In this study, we analyzed the BP during hospital admission in the days before CEA and propose a definition of how to determine awake BP. METHODS: In our cohort of 1180 CEA-patients, all noninvasive BP measurements were retrospectively analyzed. BP was measured during preoperative outpatient screening (POS), the last three days before surgery at the ward and in the operating room (OR) directly before anesthesia. Primary outcome was the comparability of all these preoperative BP measurements. Secondary outcome was the comparability of preoperative BP measurements stratified for postoperative stroke within 30 days. RESULTS: POS BP (148±22/80±12 mmHg [mean arterial pressure, MAP: 103±14 mmHg]) and the BP measured on the ward 3, 2, 1 days before surgery and on the day of surgery (146±25/77±13 [MAP: 100±15]), (142±23/76±13 [MAP: 98±15]), (145±23/76±12 [MAP: 99±14]) and (144±22/75±12 mmHg [MAP: 98±14]) were comparable (all P=NS). However, BP in the OR directly before anesthesia was higher, (163±27/88±15 mmHg [MAP: 117±18mmHg]) (P<0.01 vs. all other preoperative moments). A significant higher preinduction systolic BP and MAP was observed in patients suffering a stroke within 30 days compared to patients without (P=0.03 and 0.04 respectively). CONCLUSIONS: Awake BP should be determined by averaging available BP values collected preoperatively on the ward and POS. BP measured in the OR directly before induction of anesthesia overestimates "awake" BP; and therefore, it should not be used.

Intra-Operative Hypotension is a Risk Factor for Post-operative Silent Brain Ischaemia in Patients With Pre-operative Hypertension Undergoing Carotid Endarterectomy.

OBJECTIVE: Intra-operative haemodynamic instability during carotid endarterectomy (CEA) has been associated with an increased risk of procedural stroke. Diffusion weighted imaging (DWI) lesions have been proposed as a surrogate marker for peri-operative silent cerebral ischaemia. This study aimed to investigate the relationship between peri-operative blood pressure (BP) and presence of post-operative DWI lesions in patients undergoing CEA. METHODS: A retrospective analysis was performed based on patients with symptomatic CEA included in the MRI substudy of the International Carotid Stenting Study. Relative intra-operative hypotension was defined as a decrease of intra-operative systolic BP ≥ 20% compared with pre-operative ('baseline') BP, absolute hypotension was defined as a drop in systolic BP < 80  mmHg. The primary endpoint was the presence of any new DWI lesions on post-operative MRI (DWI positive). The occurrence and duration of intra-operative hypotension was compared between DWI positive and DWI negative patients as was the magnitude of the difference between pre- and intra-operative BP. RESULTS: Fifty-five patients with symptomatic CEA were included, of whom eight were DWI positive. DWI positive patients had a significantly higher baseline systolic (186 ± 31 vs. 158 ± 27 mmHg, p = .011) and diastolic BP (95 ± 15 vs. 84 ± 13 mmHg, p = .046) compared with DWI negative patients. Other pre-operative characteristics did not differ. Relative intra-operative hypotension compared with baseline occurred in 53/55 patients (median duration 34 min; range 0-174). Duration of hypotension did not differ significantly between the groups (p = .088). Mean systolic intra-operative BP compared with baseline revealed a larger drop in BP (-37 ± 29 mmHg) in DWI positive compared with DWI negative patients (-14 ± 26 mmHg, p = .024). Absolute intra-operative systolic BP values did not differ between the groups. CONCLUSION: In this exploratory study, high pre-operative BP and a larger drop of intra-operative BP were associated with peri-procedural cerebral ischaemia as documented with DWI. These results call for confirmation in an adequately sized prospective study, as they suggest important consequences for peri-operative haemodynamic management in carotid revascularisation.

Preoperative hypertension is associated with atherosclerotic intraplaque hemorrhage in patients undergoing carotid endarterectomy.

BACKGROUND AND AIMS: Both hypertension and atherosclerotic plaque characteristics such as intraplaque hemorrhage (IPH) are associated with cardiovascular events (CVE). It is unknown if hypertension is associated with IPH. Therefore, we studied if hypertension is associated with unstable atherosclerotic plaque characteristics in patients undergoing carotid endarterectomy (CEA). METHODS: Prospectively collected data of CEA-patients (2002-2014) were retrospectively analyzed. Blood pressure (BP) was the mean of 3 preoperative measurements. Preoperative hypertension was defined as systolic BP ≥ 160 mmHg. Post-CEA, carotid atherosclerotic plaques were analyzed for the presence of calcifications, collagen, smooth muscle cells, macrophages, lipid core, IPH and microvessel density. Associations between BP (systolic and diastolic), patient characteristics and carotid plaque characteristics were assessed with univariate and multivariate analyses with correction for potential confounders. Results were replicated in a cohort of patients that underwent iliofemoral endarterectomy. RESULTS: Within CEA-patients (n = 1684), 708 (42%) had preoperative hypertension. Increased systolic BP was associated with the presence of plaque calcifications (adjusted OR1.11 [95% CI 1.01-1.22], p = 0.03), macrophages (adjusted OR1.12 [1.04-1.21], p < 0.01), lipid core >10% of plaque area (adjusted OR1.15 [1.05-1.25], p < 0.01), IPH (adjusted OR1.12 [1.03-1.21], p = 0.01) and microvessels (adjusted beta 0.04 [0.00-0.08], p = 0.03). Increased diastolic BP was associated with macrophages (adjusted OR1.36 [1.17-1.58], p < 0.01), lipid core (adjusted OR1.29 [1.10-1.53], p < 0.01) and IPH (adjusted OR1.25 [1.07-1.46], p < 0.01) but not with microvessels nor plaque calcifications. Replication in an iliofemoral-cohort (n = 657) showed that increased diastolic BP was associated with the presence of macrophages (adjusted OR1.78 [1.13-2.91], p = 0.01), lipid core (adjusted OR1.45 [1.06-1.98], p = 0.02) and IPH (adjusted OR1.48 [1.14-1.93], p < 0.01). CONCLUSIONS: Preoperative hypertension in severely atherosclerotic patients is associated with the presence of carotid plaque macrophages, lipid core and IPH. IPH, as a plaque marker for CVE, is associated with increased systolic and diastolic BP in both the CEA and iliofemoral population.

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.

Effect of Phenylephrine and Ephedrine on Cerebral (Tissue) Oxygen Saturation During Carotid Endarterectomy (PEPPER): A Randomized Controlled Trial.

BACKGROUND: Short-acting vasopressor agents like phenylephrine or ephedrine can be used during carotid endarterectomy (CEA) to achieve adequate blood pressure (BP) to prevent periprocedural stroke by preserving the cerebral perfusion. Previous studies in healthy subjects showed that these vasopressors also affected the frontal lobe cerebral tissue oxygenation (rSO2) with a decrease after administration of phenylephrine. This decrease is unwarranted in patients with jeopardized cerebral perfusion, like CEA patients. The study aimed to evaluate the impact of both phenylephrine and ephedrine on the rSO2 during CEA. METHODS: In this double-blinded randomized controlled trial, 29 patients with symptomatic carotid artery stenosis underwent CEA under volatile general anesthesia in a tertiary referral medical center. Patients were preoperative allocated randomly (1:1) for receiving either phenylephrine (50 µg; n = 14) or ephedrine (5 mg; n = 15) in case intraoperative hypotension occurred, defined as a decreased mean arterial pressure (MAP) ≥ 20% compared to (awake) baseline. Intraoperative MAP was measured by an intra-arterial cannula placed in the radial artery. After administration, the MAP, cardiac output (CO), heart rate (HR), stroke volume, and rSO2 both ipsilateral and contralateral were measured. The timeframe for data analysis was 120 s before, until 600 s after administration. RESULTS: Both phenylephrine (70 ± 9 to 101 ± 22 mmHg; p < 0.001; mean ± SD) and ephedrine (75 ± 11 mmHg to 122 ± 22 mmHg; p < 0.001) adequately restored MAP. After administration, HR did not change significantly over time, and CO increased 19% for both phenylephrine and ephedrine. rSO2 ipsilateral and contralateral did not change significantly after administration at 300 and 600 s for either phenylephrine or ephedrine (phenylephrine 73%, 73%, 73% and 73%, 73%, 74%; ephedrine 72%, 73%, 73% and 75%, 74%, 74%). CONCLUSIONS: Within this randomized prospective study, MAP correction by either phenylephrine or ephedrine showed to be equally effective in maintaining rSO2 in patients who underwent CEA. Clinical Trial Registration ClincalTrials.gov, NCT01451294.

Technical improvements in carotid revascularization based on the mechanism of procedural stroke.

The benefit of carotid revascularization in patients with severe carotid artery stenosis is hampered by the risk of stroke due to the intervention itself. The risk of periprocedural strokes is higher for carotid artery stenting (CAS) as compared to carotid endarterectomy (CEA). Over the past years, the pathophysiological mechanism responsible for periprocedural stroke seems to unfold step by step. Initially, all procedural strokes were thought to be the result of technical errors during surgical repair: cerebral ischemia due to clamping time of the carotid artery, cerebral embolization of atherosclerotic debris due to manipulation of the atheroma or thrombosis of the artery. Following improvements in surgical techniques, technical skills, new intraoperative monitoring technologies such as angioscopy, and the results of the first large clinical randomized controlled trials (RCT) it was believed that most periprocedural strokes were of thromboembolic nature, while a large part of these caused by technical error. Nowadays, analyses of underlying pathophysiological mechanisms of procedural stroke make a clinically relevant distinction between intra-procedural and postprocedural strokes. Intra-procedural stroke is defined as hypoperfusion due to clamping (CEA) or dilatation (CAS) and embolization from the carotid plaque (both CEA and CAS). Postprocedural stroke can be caused by thrombo-embolisation but seems to have a primarily hemodynamic origin. Besides thrombotic occlusion of the carotid artery, cerebral hyperperfusion syndrome (CHS) due to extensively increased cerebral revascularization is the most reported pathophysiological mechanism of postprocedural stroke. Multiple technical improvements have attempted to lower the risk of periprocedural stroke. The introduction of antiplatelet therapy (APT) has significantly reduced the risk of thromboembolic events in patients with carotid stenosis. Over the years, recommendations regarding APT changed. While for a long time APT was discontinued prior to surgery because of a fear of increased bleeding risk, nowadays continuation of APT during carotid intervention (aspirin monotherapy or even dual APT including clopidogrel) is found to be safe and effective. In CAS patients, dual APT up to three months' postprocedural is considered best. Stent design and cerebral protection devices (CPD) for CAS procedure are continuously under development. Trials have suggested a benefit of closed-cell stent design over open-cell stent design in order to reduce procedural stroke, while the benefit of CPD during stenting is still a matter of debate. Although CPD reduce the risk of procedural stroke, a higher number of new ischemic brain lesions detected on diffusion weighted imaging was found in patients treated with CPD. In patients undergoing CEA under general anesthesia, adequate use of cerebral monitoring (EEG and transcranial Doppler [TCD]) has reduced the number of intraoperative stroke by detecting embolization and thereby guiding the surgeon to adjust his technique or to selectively shunt the carotid artery. In addition, TCD is able to adequately identify and exclude patients at risk for CHS. For CAS, the additional value of periprocedural cerebral monitoring to prevent strokes needs urgent attention. In conclusion, this review provides an overview of the pathophysiological mechanism of stroke following carotid revascularization (both CAS and CEA) and of the technical improvements that have contributed to reducing this stroke risk.