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Abstract
Objective A rare complication of neuroendovascular procedures is acute thromboembolism. In the setting of intraprocedural or periprocedural embolism, thrombolytics present a potentially useful therapeutic strategy. A series of patients in whom eptifibatide (a platelet glycoprotein IIb/IIIa receptor inhibitor) was used in the treatment of iatrogenic thromboembolic events occurring during elective neuroendovascular procedures is described.
Methods Consecutive cases between May 2009 and July 2011 in which eptifibatide was administered were identified and individually reviewed for inclusion in this study (n=12). All study patients received a uniform, weight based bolus dose of 180 μg/kg of eptifibatide administered either intra-arterially through the guide catheter or intravenously. Eptifibatide infusion (2 μg/kg/min) for 24 h after bolus dose administration was continued at the discretion of the surgeon. Procedural details are described and illustrative cases presented.
Results Three major categories of thromboembolic events were isolated in the course of review of study cases: acute focal neurological decline and no radiographic findings of flow limitation (eight patients), radiographic findings with or without symptoms (two patients) and persistent particulate debris during flow reversal as part of a carotid revascularization procedure (two patients). Following eptifibatide administration, no patient experienced hemorrhagic complications, and neurologic improvement to baseline level was noted in 10 of 12 patients.
Conclusion Eptifibatide may be an effective therapeutic strategy in the event of thromboembolism during elective neuroendovascular procedures.
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Introduction
A rare complication of neuroendovascular procedures is acute thromboembolism. In the setting of intraprocedural or periprocedural embolism, thrombolytics present a potentially useful therapeutic strategy. The perioperative intra-arterial (IA) and intravenous use of abciximab in this setting has been extensively described.1 In five series consisting of 13–42 patients each, rates of vessel revascularization varied from 66% to 100%, with low risk of hemorrhage (0–9%) and generally acceptable neurological outcome.1–5
Eptifibatide has a similar mechanism of action to abciximab but represents a more cost effective option.6 Like abciximab, it is an inhibitor of platelet glycoprotein IIb/IIIa designed for intravenous (coronary) use. Its use has displayed a similar revascularization profile compared with abciximab, with a lower incidence of gastrointestinal hemorrhage7 and thrombocytopenia.8 It may have more potent clot dissolution ability compared with abciximab with less risk of hemorrhage.9 These characteristics make eptifibatide an ideal rescue treatment in the setting of iatrogenic thromboembolism during endovascular procedures.
Experience with eptifibatide administration in the setting of acute stroke has been previously discussed,10 and limited experience with IA11 and intravenous12 eptifibatide in the setting of acute iatrogenic thromboembolism has been described. To expand on this experience, a series of patients in whom eptifibatide was used in the treatment of iatrogenic thromboembolic events occurring during elective neuroendovascular procedures is described. This report might serve as a guide for the application of eptifibatide rescue therapy in this setting.
Methods
A prospectively maintained database of elective and emergent endovascular procedures at our hospital was reviewed. Consecutive cases of diagnostic and elective neuroendovascular procedures between May 2009 and July 2011 were identified. This comprised 3585 consecutive cases, including 2616 diagnostic angiograms, and excluded all acute stroke revascularization procedures and other emergent cases. Those cases in which eptifibatide was administered were then identified and individually reviewed for inclusion in this study (n=12).
Interventional procedures were performed with the patient under conscious sedation and after heparin anticoagulation for a goal activated coagulation time (ACT) of ≥250 s. All study patients received a uniform, weight based bolus dose of 180 μg/kg of eptifibatide administered either intra-arterially through the guide catheter or intravenously. Eptifibatide infusion (2 μg/kg/min) for 24 h after bolus dose administration was continued at the discretion of the endovascular neurosurgeon (platelet counts are monitored every 6 h after starting eptifibatide).
Procedural details, including neurological changes and flow limitation, if present, were recorded. For cases in which radiographically evident flow limitation was found, flow was estimated by the Thrombolysis in Myocardial Infarction (TIMI) Scale before and after dosage of eptifibatide. Each case was assessed for details of postoperative events, including intracranial or other hemorrhage and discharge modified Rankin Scale score. Illustrative cases are presented.
Results
Each of the 12 study patients received a uniform, weight based bolus dose of 180 μg/kg of eptifibatide. This was given intra-arterially in seven patients and intravenously in five patients. Ten patients were also continued on the intravenous eptifibatide infusion (2 μg/kg/min for 24 h) after administration of the IA dose. No patients had hemorrhagic complications. A summary of the cases is displayed in table 1.
Cases in which eptifibatide was used in the treatment of acute thromboembolic events during elective neuroendovascular procedures
Three major categories of thromboembolic events were isolated in the course of our review of study cases: acute focal neurological decline and no radiographic findings (eight patients), radiographic findings of flow limitation, with (one patient) or without (one patient) symptoms and particulate aspiration during flow reversal as part of the carotid revascularization procedure (two patients, one of whom had symptoms). A representative case for each event category is presented below.
In the two patients with radiographic findings of flow limitation, perfusion improved from TIMI 1 and TIMI 2, respectively, to TIMI 3 flow after administration of eptifibatide. Among 10 patients with neurologic sequelae, all had complete or near complete resolution of symptoms to baseline level following administration of eptifibatide. Two of these patients had subsequent neurologic decline during hospitalization (case Nos 6 and 8). Case No 6 was scheduled for elective stent assisted coiling of a symptomatic unruptured giant intracranial aneurysm. This patient developed dysarthria and right-sided weakness during the procedure that did not improve despite treatment with eptifibatide (IA and then an intravenous infusion) and ultimately died 6 days postoperatively as a result of complications from the ischemic stroke. Case No 8 was scheduled for an elective angiogram requested as part of an investigation for suspected vasculitis. This patient developed a severe expressive aphasia, which was noted at the conclusion of the angiogram. An eptifibatide bolus was administered intravenously, and an intravenous infusion was continued. The patient's aphasia improved; however, speech did not return to baseline levels.
Acute and focal neurological decline and no radiographic findings
A patient (aged in their late-60s) who underwent right carotid artery stenting for asymptomatic carotid stenosis 6 years previously presented with progressive in-stent stenosis in excess of 90% (figure 1A; case No 1 in table 1). The patient was admitted for elective cutting balloon angioplasty. After diagnostic angiography, heparin was given to an ACT in excess of 250 s. After three cutting balloon dilations, an adequate revascularization of the stented vessel was accomplished (figure 1B). At this point, a routine neurological examination was performed, revealing a new left-sided hemiparesis. A cerebral angiogram revealed no evidence of acute thrombus. A bolus dose of eptifibatide (180 μg/kg) was administered through the guide catheter. The patient's hemiparesis improved to nearly full strength within minutes. Additional cerebral angiography revealed no evidence of acute thrombus. A postprocedure CT scan revealed no evidence of hemorrhage or perfusion asymmetry. The patient was then continued on an eptifibatide infusion (2 μg/kg/min) for 24 h after bolus dose administration. Neurological examination improved to baseline level, and the patient was discharged on postoperative day 3.
Digital subtraction angiograms, lateral view. (A) High grade in-stent stenosis of the right carotid artery lesion. (B) After cutting balloon angioplasty, adequate revascularization is seen.
Asymptomatic arterial thrombus with radiographic findings
A patient (aged in their mid-40s) with a previously ruptured giant ophthalmic artery aneurysm presented with cranial nerve palsy (case No 2 in table 1). The aneurysm was previously treated with coil embolization but had significant residual at the time of the 3 month follow-up angiogram due to coil compaction (figure 2A). Coil embolization of the residual was planned, along with placement of a stent in the parent vessel owing to an unfavorable aneurysm dome configuration for primary coiling. After a bolus of 5000 units of heparin had been administered to achieve an ACT of 250 s, a stent was placed without incident. Following the placement of nine coils, a lucency in the distal portion of the stent was appreciated, suggesting intraluminal thrombus (figure 2B). The microcatheter was removed, and eptifibatide (180 μg/kg bolus dose) was administered through the guide catheter with improved filling of the vessel within the stent, suggesting resolution of the thrombus (figure 2C). No new neurological deficit was detected throughout the procedure. An eptifibatide infusion (2 μg/kg/min) was started after the bolus dose and continued for 24 h after the bolus dose. The patient remained neurologically stable with third nerve palsy throughout the procedure and postoperative course, and was discharged to home on postoperative day 4 following a repeat angiogram revealing no residual in-stent thrombus or stenosis.
Digital subtraction angiograms, anteroposterior view. (A) Residual aneurysm. (B) Following coiling, a filling defect, suggesting thrombus, is seen within the middle cerebral artery (arrow). (C) After eptifibatide administration, there is normal filling of the middle cerebral artery.
Particulates aspirated during carotid artery stenting
A patient (aged in their mid-70s) presented with a transient ischemic attack consisting of slurred speech and confusion (case No 3 in table 1). On presentation, the symptoms had resolved. Angiography revealed an irregular left carotid stenosis with ulceration (figure 3A). Due to the complexity of the lesion, a proximal protection device was employed during the stenting procedure. After a bolus of 7500 units of heparin had been administered to achieve an ACT of 296 s, the proximal protection balloon was inflated for flow reversal. A stent was placed without incident and with good revascularization. Aspiration of blood through the guide catheter was littered with embolic material (figure 3B). After aspiration of 120 ml of blood, particulate debris remained present. At this time, a neurological examination was performed, without focal deficit elicited. Due to persistent particulate debris, IA eptifibatide (180 μg/kg) was administered through the guide catheter. Immediately thereafter, the proximal protection device balloon was deflated. Occlusion time was approximately 14 min. Cerebral angiography revealed no evident cerebral emboli. An eptifibatide infusion (2 μg/kg/min) was commenced after the bolus dose and continued for 24 h. The patient's neurologic examination remained intact throughout admission. The patient was discharged to home on postoperative day 2.
(A) Digital subtraction angiogram, lateral view, of the stenotic lesion, revealing an ulcerated lesion with irregular plaque. (B) Macroemboli seen in the protection device filters with aspiration after placement of the stent.
Discussion
In this report, the use of eptifibatide in the treatment of acute iatrogenic thromboembolism during elective neuroendovascular procedures is described. Standardized dosing13 of eptifibatide resulted in improved neurological examinations in most symptomatic patients (nine out of 10). Two patients with radiographically detectable thromboembolism had improved flow after eptifibatide dose. No clinically relevant difference was noted between intravenous and IA bolus dose administration. No intracranial hemorrhage or bleeding complication was observed.
This experience builds on previously published reports of eptifibatide use after iatrogenic thromboembolism in the setting of neuroendovascular procedures. Katsaridis et al 11 reported four patients undergoing endovascular embolization of aneurysms (three ruptured; one recurrent) with intraprocedural cerebral vessel thrombosis. All patients were treated with IA eptifibatide with recanalization of the affected vessels. Furthermore, all patients had excellent neurological outcomes. Yahia et al 12 reported excellent revascularization and neurological outcomes in three patients with delayed symptomatic thromboembolic events 6 days or more after intracranial stent placement for aneurysm treatment. All patients were treated with intravenous eptifibatide, with resolution of symptoms.
The series of patients presented here highlights the importance of utilization (when possible) of conscious sedation (rather than general anesthesia) and frequent performance of neurological examination during neuroendovascular procedures.14 ,15 As demonstrated in case No 1, neurological decline from thromboembolism may occur in the absence of evident radiographic abnormality. In fact, in this series, all patients with neurological decline had no recognizable vessel filling defect appreciated on cerebral angiography. Such events are presumably from cortical microembolism. Furthermore, patients with obvious intraluminal thrombus did not necessarily have detectable change in neurological status, as in case No 2.
Conclusion
Administration of eptifibatide, a platelet glycoprotein IIb/IIIa receptor inhibitor, may be an effective therapeutic strategy in the event of thromboembolism during neuroendovascular procedures.
Acknowledgments
The authors thank Paul Dressel, BFA, for help with preparation of the illustrations and Debra J Zimmer, AAS CMA-A, for editorial assistance.
References
Footnotes
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Competing interests LNH receives grant/research support from Toshiba; serves as a consultant to Abbott, Boston Scientific*, Cordis, Micrus and WL Gore; holds a financial interest in AccessClosure, Augmenix, Boston Scientific*,Claret Medical Inc, Micrus and Valor Medical; has a board/trustee/officer position with AccessClosure, Claret Medical Inc and Micrus (until September 2010); belongs to the Abbott Vascular speakers' bureau; and receives honoraria from Bard, Boston Scientific*, Cordis, Memorial Healthcare System, Complete Conference Management, SCAI and Cleveland Clinic. EIL receives research grant support (principal investigator: Stent-Assisted Recanalization in acute Ischemic Stroke, SARIS), other research support (devices) and honoraria from Boston Scientific* and research support from Codman and Shurtleff Inc and ev3/Covidien Vascular Therapies; has ownership interests in Intratech Medical Ltd and Mynx/Access Closure; serves as a consultant on the board of Scientific Advisors to Codman and Shurtleff Inc; serves as a consultant per project and/or per hour for Codman and Shurtleff Inc, ev3/Covidien Vascular Therapies and TheraSyn Sensors, Inc; and receives fees for carotid stent training from Abbott Vascular and ev3/Covidien Vascular Therapies. EIL receives no consulting salary arrangements. All consulting is per project and/or per hour. (*Boston Scientific's neurovascular business has been acquired by Stryker.) AHS has received research grants from the National Institutes of Health (co-investigator: NINDS 1R01NS064592-01A1, Hemodynamic induction of pathologic remodeling leading to intracranial aneurysms; not related to present manuscript) and the University at Buffalo (Research Development Award); holds financial interests in Hotspur, Intratech Medical, StimSox and Valor Medical; serves as a consultant to Codman and Shurtleff Inc, Concentric Medical, ev3/Covidien Vascular Therapies, GuidePoint Global Consulting and Penumbra; belongs to the speakers' bureaus of Codman and Shurtleff Inc and Genentech; serves on an advisory board for Codman and Shurtleff; and has received honoraria from Abbott Vascular, American Association of Neurological Surgeons' courses, an emergency medicine conference, Genentech, Neocure Group LLC, an Emergency Medicine Conference and from Abbott Vascular and Codman and Shurtleff Inc. for training other neurointerventionists in carotid stenting and for training physicians in endovascular stenting for aneurysms. AHS receives no consulting salary arrangements. All consulting is per project and/or per hour. KVS serves as a consultant to, a member of the speakers' bureau and has received honoraria from Toshiba. He serves as a member of the speakers' bureau for ev3 and The Stroke Group (consultants to the healthcare industry, Littleton CO) and has received honoraria from these entities.
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Ethics approval Procedures were performed at Millard Fillmore Gates Circle Hospital (a University at Buffalo affiliate). The institutional review board at the University at Buffalo approved the study, and a standard Health Insurance Portability and Accountability Act (HIPAA) compliant protocol was followed.
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Provenance and peer review Not commissioned; externally peer reviewed.