Safety of high doses of urokinase and reteplase for acute ischemic stroke.

BACKGROUND AND PURPOSE: ET is considered in selected patients with AIS with persistent arterial occlusion after receiving IVT. Limited data exist on the safety of IA high doses of UK and RT for ET. We investigated any correlation between IA doses of UK or RT and safety outcomes in patients who underwent ET. MATERIALS AND METHODS: We identified all patients from our stroke registry who received UK or RT for ET from 1998 to 2008. Demographics, baseline National Institutes of Health Stroke Scale scores, recanalization rates, rates of attempted MT, mortality, SICH, and discharge modified Rankin Scale scores were collected. RESULTS: Of 197 patients; 72 received UK and 125 received RT. More than 90% of patients in both groups had received prior IVT. The median IA dose of UK was 200,000 U (range, 25,000-1,500,000 U) and of RT was 2 mg (range, 1-8 mg). Concurrent MT was attempted in 59.7% of UK-treated patients and 72.0% of RT-treated patients, with SICH rates of 4.2% and 8.0%, respectively. Logistic regression adjusting for prior IVT and MT revealed no correlation between SICH and doses of UK (OR, 1.00; 95% CI, 0.99-1.00; P = .94) or RT (OR, 0.803; 95% CI, 0.48-1.33; P = .39). There was no correlation between mortality and doses of UK (OR, 1.00; 95% CI, 0.99-1.00; P = .51) or RT (OR, 1.048; 95% CI, 0.77-1.42; P = .75). CONCLUSIONS: High IA doses of UK and RT may be safe when given with or without MT in patients with AIS despite receiving a full dose of intravenous recombinant tissue plasminogen activator. These results need prospective validation.

Intraventricular hemorrhage: Anatomic relationships and clinical implications.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is frequently associated with intraventricular hemorrhage (IVH), which is an independent predictor of poor outcome. The purpose of this study was to examine the relationship between ICH volume and anatomic location to IVH, and to determine if ICH decompression into the ventricle is truly beneficial. METHODS: We retrospectively analyzed the CT scans and charts of all patients with ICH admitted to our stroke center over a 3-year period. Outcome data were collected using our prospective stroke registry. RESULTS: We identified 406 patients with ICH. A total of 45% had IVH. Thalamic and caudate locations had the highest IVH frequency (69% and 100%). ICH volume and ICH location were predictors of IVH (p < 0.001). Within each location, decompression ranges (specific volume ranges where ventricular rupture tends to occur) were established. Patients with IVH were twice as likely to have a poor outcome (discharge modified Rankin scale of 4 to 6) (OR 2.25, p = 0.001) when compared to patients without IVH. Caudate location was associated with a good outcome despite 100% incidence of IVH. Spontaneous ventricular decompression was not associated with better outcome, regardless of parenchymal volume reduction (p = 0.72). CONCLUSIONS: Intraventricular hemorrhage (IVH) occurs in nearly half of patients with spontaneous intracerebral hemorrhage (ICH) and is related to ICH volume and location. IVH is likely to occur within the "decompression ranges" that take into account both ICH location and volume. Further, spontaneous ventricular decompression does not translate to better clinical outcome. This information may prove useful for future ICH trials, and to the clinician communicating with patients and families.

Early care limitations independently predict mortality after intracerebral hemorrhage.

OBJECTIVE: Intracerebral hemorrhage (ICH) is associated with a high early mortality rate. We examined the impact of early do not resuscitate (DNR) orders and other limitations in aggressive care on mortality after ICH in a community-based study. METHODS: Cases of spontaneous ICH from 2000 to 2003 were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project, with deaths ascertained through 2005. Charts were reviewed for early (<24 hours from presentation) DNR orders, withdrawal of care, or deferral of other life sustaining interventions, analyzed together as combined DNR (C-DNR). Multivariable Cox-proportional hazards models were used to examine the association between short- and long-term all-cause mortality and early C-DNR, adjusted for demographics and established predictors of mortality after ICH. RESULTS: Of 18,393 subjects screened for cerebrovascular disease, 270 non-traumatic ICH cases were included. Cumulative mortality risk was 0.43 at 30 days and 0.55 over the study course. Early C-DNR was noted in 34% of cases and was associated with a doubling in the hazard of death both at 30 days (hazard ratio [HR] 2.17, 95% CI 1.38, 3.41) and at end of follow-up (HR 1.92, 95% CI 1.29, 2.87) despite adjustment for age, gender, ethnicity, Glasgow Coma Scale, ICH volume, intraventricular hemorrhage, and infratentorial hemorrhage. CONCLUSIONS: Early care limitations are independently associated with both short- and long-term all-cause mortality after intracerebral hemorrhage (ICH) despite adjustment for expected predictors of ICH mortality. Physicians should carefully consider the effect of early limitations in aggressive care to avoid limiting care for patients who may survive their acute illness.

Myocardial injury in patients with intracerebral hemorrhage treated with recombinant factor VIIa.

We report myocardial injury in 20 recombinant factor VIIa (rFVIIa) treated and 110 nontreated patients with intracerebral hemorrhage. Patients were treated or received standard medical management. All received EKG and cardiac enzyme testing. Elevated troponin occurred in 20% treated vs 3% nontreated (p = 0.02). Myocardial infarction occurred in 10% vs 1% (p = 0.01). We found a significant increase in myocardial injury in rFVIIa treated patients.

Intra-arterial reteplase compared to urokinase for thrombolytic recanalization in acute ischemic stroke.

BACKGROUND AND PURPOSE: Reteplase (RP) and urokinase (UK) are being used "off-label" to treat acute ischemic stroke. The safety and efficacy of intra-arterial RP or UK in the treatment of acute ischemic stroke, however, has yet to be proved. We aim to evaluate the safety and efficacy of RP compared with UK in acute ischemic stroke patients with large vessel occlusion. METHODS: Retrospective analysis was conducted of cases from a prospectively collected stroke data base on consecutive acute ischemic stroke patients with large vessel occlusion by digital subtraction angiography treated with intra-arterial RP or UK. Thrombolytic dosage, recanalization rate, intracerebral hemorrhage (ICH), mortality, and outcome were determined. RESULTS: Thirty-three patients received RP and 22 received UK (mean doses, 2.5 +/- 1.4 mg and 690,000 +/- 562,000 U, respectively). Vascular occlusions included 9 basilar arteries (BAs), 7 internal carotid arteries (ICAs), and 17 middle cerebral arteries (MCAs) with RP and 9 BAs, 4 ICAs, and 9 MCAs with UK. Median baseline National Institutes of Health Stroke Scales were as follows: 16 (range, 5-25; 81% > or = 10) with RP and 17 (range, 6-38; 85% > or =10) with UK. Mean time from symptom onset to thrombolytic initiation: 333 +/- 230 minutes with RP and 343 +/- 169 minutes with UK. Recanalization rates were as follows: 82% with RP and 64% with UK (P = .13). Symptomatic ICH rates were as follows: 12% with RP and 4.5% with UK (P = .50). The mortality rate was 24% with RP and 27% with UK (P = .8). CONCLUSION: Although limited in statistical power, our study suggests that, although IA thrombolysis with RP shows a trend for higher recanalization rates and hemorrhage rates, IA thrombolysis with RP is not significantly different in recanalization, outcome, mortality, and ICH compared with that of UK or rates reported with IA pro-UK.

Presentation of intracerebral haemorrhage in a community.

BACKGROUND: Studies on intracerebral haemorrhage (ICH) from tertiary care centres may not be an accurate representation of the true spectrum of disease presentation. OBJECTIVE: To describe the clinical and imaging presentation of ICH in a community devoid of the referral bias of an academic medical centre; and to investigate factors associated with lower Glasgow coma scale (GCS) score at presentation, as GCS is crucial to early clinical decision making. METHODS: The study formed part of the BASIC project (Brain Attack Surveillance in Corpus Christi), a population based stroke surveillance study in a bi-ethnic Texas community. Cases of first non-traumatic ICH were identified from years 2000 to 2003, using active and passive surveillance. Clinical data were collected from medical records by trained abstractors, and all computed tomography (CT) scans were reviewed by a study physician. Multivariable linear regression was used to identify clinical and CT predictors of a lower GCS score. RESULTS: 260 cases of non-traumatic ICH were identified. Median ICH volume was 11 ml (interquartile range 3 to 36) with hydrocephalus noted in 45%. Median initial GCS score was 12.5 (7 to 15). Hydrocephalus score (p = 0.0014), ambient cistern effacement (p = 0.0002), ICH volume (p = 0.014), and female sex (p = 0.024) were independently associated with lower GCS score at presentation, adjusting for other variables. CONCLUSIONS: ICH has a wide range of severity at presentation. Hydrocephalus is a potentially reversible cause of a lower GCS score. Since early withdrawal of care decisions are often based on initial GCS, recognition of the important influence of hydrocephalus on GCS is warranted before withdrawal of care decisions are made.

Differences in intracerebral hemorrhage between Mexican Americans and non-Hispanic whites.

BACKGROUND: Mexican Americans (MAs) have higher incidence rates of intracerebral hemorrhage (ICH) than non-Hispanic whites (NHWs). The authors present clinical and imaging characteristics of ICH in MAs and NHWs in a population-based study. METHODS: This work is part of the Brain Attack Surveillance in Corpus Christi (BASIC) project. Cases of nontraumatic ICH were identified from 2000 to 2003. Multivariable logistic regression was used to assess the independent associations between ethnicity and ICH location (lobar vs nonlobar) and volume (> or = 30 vs < 30 mL), adjusting for demographics and baseline clinical characteristics. Logistic regression was also used to determine the association between ethnicity and in-hospital mortality, adjusting for confounders. RESULTS: A total of 149 MAs and 111 NHWs with ICH were identified. MAs were younger (70 vs 77, p < 0.001), more often male (55% vs 42%, p = 0.04), had a lower prevalence of atrial fibrillation (2.0% vs 13%, p < 0.001), and a higher prevalence of diabetes (39% vs 19%, p < 0.001). MA ethnicity was independently associated with nonlobar hemorrhage (OR 2.08, 95% CI: 1.15, 3.70). MAs had over two times the odds of having small (< 30 mL) hemorrhages compared with NHWs (OR = 2.41, 95% CI: 1.31, 4.46). NHWs had higher in-hospital mortality, though this association was no longer significant after adjustment for ICH volume, location, age, and sex. CONCLUSIONS: There are significant differences in the characteristics of ICH in MAs and NHWs, with MA patients more likely to have smaller, nonlobar hemorrhages. These differences may be used to examine the underlying pathophysiology of ICH.