scholarly journals Causes, Predictors, and Timing of Early Neurological Deterioration and Symptomatic Intracranial Hemorrhage After Administration of IV tPA

Author(s):  
Kavit Shah ◽  
Alexander Clark ◽  
Shashvat M. Desai ◽  
Ashutosh P. Jadhav
Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013049
Author(s):  
Aristeidis H Katsanos ◽  
Konark Malhotra ◽  
Niaz Ahmed ◽  
Georgios Seitidis ◽  
Eva A. Mistry ◽  
...  

Objective:To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO).Methods:A study was eligible if it enrolled AIS patients older than 18 years, with an LVO treated with either successful or unsuccessful EVT, and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed using a generalized linear mixed-effects model.Results:A total of 5874 patients (mean age: 69±14 years, 50% women, median NIHSS on admission: 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common OR=0.82, 95%CI:0.80-0.85; adjusted common OR=0.88, 95%CI:0.84-0.93) and modified Ranking Scale score≤2 (unadjusted OR=0.82, 95%CI:0.79-0.85; adjusted OR=0.87, 95%CI:0.82-0.93), and a higher odds of all-cause mortality (unadjusted OR=1.18, 95%CI:1.13-1.24; adjusted OR=1.15, 95%CI:1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurological deterioration (unadjusted OR=1.14, 95%CI:1.07-1.21; adjusted OR=1.14, 95%CI:1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR=1.20, 95%CI:1.09-1.29; adjusted OR=1.20, 95%CI:1.03-1.38) after EVT.Conclusion:Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurological deterioration, three-month mortality, and worse three-month functional outcomes.


2020 ◽  
Vol 26 ◽  
pp. 107602962090413 ◽  
Author(s):  
Ling-Shan Zhou ◽  
Xiao-Qiu Li ◽  
Zhong-He Zhou ◽  
Hui-Sheng Chen

There is a lack of studies on anticoagulant plus antiplatelet therapy for acute ischemic stroke. The present study made a pilot effort to investigate the efficacy and safety of argatroban plus dual antiplatelet therapy (DAPT) in patients with acute posterior circulation ischemic stroke (PCIS). We retrospectively collected patients diagnosed with acute PCIS according to inclusion/exclusion criteria. According to treatment drugs, patients were divided into an argatroban plus DAPT group and a DAPT group. The primary efficacy end point was the proportion of early neurological deterioration (END). The primary safety outcome was symptomatic intracranial hemorrhage. All outcomes were compared between the 2 groups before and after propensity score matching (PSM). A total of 502 patients were enrolled in the study, including 35 patients with argatroban plus DAPT and 467 patients with DAPT. There was a higher National Institutes of Health Stroke Scale (NIHSS) score in the argatroban plus DAPT group than the DAPT group before PSM (3 vs 2, P = .017). Compared with the DAPT group, the argatroban plus DAPT group had no END (before PSM: 0% vs 6.2%, P = .250; after PSM: 0% vs 5.9%, P = .298). Argatroban plus DAPT yielded a significant decrease in the NIHSS score from baseline to 7 days after hospitalization, compared with that of the DAPT group before PSM ( P = .032), but not after PSM ( P = .369). No symptomatic intracranial hemorrhage was found in any patient. A short-term combination of argatroban with DAPT appears safe in acute minor PCIS.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Christa D Brown ◽  
Gilda Avila-Rinek ◽  
Nerses Sanossian ◽  
Sidney Starkman ◽  
Scott Hamilton ◽  
...  

Background: Early neurological deterioration (END) is a feared complication of acute cerebral ischemia. However, estimates of END frequency vary widely, rates have not been systematically examined in hyperacute patients presenting within the first 2h of onset, nor separately in patients treated with and without thrombolysis, and risk factors for END have not been well delineated. Methods: We analyzed patients with a final diagnosis of acute cerebral ischemia in the NIH FAST-MAG Phase 3 multicenter clinical trial. END was defined as worsening post-admission by ≥ 4 NIHSS points up to Day 4. We separately analyzed patients who did and did not receive IV tPA. Results: Among 1245 acute cerebral ischemia patients transported by EMS to 55 stroke centers, time from last known well (LKW) to ED arrival was median 59 mins (IQR 80-46), and 36.1% received IV tPA. Overall, 211 (16.9%) experienced END by Day 4, with a greater proportion of END in tPA than non-tPA patients (21.2% vs 14.5%, p=0.003). In multivariate analysis, from 26 candidate variables, among tPA recipients, independent predictors of END were: age (OR 1.03/year, 95%CI 1.01-1.05), diastolic BP (OR 1.01/mm Hg, 95%CI 1.00-1.03), prior stroke (OR 1.65, 95%CI 0.98-2.77), glucose (OR 11.06/10 fold increase, 95%CI 1.90-64.44), and worse ASPECTS score (OR 0.85/point, 95%CI 0.78-0.92). Among non-tPA recipients, independent predictors of END were: more severe NIHSS (OR 1.08/point, 95%CI 1.05-1.11), glucose (OR 8.88/10 fold increase, 95%CI 1.83-43.12), and h/o hypertension (OR 2.62/mm Hg, 95%CI 1.25-5.48), with Akaike information criteria identifying SBP, shorter LKW-to-ED time, and absence of anticoagulant agents as additional contributors. C statistics for these models were 0.68 for tPA patients and 0.73 for non-tPA patients. Conclusions: Among hyperacute cerebral ischemia patients, END occurs in 1 in 5 who receive tPA, and 1 in 7 who do not receive tPA. Greater initial stroke severity (on neurologic exam or imaging), higher glucose, and hypertension increase risk of END for both lytic and non-lytic patients, with older age and prior stroke additionally increasing END risk with tPA. Models based on these risk factors show fair to good performance identifying patients who will experience END after hospital admission.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Jeffrey C Wagner ◽  
Alessandro Orlando ◽  
Christopher V Fanale ◽  
Michelle Whaley ◽  
Kathryn L McCarthy ◽  
...  

OBJECTIVE: To describe the 4-year symptomatic intracranial hemorrhage (sICH) rate at a high-volume comprehensive stroke center. METHODS: This was a retrospective observational cohort study. All admitted adult (≥18 years) patients presenting with an ischemic stroke (IS) from 2010 to 2013 were included in this study. Chi-square, Wilcoxon rank-sum, Student’s t-tests and Cochran-Armitage trend tests were used to compare groups and analyze data. sICHs were defined by a 4-point increase in NIHSS within 36h with new ICH seen on CT; sICHs were included only if they were directly related to IV-tPA treatment. Favorable mRS outcome was defined as a score ≤2. In-patient stroke alerts were excluded from door-to-needle (DTN) times. RESULTS: 2673 patients were admitted with IS. Of these, 627 (23%) were treated with IV-tPA (90% <3h from symptom onset, 69% at an outside facility). There was a significant increase in the percentage of IS patients treated with IV-tPA over the four years (p-trend=0.02). Compared to patients not receiving IV/IA therapy, patients receiving IV-tPA had significantly higher NIHSS scores, higher prevalence of atrial fibrillation, hyperlipidemia, and cardioembolic etiology, and lower proportion of small vessel occlusive IS. The median (IQR) DTN was 41m (32-53). In the 627 IS patients treated with IV-tPA, 11 (1.8%) developed a sICH; in 2013, the sICH rate was 0.6% (1/158). IV-tPA patients who developed a sICH were similar to those who were sICH-free; however, sICH patients had a significantly higher proportion of coronary artery disease (p=0.04) and severe strokes (p=0.19), and higher median symptom to arrival times (237m vs 187m, p=0.19), but similar median DTN (40m vs 41m, p=0.84). The in-hospital mortality rate for the IV-tPA group was 11% (n=71), and 37% had favorable mRS discharge scores. CONCLUSIONS: These data show that expeditious care and careful selection of patients for IV-tPA treatment can lead to very low rates of sICHs. The few sICHs subsequent to IV-tPA are likely to be a consequence of long symptom-to-arrival times and stroke severity.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Javaad Ahmad ◽  
Mohammed Hussain ◽  
Siddhart Mehta ◽  
Jaskiran Brar ◽  
Harina Chahal ◽  
...  

Background and Objective: It is considered unconventional to initiate antiplatelet regimen within 24 hours of IV tPa administration in acute ischemic strokes. There has been an increasing amount of literature assessing combination therapy of IV r- tPA and IV Eptifibatide in acute ischemic stroke. Our objectives were to evaluate the safety (hemorrhagic complications) and efficacy (discharge mRS) of administering IV Eptifibatide within the first 24 hours of receiving full dose IV r-tPA respectively. Materials and Methods: All patients that presented to our university affiliated stroke center from 2010-13 with an acute ischemic stroke were included and retrospectively classified into two groups. Group A underwent full dose IV r- tPa (.9 mg/kg) (+/- Endovascular intervention). Group B underwent full dose IV r-tPa (.9mg/kg) and IV Eptifibatide (+/- Endovascular intervention). Epitafibide was administered as a bolus of 135 mcg/kg IV followed by .5 mcg/kg/min for 20 hours. The primary endpoint of bleeding is classified as major (symptomatic intracranial hemorrhage or hemoglobin decrease by >5 mg/dl), minor (asymptomatic intracranial hemorrhage or hemoglobin decrease by 3-5 mg/dl) and insignificant as proposed by TIMI score. The efficacy endpoint was discharge mRS of 0-1 as favorable, with 2 and above being unfavorable. Results: We reviewed 2,016 patients with ischemic stroke, of which 170 received IV tPA. Among the group, 118 received IV r-tPa alone and 52 received combined modalities of IV r-tPa and IV Eptifibatide. In group A, there were 7 patients who had a major complication of symptomatic intracranial hemorrhage, while 1 patient had a minor complication of asymptomatic intracranial hemorrhage. In group B, there were 3 patients who had major complication of symptomatic intracranial hemorrhage and 5 with minor complications of asymptomatic intracranial hemorrhage. In group A , 9% (n=4) had a favorable outcome (OR=2.389, 95% CI 0.6645 to 8.589, p= 0.2217). Of the 52 patients in group B, 18% (n=8) had a favorable outcome. Conclusion: IV Eptifibatide, within the first 24 hours of ischemic stroke in combination with full dose IV r-tPA was found to be safe and efficacious. Further, larger prospective trials are needed to corroborate our findings.


Author(s):  
Shreyansh Shah ◽  
Li Liang ◽  
Andrzej Kosinski ◽  
Adrian F. Hernandez ◽  
Lee H. Schwamm ◽  
...  

Background Guidelines recommend against the use of intravenous tPA (tissue-type plasminogen activator; IV tPA) in acute ischemic stroke patients with prior ischemic stroke within 3 months. However, there are limited data on the safety of IV tPA in this population. Methods and Results A retrospective observational study of patients ≥66 years of age linked to Medicare claims and treated with IV tPA at Get With The Guidelines–Stroke hospitals (February 2009 to December 2015). We identified 293 patients treated with IV tPA who had a prior ischemic stroke within 3 months and 30 655 with no history of stroke. Patients with prior stroke had a higher stroke severity (median National Institutes of Health Stroke Scale, 11 [6–19] versus 11 [6–18]; absolute standardized difference, 11.2%) and a higher prevalence of cardiovascular comorbidities. Patients with prior stroke had a higher unadjusted risk for symptomatic intracranial hemorrhage (7.7% versus 4.8%) and in-hospital mortality (12.6% versus 8.9%), but these differences were not statistically significant after adjustment. When stratified by prespecified time epochs, the elevated risk for symptomatic intracranial hemorrhage was seen only within the first 14 days (16.3% versus 4.8%; adjusted odds ratio [aOR], 3.7 [95% CI, 1.62–8.43]) but not in other epochs (2.1% versus 4.8%; aOR, 0.38 [95% CI, 0.05–2.79] for 15–30 days and 7.4% versus 4.8%; aOR, 1.36 [95% CI, 0.77–2.40] for 31–90 days). In addition, patients with prior stroke were significantly more likely to have a combined outcome of in-hospital mortality or discharge to hospice (25.9% versus 17.0%; aOR, 1.70 [95% CI, 1.21–2.38]), less likely to be discharged to home (28.3% versus 32.3%; aOR, 0.72 [95% CI, 0.54–0.98]), or to have good functional outcomes at discharge (modified Rankin Scale, 0–1; 11.3% versus 20.0%; aOR, 0.46 [95% CI, 0.24–0.89]). Conclusions Stroke providers need to continue to be vigilant about the safety of IV tPA in patients with prior stroke, particularly those with an event in the previous 14 days.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Alexander Clark ◽  
Kavit Shah ◽  
Shashvat Desai ◽  
Ashutosh Jadhav

Introduction: Current guidelines recommend that patients given intravenous tPA (IV tPA) for acute ischemic stroke (AIS) receive comprehensive stroke care for 24 hours post-treatment to monitor key physiologic variables. 1,2,3 Early de-escalation of monitoring is likely feasible in a particular subset of patients, which may have implications in the post-COVID era. 4 In this study, we examined when patients with AIS are susceptible to early neurologic decline (END) and symptomatic intracranial hemorrhage (sICH) after IV tPA and whether those at low clinical risk of neurologic deterioration may be suitable for earlier transition to lower level of care. Methods: We performed a retrospective analysis of AIS receiving IV tPA based on AHA/ASA guidelines. We included those that presented within 4.5 hours of last seen well (LSW) without large vessel occlusion (LVO) or flow-limiting stenosis (FLS) on non-invasive angiographic imaging. Outcomes included END (≥4-point worsening of NIHSS at 24 hours) from any cause, parenchymal hemorrhage (PH1 or PH2), and/ or symptomatic intracranial hemorrhage (sICH; ≥4-point NIHSS worsening with presence of hemorrhage). Results: 1238 patients were included from 1/2013 - 6/2019. END and ICH occurred in 7.4% (91) and 9.4% (116), respectively. 63.7% of patients with END did not have ICH within 24 hours. In those with NIHSS <12, 82% had END within 12 hours and most occurred within 5 hours. Predictive factors included older patients (72.6 ±16.1 vs 69.1 ±14.8, p=0.03), history of tobacco use (OR-2.1 [1.1-4.3], p = 0.04) and hyperlipidemia (OR-1.7 [1.1-2.8] p = 0.02). ICH occurred within 12 hours in 30% of patients, predictors included older age (74.6 ± 12.4 vs 68.8 ± 15.1, p ≤ 0.01), higher NIHSS (14.6 ± 7.3 vs 10.8 ± 7.9, p ≤ 0.01), and higher presentation serum glucose levels (155.1 ± 87.5 vs 140.4 ± 70.5, p = 0.04). Overall, only 2.7% (33) of patients developed sICH. There were no independent predictive factors for delayed ICH (≥ 12 hours). Conclusion: In our selected post-IV tPA patients, a relatively small proportion suffered sICH and END; most often within 12 hours of tPA administration. These findings may support earlier de-escalation of higher acuity monitoring for clinically stable post-IV tPA patients.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Kristina Shkirkova ◽  
Gregory Wong ◽  
Julius Weng ◽  
Jeffrey L Saver ◽  
Sidney Starkman ◽  
...  

Background: The patterns and outcomes of deterioration during prehospital transport and the first phase of ED care are important for planning for design of prehospital intracranial hemorrhage (ICH) treatment trials. Methods: Patients were enrolled in the NIH Phase 3 Field Administration of Stroke Therapy - Magnesium (FAST-MAG) prehospital trial within 2h of last known well (LKW). Deterioration was defined as worsening by ≥2 on the Glasgow Coma Scale (GCS), performed serially by paramedics in the field, upon ED arrival, and after the early ED course Results: Among 213 patients with ICH, age was 65.4 (±13.4), 33.3% female. Times from LKW to GCS assessments were: paramedic, 23 mins (IQR 14-39); ED arrival, 57 mins (IQR 45-75); and after early ED course, 89 mins (IQR 65-107). Overall, 38.5% experienced neurological deterioration, including 12.7% in prehospital phase only, 12.2% in early ED phase only, and 10.3% in both. Granular patterns of deficit progression were: Prehospital Sustained - prehospital deterioration, then stable early ED phase, 6.1% (13); Dippers - prehospital deterioration, then early ED improvement, 6.6% (14); Delayed - stable prehospital, then ED deterioration, 12.2% (26); and Continuous - prehospital deterioration, then further deterioration in ED, 10.3% (22) (Figure). ICH patients who experienced any U-END had lower prehospital GCS scores, 15 (IQR 12-15) vs 15 (IQR 15-15), p<0.001, greater prehospital focal weakness, LAMS 4.4 vs 3.9, p<0.001, history of hypertension, 87.4% vs 74.9%, p<0.001, higher ED SBP, 186 vs 174, p<0.001, and larger ICH volume, 45.8 vs 21.8 cm 3 , p<0.001. U-END was associated with higher dependence or death (mRS 3-6) at 90d, 90.1% vs 61.6%, p<0.001. Conclusions: Ultra-early neurological deterioration occurs in more than one-third of EMS-transported ICH patients, is associated with elevated BP, and leads to unfavorable outcome. Clinical trials testing prehospital initiation of BP-lowering therapy for ICH are desirable.


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