导语：缺血性卒中是全球严重的长期残疾和死亡的主要原因，也是我院神经内科收治最多的病种，这篇来自1区JACC2021年最新文献提示，血管内机械血栓切除术与各种术前、围术期和术后并发症相关，这些并发症可能会影响介入治疗的发病率和死亡率，进而影响治疗效果和临床预后。本文旨在讨论与 EVT 相关的最常见的并发症类型、可能的损伤机制以及处理并发症的有效方法。损伤机制，以及管理和预防并发症的有效方法。
这是一篇很好的多学科交叉及流行病学调查研究。涵盖了心内、心外、医学影像学科。高质量的文献和研究既提示我们学科融合、学科交叉的重要性，也给我们科学研究带来了新的思路。通读本文后，给我们研究者带来继续进行深入研究的思路和冲动。身处心血管病专科医院，上述病例和数据不难获得，要的就是十年如一日的科研坚持和随访。
下面我们就来阅读整篇文献。
ABSTRACT
Endovascular mechanical thrombectomy (EVT) is widely accepted as the first-line treatment for acute ischemic stroke in patients with large vessel occlusion. Being an invasive treatment, this method is associated with various preoperative, perioperative, and postoperative complications. These complications may influence perinterventional morbidity and mortality and therefore treatment efficacy and clinical outcome. The aim of this review is to discuss the most common types of complications associated with EVT, the probable mechanisms of injury, and effective methods to manage and prevent complications.
INTRODUCTION
The introduction of endovascular
mechanical thrombectomy (EVT) using stent retriever devices has led to improvements in technical success, recanalization rates, and outcomes in selected patients with ischemic stroke caused by large vessel occlusion (LVO). There is also limited but promising
evidence for safety and efficacy using EVT formiddlevessel occlusions or for isolated occlusion of the posterior cerebral artery.1 Nevertheless, despite the technical advancement and high success rates, device- or procedure-related complications reported from randomized controlled trials (RCTs) are between 4% and 29%.The indications for EVT are continuously being expanded for example, to prolonged time windows. Several RCTs are currently seeking to examine further open questions regarding patient selection and efficacy of EVT—for example, in cases of LVO with low National Institutes of Health Stroke Scale (NIHSS) score or large infarct volumes. The increasing number of patients eligible for EVT might also lead to an increase in the incidence of complications or a shift towards certain complications. Therefore, awareness of potential complications of EVT, immediate recognition, appropriate management, and implementation of prevention strategies are
crucial.
We can divide the types of complications into two groups: extracranial and intracranial. Extracranial complications mainly arise from access difficulties and can lead to iatrogenic dissection or vasospasm of the access vessel. Intracranial complications can
be further subdivided into hemorrhagic and ischemic complications. These include symptomatic intracranial hemorrhage (sICH) and subarachnoid hemorrhage (SAH) or embolization within the same or a new vascular territory.
Furthermore, mechanical strain on intracranial vessels caused by EVT may lead to longterm complications and sequelae, such as intracranial stenosis or chronic dissection. The aim of this review is to discuss the most common types of complications associated with EVT, the probable mechanisms of injury, and effective methods to manage and prevent complications.
Extracranial or access site complications
Gaining straightforward access and overcoming access difficulties are important to minimize procedure time. Prolonged procedure times delay clot retrieval, can
lead to increased complication rates, and eventually, result in worse clinical outcome. Groin hematoma is the most frequent access site complication and arange of 2-10% is repor-ted in RCTs. Next to groin hematoma, groin infection, nerve and vessels injury have been described, but are rare and need to be handled in each kind of endovascular treatment. The value of radial access for patients with challenging vascular anatomy is more and more discussed but so fas has not been established as a standard procedure in
treatment of LVOs.
The management of a groin hematoma varies from watchful observation to emergency vascular surgery. Treatment options such as implantation of covered stents or the minimal invasive option of percutaneous throm-bin injection to treat growing pseudoaneurysms should be available.
Gaining vascular access under ultrasound guidance minimizes the number of puncture attempts and reduces access site complications such as groin or retroperitoneal hematoma, formation of pseudoaneurysms or arteriovenous fistulae, nerve injury, or
lower extremity ischemia.
Vasospasm
Vasospasm can be induced through mechanical irritation of the vessel wall during catheter or guidewire manipulation. The rate of vasospasm reported in RCTs is 3.9 -23%. Vasospasm can decrease cerebral blood flow and sometimes leads to misidentification of a residual thrombus or intracranial stenosis. Residual thrombus and vessel wall
irregularities after thrombectomy are predictors of early reocclusion and associated with an unfavorable outcome. However, clinical deterioration directly linked to extracranial vasospasm has not yet been reported.
Selective injection of a calcium blocker such as nimodipine (0.5–1 mg/500 mL infusion), either as a bolus or continuously
through the flushing line of the guiding catheter, can be considered. It is important to avoid at the same time systemic hypotension which might occur while the infusion is being administered, particularly in a patient with acute LVO. Therefore, it is essential to monitor for a drop in blood pressure and to take counteractive measures, if necessary.
Administration of nimodipine as a prophylactic measure against vasospasm in EVT is not recommended owing to the potential risks of hypotension and induction of a cerebral steal phenomenon in patients with LVO.
Iatrogenic arterial dissections can occur at the puncture site or during any catheter or guidewire manipulation. Dissections during EVT of acute ischemic stroke are more prevalent in the cervical vessel (83%)
than at the puncture site or in intracranial vessels (17%)Besides vessel tortuosity, smoking seems to be a risk factor for iatro-
genic dissections. The rates of dissection during EVT reported in RCTs range between 0.6% and 3.9%.
To manage dissection, it is essential to diagnose it as early as possible.A dissection with penetration of the adventitia can be seen as contrast extravasation, whereas an intimal flap can be seen as double lumen or a contrast pocket on digital subtraction angiography (DSA) images. Indirect signs indicating a dissection are newly appearing
stenosis with the so-called string sign on angiography, or an evolvin pseudoaneurysm. Bearing in mind the benign course of iatrogenic dissections, especially in the case of a small flap, watchful observation seems justified. In the case of progression or increasing stenosis leading to hemodynamic impairment or thromboembolic complications, treatment of the dissection by stent placement may be necessary. However, the consequent need to administer antiplatelet
therapy can increase the risk of sICH.
The risk for iatrogenic dissection is increased in tortuous anatomy.
Evaluation of the access vessel anatomy on non-invasive imaging in patients undergoing EVT is important to plan the interventional approach (ie, use of distal access catheter).
Intracranial complications
Procedure-related complications of EVT using stent retriever
devices can be classified as follows:
1. Hemorrhagic complications due to vessel perforation causing subarachnoid or intracerebral hemorrhage and hemorrhagic transformation.
2. Embolic complications with thrombus embolization (1) in previously unaffected (ie, not initially hypoperfused) territories, or (2) in the distal vascular bed of the initially occluded territory.
3. Device-related complications (eg, inadvertent device detachment).
Hemorrhagic complications
Hemorrhagic complications are feared complications of acut ischemic stroke treatment. According to the classification of bleeding events after ischemic stroke and reperfusion therapy consensus (Heidelberg Bleeding Classification),the following
subtypes can be differentiated anatomically: hemorrhagic transformations, intracerebral hemorrhage, remote parenchymal
hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, and subdural hemorrhage (table 1). According to the
consensus, hemorrhage is classified as symptomatic if worsening of the NIHSS score ≥4 points occurs or worsening by ≥2 points
occurs in one NIHSS category and if alternative explanations for this deterioration are lacking. However, several different
classifications for hemorrhagic complications have been used in the past, thus reporting is not uniform and comparison between trials may be difficult.
Reasons for hemorrhagic complications can vary depending on whether they occur before, during, or after the thrombectomy procedure, and on the patient’s comorbidities and blood pressure.
Vessel perforation
One of the most feared and serious complications is arterial perforation with a microwire, microcatheter or stent retriever
(SR), because it may result in poor functional outcome in up to 75% of cases and high mortality, exceeding 50%. Arterial perforation is usually identified by extravasation of contrast agent in a DSA run (figure 2) and can cause a cushing reflex. Vessel perforation has been reported in 0.6% to 4.9% of patients undergoing EVT in large randomized series of patients with
anterior circulation stroke. A large retrospective review found a prevalence of 1.0%. Most perforations occur either when
there are difficulties crossing the occlusion site or during deployment or retrieval of the SR. EVT in calcified thrombi has also been reported to be linked to a higher rate of vessel perforation. The current trend of expanding the indications for EVT to
medium and distal vessel occlusions might result in an increased incidence of vessel perforation or hemorrhagic complications.
Arterial perforation requires rapid action, but the perforating device should not be pulled back immediately as it might be sealing the perforation site. To control active bleeding, detachable coils can be used at the perforation site. A promising strategy is to deploy the coil without detaching it, since the flow arrest achieved by the coil deployment is often enough to reach hemostasis and to seal the site of injury without the need to sacrifice the affected vessel segment. The size of the coil should more or less match the diameter of the perforated vessel. Alternatively, inflation of a balloon for several minutes
can be performed in the affected vessel proximal to the hemorrhage site; however, the device preparation takes longer than for the use of coils. If bleeding persists after a period of coil placements or balloon inflations (each attempt up to 5–10 min), permanent occlusion of the affected vessel segment by detaching the coils or injection of a liquid embolic agent (eg, n-butyl cyanoacrylate as glue, Onyx, or precipitating hydrophobic injectable liquid) is necessary (figure 2).
The number of attempts that are made before permanent occlusion of the affected vessel is necessary should be determined according to the clinical setting and situation. Nevertheless, a further supportive measure if bleeding occurs is the temporary reduction of blood pressure. A flat panel cone beam CT scan is a valuable tool for immediate
depiction of the extension and location of the hemorrhage to enable a decision to be made on whether immediate neurosurgical intervention—for example, insertion of a ventricular drain or hematoma evacuation, is needed.
Using a J-shaped microwire tip for navigation across and distal to
the occlusion site reduces the risk of perforation by inadvertently catheterizing small vessel branches. Using a microcatheter alone without a microwire crossing a lesion can be an option, but does not prevent perforation, which is also possible with a microcatheter on its own. The use of first-line aspiration techniques compared with first-line stent retriever, for example, did not
show fewer arterial perforations in the ASTER Trial. Furthermore, deployment of a SR by unsheathing rather than pushing it out of the microcatheter ensures that the SR is deployed in a catheterizable vessel. Uncontrolled forward pushing of the
SR out of the microcatheter during deployment carries the risk of perforation, especially at a bifurcation site. If the vascular
anatomy is unclear, a selective microcatheter injection helps to define the optimal device deployment zone. For EVT of medium
or distal vessel occlusion, the use of dedicated SR devices adapted to the smaller vessel diameter or of a semi-deployed
SR can help to reduce the mechanical strain on the arterial wall and on small perforating arteries arising from the vessel segment
during device deployment and retrieval.
Subarachnoid hemorrhage (SAH)
SAH after EVT is not exclusively observed after vessel perforation or dissection, but may occur, even if no contrast extravasation is visible during the intervention, as angiographically
occult SAH. This type of treatment-related SAH is believed to be caused by stretching or avulsion of small perforating arteries in the subarachnoid space, typically in the Sylvian fissure or at the level of the insula, by mechanical traction of the device during the retrieval maneuver. Emerging evidence suggests that angiographically occult SAH is not related to neurological outcome.15 Some retrospective studies suggested fewer
SAHs after the use of aspiration techniques than after use of SR techniques. However, recent RCTs have not confirmed these results.
Hemorrhagic transformations and symptomatic intracranial hemorrhage
Hemorrhagic transformation usually occurs in infarcted brain parenchyma.21 However, remote parenchymal hematomas of
non-ischemic brain tissue have also been observed.22 The Heidelberg Bleeding Classification distinguishes between hemorrhagic infarction HI1, HI2, parenchymatous hematoma PH1 and PH2,
of which only the latter has been shown to cause clinical deterioration and is associated with worse outcome.
出血性转化和症状性颅内出血
出血性转化通常发生在梗死的脑实质中。然而，非缺血性脑组织的远端脑实质血肿也已被排除。海德堡出血分类区分出血性梗死HI 1、HI 2、脑实质血肿PH 1和PH 2，其中只有后者已被证明会导致临床恶化，并与更差的结局相关。
Embolic and ischemic complications
The modified thrombolysis in cerebral infarction (mTICI) grading system is a tool for determining the response of EVT and
thrombolytic therapies, with grade 3 meaning complete perfusion and grade 0 meaning no perfusion.Embolic complications influence this score, although patients with complete (mTICI3) and near-complete (mTICI 2c) reperfusions seem to have comparable outcomes.26 Two types of embolic complications can occur during mechanical thrombectomy maneuvers: (1) emboli in previously unaffected (ie, not initially hypoperfused) territories, or (2) emboli in the distal vascular bed of the initially
occluded territory, leading to incomplete (
tion are thought to arise from fragmentation of the clot during retrieval, while only a minority of distal emboli are already present before the intervention.
Several prevalent factors
influencing the likelihood of embolic complications have been suggested. These include physical and histological clot proper-
ties, use of protection and flow-arrest devices (balloon-guide catheters and/or distal aspiration), and pretreatment with intravenous tissue plasminogen activator,35 and are potentially increased when using contact aspiration rather than a SR. Both
embolization in new territories and distal embolization have generally been associated with worse outcome, because they
may cause new ischemic lesions,and also aggravate ischemia by impairing the collateral circulation to the primarily affected
territory. However, not all emboli cause infarcts and thus not all are clinically apparent. According to a recent systematic
literature review, the combined incidence of distal arterial embolization and infarcts in new vascular territories during EVT for anterior circulation stroke has been reported to be 4–6%.
Distal embolization
Because around 90% of intracranial thrombi in LVO are found to be unilocular, in theory, a rate of TICI 2a and TICI 2b reperfusion exceeding 10% must be regarded as caused, at least partially, by iatrogenic distal embolization. However, there
is no consensus on how to classify distal embolization, and most studies have reported its incidence as a separate variable from
the TICI score. The incidence of distal embolization during interventions for posterior circulation stroke has been reported
to be as high as 30%, which is higher than for anterior circulation strokes.Different rates of distal embolization between anterior and posterior circulation strokes probably arise from the lack of flow arrest during posterior circulation stroke interventions.New thrombectomy devices designed to further
increase complete reperfusion rates and to reduce the rates of peri-interventional distal embolization are currently being eval-
uated. Options include incorporation of a distal protection zone in the SR design or larger-bore aspiration catheters.
Emboli and infarcts in a new vascular territory
Emboli in new vascular territory are usually graded based on the latest angiographic control runs, while the classification of an infarct in new territory requires postinterventional imaging.
To classify emboli or infarcts as occurring in a ‘new territory’, the vascular territory at risk has to be identified and preinter-
ventional imaging has to be carefully evaluated for the presence of concomitant vessel occlusion prior to the interventional
procedure.
新血管区域的栓塞和梗死
通常根据最新的血管造影控制运行对新血管区域中的栓塞进行分级，而新区域中的梗死分类需要介入后成像。为了将栓塞或梗死分类为发生在“新区域”，必须识别风险血管区域，并在介入手术前仔细评估介入前成像是否存在伴随血管闭塞。
The clinical benefit from the management of distal emboli should always outweigh the risks of clinical deterioration. If the affected vessel branch is eloquent, meaning that a potentially new or additional disabling clinical deficit is to be expected, EVT should be attempted. In the case of an inaccessible occlusion and/or in the absence of contraindications, intra-arterial thrombol-
ysis using urokinase or recombinant tissue plasminogen activator can also be considered as a bail-out option.
远端栓塞治疗的临床益处应始终大于临床恶化的风险。如果受影响的血管分支是有可以明显发现的，这意味着预期会出现潜在的新的或额外的致残性临床缺陷，应尝试EVT。在无法触及的闭塞和/或无禁忌症的情况下，使用尿激酶或重组组织型纤溶酶原激活剂进行动脉内溶栓也可被视为一种补救选择。
The use of balloon-guide catheters (BGCs) and distal aspiration catheters has been reported to result in less frequent embolization,although many factors can influence the outcome. A meta-analysis and review that included more than 2000 patients
was recently published by Brinjikji et al (2018). They found that using a BGC during EVT for stroke treatment led to signifi-
cantly higher rates of good neurological outcome and nearly half the mortality rate of non-BGC-treated patients. The TICI 3 reca-
nalization rates were 20% higher than in the non-BGC-treatedpatients and a reduction in procedure time of over 20 min was also noted.
据报告，使用球囊扩张导引导管（BGC）和远端抽吸导管导致栓塞发生率较低，尽管有许多因素会影响结局。Brinjikji et al（2018）最近发表了一项纳入2000多例患者的Meta分析和综述。他们发现，在EVT治疗中风期间使用BGC可显著提高神经系统良好结局的发生率，其死亡率几乎是未使用BGC治疗患者的一半。TICI 3级再通率比未接受BGC治疗的患者高20%，手术时间也缩短了20分钟以上。
Device-related adverse events
Inadvertent detachment of the SR is rare. An overall incidence of <1% to 4% of this device-related complication during the
treatment of anterior and posterior circulation stroke has been reported.Inadvertent detachment has been shown to be
associated with a higher number of retrieval attempts and to result in a significant increase of sICH and poor outcome. SRs
currently in use are not detachable, and the stent part of the device is firmly molded onto the delivery/push wire. Attempts to
remove detached SRs employing a wide range of techniques have been reported. These included the use of microsnare devices, manual aspiration, or use of a second mechanical thrombectomy
device.The risk–benefit ratio of the different recapture techniques has to be considered since retrieval of the SR may
lead to further complications, such as vessel wall injury, causing vessel perforation, dissection, or severe vasospasm. Another
approach is to leave the stent in place and use conservative management with long-term antiplatelet therapy.The administration of antiplatelet medications in the acute phase of ischemic stroke may be associated with an increased risk of sICH.
器械相关不良事件
SR意外脱离是罕见的。在治疗前循环和后循环卒中期间，该器械相关并发症的总体发生率<1%至4%。已证实意外脱离与更高的回收尝试次数相关，并导致sICH显著增加和不良结局。目前使用的SR不可分离，器械的支架部分牢固地模制在输送/推送金属丝上。有研究尝试采用各种技术取出分离的SR。这些措施包括使用微圈套器、手动抽吸或使用第二个机械血栓切除装置。必须考虑不同回收技术的风险受益比，因为回收SR可能导致进一步的并发症，如血管壁损伤，导致血管穿孔、夹层或严重血管痉挛。另一种方法是将支架留在原位，并使用长期抗血小板治疗的保守治疗。在缺血性卒中急性期给予抗血小板药物可能与sICH风险增加相关。
Long-term complications after EVT
It is more than 5 years since RCTs established EVT as the standard treatment procedure for LVO, but few studies of long-term complications and sequelae after EVT have been published. SRs expose the endothelium to mechanical forces, which may damage the wall of the target vessels, as demonstrated by in vivo animal studies. In a case series of 116 patients, follow-up DSA was performed after EVT to investigate morphological changes of the target vessel. Secondary vessel occlusion was found in one (0.9%) and de novo stenosis in four patients (3.4%); however, all lesions were clinically asymptomatic.50 The most likely mechanism of stenosis formation after EVT is induced by endothelial trauma or microdissection.
EVT后的长期并发症
自RCT将EVT确立为LVO的标准治疗程序以来已有5年多，但很少有关于EVT后长期并发症和后遗症的研究发表。有一项体内动物研究所证明，SR使内皮暴露于机械力，这可能损伤靶血管的壁。对116例患者进行了EVT后DSA随访，观察靶血管的形态学变化。1例（0.9%）患者发生继发性血管闭塞，4例（3.4%）患者发生原发性狭窄;然而，所有病变均无临床症状。对116例患者进行了EVT后DSA随访，观察靶血管的形态学变化。1例（0.9%）患者发生继发性血管闭塞，4例（3.4%）患者发生原发性狭窄;然而，所有病变均无临床症状。
Potentially, iatrogenic microdissec-
tion of the vessel wall can lead to the formation of a pseudoan eurysm, which is a rare but recognized late complication after
EVT, as we show in figure 4. In two other case series, follow-up MR angiography was performed after 3 months in 27 patients
and after 12 months in 39 patients. Vessel abnormalities were observed in 2 (8.3%) in the first study and 10 patients (13%)
in the second.51 52 Antiplatelet therapy has been shown to have an inhibitory effect on intimal hyperplasia and on restenosis
and is usually administered after stroke treatment for secondary prevention, which might help to explain why significant or
symptomatic stenosis is rarely seen after EVT.
在另外两个病例系列中，27例患者在3个月后和39例患者在12个月后进行了随访MR血管造影。在第一项研究中观察到2例（8.3%）血管异常，在第二项研究中观察到10例（13%）血管异常。抗血小板治疗已被证明对内膜增生和再狭窄具有抑制作用，并且通常在中风治疗后进行这可能有助于解释为什么EVT后很少看到显著或症状性狭窄。
CONCLUSION
RCTs and case series investigating EVT are primarily focused on recanalization rates and clinical outcome. Although the evidence-based use of EVT is recommended in multiple international guidelines, few recommendations for the management of
complications are available (for summary see table 2). Interestingly an extended time window up to 24 hours for EVT in the
DAWN or DEFUSE trial for carefully selected patients did not increase complication rates substantially. However, a systematic classification of complications of endovascular stroke treatment is lacking. Different classification syste-ms,nomenclatures,and definitions of complications exist, making it hard, or even
impossible, to compare complications and their management.There is therefore a need for classification and reporting standards for clinical practice and trial conduct. This would pave the way for the development of guidelines and treatment standards
for the management of complications of endovascular stroke treatment.
结论
研究EVT的RCT和病例系列主要关注再通率和临床结局。尽管多个国际指南建议使用EVT，但并发症管理的建议很少（总结见表2）。有趣的是，在DAWN或DEFUSE试验中，对于精心选择的患者，EVT的时间窗延长至24小时，并未显著增加并发症发生率。然而，血管内卒中治疗的并发症缺乏系统的分类。不同的分类系统，术语和并发症的定义存在，使得很难，甚至不可能，比较并发症及其管理。因此，有必要为临床实践和试验开展制定分类和报告标准。为血管内卒中治疗并发症管理指南和治疗的制定标准铺平道路。
结束语：
神经内科3病区全体，预祝大家2024年万事如意、心想事成！