Intravenous Tissue Plasminogen Activator in Patients With Cocaine-Associated Acute Ischemic Stroke
Background and Purpose— The safety of thrombolytic therapy in patients with cocaine-associated acute ischemic stroke (CIS) is unknown.
Methods— We conducted a retrospective review of patients with CIS who presented to our stroke center. Thrombolytic treatment was compared between cocaine-positive (n=29) and cocaine-negative (n=75) patients. We also compared patients with CIS treated with tissue plasminogen activator versus those who did not receive tissue plasminogen activator (n=58). Safety outcomes were determined by the incidence of symptomatic intracerebral hemorrhage, in-hospital mortality, and modified Rankin Scale at hospital discharge.
Results— There were no complications in tissue plasminogen activator-treated patients with CIS. Cocaine-positive and cocaine-negative treated patients had similar stroke severity and safety outcomes. Patients with CIS treated with tissue plasminogen activator had more severe strokes on baseline National Institutes of Health Stroke Scale but similar safety outcomes compared with nontreated patients with CIS.
Conclusion— Thrombolytic therapy for CIS appears to be safe in this small study. Further research is needed to more definitively assess safety and efficacy of tissue plasminogen activator for CIS.
Cocaine causes acute cerebrovascular disorders such as ischemic stroke and intracranial hemorrhage.1,2⇓ The potential mechanisms of acute ischemic stroke associated with cocaine (CIS) include arrhythmias, cardiomyopathies, septic emboli from endocarditis in intravenous drug abusers, promotion of a prothrombotic state,3 postmyocardial infarction-related thromboembolism, vasospasm, and vasculitis.4 Several of these mechanisms may pose an increased risk for intracerebral hemorrhage (ICH) after intravenous tissue plasminogen activator (tPA). Cocaine causes acute hypertension, which may also pose an increased risk of ICH after intravenous tPA. Indeed, ICH has been reported to occur in patients with cocaine-associated acute coronary syndromes treated with thrombolytics.5 Given these concerns, physicians are recommended to exercise caution in considering the use of intravenous tPA for CIS6 in the absence of any published data. We therefore retrospectively analyzed a consecutive series of prospectively collected patients with CIS treated with tPA and compared their safety and outcomes with toxicology-proven cocaine-negative patients who received tPA within 3 hours of symptom onset. We also compared the safety and outcome of patients with CIS treated with tPA versus those who did not receive tPA.
A retrospective chart review was performed of prospectively collected data of patients admitted to our stroke service during 2004 to 2007 who were identified as having recent cocaine exposure confirmed by a positive urine toxicology screen for the cocaine metabolite, benzoylecgonine. Baseline demographics, admission vital signs, National Institutes of Health Stroke Scale (NIHSS) scores, neuroimaging, creatinine kinase, troponin, and glucose were obtained. We also obtained intravenous tPA use, hemorrhagic transformation, symptomatic ICH (sICH), discharge disposition, and modified Rankin Scale (mRS) scores on discharge. Symptomatic ICH was defined as a parenchymal hematoma (PH-1 or PH-2) with an increase in the NIHSS of ≥4 points. Asymptomatic ICH was defined as any other hemorrhagic infarction. Favorable outcome was defined as discharge mRS score ≤2. Favorable disposition was defined as inpatient rehabilitation or home. We compared patients with CIS who received intravenous tPA within 3 hours of symptom onset versus patients who received intravenous tPA during the same time period but had no detectable cocaine metabolites on urine drug screening. Our center has no formal policy on selection of patients for toxicology screening. In addition, we compared patients with CIS who were treated and not treated with intravenous tPA. For statistical analysis, categorical variables were compared using χ2 or Fisher exact tests where appropriate. Continuous variables were compared using 2-sample t tests or Mann-Whitney U tests where appropriate.
We identified 87 patients who had CIS (median age, 48 years; 71% male and 69% black). The median NIHSS at presentation was 7 (range, 0 to 40). Favorable outcome was seen in 46 patients (57%).
Intravenous tPA was administered in 29 patients with CIS (33.3%) and in 75 patients with a negative urine cocaine study (Table 1). Cocaine users were younger and more frequently male. Cocaine users had higher initial diastolic blood pressure and lower glucose levels. Cocaine users had higher creatine kinase levels, but there were no statistical differences in CK-MB or troponin. Patients in both groups had similar baseline NIHSS. There were no significant differences in safety or outcome (hemorrhagic transformation, sICH, mRS at discharge, discharge disposition, or mortality) regardless of whether the patients used cocaine.
Patients with CIS treated with intravenous tPA had significantly higher median NIHSS scores compared with those patients who did not receive tPA (Table 2). Despite the increased stroke severity, the rates of sICH, mortality, favorable disposition, and favorable mRS at the time of discharge were similar between tPA- and non-tPA-treated groups. Finally, we also report stroke etiologies between cocaine-positive and cocaine-negative patients (Table 3). We found a difference in the distribution of Trial of Org 10172 in Acute Treatment classifications among patients with acute ischemic stroke based on cocaine exposure (Fisher exact=0.016).
Cocaine is a well-known precipitant of ischemic stroke1,4⇓ and there is concern cocaine may pose an enhanced risk for ICH after tPA.5 Although the safety of tPA in the setting of CIS is unknown, the short time window to administer tPA within 3 hours of acute ischemic stroke onset may make determining the presence of cocaine unfeasible. We report the largest series of patients with CIS to our knowledge and treated with tPA and find that there were no events of sICH after tPA. Compared with cocaine-negative patients who received tPA, mortality was lower in the cocaine-positive tPA-treated patients; however, this difference was not statistically significant. Both cocaine-positive and cocaine-negative treated patients had similar outcomes at hospital discharge. Diastolic blood pressures were higher in the cocaine-positive group compared with the cocaine-negative group. However, all patients treated with tPA met American Heart Association blood pressure guidelines for thrombolysis and did not experience acute spikes in blood pressure during or after tPA infusion. Moreover, despite having more severe deficits, patients with CIS who received tPA did not have significant differences in sICH or mortality compared with those patients with CIS who did not receive tPA. Interestingly, it has been suggested that long-term cognitive impairment in cocaine users is the result of diffuse cerebral small vessel disease.7 Such patients might therefore be at increased risk for intracerebral hemorrhage; although we did find an increased incidence of small vessel disease in cocaine-positive patients, we did not see an increased risk of sICH in this population.
This study has several limitations, including its retrospective approach and small sample number. Although we report a large series of patients, this retrospective study is not powered to detect significant differences in sICH. Accordingly, the results must be interpreted with caution given that the outcomes of tPA-treated patients may be different if a substantially higher number of patients with CIS were studied. There is a selection bias in designing a “cocaine-negative” patient group because not all patients on our stroke service undergo a toxicology screen, and older patients with vascular risk factors can have positive toxicology studies.8 Finally, the standard urine toxicology screen for the cocaine metabolite used at our hospital tests positive for 3 days after cocaine use. Therefore, this study does not rule out the possibility that acutely intoxicated patients may have a worse outcome after tPA administration.
In conclusion, the results from this study suggest that tPA may be safe to administer in CIS and that early outcomes after CIS do not appear to be adversely affected by tPA. Often, in an emergency department setting, physicians do not know if a patient with acute ischemic stroke was using cocaine because the toxicology screen may not return in time to consider intravenous tPA. We provide preliminary evidence that intravenous tPA could be used in this patient population, but further studies are needed to more definitively determine the safety and efficacy of intravenous tPA for patients with CIS.
Sources of Funding
This work was supported by American Heart Association Award 0475008N (S.I.S.), National Institutes of Health training grant T32NS04712, and P50 NS044227.
- Received June 8, 2009.
- Revision received July 16, 2009.
- Accepted July 21, 2009.
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- ↵McCord J, Jneid H, Hollander JE, de Lemos JA, Cercek B, Hsue P, Gibler WB, Ohman EM, Drew B, Philippides G, Newby LK. Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Circulation. 2008; 117: 1897–1907.
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