Field Administration Of Stroke Therapy-Magnesium Research Articles

Modified Rankin Scale disability status at day 4 poststroke is an informative predictor of long-term day 90 outcome

BackgroundLong-term disability after stroke is standardly assessed 3 months post-onset, using the modified Rankin Scale (mRS). The value of an early, day 4 mRS assessment for projecting the 3-month disability outcome has not been formally investigated. MethodsIn this cohort of patients with acute cerebral ischemia and intracranial hemorrhage, we analyzed day 4 and day 90 mRS assessments in the NIH Field Administration of Stroke Therapy– Magnesium (FAST-MAG) Phase 3 trial. The performance of day 4 mRS, alone and as part of multivariate models, in predicting day 90 mRS was assessed using correlation coefficients, percent agreement, and the kappa statistics. ResultsAmong the 1573 acute cerebrovascular disease (ACVD) patients, 1206 (76.7%) had acute cerebral ischemia (ACI), while 367 (23.3%) had intracranial hemorrhage. Among all 1573 ACVD patients, day 4 mRS and day 90 mRS correlated strongly, Spearman's rho=0.79, in unadjusted analysis with weighted kappa of 0.59. For dichotomized outcomes, simple carry-forward of the day 4 mRS performed fairly well in agreeing with day 90 mRS: mRS 0-1 (kappa=0.67), 85.4%; mRS 0-2 (k=0.59), 79.5%; fatal outcome, 88% (k=0.33). Correlations of 4d and 90d mRS were stronger for ACI than ICH patients, 0.76 vs 0.71. ConclusionsIn this acute cerebrovascular disease patient cohort, assessment of global disability performed on day 4 is highly informative regarding long-term, 3-month mRS disability outcome, alone, and even more strongly in combination with baseline prognostic variables. The day 4 mRS is a useful measure for imputing the final patient disability outcome in clinical trials and quality improvement programs.

Abstract TP77: Stroke Rank Order Correlation but Moderate Absolute Value Drift Between Early Day 2/4 and Day 90 Stroke Outcome Scales: mRS, BI, and NIHSS

Background: In acute stroke trials, the three most commonly used outcome scales are the modified Rankin Scale (mRS) to assess global disability, the Barthel Index (BI) to assess instrumental activities of daily living, and the National Institutes of Health Stroke Scale (NIHSS) to assess neurologic deficit severity. The value of early scale assessments to forecast 3-month disability outcomes has not been formally investigated. Methods: In this cohort study of patients with acute ischemic stroke (AIS) in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial, we assessed the performance of day 2, 4, and 30, BI, and NIHSS to forecast their day 90 counterparts using correlation coefficients and absolute differences. Results: Among 1041 with AIS, mRS on d2 (r=0.67) and d4 (r=0.72) showed strong correlation and mRS on d30 (r=0.89) very strong correlation with d90 mRS. However, value shifts were common. For example, d4 mRS exactly matched d90 mRS in only 35.8%, while 40.2 % had better and 24 % had worse outcomes. D4 BI exactly matched d90 BI in only 41.2%, while 48.5% had better and 11.2% had worse outcomes. For NIHSS, d4 exactly matched d90 value in only 20.5%, while 57.9% had better and 22.6% had worse outcomes. (Figure) Conclusions: mRS, BI, and NIHSS outcomes as early as days 2 and 4 post-stroke correlate strongly with their longterm, 3m outcome rank ordering but only moderately with their absolute values. Delineation of this outcome trajectory provides a foundation for imputing final patient disability, ADL, and deficit outcomes in clinical trials and quality improvement programs.

Abstract 91: Patients With Intracranial Hemorrhage Have Greater Post-Stroke Mood Disturbance Than Those With Ischemic Stroke

Background: Patients with stroke frequently suffer from post-stroke mood disturbances (PSMD) which decrease their quality of life. It remains unclear whether the prevalence of PSMD differs according to stroke subtype. The aim of our study was to investigate PSMD incidence among stroke subtypes in the large, prospective Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Trial. Methods: In the publicly-available FAST-MAG database, we identified all patients with imaging-confirmed diagnoses of ischemic stroke (IS), transient ischemic attack (TIA), and intracerebral hemorrhage (ICH). Data on age, sex, NIHSS at presentation, stroke subtypes, and Stroke Impact Scale (SIS) 64 v3.0 at 90 days were collected. Differences in SIS Emotion Domain scores between IS, TIA, and ICH were assessed using the Mann-Witney U Test. Results: SIS Emotion Domain scores were available in 1239/1370 (90.4%) of patients. Mean age was 68.7 years (SD 13.4), and 41% were female. Median NIHSS was 7.0 (IQR 3-14). 65.3% had IS, 14.3% TIA, and 20.3% ICH. The preponderance of SIS-64 scores were patient-reported (86%) with the remainder completed by a patient proxy (14%). Emotion domain scores at 3 months were: lowest (most abnormal) in ICH patients (median 77.8, IQR 58.3-88.9); intermediate in IS patients (median 83.3, IQR 66.7-94.4); and highest in TIA patients (median 88.9, IQR 72.2-97.2), p<.01) (Figure). Neither age nor sex were strongly associated, but more abnormal mood scores were associated with greater presenting deficit severity (NIHSS 0-4: median SIS-64 mood score 88.9; NIHSS 5-14: 81.3; NIHSS ≥15: 75.0; Spearman’s rho: -0.30, p<.01). Conclusions: In this prospective study of a large population with broad enrollment criteria, mood disturbances at 90 days were most common among ICH patients and least common among TIA patients. Further work should investigate the driving factors of greater PSMD in patients with ICH compared to other patients with acute cerebrovascular disease.

Essential information for neurorecovery clinical trial design: trajectory of global disability in first 90 days post-stroke in patients discharged to acute rehabilitation facilities

BackgroundMany stroke recovery interventions are most beneficial when started 2-14d post-stroke, a time when patients become eligible for inpatient rehabilitation facilities (IRF) and neuroplasticity is often at its peak. Clinical trials focused on recovery need to expand the time from this plasticity to later outcome timepoints.MethodsThe disability course of patients with acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) enrolled in Field Administration of Stroke Therapy Magnesium (FAST-MAG) Trial with moderate-severe disability (modified Rankin Scale [mRS] 3–5) on post-stroke day4 who were discharged to IRF 2-14d post-stroke were analyzed.ResultsAmong 1422 patients, 446 (31.4%) were discharged to IRFs, including 23.6% within 2-14d and 7.8% beyond 14d. Patients with mRS 3–5 on day4 discharged to IRFs between 2-14d accounted for 21.7% (226/1041) of AIS patients and 28.9% (110/381) of ICH patients, (p < 0.001). Among these AIS patients, age was 69.8 (± 12.7), initial NIHSS median 8 (IQR 4–12), and day4 mRS = 3 in 16.4%, mRS = 4 in 50.0%, and mRS = 5 in 33.6%. Among these ICH patients, age was 62.4 (± 11.7), initial NIHSS median 9 (IQR 5–13), day 4 mRS = 3 in 9.4%, mRS = 4 in 45.3%, and mRS = 5 in 45.3% (p < 0.01 for AIS vs ICH). Between day4 to day90, mRS improved ≥ 1 levels in 72.6% of AIS patients vs 77.3% of ICH patients, p = 0.3. For AIS, mRS improved from mean 4.17 (± 0.7) to 2.84 (± 1.5); for ICH, mRS improved from mean 4.35 (± 0.7) to 2.75 (± 1.3). Patients discharged to IRF beyond day14 had less improvement on day90 mRS compared with patients discharged between 2-14d.ConclusionsIn this acute stroke cohort, nearly 1 in 4 patients with moderate-severe disability on post-stroke day4 were transferred to IRF within 2-14d post-stroke. ICH patients had nominally greater mean improvement on mRS day90 than AIS patients. This course delineation provides a roadmap for future rehabilitation intervention studies.

Aspirin for suspected stroke patients?

Journal of Paramedic PracticeVol. 15, No. 3 CommentAspirin for suspected stroke patients?Graham McClellandGraham McClellandEmail:E-mail Address: [email protected]Visiting Clinical Researcher, Newcastle University; Paramedic Research Fellow, North East Ambulance Service NHS Foundation Trust, Newcastle Upon Tyne, UKSearch for more papers by this authorGraham McClellandPublished Online:6 Mar 2023https://doi.org/10.12968/jpar.2023.15.3.98AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Bath PM, Woodhouse LJ, Krishnan K et al.. Prehospital Transdermal Glyceryl Trinitrate for Ultra-Acute Intracerebral Hemorrhage: data From the RIGHT-2 Trial. Stroke. 2019;50:3064–3071. Crossref, Google ScholarBerkowitz AL, Westover MB, Bianchi MT, Chou SH. Aspirin for acute stroke of unknown etiology in resource-limited settings: a decision analysis. Neurology. 2014;83:787–793. Crossref, Google ScholarChen ZM, Sandercock P, Pan HC et al.. Indications for early aspirin use in acute ischemic stroke: A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke. 2000;31:1240–1249. Crossref, Google ScholarNational Institute for Health and Care Excellence. Stroke and tranisent ischaemic attack in over 16s: diagnosis and initial management [NG128]. 2019. https://www.nice.org.uk/guidance/ng128/evidence/a-aspirin-pdf-6777399566 (accessed 22 February 2023) Google ScholarNational Institute for Health and Care Excellence.. Stroke and transient ischaemic attack in over 16s: diagnosis and initial management [NG128]. 2022. https://www.nice.org.uk/guidance/ng128 (accessed 22 February 2023) Google ScholarPrust ML, Saylor D, Zimba S et al.. Inpatient management of acute stroke of unknown type in resource-limited settings. Stroke. 2022;53:e108–e117. Crossref, Google ScholarQuaas J. Aspirin given immediately for a major heart attack (STEMI). 2009. https://www.thennt.com/nnt/aspirin-for-major-heart-attack/ (accessed 22 February 2023) Google ScholarRothwell PM, Algra A, Chen Z, Diener HC, Norrving B, Mehta Z. Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials. Lancet. 2016;388:365–375 Crossref, Google ScholarSaver JL, Eckstein M, Stratton S et al.. The field administration of stroke therapy - Magnesium (FAST-MAG) phase 3 trial: Primary results. Stroke. 2014;45. Google Scholar FiguresReferencesRelatedDetails 2 March 2023Volume 15Issue 3ISSN (print): 1759-1376ISSN (online): 2041-9457 Metrics History Published online 6 March 2023 Published in print 2 March 2023 Information© MA Healthcare LimitedPDF download

Abstract WMP35: Distinct Multivariate Models Predict 3 Month Disability Outcomes From Day 4 Modified Rankin Scale In Patients With Acute Cerebral Ischemia Vs Patients With Intracranial Hemorrhage

Background: Long-term disability after stroke is standardly assessed 3m post-onset, using the modified Rankin Scale (mRS), but clinical trial patients lost to follow-up require imputation of likely outcome. An early post-onset, e.g. day 4, mRS is often available but its utility to forecast outcome in ischemic and in hemorrhagic stroke patients has not been delineated. Methods: We analyzed all patients with acute cerebral ischemia (ACI) and with intracranial hemorrhage (ICH) enrolled in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial. The performance of ordinal day 4 mRS, alone and as part of multivariate models, in predicting ordinal day 90 mRS was assessed using Spearman correlation coefficients (r s ) and kappa (chance corrected agreement) statistics. Results: Among the 1206 acute cerebral ischemic patients, age was 70.9, 45.5 % were female, and initial NIHSS was 9.28 ± 8.28. In univariate analysis, day 4 mRS and day 90 mRS correlated strongly, r s = 0.76, weighted kappa = 0.71 increasing in multivariate analysis to r s = 0.78 and weighted kappa = 0.76 (Figure 1A). Among the 367 intracranial hemorrhage patients, age was 65.4, 32.7% were female, and initial NIHSS was 18.3 ± 11. In univariate analysis, day 4 mRS and day 90 mRS also correlated moderately r s = 0.64, weighted kappa = 0.63, increasing in multivariate analysis to r s = 0.81 and weighted kappa = 0.78 (Figure 1B). In the multivariate predictive models, day 4 mRS was the most determinative variable along with age and initial NIHSS for both ICH and ACI. Conclusion: For both acute cerebral ischemia and intracranial hemorrhage patients, long-term, 3m mRS disability outcomes can be predicted well using mRS assessment on day 4, alone and even more accurately in combination with baseline prognostic variables. Age and baseline NIHSS exert more additional influence on 3m mRS outcome in ICH than ACI, likely reflecting the better functional recovery among ICH than ACI stroke survivors.

Association Between Hyperacute Blood Pressure Variability and Hematoma Expansion After Intracerebral Hemorrhage: Secondary Analysis of the FAST-MAG Database.

Blood pressure variability (BPV) has emerged as a significant factor associated with clinical outcomes after intracerebral hemorrhage (ICH). Although hematoma expansion (HE) is associated with clinical outcomes, the relationship between BPVthat encompassesprehospital data and HE is unknown. We hypothesized that BPV was positively associated with HE. We analyzed 268 patients with primary ICH enrolled in the National Institutes of Health-funded Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study who received head computed tomography or magnetic resonance imaging on arrival to the emergency department (ED) and repeat imaging within 6-48h. BPV was calculated by standard deviation (SD) and coefficient of variation (CV) from prehospital data as well as systolic blood pressure (SBP) measurements taken on ED arrival, 15min post antihypertensive infusion start, 1h post maintenance infusion start, and 4h after ED arrival. HE was defined by hematoma volume expansion increase > 6mL or by 33%. Univariate logistic regression was used for presence of HE in quintiles of SD and CV of SBP for demographics and clinical characteristics. Of the 268 patients analyzed from the FAST-MAG study, 116 (43%) had HE. Proportions of patients with HE were not statistically significant in the higher quintiles of the SD and CV of SBP for either the hyperacute or the acute period. Presence of HE was significantly more common in patients on anticoagulation. Higher BPV was not found to be associated with occurrence of HE in the hyperacute or the acute period of spontaneous ICH. Further study is needed to determine the relationship.

Quantifying the amount of greater brain ischemia protection time with pre-hospital vs. in-hospital neuroprotective agent start.

The objective of this study is to quantify the increase in brain-under-protection time that may be achieved with pre-hospital compared with the post-arrival start of neuroprotective therapy among patients undergoing endovascular thrombectomy. In order to do this, a comparative analysis was performed of two randomized trials of neuroprotective agents: (1) pre-hospital strategy: Field administration of stroke therapy-magnesium (FAST–MAG) Trial; (2) in-hospital strategy: Efficacy and safety of nerinetide for the treatment of acute ischemic stroke (ESCAPE-NA1) Trial. In the FAST-MAG trial, among 1,041 acute ischemic stroke patients, 44 were treated with endovascular reperfusion therapy (ERT), including 32 treated with both intravenous thrombolysis and ERT and 12 treated with ERT alone. In the ESCAPE-NA1 trial, among 1,105 acute ischemic stroke patients, 659 were treated with both intravenous thrombolysis and ERT, and 446 were treated with ERT alone. The start of the neuroprotective agent was sooner after onset with pre-hospital vs. in-hospital start: 45 m (IQR 38–56) vs. 122 m. The neuroprotective agent in FAST–MAG was started 8 min prior to ED arrival compared with 64 min after arrival in ESCAPE–NA1. Projecting modern endovascular workflows to FAST–MAG, the total time of “brain under protection” (neuroprotective agent start to reperfusion) was greater with pre-hospital than in-hospital start: 94 m (IQR 90–98) vs. 22 m. Initiating a neuroprotective agent in the pre-hospital setting enables a faster treatment start, yielding 72 min additional brain protection time for patients with acute ischemic stroke. These findings provide support for the increased performance of ambulance-based, pre-hospital treatment trials in the development of neuroprotective stroke therapies.

Beyond the Golden Hour: Treating Acute Stroke in the Platinum 30 Minutes.

To emphasize treatment speed for time-sensitive conditions, emergency medicine has developed not only the concept of the golden hour, but also the platinum half-hour. Patients with acute stroke treated within the first half-hour of onset have not been previously characterized. In this cohort study, we analyzed patients enrolled in the FAST-MAG (Field Administration of Stroke Therapy-Magnesium) trial, testing paramedic prehospital start of neuroprotective agent ≤2 hours of onset. The features of all acute cerebral ischemia, and intracranial hemorrhage patients with treatment starting at ≤30 m of last known well were compared with later-treated patients. Among 1680 patients, 203 (12.1%) received study agents within 30 minutes of last known well. Among platinum half-hour patients, median onset-to-treatment time was 28 minutes (interquartile range, 25-30), and final diagnoses were acute cerebral ischemia in 71.8% (ischemic stroke, 61.5%, TIA 10.3%); intracranial hemorrhage in 26.1%; and mimic in 2.5%. Clinical features among platinum half-hour patients were largely similar to later-treated patients and included age 69 (interquartile range, 57-79), 44.8% women, prehospital Los Angeles Motor Scale median 4 (3-5), and early-postarrival National Institutes of Health Stroke Scale deficit 8 (interquartile range, 3-18). Platinum half-hour acute cerebral ischemia patients did have more severe prehospital motor deficits and younger age; platinum half-hour intracranial hemorrhage patients had more severe motor deficits, were more often female, and less often of Hispanic ethnicity. Outcomes at 3 m in platinum half-hour patients were comparable to later-treated patients and included freedom-from-disability (modified Rankin Scale score, 0-1) in 35.5%, functional independence (modified Rankin Scale score, 0-2) in 53.2%, and mortality in 17.7%. Prehospital initiation permits treatment start within the platinum half-hour after last known well in a substantial proportion of acute ischemic and hemorrhagic stroke patients, accounting for more than 1 in 10 enrolled in a multicenter trial. Hyperacute platinum half-hour patients were largely similar to later-treated patients and are an attainable target for treatment in prehospital stroke trials.

Magnesium Sulfate and Hematoma Expansion: An Ancillary Analysis of the FAST-MAG Randomized Trial.

Intracerebral hemorrhage (ICH) is the deadliest form of stroke. In observational studies, lower serum magnesium has been linked to more hematoma expansion (HE) and intracranial hemorrhage, implying that supplemental magnesium sulfate is a potential acute treatment for patients with ICH and could reduce HE. FAST-MAG (Field Administration of Stroke Therapy - Magnesium) was a clinical trial of magnesium sulfate started prehospital in patients with acute stroke within 2 hours of last known well enrolled. CT was not required prior to enrollment, and several hundred patients with acute ICH were enrolled. In this ancillary analysis, we assessed the effect of magnesium sulfate treatment upon HE in patients with acute ICH. We retrospectively analyzed data that were prospectively collected in the FAST-MAG study. Patients received intravenous magnesium sulfate or matched placebo within 2 hours of onset. We compared HE among patients allocated to intravenous magnesium sulfate or placebo with a Mann-Whitney U. We used the same method to compare neurological deficit severity (National Institutes of Health Stroke Scale) and global disability (modified Rankin Scale) at 3 months. Among 268 patients with ICH meeting study entry criteria, mean 65.4±13/4 years, 33% were female, and 211 (79%) had a history of hypertension. Initial deficit severities were median (interquartile range) of 4 (3-5) on the Los Angeles Motor Scale in the field and National Institutes of Health Stroke Scale score of 16 (9.5-25.5) early after hospital arrival. Follow-up brain imaging was performed a median of 17.1 (11.3-22.7) hours after first scan. The magnesium and placebo groups did not statistically differ in hematoma volume on arrival, 10.1 (5.6-28.7) versus 12.4 (5.6-28.7) mL (P=0.6), or HE, 2.0 (0.1-7.4) versus 1.5 (-0.2 to 8) mL (P=0.5). There was no difference in functional outcomes (modified Rankin Scale score of 3-6), 59% versus 50% (P=0.5). Magnesium sulfate did not reduce HE or improve functional outcomes at 90 days. A benefit for patients with initial hypomagnesemia was not addressed. URL: https://www. gov; Unique identifier: NCT00059332.

Abstract WP134: Association Between Hyperacute Blood Pressure Variability And Hematoma Expansion In Patients With Intracerebral Hemorrhage: Secondary Analysis Of The Field Administration Of Stroke Therapy - Magnesium Database

Background: Blood pressure variability (BPV) has emerged as a significant factor associated with clinical outcomes after intracerebral hemorrhage (ICH). While hematoma expansion (HE) is also associated with clinical outcomes, the relationship between BPV and HE has not been established. In this secondary database analysis, we aim to describe the association between BPV and HE. We hypothesized that BPV was positively associated with HE. Methods: Among 1,690 enrolled in the NIH-funded Field Administration of Stroke Therapy - Magnesium (FAST-MAG) study, 268 patients sustained ICH and received repeat CT or MRI head imaging within 6 to 48 hours of arrival. BPV was calculated by standard deviation (SD) and coefficient of variation (CV) of the hyperacute, prehospital data using the systolic blood pressure (SBP) measurements taken on ED arrival, 15min-post maintenance infusion start, 1-hour post maintenance infusion start, 4-hours after ED arrival. HE was defined by hematoma volume expansion greater than 6ml. Multivariate logistic regression was used for presence of HE in quintiles of SD and CV of SBP. Results: Of the 268 patients from the FAST-MAG study who had follow up head imaging, 116 (43%) had HE. Proportions of patients with HE was not statistically significant in the higher quintiles of the SD and CV of SBP for either hyperacute or acute period. Conclusions: HE was not found to be associated with higher quintiles of BPV using SD and CV of SBP in the hyperacute or the acute period. Expanded inclusion criteria or new statistical markers for BPV incorporating temporality for SBP could help in future studies.

Abstract TMP100: The Effect Of Prehospital Treatment With Magnesium On Symptomatic Hemorrhagic Transformation In Cerebral Ischemia

Introduction: Symptomatic hemorrhagic transformation (sHT) is a known complication of acute ischemic stroke and is associated with worse outcomes. Previously, low serum magnesium levels have been associated with higher rates of sHT. This study evaluated the effect of prehospital treatment with intravenous magnesium on rates of sHT. Methods: Subjects were participating in the NIH Field Administration of Stroke Therapy Magnesium (FAST-MAG) clinical trial. A total of 20 grams of magnesium or matching placebo was administered via 4 gram bolus in the field followed by 16 gram infusion over 24 hours. All subjects with cerebral ischemia were evaluated for the presence of symptomatic hemorrhagic transformation defined as an increase in NIHSS &gt;=4 points in the setting of imaging showing new hemorrhage within the ischemia territory. Results: A total of 1245 cases of cerebral ischemia were evaluated by paramedics on average 40 (SD 85) minutes and treated with magnesium or placebo on average 63 (SD 85) minutes after last known well time. Study population was age 71 (SD 18), 45% female, 78% white, 14% black, 8% Asian, 20% Hispanic ethnicity, 36% were treated with intravenous TPA, 78% hypertensive and 23% diabetic. Median NIHSS at ED arrival was 7 [IQR2-15]. There were 187 cases of clinical deterioration of which 43 were due to hemorrhagic transformation (3.4%). Rates of sHT were not statistically different in those who received magnesium vs. placebo (17/632 [2.7%] vs 26/613 [4.2%], p=0.134). Although HT was more common in TPA cases (6% vs 2%, p&lt;0.001), magnesium had no effect on sHT in this subgroup 5.3% vs 7.3%, p-0.399 Conclusions: Hyper-acute high-dose intravenous magnesium did not lead to a significant decrease in rates of sHT following acute ischemic stroke. It is possible that a subgroup with low baseline magnesium levels could have benefited.

Abstract TP5: Early Intubation Of Hyperacute Stroke Patients In The Emergency

Background: Stroke patients at times will present to the emergency department in unstable condition necessitating early intubation. Given the time-sensitive nature of thrombolysis for ischemic stroke, we sought to characterize the rates and predictors of intubation on ED arrival for hyperacute stroke patients transported by paramedics. Methods: Subjects were participating in the NIH Field Administration of Stroke Therapy Magnesium (FAST-MAG) clinical trial. Subjects were enrolled in the field ambulance within 2 hours of last known well and taken to their usual care emergency department. Early intubation was noted by study nurses on their initial NIHSS after ED arrival. Results: A total of 1700 cases were included, aged 69±13 years, 42.6% were women, median NIHSS on ED arrival was 9 [IQR 3-17], final diagnosis was cerebral ischemia in 73.3%, intracranial hemorrhage (ICH) in 22.8%, and a stroke-mimicking condition in 3.9%. The median time form last known to ED arrival was 59 minutes. Early ED intubation was more common in ICH compared to CI or mimic (18% vs. 1% vs. 3%, p&lt;0.001). Early intubation was associated with higher NIHSS [32 v 9]. The final diagnosis for both stroke mimic cases with early intubation was seizure. Among the 88 cases intubated early in the ED, there were 71 (81%) ICH, 15 (17%) ischemia and 2 (3%) mimics. Rates of TPA utilization in cerebral ischemia cases were 53% in the intubated group and 36% in the non-intubated group. Conclusion: Early intubation in the ED was more common in the ICH cases and occurred in only 1% of cerebral ischemia cases.

Quality of Acute Stroke Care at Primary Stroke Centers Before and After Certification in Comparison to Never-Certified Hospitals.

Background and Purpose: Primary stroke center (PSC) certification is associated with improvements in stroke care and outcome. However, these improvements may reflect a higher baseline level of care delivery in hospitals eventually achieving certification. This study examines whether advancements in acute stroke care at PSCs are due to certification or factors intrinsic to the hospital.Methods: Data was obtained from the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial with participation of 40 Emergency Medical System agencies, 315 ambulances, and 60 acute receiving hospitals in Los Angeles and Orange Counties. Subjects were transported to one of three types of destinations: PSC certified hospitals (PSCs), hospitals that were not PSCs at time of enrollment but would later become certified (pre-PSCs), and hospitals that would never be certified (non-PSCs). Metrics of acute stroke care quality included time arrival to imaging, use of intravenous tPA, and arrival to treatment.Results: Of 1,700 cases, 856(50%) were at certified PSCs, 529(31%) were at pre-PSCs, and 315 (19%) were at non-PSCs. Mean (SD) was 33min (±76.1) at PSCs, 47(±86.6) at pre-PSCs, and 49(±71.7) at non-PSCs. Of 1,223 cerebral ischemia cases, rate of tPA utilization was 43% at PSCs, 27% at pre-PSCs, and 28% at non-PSCs. Mean ED arrival to thrombolysis was 71(±32.7) at PSC, 98(±37.6) at pre-PSC, and 95(±45.0) at non-PSCs. PSCs had improved time to imaging (p = 0.014), percent tPA use (p < 0.001), and time to treatment (p = 0.003).Conclusions: Stroke care at hospitals prior to PSC certification is equivalent to care at non-PSCs.Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.

Paramedic Global Impression of Change During Prehospital Evaluation and Transport for Acute Stroke.

Background and Purpose- The prehospital setting is a promising site for therapeutic intervention in stroke, but current stroke screening tools do not account for the evolution of neurological symptoms in this early period. We developed and validated the Paramedic Global Impression of Change (PGIC) Scale in a large, prospective, randomized trial. Methods- In the prehospital FAST-MAG (Field Administration of Stroke Therapy-Magnesium) randomized trial conducted from 2005 to 2013, EMS providers were asked to complete the PGIC Scale (5-point Likert scale values: 1-much improved, 2-mildly improved, 3-unchanged, 4-mildly worsened, 5-much worsened) for neurological symptom change during transport for consecutive patients transported by ambulance within 2 hours of onset. We analyzed PGIC concurrent validity (compared with change in Glasgow Coma Scale, Los Angeles Motor Scale), convergent validity (compared with National Institutes of Health Stroke Scale severity measure performed in the emergency department), and predictive validity (of neurological deterioration after hospital arrival and of final 90-day functional outcome). We used PGIC to characterize differential prehospital course among stroke subtypes. Results- Paramedics completed the PGIC in 1691 of 1700 subjects (99.5%), among whom 635 (37.5%) had neurological deficit evolution (32% improvement, 5.5% worsening) during a median prehospital care period of 33 (IQR, 27-39) minutes. Improvement was associated with diagnosis of cerebral ischemia rather than intracranial hemorrhage, milder stroke deficits on emergency department arrival, and more frequent nondisabled and independent 3-month outcomes. Conversely, worsening on the PGIC was associated with intracranial hemorrhage, more severe neurological deficits on emergency department arrival, more frequent treatment with thrombolytic therapy, and poor disability outcome at 3 months. Conclusions- The PGIC scale is a simple, validated measure of prehospital patient course that has the potential to provide information useful to emergency department decision-making. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00059332.

Subject Retention in Prehospital Stroke Research Using a Telephone-Based Physician-Investigator Driven Enrollment Method

Background and Purpose: Subject retention into clinical trials is vital, and prehospital enrollment may be associated with higher rates of subject withdrawal than more traditional methods of enrollment. We describe rates of subject retention in a prehospital trial of acute stroke therapy. Methods: All subjects were enrolled into the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial. Paramedics screened eligible subjects and contacted the physician-investigator using a dedicated in-ambulance cellular phone. Physician-investigators obtained explicit informed consent from the subject or on-scene legally authorized representative (LAR) who reviewed and signed a consent form. Exception from informed consent (EFIC) was utilized in later stages of the study. Results: There were 1,700 subjects enrolled; 1,017 provided consent (60%), 662 were enrolled via LAR (39%), and 21 were enrolled via EFIC (1%). Of the 1,700 patients, 1,413 (83%) completed the 90-day visit, 265 (16%) died prior to the 90-day visit, and 22 (1.3%) withdrew from the study before completion. There were no differences in rates of withdrawal by method of study enrolment, i.e., self-consent (n = 14), 1.4%; LAR (n = 8), 1.2%; EFIC (n = 0) 0%. Conclusion: There was a high rate of retention when subjects were enrolled into prehospital stroke research using a phone-based method to obtain explicit consent.

Abstract TMP61: Enrolling Stroke Patients in Prehospital Research During Late Night and Early Morning Times

Background: Enrolling stroke patients into clinical research studies often necessitates having investigators available to field calls (from paramedics, potential subjects and ED personnel) as well as study nurses available at enrolment sites. Enrolment of patients overnight may thus not be cost effective if there are low numbers. Late night enrolment may have different characteristics such as more severe stroke or greater proportion of intracerebral hemorrhage. Methods: The Field Administration of Stroke Therapy-Magnesium (FAST-MAG) clinical trial enrolled patients 24 hours per day with designated on-call enrolling investigators and study nurses. We compared enrolment in the late night and early morning period defined as 10:00PM through 5:59AM compared to standard hours of 6:00AM through 9:59PM. We also considered implications of changing the late night/early morning definition to Midnight and 8:00AM. Results: Of 1700 enrolments, 171 (10%) occurred between 10PM-6AM. There was no significant differences in the late-night enrolments in stroke subtype (27% vs 22% ICH, p=0.268), age, ethnicity, race, vascular risk factors, prehospital stroke severity (LAMS) or hospital arrival stroke severity (NIHSS). Late night enrolments were less likely to be women (35% v 44%, p=0.035). There were 61 enrolments (3.4%) between midnight to 5:59AM. Expanding the early morning period from 6AM to 8AM would lead to 76 (4.4%) less enrollments. Conclusions: Late night/early morning enrolments are not clinically or demographically different from those during regular hours and accounted for 10% of overall enrolments. Less than 4% of enrolments occurred between midnight and 6:00AM. Future prehospital stroke trials can consider deferring enrolment in the late night/early morning period to help with resource allocation.

Abstract TP426: Description of Early Hematoma Expansion Trajectory and Rate of Expansion in Patients With Intracranial Hemorrhage

Introduction: Expansion of intracerebral hemorrhage (ICH) is associated with increased disability and mortality. The trajectory and rate of hematoma expansion (HE) have not been well described. We evaluated ultra-early baseline and follow up CT and MRI scans to describe the direction and rate of expansion. Methods: We analyzed consecutive ICH patients enrolled in the multicenter, NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) clinical trial with baseline and follow up imaging between 6 to 48 hours. HE was defined as growth more than 33% or more than 6mL. Topographic locations were determined using x-, y-, and z- coordinates on OsiriX software. Direction of HE was described by a change in coordinates and correlated with anatomic location. Hematoma growth (HG) rate was described as hematoma volume divided by symptoms onset to scan time in hours. HE rate was described as change in hematoma volume between initial and follow up imaging divided by the time lapse in hours. Results: There were 387 patients with intracerebral hemorrhage enrolled in the FAST-MAG clinical trial. 260 patients had initial and follow up imaging without undergoing hematoma evacuation. The median age was 64, 176 (66.7%) were male. 97 patients were on antiplatelets and 25 were on anticoagulation. Median SBP on admission was 178 and median DBP was 95. 80 (30.7%) patients demonstrated hematoma expansion. The most common location observed was the basal ganglia (69.6%). These hemorrhages tend to expand in all x-, y- and z- coordinates with the greatest change in z- expanding cortically through the corona radiata. There is a high rate of intraventricular hemorrhage (51.5%). Average HG rate was 18.09mL/hr (17.9) and the average HE rate was 1.37mL/hr (1.86). Interestingly, basal ganglia and thalamic hemorrhages had higher rates of expansion. Both HG rate and HE rate were influenced by changes in blood pressure and use of antiplatelets or anticoagulantion. Conclusion: Hematoma expansion location can be predicted based on the location of the initial hemorrhage location. Hematoma trajectory and HE rate can help predict poor outcomes in ICH.

Frequency, Predictors, and Outcomes of Prehospital and Early Postarrival Neurological Deterioration in Acute Stroke

Studies of neurological deterioration in stroke have focused on the subacute period, but stroke treatment is increasingly migrating to the prehospital setting, where the neurological course has not been well delineated. To describe the frequency, predictors, and outcomes of neurological deterioration among patients in the ultra-early period following ischemic stroke or intracranial hemorrhage. Exploratory analysis of the prehospital, randomized Field Administration of Stroke Therapy-Magnesium (FAST-MAG) Trial conducted from 2005 to 2013 within 315 ambulances and 60 stroke patient receiving hospitals in Southern California. Participants were consecutively enrolled patients with suspected acute stroke who were transported by ambulance within 2 hours of stroke onset. The main outcome was neurological deterioration, defined as a worsening of 2 or more points on the Glasgow Coma Scale (GCS), a level of consciousness scale ranging from 3 to 15, with higher scores indicating more alertness. Imaging outcomes were ischemic or hemorrhagic injury extent identified during the first brain imaging scan. Outcomes at 3 months included global disability level (assessed using the modified Rankin Scale [mRS]; range, 0-6, with higher numbers indicating greater disability) and mortality. Among the 1690 patients (99.4%), the mean (SD) age was 69.4 (13.5) years, and 43% were female. Final diagnoses were acute cerebral ischemia in 1237 patients (73.2%), intracranial hemorrhage in 386 patients (22.8%), and neurovascular mimic in 67 patients (4.0%). The median (interquartile range [IQR]) minutes between the last well-known time and GCS assessments were 23 (14-42) minutes for prehospital, 58 (46-79) minutes for ED arrival, and 149 (120-180) minutes for early ED course assessments. From prehospital to early postarrival, ultra-early neurological deterioration (U-END) occurred in 200 of 1690 patients (11.8%), more often among patients with intracranial hemorrhage than among those with acute cerebral ischemia (119 of 386 [30.8%] vs 75 of 1237 [6.1%], P < .001). Patterns of U-END were prehospital U-END without early recovery in 30 of 965 patients (3.1%), stable prehospital course but early ED deterioration in 49 of 965 patients (5.1%), and continuous deterioration in both prehospital and early ED phases in 27 of 965 patients (2.8%). Ultra-early neurological deterioration was associated with worse 3-month outcomes, including increased global disability (mRS score, 4.6 vs 2.4; P < .001), reduced functional independence (mRS score 0-2, 32 of 200 [16.0%] vs 844 of 1490 [56.6%]; P < .001), and increased mortality (87 of 200 [43.5%] vs 176 of 1490 [11.8%]; P < .001). Ultra-early neurological deterioration occurs in 1 in 8 ambulance-transported patients with acute cerebrovascular disease, including 1 in 3 patients with intracranial hemorrhage and 1 in 16 patients with acute cerebral ischemia, and is associated with markedly reduced functional independence and increased mortality. Averting U-END may be a target for future prehospital therapeutics. ClinicalTrials.gov Identifier: NCT00059332.

Abstract WP249: Speed of 911 Alarms and EMS Care in Hyperacute Intracranial Hemorrhage and Cerebral Ischemic Patients

Introduction: Among all stroke patients, intracranial hemorrhage (ICH) patients activate the 911 system sooner than cerebral ischemia (CI) patients. However, the temporal profiles of EMS alarm and response among hyperacute patients who may be enrolled in prehospital treatment trials has not been well delineated. Methods: We analyzed all final diagnosis acute cerebrovascular disease patients enrolled in the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) trial, in 315 ambulances transporting to 60 receiving stroke centers. Results: Among 1632 hyperacute cerebrovascular disease patients, final diagnosis was ICH in 23.7% and CI in 76.3%. Compared with CI patients, ICH patients were younger (65.3 vs 70.9, p &lt; 0.001), less often female (33.3% vs 45.3%, p&lt;0.001), and had greater deficits in the field (LAMS 4.1 vs 3.7, p&lt;0.001), and upon ED arrival (NIHSS median 12 vs 7, p&lt;0.001). Intervals from last known well to 911 call (LKW-to-alarm) did not differ between ICH and ACI patients (median 15 vs 16 mins, p=0.32); however, fewer ICH patients had prolonged LKW-to-alarm times ≥ 30 mins (25.1% vs 30.3%, p = .049). Intervals from symptoms first observed to 911 call (SFO-to-alarm) did not differ (11 vs 12 mins, p=0.40). Times from 911 call to paramedic arrival (alarm-to-on patient) were similar for ICH and CI patients (median 6 vs 6 mins, p=0.80), as were times from paramedic arrival on patient to ED arrival (scene-to-door) (median 32 vs 33 mins, p=0.46) and overall 911 call to ED arrival (alarm-to-door) (median 39 vs 39 mins, p=0.51). The nationally recommended alarm-to-on patient interval ≤ 8 minutes was achieved in 76% of ICH and 78% of CI patients. Conclusion: Speed of prehospital care is swift among hyperacute cerebrovascular disease patients, including 911 calls at 15 minutes after last known well, paramedic arrival on patient 6 minutes after 911 activation, and ED arrival 39 minutes after 911 activation. In the hyperacute window, ICH patients call 911 only slightly faster than ACI patients, and subsequent prehospital intervals of care are similar. In a busy metropolitan region, national alarm-to-on patient time targets were achieved in more than three-quarters of patients.