Article Text
Abstract
Objective To examine the safety and efficacy of mechanical thrombectomy using a retrievable stent for thromboembolic occlusion occurring during coil embolization of ruptured intracranial aneurysms.
Methods Between June 2011 and June 2015, 631 consecutive patients with ruptured intracranial aneurysms underwent coil embolization at 6 hospitals. Among 53 patients who had thromboembolic complications, 15 patients harboring 15 aneurysms underwent rescue mechanical thrombectomy with a retrievable stent for the treatment of thromboembolic occlusion during the coiling of ruptured aneurysms. The patients' clinical and radiologic outcomes were retrospectively reviewed.
Results Of the 15 aneurysms, coiling alone was used for 13 (86.7%), and stent-assisted coiling was performed for 2 (13.3%). Thromboembolic occlusion most frequently occurred distal to the aneurysm (n=10, 66.7%), followed by proximal to the aneurysm (n=3, 20%), and at the coil−parent vessel interface (n=2, 13.3%). All patients underwent mechanical thrombectomy with a retrievable stent, including 5 patients who were initially treated with an IA tirofiban infusion. Complete recanalization (Thrombolysis in Cerebral Infarction (TICI) 3) was obtained in 13 (86.7%) and partial recanalization (TICI 2b) in 2 (13.3%). Two patients who had received IA tirofiban before mechanical thrombectomy had hemorrhagic complications. At 6 months after discharge, 9 patients had a modified Rankin Scale (mRS) score of 1, 3 patients were mRS 2, 1 patient was mRS 3, 1 patient was mRS 4, and 1 patient was mRS 6.
Conclusions Rescue mechanical thrombectomy using a retrievable stent can be a useful treatment for thromboembolic occlusion occurring during coil embolization of ruptured intracranial aneurysms.
- Thrombectomy
- Aneurysm
- Coil
Statistics from Altmetric.com
Introduction
Despite various attempts at decreasing the incidence of periprocedural complications during coil embolization for ruptured intracranial aneurysms, thromboembolism is still a major complication. In endovascular treatment of ruptured intracranial aneurysms, in particular, preventive protocols, such as systemic heparinization and preoperative antiplatelet treatment, are limited, and thromboembolism is more often seen. The causes of thrombus formation are reported to be the presence of foreign materials, the electric current used for detachment of the coils, and the hypercoagulable state after subarachnoid hemorrhage.1–4 Thromboembolism can result in partial or total occlusion of vascular branches and may result in transient or permanent neurologic symptoms.
Until recently, many studies have suggested the use of glycoprotein (Gp) IIb/IIIa inhibitors or fibrinolytic agents, such as tissue plasminogen activator and urokinase, as a rescue therapy for intraprocedural thrombus formation during coil embolization of intracranial aneurysms.1 ,3 ,5–13 While IA infusion of those agents are considered as the treatment strategy for an acute thromboembolism, the efficacy and safety of mechanical thrombectomy with a retrievable stent as rescue therapy for thromboembolic occlusion has rarely been reported. Therefore, we report our experience and results of rescue mechanical thrombectomy using a retrievable stent during endovascular treatment of ruptured intracranial aneurysms.
Patients and methods
Patient characteristics
Between June 2011 and June 2015, 631 patients who presented with ruptured intracranial aneurysms underwent endovascular coil embolization at six hospitals. Among these patients, thromboembolism occurred in 53 patients (8.3%) during the procedure. In 38 of these 53 patients, 18 patients were managed conservatively, and 20 patients with partially occlusive thromboembolism were treated by IA tirofiban infusion (a non-peptide Gp IIb/IIIa antagonist). Finally, we retrospectively reviewed the remaining 15 patients treated by mechanical thrombectomy with retrievable stent for complete thromboembolic occlusion. This study was approved by Hallym University institutional review board.
Procedures
All endovascular procedures were performed with the patients under general anesthesia. Systemic anticoagulation with IV heparinization was started after formation of the first coil frame. Heparin was usually administered as a 3000−4000 IU bolus intravenously followed by 1000 IU/hour. Heparin was given to achieve an activated clotting time (ACT) of approximately twice normal. The ACT was checked every 30 min. The total amount of infused heparin during a procedure ranged from 3000 to 5000 IU. In cases with an unfavorable, wide-necked aneurysmal configuration, which required stent assisted coil embolization, antiplatelet treatment with 300 mg of clopidogrel and 300 mg of aspirin was administered after stent deployment. In cases with large intraventricular hemorrhage, if external ventricular drainage was planned, a single antiplatelet agent was given.
Thromboembolism during procedure
Each thromboembolism was classified according to its location relative to the aneurysm, as follows: (1) interface, thromboembolism at the coil−parent vessel interface; (2) proximal, thromboembolism proximal to the aneurysm; (3) distal, thromboembolism distal to the aneurysm.
When thrombus formation was detected during coil embolization, the partially occluded parent artery with patent antegrade flow was monitored closely every 5 min. If the thrombus formation increased or the parent artery was completely occluded, we carried out IA tirofiban infusion or mechanical thrombectomy with a retrievable stent. Mechanical thrombectomy without IA tirofiban was preferred for a proximal or distal thrombus with complete occlusion of the involved artery. IA tirofiban was preferred for a partially occluded thrombus with intact antegrade flow, an interface-type thrombus, and a thrombus with far distal occlusion not suitable for mechanical thrombectomy. Doses of 0.3−1.0 mg were infused intra-arterially via a microcatheter near the thrombus. Despite the use of a maximum dose of IA tirofiban, if the parent artery was not recanalized, mechanical thrombectomy with a stent retriever was performed.
The Solitaire FR (Covidien, Irvine, California, USA) was used for mechanical thrombectomy. After removing a microcatheter for coiling, a new larger microcatheter equipped with a microguidewire was placed about 1 cm distal to the thrombus. After the position of the microcatheter had been confirmed, microcatheter angiography was performed to confirm the patency of the artery distal to the thrombus. The retrievable stent was advanced through the microcatheter and deployed across the thrombus. The stent remained deployed at the lesion for 3–5 min before retrieval. The microcatheter was then withdrawn with the retrievable stent while manual suction with a syringe was applied to the guiding catheter.
Angiographic and clinical outcome
Aneurysm occlusion was graded according to the Raymond scale.14 Angiographic recanalization was assessed using the Thrombolysis in Cerebral Infarction (TICI) perfusion scale.15 All patients underwent CT angiography or MR angiography within 1 week after the procedure to evaluate the patency of the artery and to detect hemorrhagic or ischemic complications. Two experienced neurointerventionalists who were blinded to the patient information independently reviewed the angiographic outcomes. At 6 months after discharge, clinical outcomes were evaluated with the modified Rankin Scale (mRS),16 which was estimated by neurointerventionalists at six hospitals based on retrospective review of charts. All statistical analyses were done using IBM SPSS software V.22.0 (IBM Inc, Armonk, New York, USA). Descriptive values are expressed as the mean±SD of the mean.
Results
Patient population
The mean patient age at the time of procedure was 54.7±11.8 (range 35–79 years). Nine patients were women. Initial mental status was assessed using the Hunt and Hess grade. Maximal diameters of aneurysms treated ranged from 3.3 to 10.1 mm (mean 5.4±2.1 mm). Most aneurysms were wide-necked (9/15, 53%), with depth to neck ratios <1.5. The treated aneurysms were located on the posterior communicating artery in 6 (40%), anterior communicating artery in 4 (26.7%), middle cerebral artery (MCA) in 2 (13.3%), anterior choroidal artery in 1 (6.7%), paraclinoid internal carotid artery (ICA) in 1 (6.7%), and vertebral artery (VA) in 1 case (6.7%).
Endovascular coiling and thrombus treatment
The patients' characteristics and outcomes are summarized in table 1. A single-microcatheter technique was the most frequently used (10/15, 66.7%), followed by a double-microcatheter technique in 3 (20%), and stent-assisted coil embolization in 2 cases (13.3%). After coil embolization, complete occlusion of the aneurysm (Raymond 1) was achieved in 12 cases (80%) and neck filling (Raymond 2) was achieved in 3 cases (20%).
The thromboembolic occlusion was most frequently located in the MCA in 11 patients (73.3%), followed by the distal ICA in 2 (13.3%), the proximal ICA in 1 (6.7%), and the VA in 1 (6.7%). Relative to the location of the aneurysm, the thromboembolisms were interface in 2 (13.3%), proximal in 3 (20%), and distal in 10 patients (66.7%). Thromboembolism occurred before coiling (during the positioning of the guiding catheter or microcatheter) in 5 (33.3%), during coiling in 4 (26.7%), and after coiling in 6 patients (40%).
IA tirofiban before mechanical thrombectomy was administered in five patients, including two with an interface and three with a distal thromboembolism. In these patients, thrombus formation was further aggravated and resulted in complete occlusion of the involved artery despite the IA tirofiban infusion. Including the five patients treated with IA tirofiban, all 15 patients underwent mechanical thrombectomy for thromboembolic occlusion.
Angiographic and clinical outcomes
According to the grading system of recanalization, cerebral angiography at the end of procedure demonstrated TICI 3 in 13 cases (86.7%), and TICI 2b in 2 (13.3%). The mean time from onset of occlusion to recanalization was 36.3±22.6 (range 15–90 min). Postoperative hemorrhagic complications developed in two patients, who had received IA tirofiban before mechanical thrombectomy. One patient with subcortical intracerebral hemorrhage (ICH) at the frontal lobe was managed conservatively and discharged with slight disability (mRS 2). The other patient underwent surgical removal of the hematoma at the parieto-occipital lobe, and discharged with moderate disability (mRS 3). Ischemic complications developed in three patients, including two of focal infarction at the frontal lobe (mRS 2) and basal ganglia (mRS 4). The remaining patient died from MCA territory infarction (mRS 6). In this patient, the proximal ICA was occluded owing to thrombus formation during coiling of the ruptured anterior communicating artery aneurysm. Although repetitive mechanical thrombectomy resulted in recanalization (TICI 2b), the recanalization time was 90 min and MCA territory infarction developed. The patient died from uncontrolled brain swelling despite decompressive craniectomy. At 6 months after discharge, nine patients were mRS 1, three were mRS 2, one was mRS 3, one was mRS 4, and one was mRS 6.
Illustrative case 1 (patient No 6)
A middle-aged patient presented with severe headache. The patient's Hunt and Hess grade was 2 and Fisher grade was 3. Cerebral angiography demonstrated a ruptured aneurysm at the anterior communicating artery (figure 1). The patient underwent coil embolization with a single-microcatheter technique. After the frame was constructed using the first coil, heparin (4000 IU) was administered intravenously. During the coiling, an acute thrombus developed in the distal ICA, and complete occlusion was found by angiography. Coil embolization was continued until complete obliteration of the aneurysm was achieved. Another microcatheter for mechanical thrombectomy was then advanced through the thrombus and placed distal to the thrombus. A Solitaire stent was deployed from the right MCA to the distal ICA across the thrombus, and left for 3 min before retrieval. The deployed stent was withdrawn through the guiding catheter while manual suction with a syringe was applied. Follow-up angiography showed a recanalized ICA and anterior cerebral artery (ACA), but the right MCA remained completely occluded. Thrombectomy was repeated and complete recanalization of the MCA (TICI 3) was obtained. The time from onset of occlusion to recanalization was 20 min. The patient was discharged free of neurologic deficits (mRS 1).
Illustrative case 2 (patient No 7)
A middle-aged patient presented with altered mentality. The patient's Hunt and Hess grade was 3 and Fisher grade was 4. Cerebral angiography revealed a ruptured aneurysm at the posterior communicating artery (figure 2). After positioning the guiding catheter at the cervical ICA, thromboembolic occlusion developed in the proximal MCA. A microcatheter for mechanical thrombectomy was advanced to the distal MCA across the thrombus. A Solitaire stent was deployed for 3 min, and withdrawn through the guiding catheter while manual suction with a syringe was applied. Follow-up angiography showed complete recanalization (TICI 3) of the MCA. The time from onset of occlusion to recanalization was 15 min. Coil embolization was then performed, and complete obliteration of the ruptured aneurysm was achieved. The patient recovered gradually and was discharged free from neurologic deficits (mRS 1).
Illustrative case 3 (patient No 13)
A middle-aged patient presented with altered mentality. The patient's Hunt and Hess grade was 3 and Fisher grade was 4. An initial CT scan showed a diffuse subarachnoid hemorrhage at the basal cistern and intraventricular hemorrhage at the fourth ventricle. Cerebral angiography revealed a ruptured aneurysm at the anterior communicating artery (figure 3). The patient underwent coil embolization with a double-microcatheter technique and the ruptured aneurysm was completely occluded. Final angiography showed unexpected occlusion of the angular artery, which was not covered in the working projection of the aneurysm. A microcatheter was located proximal to the occlusive thrombus and an IA tirofiban infusion (1.0 mg) was carried out. Despite IA tirofiban, recanalization was not obtained. We planned mechanical thrombectomy after confirmation of poor leptomeningeal collateral flow from posterior cerebral artery to MCA. Another microcatheter for mechanical thrombectomy was advanced to the distal angular artery across the thrombus. A Solitaire stent was deployed for 4 min, and withdrawn through the guiding catheter while manual suction with a syringe was applied. Final angiography showed complete recanalization (TICI 3) of the angular artery. The time from onset of occlusion to recanalization was 70 min. Follow-up CT showed acute ICH at the left parieto-occipital lobe. The patient underwent surgical removal of the hematoma, and was discharged with moderate disability (mRS 3).
Discussion
Thromboembolic complication during coil embolization of intracranial aneurysms is a major concern, occurring in 2.5−28% of patients.1 ,5 ,17–19 In our series of 631 patients with ruptured aneurysms, 53 (8.4%) had a thromboembolism during the procedure. A relatively high incidence of thromboembolism in ruptured aneurysms compared with unruptured aneurysms can be attributed to the limited use of preoperative antiplatelet treatment and the hypercoagulable status in ruptured aneurysms. Among the thromboembolisms which occur during the procedure, the occlusion of the cerebral artery by thrombus is a serious complication, which requires urgent recanalization. In this study, we focused on the management of occlusive thrombus with mechanical thrombectomy using a retrieval stent. Our results have shown that favorable recanalization can be achieved by a retrievable stent in patients with occlusive thrombus occurring during coil embolization of ruptured aneurysms.
The usual treatment for an acute thromboembolism during coil embolization of ruptured intracranial aneurysms includes the use of IA fibrinolytic agents or Gp IIb/IIIa inhibitors.1 ,3 ,5–13 According to recent reports, Gp IIb/IIIa inhibitors have been used more often than fibrinolytic agents, and have provided better outcomes.5 ,11 ,13 A study of 372 ruptured intracranial aneurysms found that 39 patients (10.5%) received an IA tirofiban injection.6 Although a high rate of recanalization (87.2%) was obtained in these patients, ICH occurred in 5.1% and cerebral infarction developed in 20.5%. Bruening et al1 reported on 16 patients who received IV tirofiban therapy. In these patients, complete recanalization was achieved in 88%, and 18.8% developed minor localized bleeding. Although rescue treatment with tirofiban generally appears to be an effective treatment for thromboembolism in patients with ruptured aneurysms, concerns about recanalization failure and procedure-related hemorrhage still remain. We also observed hemorrhagic complications in two of five patients who had received IA tirofiban before mechanical thrombectomy, whereas none were found in patients treated by mechanical thrombectomy only. If the patients presented with concomitant ICH, or aneurysms were not secured by coils, the risk of hemorrhagic complication was not negligible after IA tirofiban infusion.
Mechanical thrombectomy using the Penumbra system has been tried for rescue therapy for a small number of cases in which pharmacologic therapy for thromboembolism has failed.20 Kang et al20 reported two cases of successful recanalization after forced-suction rescue thrombectomy using the Penumbra system for thromboembolism occurring during coil embolization of a ruptured cerebral aneurysm. However, the Penumbra system requires the use of a large guide catheter and positioning of a large aspiration catheter at the level of thrombus,21 which is not suitable for distal-type thrombus. Furthermore, the potential risk of aneurysm rupture or coil migration caused by a suction force close to the aneurysm may not be negligible.
Most of the thromboembolism reported previously was partially occluded thrombus detected at the coil−parent vessel interface.1 ,6 ,8 ,9 ,12 However, thromboembolism can develop anywhere during coil embolization, including areas proximal and distal to the aneurysms. We preferred mechanical thrombectomy without pharmacologic therapy for completely occluded thrombus, which was more frequently detected at the distal artery. Total occlusions of the distal artery tend to be refractory to pharmacologic therapy.6 ,12 ,22 Sedat et al12 reported that 37.5% of distal and 70.5% of proximal thromboembolisms treated with Gp IIb/IIIa inhibitors (eptifibatide) were completely recanalized, whereas all cases of thrombus at the coil−parent vessel interface were completely recanalized. Cho et al6 reported a different recanalization rate with IA tirofiban infusion, depending on the extent of the occlusion. In their study, patients with complete occlusion showed a relatively poor response compared with those with partial occlusion. These findings suggest that antegrade flow is a key factor for the effective delivery of tirofiban into the thrombus. The efficacy of IA tirofiban is limited in the case of complete occlusion without antegrade flow. Therefore, mechanical thrombectomy might be considered as a useful treatment in patients with distal arterial occlusion and in patients unresponsive to an IA tirofiban infusion.
Although most distal occlusions were located in the M1 or M2 segment of the MCA, which was accessible by microcatheter for the stent retriever in our series, the use of mechanical thrombectomy in small vessels located far distally requires careful consideration. In particular, for far distal arterial occlusion refractory to IA tirofiban, such as angular artery occlusion in our cases, rescue mechanical thrombectomy with a retrievable stent has a potential risk for hemorrhage. The use of IA tirofiban and additional mechanical injury caused by difficulty in positioning the microcatheter or withdrawal of the stent in small vessels might result in hemorrhagic complication. Therefore, early detection of thrombus with careful angiography and early use of IA tirofiban before the occurrence of complete occlusion is important to obtain a satisfactory outcome.
One of our major concerns about mechanical thrombectomy performed with a retrievable stent was coil herniation and injury of the aneurysm neck during the procedure, especially for interface and distal thromboembolisms. During withdrawal of the retrievable stent, herniation of the coil mass and injury of the aneurysm neck can be caused by stent struts. However, in our experience, if coils are properly located within the aneurysm without protrusion into the parent artery, coil herniation and injury of the aneurysm neck seldom occur. The only problem with the retrievable stent was vasospasm of the parent vessels. Therefore, special care should be taken during passage of the stent strut through the parent artery of the coiled aneurysm. Zhang et al23 carried out two cases of mechanical thrombectomy with a Solitaire stent during the coil embolization of ruptured aneurysms, and successful recanalization was obtained without vascular injury or emboli. Considering the fatal outcome of thromboembolic occlusion refractory to IA tirofiban, mechanical thrombectomy with a retrievable stent can be considered as a rescue treatment.
Some potential limitations of this study should be considered. First, the use of a retrievable stent is limited in patients with tortuous vessel anatomy, for thromboembolisms located too distally in small-caliber vessels not suitable for thrombectomy, and when stents for coiling have already been deployed. Second, the outcomes of patients were not independently assessed. Third, we did not have a prespecified protocol to decide whether IA tirofiban should be administered before the retrievable stent. Fourth, the absence of a control group and the retrospective design of the study with a relatively small number of cases are not sufficient to ascertain the safety and efficacy of mechanical thrombectomy with a retrievable stent in ruptured intracranial aneurysms. Further prospective studies are needed.
Conclusion
Thromboembolic occlusion during coil embolization of ruptured intracranial aneurysms is a major concern for neurointerventionalists. Rescue mechanical thrombectomy using a retrievable stent can be a useful treatment, with a high rate of recanalization in cases where IA tirofiban fails or is definitely contraindicated. More data and prospective studies are needed to validate our preliminary results.
References
Footnotes
Contributors All authors: conception, design, and acquisition of the data. JHA and IBC: analysis, interpretation of the data, and drafting of the article. All authors: critically revision of the article. IBC is the guarantor of the study and takes responsibility for its content.
Competing interests None declared.
Ethics approval Hallym Sacred Heart Hospital Institutional review board.
Provenance and peer review Not commissioned; externally peer reviewed.