Published Online
on November 30, 2006

A more recent version of this article appeared on January 1, 2007

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Submitted on August 14, 2006
Accepted on August 28, 2006

Clinical Deterioration After Intravenous Recombinant Tissue Plasminogen Activator Treatment. A Multicenter Transcranial Doppler Study

Maher Saqqur MD, FRPC^*; Carlos A. Molina MD; Abdul Salam Msc; Muzaffar Siddiqui MD, FRCPC; Marc Ribo MD; Ken Uchino MD; Sergio Calleja MD; Zsolt Garami MD; Khaurshid Khan MD, FRCPC; Naveed Akhtar MD; Finton O’Rourke; Ashfaq Shuaib MD, FRCPC; Andrew M. Demchuk MD, FRCPC; Andrei V. Alexandrov MD; for the CLOTBUST Investigators

From the Department of Medicine (Neurology) (M.S., A.S., M.S., K.K., N.A., F.O., A.S.), University of Alberta, Alberta, Canada; Vall d’Hebron Hospital (C.A.M.), Barcelona, Spain; the University of Texas-Houston Medical School (M.R., S.C., Z.G.), Houston, Texas; the University of Pittsburgh (K.U.), Pittsburgh, Pennsylvania; the Department of Clinical Neurosciences (A.M.D.), University of Calgary, Alberta, Canada; and Barrow Neurological Institute (A.V.A.), Phoenix, Arizona.

^* To whom correspondence should be addressed. E-mail: msaqqur{at}ualberta.ca.

Background and Purpose--Patients may experience clinical deterioration (CD) after treatment with intravenous recombinant tissue plasminogen activator (rt-PA). We evaluated the ability of flow findings on transcranial Doppler to predict CD and outcomes on modified Rankin Scale.

Methods--Patients with acute stroke received intravenous rt-PA within 3 hours of symptom onset at four academic centers. CD was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score by 4 points or more within 24 hours. Poor long-term outcome was defined by modified Rankin Scale 2 at 3 months. Transcranial Doppler findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion, or complete recanalization. Multiple regression analysis was used to identify transcranial Doppler flow as a predictor for CD after controlling for age, sex, baseline NIHSS, hypertension, and glucose.

Results--A total of 374 patients received intravenous rt-PA at 142±60 minutes (median pretreatment NIHSS score 16 points). At the end of intravenous rt-PA infusion, transcranial Doppler showed persistent arterial occlusion in 219 patients (59%), arterial reocclusion in 54 patients (14%), and complete recanalization in 101 patients (27%). CD occurred in 44 patients: 36 had persistent arterial occlusion or reocclusion (82%), 13 symptomatic intracerebral hemorrhage (29%), and both persistent occlusion/reocclusion and symptomatic intracerebral hemorrhage in 10 patients (23%). After adjustment, patient risk for CD with persistent occlusion was OR 1.7 (95% CI: 0.7 to 4) and with arterial reocclusion 4.9 (95% CI: 1.7 to 13) (P=0.002). Patient risk for poor long-term outcomes with persistent occlusion, partial recanalization, or reocclusion was OR 5.2 (95% CI: 2.7 to 9, P=0.001).

Conclusions--Inability to achieve or sustain vessel patency at the end of rt-PA infusion correlates with the likelihood of clinical deterioration and poor long-term outcome. Early arterial reocclusion on transcranial Doppler is highly predictive of CD and poor outcome.

Key words: acute stroke • diagnostic methods • outcome • transcranial Doppler • therapy • thrombolysis

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