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Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients
Eur J Vasc Endovasc Surg (2018)
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1e8
Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients Michele Piazza *, Marco Zavatta, Margherita Lamaina, Jacopo Taglialavoro, Francesco Squizzato, Franco Grego, Michele Antonello Clinic of Vascular and Endovascular Surgery, Padova University School of Medicine, Padua, Italy
WHAT THIS PAPER ADDS Routine shunting with device insertion just after rapid carotid endarterectomy (CEA) is a valid technique, able to optimise the benefit of continuous cerebral perfusion together with a reduced risk of related complications. This specific method, together with standardisation of the procedure, leads to a neurological complication rate <1%, which can be consistently maintained over time and independently from different operators. In asymptomatic patients with significant carotid stenosis, this approach offers patients the modern reliable CEA low stroke risk rate they expect.
Objective/background: The aim was to evaluate early outcomes of carotid endarterectomy (CEA) in asymptomatic patients using a standardised technique based on routine shunting after rapid plaque removal (“delayed”). Methods: A retrospective review of all asymptomatic patients who underwent CEA during a 10 year single centre experience (January 2007eDecember 2016) was performed. The technique was based on rapid endarterectomy with distal intimal edge visualisation, followed by routine shunt insertion; subsequent time spent on the manoeuvre and closure were completed under shunting. Primary endpoints were relevant neurological complication rate (RNCR) and death within 30 days. To better identify any difference related to changes in medical therapy, anaesthetic management, and different operators over time, patients were divided into group A (underwent CEA in the first 5 year period) and group B (underwent CEA during the second 5 year period). Univariate analysis of factors associated with RNCR was performed. Operator experience (seniority), expertise (CEA volume per year), and time period were incorporated. Results: In total, 1745 patients matched the inclusion criteria and were enrolled. Altogether, 147 (8.9%) had contemporary contralateral stenosis 70% and 58 (3.5%) had contralateral internal carotid artery chronic occlusion. No patient died peri-operatively; major myocardial infarction occurred in 19 patients (1.1%). Overall, peri-operative RNCR was 0.6% (major stroke: n ¼ 6 [0.4%]; minor stroke: n ¼ 4 [0.2%]). RNCR distribution was maintained equally comparing group A and B (0.8% vs. 0.4%; p ¼ 0.17). No differences were found in RNCR when comparing operator experience (p ¼ 0.88) and expertise (p ¼ 0.93). Univariable analysis found diabetes as the only clinical factor influencing RNCR (odds ratio 3.79, 95% confidence interval 1.06e13.50; p ¼ 0.04); none of the other factors, such as time period, operator experience, and expertise, reached statistical significance. Conclusions: Routine delayed shunting associated with standardisation of the technique seems to be a safe and effective technique and contributes to maintaining the RNCR < 1% over time and independently from operators and other clinical factors. Ó 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved. Article history: Received 7 March 2018, Accepted 11 June 2018, Available online XXX Keywords: Carotid endarterectomy, CEA, Shunt, Standardisation
INTRODUCTION Carotid endarterectomy (CEA) is widely recognised as the gold standard surgical approach to the prevent of major cerebral * Corresponding author. Clinic of Vascular and Endovascular Surgery, Padova University School of Medicine, Via Giustiniani 2, 35128 Padova (PD), Italy. E-mail address: [email protected] (Michele Piazza). 1078-5884/Ó 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved. https://doi.org/10.1016/j.ejvs.2018.06.030
events in patients with significant carotid stenosis.1 The results of trials such as the Asymptomatic Carotid Atherosclerosis Study (ACAS)2 and the Asymptomatic Carotid Surgery Trial (ACST),3 performed in the 1990s, favoured CEA plus medical therapy over medical therapy alone in the management of asymptomatic patients with significant carotid stenosis. As emphasised in the literature,4 these findings hold true only if the cumulative risk of relevant neurological complication rate (RNCR) and peri-operative mortality during surgery is <3%.
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
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Despite the fact that CEA has been performed for decades, specific operative techniques remain highly variable, especially techniques for cerebral monitoring and protection.5 While shunting aims to minimise the cerebral ischaemia time during clamping and therefore to reduce RNCR, on the other side device insertion itself is a delicate manoeuvre that requires operator expertise. Brain embolisation from plaque fragments, intimal lesions with ICA dissection, and shunt malfunctions are some of these aspects. Also, the CEA procedure itself, type of anaesthesia, closure methods, and neurological monitoring have a wide range of approaches depending on operator expertise and preferences. The absence of a standardised procedure is one of the aspects that may be responsible for the wide range in RNCR, depending on the series analysed (from 0.7% to 4%).6 The objective of this study was to evaluate early surgical and neurological outcomes (within 30 days of surgery) of CEA in asymptomatic patients with stenosis 70% using a specific standardised technique based on rapid endarterectomy with accurate assessment of distal intimal break off edge, followed by routine “delayed” shunt insertion. Also evaluated was whether other factors such as time period or surgeon’s experience may influence outcomes in terms of RNCR. MATERIALS AND METHODS A retrospective review of all patients admitted to the Clinic of Vascular and Endovascular Surgery of Padua University who underwent CEA between January 2007 and December 2016 was performed. All data were prospectively collected in a dedicated database. Institutional Review Board requirements were waived for this study. Patient selection Only asymptomatic patients with 70% carotid stenosis were enrolled. Patients with significant contralateral carotid stenosis or occlusion were also included. All symptomatic patients and asymptomatic patients with pre-operative computed tomography (CT) or magnetic resonance imaging (MRI) evidence of recent onset (<30 days) ipsilateral ischaemic lesions were excluded. Patients affected by carotid aneurysms, dissections, restenosis, or CEA performed in association with other surgical procedures (coronary artery bypass, common carotid artery stenting at its origin from the arch) were also excluded. Patients were divided into two groups: those undergoing CEA in the first 5 year time period (2007e11; group A) and those treated during the second 5 year period (2012e16; group B). This was done to better identify any difference in outcomes in relation to improvement in medical therapy, anaesthetic management, and different operators over time. Treatment and definitions Demographic baseline characteristics, risk factors, and preoperative medical therapy were obtained by reviewing all available medical records at the time of operation.
Michele Piazza et al.
The cardiovascular risk factors considered were hypertension, dyslipidaemia, diabetes, chronic obstructive pulmonary disease, history of coronary artery revascularisation (coronary artery bypass graft or percutaneous transluminal coronary angioplasty [PTCA]). Pre-operative assessment also included information on medical therapy (antiplatelet, anticoagulant, statin therapy). Pre-operative imaging was routinely performed with carotid duplex ultrasound (DUS) followed by CT or MR angiography scan of the supra-aortic and intracranial vessels; a cerebral CT scan was performed to identify any recent ischaemic lesions. The grade of stenosis was defined based on DUS with the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method;7 if a stenosis 70% was identified, a subsequent CT angiogram of the supra-aortic and intracranial vessels was obtained in order to corroborate DUS findings and to evaluate carotid disease extension based on Society for Vascular Surgery (SVS)/European Society for Vascular Surgery (ESVS) guidelines.8,9 The definition of asymptomatic was based on SVS/ESVS extracranial carotid disease guidelines (no previous symptoms or no symptoms in the preceding 6 months).8,9 Operative factors considered were clamping times, electroencephalogram (EEG) variations during cross clamping, eventual complications during endarterectomy and shunt insertion, type of closure, and additional intra-operative procedures. Technical success was defined as an uneventful endarterectomy without the need for additional procedures during surgery or on waking. Post-operative transient ischaemic attack (TIA), minor and major stroke were defined according to the current reporting standards.10 The National Institute of Health Stroke Scale (NIHSS) was used for neurological assessment pre-operatively, at patient awakening, and 6 and 24 h after the procedure. In case of altered NIHSS, the patient was subsequently evaluated by a neurologist for accurate evaluation and management strategy. All patients with the onset of a new neurological deficit after surgery underwent an urgent carotid DUS and cerebral CT. Eventual subsequent imaging by CT angiogram or any type of interventions, were considered on a case by case basis. Any other new clinical or neurological findings after discharge and within 30 days were assessed with telephone interviews at 30 days by a dedicated doctor. If a patient referred to any type of symptom, he or she was scheduled for an outpatient clinic visit and eventual additional examinations were required for a precise diagnosis. If a patient developed any acute episode requiring urgent/emergency hospitalisation, the medical records of Padova Hospital Area Intranet System (allowing for visualisation of medical records of all Padova area hospitals and outpatients clinics) were reviewed. All surgical, cardiac, and neurological complications were categorised in accordance with the SVS reporting standards for carotid interventions.8 Primary endpoints were to compare RNCR (minor and major stroke) and related death 30 days after CEA between the two different time periods (groups A and B).
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
Early Outcomes of Routine Delayed Shunting
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Figure 1. (A) Insertion of a Pruitt-Inahara shunt into the internal carotid artery under visual control over the endarterectomy endpoint. (B) Test of correct functioning of the Pruitt-Inahara shunt. Blood flow is checked by opening the red T-port.
A subgroup analysis for RNCR was performed based on “surgeon experience”, defined as years of seniority (senior consultants: > 20 years of experience; experienced consultants: > 5 years of experience; junior consultant: < 5 years of experience), and “surgeon expertise”, which was defined based on surgeon volume of interventions per year (high volume: > 30; medium volume: 15e30; low volume: < 15 CEAs/year). Operative technique All CEAs were performed by vascular surgeons of the Vascular and Endovascular Surgery Clinic of Padua University during the study time period (January 2007eDecember 2016). All CEAs were performed under general anaesthesia and continuous EEG monitoring, which was used to detect any type of unexpected cerebral hypoperfusion or shunt malfunction. A longitudinal cut down on the anterior margin of the sternocleidomastoid muscle was performed and the carotid bifurcation was exposed. After systemic heparinisation with 100 U/kg heparin, the external carotid artery, internal carotid artery (ICA), and common carotid artery (CCA) were clamped. Two methods of endarterectomy were considered: standard endarterectomy with longitudinal arteriotomy of the bulb and ICA origin followed by patch closure (Gore Acuseal CardioVascular Patch) for a straight ICA, or eversion with ICA resection at the bulb and its re-implantation (for an ICA with kinking or redundant coiling). In both cases, a rapid endarterectomy was performed, followed by accurate distal endpoint assessment of the resulting intimal edge. At this point, independently from eventual EEG modifications, a Pruitt-Inahara shunt was routinely inserted in the ICA under direct visual assessment of the endpoint (Fig. 1A); the same manoeuvre was performed in the CCA and shunt correct functioning was checked from the red T port to assure a pulsatile blood flow (Fig. 1B). Once the correct shunt function was tested, accurate removal of small
fragments of loose debris from the endarterectomised surface and closure were performed. For a standard endarterectomy the artery was closed with a 6.0 Prolene running suture of a synthetic polytetrafluoroethylene patch. For an eversion endarterectomy, the ICA was re-everted on the shunt tube for distal endpoint recheck, adjusted for length and then re-implanted. In both cases, before suture completion, the shunt was removed, the arteries were flushed, and the suture finally secured. During all procedures, any EEG modifications were recorded. Statistical analysis Considering an anticipated RNCR of 1%, the minimum sample size to detect a 2% difference was calculated to be 719 patients per group, with a significance level of 0.05 and a power of 0.80. Continuous variables are presented as mean SD, categorical data as n (%). Uni- and bivariable analyses were performed using the t-test or Wilcoxon rank sum for continuous variables and a two tailed chi-square test for categorical variables. Univariable analysis of factors associated with RNCR was performed. Operator experience, expertise, and time period were incorporated in the analysis. Multivariable analysis was not performed to avoid the risk of over fitting due to the limited numbers of events compared with the number of independent variables. A p value < 0.05 was considered statistically significant for all analyses. Data analysis was performed using STATA 14.1 (Stata Corp., College Station, TX, USA). RESULTS During the study period, a total of 1852 CEAs were performed. In total, 1745 patients (94.2%) matched the inclusion criteria and were enrolled in the study. Of these,
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
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Michele Piazza et al.
Table 1. Analysis of baseline and anatomical preoperative characteristics of patients who underwent CEA, comparing patients of the first 5year time period (Group A, 2007e2011) to patients of the second (Group B, 2012e2016). Variable
Overall (1745 pts.)
Demographics Age, years SD 72.6 7.9 Age < 75 years 1037 (59.4%) Male gender 1108 (63.5%) Risk factors Hypertension 1451 (83.1%) Dyslipidemia 1174 (67.3%) COPD 119 (6.8%) Prior PCI 184 (10.5%) Prior CABG 132 (7.6%) Diabetes 480 (27.5%) Previous therapy Single antiplatelet 1415 (81.1%) Double antiplatelet 121 (6.9%) Oral anticoagulant 167 (9.6%) N. of cardiac drugs 1.6 1.2 Statin 1129 (64.7%) Anatomical characteristics Kinking/coiling 523 (29.9%) CT brain lesions 7 (0.4%) Contralateral ICA Stenosis >70% 147 (8.4%) Occlusion 58 (3.3%) Bold ¼ Statistically significant. COPD, chronic obstructive pulmonary artery bypass graft.
868 (49.7%) patients were treated between 2007 and 2011 (group A) and 877 (50.3%) between 2012 and 2016 (group B). The overall age was 72.6 7.9 years, and the majority of enrolled patients were male (n ¼ 1108 [63.5%]). Overall baseline and anatomical pre-operative characteristics, and their distribution in groups A and B, are reported in Table 1. Comparing the two groups, in the most recent 5 year period the percentage of patients diagnosed with dyslipidaemia increased significantly (75.9% vs. 63.3%; p < 0.001) and a history of previous PTCA was more frequent (13% vs. 8.8%; p ¼ 0.006), probably reflecting the real world trend in cardiovascular disease treatment and changes in medical therapy. In fact, in this cohort the number of patients on double antiplatelet therapy increased with time (9.8% vs. 5.1%; p < 0.001), as did use of statins (75.2% vs. 63.8%; p < 0.001). Overall, technical success was achieved in 99.9% of cases. In eight cases carotid bypass was required (in five cases the atherosclerotic plaque was firmly adherent and its endarterectomy caused injury to the vessel which necessitated interposition; in the remaining three cases the distal endpoint of the endarterectomy into the ICA could not be adequately finished because of intimal dissection). Patch closure was the most used technique (1205 patients [69.2%]), whereas eversion and reimplantation was used only for ICA coiling and/or kinking (523 patients [30%]). When comparing the two subgroups, no differences were identified in operative characteristics (Table 2).
Group A (868 pts.)
Group B (877 pts.)
p Value
72.5 7.8 526 (60.6%) 545 (62.8%)
72.8 8 511 (58.3%) 563 (64.3%)
0.511 0.321 0.520
694 (79.9%) 518 (59.7%) 59 (6.7%) 72 (8.2%) 63 (7.3%) 237 (27.3%)
757 (86.3%) 656 (74.8%) 60 (6.8%) 112 (12.7%) 69 (7.9%) 243 (27.7%)
0.087 <0.001 0.836 0.006 0.834 0.712
701 (80.7%) 40 (4.6%) 100 (11.5%) 1.9 1.2 504 (58.1%)
714 (81.4%) 81 (9.2%) 67 (7.6%) 1.9 1.3 625 (71.2%)
0.26 <0.001 0.002 0.728 <0.001
252 (29%) 2 (0.2%)
271 (30.9%) 5 (0.6%)
0.430 .0280
70 (8.0%) 77 (8.7%) 0.869 28 (3.2%) 30 (3.4%) 0.997 disease; PCI, percutaneous coronary interventions; CABG, coronary
No patients died; intra- or peri-operative (30 days) onset of myocardial infarction was detected in 19 patients (1.1%). At 30 days, 12 TIA (0.7%), four minor strokes (0.2%), and six major strokes (0.4%) were recorded, and none of these was a shunt related complication. In particular, of the 10 patients developing post-operative stroke, two had significant contralateral carotid stenosis and one had chronic contralateral carotid occlusion. None of them experienced EEG variations during clamping or shunting. The overall RNCR was 0.6%; when the yearly RNCR was analysed over the 10 years, it was found to be maintained below 1% (Fig. 2). No significant differences between group A and B were found in major early outcomes, considering surgical, cardiac, and neurological complications, which was also the case for RNCR (group A 0.8%, group B 0.4%; p ¼ 0.175) (Table 3). Operator experience had no impact on peri-operative complication rates and, in particular, on RNCR (senior consultants: 0.7%; experienced consultants: 0.5%; young consultants: 0.7% [p ¼ 0.883]). Similarly, RNCR was not influenced by operator expertise, considered as operator volume of interventions per year (high volume: 0.6%; medium volume: 0.5%; low volume: 0.7% [p ¼ 0.931]) (Table 4). Finally, univariable regression analysis demonstrated that the only factor influencing RNCR was diabetes (p ¼ 0.040) (Table 5). None of the other major clinical or anatomical factors, including contralateral significant carotid stenosis or occlusion, operator experience and expertise, and time period, had any significant impact.
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
Early Outcomes of Routine Delayed Shunting
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Table 2. Intraoperative characteristics of patients who underwent CEA, comparing patients of the first 5-year time period (Group A, 2007e 2011) to patients of the second (Group B, 2012e2016). Variable
Overall (1745 pts.)
Operative characteristics Operative time, min SD 95.7 27.9 Clamping time, min SD 4 1.3 EEG variations 41 (2.3%) Closure technique Patch 1205 (69%) ICA replantation 523 (29.9%) By-pass 8 (0.5%) EEG, electroencephalography; ICA, internal carotid artery.
DISCUSSION Atherosclerosis of the supra-aortic vessels and especially of the carotid bifurcation is widely recognised as a major cause of recurrent ischaemic stroke. There is evidence that it accounts for approximately 20% of all strokes,9 and nearly 80% of these may occur with no warning.10e14 SVS guidelines suggest that neurologically asymptomatic patients with 60% carotid stenosis should be considered for CEA for the reduction of long-term risk of stroke if the patient has a 3e5 year life expectancy and a peri-operative stroke or death rate of 3% (grade 1, level of evidence A).9 The 3% risk threshold has been defined on the basis of studies conducted before the introduction of modern medical therapy.15,16 These studies demonstrated that the annual risk of ischaemic stroke in adults with asymptomatic carotid stenosis treated with medical therapy alone accounted for 2e5%. Therefore, these findings may not be applicable to contemporary clinical practice.17 A meta-analysis of incidence rate data from prospective single group cohorts of medical therapy alone for asymptomatic carotid stenosis showed that the incidence rate of ipsilateral stroke was lower (1.68% per year),18 particularly in studies conducted in the last decade (1.13% per year). These recent findings raise doubt as to whether CEA is still the gold standard for the management of asymptomatic patients with significant carotid stenosis. In this setting, suggestions are that only a limited number of all asymptomatic patients may benefit from prophylactic CEA.19 The most recent guidelines for the treatment of asymptomatic carotid stenosis, published in August 2017 from a consensus between cardiologists and vascular surgeons in Europe, recommend consideration of CEA in “average surgical risk”
Group A (868 pts.)
Group B (877 pts.)
p Value
93.7 30.2 3.9 1.4 20 (2.3%)
97.5 25.3 4 1.1 21 (2.3%)
0.997 0.979 0.901
601 (69.2%) 252 (29%) 6 (0.7%)
604 (68.8%) 271 (30.9%) 2 (0.2%)
0.755 0.430 0.150
patients with an asymptomatic 60e99% stenosis, in the presence of clinical and/or imaging characteristics that may be associated with an increased risk of late ipsilateral stroke; again only if the documented peri-operative stroke/ death rate is <3% and the patient’s life expectancy is > 5 years (class of recommendation IIa, level of evidence B).8 In the authors’ opinion, being at relatively low risk of ipsilateral stroke, asymptomatic patients receiving best available medical therapy may benefit from a revascularisation procedure only if peri-procedural complications can be minimised by more than the 3% reported in historical guidelines. Moreover, it must be considered that outcomes reported in randomised controlled trials may not always reflect practice in the “real world”: while centres seeing a high volume of interventions per year are able to guarantee a peri-operative RNCR of 1%, other institutions report a higher complication rate. A 2016 systematic review by Paraskevas et al., analysed all available administrative data set registries reporting outcomes after CEA and carotid artery stenting from 2008 to 2016.6 Twenty-one registries were included in the analysis, accounting for more than 1,500,000 procedures. For asymptomatic patients at average risk of CEA, only four registries (19%) reported a RNCR/mortality cumulative risk after CEA <1%, 16 comprised 1e3% (76%), and one (almost 5%) >3%. These significant differences in early outcomes, especially with regard to peri-operative neurological events, may reflect the variability and differences in surgical techniques between different operators and/or institutions. This also includes technical aspects, such as intra-operative cerebral monitoring systems and shunting techniques.
Figure 2. Analysis of yearly relevant neurological complication rate (RNCR) during the 10 year study period. Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
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Table 3. Analysis of intra-operative and early complications in the 1745 patients enrolled comparing the first 5-year time period (Group A, 2007e2011) to the second (Group B, 2012e2016). Variable
Overall Group A Group B p Value (1745 pts.) (868 pts.) (877 pts.)
Surgical ICA dissection 3 (0.1%) 0 3 (0.3%) 0.092 Cranial Nerve 21 (1.2%) 11 (1.2%) 10 (1.1%) 0.728 injury Cervical 41 (2.3%) 17 (1.9%) 24 (2.7%) 0.352 Hematoma Cardiac Arrhythmias 26 (1.4%) 11 (1.2%) 15 (1.7%) 0.517 Myocardial 19 (1%) 7 (0.8%) 12 (1.3%) 0.302 infarction Neurologic Subarachnoid 1 (0.05%) 0 1 (0.1%) 0.331 hemorrhage TIA 12 (0.6%) 8 (0.9%) 4 (0.4%) 0.209 Minor Stroke 4 (0.2%) 2 (0.2%) 2 (0.2%) 0.955 Major Stroke 6 (0.3%) 5 (0.5%) 1 (0.1%) 0.088 Deaths 0 0 0 e RNCR 10 (0.5%) 7 (0.8%) 3 (0.3%) 0.175 ICA, internal carotid artery; TIA, transient ischemic attack; RNCR, relevant neurologic complication rate.
In particular, the use of shunting in CEA is controversial. As reported in the literature shunt use is probably unnecessary in approximately 85% of patients, and may be associated with complications including atheromatous or air emboli, arterial dissection, and acute occlusion.5,20 Nevertheless, there is no evidence in the literature of a significant increase in complication rate related to shunt insertion.21 On the contrary, shunting undoubtedly guarantees the maintenance of an optimal cerebral blood flow during clamping time,22 allowing an unhurried endarterectomy and closure. A Cochrane review published in 2014 reviewed all available randomised controlled prospective trials comparing routine and selective shunting and risk of perioperative complications, including stroke and death;23 this review concluded that data were insufficient to support or
Table 5. Univariable regression analysis of RNCR. Variable
RNCR OR 95% CI p Senior consultants Reference Experienced consultants 0.72 0.14e3.59 0.690 Young consultants 0.99 0.14e7.01 0.991 High volume Reference Medium volume 0.99 0.22e4.45 0.992 Low volume 1.29 0.29e5.81 0.737 2007e11 time period Reference 2012e16 time period 0.40 0.10e1.56 0.189 Contralateral stenosis >70% 1.13 0.14e9.02 0.905 Contralateral occlusion 3.08 0.38e24.73 0.290 Kinking/coiling 0.99 0.26e3.87 0.998 Diabetes 3.79 1.06e13.50 0.040 Previous PCI 0.90 0.11e7.17 0.923 Previous CABG 2.97 0.62e14.11 0.172 Note. Bold ¼ Statistically significant. RNCR ¼ relevant neurological complication rate; OR ¼ odds ratio; CI ¼ confidence interval; PCI ¼ percutaneous coronary interventions; CABG ¼ coronary artery bypass graft.
refute the use of selective or routine shunting. Based on this evidence, the European Society of Cardiology/ESVS guidelines recommend (level of evidence class 1, level C) that the choice of shunting (routine, selective, never) should be left to the discretion of the operating surgeon.8 While in the literature there are plentiful data regarding the “timing” for shunt (routine or selective), no studies have focused their attention on the technique used for its insertion. To the authors’ knowledge, most commonly the distal end of the shunt is inserted into the ICA with the plaque “in situ” and the endarterectomy performed after shunt insertion. The authors’ choice of routine and delayed use of the Pruitt-Inahara shunt aims first of all, to minimise the complications related to its insertion including microembolisation and arterial dissection. This aspect is particularly emphasised in symptomatic cases, where the risk of micro-embolisation is higher owing to more frequent
Table 4. Analysis of early neurological complications in the 1745 patients enrolled stratified by surgeon experience and expertise. Variable
Senior consultants Experienced consultants Young consultants p (n ¼ 273 patients) (n ¼ 1133 patients) (n ¼ 276 patients) Subarachnoid haemorrhage 0 1 (0.1) 0 0.785 TIA 2 (0.7) 7 (0.6) 3 (1.1) 0.708 Minor stroke 1 (0.4) 2 (0.2) 1 (0.4) 0.760 Major stroke 1 (0.4) 4 (0.4) 1 (0.4) 0.999 Deaths 0 0 0 e RNCR 2 (0.7) 6 (0.5) 2 (0.7) 0.883 Variable High volume Medium volume Low volume (n ¼ 735 patients) (n ¼ 563 patients) (n ¼ 444 patients) Subarachnoid haemorrhage 1 (0.1) 0 0 0.513 TIA 2 (0.3) 8 (1.4) 2 (0.5) 0.036 Minor stroke 2 (0.3) 1 (0.2) 1 (0.2) 0.944 Major stroke 2 (0.3) 2 (0.4) 2 (0.5) 0.860 Deaths 0 0 0 e RNCR 4 (0.5) 3 (0.5) 3 (0.7) 0.931 Note. Data are n (%). Bold ¼ Statistically significant. TIA ¼ transient ischaemic attack; RNCR ¼ relevant neurological complication rate. Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
Early Outcomes of Routine Delayed Shunting
unstable plaque; for this reason, this technique is adopted in this setting, too. In asymptomatic patients, it is believed the major benefit related to shunting is to guarantee direct cerebral perfusion during the largest part of the surgical procedure and reduce the risk of hypoperfusion. In fact, in the present authors’ experience, the time needed for endarterectomy rarely exceeds 3 min and subsequent shunt insertion is easily accomplished after plaque removal and under visual distal endpoint control. The following time consuming manoeuvre of removal of small fragments of loose debris from the endarterectomised surface, distal and proximal endpoint re-check, external carotid artery ostium control, and sutures for artery closure, can be performed with no rush. All surgeons in the authors’ team use this technique routinely in order to also allow the operator to be extremely confident with shunt use. The opinion of the authors is corroborated by the findings of Goodney et al.,24 who in a study on the impact of practice patterns in shunt use during CEA, reported that the 30 day stroke/death rate for patients shunted during CEA was higher if the surgeon used it selectively rather than routinely. Finally, the use of the Pruitt-Inahara shunt rather than a standard tube has two advantages. The first is that the balloon inflated in the ICA has a “secure system” that avoids balloon over-inflation with a lower risk of arterial intimal lesion; the second is that with the “T” configuration, it is possible to check, at any time, the pulsatile flow and correct shunt function. This study demonstrates that this particular technique seems to be effective and guarantees low peri-procedural complication rates, with a combined mortality/RNCR of <1%. Moreover, since 2000, all surgeons at the authors’ clinic follow the same precise steps for arterial access, plaque removal, routine “delayed” shunting, peeling, and closure technique. The high level of standardisation of the procedure has been a key point. In fact, this has allowed maintenance of outcomes, despite the presence of a contralateral significant stenosis or occlusion, the time period analysed (changes in anaesthesia techniques, pharmacological management), and, most importantly, despite differences in surgeons’ experience and expertise. As suggested by Flanigan et al.,25 the application of a specific and standardised surgical technique leads to excellent and constant results. The present outcomes, in the authors’ opinion, were the result of the association between a specific technique together with its standardisation; these two factors together allow for an RNCR <1% and this be maintained consistently low in order to offer patients a reliably low risk of stroke. The study has some limitations. This was a retrospective, non-randomised study; subgroup analysis and multivariable analysis were not feasible owing to the limited number of events. New guidelines are expected to change the treatment paradigm for asymptomatic patients with carotid
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artery stenosis, supported by evidence that modern medical therapy has improved its outcomes in preventing cerebral events. The study demonstrates that CEA still has a role in this particular category of patients. The choice of optimal surgical technique and standardisation of the procedure have a key role in minimizing complication rates and maintaining results over time. CONCLUSIONS The routine use of delayed shunting in asymptomatic patients contributed to maintenance of a peri-operative stroke/death rate of <1% over a decade, independently from operators, time period, and other major clinical factors. CEA technique standardisation is mandatory to guarantee and maintain a valid role in stroke risk prevention over time. CONFLICT OF INTEREST None. FUNDING None. REFERENCES 1 Mitka M. Study findings offer conflicting views on future role of carotid artery stenting. JAMA 2010;303:1584e6. 2 ACAS Executive committee. Endarterectomy for asymptomatic carotid artery stenosis. Executive committee for the asymptomatic carotid Atherosclerosis study. JAMA 1995;273:1421e8. 3 Halliday A, Harrison M, Hayter E, Kong X, Mansfield A, Marro J, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet 2010;376:1074e84. 4 Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:517e84. 5 AbuRahma AF, Stone PA, Hass SM, Dean LS, Habib J, Keiffer T, et al. Prospective randomized trial of routine versus selective shunting in carotid endarterectomy based on stump pressure. J Vasc Surg 2010;51:1133e8. 6 Paraskevas KI, Kalmykov EL, Naylor AR. Stroke/death rates following carotid artery stenting and carotid endarterectomy in contemporary administrative dataset registries: a systematic review. Eur J Vasc Endovasc Surg 2016;51:3e12. 7 Ferguson GG, Eliasziw M, Barr HWK, Clagett GP, Barnes RW, Wallace MC, et al. the North American symptomatic carotid endarterectomy trial: surgical results in 1415 patients. Stroke 1999;30:1751e8. 8 Aboyans V, Ricco JB, Bartelink MLEL, Björck M, Brodmann M, Cohnert T, et al. 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European society for vascular surgery (ESVS). Eur J Vasc Endovasc Surg 2018;55:305e68. 9 Ricotta JJ, Aburahma A, Ascher E, Eskandari M, Faries P, Lal BK. Updated Society for Vascular Surgery guidelines for management of extracranial carotid disease. J Vasc Surg 2011;54:e1e 31.
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8 10 Timaran CH, McKinsey JF, Schneider PA, Littooy F. Reporting standards for carotid interventions from the society for vascular surgery. J Vasc Surg 2011;53:1679e95. 11 Veith FJ, Amor M, Ohki T, Beebe HG, Bell PRF, Bolia A, et al. Current status of carotid bifurcation angioplasty and stenting based on a consensus of opinion leaders. J Vasc Surg 2011;33: S111e6. 12 Bogousslavsky J, Van Melle G, Regli F. The lausanne stroke registry: analysis of 1,000 consecutive patients with first stroke. Stroke 1988;19:1083e92. 13 Foulkes MA, Wolf PA, Price TR, Mohr JP, Hier DB. The Stroke Data Bank: design, methods, and baseline characteristics. Stroke 1988;19:547e54. 14 Inzitari D, Eliasziw M, Gates P, Sharpe BL, Chan RKT, Meldrum HE, et al. The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. N Engl J Med 2000;342:1693e701. 15 Kartchner MM, McRae LP. Noninvasive evaluation and management of the “asymptomatic” carotid bruit. Surgery 1977;82: 840e7. 16 Thompson JE, Patman RD, Talkington CM. Asymptomatic carotid bruit: long-term outcome of patients having endarterectomy compared with unoperated controls. Ann Surg 1978;188: 308e16. 17 Naylor AR. Why is the management of asymptomatic carotid disease so controversial? Surgeon 2015;13:34e43. 18 Raman G, Moorthy D, Hadar N, Dahabreh IJ, O’Donnell TF, Thaler DE, et al. Management strategies for asymptomatic
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21 22
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carotid stenosis: a systematic review and meta-analysis. Ann Intern Med 2013;158:676e85. Spence JD, Naylor AR. Endarterectomy, stenting, or neither for asymptomatic carotid-artery stenosis. N Engl J Med 2016;374: 1087e8. Calligaro KD, Dougherty MJ. Correlation of carotid artery stump pressure and neurologic changes during 474 carotid endarterectomies performed in awake patients. J Vasc Surg 2005;42: 684e9. AbuRahma AF, Mousa AY, Stone PA. Shunting during carotid endarterectomy. J Vasc Surg 2011;54:1502e10. Cuadra SA, Zwerling JS, Feuerman M, Gasparis AP, Hines GL. Cerebral oximetry monitoring during carotid endarterectomy: effect of carotid clamping and shunting. Vasc Endovasc Surg 2003;37:407e13. Chongruksut W, Vaniyapong T, Rerkasem K. Routine or selective carotid artery shunting for carotid endarterectomy (and different methods of monitoring in selective shunting). Cochrane Database Syst Rev 2014;6:CD000190. Goodney PP, Wallaert JB, Scali ST, Stone DH, Patel V, Shaw P, et al. Impact of practice patterns in shunt use during carotid endarterectomy with contralateral carotid occlusion. J Vasc Surg 2012;55:61e76. Flanigan DP, Flanigan ME, Dorne AL, Harward TRS, Razavi MK, Ballard JL. Long-term results of 442 consecutive, standardized carotid endarterectomy procedures in standard-risk and highrisk patients. J Vasc Surg 2007;46:876e82.
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
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Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients Michele Piazza *, Marco Zavatta, Margherita Lamaina, Jacopo Taglialavoro, Francesco Squizzato, Franco Grego, Michele Antonello Clinic of Vascular and Endovascular Surgery, Padova University School of Medicine, Padua, Italy
WHAT THIS PAPER ADDS Routine shunting with device insertion just after rapid carotid endarterectomy (CEA) is a valid technique, able to optimise the benefit of continuous cerebral perfusion together with a reduced risk of related complications. This specific method, together with standardisation of the procedure, leads to a neurological complication rate <1%, which can be consistently maintained over time and independently from different operators. In asymptomatic patients with significant carotid stenosis, this approach offers patients the modern reliable CEA low stroke risk rate they expect.
Objective/background: The aim was to evaluate early outcomes of carotid endarterectomy (CEA) in asymptomatic patients using a standardised technique based on routine shunting after rapid plaque removal (“delayed”). Methods: A retrospective review of all asymptomatic patients who underwent CEA during a 10 year single centre experience (January 2007eDecember 2016) was performed. The technique was based on rapid endarterectomy with distal intimal edge visualisation, followed by routine shunt insertion; subsequent time spent on the manoeuvre and closure were completed under shunting. Primary endpoints were relevant neurological complication rate (RNCR) and death within 30 days. To better identify any difference related to changes in medical therapy, anaesthetic management, and different operators over time, patients were divided into group A (underwent CEA in the first 5 year period) and group B (underwent CEA during the second 5 year period). Univariate analysis of factors associated with RNCR was performed. Operator experience (seniority), expertise (CEA volume per year), and time period were incorporated. Results: In total, 1745 patients matched the inclusion criteria and were enrolled. Altogether, 147 (8.9%) had contemporary contralateral stenosis 70% and 58 (3.5%) had contralateral internal carotid artery chronic occlusion. No patient died peri-operatively; major myocardial infarction occurred in 19 patients (1.1%). Overall, peri-operative RNCR was 0.6% (major stroke: n ¼ 6 [0.4%]; minor stroke: n ¼ 4 [0.2%]). RNCR distribution was maintained equally comparing group A and B (0.8% vs. 0.4%; p ¼ 0.17). No differences were found in RNCR when comparing operator experience (p ¼ 0.88) and expertise (p ¼ 0.93). Univariable analysis found diabetes as the only clinical factor influencing RNCR (odds ratio 3.79, 95% confidence interval 1.06e13.50; p ¼ 0.04); none of the other factors, such as time period, operator experience, and expertise, reached statistical significance. Conclusions: Routine delayed shunting associated with standardisation of the technique seems to be a safe and effective technique and contributes to maintaining the RNCR < 1% over time and independently from operators and other clinical factors. Ó 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved. Article history: Received 7 March 2018, Accepted 11 June 2018, Available online XXX Keywords: Carotid endarterectomy, CEA, Shunt, Standardisation
INTRODUCTION Carotid endarterectomy (CEA) is widely recognised as the gold standard surgical approach to the prevent of major cerebral * Corresponding author. Clinic of Vascular and Endovascular Surgery, Padova University School of Medicine, Via Giustiniani 2, 35128 Padova (PD), Italy. E-mail address: [email protected] (Michele Piazza). 1078-5884/Ó 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved. https://doi.org/10.1016/j.ejvs.2018.06.030
events in patients with significant carotid stenosis.1 The results of trials such as the Asymptomatic Carotid Atherosclerosis Study (ACAS)2 and the Asymptomatic Carotid Surgery Trial (ACST),3 performed in the 1990s, favoured CEA plus medical therapy over medical therapy alone in the management of asymptomatic patients with significant carotid stenosis. As emphasised in the literature,4 these findings hold true only if the cumulative risk of relevant neurological complication rate (RNCR) and peri-operative mortality during surgery is <3%.
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
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Despite the fact that CEA has been performed for decades, specific operative techniques remain highly variable, especially techniques for cerebral monitoring and protection.5 While shunting aims to minimise the cerebral ischaemia time during clamping and therefore to reduce RNCR, on the other side device insertion itself is a delicate manoeuvre that requires operator expertise. Brain embolisation from plaque fragments, intimal lesions with ICA dissection, and shunt malfunctions are some of these aspects. Also, the CEA procedure itself, type of anaesthesia, closure methods, and neurological monitoring have a wide range of approaches depending on operator expertise and preferences. The absence of a standardised procedure is one of the aspects that may be responsible for the wide range in RNCR, depending on the series analysed (from 0.7% to 4%).6 The objective of this study was to evaluate early surgical and neurological outcomes (within 30 days of surgery) of CEA in asymptomatic patients with stenosis 70% using a specific standardised technique based on rapid endarterectomy with accurate assessment of distal intimal break off edge, followed by routine “delayed” shunt insertion. Also evaluated was whether other factors such as time period or surgeon’s experience may influence outcomes in terms of RNCR. MATERIALS AND METHODS A retrospective review of all patients admitted to the Clinic of Vascular and Endovascular Surgery of Padua University who underwent CEA between January 2007 and December 2016 was performed. All data were prospectively collected in a dedicated database. Institutional Review Board requirements were waived for this study. Patient selection Only asymptomatic patients with 70% carotid stenosis were enrolled. Patients with significant contralateral carotid stenosis or occlusion were also included. All symptomatic patients and asymptomatic patients with pre-operative computed tomography (CT) or magnetic resonance imaging (MRI) evidence of recent onset (<30 days) ipsilateral ischaemic lesions were excluded. Patients affected by carotid aneurysms, dissections, restenosis, or CEA performed in association with other surgical procedures (coronary artery bypass, common carotid artery stenting at its origin from the arch) were also excluded. Patients were divided into two groups: those undergoing CEA in the first 5 year time period (2007e11; group A) and those treated during the second 5 year period (2012e16; group B). This was done to better identify any difference in outcomes in relation to improvement in medical therapy, anaesthetic management, and different operators over time. Treatment and definitions Demographic baseline characteristics, risk factors, and preoperative medical therapy were obtained by reviewing all available medical records at the time of operation.
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The cardiovascular risk factors considered were hypertension, dyslipidaemia, diabetes, chronic obstructive pulmonary disease, history of coronary artery revascularisation (coronary artery bypass graft or percutaneous transluminal coronary angioplasty [PTCA]). Pre-operative assessment also included information on medical therapy (antiplatelet, anticoagulant, statin therapy). Pre-operative imaging was routinely performed with carotid duplex ultrasound (DUS) followed by CT or MR angiography scan of the supra-aortic and intracranial vessels; a cerebral CT scan was performed to identify any recent ischaemic lesions. The grade of stenosis was defined based on DUS with the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method;7 if a stenosis 70% was identified, a subsequent CT angiogram of the supra-aortic and intracranial vessels was obtained in order to corroborate DUS findings and to evaluate carotid disease extension based on Society for Vascular Surgery (SVS)/European Society for Vascular Surgery (ESVS) guidelines.8,9 The definition of asymptomatic was based on SVS/ESVS extracranial carotid disease guidelines (no previous symptoms or no symptoms in the preceding 6 months).8,9 Operative factors considered were clamping times, electroencephalogram (EEG) variations during cross clamping, eventual complications during endarterectomy and shunt insertion, type of closure, and additional intra-operative procedures. Technical success was defined as an uneventful endarterectomy without the need for additional procedures during surgery or on waking. Post-operative transient ischaemic attack (TIA), minor and major stroke were defined according to the current reporting standards.10 The National Institute of Health Stroke Scale (NIHSS) was used for neurological assessment pre-operatively, at patient awakening, and 6 and 24 h after the procedure. In case of altered NIHSS, the patient was subsequently evaluated by a neurologist for accurate evaluation and management strategy. All patients with the onset of a new neurological deficit after surgery underwent an urgent carotid DUS and cerebral CT. Eventual subsequent imaging by CT angiogram or any type of interventions, were considered on a case by case basis. Any other new clinical or neurological findings after discharge and within 30 days were assessed with telephone interviews at 30 days by a dedicated doctor. If a patient referred to any type of symptom, he or she was scheduled for an outpatient clinic visit and eventual additional examinations were required for a precise diagnosis. If a patient developed any acute episode requiring urgent/emergency hospitalisation, the medical records of Padova Hospital Area Intranet System (allowing for visualisation of medical records of all Padova area hospitals and outpatients clinics) were reviewed. All surgical, cardiac, and neurological complications were categorised in accordance with the SVS reporting standards for carotid interventions.8 Primary endpoints were to compare RNCR (minor and major stroke) and related death 30 days after CEA between the two different time periods (groups A and B).
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
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Figure 1. (A) Insertion of a Pruitt-Inahara shunt into the internal carotid artery under visual control over the endarterectomy endpoint. (B) Test of correct functioning of the Pruitt-Inahara shunt. Blood flow is checked by opening the red T-port.
A subgroup analysis for RNCR was performed based on “surgeon experience”, defined as years of seniority (senior consultants: > 20 years of experience; experienced consultants: > 5 years of experience; junior consultant: < 5 years of experience), and “surgeon expertise”, which was defined based on surgeon volume of interventions per year (high volume: > 30; medium volume: 15e30; low volume: < 15 CEAs/year). Operative technique All CEAs were performed by vascular surgeons of the Vascular and Endovascular Surgery Clinic of Padua University during the study time period (January 2007eDecember 2016). All CEAs were performed under general anaesthesia and continuous EEG monitoring, which was used to detect any type of unexpected cerebral hypoperfusion or shunt malfunction. A longitudinal cut down on the anterior margin of the sternocleidomastoid muscle was performed and the carotid bifurcation was exposed. After systemic heparinisation with 100 U/kg heparin, the external carotid artery, internal carotid artery (ICA), and common carotid artery (CCA) were clamped. Two methods of endarterectomy were considered: standard endarterectomy with longitudinal arteriotomy of the bulb and ICA origin followed by patch closure (Gore Acuseal CardioVascular Patch) for a straight ICA, or eversion with ICA resection at the bulb and its re-implantation (for an ICA with kinking or redundant coiling). In both cases, a rapid endarterectomy was performed, followed by accurate distal endpoint assessment of the resulting intimal edge. At this point, independently from eventual EEG modifications, a Pruitt-Inahara shunt was routinely inserted in the ICA under direct visual assessment of the endpoint (Fig. 1A); the same manoeuvre was performed in the CCA and shunt correct functioning was checked from the red T port to assure a pulsatile blood flow (Fig. 1B). Once the correct shunt function was tested, accurate removal of small
fragments of loose debris from the endarterectomised surface and closure were performed. For a standard endarterectomy the artery was closed with a 6.0 Prolene running suture of a synthetic polytetrafluoroethylene patch. For an eversion endarterectomy, the ICA was re-everted on the shunt tube for distal endpoint recheck, adjusted for length and then re-implanted. In both cases, before suture completion, the shunt was removed, the arteries were flushed, and the suture finally secured. During all procedures, any EEG modifications were recorded. Statistical analysis Considering an anticipated RNCR of 1%, the minimum sample size to detect a 2% difference was calculated to be 719 patients per group, with a significance level of 0.05 and a power of 0.80. Continuous variables are presented as mean SD, categorical data as n (%). Uni- and bivariable analyses were performed using the t-test or Wilcoxon rank sum for continuous variables and a two tailed chi-square test for categorical variables. Univariable analysis of factors associated with RNCR was performed. Operator experience, expertise, and time period were incorporated in the analysis. Multivariable analysis was not performed to avoid the risk of over fitting due to the limited numbers of events compared with the number of independent variables. A p value < 0.05 was considered statistically significant for all analyses. Data analysis was performed using STATA 14.1 (Stata Corp., College Station, TX, USA). RESULTS During the study period, a total of 1852 CEAs were performed. In total, 1745 patients (94.2%) matched the inclusion criteria and were enrolled in the study. Of these,
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
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Table 1. Analysis of baseline and anatomical preoperative characteristics of patients who underwent CEA, comparing patients of the first 5year time period (Group A, 2007e2011) to patients of the second (Group B, 2012e2016). Variable
Overall (1745 pts.)
Demographics Age, years SD 72.6 7.9 Age < 75 years 1037 (59.4%) Male gender 1108 (63.5%) Risk factors Hypertension 1451 (83.1%) Dyslipidemia 1174 (67.3%) COPD 119 (6.8%) Prior PCI 184 (10.5%) Prior CABG 132 (7.6%) Diabetes 480 (27.5%) Previous therapy Single antiplatelet 1415 (81.1%) Double antiplatelet 121 (6.9%) Oral anticoagulant 167 (9.6%) N. of cardiac drugs 1.6 1.2 Statin 1129 (64.7%) Anatomical characteristics Kinking/coiling 523 (29.9%) CT brain lesions 7 (0.4%) Contralateral ICA Stenosis >70% 147 (8.4%) Occlusion 58 (3.3%) Bold ¼ Statistically significant. COPD, chronic obstructive pulmonary artery bypass graft.
868 (49.7%) patients were treated between 2007 and 2011 (group A) and 877 (50.3%) between 2012 and 2016 (group B). The overall age was 72.6 7.9 years, and the majority of enrolled patients were male (n ¼ 1108 [63.5%]). Overall baseline and anatomical pre-operative characteristics, and their distribution in groups A and B, are reported in Table 1. Comparing the two groups, in the most recent 5 year period the percentage of patients diagnosed with dyslipidaemia increased significantly (75.9% vs. 63.3%; p < 0.001) and a history of previous PTCA was more frequent (13% vs. 8.8%; p ¼ 0.006), probably reflecting the real world trend in cardiovascular disease treatment and changes in medical therapy. In fact, in this cohort the number of patients on double antiplatelet therapy increased with time (9.8% vs. 5.1%; p < 0.001), as did use of statins (75.2% vs. 63.8%; p < 0.001). Overall, technical success was achieved in 99.9% of cases. In eight cases carotid bypass was required (in five cases the atherosclerotic plaque was firmly adherent and its endarterectomy caused injury to the vessel which necessitated interposition; in the remaining three cases the distal endpoint of the endarterectomy into the ICA could not be adequately finished because of intimal dissection). Patch closure was the most used technique (1205 patients [69.2%]), whereas eversion and reimplantation was used only for ICA coiling and/or kinking (523 patients [30%]). When comparing the two subgroups, no differences were identified in operative characteristics (Table 2).
Group A (868 pts.)
Group B (877 pts.)
p Value
72.5 7.8 526 (60.6%) 545 (62.8%)
72.8 8 511 (58.3%) 563 (64.3%)
0.511 0.321 0.520
694 (79.9%) 518 (59.7%) 59 (6.7%) 72 (8.2%) 63 (7.3%) 237 (27.3%)
757 (86.3%) 656 (74.8%) 60 (6.8%) 112 (12.7%) 69 (7.9%) 243 (27.7%)
0.087 <0.001 0.836 0.006 0.834 0.712
701 (80.7%) 40 (4.6%) 100 (11.5%) 1.9 1.2 504 (58.1%)
714 (81.4%) 81 (9.2%) 67 (7.6%) 1.9 1.3 625 (71.2%)
0.26 <0.001 0.002 0.728 <0.001
252 (29%) 2 (0.2%)
271 (30.9%) 5 (0.6%)
0.430 .0280
70 (8.0%) 77 (8.7%) 0.869 28 (3.2%) 30 (3.4%) 0.997 disease; PCI, percutaneous coronary interventions; CABG, coronary
No patients died; intra- or peri-operative (30 days) onset of myocardial infarction was detected in 19 patients (1.1%). At 30 days, 12 TIA (0.7%), four minor strokes (0.2%), and six major strokes (0.4%) were recorded, and none of these was a shunt related complication. In particular, of the 10 patients developing post-operative stroke, two had significant contralateral carotid stenosis and one had chronic contralateral carotid occlusion. None of them experienced EEG variations during clamping or shunting. The overall RNCR was 0.6%; when the yearly RNCR was analysed over the 10 years, it was found to be maintained below 1% (Fig. 2). No significant differences between group A and B were found in major early outcomes, considering surgical, cardiac, and neurological complications, which was also the case for RNCR (group A 0.8%, group B 0.4%; p ¼ 0.175) (Table 3). Operator experience had no impact on peri-operative complication rates and, in particular, on RNCR (senior consultants: 0.7%; experienced consultants: 0.5%; young consultants: 0.7% [p ¼ 0.883]). Similarly, RNCR was not influenced by operator expertise, considered as operator volume of interventions per year (high volume: 0.6%; medium volume: 0.5%; low volume: 0.7% [p ¼ 0.931]) (Table 4). Finally, univariable regression analysis demonstrated that the only factor influencing RNCR was diabetes (p ¼ 0.040) (Table 5). None of the other major clinical or anatomical factors, including contralateral significant carotid stenosis or occlusion, operator experience and expertise, and time period, had any significant impact.
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
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Table 2. Intraoperative characteristics of patients who underwent CEA, comparing patients of the first 5-year time period (Group A, 2007e 2011) to patients of the second (Group B, 2012e2016). Variable
Overall (1745 pts.)
Operative characteristics Operative time, min SD 95.7 27.9 Clamping time, min SD 4 1.3 EEG variations 41 (2.3%) Closure technique Patch 1205 (69%) ICA replantation 523 (29.9%) By-pass 8 (0.5%) EEG, electroencephalography; ICA, internal carotid artery.
DISCUSSION Atherosclerosis of the supra-aortic vessels and especially of the carotid bifurcation is widely recognised as a major cause of recurrent ischaemic stroke. There is evidence that it accounts for approximately 20% of all strokes,9 and nearly 80% of these may occur with no warning.10e14 SVS guidelines suggest that neurologically asymptomatic patients with 60% carotid stenosis should be considered for CEA for the reduction of long-term risk of stroke if the patient has a 3e5 year life expectancy and a peri-operative stroke or death rate of 3% (grade 1, level of evidence A).9 The 3% risk threshold has been defined on the basis of studies conducted before the introduction of modern medical therapy.15,16 These studies demonstrated that the annual risk of ischaemic stroke in adults with asymptomatic carotid stenosis treated with medical therapy alone accounted for 2e5%. Therefore, these findings may not be applicable to contemporary clinical practice.17 A meta-analysis of incidence rate data from prospective single group cohorts of medical therapy alone for asymptomatic carotid stenosis showed that the incidence rate of ipsilateral stroke was lower (1.68% per year),18 particularly in studies conducted in the last decade (1.13% per year). These recent findings raise doubt as to whether CEA is still the gold standard for the management of asymptomatic patients with significant carotid stenosis. In this setting, suggestions are that only a limited number of all asymptomatic patients may benefit from prophylactic CEA.19 The most recent guidelines for the treatment of asymptomatic carotid stenosis, published in August 2017 from a consensus between cardiologists and vascular surgeons in Europe, recommend consideration of CEA in “average surgical risk”
Group A (868 pts.)
Group B (877 pts.)
p Value
93.7 30.2 3.9 1.4 20 (2.3%)
97.5 25.3 4 1.1 21 (2.3%)
0.997 0.979 0.901
601 (69.2%) 252 (29%) 6 (0.7%)
604 (68.8%) 271 (30.9%) 2 (0.2%)
0.755 0.430 0.150
patients with an asymptomatic 60e99% stenosis, in the presence of clinical and/or imaging characteristics that may be associated with an increased risk of late ipsilateral stroke; again only if the documented peri-operative stroke/ death rate is <3% and the patient’s life expectancy is > 5 years (class of recommendation IIa, level of evidence B).8 In the authors’ opinion, being at relatively low risk of ipsilateral stroke, asymptomatic patients receiving best available medical therapy may benefit from a revascularisation procedure only if peri-procedural complications can be minimised by more than the 3% reported in historical guidelines. Moreover, it must be considered that outcomes reported in randomised controlled trials may not always reflect practice in the “real world”: while centres seeing a high volume of interventions per year are able to guarantee a peri-operative RNCR of 1%, other institutions report a higher complication rate. A 2016 systematic review by Paraskevas et al., analysed all available administrative data set registries reporting outcomes after CEA and carotid artery stenting from 2008 to 2016.6 Twenty-one registries were included in the analysis, accounting for more than 1,500,000 procedures. For asymptomatic patients at average risk of CEA, only four registries (19%) reported a RNCR/mortality cumulative risk after CEA <1%, 16 comprised 1e3% (76%), and one (almost 5%) >3%. These significant differences in early outcomes, especially with regard to peri-operative neurological events, may reflect the variability and differences in surgical techniques between different operators and/or institutions. This also includes technical aspects, such as intra-operative cerebral monitoring systems and shunting techniques.
Figure 2. Analysis of yearly relevant neurological complication rate (RNCR) during the 10 year study period. Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
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Table 3. Analysis of intra-operative and early complications in the 1745 patients enrolled comparing the first 5-year time period (Group A, 2007e2011) to the second (Group B, 2012e2016). Variable
Overall Group A Group B p Value (1745 pts.) (868 pts.) (877 pts.)
Surgical ICA dissection 3 (0.1%) 0 3 (0.3%) 0.092 Cranial Nerve 21 (1.2%) 11 (1.2%) 10 (1.1%) 0.728 injury Cervical 41 (2.3%) 17 (1.9%) 24 (2.7%) 0.352 Hematoma Cardiac Arrhythmias 26 (1.4%) 11 (1.2%) 15 (1.7%) 0.517 Myocardial 19 (1%) 7 (0.8%) 12 (1.3%) 0.302 infarction Neurologic Subarachnoid 1 (0.05%) 0 1 (0.1%) 0.331 hemorrhage TIA 12 (0.6%) 8 (0.9%) 4 (0.4%) 0.209 Minor Stroke 4 (0.2%) 2 (0.2%) 2 (0.2%) 0.955 Major Stroke 6 (0.3%) 5 (0.5%) 1 (0.1%) 0.088 Deaths 0 0 0 e RNCR 10 (0.5%) 7 (0.8%) 3 (0.3%) 0.175 ICA, internal carotid artery; TIA, transient ischemic attack; RNCR, relevant neurologic complication rate.
In particular, the use of shunting in CEA is controversial. As reported in the literature shunt use is probably unnecessary in approximately 85% of patients, and may be associated with complications including atheromatous or air emboli, arterial dissection, and acute occlusion.5,20 Nevertheless, there is no evidence in the literature of a significant increase in complication rate related to shunt insertion.21 On the contrary, shunting undoubtedly guarantees the maintenance of an optimal cerebral blood flow during clamping time,22 allowing an unhurried endarterectomy and closure. A Cochrane review published in 2014 reviewed all available randomised controlled prospective trials comparing routine and selective shunting and risk of perioperative complications, including stroke and death;23 this review concluded that data were insufficient to support or
Table 5. Univariable regression analysis of RNCR. Variable
RNCR OR 95% CI p Senior consultants Reference Experienced consultants 0.72 0.14e3.59 0.690 Young consultants 0.99 0.14e7.01 0.991 High volume Reference Medium volume 0.99 0.22e4.45 0.992 Low volume 1.29 0.29e5.81 0.737 2007e11 time period Reference 2012e16 time period 0.40 0.10e1.56 0.189 Contralateral stenosis >70% 1.13 0.14e9.02 0.905 Contralateral occlusion 3.08 0.38e24.73 0.290 Kinking/coiling 0.99 0.26e3.87 0.998 Diabetes 3.79 1.06e13.50 0.040 Previous PCI 0.90 0.11e7.17 0.923 Previous CABG 2.97 0.62e14.11 0.172 Note. Bold ¼ Statistically significant. RNCR ¼ relevant neurological complication rate; OR ¼ odds ratio; CI ¼ confidence interval; PCI ¼ percutaneous coronary interventions; CABG ¼ coronary artery bypass graft.
refute the use of selective or routine shunting. Based on this evidence, the European Society of Cardiology/ESVS guidelines recommend (level of evidence class 1, level C) that the choice of shunting (routine, selective, never) should be left to the discretion of the operating surgeon.8 While in the literature there are plentiful data regarding the “timing” for shunt (routine or selective), no studies have focused their attention on the technique used for its insertion. To the authors’ knowledge, most commonly the distal end of the shunt is inserted into the ICA with the plaque “in situ” and the endarterectomy performed after shunt insertion. The authors’ choice of routine and delayed use of the Pruitt-Inahara shunt aims first of all, to minimise the complications related to its insertion including microembolisation and arterial dissection. This aspect is particularly emphasised in symptomatic cases, where the risk of micro-embolisation is higher owing to more frequent
Table 4. Analysis of early neurological complications in the 1745 patients enrolled stratified by surgeon experience and expertise. Variable
Senior consultants Experienced consultants Young consultants p (n ¼ 273 patients) (n ¼ 1133 patients) (n ¼ 276 patients) Subarachnoid haemorrhage 0 1 (0.1) 0 0.785 TIA 2 (0.7) 7 (0.6) 3 (1.1) 0.708 Minor stroke 1 (0.4) 2 (0.2) 1 (0.4) 0.760 Major stroke 1 (0.4) 4 (0.4) 1 (0.4) 0.999 Deaths 0 0 0 e RNCR 2 (0.7) 6 (0.5) 2 (0.7) 0.883 Variable High volume Medium volume Low volume (n ¼ 735 patients) (n ¼ 563 patients) (n ¼ 444 patients) Subarachnoid haemorrhage 1 (0.1) 0 0 0.513 TIA 2 (0.3) 8 (1.4) 2 (0.5) 0.036 Minor stroke 2 (0.3) 1 (0.2) 1 (0.2) 0.944 Major stroke 2 (0.3) 2 (0.4) 2 (0.5) 0.860 Deaths 0 0 0 e RNCR 4 (0.5) 3 (0.5) 3 (0.7) 0.931 Note. Data are n (%). Bold ¼ Statistically significant. TIA ¼ transient ischaemic attack; RNCR ¼ relevant neurological complication rate. Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
Early Outcomes of Routine Delayed Shunting
unstable plaque; for this reason, this technique is adopted in this setting, too. In asymptomatic patients, it is believed the major benefit related to shunting is to guarantee direct cerebral perfusion during the largest part of the surgical procedure and reduce the risk of hypoperfusion. In fact, in the present authors’ experience, the time needed for endarterectomy rarely exceeds 3 min and subsequent shunt insertion is easily accomplished after plaque removal and under visual distal endpoint control. The following time consuming manoeuvre of removal of small fragments of loose debris from the endarterectomised surface, distal and proximal endpoint re-check, external carotid artery ostium control, and sutures for artery closure, can be performed with no rush. All surgeons in the authors’ team use this technique routinely in order to also allow the operator to be extremely confident with shunt use. The opinion of the authors is corroborated by the findings of Goodney et al.,24 who in a study on the impact of practice patterns in shunt use during CEA, reported that the 30 day stroke/death rate for patients shunted during CEA was higher if the surgeon used it selectively rather than routinely. Finally, the use of the Pruitt-Inahara shunt rather than a standard tube has two advantages. The first is that the balloon inflated in the ICA has a “secure system” that avoids balloon over-inflation with a lower risk of arterial intimal lesion; the second is that with the “T” configuration, it is possible to check, at any time, the pulsatile flow and correct shunt function. This study demonstrates that this particular technique seems to be effective and guarantees low peri-procedural complication rates, with a combined mortality/RNCR of <1%. Moreover, since 2000, all surgeons at the authors’ clinic follow the same precise steps for arterial access, plaque removal, routine “delayed” shunting, peeling, and closure technique. The high level of standardisation of the procedure has been a key point. In fact, this has allowed maintenance of outcomes, despite the presence of a contralateral significant stenosis or occlusion, the time period analysed (changes in anaesthesia techniques, pharmacological management), and, most importantly, despite differences in surgeons’ experience and expertise. As suggested by Flanigan et al.,25 the application of a specific and standardised surgical technique leads to excellent and constant results. The present outcomes, in the authors’ opinion, were the result of the association between a specific technique together with its standardisation; these two factors together allow for an RNCR <1% and this be maintained consistently low in order to offer patients a reliably low risk of stroke. The study has some limitations. This was a retrospective, non-randomised study; subgroup analysis and multivariable analysis were not feasible owing to the limited number of events. New guidelines are expected to change the treatment paradigm for asymptomatic patients with carotid
7
artery stenosis, supported by evidence that modern medical therapy has improved its outcomes in preventing cerebral events. The study demonstrates that CEA still has a role in this particular category of patients. The choice of optimal surgical technique and standardisation of the procedure have a key role in minimizing complication rates and maintaining results over time. CONCLUSIONS The routine use of delayed shunting in asymptomatic patients contributed to maintenance of a peri-operative stroke/death rate of <1% over a decade, independently from operators, time period, and other major clinical factors. CEA technique standardisation is mandatory to guarantee and maintain a valid role in stroke risk prevention over time. CONFLICT OF INTEREST None. FUNDING None. REFERENCES 1 Mitka M. Study findings offer conflicting views on future role of carotid artery stenting. JAMA 2010;303:1584e6. 2 ACAS Executive committee. Endarterectomy for asymptomatic carotid artery stenosis. Executive committee for the asymptomatic carotid Atherosclerosis study. JAMA 1995;273:1421e8. 3 Halliday A, Harrison M, Hayter E, Kong X, Mansfield A, Marro J, et al. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial. Lancet 2010;376:1074e84. 4 Goldstein LB, Bushnell CD, Adams RJ, Appel LJ, Braun LT, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:517e84. 5 AbuRahma AF, Stone PA, Hass SM, Dean LS, Habib J, Keiffer T, et al. Prospective randomized trial of routine versus selective shunting in carotid endarterectomy based on stump pressure. J Vasc Surg 2010;51:1133e8. 6 Paraskevas KI, Kalmykov EL, Naylor AR. Stroke/death rates following carotid artery stenting and carotid endarterectomy in contemporary administrative dataset registries: a systematic review. Eur J Vasc Endovasc Surg 2016;51:3e12. 7 Ferguson GG, Eliasziw M, Barr HWK, Clagett GP, Barnes RW, Wallace MC, et al. the North American symptomatic carotid endarterectomy trial: surgical results in 1415 patients. Stroke 1999;30:1751e8. 8 Aboyans V, Ricco JB, Bartelink MLEL, Björck M, Brodmann M, Cohnert T, et al. 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European society for vascular surgery (ESVS). Eur J Vasc Endovasc Surg 2018;55:305e68. 9 Ricotta JJ, Aburahma A, Ascher E, Eskandari M, Faries P, Lal BK. Updated Society for Vascular Surgery guidelines for management of extracranial carotid disease. J Vasc Surg 2011;54:e1e 31.
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030
8 10 Timaran CH, McKinsey JF, Schneider PA, Littooy F. Reporting standards for carotid interventions from the society for vascular surgery. J Vasc Surg 2011;53:1679e95. 11 Veith FJ, Amor M, Ohki T, Beebe HG, Bell PRF, Bolia A, et al. Current status of carotid bifurcation angioplasty and stenting based on a consensus of opinion leaders. J Vasc Surg 2011;33: S111e6. 12 Bogousslavsky J, Van Melle G, Regli F. The lausanne stroke registry: analysis of 1,000 consecutive patients with first stroke. Stroke 1988;19:1083e92. 13 Foulkes MA, Wolf PA, Price TR, Mohr JP, Hier DB. The Stroke Data Bank: design, methods, and baseline characteristics. Stroke 1988;19:547e54. 14 Inzitari D, Eliasziw M, Gates P, Sharpe BL, Chan RKT, Meldrum HE, et al. The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. N Engl J Med 2000;342:1693e701. 15 Kartchner MM, McRae LP. Noninvasive evaluation and management of the “asymptomatic” carotid bruit. Surgery 1977;82: 840e7. 16 Thompson JE, Patman RD, Talkington CM. Asymptomatic carotid bruit: long-term outcome of patients having endarterectomy compared with unoperated controls. Ann Surg 1978;188: 308e16. 17 Naylor AR. Why is the management of asymptomatic carotid disease so controversial? Surgeon 2015;13:34e43. 18 Raman G, Moorthy D, Hadar N, Dahabreh IJ, O’Donnell TF, Thaler DE, et al. Management strategies for asymptomatic
Michele Piazza et al.
19
20
21 22
23
24
25
carotid stenosis: a systematic review and meta-analysis. Ann Intern Med 2013;158:676e85. Spence JD, Naylor AR. Endarterectomy, stenting, or neither for asymptomatic carotid-artery stenosis. N Engl J Med 2016;374: 1087e8. Calligaro KD, Dougherty MJ. Correlation of carotid artery stump pressure and neurologic changes during 474 carotid endarterectomies performed in awake patients. J Vasc Surg 2005;42: 684e9. AbuRahma AF, Mousa AY, Stone PA. Shunting during carotid endarterectomy. J Vasc Surg 2011;54:1502e10. Cuadra SA, Zwerling JS, Feuerman M, Gasparis AP, Hines GL. Cerebral oximetry monitoring during carotid endarterectomy: effect of carotid clamping and shunting. Vasc Endovasc Surg 2003;37:407e13. Chongruksut W, Vaniyapong T, Rerkasem K. Routine or selective carotid artery shunting for carotid endarterectomy (and different methods of monitoring in selective shunting). Cochrane Database Syst Rev 2014;6:CD000190. Goodney PP, Wallaert JB, Scali ST, Stone DH, Patel V, Shaw P, et al. Impact of practice patterns in shunt use during carotid endarterectomy with contralateral carotid occlusion. J Vasc Surg 2012;55:61e76. Flanigan DP, Flanigan ME, Dorne AL, Harward TRS, Razavi MK, Ballard JL. Long-term results of 442 consecutive, standardized carotid endarterectomy procedures in standard-risk and highrisk patients. J Vasc Surg 2007;46:876e82.
Please cite this article in press as: Piazza M, et al., Early Outcomes of Routine Delayed Shunting in Carotid Endarterectomy for Asymptomatic Patients, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.06.030