Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator

被引:371
作者
Molina, CA [1 ]
Ribo, M [1 ]
Rubiera, M [1 ]
Montaner, J [1 ]
Santamarina, E [1 ]
Delgado-Mederos, R [1 ]
Arenillas, JF [1 ]
Huertas, R [1 ]
Purroy, F [1 ]
Delgado, P [1 ]
Alvarez-Sabín, J [1 ]
机构
[1] Univ Autonoma Barcelona, Hosp Vall dHebron, Neurovasc Unit, Dept Neurol, Barcelona 08035, Spain
关键词
microbubbles; stroke; thrombolysis; ultrasonography;
D O I
10.1161/01.STR.0000199064.94588.39
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-We sought to evaluate the effects of administration of microbubbles (MBs) on the beginning, speed, and degree of middle cerebral artery (MCA) recanalization during systemic thrombolysis and continuous 2-MHz pulsed-wave transcranial Doppler (TCD) monitoring. Methods-We evaluated 111 patients with acute stroke attributable to MCA occlusion treated with intravenous tissue plasminogen activator (tPA). Thirty-eight patients were treated with tPA plus continuous 2-hour TCD monitoring plus 3 doses of 2.5 g (400 mg/mL) of galactose-based MBs given at 2, 20, and 40 minutes after tPA bolus (MB group). These patients were compared with 73 patients who were allocated to receive tPA plus continuous 2-hour TCD ultrasound (US) monitoring (tPA/US group) or tPA plus placebo monitoring (tPA group), most of whom were enrolled in a previous study of US-enhanced thrombolysis. The beginning, degree, and time to maximum completeness of recanalization during the first 2 hours of tPA bolus were recorded. Results-Median prebolus National Institutes of Health Stroke Scale (NIHSS) score was 18. Eighty patients (72%) had a proximal and 31 (28%) a distal MCA occlusion on TCD. Thirty-seven patients (33%) received tPA/US, 38 (34%) received tPA/US/MB, and 36 (32%) were treated with tPA alone. Stroke severity, time to treatment, location of MCA occlusion, and presence of carotid artery disease were similar among groups. Two-hour recanalization was seen in 14 (39%), 25 (68%), and 27 patients (71%) in the tPA, tPA/US, and tPA/US/MB groups, respectively (P=0.004). Two-hour complete recanalization rate was significantly (P=0.038) higher in the tPA/US/MB group (54.5%) compared with tPA/US (40.8%) and tPA (23.9%) groups. The time to beginning of recanalization after tPA bolus was 26 +/- 18 minutes in the tPA/US group and 19 +/- 12 minutes in the tPA/US/MB group (P=0.12). Four patients (3.6%) experienced symptomatic intracranial hemorrhage: 2 (5.5%), 1 (2.7%), and 1 patient (2.6%) who received tPA only, tPA/US, and tPA/US/MB, respectively, experienced symptomatic intracranial hemorrhage. At 24 hours, 31%, 41%, and 55% of tPA, tPA/US, and tPA/US/MB improved >4 points in the NIHSS score. Conclusions-Administration of MBs induces further acceleration of US-enhanced thrombolysis in acute stroke, leading to a more complete recanalization and to a trend toward better short- and long-term outcome.
引用
收藏
页码:425 / 429
页数:5
相关论文
共 22 条
[1]   ENSURING RELIABILITY OF OUTCOME MEASURES IN MULTICENTER CLINICAL-TRIALS OF TREATMENTS FOR ACUTE ISCHEMIC STROKE - THE PROGRAM DEVELOPED FOR THE TRIAL OF ORG-10172 IN ACUTE STROKE TREATMENT (TOAST) [J].
ALBANESE, MA ;
CLARKE, WR ;
ADAMS, HP ;
WOOLSON, RF ;
BENDIXEN, BH ;
DAVIS, PH ;
JACOBY, MR ;
GOMEZ, FJ ;
DYKEN, ME ;
UC, EY ;
WOJCIESZEK, JM ;
KAPPELLE, LJ ;
TANNA, AB ;
MITCHELL, VL ;
GOMEZ, CR ;
MALKOFF, MD ;
TULYAPRONCHOTE, R ;
SAUER, CM ;
RIAZ, G ;
SCHMIDT, JG ;
MALIK, MM ;
BANET, GA ;
KARANJIA, PN ;
MADDEN, KP ;
RUGGLES, KH ;
MICKEL, SF ;
GOTTSCHALK, PG ;
HANSOTIA, PL ;
SORENSON, RW ;
JACOBSON, DM ;
HINER, BC ;
MANCL, K ;
LUKASIK, E ;
BRUNO, A ;
LAKIND, ED ;
JEFFREY, DR ;
MLADINICH, EK ;
IQBAL, J ;
REINERS, M ;
BARRETT, DW ;
SHIBUYA, D ;
WILLIAMS, JK ;
RUSSELL, P ;
KING, MK ;
CHAPIN, JE ;
CARTER, S ;
JEFFRIES, L ;
HIER, DB ;
SHAPIRO, RA ;
BRINT, SU .
STROKE, 1994, 25 (09) :1746-1751
[2]   Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke [J].
Alexandrov, AV ;
Molina, CA ;
Grotta, JC ;
Garami, Z ;
Ford, SR ;
Alvarez-Sabin, J ;
Montaner, J ;
Saqqur, M ;
Demchuk, AM ;
Moye, LA ;
Hill, MD ;
Wojner, AW ;
Al-Senani, F ;
Burgin, S ;
Calleja, S ;
Campbell, M ;
Chen, CI ;
Chernyshev, O ;
Choi, J ;
El-Mitwalli, A ;
Felberg, R ;
Ford, S ;
Garami, Z ;
Irr, W ;
Grotta, J ;
Hall, C ;
Iguchi, Y ;
Ireland, J ;
Labiche, L ;
Malkoff, M ;
Morgenstern, L ;
Noser, E ;
Okon, N ;
Piriyawat, P ;
Robinson, D ;
Shaltoni, H ;
Shaw, S ;
Uchino, K ;
Yatsu, F ;
Alvarez-Sabín, J ;
Arenillas, JF ;
Huertas, R ;
Molina, C ;
Montaner, J ;
Ribó, M ;
Rubiera, M ;
Santamarina, E ;
Saqqur, M ;
Alchtar, N ;
O'Rourke, F .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (21) :2170-2178
[3]   Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy - Sonographic classification and short-term improvement [J].
Alexandrov, AV ;
Burgin, WS ;
Demchuk, AM ;
El-Mitwalli, A ;
Grotta, JC .
CIRCULATION, 2001, 103 (24) :2897-2902
[4]   Transcranial color duplex sonography in cerebrovascular disease: A systematic review [J].
Baumgartner, RW .
CEREBROVASCULAR DISEASES, 2003, 16 (01) :4-13
[5]   Transcranial ultrasound-improved thrombolysis: Diagnostic vs. therapeutic ultrasound [J].
Behrens, S ;
Spengos, K ;
Daffertshofer, M ;
Schroeck, H ;
Dempfle, CE ;
Hennerici, M .
ULTRASOUND IN MEDICINE AND BIOLOGY, 2001, 27 (12) :1683-1689
[6]   Transcranial Doppler ultrasound criteria for recanalization after thrombolysis for middle cerebral artery stroke [J].
Burgin, WS ;
Malkoff, M ;
Felberg, RA ;
Demchuk, AM ;
Christou, I ;
Grotta, JC ;
Alexandrov, AV .
STROKE, 2000, 31 (05) :1128-1132
[7]   Enhancement of enzymatic fibrinolysis with 2-MHz ultrasound and microbubbles [J].
Cintas, P ;
Nguyen, F ;
Boneu, B ;
Larrue, V .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2004, 2 (07) :1163-1166
[8]   Intracranial clot lysis with intravenous microbubbles and transcranial ultrasound in swine [J].
Culp, WC ;
Porter, TR ;
Lowery, J ;
Xie, F ;
Roberson, PK ;
Marky, L .
STROKE, 2004, 35 (10) :2407-2411
[9]   Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia - Increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator - Results of a phase II clinical trial [J].
Daffertshofer, M ;
Gass, A ;
Ringleb, P ;
Sitzer, M ;
Sliwka, U ;
Els, T ;
Sedlaczek, O ;
Koroshetz, WJ ;
Hennerici, MG .
STROKE, 2005, 36 (07) :1441-1446
[10]   Ultrasound in the treatment of ischaemic stroke [J].
Daffertshofer, M ;
Hennerici, M .
LANCET NEUROLOGY, 2003, 2 (05) :283-290