Mechanical thrombectomy and postoperative complications after acute ischemic stroke with large vessel occlusion

WANG Yi-tian, AI Xiang-bai, HUANG Xiao-gan, FU Chuan-yi, ZHAO Jian-nong

Hainan Hospital Affiliated to Hainan Medical University, Hainan Provincial People's Hospital, Haikou 570102, China

Keywords:

ABSTRACT Acute ischemic stroke is one of the common diseases in Chinese, among which acute ischemic stroke with large vessel occlusion AIS-LVO) has the most serious complications and has the risk of death.Studies have shown that reperfusion is a first-line treatment for the effective rescue of ischemic brain tissue, usually mainly by mechanical thrombectomy(MT), supplemented by intravenous thrombolysis.However, there are still complications after large blood vessel occlusion and MT.such as bleeding and infection at the puncture point, vasospasm, vascular dissection, subarachnoid hemorrhage, hemorrhagic transfomation,reembolization, and massive cerebral infarction, etc.The high risk factors and corresponding measures of complications after MT by reviewing the research analysis.

1.Background

Stroke is one of the common causes of death and disability in humans, especially acute ischemic stroke with large vessel occlusion(AIS-LVO).Currently, using endovascular device to mechanical thrombectomy is a breakthrough treatment for acute ischemic stroke.Five randomized controlled trials of MR CLEAN[1],ESCAPE[2], EXTEND-IA[3], SWIFT PRIME[4], and REVASCAT[5]in Holland、Spain and other countries, indicated that mechanical thrombectomy and intravenous thrombolysis improved the survival benefit of patients with AIS-LVO.And the treatment time window was extended to 16-24 h to provide a safely and effectively evidence for AIS-LVO thrombectomy guidelines.At the same time, the domestic MT technology also development rapidly.Our country specialist consensus suggests improving the people and pre-hospital emergency physician understanding of stroke and treatment[6], such as strengthening social propagantion for the acute ischemic stroke and MT.Making stroke patients get shorter recanalization time and more effectively save ischemic and anoxia brain tissue, improve the treatment and prognosis of patients.Nevertheless, there are still some patients with complications such as puncture point bleeding and infection, vasospasm, vascular dissection, hemorrhage, subarachnoid hemorrhage, cerebral parenchymal hemorrhage, reembolization, and massive cerebral infarction during and after MT, which affect the treatment effect and prognosis of stroke patients.The incidence of these complications is between 4% and 29%[7].Therefore, the purpose of this paper is to explain the AIS-LVO related removal methods, complications and corresponding remedial measures after MT.

2.Conditongs and methods of mechanical thrombectomy for AIS-LVO

When AIS-LVO occurs, conditions permit and within the time window of thrombolysis, the use of intravenous thrombolytic drugs is preferred, and if the efficacy is poor.If the course of the disease exceeds the time window of thrombolysis, and the NIHSS score ＞ 7, the transcatheter intracranial vascular thrombosis can be removed through the hospital green channel after iconography imaging evaluation.Among them, thrombus removal methods include stent retriever, direct aspiration and combined use of a stent retriever and a direct aspiration technique.The study express that the rate of revascular , good prognosis, subarachnoid hemorrhage and mortality rate were not statistically significant by stent retriever and direct aspiration[8].However, a meta-analysis showedthat the stent retriever has a higher risk of vasospasm compared with the direct aspiration.After direct aspiration failure, combined stent retriever had higher recanalization rate and risk of cerebral parenchymal hemorrhage than thrombectomy alone[9].CAPTIVE The technology is direct aspiration combined with stent retriever, which is more effective in opening vascular[10] than individual stent retriever.Therefore,the method of thrombectomy is selected should be combined with the actual situation, the study found that cerebral artery thrombosis and other parts of fibrin, platelets, erythrocytes and leukocytes,but the proportion of different sources of thrombus components different[11,12], such as the previous atrial fibrillation patients common embolus is composed of a large number of erythrocytes,loose texture, consideration direct aspiration; if considered chronic embolization, atherosclerosis patients, the common embolus lower erythrocytes, higher fibrin content, tight texture and sorption with strong capacity in vessel endothelium, direct aspiration is difficultly,stent retriever is easily[13].

3.Complication

According to the site of complications, we will divide them into extracranial complications and intracranial complications.Extracranial complications include vascular complications related to the puncture point and the path.Intracranial complications include puncture vessels wall, inadvertent detachment of stent retrievers,vasospasm, vascular dissection, subarachnoid hemorrhage, cerebral parenchymal hemorrhage, thrombus reformation, etc.

3.1 Complication of Puncture Point

In the randomized control trials (RCTs), the incidence of puncturerelated complications ranged from 2%～10%, mainly bleeding from the arteria cruralis, possibly with infection, pressure sores,and neurovascular related injuries[2,3,5,14].We routinely apply the bandage to the puncture point, which requires the patient and their family members to cooperate with braking and pressing.The puncture point compression feels uncomfortable and skin pressure ulcers and infection may occur.With the progress of technology and the economic needs of patients, the femoral artery hemostat of electronic compression can be used to reduce bleeding, skin damage, blisters, lower limb edema, and improve the comfort of the compression process[15].It can be localized by ultrasound puncture to reduce the nerve and vascular damage[16].

3.2 Angiospasm

In the relevant RCTs of AIS-LVO thrombectomy, the rates of vasospasm was 3.9% -23%[4,5,17].The compression and pulling of blood vessels by mechanical stimulation (stent thrombectomy),contrast agent and other chemical stimuli lead to continuous constriction of blood vessels, which reduces the diameter of the vascular lumen.In addition to vasospasm caused by thrombectomy,subarachnoid hemorrhage (SAH) is also the main cause of vasospasm.If the spasm cannot be removed in time, blood flow will slow down and the reperfusion of ischemic brain tissue will be affected, which may also be a risk factor for thrombosis reformation and lead to poor prognosis.Therefore, in order to improve the prognosis of thrombectomy patients, vascular spasm should be actively prevented and treated.At present, the prevention and treatment of vasospasm after thrombolectomy mainly include balloon dilation and nimodipine.Studies have shown that balloon dilation can relieve 60～80% of vasospasm[18].Guidelines state that the use of calcium blocker nimodipine in subarachnoid hemorrhage can prevent and treat cerebral vasospasm and reduce arachnoid hemorrhage.Niacin for injection can reduce the probability of vasospasm after thrombectomy and increase cerebral perfusion blood flow[19], which has a good influence on the prognosis of patients with thrombectomy.If blood vessel spasm occurs after thrombectomy, balloon dilation and antispasmolytic drugs such as niacin should be used for relief.If SAH occurs in postoperative review, nimodipine can be used and blood pressure can be monitored.Because nimodipine has antihypertensive effect and reduces intracranial blood perfusion, it is not suitable for preventive use.

3.3 Hemorrhagic Transfomation (HT)

Hemorrhage transformation at infarction site is one of the common complications of cerebral infarction.Studies have shown that the probability of complicated parenchymal hemorrhage is as high as 46.1%, and the incidence of symptomatic HT is 16%[20].The cause of bleeding is the change of vascular permeability, mainly due to the occurrence of AIS, which leads to brain tissue ischemia and hypoxia, so that oxygen free radicals, inflammatory factors and other tissue damage factors increase, and destroy the integrity of vascular endothelium and vascular wall.In addition, the appeal study elaborated that the number of stent thrombectomy ＞ 3, ASPECTS score ＜ 7, time from onset to femoral artery puncture ＞ 270 minutes,poor collateral circulation, increased neutrophil/lymphocyte rate and other factors would increase the risk of bleeding after mechanical thrombectomy of AIS-LVO[20].Of course, vascular diseases such as amyloidosis, hypertension and other factors are also one of the causes of intracranial hemorrhage, which needs to identify contrast extravasation.Therefore, we should comprehensively evaluate the patient’s condition and embolus nature, select the way of thrombectomy, and minimize the number of operations to avoid vascular injury and reduce the possibility of bleeding.Of course,some acute stroke thrombectomy patients are bridge patients, and whether intravenous thrombolysis drugs have any effect on bleeding has been explained in many studies that intravenous drug use has no significance with cerebral hemorrhage[21].Symptomatic HT seriously affects postoperative recovery and prognosis of patients, which were divided into: 1) asymptomatic HT:NIHSS score did not increase in spite of the presence of HT; 2) Mild symptoms of HT: NIHSS score increased by 1 ～ 3 points; 3) Severe symptoms of HT: NIHSS score increased by 4 points[22].In terms of treatment, asymptomatic or mild patients can be mainly given conservative treatment, such as keeping quiet, controlling blood pressure, controlling blood sugar, nourishing nerves and reducing intracranial pressure treatment.For severe patients with progressive disturbance of consciousness, obvious intracranial space occupying effect shown by CT, intracranial pressure ＞ 30 mmHg and ineffective medical treatment, or even dilated pupils, craniotomy decompression can be performed as soon as possible to improve the prognosis[23].

3.4 Subarachnoid hemorrahage (SAH)

Subarachnoid hemorrhage (SAH) is also one of the common complications after mechanical thrombectomy of AIS LVO.Blood flows into subarachnoid space due to mechanical damage, oxygen free radicals, and inflammatory factors in the blood vessels at the base or surface of the brain after thrombectomy.SAH is usually recessive during operation, and postoperative CT examination suggests that SAH is more common.The main clinical symptoms were headache, nausea, vomiting and other elevated intracranial pressure.There will also be neurological impairment, epilepsy and other symptoms, serious cases will appear consciousness disorders,life-threatening, reduce the quality of treatment.

Our guidelines suggest that smoking, alcoholism, hypertension,hypolipemia, long-term use of estrogen, family history of aneurysm or SAH, aneurysm, cerebral artery malocclusion, and autosomal dominant polycystic kidney disease[24] are independent risk factors for increasing SAH.Studies on AIS-LVO mechanical thrombectomy complicated with subarachnoid hemorrhage have shown that MCA quillary, multiple thrombectomy, longer stent in MCA M2 segment and thrombectomy in M2 segment can increase the risk of SAH in patients with acute cerebral infarction after stent retriever thrombectomy[25].Aneurysm is a common cause of subarachnoid hemorrhage.If the presence of aneurysms in infarcts or other intracranial arteries is found during DSA, aneurysm plugging can be performed, and the occurrence of subarachnoid hemorrhage should be noted and timely treatment should be conducted.Such as the use of mannitol to reduce intracranial pressure, the use of aminocaproic acid to prevent rebleeding.Common complications of SAH include vasospasm, delayed cerebral ischemia and so on.Management of vasospasm as described above.The pathogenesis of delayed cerebral ischemia is unknown, and it has been recognized as one of the important causes of death and disability after SAH,which may be related to vasospasm, microthrombus, cortical diffusion depolarization, and brain autonomic regulation disorder,etc.[24].Nimodipine can effectively treat delayed cerebral ischemia,and mannitol can be used to reduce intracranial pressure when intracranial pressure increases.

3.5 Embolus Escape and Thrombosis Reformation

In the process of MT, partial embolus fragmentation is likely to cause embolus escape and lead to distal vascular infarction.Due to the small diameter of the distal vessel, the thrombectomy catheter could not reach the location where the embolus escaped, resulting in poor vascular opening effect after infarction.At present, after embolus escape, arterial thrombolytic drug therapy can be given,but alteplase is not recommended, and bridging thrombectomy is generally longer than 4.5 h, with contraindications[21].The brain is rich in blood supply, so medication is not necessary, which may increase the risk of bleeding.

In situ thrombus reformation does not benefit the patient, and the NIHSS score may increase after thrombus formation.The patient’s ability to tolerate the surgery should be evaluated during re-thrombectomy or decompressive craniectomy, and the risk of bleeding should be considered if re-thrombectomy is performed.Joao Pedro et al.found that statin therapy before admission was negatively correlated with re-embolization, while distal internal carotid artery occlusion, short re-occlusion during thrombus removal,device passage times, atherosclerosis, residual thrombosis or narrow dissection after recanalization were positively correlated with 24 h re-occlusion[26].Statins, atherosclerosis and other factors are related to blood lipid and blood viscosity, which may promote thrombosis re-formation.Meanwhile, Osama et al.found in their study that the thrombus blocked by the distal end of the internal carotid artery was longer and the efficiency of one-time opening was poor[27],which increased the difficulty of thrombectomy and may require multiple thrombectomy to increase the risk of vascular injury and promote platelet aggregation and thrombosis formation.Residual thrombus and changes in vessel diameter are also factors of embolus formation.

CAPTIVE suction combined with stent thrombectomy techniques can quickly and effectively open vessels, shorten the opening time,reduce embolus escape and vascular injury, and do not increase symptomatic intracranial hemorrhage and other complications, thus improving the prognosis of clinical patients[10].Atherosclerosis is one of the main causes of thrombosis.In addition to routine postoperative administration of dual antibody and statins, intraoperative antiplatelet aggregation therapy can be given by transarterial Tirofiban.Studies have shown that low-dose administration of tirofiban through arteries after thrombectomy in patients with atherosclerosis can prevent the occurrence of vascular re-occlusion and improve the prognosis of patients[28].Tirofiban is an antiplatelet aggregator.Factors that promote platelet aggregation, such as thrombus residual and vascular endothelial injury, can also be treated with Tirofiban preventative treatment.However, kellert et al.found that the use of tirofiban with unsatisfactory thrombectomy effect would increase the risk of bleeding and lead to poor prognosis[29].However, most studies have shown that tirofiban is effective in inhibiting thrombus reformation and has a good prognosis at 90 d after surgery.

3.6 Reperfusion Injury

Reperfusion injury has “waterfall effect”, which means that when the blood flow is recanalized after acute occlusion of the great blood vessels, the function of tissues and organs is not improved, but further damage of function will occur, which can occur in various organs in the body.Cerebral tissue reperfusion injury will also occur after mechanical thrombectomy and revascularization after acute cerebral vascular occlusion, which is an inevitable complication and further aggravates the brain tissue injury, the degree of injury may be mild or severe.Its pathogenesis is very complex, and is related to multiple mechanisms such as excessive formation of free radicals, toxic effects of excitatory amino acids, intracellular calcium overload, mitochondrial damage and inflammatory response[30].These factors impair the function of brain cells and further change the permeability of cell membranes, leading to tissue edema,increased intracranial pressure, aggravating brain tissue injury, or the formation of cerebral hernia, which is life-threatening.

Reperfusion injury involves a wide range of related signaling pathways, Such as phosphatidylinositol 3-kinase (P13K)/Serinethreonine protein kinase (AKT) signaling pathway, NF-KB signaling pathway, mitogen activated protein kinase (MAPK) signaling pathway, Notch signaling pathway, Janus kinase signal transducers and transcriptional activators (JAK/sTAT) signaling pathway,etc[31].For example, P13K/AKT is involved in signaling pathways related to the regulation of cell metabolism, proliferation, apoptosis,and migration[32], and Notch signaling pathway is involved in the maturation and activation of microglia cells, which can promote inflammation and aggravate post-perfusion injury[33].

Reperfusion injury is mainly treated with drugs.Anesthetic drugs can reduce brain cell metabolism and reduce inflammation; statin drugs can reduce inflammation and antioxidant; n-acetylcysteine and edaravone can remove oxygen free radicals[34], which can protect brain tissue and reduce the risk of further tissue damage.In addition,Chinese medicine also has the effect of protecting brain tissue.Studies have proved that saponins, flavonoids, phenols and alkaloids have protective effects on brain tissue in rats with cerebral ischemia reperfusion injury[35].Clinically, Edaravone, butylphthalein, ginkgo biloba extract, Danshen ligustrazine and other drugs are often used to remove free radicals, improve local blood circulation, antioxidant,etc., protect brain tissue and prevent further damage to brain tissue after vascular occlusion.

DWI double index model can better evaluate the risk of reperfusion injury after revascularization in patients with acute cerebral infarction[36].Conditions permit the evaluation of this test or multimodal imaging, providing reference for active prevention of severe reperfusion injury.

3.7 Other Complications

The complication rate of vascular dissection is relatively small, and dissection is also one of the causes of cerebrovascular occlusion and re-occlusion.No thrombus was removed during thrombectomy, and the improvement of blood flow is not obvious.Cerebral infarction caused by dissection or stenosis can be considered and confirmed by angiography.The main treatment methods are balloon dilation and stent implantation, so as to attach the interlayer[37] and restore the unobstructed blood flow.

Inadvertent detachment of stent retrievers is one of the rare complications during thrombectomy, but it can cause complications such as vascular dissection, vasospasm, and angiorrhexis after stent loss, leading to poor prognosis.A multicenter retrospective study showed that stent removal was easy to come out after 6 times of thrombectomy[38], or atherosclerosis led to intracranial vascular wall hardening and narrowing, and changing its force direction increased the risk of stent retrieval device loss and was one of the reasons for stent loss[39].After the stent is detached, a new stent retriever can be used to remove the fallen stent[40].If the patient has good collateral circulation or the vessel remains open after stent removal, the stent can be left in the body[38, 39], and double antibody can be used to prevent thrombosis that may be caused by the stent.

Epilepsy is one of the most complications after brain tissue injury,and AIS-LVO is naturally no exception, but the complication rate of epilepsy after intravascular thrombectomy is lower than that of patients without thrombectomy[41].The occurrence of epilepsy may be related to infarct location and volume.Clinical patients and medical staff should improve the prevention awareness of epilepsy, pay attention to whether patients have lapses, involuntary movements, muscle rigidity, muscle spasm and other epilepsy symptoms, timely administration of sodium valproate, carbamazil equal antiepileptic drugs for control, to avoid the occurrence of major epilepsy and poor prognosis.

4.Conclusion

In conclusion, endovascular mechanical thrombectomy is currently the first-line treatment for acute large vessel occlusive cerebral infarction, which can effectively save the ischemic and hypoxic brain tissue of patients after vascular infarction, reduce aphasia,hemiplegia and other neurological damage symptoms of patients after brain tissue injury, and save the lives of severe patients.Although mechanical thrombectomy has proved to be safe and effective in experiments, there are still high complications, especially bleeding, thrombosis and other complications, which can lead to increased intracranial pressure or cerebral herniation, which is lifethreatening.Therefore, by describing the relevant high-risk factors of complications and treatment methods, such as hyperlipidemia,coagulation function, thrombolysis and other factors, complications were effectively reduced in this paper, and relevant complications were found timely through CT, MRI and physical examination,and corresponding treatment was given to improve the treatment quality of patients.However, the control, detection and treatment of complications have a long way to go and need further research.

All authors declare no conflict of interest.

Authors’ contribution

Wang Yitian: Topic selection, writing and modification of thesis;Huang Xiaogan, Ai Xiangbai, Fu Chuanyi: Paper Review and revision; Zhao Jiannong: Instructor.