Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator.
OBJECTIVE
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.
Molina
Carlos A
CA
Department of Neurology, Universitat Autonoma de Barcelona, Hospital Vall d'Hebrón, Barcelona, Spain. cmolina@vhebron.net
Ribo
Marc
M
Rubiera
Marta
M
Montaner
Joan
J
Santamarina
Esteban
E
Delgado-Mederos
Raquel
R
Arenillas
Juan F
JF
Huertas
Rafael
R
Purroy
Francisco
F
Delgado
Pilar
P
Alvarez-Sabín
José
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000473:pathology; D016503:Drug Delivery Systems; D005260:Female; D005690:Galactose / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D045423:Microbubbles; D008875:Middle Aged; D010919:Placebos; D011994:Recombinant Proteins / Q000008:administration & dosage*; D020521:Stroke / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome; D014465:Ultrasonics; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods
D010919:Placebos; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; D005690:Galactose