- Email: [email protected]
Improvement in Door-to-Needle Time in Patients with Acute Ischemic Stroke via a Simple Stroke Activation Protocol
ARTICLE IN PRESS
Improvement in Door-to-Needle Time in Patients with Acute Ischemic Stroke via a Simple Stroke Activation Protocol Benjamin Y.Q. Tan, MBBS, MRCP,* Nicholas J.H. Ngiam, MBBS,* Sibi Sunny, MBBS, MRCP,* Wan Yee Kong, MBBS, MRCP,* Howen Tam, MBBS,† Tiong Beng Sim, MBBS,† Benjamin S.H. Leong, MBBS,† Chandra Bhartendu, MBBS, MRCP,* Prakash R. Paliwal, MBBS, MRCP,* Raymond C.S. Seet, MBBS, MRCP,* Bernard P.L. Chan, MBBS, MRCP,* Hock Luen Teoh, MBBS, MRCP,* Vijay K. Sharma, MBBS, MRCP,*,‡ and Leonard L.L. Yeo, MBBS, MRCP*,§
Background: In acute ischemic stroke (AIS), treatment with intravenous tissue-type plasminogen activator (IV-tPA) is time-sensitive. All stroke centers make continual efforts to reduce door-to-needle time (DNT) with varying success. We present the impact of modifications to our stroke activation protocol on DNT. Methods: We included 404 consecutive patients with AIS receiving IV-tPA between January 2014 and December 2016. First changes in stroke activation protocol were made in March 2015 in the form of prenotification by paramedics, direct transfer from ambulance to computed tomography (CT) scanner, and rapid en route neurological assessment by an emergency physician and neurologist. In March 2016, a second amendment was made where a stroke nurse accompanied the patient to expedite various steps in the treatment pathway, including endovascular treatment in eligible cases. Results: Both protocol amendments resulted in improvement in DNT and door-to-CT time from 84 ± 47 minutes before intervention to 69 ± 33 minutes after protocol amendment 1 to 59 ± 37 minutes after protocol amendment 2. In particular, the second amendment (144 patients) showed significant shortening of DNT compared with the 137 patients before (59 ± 37 minutes versus 69 ± 33 minutes, P = .020), with a higher percentage achieving the target of 60 minutes (68.1% versus 48.2%, P < .001). This finding was attributed to a reduction in both door-to-CT time and CT-to-needle time. This improvement remained consistent over subsequent months. Conclusions: The application of a simple systems-based, multidisciplinary stroke activation protocol may help in significant reduction in DNT. Encouraging increased patient ownership by stroke nurses appeared to be a promising approach for timely administration of definitive acute therapies. Key Words: Acute ischaemic stroke—door-to-needle time—stroke activation protocol—clinical outcomes. © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.
From the *Division of Neurology, Department of Medicine; †Department of Emergency Medicine, National University Health System, Singapore, Singapore; ‡Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; and §Department of Clinical Neuroscience, Karolinska Institutet and Department of Neurology, Karolinska University Hospital, Stockholm, Sweden. Received November 10, 2017; revision received November 30, 2017; accepted January 1, 2018. Address correspondence to Leonard L.L. Yeo, MBBS, MRCP, National University Health System, 1 E Kent Ridge Road, 119228, Singapore. E-mail: [email protected]. 1052-3057/$ - see front matter © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.01.005
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2018: pp ■■–■■
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ARTICLE IN PRESS B.Y.Q. TAN ET AL.
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Introduction In acute ischemic stroke (AIS), the effectiveness of intravenously administered tissue-type plasminogen activator (IV-tPA) is time dependent. Pooled data from major IVtPA trials suggest that the therapeutic benefit is maximal when thrombolysis is initiated rapidly and worsens rapidly with the passing of time.1-4 Accordingly, the number needed to treat to achieve a good functional outcome (modified Rankin scale 0-1) is only 4.5 when IV-tPA is initiated within 90 minutes.2 Furthermore, early initiation of the treatment translated into improved patient outcomes.5 The door-to-needle time (DNT) is an acceptable measurable standard of acute stroke care. The reduction of the DNT is a complex process, which requires a close coordination across several departments to provide a rapid administration of acute revascularization therapy in AIS.6,7 Many protocols, including the Toyota system, have been implemented to good effect.5,6 Nonetheless, these improvements need to be individualized for each center to be effective. For example, the Helsinki protocol and the value stream analysis, proven effective at the Washington University in reducing DNT, failed to show any effect on the “after-hours” DNT when applied at the Royal Melbourne Hospital in Australia.7-9 At our tertiary center, we launched protocol amendments in March 2015 and March 2016. We present the impact of these initiatives in reducing DNT and functional outcome.
Methods Before March 2015 at our center, paramedics evaluated patients with AIS and performed a point-of-care glucose test. Upon arrival to our emergency department, patients were further evaluated by emergency physicians. An urgent computed tomography (CT) scan of the brain was performed if the patient was considered potentially eligible for acute revascularization treatment. Stroke neurologist was simultaneously alerted. An intravenous line was set and blood was sent to the laboratory while waiting for the CT. Neurologist would review the patient and CT scan, as well as perform the National Institutes Health Stroke Scale (NIHSS). The patient was transferred to the neurology high-dependency ward for IV-tPA treatment. The decision for further endovascular therapy was made during the tPA infusion. In an attempt to improve the delivery of acute revascularization measures, we evaluated the existing workflow in February 2015 and identified steps that could be shortened or modified. As a result, the first protocol amendments were made in March 2015 (Fig 1) and the second amendment in March 2016. In the first protocol amendment, we introduced a prenotification sent to the emergency physician by the paramedics from patients’ home if AIS was suspected. Paramedics would also perform pointof-care glucose test on the site and insert an intravenous line. The radiographer, radiologist, and stroke neurologist were simultaneously alerted. Patients with AIS were
Figure 1. Change in workflow with implementation of a simple multidisciplinary stroke activation protocol. Abbreviations: CT, computed tomography; HDU, high-dependency unit; IV-tPA, intravenous tissue-type plasminogen activator.
ARTICLE IN PRESS DOOR-TO-NEEDLE TIME IN PATIENTS WITH AIS
given top priority for using the CT scanner. The neurologist (during office hours) and emergency physician would await the ambulance in the emergency department and transfer the patient to the CT scanner immediately upon arrival. A rapid clinical examination and NIHSS scoring would be performed during the transfer or in the CT room. In eligible patients, IV-tPA bolus was administered based on the estimation of body weight. After IV-tPA bolus, the patient was transferred to neurology high-dependency ward, equipped with weighing beds. Adjustments were made to the total tPA dose. Decision for rescue endovascular therapy was made during the tPA infusion. In the second protocol amendment, we trained 6 specialized nurses who were already working in the neurology high-dependency ward. They were trained in early assessment of AIS, including performing NIHSS, sending necessary blood investigations, and basic reading of the CT scans for early ischemic signs. Subsequently, these stroke nurses were added to the 24-hour stroke response team. IV-tPA bolus was administered on the CT table in eligible patients, followed by CT-angiography. In patients with large vessel occlusion, neurointerventionist and anesthetist were immediately alerted for possible endovascular treatment. IV-tPA infusion was completed in the emergency room, instead of transferring the patients to the neurology high-dependency unit. Eligible patients were transferred to the angiography suite for rescue endovascular revascularization if needed. Data were collected for all consecutive patients with AIS who received systemic thrombolysis during the study period. Comparisons were made between before and after intervention, in terms of DNT, door-to-CT time, CT-toneedle time, and onset-to-needle time. Where appropriate, the groups were compared using Student’s t tests for continuous variables and chi-square tests for categorical variables. A histogram was plotted to demonstrate the distribution of patients across various DNTs before and after intervention. Data were analyzed using SPSS version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.), and a P value < .05 was considered significant.
Results Of the 410 consecutive patients with AIS treated with IV-tPA during the study period, 129 patients (31%) before amendment 1 served as the control group. A total of 137 patients (33%) were treated according to amendment 1 (from March 2015 to February 2016) and 144 (35%) followed the amendment 2 treatment protocol (from March 2016 to December 2016). The DNT showed a stepwise reduction from the control group according to protocol amendment 1 and subsequently protocol amendment 2 (84 ± 47 minutes versus 69 ± 33 minutes versus 59 ± 37 minutes; P < .001). Furthermore, a considerably higher proportion of patients
3
was treated within the recommended DNT of 60 minutes with each protocol amendment (19.4%, 48.2%, and 68.1%, respectively; P < .001) (Fig 2). Further analyses showed that the reduction in the DNT as a result of the 2 protocol amendments was predominantly due to the reduction in door-to-CT time (31 ± 37 minutes in the control group, 14 ± 24 minutes after protocol amendment 1, and 10 ± 25 min after protocol amendment 2, respectively; P < .001). CT-to-needle time showed a nonsignificant reduction after protocol amendment 2 (49 ± 23 minutes versus to 54 ± 22 minutes after protocol amendment 1). Interestingly, the onset-to-needle time remained comparable among the 3 groups (167 ± 53, 153 ± 58, and 160 ± 80 minutes, respectively; P = .371). Overall, our protocol amendments increased the proportion of patients with AIS who could be treated within window for thrombolysis; 14.7% before intervention to 16.7% after protocol amendment 1 and 19.3% after protocol amendment 2, although this trend was not statistically significant. We compared functional outcomes of patients between protocol amendments 1 and 2. Comparing the 2 protocols, we found no significant difference in terms of change in NIHSS at 48 hours, good functional outcome rates (as defined as modified Rankin scale 0-2 at 3 months), mortality, or symptomatic intracranial hemorrhage. Although not statistically significant, there was a trend toward better NIHSS scores at 48 hours (9.1 versus 7.2, P = .076) and higher incidence of symptomatic intracranial hemorrhage in protocol amendment 2 (6.3% versus 2.2%, P = .093).
Discussion Our study showed that better organization of various concurrent multidisciplinary activities involved in acute stroke care effectively reduced the DNT. The induction of a 24-hour stroke nurse into the acute stroke care program was the most important action for ensuring an expedited treatment protocol.
Need to Improve Speed The benefits of IV-tPA decrease rapidly with elapsing time from stroke onset.10 The American Heart Association developed the Target Stroke campaign in 2010 with the intention to reduce DNT to less than 60 minutes.11 Later, the Stroke Phase II program recommended more aggressive goals for participating hospitals such as achieving DNT within 60 minutes in 75% of treated patients and within 45 minutes in 50% of treated patients.12
Strategies Adopted DNT varies widely among the stroke centers. The Safe Implementation of Treatments in Stroke registry of more than 80,000 patients from more than 1000 centers reported a median DNT of 65 minutes. In contrast, many
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Figure 2. Significant reduction in door-to-needle times with implementation of stroke activation protocol.
B.Y.Q. TAN ET AL.
ARTICLE IN PRESS DOOR-TO-NEEDLE TIME IN PATIENTS WITH AIS
centers in Europe have reported much lower DNT, reaching as low as 20 minutes in Helsinki, Finland.11,13,14 All mature stroke centers make continual efforts to reduce their DNT. Factors reported as most effective in reducing the DNT are rapid triage protocol and stroke team notification, single-call activation system, and tPA being stored in the emergency department.15 Interestingly, simultaneous implementation of greater number of strategies was strongly associated with a shorter DNT.16,17 Setting up of a successful stroke thrombolysis program is a time-consuming affair.11 At our tertiary center, it took nearly 2 years to develop a reliable system of expedited acute stroke care at the emergency department. To maintain a consistent improvement, we introduced roundthe-clock availability of a stroke nurse who facilitated a streamlined flow of processes in an expedited manner. She was also responsible for maintaining communication between the family members and various stakeholders in acute stroke care. Another important action for reducing DNT was the removal of formal informed consent. This is considered acceptable because IV-tPA therapy is the current standard of care.18
Lack of Improvement in Functional Outcome Despite significant improvement in DNT after protocol amendments 1 and 2, we could not demonstrate any improvement in functional outcomes in terms of change in NIHSS, good functional outcomes at 3 months, or mortality. This may be due to the fact that improvement in DNT was offset by patients with a delayed presentation to the emergency department, as evidenced by the similar onset-to-needle times across all groups. Other reasons may include a relatively small sample size or changing patterns of stroke subtypes over the years. Of further concern also is the trend toward increasing incidence of symptomatic intracranial hemorrhage in protocol amendment 2. Although not statistically significant, more study is warranted to evaluate if such strategies truly contribute to higher risks of bleeding.
5
Table 1. Measures to reduce stroke timing indices based on existing literature Measures to reduce the door-to-needle time Single call activation system15 Rapid triage at the emergency department15 Prenotification warning of incoming patients with stroke by paramedics8 Premixing of tPA15 Direct transportation of patient from ambulance to scanner9 Optimized scan protocols for speed15 Streamlined consent taking or abolishing consent taking Team assembled in the emergency department awaiting patient’s arrival8 Scans read by team as it is being done9 Bolus of IV-tPA given on the scanner table after initial scans9 Delay nonurgent cases so scanner is available8 Paramedics insert intravenous access and perform point-of-care glucose test in ambulance8 Emergency physician and neurologist assesses patient simultaneously in the emergency department15 tPA stored in the emergency department next to scanner15 Stroke chronometer in the form of a ticking clock to impart urgency19 Neuroscience training to emergency physicians4 Abbreviation: IV-tPA, intravenous tissue-type plasminogen activator.
use of a Stroke Chronometer where a ticking clock is visible to all members of the acute stroke care team, which imparts a sense of urgency.19 Providing regular training to the emergency physicians is another effective strategy for rapid stroke care especially during “after-hours” care4 (Table 1). Finally, attempts should be made to start IV-tPA infusion as soon as possible after the bolus injection because a bolus-to-infusion interval of more than 5 minutes may reduce its efficacy.20
Limitations Strategies for Future Continued efforts are needed in maintaining and further reducing the DNT. Being the first professional contact for patients with AIS and their families, ambulance paramedics constitute the most important link in the chain of acute stroke care. In addition to paramedics’ training for better diagnosis and rapid response, it is important to involve them in the initial management process in the emergency room. Regular feedback on the final outcome of patients with AIS to the paramedics, emergency physicians, and radiologists may also be considered not only for the maintenance of an expedited acute stroke care program but also to identify any additional areas for further improvement. Implementation of technological solutions may also be beneficial to the acute care centers. One example is the
Several limitations should be acknowledged. This is a single center study and the results may not be generalized, largely owing to the inherent variations among stroke centers. We present only the initial reduction of DNT as a result of various interventions in the early stroke care. Whether these results can be sustained in the long term or improved further need a longer observation period. While we focused on the DNT, we did not target onsetto-treatment time. Although we did not encounter this problem, in-hospital delays have previously been shown to be longer in patients with AIS arriving earlier.20,21 While it may be difficult to explain why reducing DTN time did not translate into better functional outcomes, nonavailability of an in-house stroke neurologist after office hours could have resulted in inadvertent delays (about
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Table 2. Comparison of door-to-needle time in thrombolysed acute ischaemic stroke patients before and after interventions
Mean door-to-needle time in minutes Thrombolysis initiated within 60 min of arrival Mean door-to-CT time (min) Mean CT-to-needle time (min) Mean onset-to-needle time (min)
No intervention (n = 129)
Protocol 1 (n = 137)
Protocol 2 (n = 144)
84 (±47) 19.4% 31 (±37) 53 (±25) 167 (±53)
69 (±33)* 48.2%* 14 (±24)* 54 (±22) 153 (±58)
59 (±37)*,† 68.1%*,† 10 (±25)* 49 (±23) 160 (±80)
Abbreviation: CT, computed tomography. *Bonferroni post hoc analysis, compared with no intervention, P < .005. †Bonferroni post hoc analysis, compared with protocol 1, P < .05.
50 minutes) in the administration of IV-tPA despite a faster access to the CT scanner (Table 2).
7.
Conclusions Our study reinforces the finding that the application of a simple systems-based and reorganization of multidisciplinary stroke activation protocol may help in significant reduction in DNT and improvement in acute stroke care delivery. An increased involvement of dedicated stroke nurses and patient ownership may facilitate timely administration of definitive therapies for ensuring better outcomes. Our current model of care could serve as an example for setting up acute stroke centers.
8.
9.
10.
11.
Appendix: Supplementary Material Supplementary data to this article can be found online at doi:10.1016/j.jstrokecerebrovasdis.2018.01.005.
12.
References 1. Marler JR, Tilley BC, Lu M, et al. Early stroke treatment associated with better outcome: the NINDS rt-PA stroke study. Neurology 2000;55:1649-1655. 2. Lees KR, Bluhmki E, von Kummer R, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010;375:1695-1703. 3. Lansberg MG, Schrooten M, Bluhmki E, et al. Treatment time-specific number needed to treat estimates for tissue plasminogen activator therapy in acute stroke based on shifts over the entire range of the modified Rankin scale. Stroke 2009;40:2079-2084. 4. Greenberg K, Maxwell CR, Moore KD, et al. Improved door-to-needle times and neurologic outcomes when IV tissue plasminogen activator is administered by emergency physicians with advanced neuroscience training. Am J Emerg Med 2015;33:234-237. 5. Liang Z, Ren L, Wang T, et al. Effective management of patients with acute ischemic stroke based on lean production on thrombolytic flow optimization. Australas Phys Eng Sci Med 2016;39:987-996. 6. Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European
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Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017-1025. Ford AL, Williams JA, Spencer M, et al. Reducing door-to-needle times using Toyota’s lean manufacturing principles and value stream analysis. Stroke 2012;43:33953398. Meretoja A, Strbian D, Mustanoja S, et al. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology 2012;79:306-313. Meretoja A, Weir L, Ugalde M, et al. Helsinki model cut stroke thrombolysis delays to 25 minutes in Melbourne in only 4 months. Neurology 2013;81:1071-1076. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014;384:1929-1935. Fonarow GC, Smith EE, Saver JL, et al. Improving door-to-needle times in acute ischemic stroke: the design and rationale for the American Heart Association/ American Stroke Association’s Target: Stroke initiative. Stroke 2011;42:2983-2989. Target stroke phase 2 webpage. Available at: http:// www.strokeassociation.org/STROKEORG/ Professionals/TargetStroke/Target-Stroke_UCM_314495 _SubHomePage.jsp. Accessed April 17, 2017. Sobesky J, Frackowiak M, Zaro Weber O, et al. The Cologne stroke experience: safety and outcome in 450 patients treated with intravenous thrombolysis. Cerebrovasc Dis 2007;24:56-65. Tveiten A, Mygland A, Ljostad U, et al. Intravenous thrombolysis for ischaemic stroke: short delays and high community-based treatment rates after organisational changes in a previously inexperienced centre. Emerg Med J 2009;26:324-326. Xian Y, Smith EE, Zhao X, et al. Strategies used by hospitals to improve speed of tissue-type plasminogen activator treatment in acute ischemic stroke. Stroke 2014;45:1387-1395. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013; 309:2480-2488. Saver JL, Smith EE, Fonarow GC, et al. The “golden hour” and acute brain ischemia: presenting features and lytic therapy in >30,000 patients arriving within 60 minutes of stroke onset. Stroke 2010;41:1431-1439. Tai YJ, Yan B. Minimising time to treatment: targeted strategies to minimize time to thrombolysis for acute ischaemic stroke. Intern Med J 2013;43:1176-1182.
ARTICLE IN PRESS DOOR-TO-NEEDLE TIME IN PATIENTS WITH AIS 19. de Seabra Marto JP, Borbinha C, Calado S, et al. The stroke chronometer—a new strategy to reduce door-toneedle time. J Stroke Cerebrovasc Dis 2016;25:23052307. 20. Ferrari J, Knoflach M, Kiechl S, et al. Stroke thrombolysis: having more time translates into delayed therapy: data
7 from the Austrian Stroke Unit Registry. Stroke 2010; 41:2001-2004. 21. Choi HY, Kim EH, Yoo J, et al. Decision-making support using a standardized script and visual decision aid to reduce door-to-needle time in stroke. J Stroke 2016;18:239241.
Improvement in Door-to-Needle Time in Patients with Acute Ischemic Stroke via a Simple Stroke Activation Protocol Benjamin Y.Q. Tan, MBBS, MRCP,* Nicholas J.H. Ngiam, MBBS,* Sibi Sunny, MBBS, MRCP,* Wan Yee Kong, MBBS, MRCP,* Howen Tam, MBBS,† Tiong Beng Sim, MBBS,† Benjamin S.H. Leong, MBBS,† Chandra Bhartendu, MBBS, MRCP,* Prakash R. Paliwal, MBBS, MRCP,* Raymond C.S. Seet, MBBS, MRCP,* Bernard P.L. Chan, MBBS, MRCP,* Hock Luen Teoh, MBBS, MRCP,* Vijay K. Sharma, MBBS, MRCP,*,‡ and Leonard L.L. Yeo, MBBS, MRCP*,§
Background: In acute ischemic stroke (AIS), treatment with intravenous tissue-type plasminogen activator (IV-tPA) is time-sensitive. All stroke centers make continual efforts to reduce door-to-needle time (DNT) with varying success. We present the impact of modifications to our stroke activation protocol on DNT. Methods: We included 404 consecutive patients with AIS receiving IV-tPA between January 2014 and December 2016. First changes in stroke activation protocol were made in March 2015 in the form of prenotification by paramedics, direct transfer from ambulance to computed tomography (CT) scanner, and rapid en route neurological assessment by an emergency physician and neurologist. In March 2016, a second amendment was made where a stroke nurse accompanied the patient to expedite various steps in the treatment pathway, including endovascular treatment in eligible cases. Results: Both protocol amendments resulted in improvement in DNT and door-to-CT time from 84 ± 47 minutes before intervention to 69 ± 33 minutes after protocol amendment 1 to 59 ± 37 minutes after protocol amendment 2. In particular, the second amendment (144 patients) showed significant shortening of DNT compared with the 137 patients before (59 ± 37 minutes versus 69 ± 33 minutes, P = .020), with a higher percentage achieving the target of 60 minutes (68.1% versus 48.2%, P < .001). This finding was attributed to a reduction in both door-to-CT time and CT-to-needle time. This improvement remained consistent over subsequent months. Conclusions: The application of a simple systems-based, multidisciplinary stroke activation protocol may help in significant reduction in DNT. Encouraging increased patient ownership by stroke nurses appeared to be a promising approach for timely administration of definitive acute therapies. Key Words: Acute ischaemic stroke—door-to-needle time—stroke activation protocol—clinical outcomes. © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.
From the *Division of Neurology, Department of Medicine; †Department of Emergency Medicine, National University Health System, Singapore, Singapore; ‡Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; and §Department of Clinical Neuroscience, Karolinska Institutet and Department of Neurology, Karolinska University Hospital, Stockholm, Sweden. Received November 10, 2017; revision received November 30, 2017; accepted January 1, 2018. Address correspondence to Leonard L.L. Yeo, MBBS, MRCP, National University Health System, 1 E Kent Ridge Road, 119228, Singapore. E-mail: [email protected]. 1052-3057/$ - see front matter © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.01.005
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2018: pp ■■–■■
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Introduction In acute ischemic stroke (AIS), the effectiveness of intravenously administered tissue-type plasminogen activator (IV-tPA) is time dependent. Pooled data from major IVtPA trials suggest that the therapeutic benefit is maximal when thrombolysis is initiated rapidly and worsens rapidly with the passing of time.1-4 Accordingly, the number needed to treat to achieve a good functional outcome (modified Rankin scale 0-1) is only 4.5 when IV-tPA is initiated within 90 minutes.2 Furthermore, early initiation of the treatment translated into improved patient outcomes.5 The door-to-needle time (DNT) is an acceptable measurable standard of acute stroke care. The reduction of the DNT is a complex process, which requires a close coordination across several departments to provide a rapid administration of acute revascularization therapy in AIS.6,7 Many protocols, including the Toyota system, have been implemented to good effect.5,6 Nonetheless, these improvements need to be individualized for each center to be effective. For example, the Helsinki protocol and the value stream analysis, proven effective at the Washington University in reducing DNT, failed to show any effect on the “after-hours” DNT when applied at the Royal Melbourne Hospital in Australia.7-9 At our tertiary center, we launched protocol amendments in March 2015 and March 2016. We present the impact of these initiatives in reducing DNT and functional outcome.
Methods Before March 2015 at our center, paramedics evaluated patients with AIS and performed a point-of-care glucose test. Upon arrival to our emergency department, patients were further evaluated by emergency physicians. An urgent computed tomography (CT) scan of the brain was performed if the patient was considered potentially eligible for acute revascularization treatment. Stroke neurologist was simultaneously alerted. An intravenous line was set and blood was sent to the laboratory while waiting for the CT. Neurologist would review the patient and CT scan, as well as perform the National Institutes Health Stroke Scale (NIHSS). The patient was transferred to the neurology high-dependency ward for IV-tPA treatment. The decision for further endovascular therapy was made during the tPA infusion. In an attempt to improve the delivery of acute revascularization measures, we evaluated the existing workflow in February 2015 and identified steps that could be shortened or modified. As a result, the first protocol amendments were made in March 2015 (Fig 1) and the second amendment in March 2016. In the first protocol amendment, we introduced a prenotification sent to the emergency physician by the paramedics from patients’ home if AIS was suspected. Paramedics would also perform pointof-care glucose test on the site and insert an intravenous line. The radiographer, radiologist, and stroke neurologist were simultaneously alerted. Patients with AIS were
Figure 1. Change in workflow with implementation of a simple multidisciplinary stroke activation protocol. Abbreviations: CT, computed tomography; HDU, high-dependency unit; IV-tPA, intravenous tissue-type plasminogen activator.
ARTICLE IN PRESS DOOR-TO-NEEDLE TIME IN PATIENTS WITH AIS
given top priority for using the CT scanner. The neurologist (during office hours) and emergency physician would await the ambulance in the emergency department and transfer the patient to the CT scanner immediately upon arrival. A rapid clinical examination and NIHSS scoring would be performed during the transfer or in the CT room. In eligible patients, IV-tPA bolus was administered based on the estimation of body weight. After IV-tPA bolus, the patient was transferred to neurology high-dependency ward, equipped with weighing beds. Adjustments were made to the total tPA dose. Decision for rescue endovascular therapy was made during the tPA infusion. In the second protocol amendment, we trained 6 specialized nurses who were already working in the neurology high-dependency ward. They were trained in early assessment of AIS, including performing NIHSS, sending necessary blood investigations, and basic reading of the CT scans for early ischemic signs. Subsequently, these stroke nurses were added to the 24-hour stroke response team. IV-tPA bolus was administered on the CT table in eligible patients, followed by CT-angiography. In patients with large vessel occlusion, neurointerventionist and anesthetist were immediately alerted for possible endovascular treatment. IV-tPA infusion was completed in the emergency room, instead of transferring the patients to the neurology high-dependency unit. Eligible patients were transferred to the angiography suite for rescue endovascular revascularization if needed. Data were collected for all consecutive patients with AIS who received systemic thrombolysis during the study period. Comparisons were made between before and after intervention, in terms of DNT, door-to-CT time, CT-toneedle time, and onset-to-needle time. Where appropriate, the groups were compared using Student’s t tests for continuous variables and chi-square tests for categorical variables. A histogram was plotted to demonstrate the distribution of patients across various DNTs before and after intervention. Data were analyzed using SPSS version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.), and a P value < .05 was considered significant.
Results Of the 410 consecutive patients with AIS treated with IV-tPA during the study period, 129 patients (31%) before amendment 1 served as the control group. A total of 137 patients (33%) were treated according to amendment 1 (from March 2015 to February 2016) and 144 (35%) followed the amendment 2 treatment protocol (from March 2016 to December 2016). The DNT showed a stepwise reduction from the control group according to protocol amendment 1 and subsequently protocol amendment 2 (84 ± 47 minutes versus 69 ± 33 minutes versus 59 ± 37 minutes; P < .001). Furthermore, a considerably higher proportion of patients
3
was treated within the recommended DNT of 60 minutes with each protocol amendment (19.4%, 48.2%, and 68.1%, respectively; P < .001) (Fig 2). Further analyses showed that the reduction in the DNT as a result of the 2 protocol amendments was predominantly due to the reduction in door-to-CT time (31 ± 37 minutes in the control group, 14 ± 24 minutes after protocol amendment 1, and 10 ± 25 min after protocol amendment 2, respectively; P < .001). CT-to-needle time showed a nonsignificant reduction after protocol amendment 2 (49 ± 23 minutes versus to 54 ± 22 minutes after protocol amendment 1). Interestingly, the onset-to-needle time remained comparable among the 3 groups (167 ± 53, 153 ± 58, and 160 ± 80 minutes, respectively; P = .371). Overall, our protocol amendments increased the proportion of patients with AIS who could be treated within window for thrombolysis; 14.7% before intervention to 16.7% after protocol amendment 1 and 19.3% after protocol amendment 2, although this trend was not statistically significant. We compared functional outcomes of patients between protocol amendments 1 and 2. Comparing the 2 protocols, we found no significant difference in terms of change in NIHSS at 48 hours, good functional outcome rates (as defined as modified Rankin scale 0-2 at 3 months), mortality, or symptomatic intracranial hemorrhage. Although not statistically significant, there was a trend toward better NIHSS scores at 48 hours (9.1 versus 7.2, P = .076) and higher incidence of symptomatic intracranial hemorrhage in protocol amendment 2 (6.3% versus 2.2%, P = .093).
Discussion Our study showed that better organization of various concurrent multidisciplinary activities involved in acute stroke care effectively reduced the DNT. The induction of a 24-hour stroke nurse into the acute stroke care program was the most important action for ensuring an expedited treatment protocol.
Need to Improve Speed The benefits of IV-tPA decrease rapidly with elapsing time from stroke onset.10 The American Heart Association developed the Target Stroke campaign in 2010 with the intention to reduce DNT to less than 60 minutes.11 Later, the Stroke Phase II program recommended more aggressive goals for participating hospitals such as achieving DNT within 60 minutes in 75% of treated patients and within 45 minutes in 50% of treated patients.12
Strategies Adopted DNT varies widely among the stroke centers. The Safe Implementation of Treatments in Stroke registry of more than 80,000 patients from more than 1000 centers reported a median DNT of 65 minutes. In contrast, many
4
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Figure 2. Significant reduction in door-to-needle times with implementation of stroke activation protocol.
B.Y.Q. TAN ET AL.
ARTICLE IN PRESS DOOR-TO-NEEDLE TIME IN PATIENTS WITH AIS
centers in Europe have reported much lower DNT, reaching as low as 20 minutes in Helsinki, Finland.11,13,14 All mature stroke centers make continual efforts to reduce their DNT. Factors reported as most effective in reducing the DNT are rapid triage protocol and stroke team notification, single-call activation system, and tPA being stored in the emergency department.15 Interestingly, simultaneous implementation of greater number of strategies was strongly associated with a shorter DNT.16,17 Setting up of a successful stroke thrombolysis program is a time-consuming affair.11 At our tertiary center, it took nearly 2 years to develop a reliable system of expedited acute stroke care at the emergency department. To maintain a consistent improvement, we introduced roundthe-clock availability of a stroke nurse who facilitated a streamlined flow of processes in an expedited manner. She was also responsible for maintaining communication between the family members and various stakeholders in acute stroke care. Another important action for reducing DNT was the removal of formal informed consent. This is considered acceptable because IV-tPA therapy is the current standard of care.18
Lack of Improvement in Functional Outcome Despite significant improvement in DNT after protocol amendments 1 and 2, we could not demonstrate any improvement in functional outcomes in terms of change in NIHSS, good functional outcomes at 3 months, or mortality. This may be due to the fact that improvement in DNT was offset by patients with a delayed presentation to the emergency department, as evidenced by the similar onset-to-needle times across all groups. Other reasons may include a relatively small sample size or changing patterns of stroke subtypes over the years. Of further concern also is the trend toward increasing incidence of symptomatic intracranial hemorrhage in protocol amendment 2. Although not statistically significant, more study is warranted to evaluate if such strategies truly contribute to higher risks of bleeding.
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Table 1. Measures to reduce stroke timing indices based on existing literature Measures to reduce the door-to-needle time Single call activation system15 Rapid triage at the emergency department15 Prenotification warning of incoming patients with stroke by paramedics8 Premixing of tPA15 Direct transportation of patient from ambulance to scanner9 Optimized scan protocols for speed15 Streamlined consent taking or abolishing consent taking Team assembled in the emergency department awaiting patient’s arrival8 Scans read by team as it is being done9 Bolus of IV-tPA given on the scanner table after initial scans9 Delay nonurgent cases so scanner is available8 Paramedics insert intravenous access and perform point-of-care glucose test in ambulance8 Emergency physician and neurologist assesses patient simultaneously in the emergency department15 tPA stored in the emergency department next to scanner15 Stroke chronometer in the form of a ticking clock to impart urgency19 Neuroscience training to emergency physicians4 Abbreviation: IV-tPA, intravenous tissue-type plasminogen activator.
use of a Stroke Chronometer where a ticking clock is visible to all members of the acute stroke care team, which imparts a sense of urgency.19 Providing regular training to the emergency physicians is another effective strategy for rapid stroke care especially during “after-hours” care4 (Table 1). Finally, attempts should be made to start IV-tPA infusion as soon as possible after the bolus injection because a bolus-to-infusion interval of more than 5 minutes may reduce its efficacy.20
Limitations Strategies for Future Continued efforts are needed in maintaining and further reducing the DNT. Being the first professional contact for patients with AIS and their families, ambulance paramedics constitute the most important link in the chain of acute stroke care. In addition to paramedics’ training for better diagnosis and rapid response, it is important to involve them in the initial management process in the emergency room. Regular feedback on the final outcome of patients with AIS to the paramedics, emergency physicians, and radiologists may also be considered not only for the maintenance of an expedited acute stroke care program but also to identify any additional areas for further improvement. Implementation of technological solutions may also be beneficial to the acute care centers. One example is the
Several limitations should be acknowledged. This is a single center study and the results may not be generalized, largely owing to the inherent variations among stroke centers. We present only the initial reduction of DNT as a result of various interventions in the early stroke care. Whether these results can be sustained in the long term or improved further need a longer observation period. While we focused on the DNT, we did not target onsetto-treatment time. Although we did not encounter this problem, in-hospital delays have previously been shown to be longer in patients with AIS arriving earlier.20,21 While it may be difficult to explain why reducing DTN time did not translate into better functional outcomes, nonavailability of an in-house stroke neurologist after office hours could have resulted in inadvertent delays (about
ARTICLE IN PRESS B.Y.Q. TAN ET AL.
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Table 2. Comparison of door-to-needle time in thrombolysed acute ischaemic stroke patients before and after interventions
Mean door-to-needle time in minutes Thrombolysis initiated within 60 min of arrival Mean door-to-CT time (min) Mean CT-to-needle time (min) Mean onset-to-needle time (min)
No intervention (n = 129)
Protocol 1 (n = 137)
Protocol 2 (n = 144)
84 (±47) 19.4% 31 (±37) 53 (±25) 167 (±53)
69 (±33)* 48.2%* 14 (±24)* 54 (±22) 153 (±58)
59 (±37)*,† 68.1%*,† 10 (±25)* 49 (±23) 160 (±80)
Abbreviation: CT, computed tomography. *Bonferroni post hoc analysis, compared with no intervention, P < .005. †Bonferroni post hoc analysis, compared with protocol 1, P < .05.
50 minutes) in the administration of IV-tPA despite a faster access to the CT scanner (Table 2).
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Conclusions Our study reinforces the finding that the application of a simple systems-based and reorganization of multidisciplinary stroke activation protocol may help in significant reduction in DNT and improvement in acute stroke care delivery. An increased involvement of dedicated stroke nurses and patient ownership may facilitate timely administration of definitive therapies for ensuring better outcomes. Our current model of care could serve as an example for setting up acute stroke centers.
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Appendix: Supplementary Material Supplementary data to this article can be found online at doi:10.1016/j.jstrokecerebrovasdis.2018.01.005.
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