- Email: [email protected]
A Stroke Alert Protocol Decreases the Time to Diagnosis of Brain Attack Symptoms in a Pediatric Emergency Department
ORIGINAL ARTICLES A Stroke Alert Protocol Decreases the Time to Diagnosis of Brain Attack Symptoms in a Pediatric Emergency Department Dana B. Harrar, MD, PhD1,2,a, Catherine L. Salussolia, MD, PhD1, Kush Kapur, PhD1, Amy Danehy, MD2,3, Monica E. Kleinman, MD4, Rebekah Mannix, MD5, and Michael J. Rivkin, MD1,2,3,6 Objective To determine whether a stroke alert system decreases the time to diagnosis of children presenting to the emergency department (ED) with acute-onset focal neurologic deficits. Study design We performed a retrospective comparison of clinical and demographic information for patients who presented to the ED of a tertiary children’s hospital with acute-onset focal neurologic deficits during the 2.5 years before (n = 14) and after (n = 65) the implementation of a stroke alert system. The primary outcome was the median time to neuroimaging analyzed using a Wilcoxon rank-sum test. Results The median time from ED arrival to neuroimaging for patients with acute-onset focal neurologic deficits decreased significantly after implementation of a stroke alert system (196 minutes; IQR, 85-230 minutes before [n = 14] vs 82 minutes; IQR, 54-123 minutes after [n = 65]; P < .01). Potential intravenous tissue plasminogen activator candidates experienced the shortest time to neuroimaging after implementation of a stroke alert system (54 minutes; IQR, 34-66 minutes [n = 13] for intravenous tissue plasminogen activator candidates vs 89.5 minutes; IQR, 62-126.5 minutes [n = 52] for non-intravenous tissue plasminogen activator candidates; P < .01). Conclusions A stroke alert system decreases the median time to diagnosis by neuroimaging of children presenting to the ED with acute-onset focal neurologic deficits by more than one-half. Such a protocol constitutes an important step in ensuring that a greater proportion of children with arterial ischemic stroke are diagnosed in a time frame that enables hyperacute treatment. (J Pediatr 2019;-:1-6).
H
yperacute therapies, including intravenous tissue plasminogen activator (IV-tPA) and mechanical thrombectomy, have revolutionized the care of adults with arterial ischemic stroke (AIS). Increasingly, children with AIS are also being treated successfully with IV-tPA and mechanical thrombectomy.1-6 The implementation of hyperacute therapies requires the timely identification of stroke, which has historically proved challenging in children; the median time from symptom onset to diagnosis of AIS in children is more than 20 hours.7-12 A delay in diagnosis, coupled with the apparent safety and efficacy of IV-tPA in children, prompted 23 pediatric centers in North America to develop multidisciplinary stroke teams capable of emergent, around-the-clock response to patients with acute-onset focal neurologic deficits,13,14 otherwise known as brain attack symptoms.15,16 Shack et al12 reported a variable impact of a stroke alert system on the time to diagnosis of children with AIS occurring in the preceding 14 days. In that study, in which only one-half to three-quarters of patients presented with acute onset focal neurologic deficits, implementation of a stroke alert protocol led to a reduction in the in-hospital component of the delay in the time to diagnosis for children with AIS presenting with mild symptoms; however, the in-hospital delay in the time to diagnosis for all children with AIS was unchanged. Because Shack et al considered children with AIS presenting as many as 14 days from symptom onset, it remains unknown whether the establishment of a pediatric stroke alert protocol decreases the time to diagnosis of children with acute-onset focal neurologic deficits who present within a time frame from symptom onset that makes them eligible for treatment with hyperacute therapies. We aimed to determine whether a stroke alert system at a tertiary care pediatric hospital decreases the time to diagnosis of patients presenting to the emergency department (ED) with acute-onset focal neurologic deficits.
Methods We conducted a retrospective review of the medical records of patients who presented to the ED of a free-standing tertiary children’s hospital with acute-onset focal neurologic deficits during the 2.5 years before and after the implementation
From the 1Department of Neurology, 2Stroke and Cerebrovascular Center, 3Department of Radiology, Boston Children’s Hospital, 4Department of Anesthesiology, Critical Care, and Pain Medicine, 5 Division of Emergency Medicine, and 6Department of Psychiatry, Boston Children’s Hospital, Boston, MA a
AIS ED IV-tPA MRA MRI PedNIHSS
Arterial ischemic stroke Emergency department Intravenous tissue plasminogen activator Magnetic resonance angiography Magnetic resonance imaging Pediatric National Institutes of Health Stroke Scale
Present address: Division of Neurology, Children’s National Hospital, Washington, DC. The authors declare no conflicts of interest. Portions of this study were presented as a poster at the European Stroke Organisation Conference, May 16-18, 2018, Gothenburg, Sweden.
0022-3476/$ - see front matter. ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jpeds.2019.09.027
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of a stroke alert system in June 2014. Before the implementation of the stroke alert system, patients presenting to the ED with brain attack symptoms were evaluated by the stroke and cerebrovascular disorders service at the discretion of the treating ED provider. After the implementation of the stroke alert system, patients presenting to the ED with brain attack symptoms were managed according to a standard protocol that mandates consultation of the stroke and cerebrovascular disorders service (Figure 1; available at www.jpeds.com).17 In brief, a stroke alert is activated when a patient presents with brain attack symptoms, defined as a focal neurologic deficit (ie, vision loss or double vision, unilateral weakness or sensory change, speech difficulty, dizziness, or trouble walking) with acute onset or worsening within the past 5 hours. If the patient meets criteria for intravenous thrombolysis, the patient is taken for emergent magnetic resonance imaging (MRI) of the brain and magnetic resonance angiography (MRA) of the head and neck. If MRI cannot be obtained emergently, a computed tomography scan and computed tomography angiography are performed. Patients who are not IV-tPA candidates and therefore do not meet the criteria for emergent imaging may still undergo urgent imaging at the discretion of the treating providers. Implementation of the stroke alert protocol was coupled with extensive internal educational efforts aimed at providers throughout the hospital. Study data were collected and managed using Research Electronic Data Capture tools hosted at Boston Children’s Hospital.18 Patients who presented to the ED with brain attack symptoms and were evaluated by the stroke service between July 2011 and December 2013, before the implementation of the stroke alert system, were identified using a prospective Boston Children’s Hospital Stroke and Cerebrovascular Center database. Patients who presented to the ED between June 2014 and December 2016 with brain attack symptoms warranting activation of the stroke alert system were identified using a prospective hospital communications center database of stroke alerts. For patients who presented to the ED with brain attack symptoms on multiple occasions, each presentation was analyzed independently and is referred to as a stroke alert. No information was collected for patients who presented to the ED with brain attack symptoms between January 2014 and May 2014 because the stroke alert system was in the process of being implemented during this time. For all patients, diagnosis by neuroimaging is as recorded in the medical record by the neuroradiologist at the time of the stroke consult or stroke alert. Clinical diagnosis is the diagnosis listed in the electronic medical record by the stroke and cerebrovascular disorders service attending at the time of the stroke consult or stroke alert. The primary outcome was the median time from ED arrival to neuroimaging. Secondary outcomes included median time from onset of symptoms to presentation to the ED and median time from presentation to the ED to evaluation by a physician from the ED and from neurology. Demographic and clinical characteristics were summarized with descriptive statistics. Time of onset of symptoms, time of ED physician and 2
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neurology evaluations, and Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score were not available for all patients; statistics were performed with available data, and the number of patients or stroke alerts on which the statistics were performed is noted in each instance.19 The primary and secondary continuous variables were analyzed using Wilcoxon rank-sum test owing to small sample sizes. The associations between the predictor and the categorical outcome were analyzed using the c2 tests and/or Fisher exact tests. A P value of less than .05 was considered significant. The entire analysis was performed using statistical software (SAS, version 9.4, Cary, North Carolina). This study was approved by the Boston Children’s Hospital Institutional Review Board. Consent was not required.
Results Eighty-two patients presented to the ED with brain attack symptoms and were urgently evaluated by the stroke and cerebrovascular disorders service during the 2.5 years before and after implementation of the stroke alert system. Fourteen patients (17%) presented before institution of the stroke alert system. Their median age was 15.5 years (range, 4-25 years). Nine of the 14 patients (64%) presenting before implementation of the stroke alert system had at least 1 prior neurologic diagnosis (Table I; available at www.jpeds.com). Two patients (14%) had sickle cell disease, one (50%) of whom had multiple prior neurologic diagnoses (Table I). Sixty-eight patients (83%) presented to the ED with brain attack symptoms after implementation of the stroke alert system; 3 patients presented twice each, for a total of 71 stroke alerts. Six stroke alerts were deemed nonurgent by the responding stroke service and were excluded from further analyses, resulting in 65 stroke alerts warranting emergent evaluation. One patient warranted 2 emergent evaluations, and each presentation was analyzed as an independent stroke alert. The median age was 12 years (range, 1-27 years). Thirty-nine of the 64 patients (61%) presenting after implementation of the stroke alert system had at least 1 prior neurologic diagnosis (Table I). Sixteen patients (25%) had congenital heart disease or sickle cell disease, 11 (69%) of whom had at least 1 prior neurologic diagnosis (Table I). Presenting Symptoms Before the stroke alert system, the most common presenting symptoms were arm weakness (n = 7 [50%]), headache (n = 6 [43%]), leg weakness (n = 5 [36%]), and language disturbance (n = 4 [29%]) (Table II). PedNIHSS scores were not routinely obtained before the stroke alert system. After the stroke alert system, the most common presenting symptoms were arm weakness (n = 30 [46%]), leg weakness (n = 22 [34%]), sensory deficit (n = 22 [34%]), and headache (n = 21 [32%]) (Table II). Twenty-one stroke alerts (32%) had a PedNIHSS score of 4 or higher (median, 8; range, 426), 42 (65%) had a PedNIHSS score of less than 4, and 2 (3%) did not have a documented PedNIHSS. Harrar et al
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Table II. Presenting symptoms of patients
Presenting symptoms Arm weakness Leg weakness Sensory deficit Headache Dysarthria Facial weakness Language disturbance Visual complaint Altered mental status/confusion Depressed consciousness/loss of consciousness Gait abnormality Dizziness or vertigo Seizure Ataxia
Stroke consults Stroke alerts before stroke after stroke alert system alert system P (n = 14), n (%) (n = 65), n (%) value 7 (50) 5 (36) 3 (21) 6 (43) 3 (21) 3 (21) 4 (29) 3 (21) 2 (14) 3 (21)
30 (46) 22 (34) 22 (34) 21 (32) 16 (25) 13 (20) 13 (20) 12 (18) 12 (18) 10 (15)
.79 .89 .53 .47 0.99 0.99 .49 0.99 0.99 .69
2 (14) 2 (14) 0 1 (7)
7 (11) 6 (9) 5 (8) 3 (5)
.66 .63 .58 .56
Time from Onset of Symptoms to Presentation to the ED There was no difference in the median time from onset of symptoms to presentation to the ED before (163 minutes; IQR, 120-331 minutes; n = 12) and after (165 minutes; IQR, 106-262 minutes; n = 59) implementation of the stroke alert system (P = .39) (Figure 2; available at www.jpeds.com). For stroke alerts, there was no difference in the median time to presentation based on PedNIHSS (140 minutes; IQR, 67223 minutes for a PedNIHSS of ³4 [n = 19] vs 169 minutes; IQR, 113-268 minutes for a PedNIHSS of <4 [n = 39]; P = .14) (Figure 2). Time from ED Arrival to Clinician Evaluation The median time from ED arrival to evaluation by an ED physician was zero minutes both before (IQR, 0-54 minutes; n = 11) and after (IQR, 0-2 minutes; n = 61) the stroke alert system (P = .09). There was no difference in the median time to neurology evaluation before (27 minutes; IQR, 5-59 minutes; n = 9) and after (7 minutes; IQR, 0-22 minutes; n = 61) implementation of the stroke alert system (P = .10). There was also no difference in the median time to neurology evaluation based on the PedNIHSS after implementation of the stroke alert system (7.5 minutes; IQR, 025 minutes for a PedNIHSS of ³4, n = 20 vs 7.5 minutes; IQR, 1.5-24.5 minutes for a PedNIHSS of <4, n = 40; P = .50). Time from ED Arrival to Neuroimaging The median time from ED arrival to neuroimaging for patients who presented with brain attack symptoms before the stroke alert system (196 minutes; IQR, 85-230 minutes; n = 14) was significantly longer than the median time from arrival to neuroimaging for stroke alerts who presented with brain attack symptoms after implementation of the stroke alert system (82 minutes; IQR, 54-123 minutes; n = 65; P < .01) (Figure 3). Among stroke alerts who presented after implementation of the stroke alert system, there was no difference in the median time to neuroimaging for stroke
Figure 3. Median time from ED arrival to neuroimaging. Box plots showing the median, second (bottom box), and third (top box) quartiles, and the minimum and maximum time from ED arrival to neuroimaging. Stratification by Ped NIHSS and IVtPA candidacy is presented only for patients after implementation of the stroke alert system.
alerts with a PedNIHSS of 4 or greater (66 [IQR 47-83] minutes, n = 21) compared with those with PedNIHSS <4 (92 minutes; IQR, 61-128 minutes; n = 42; P = .06). Notably, after implementation of the stroke alert system, the median time from ED arrival to neuroimaging for stroke alerts who were considered IV-tPA candidates before neuroimaging (n = 13) was 54 minutes (IQR, 34-66 minutes). This was significantly shorter than the median time to neuroimaging for stroke alerts who were not considered IV-tPA candidates (89.5 minutes; IQR, 62-126.5 minutes; n = 52; P < .01). MRI with or without MRA and/or magnetic resonance venography was the first imaging study obtained in 55 stroke alerts (85%). Ten (15%) had a computed tomography scan with or without computed tomography angiography as the initial imaging study, 7 (70%) of whom required subsequent MRI for diagnosis. Sixteen stroke alerts (25%) required sedation by an anesthesiologist to obtain neuroimaging; sedation for neuroimaging is not provided by ED physicians at our institution. All stroke alerts requiring sedation were treated with propofol at minimum, and one-half (n = 8) required endotracheal intubation. There was no difference in the median time from ED arrival to neuroimaging for stroke alerts requiring sedation (88 minutes; IQR, 70-127.5 minutes; n = 16) compared with those not requiring sedation (82 minutes; IQR, 47-119 minutes; n = 47; P = .22) (Figure 4). Thirteen stroke alerts (20%) required imaging overnight (between 23:00 and 06:00), and 3 of those required sedation. There was no difference in the median time from ED arrival to neuroimaging for stroke alerts requiring imaging overnight (82 minutes; IQR, 64-102 minutes; n = 13) compared with those whose imaging occurred during the daytime (80 minutes; IQR, 48.5-123 minutes; n = 52; P = .72).
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Table III. Final diagnoses Stroke consults Stroke alerts before stroke after stroke alert system alert system P (n = 14), n (%) (n = 65), n (%)* value
Diagnoses Acute AIS Intraparenchymal hemorrhage Transient ischemic attack Migraine or other headache Seizure Conversion or other psychogenic disorder Infectious or inflammatory disorder Other† Unspecified
3 (21) 0 4 (29) 3 (21) 0 1 (7)
6 (9) 1 (2) 11 (17) 23 (35) 7 (11) 3 (5)
.19 0.99 .43 .36 .34 .56
0
5 (8)
0.99
2 (14) 1 (7)
11 (17) 2 (3)
*Seven patients had 2 final diagnoses. †Bell’s palsy or other peripheral neuropathy, dystonia, necrotizing granulomatous lesion, intracranial neoplasm or other oncologic process, peripheral vertigo, recrudescence of prior stroke symptoms, subdural fluid collection, symptomatic anemia, syncope, or vaso-occlusive crisis without central nervous system involvement.
drome, disqualifying the patient from thrombolysis. The other patient had a large middle cerebral artery infarct, the size of which precluded treatment with IV-tPA; in addition, there was no diffusion–perfusion mismatch, precluding any potential benefit of endovascular intervention. One stroke alert underwent hemicraniectomy for a full territory middle cerebral artery infarct, and one underwent exchange transfusion for stroke in the setting of sickle cell disease. Figure 4. Median time from ED arrival to neuroimaging stratified by requirement for sedation. Box plots showing the median, second (bottom box), and third (top box) quartiles, and the minimum and maximum time from ED arrival to neuroimaging.
Diagnosis Final diagnoses are presented in Table III. Of the patients who presented with brain attack symptoms before the stroke alert system, 3 (21%) had an acute AIS and 4 (29%) had a transient ischemic attack. Three patients (21%) had a migraine or other headache, and none had a seizure. Of the stroke alerts, 18 (28%) had a stroke or other cerebrovascular disorder; 6 (9%) had an acute AIS, 1 (1.5%) had an intraparenchymal hemorrhage, and 11 (17%) had a transient ischemic attack. An additional 12 stroke alerts (18%) had other neurologic emergencies, including seizure (n = 7 [11%]) or an infectious or inflammatory disorder (n = 5 [8%]). Migraine or other headache (n = 23 [35%]) was the most common stroke mimic. Of the 3 patients with AIS before the stroke alert system, one was successfully treated with IV-tPA, and one underwent exchange transfusion for stroke in the setting of sickle cell disease. Two stroke alerts were considered potential IV-tPA candidates before neuroimaging; however, neither was treated with IV-tPA or mechanical thrombectomy. Of these 2 patients, one was newly diagnosed with moyamoya syn4
Discussion The rapid diagnosis of children with AIS has historically proved challenging. Part of the delay in diagnosis relates to delay in arrival of the child to the ED and likely stems, in part, from a lack of community awareness about the possibility of stroke in children.11 However, a significant proportion of the delay also occurs after the child arrives at the hospital.9,11 With the advent of hyperacute therapies for the treatment of AIS and emerging evidence that these interventions may be safe and effective in children, it is imperative that children with AIS are identified in a timely fashion.1-6 This requires enhanced community education and an organized system of evaluation and management once a patient presents for medical care.20 We have shown that the establishment of a stroke alert system at a tertiary children’s hospital, coupled with extensive internal educational efforts, significantly decreases the median time to diagnosis by neuroimaging of patients presenting to the ED with brain attack symptoms. This finding represents an important first step in ensuring that a greater proportion of children with AIS are diagnosed within a time frame that enables treatment with acute interventions. The institution of a stroke alert system at our children’s hospital decreased by more than one-half the median time from arrival in the ED to diagnosis by neuroimaging of patients presenting with brain attack symptoms. Potential candidates for IV-tPA were imaged even more rapidly, almost 4 Harrar et al
- 2019 times as fast as patients who presented with brain attack symptoms before the stroke alert system. This difference may reflect, at least in part, our policy that an ongoing non-emergent MRI is interrupted so that an MRI scanner can be made immediately available for a patient whose imaging is considered emergent based on IV-tPA candidacy. Our findings are consistent with reports from pediatric stroke teams in Tennessee and France. Ladner et al21 reported a median time of 79 minutes from arrival to initial imaging for patients presenting with focal neurologic deficits to a children’s hospital ED in Tennessee after the establishment of a stroke alert system. Similarly, Tabone et al1 reported a median time of 165 minutes from symptom onset to MRI for patients who underwent mechanical thrombectomy as part of a regional pediatric acute stroke protocol in France. It is unknown whether these represent improvements in the time to evaluation of these patients compared with those who presented with brain attack symptoms before the establishment of these stroke alert systems. In contrast to our findings, Shack et al12 reported no change in the in-hospital delay to diagnosis for children presenting as outpatients with AIS after establishment of an acute stroke protocol at a tertiary children’s hospital in Canada. Moreover, the in-hospital delay to diagnosis for children presenting as outpatients with AIS after establishment of a stroke protocol was significantly longer (10.5 hours) than in our cohort; however, that study included all patients presenting within 14 days of AIS onset and only two-thirds to three-quarters of children presenting as outpatients had acute-onset focal neurologic deficits. There was, however, a statistically significant decrease in the inhospital delay in diagnosis for the subset of children presenting as outpatients with AIS with mild symptoms. The pathway from ED arrival to neuroimaging for patients with suspected AIS includes rapid evaluation by a triage nurse, ED physician, and neurologist, and preparation for and initiation of neuroimaging. The majority of patients who present to our ED with brain attack symptoms are seen by an ED physician immediately upon arrival, and implementation of the stroke alert system did not affect this. Interestingly, the stroke alert system did not significantly influence the median time from ED arrival to neurology evaluation, although there was a trend toward a more rapid evaluation after implementation of the stroke alert system. The lack of a significant effect on the median time from arrival to neurology evaluation may reflect the around-theclock presence of a neurology resident in our hospital both before and after implementation of the stroke alert system. It is also possible that the small number of patients who had a stroke consultation in the ED before implementation of the stroke alert system precluded detection of an effect on this measure. There was no difference in the median time from ED arrival to neuroimaging for patients who required sedation to obtain neuroimaging compared with those who did not require sedation. Given that considerably more children who present to the ED with brain attack symptoms have a stroke mimic rather than an AIS, our criteria for administra-
ORIGINAL ARTICLES tion of IV-tPA require that a patient have diffusion restriction on MRI and vessel obstruction on MRA. The use of MRI and MRA can require sedation for acquisition of reliable imaging, raising concern for delay in diagnosis caused by the need for sedation. It is reassuring that the need for sedation did not delay neuroimaging in our system. This may be due to the availability of pediatric anesthesiologists in the hospital around the clock as well as their rapid deployment in the setting of a stroke alert, based on their inclusion in the stroke alert activation page. Although we have decreased by more than one-half the median time from ED arrival to diagnosis for patients presenting with brain attack symptoms, the median time from arrival to imaging is still almost 1 hour for those patients considered potential IV-tPA candidates. Given a median time from onset of symptoms to arrival in the ED of almost 3 hours and the historical windows of 4.5 and 6 hours after a patient’s last seen well time for thrombolysis and thrombectomy, respectively, this leaves little room for unexpected delays in initiating neuroimaging. Performance improvement efforts aimed at identifying the root causes of this continued delay will be paramount to diagnosing more children within a time frame that enables acute intervention. Although new results from large trials of adults with AIS indicate that thrombectomy can be safe and effective up to 24 hours from symptom onset in select patients, the number of patients who meet criteria for treatment beyond 6 hours is small.22,23 Efforts are also underway to identify pediatric patients who may benefit from mechanical thrombectomy in an extended time window. Given the possibility of mechanical thrombectomy up to 24 hours from symptom onset in a subset of adult patients, we are reviewing our acute stroke protocol to determine if the time frame for treatment can be extended for children with certain clinical features who present with acute stroke. Nonetheless, earlier treatment results in better outcomes, and as such rapid diagnosis remains imperative.24 Therefore, we continue to strive to decrease our delay to diagnosis as we anticipate that the shortest time from symptom onset to recanalization is likely to provide the best possible outcome. Many more patients were evaluated by the stroke service in the ED after implementation of our stroke alert system compared with before its implementation (68 vs 14). This likely reflects, in part, an increased awareness of stroke as a potential underlying etiology for brain attack symptoms in children as the implementation of our stroke alert system was coupled with extensive, internal educational efforts. Indeed, the total number of stroke consultations performed throughout the hospital increased during this time from 152 to 224, excluding consultations performed on neonates. The increase in stroke alerts also likely reflects the expectation established with the implementation of the stroke alert system that a patient presenting to the ED with a focal neurologic deficit with acute onset or worsening within the past 5 hours be evaluated by the stroke and cerebrovascular disorders service as a stroke alert. In keeping with this, the relative percentage of stroke consultations performed in the ED
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increased over this time period, from 9.2% before the stroke alert system to 29.0% after the stroke alert system. As noted above, before the implementation of the stroke alert system, patients presenting to the ED with brain attack symptoms were evaluated by the stroke and cerebrovascular disorders service at the discretion of the treating ED provider. Although implementation of our stroke alert system led to faster diagnosis of patients presenting to the ED with brain attack symptoms, further study is required to determine whether faster diagnosis in the ED results in more frequent use of acute therapies and improved outcome in children with AIS, as it has in adults. This research will require continued collection of clinical data for children who present to the ED with brain attack symptoms as well as continued efforts to decrease the time from onset of symptoms to diagnosis. Our study has limitations inherent in the retrospective nature of our study design. Although cases were collected prospectively, the retrospective nature of our data review meant that not all data points were available for every patient in our cohort. Moreover, all of our data come from a single center and may not be generalizable to other pediatric centers. For example, our institution has 7 non-operating room–based MRI scanners; many pediatric centers likely have fewer scanners available for emergent imaging. Finally, our preimplementation group was quite small and, although we were able to detect a significant improvement in the median time from ED arrival to neuroimaging, our study may have been underpowered to detect other, more subtle impacts of our stroke alert system. The establishment of a stroke alert system at a children’s hospital decreases the median time to diagnosis of patients presenting to the ED with brain attack symptoms by more than 50%. This constitutes an important first step in ensuring that a greater proportion of children with AIS are diagnosed in a time frame that permits treatment with hyperacute therapies. Substantial work remains to reduce further the time not only from arrival to neuroimaging but also from onset of symptoms to neuroimaging. Ongoing educational and quality improvement efforts will be critical to ensure that a greater number of children are diagnosed within a time frame that enables treatment with acute interventions. n Submitted for publication May 16, 2019; last revision received Aug 14, 2019; accepted Sep 12, 2019. Reprint requests: Dana B. Harrar, MD, PhD, Division of Neurology, Children’s National Hospital, 111 Michigan Avenue NW, Washington, DC 20010. E-mail: [email protected]
Data Statement Data sharing statement available at www.jpeds.com.
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2. Satti S, Chen J, Sivapatham T, Jayaraman M, Orbach D. Mechanical thrombectomy for pediatric acute ischemic stroke: review of the literature. J Neurointerv Surg 2017;9:732-7. 3. Bigi S, Dulcey A, Gralla J, Bernasconi A, Mellinger A, Datta AN, et al. Feasibility, safety, and outcome of recanalization treatment in childhood stroke. Ann Neurol 2018;83:1125-32. 4. Cappellari M, Moretto G, Grazioli A, Ricciardi GK, Bovi P, Ciceri EFM. Primary versus secondary mechanical thrombectomy for anterior circulation stroke in children: an update. J Neuroradiol 2018;45:102-7. 5. Sporns PB, Kemmling A, Hanning U, Minnerup J, Strater R, Niederstadt T, et al. Thrombectomy in childhood stroke. J Am Heart Assoc 2019;8:e011335. 6. Sun LR, Felling RJ, Pearl MS. Endovascular mechanical thrombectomy for acute stroke in young children. J Neurointerv Surg 2019;11:554-8. 7. Gabis LV, Yangala R, Lenn NJ. Time lag to diagnosis of stroke in children. Pediatrics 2002;110:924-8. 8. McGlennan C, Ganesan V. Delays in investigation and management of acute arterial ischaemic stroke in children. Dev Med Child Neurol 2008;50:537-40. 9. Rafay MF, Pontigon AM, Chiang J, Adams M, Jarvis DA, Silver F, et al. Delay to diagnosis in acute pediatric arterial ischemic stroke. Stroke 2009;40:58-64. 10. Srinivasan J, Miller SP, Phan TG, Mackay MT. Delayed recognition of initial stroke in children: need for increased awareness. Pediatrics 2009;124:e227-34. 11. Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T, et al. Diagnostic delays in paediatric stroke. J Neurol Neurosurg Psychiatry 2015;86:917-21. 12. Shack M, Andrade A, Shah-Basak PP, Shroff M, Moharir M, Yau I, et al. A pediatric institutional acute stroke protocol improves timely access to stroke treatment. Dev Med Child Neurol 2017;59:31-7. 13. Bernard TJ, Rivkin MJ, Scholz K, deVeber G, Kirton A, Gill JC, et al. Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke trial. Stroke 2014;45:2018-23. 14. Rivkin MJ, deVeber G, Ichord RN, Kirton A, Chan AK, Hovinga CA, et al. Thrombolysis in pediatric stroke study. Stroke 2015;46:880-5. 15. Mackay MT, Chua ZK, Lee M, Yock-Corrales A, Churilov L, Monagle P, et al. Stroke and nonstroke brain attacks in children. Neurology 2014;82: 1434-40. 16. Mackay MT, Monagle P, Babl FE. Brain attacks and stroke in children. J Paediatr Child Health 2016;52:158-63. 17. Rivkin MJ, Bernard TJ, Dowling MM, Amlie-Lefond C. Guidelines for urgent management of stroke in children. Pediatr Neurol 2016;56: 8-17. 18. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377-81. 19. Ichord RN, Bastian R, Abraham L, Askalan R, Benedict S, Bernard TJ, et al. Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke 2011;42:613-7. 20. Ferriero DM, Fullerton HJ, Bernard TJ, Billinghurst L, Daniels SR, DeBaun MR, et al. Management of stroke in neonates and children: a scientific statement from the American Heart Association/American Stroke Association. Stroke 2019;50:e51-96. 21. Ladner TR, Mahdi J, Gindville MC, Gordon A, Harris ZL, Crossman K, et al. Pediatric acute stroke protocol activation in a children’s hospital emergency department. Stroke 2015;46:2328-31. 22. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 2018;378:708-18. 23. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 2018;378:11-21. 24. Saver JL, Fonarow GC, Smith EE, Reeves MJ, Grau-Sepulveda MV, Pan W, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013;309: 2480-8.
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Acute Stroke Guideline: INITIAL APPROACH 1. Any child with potential stroke Including all BCH ED and children from outside BCH via Critical Care Transport Team (BCH or other)
2. Stroke Screening Questions I. Is there a focal neurological deficit? a. Vision loss or double vision b. Unilateral weakness or sensory change c. Speech difficulty d. Dizziness or trouble walking II. Did the problem appear or worsensuddenly? III. Has the problem been present for less than 5 hours? (When was the child last seen well?)
4a. ED or responsible service supports airway, breathing & circulation (consider ICU STAT on wards), starts IV x 2 if not already in place, draws stat INR, PTT, type and screen, CBC, PLTs, fibrinogen, glucose, electrolytes
Stroke Stat team: Stroke Attending ED Neurology resident Neuroradiologist ED Pharmacist [MSICU Fellow, Intensive Care Neurology resident, Anesthesia (FYI Only)] See Acute Stroke Team Activation Plan
3. Child meets all acute stroke criteria (I-III)
No
Yes/ Not sure
Consider urgent consult to Neurology and urgent MR while considering other diagnoses and initiating neuroprotective care
4. Call Stroke Stat IMMEDIATELY Via Comm Center (x5-2170) ALL HOURS o
5. Possible stroke confirmed by ED neurology resident in consultation with stroke attending Pediatric NIHSS performed
No
Initial Supportive Rx: • NPO, head of bed flat • Normotension: target SBP is between 50th and 90th %ile for age, treat low BP with NS +/- pressors, treat significant HTN with labetalol to lower by ~25% over 24 hours (more quickly if tPA candidate, see page 2) • Normovolemia: Isotonic fluid (ie, 0.9% NaCl) at maintenance with bolus prn • Normoglycemia: For age >2, no glucose in IV fluids unless hypoglycemic; for age <2, use glucosecontaining fluids, eg: D50.9%NaCl • Normal O2, CO2 and pH • Normothermia: treat patient w/ T>37o with acetaminophen • Seizure control: AED ASAP with any suspected seizure activity
Yes
6. Neurology resident or ED/ward staff request emergent MRI (page neuroradiology attending on call)
See PAGE 3 for ALTERNATIVE workflow if MRI unavailable
7. Prepare patient for transport to MRI with appropriate equipment and personnel
Go to PAGE 2
If patient on the ward, transfer to MSICU
Adapted from algorithm developed at Toronto Hospital for Sick Children
Figure 1. Boston Children’s Hospital Acute Stroke Response Algorithm. ABC, airway, breathing, circulation; AED, automated external defibrillator; ASA, aspirin; ASAP, as soon as possible; AVM, arteriovenous malformation; (Continues) A Stroke Alert Protocol Decreases the Time to Diagnosis of Brain Attack Symptoms in a Pediatric Emergency Department
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Figure 1. BCH, Boston Children’s Hospital; CBC, complete blood count; COW, circle of Willis; CT, computed tomography; CTA, angiography; DWI, diffusion-weighted imaging; FLAIR, fluid attenuated inversion recovery; (Continues) 6.e2
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Acute Stroke Guideline: Acute Response MRI Unavailable Stroke Stat team: Stroke Attending ED Neurology resident Neuroradiologist ED Pharmacist [Anesthesia, MSICU Fellow, Intensive Care Neurology Resident (FYI Only) ]
1. Neurology resident or ED staff requests emergent CT with CTA (page neuroradiology attending on call)
See Acute Stroke Team Activation Plan
2. Transport patient to CT accompanied by appropriate personnel and equipment
3. Perform CT scan with CTA
5a. Transport pt. to MRI if now available, otherwise back to ED or MSICU
No
5. CT/ CTA shows ALL of: a. No hemorrhage or alternate diagnosis, b. Parenchyma normal or early signs of cerebral ischemia consistent with stroke, and c. Definitive evidence of arterial occlusion
Yes
Time from onset + estimated time to arrival > 4.5 hrs, or age < 2 years, or resolving deficit, or tPA contraindication (see page 2)
Time from onset + estimated time to arrival < 4.5 hours, and age > 2 years, and persistent focal deficit, and no tPA contraindication (see page 2)
Yes Yes
tPA CANDIDATE Admit patient and provide neuroprotective and supportive acute stroke treatment per stroke/ICU service
Consider other diagnostic imaging (eg: cerebral angiography) and/or IA tPA or other endovascular therapy
7. Stroke team member calls ED pharmacist (x51894) with phone request to prepare tPA infusion and places order in CHAMPS using “ED Stroke Orderset” and “STAT” designation
8. Stroke Neurologist confirms final intention to treat with IV tPA and calls ED Pharmacist (x51894); admit patient to MSICU
Go to PAGE 4
Figure 1. FYI, first year intern; GI, gastrointestinal; GU, genitourinary; HOB, head of bed; HTN, hypertension; IA, intra-arterial; ICP, intracranial pressure; ICU, intensive care unit; INR, international normalized ratio; (Continues) A Stroke Alert Protocol Decreases the Time to Diagnosis of Brain Attack Symptoms in a Pediatric Emergency Department
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IV tPA TREATMENT PROTOCOL IV tPA CANDIDATE < 4.5 hrs from onset, age >2 years, persistent focal deficit, no contraindications, BOTH proven infarct AND arterial occlusion on MR or CT/CTA Yes ED Pharmacy prepares tPA infusion with stat release to ED or MSICU. Bolus dose: 10% of total dose IV over 5 min Infusion dose: remaining 90% IV over 1 hour Total dose: .9 mg/kg IV Nurse/MD double checks dose with pharmacy
Maintain cardiorespiratory and BP monitoring. If agebased tPA parameters acceptable (see green box to right) begin tPA infusion as soon as available (in ED or en route to MSICU). Note: dedicated IV for tPA required to proceed.
Systolic BP should be maintained between 50th %ile for age and 15% above 95th %ile for age (see below) Treat to lower BP if > 15% above 95th %ile for age for more than 1 hr. OR If > 20% above 95th %ile for age at any time SEE CHART BELOW
Systolic Blood Pressure Parameters - Female Age
50%
95%
>15% above 95%
>20% above 95%
1 – 4 years
90
111
128
133
5 years
94
113
130
136
6 – 10 years
96
121
139
145
11 – 18 years
105
131
151
157
>18 years
110
140
161
168
Labetalol .2 mg/kg IV push over 2-3 min, repeat q15 minutes prn; consider nicardipine drip, 1 mcg/kg/min, titrate to desired BP Use with caution in patients with asthma or underlying cardiac disease
Systolic Blood Pressure Parameters - Male Age
50%
95%
>15% above 95%
>20% above 95%
1 – 4 years
90
112
129
134
5 years
95
113
130
136
6 – 10 years
96
121
139
145
11 – 18 years
105
140
161
168
>18 years
110
140
161
168
Figure 1. IV, intravenous; LMWH, low-molecular-weight heparin; MCA, middle cerebral artery; MSICU, medical-surgical intensive care unit; NG, nasogastric; NPO, nil per os; NSAID, nonsteroidal anti-inflammatory drug; (Continues) 6.e4
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POST tPA ADMINISTRATION CARE PROTOCOL
tPA administered IV
Ped NIHSS recording (by neurologist) 1. 2. 3. 4. 5. 6. 7.
50-75 mins. post tPA initiation 2 hrs. post tPA initiation 12 hrs. post tPA initiation 24 hrs. post tPA initiation 36 hrs. post tPA initiation 48 hrs. post tPA initiation Day 7 or discharge.
Neurologic status checks
Blood Pressure (BP) checks
1.
1. 2. 3. 4. 5.
2. 3.
Every 15 mins. X 2 hrs., then, Every 30 mins. X 6 hrs., then, Every 60 mins. X 16 hrs
Every 15 mins. X 4 hrs., then, Every 30 mins X 4 hrs., then, Every 60 mins X 16 hrs., then, Every 2 hrs X 24 hrs., then, Every 4 hrs X 24 hrs.
See Page 4 for BP guidelines
Any neurological deterioration Yes Provide supportive care (ABCs) Order urgent CT head Draw stat CBC, INR, PTT Order and prepare to give 6-8 units of cryoprecipitate (fibrinogen and factor VIII) Order and prepare to give 6-8 units of platelets Notify stroke neurologist Consult neurosurgery if signs of elevated ICP or CT reveals bleed or mass effect
Post-tPA Care Remains in MSICU for minimum of 24 hours; If patient’s condition permits, transfer to 9N or SUU for next 48 hours HOB flat NPO x 24 hours after tPA CBC, INR, PTT, fibrinogen, d-dimer at 6 hours No arterial punctures, invasive procedures or anti-coagulants (ASA, NSAID, UFH, LMWH) for 24 hours Avoid indwelling urinary catheter, NG tube Maintain euglycemia Maintain normothermia – avoid fever Follow-up imaging per stroke neurologist/ICU
Figure 1. PLT, platelets; prn, as needed; PT, prothrombin time; PTT, partial thrmomboplastin time; SAH, sibarachnoid hemorrhage; SBE, subacute bacterial endocarditis; SBP, systolic BP; SWI, susceptibility weighted imaging; TOF, time of flight; UFH, unfractionated heparin. (Continued) A Stroke Alert Protocol Decreases the Time to Diagnosis of Brain Attack Symptoms in a Pediatric Emergency Department
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Table I. Patient characteristics
Medical and neurologic histories
Patients before stroke alert system (n = 14*), n (%)
Patients after stroke alert system (n = 64†), n (%)
P value
Stroke Transient ischemic attack Epilepsy Migraine Cerebral vasculopathy Congenital heart disease Sickle cell disease
3 (21) 5 (36) 1 (7) 1 (7) 4 (29) 0 2 (14)
2 (3) 14 (22) 11 (17) 8 (12) 10 (15) 10 (15) 6 (9)
.04 .28 .68 0.99 .26 .19 .63
*Five patients had no prior neurologic diagnosis, and 5 patients had multiple prior neurologic diagnoses. †Twenty-five patients had no prior neurologic diagnosis, and 17 patients had multiple prior neurologic diagnoses.
Figure 2. Median time from symptom onset to ED arrival. Box plots showing the median, second (bottom box), and third (top box) quartiles, and the minimum and maximum time from symptom onset to ED arrival. Stratification by PedNIHSS is presented only for patients after implementation of the stroke alert system.
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H
yperacute therapies, including intravenous tissue plasminogen activator (IV-tPA) and mechanical thrombectomy, have revolutionized the care of adults with arterial ischemic stroke (AIS). Increasingly, children with AIS are also being treated successfully with IV-tPA and mechanical thrombectomy.1-6 The implementation of hyperacute therapies requires the timely identification of stroke, which has historically proved challenging in children; the median time from symptom onset to diagnosis of AIS in children is more than 20 hours.7-12 A delay in diagnosis, coupled with the apparent safety and efficacy of IV-tPA in children, prompted 23 pediatric centers in North America to develop multidisciplinary stroke teams capable of emergent, around-the-clock response to patients with acute-onset focal neurologic deficits,13,14 otherwise known as brain attack symptoms.15,16 Shack et al12 reported a variable impact of a stroke alert system on the time to diagnosis of children with AIS occurring in the preceding 14 days. In that study, in which only one-half to three-quarters of patients presented with acute onset focal neurologic deficits, implementation of a stroke alert protocol led to a reduction in the in-hospital component of the delay in the time to diagnosis for children with AIS presenting with mild symptoms; however, the in-hospital delay in the time to diagnosis for all children with AIS was unchanged. Because Shack et al considered children with AIS presenting as many as 14 days from symptom onset, it remains unknown whether the establishment of a pediatric stroke alert protocol decreases the time to diagnosis of children with acute-onset focal neurologic deficits who present within a time frame from symptom onset that makes them eligible for treatment with hyperacute therapies. We aimed to determine whether a stroke alert system at a tertiary care pediatric hospital decreases the time to diagnosis of patients presenting to the emergency department (ED) with acute-onset focal neurologic deficits.
Methods We conducted a retrospective review of the medical records of patients who presented to the ED of a free-standing tertiary children’s hospital with acute-onset focal neurologic deficits during the 2.5 years before and after the implementation
From the 1Department of Neurology, 2Stroke and Cerebrovascular Center, 3Department of Radiology, Boston Children’s Hospital, 4Department of Anesthesiology, Critical Care, and Pain Medicine, 5 Division of Emergency Medicine, and 6Department of Psychiatry, Boston Children’s Hospital, Boston, MA a
AIS ED IV-tPA MRA MRI PedNIHSS
Arterial ischemic stroke Emergency department Intravenous tissue plasminogen activator Magnetic resonance angiography Magnetic resonance imaging Pediatric National Institutes of Health Stroke Scale
Present address: Division of Neurology, Children’s National Hospital, Washington, DC. The authors declare no conflicts of interest. Portions of this study were presented as a poster at the European Stroke Organisation Conference, May 16-18, 2018, Gothenburg, Sweden.
0022-3476/$ - see front matter. ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jpeds.2019.09.027
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of a stroke alert system in June 2014. Before the implementation of the stroke alert system, patients presenting to the ED with brain attack symptoms were evaluated by the stroke and cerebrovascular disorders service at the discretion of the treating ED provider. After the implementation of the stroke alert system, patients presenting to the ED with brain attack symptoms were managed according to a standard protocol that mandates consultation of the stroke and cerebrovascular disorders service (Figure 1; available at www.jpeds.com).17 In brief, a stroke alert is activated when a patient presents with brain attack symptoms, defined as a focal neurologic deficit (ie, vision loss or double vision, unilateral weakness or sensory change, speech difficulty, dizziness, or trouble walking) with acute onset or worsening within the past 5 hours. If the patient meets criteria for intravenous thrombolysis, the patient is taken for emergent magnetic resonance imaging (MRI) of the brain and magnetic resonance angiography (MRA) of the head and neck. If MRI cannot be obtained emergently, a computed tomography scan and computed tomography angiography are performed. Patients who are not IV-tPA candidates and therefore do not meet the criteria for emergent imaging may still undergo urgent imaging at the discretion of the treating providers. Implementation of the stroke alert protocol was coupled with extensive internal educational efforts aimed at providers throughout the hospital. Study data were collected and managed using Research Electronic Data Capture tools hosted at Boston Children’s Hospital.18 Patients who presented to the ED with brain attack symptoms and were evaluated by the stroke service between July 2011 and December 2013, before the implementation of the stroke alert system, were identified using a prospective Boston Children’s Hospital Stroke and Cerebrovascular Center database. Patients who presented to the ED between June 2014 and December 2016 with brain attack symptoms warranting activation of the stroke alert system were identified using a prospective hospital communications center database of stroke alerts. For patients who presented to the ED with brain attack symptoms on multiple occasions, each presentation was analyzed independently and is referred to as a stroke alert. No information was collected for patients who presented to the ED with brain attack symptoms between January 2014 and May 2014 because the stroke alert system was in the process of being implemented during this time. For all patients, diagnosis by neuroimaging is as recorded in the medical record by the neuroradiologist at the time of the stroke consult or stroke alert. Clinical diagnosis is the diagnosis listed in the electronic medical record by the stroke and cerebrovascular disorders service attending at the time of the stroke consult or stroke alert. The primary outcome was the median time from ED arrival to neuroimaging. Secondary outcomes included median time from onset of symptoms to presentation to the ED and median time from presentation to the ED to evaluation by a physician from the ED and from neurology. Demographic and clinical characteristics were summarized with descriptive statistics. Time of onset of symptoms, time of ED physician and 2
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neurology evaluations, and Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score were not available for all patients; statistics were performed with available data, and the number of patients or stroke alerts on which the statistics were performed is noted in each instance.19 The primary and secondary continuous variables were analyzed using Wilcoxon rank-sum test owing to small sample sizes. The associations between the predictor and the categorical outcome were analyzed using the c2 tests and/or Fisher exact tests. A P value of less than .05 was considered significant. The entire analysis was performed using statistical software (SAS, version 9.4, Cary, North Carolina). This study was approved by the Boston Children’s Hospital Institutional Review Board. Consent was not required.
Results Eighty-two patients presented to the ED with brain attack symptoms and were urgently evaluated by the stroke and cerebrovascular disorders service during the 2.5 years before and after implementation of the stroke alert system. Fourteen patients (17%) presented before institution of the stroke alert system. Their median age was 15.5 years (range, 4-25 years). Nine of the 14 patients (64%) presenting before implementation of the stroke alert system had at least 1 prior neurologic diagnosis (Table I; available at www.jpeds.com). Two patients (14%) had sickle cell disease, one (50%) of whom had multiple prior neurologic diagnoses (Table I). Sixty-eight patients (83%) presented to the ED with brain attack symptoms after implementation of the stroke alert system; 3 patients presented twice each, for a total of 71 stroke alerts. Six stroke alerts were deemed nonurgent by the responding stroke service and were excluded from further analyses, resulting in 65 stroke alerts warranting emergent evaluation. One patient warranted 2 emergent evaluations, and each presentation was analyzed as an independent stroke alert. The median age was 12 years (range, 1-27 years). Thirty-nine of the 64 patients (61%) presenting after implementation of the stroke alert system had at least 1 prior neurologic diagnosis (Table I). Sixteen patients (25%) had congenital heart disease or sickle cell disease, 11 (69%) of whom had at least 1 prior neurologic diagnosis (Table I). Presenting Symptoms Before the stroke alert system, the most common presenting symptoms were arm weakness (n = 7 [50%]), headache (n = 6 [43%]), leg weakness (n = 5 [36%]), and language disturbance (n = 4 [29%]) (Table II). PedNIHSS scores were not routinely obtained before the stroke alert system. After the stroke alert system, the most common presenting symptoms were arm weakness (n = 30 [46%]), leg weakness (n = 22 [34%]), sensory deficit (n = 22 [34%]), and headache (n = 21 [32%]) (Table II). Twenty-one stroke alerts (32%) had a PedNIHSS score of 4 or higher (median, 8; range, 426), 42 (65%) had a PedNIHSS score of less than 4, and 2 (3%) did not have a documented PedNIHSS. Harrar et al
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ORIGINAL ARTICLES
Table II. Presenting symptoms of patients
Presenting symptoms Arm weakness Leg weakness Sensory deficit Headache Dysarthria Facial weakness Language disturbance Visual complaint Altered mental status/confusion Depressed consciousness/loss of consciousness Gait abnormality Dizziness or vertigo Seizure Ataxia
Stroke consults Stroke alerts before stroke after stroke alert system alert system P (n = 14), n (%) (n = 65), n (%) value 7 (50) 5 (36) 3 (21) 6 (43) 3 (21) 3 (21) 4 (29) 3 (21) 2 (14) 3 (21)
30 (46) 22 (34) 22 (34) 21 (32) 16 (25) 13 (20) 13 (20) 12 (18) 12 (18) 10 (15)
.79 .89 .53 .47 0.99 0.99 .49 0.99 0.99 .69
2 (14) 2 (14) 0 1 (7)
7 (11) 6 (9) 5 (8) 3 (5)
.66 .63 .58 .56
Time from Onset of Symptoms to Presentation to the ED There was no difference in the median time from onset of symptoms to presentation to the ED before (163 minutes; IQR, 120-331 minutes; n = 12) and after (165 minutes; IQR, 106-262 minutes; n = 59) implementation of the stroke alert system (P = .39) (Figure 2; available at www.jpeds.com). For stroke alerts, there was no difference in the median time to presentation based on PedNIHSS (140 minutes; IQR, 67223 minutes for a PedNIHSS of ³4 [n = 19] vs 169 minutes; IQR, 113-268 minutes for a PedNIHSS of <4 [n = 39]; P = .14) (Figure 2). Time from ED Arrival to Clinician Evaluation The median time from ED arrival to evaluation by an ED physician was zero minutes both before (IQR, 0-54 minutes; n = 11) and after (IQR, 0-2 minutes; n = 61) the stroke alert system (P = .09). There was no difference in the median time to neurology evaluation before (27 minutes; IQR, 5-59 minutes; n = 9) and after (7 minutes; IQR, 0-22 minutes; n = 61) implementation of the stroke alert system (P = .10). There was also no difference in the median time to neurology evaluation based on the PedNIHSS after implementation of the stroke alert system (7.5 minutes; IQR, 025 minutes for a PedNIHSS of ³4, n = 20 vs 7.5 minutes; IQR, 1.5-24.5 minutes for a PedNIHSS of <4, n = 40; P = .50). Time from ED Arrival to Neuroimaging The median time from ED arrival to neuroimaging for patients who presented with brain attack symptoms before the stroke alert system (196 minutes; IQR, 85-230 minutes; n = 14) was significantly longer than the median time from arrival to neuroimaging for stroke alerts who presented with brain attack symptoms after implementation of the stroke alert system (82 minutes; IQR, 54-123 minutes; n = 65; P < .01) (Figure 3). Among stroke alerts who presented after implementation of the stroke alert system, there was no difference in the median time to neuroimaging for stroke
Figure 3. Median time from ED arrival to neuroimaging. Box plots showing the median, second (bottom box), and third (top box) quartiles, and the minimum and maximum time from ED arrival to neuroimaging. Stratification by Ped NIHSS and IVtPA candidacy is presented only for patients after implementation of the stroke alert system.
alerts with a PedNIHSS of 4 or greater (66 [IQR 47-83] minutes, n = 21) compared with those with PedNIHSS <4 (92 minutes; IQR, 61-128 minutes; n = 42; P = .06). Notably, after implementation of the stroke alert system, the median time from ED arrival to neuroimaging for stroke alerts who were considered IV-tPA candidates before neuroimaging (n = 13) was 54 minutes (IQR, 34-66 minutes). This was significantly shorter than the median time to neuroimaging for stroke alerts who were not considered IV-tPA candidates (89.5 minutes; IQR, 62-126.5 minutes; n = 52; P < .01). MRI with or without MRA and/or magnetic resonance venography was the first imaging study obtained in 55 stroke alerts (85%). Ten (15%) had a computed tomography scan with or without computed tomography angiography as the initial imaging study, 7 (70%) of whom required subsequent MRI for diagnosis. Sixteen stroke alerts (25%) required sedation by an anesthesiologist to obtain neuroimaging; sedation for neuroimaging is not provided by ED physicians at our institution. All stroke alerts requiring sedation were treated with propofol at minimum, and one-half (n = 8) required endotracheal intubation. There was no difference in the median time from ED arrival to neuroimaging for stroke alerts requiring sedation (88 minutes; IQR, 70-127.5 minutes; n = 16) compared with those not requiring sedation (82 minutes; IQR, 47-119 minutes; n = 47; P = .22) (Figure 4). Thirteen stroke alerts (20%) required imaging overnight (between 23:00 and 06:00), and 3 of those required sedation. There was no difference in the median time from ED arrival to neuroimaging for stroke alerts requiring imaging overnight (82 minutes; IQR, 64-102 minutes; n = 13) compared with those whose imaging occurred during the daytime (80 minutes; IQR, 48.5-123 minutes; n = 52; P = .72).
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Table III. Final diagnoses Stroke consults Stroke alerts before stroke after stroke alert system alert system P (n = 14), n (%) (n = 65), n (%)* value
Diagnoses Acute AIS Intraparenchymal hemorrhage Transient ischemic attack Migraine or other headache Seizure Conversion or other psychogenic disorder Infectious or inflammatory disorder Other† Unspecified
3 (21) 0 4 (29) 3 (21) 0 1 (7)
6 (9) 1 (2) 11 (17) 23 (35) 7 (11) 3 (5)
.19 0.99 .43 .36 .34 .56
0
5 (8)
0.99
2 (14) 1 (7)
11 (17) 2 (3)
*Seven patients had 2 final diagnoses. †Bell’s palsy or other peripheral neuropathy, dystonia, necrotizing granulomatous lesion, intracranial neoplasm or other oncologic process, peripheral vertigo, recrudescence of prior stroke symptoms, subdural fluid collection, symptomatic anemia, syncope, or vaso-occlusive crisis without central nervous system involvement.
drome, disqualifying the patient from thrombolysis. The other patient had a large middle cerebral artery infarct, the size of which precluded treatment with IV-tPA; in addition, there was no diffusion–perfusion mismatch, precluding any potential benefit of endovascular intervention. One stroke alert underwent hemicraniectomy for a full territory middle cerebral artery infarct, and one underwent exchange transfusion for stroke in the setting of sickle cell disease. Figure 4. Median time from ED arrival to neuroimaging stratified by requirement for sedation. Box plots showing the median, second (bottom box), and third (top box) quartiles, and the minimum and maximum time from ED arrival to neuroimaging.
Diagnosis Final diagnoses are presented in Table III. Of the patients who presented with brain attack symptoms before the stroke alert system, 3 (21%) had an acute AIS and 4 (29%) had a transient ischemic attack. Three patients (21%) had a migraine or other headache, and none had a seizure. Of the stroke alerts, 18 (28%) had a stroke or other cerebrovascular disorder; 6 (9%) had an acute AIS, 1 (1.5%) had an intraparenchymal hemorrhage, and 11 (17%) had a transient ischemic attack. An additional 12 stroke alerts (18%) had other neurologic emergencies, including seizure (n = 7 [11%]) or an infectious or inflammatory disorder (n = 5 [8%]). Migraine or other headache (n = 23 [35%]) was the most common stroke mimic. Of the 3 patients with AIS before the stroke alert system, one was successfully treated with IV-tPA, and one underwent exchange transfusion for stroke in the setting of sickle cell disease. Two stroke alerts were considered potential IV-tPA candidates before neuroimaging; however, neither was treated with IV-tPA or mechanical thrombectomy. Of these 2 patients, one was newly diagnosed with moyamoya syn4
Discussion The rapid diagnosis of children with AIS has historically proved challenging. Part of the delay in diagnosis relates to delay in arrival of the child to the ED and likely stems, in part, from a lack of community awareness about the possibility of stroke in children.11 However, a significant proportion of the delay also occurs after the child arrives at the hospital.9,11 With the advent of hyperacute therapies for the treatment of AIS and emerging evidence that these interventions may be safe and effective in children, it is imperative that children with AIS are identified in a timely fashion.1-6 This requires enhanced community education and an organized system of evaluation and management once a patient presents for medical care.20 We have shown that the establishment of a stroke alert system at a tertiary children’s hospital, coupled with extensive internal educational efforts, significantly decreases the median time to diagnosis by neuroimaging of patients presenting to the ED with brain attack symptoms. This finding represents an important first step in ensuring that a greater proportion of children with AIS are diagnosed within a time frame that enables treatment with acute interventions. The institution of a stroke alert system at our children’s hospital decreased by more than one-half the median time from arrival in the ED to diagnosis by neuroimaging of patients presenting with brain attack symptoms. Potential candidates for IV-tPA were imaged even more rapidly, almost 4 Harrar et al
- 2019 times as fast as patients who presented with brain attack symptoms before the stroke alert system. This difference may reflect, at least in part, our policy that an ongoing non-emergent MRI is interrupted so that an MRI scanner can be made immediately available for a patient whose imaging is considered emergent based on IV-tPA candidacy. Our findings are consistent with reports from pediatric stroke teams in Tennessee and France. Ladner et al21 reported a median time of 79 minutes from arrival to initial imaging for patients presenting with focal neurologic deficits to a children’s hospital ED in Tennessee after the establishment of a stroke alert system. Similarly, Tabone et al1 reported a median time of 165 minutes from symptom onset to MRI for patients who underwent mechanical thrombectomy as part of a regional pediatric acute stroke protocol in France. It is unknown whether these represent improvements in the time to evaluation of these patients compared with those who presented with brain attack symptoms before the establishment of these stroke alert systems. In contrast to our findings, Shack et al12 reported no change in the in-hospital delay to diagnosis for children presenting as outpatients with AIS after establishment of an acute stroke protocol at a tertiary children’s hospital in Canada. Moreover, the in-hospital delay to diagnosis for children presenting as outpatients with AIS after establishment of a stroke protocol was significantly longer (10.5 hours) than in our cohort; however, that study included all patients presenting within 14 days of AIS onset and only two-thirds to three-quarters of children presenting as outpatients had acute-onset focal neurologic deficits. There was, however, a statistically significant decrease in the inhospital delay in diagnosis for the subset of children presenting as outpatients with AIS with mild symptoms. The pathway from ED arrival to neuroimaging for patients with suspected AIS includes rapid evaluation by a triage nurse, ED physician, and neurologist, and preparation for and initiation of neuroimaging. The majority of patients who present to our ED with brain attack symptoms are seen by an ED physician immediately upon arrival, and implementation of the stroke alert system did not affect this. Interestingly, the stroke alert system did not significantly influence the median time from ED arrival to neurology evaluation, although there was a trend toward a more rapid evaluation after implementation of the stroke alert system. The lack of a significant effect on the median time from arrival to neurology evaluation may reflect the around-theclock presence of a neurology resident in our hospital both before and after implementation of the stroke alert system. It is also possible that the small number of patients who had a stroke consultation in the ED before implementation of the stroke alert system precluded detection of an effect on this measure. There was no difference in the median time from ED arrival to neuroimaging for patients who required sedation to obtain neuroimaging compared with those who did not require sedation. Given that considerably more children who present to the ED with brain attack symptoms have a stroke mimic rather than an AIS, our criteria for administra-
ORIGINAL ARTICLES tion of IV-tPA require that a patient have diffusion restriction on MRI and vessel obstruction on MRA. The use of MRI and MRA can require sedation for acquisition of reliable imaging, raising concern for delay in diagnosis caused by the need for sedation. It is reassuring that the need for sedation did not delay neuroimaging in our system. This may be due to the availability of pediatric anesthesiologists in the hospital around the clock as well as their rapid deployment in the setting of a stroke alert, based on their inclusion in the stroke alert activation page. Although we have decreased by more than one-half the median time from ED arrival to diagnosis for patients presenting with brain attack symptoms, the median time from arrival to imaging is still almost 1 hour for those patients considered potential IV-tPA candidates. Given a median time from onset of symptoms to arrival in the ED of almost 3 hours and the historical windows of 4.5 and 6 hours after a patient’s last seen well time for thrombolysis and thrombectomy, respectively, this leaves little room for unexpected delays in initiating neuroimaging. Performance improvement efforts aimed at identifying the root causes of this continued delay will be paramount to diagnosing more children within a time frame that enables acute intervention. Although new results from large trials of adults with AIS indicate that thrombectomy can be safe and effective up to 24 hours from symptom onset in select patients, the number of patients who meet criteria for treatment beyond 6 hours is small.22,23 Efforts are also underway to identify pediatric patients who may benefit from mechanical thrombectomy in an extended time window. Given the possibility of mechanical thrombectomy up to 24 hours from symptom onset in a subset of adult patients, we are reviewing our acute stroke protocol to determine if the time frame for treatment can be extended for children with certain clinical features who present with acute stroke. Nonetheless, earlier treatment results in better outcomes, and as such rapid diagnosis remains imperative.24 Therefore, we continue to strive to decrease our delay to diagnosis as we anticipate that the shortest time from symptom onset to recanalization is likely to provide the best possible outcome. Many more patients were evaluated by the stroke service in the ED after implementation of our stroke alert system compared with before its implementation (68 vs 14). This likely reflects, in part, an increased awareness of stroke as a potential underlying etiology for brain attack symptoms in children as the implementation of our stroke alert system was coupled with extensive, internal educational efforts. Indeed, the total number of stroke consultations performed throughout the hospital increased during this time from 152 to 224, excluding consultations performed on neonates. The increase in stroke alerts also likely reflects the expectation established with the implementation of the stroke alert system that a patient presenting to the ED with a focal neurologic deficit with acute onset or worsening within the past 5 hours be evaluated by the stroke and cerebrovascular disorders service as a stroke alert. In keeping with this, the relative percentage of stroke consultations performed in the ED
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increased over this time period, from 9.2% before the stroke alert system to 29.0% after the stroke alert system. As noted above, before the implementation of the stroke alert system, patients presenting to the ED with brain attack symptoms were evaluated by the stroke and cerebrovascular disorders service at the discretion of the treating ED provider. Although implementation of our stroke alert system led to faster diagnosis of patients presenting to the ED with brain attack symptoms, further study is required to determine whether faster diagnosis in the ED results in more frequent use of acute therapies and improved outcome in children with AIS, as it has in adults. This research will require continued collection of clinical data for children who present to the ED with brain attack symptoms as well as continued efforts to decrease the time from onset of symptoms to diagnosis. Our study has limitations inherent in the retrospective nature of our study design. Although cases were collected prospectively, the retrospective nature of our data review meant that not all data points were available for every patient in our cohort. Moreover, all of our data come from a single center and may not be generalizable to other pediatric centers. For example, our institution has 7 non-operating room–based MRI scanners; many pediatric centers likely have fewer scanners available for emergent imaging. Finally, our preimplementation group was quite small and, although we were able to detect a significant improvement in the median time from ED arrival to neuroimaging, our study may have been underpowered to detect other, more subtle impacts of our stroke alert system. The establishment of a stroke alert system at a children’s hospital decreases the median time to diagnosis of patients presenting to the ED with brain attack symptoms by more than 50%. This constitutes an important first step in ensuring that a greater proportion of children with AIS are diagnosed in a time frame that permits treatment with hyperacute therapies. Substantial work remains to reduce further the time not only from arrival to neuroimaging but also from onset of symptoms to neuroimaging. Ongoing educational and quality improvement efforts will be critical to ensure that a greater number of children are diagnosed within a time frame that enables treatment with acute interventions. n Submitted for publication May 16, 2019; last revision received Aug 14, 2019; accepted Sep 12, 2019. Reprint requests: Dana B. Harrar, MD, PhD, Division of Neurology, Children’s National Hospital, 111 Michigan Avenue NW, Washington, DC 20010. E-mail: [email protected]
Data Statement Data sharing statement available at www.jpeds.com.
References 1. Tabone L, Mediamolle M, Bellesme C, Lesage F, Grevent D, Ozanne A, et al. Regional pediatric acute stroke protocol: initial experience during 3 years and 13 recanalization treatments in children. Stroke 2017;48: 2278-81. 6
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2. Satti S, Chen J, Sivapatham T, Jayaraman M, Orbach D. Mechanical thrombectomy for pediatric acute ischemic stroke: review of the literature. J Neurointerv Surg 2017;9:732-7. 3. Bigi S, Dulcey A, Gralla J, Bernasconi A, Mellinger A, Datta AN, et al. Feasibility, safety, and outcome of recanalization treatment in childhood stroke. Ann Neurol 2018;83:1125-32. 4. Cappellari M, Moretto G, Grazioli A, Ricciardi GK, Bovi P, Ciceri EFM. Primary versus secondary mechanical thrombectomy for anterior circulation stroke in children: an update. J Neuroradiol 2018;45:102-7. 5. Sporns PB, Kemmling A, Hanning U, Minnerup J, Strater R, Niederstadt T, et al. Thrombectomy in childhood stroke. J Am Heart Assoc 2019;8:e011335. 6. Sun LR, Felling RJ, Pearl MS. Endovascular mechanical thrombectomy for acute stroke in young children. J Neurointerv Surg 2019;11:554-8. 7. Gabis LV, Yangala R, Lenn NJ. Time lag to diagnosis of stroke in children. Pediatrics 2002;110:924-8. 8. McGlennan C, Ganesan V. Delays in investigation and management of acute arterial ischaemic stroke in children. Dev Med Child Neurol 2008;50:537-40. 9. Rafay MF, Pontigon AM, Chiang J, Adams M, Jarvis DA, Silver F, et al. Delay to diagnosis in acute pediatric arterial ischemic stroke. Stroke 2009;40:58-64. 10. Srinivasan J, Miller SP, Phan TG, Mackay MT. Delayed recognition of initial stroke in children: need for increased awareness. Pediatrics 2009;124:e227-34. 11. Mallick AA, Ganesan V, Kirkham FJ, Fallon P, Hedderly T, McShane T, et al. Diagnostic delays in paediatric stroke. J Neurol Neurosurg Psychiatry 2015;86:917-21. 12. Shack M, Andrade A, Shah-Basak PP, Shroff M, Moharir M, Yau I, et al. A pediatric institutional acute stroke protocol improves timely access to stroke treatment. Dev Med Child Neurol 2017;59:31-7. 13. Bernard TJ, Rivkin MJ, Scholz K, deVeber G, Kirton A, Gill JC, et al. Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke trial. Stroke 2014;45:2018-23. 14. Rivkin MJ, deVeber G, Ichord RN, Kirton A, Chan AK, Hovinga CA, et al. Thrombolysis in pediatric stroke study. Stroke 2015;46:880-5. 15. Mackay MT, Chua ZK, Lee M, Yock-Corrales A, Churilov L, Monagle P, et al. Stroke and nonstroke brain attacks in children. Neurology 2014;82: 1434-40. 16. Mackay MT, Monagle P, Babl FE. Brain attacks and stroke in children. J Paediatr Child Health 2016;52:158-63. 17. Rivkin MJ, Bernard TJ, Dowling MM, Amlie-Lefond C. Guidelines for urgent management of stroke in children. Pediatr Neurol 2016;56: 8-17. 18. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377-81. 19. Ichord RN, Bastian R, Abraham L, Askalan R, Benedict S, Bernard TJ, et al. Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke 2011;42:613-7. 20. Ferriero DM, Fullerton HJ, Bernard TJ, Billinghurst L, Daniels SR, DeBaun MR, et al. Management of stroke in neonates and children: a scientific statement from the American Heart Association/American Stroke Association. Stroke 2019;50:e51-96. 21. Ladner TR, Mahdi J, Gindville MC, Gordon A, Harris ZL, Crossman K, et al. Pediatric acute stroke protocol activation in a children’s hospital emergency department. Stroke 2015;46:2328-31. 22. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 2018;378:708-18. 23. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 2018;378:11-21. 24. Saver JL, Fonarow GC, Smith EE, Reeves MJ, Grau-Sepulveda MV, Pan W, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013;309: 2480-8.
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ORIGINAL ARTICLES
Acute Stroke Guideline: INITIAL APPROACH 1. Any child with potential stroke Including all BCH ED and children from outside BCH via Critical Care Transport Team (BCH or other)
2. Stroke Screening Questions I. Is there a focal neurological deficit? a. Vision loss or double vision b. Unilateral weakness or sensory change c. Speech difficulty d. Dizziness or trouble walking II. Did the problem appear or worsensuddenly? III. Has the problem been present for less than 5 hours? (When was the child last seen well?)
4a. ED or responsible service supports airway, breathing & circulation (consider ICU STAT on wards), starts IV x 2 if not already in place, draws stat INR, PTT, type and screen, CBC, PLTs, fibrinogen, glucose, electrolytes
Stroke Stat team: Stroke Attending ED Neurology resident Neuroradiologist ED Pharmacist [MSICU Fellow, Intensive Care Neurology resident, Anesthesia (FYI Only)] See Acute Stroke Team Activation Plan
3. Child meets all acute stroke criteria (I-III)
No
Yes/ Not sure
Consider urgent consult to Neurology and urgent MR while considering other diagnoses and initiating neuroprotective care
4. Call Stroke Stat IMMEDIATELY Via Comm Center (x5-2170) ALL HOURS o
5. Possible stroke confirmed by ED neurology resident in consultation with stroke attending Pediatric NIHSS performed
No
Initial Supportive Rx: • NPO, head of bed flat • Normotension: target SBP is between 50th and 90th %ile for age, treat low BP with NS +/- pressors, treat significant HTN with labetalol to lower by ~25% over 24 hours (more quickly if tPA candidate, see page 2) • Normovolemia: Isotonic fluid (ie, 0.9% NaCl) at maintenance with bolus prn • Normoglycemia: For age >2, no glucose in IV fluids unless hypoglycemic; for age <2, use glucosecontaining fluids, eg: D50.9%NaCl • Normal O2, CO2 and pH • Normothermia: treat patient w/ T>37o with acetaminophen • Seizure control: AED ASAP with any suspected seizure activity
Yes
6. Neurology resident or ED/ward staff request emergent MRI (page neuroradiology attending on call)
See PAGE 3 for ALTERNATIVE workflow if MRI unavailable
7. Prepare patient for transport to MRI with appropriate equipment and personnel
Go to PAGE 2
If patient on the ward, transfer to MSICU
Adapted from algorithm developed at Toronto Hospital for Sick Children
Figure 1. Boston Children’s Hospital Acute Stroke Response Algorithm. ABC, airway, breathing, circulation; AED, automated external defibrillator; ASA, aspirin; ASAP, as soon as possible; AVM, arteriovenous malformation; (Continues) A Stroke Alert Protocol Decreases the Time to Diagnosis of Brain Attack Symptoms in a Pediatric Emergency Department
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Figure 1. BCH, Boston Children’s Hospital; CBC, complete blood count; COW, circle of Willis; CT, computed tomography; CTA, angiography; DWI, diffusion-weighted imaging; FLAIR, fluid attenuated inversion recovery; (Continues) 6.e2
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Acute Stroke Guideline: Acute Response MRI Unavailable Stroke Stat team: Stroke Attending ED Neurology resident Neuroradiologist ED Pharmacist [Anesthesia, MSICU Fellow, Intensive Care Neurology Resident (FYI Only) ]
1. Neurology resident or ED staff requests emergent CT with CTA (page neuroradiology attending on call)
See Acute Stroke Team Activation Plan
2. Transport patient to CT accompanied by appropriate personnel and equipment
3. Perform CT scan with CTA
5a. Transport pt. to MRI if now available, otherwise back to ED or MSICU
No
5. CT/ CTA shows ALL of: a. No hemorrhage or alternate diagnosis, b. Parenchyma normal or early signs of cerebral ischemia consistent with stroke, and c. Definitive evidence of arterial occlusion
Yes
Time from onset + estimated time to arrival > 4.5 hrs, or age < 2 years, or resolving deficit, or tPA contraindication (see page 2)
Time from onset + estimated time to arrival < 4.5 hours, and age > 2 years, and persistent focal deficit, and no tPA contraindication (see page 2)
Yes Yes
tPA CANDIDATE Admit patient and provide neuroprotective and supportive acute stroke treatment per stroke/ICU service
Consider other diagnostic imaging (eg: cerebral angiography) and/or IA tPA or other endovascular therapy
7. Stroke team member calls ED pharmacist (x51894) with phone request to prepare tPA infusion and places order in CHAMPS using “ED Stroke Orderset” and “STAT” designation
8. Stroke Neurologist confirms final intention to treat with IV tPA and calls ED Pharmacist (x51894); admit patient to MSICU
Go to PAGE 4
Figure 1. FYI, first year intern; GI, gastrointestinal; GU, genitourinary; HOB, head of bed; HTN, hypertension; IA, intra-arterial; ICP, intracranial pressure; ICU, intensive care unit; INR, international normalized ratio; (Continues) A Stroke Alert Protocol Decreases the Time to Diagnosis of Brain Attack Symptoms in a Pediatric Emergency Department
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IV tPA TREATMENT PROTOCOL IV tPA CANDIDATE < 4.5 hrs from onset, age >2 years, persistent focal deficit, no contraindications, BOTH proven infarct AND arterial occlusion on MR or CT/CTA Yes ED Pharmacy prepares tPA infusion with stat release to ED or MSICU. Bolus dose: 10% of total dose IV over 5 min Infusion dose: remaining 90% IV over 1 hour Total dose: .9 mg/kg IV Nurse/MD double checks dose with pharmacy
Maintain cardiorespiratory and BP monitoring. If agebased tPA parameters acceptable (see green box to right) begin tPA infusion as soon as available (in ED or en route to MSICU). Note: dedicated IV for tPA required to proceed.
Systolic BP should be maintained between 50th %ile for age and 15% above 95th %ile for age (see below) Treat to lower BP if > 15% above 95th %ile for age for more than 1 hr. OR If > 20% above 95th %ile for age at any time SEE CHART BELOW
Systolic Blood Pressure Parameters - Female Age
50%
95%
>15% above 95%
>20% above 95%
1 – 4 years
90
111
128
133
5 years
94
113
130
136
6 – 10 years
96
121
139
145
11 – 18 years
105
131
151
157
>18 years
110
140
161
168
Labetalol .2 mg/kg IV push over 2-3 min, repeat q15 minutes prn; consider nicardipine drip, 1 mcg/kg/min, titrate to desired BP Use with caution in patients with asthma or underlying cardiac disease
Systolic Blood Pressure Parameters - Male Age
50%
95%
>15% above 95%
>20% above 95%
1 – 4 years
90
112
129
134
5 years
95
113
130
136
6 – 10 years
96
121
139
145
11 – 18 years
105
140
161
168
>18 years
110
140
161
168
Figure 1. IV, intravenous; LMWH, low-molecular-weight heparin; MCA, middle cerebral artery; MSICU, medical-surgical intensive care unit; NG, nasogastric; NPO, nil per os; NSAID, nonsteroidal anti-inflammatory drug; (Continues) 6.e4
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POST tPA ADMINISTRATION CARE PROTOCOL
tPA administered IV
Ped NIHSS recording (by neurologist) 1. 2. 3. 4. 5. 6. 7.
50-75 mins. post tPA initiation 2 hrs. post tPA initiation 12 hrs. post tPA initiation 24 hrs. post tPA initiation 36 hrs. post tPA initiation 48 hrs. post tPA initiation Day 7 or discharge.
Neurologic status checks
Blood Pressure (BP) checks
1.
1. 2. 3. 4. 5.
2. 3.
Every 15 mins. X 2 hrs., then, Every 30 mins. X 6 hrs., then, Every 60 mins. X 16 hrs
Every 15 mins. X 4 hrs., then, Every 30 mins X 4 hrs., then, Every 60 mins X 16 hrs., then, Every 2 hrs X 24 hrs., then, Every 4 hrs X 24 hrs.
See Page 4 for BP guidelines
Any neurological deterioration Yes Provide supportive care (ABCs) Order urgent CT head Draw stat CBC, INR, PTT Order and prepare to give 6-8 units of cryoprecipitate (fibrinogen and factor VIII) Order and prepare to give 6-8 units of platelets Notify stroke neurologist Consult neurosurgery if signs of elevated ICP or CT reveals bleed or mass effect
Post-tPA Care Remains in MSICU for minimum of 24 hours; If patient’s condition permits, transfer to 9N or SUU for next 48 hours HOB flat NPO x 24 hours after tPA CBC, INR, PTT, fibrinogen, d-dimer at 6 hours No arterial punctures, invasive procedures or anti-coagulants (ASA, NSAID, UFH, LMWH) for 24 hours Avoid indwelling urinary catheter, NG tube Maintain euglycemia Maintain normothermia – avoid fever Follow-up imaging per stroke neurologist/ICU
Figure 1. PLT, platelets; prn, as needed; PT, prothrombin time; PTT, partial thrmomboplastin time; SAH, sibarachnoid hemorrhage; SBE, subacute bacterial endocarditis; SBP, systolic BP; SWI, susceptibility weighted imaging; TOF, time of flight; UFH, unfractionated heparin. (Continued) A Stroke Alert Protocol Decreases the Time to Diagnosis of Brain Attack Symptoms in a Pediatric Emergency Department
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Table I. Patient characteristics
Medical and neurologic histories
Patients before stroke alert system (n = 14*), n (%)
Patients after stroke alert system (n = 64†), n (%)
P value
Stroke Transient ischemic attack Epilepsy Migraine Cerebral vasculopathy Congenital heart disease Sickle cell disease
3 (21) 5 (36) 1 (7) 1 (7) 4 (29) 0 2 (14)
2 (3) 14 (22) 11 (17) 8 (12) 10 (15) 10 (15) 6 (9)
.04 .28 .68 0.99 .26 .19 .63
*Five patients had no prior neurologic diagnosis, and 5 patients had multiple prior neurologic diagnoses. †Twenty-five patients had no prior neurologic diagnosis, and 17 patients had multiple prior neurologic diagnoses.
Figure 2. Median time from symptom onset to ED arrival. Box plots showing the median, second (bottom box), and third (top box) quartiles, and the minimum and maximum time from symptom onset to ED arrival. Stratification by PedNIHSS is presented only for patients after implementation of the stroke alert system.
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