Tempo de atendimento após implementação de protocolos para AVC isquêmico agudo: revisão sistemática

Leite, Karina Fonseca de Souza; Santos, Samuel Ribeiro dos; Andrade, Rubia Laine de Paula; Faria, Mariana Gaspar Botelho Funari de; Saita, Nanci Michele; Arcêncio, Ricardo Alexandre; Isaac, Igor Simões da Silva; Rezende, Carlos Eduardo Menezes de; Villa, Tereza Cristina Scatena; Pontes Neto, Octavio Marques; Monroe, Aline Aparecida

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Arquivos de Neuro-Psiquiatria

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Sumário

View and Review • Arq. Neuropsiquiatr. 80 (7) • Jul 2022 • https://doi.org/10.1055/s-0042-1755194 copiar

Tempo de atendimento após implementação de protocolos para AVC isquêmico agudo: revisão sistemática

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

Antecedentes

O tratamento do acidente vascular cerebral (AVC) isquêmico com terapia de reperfusão requer rápido atendimento e reconhecimento dos sintomas.

Objetivo

Analisar a efetividade da implementação de protocolos para AVC isquêmico agudo na redução do tempo de atendimento.

Métodos

Revisão sistemática realizada com estudos primários em português, inglês e espanhol publicados entre 2011 e 2020. Critérios de inclusão: a população do estudo foi constituída por pessoas com AVC isquêmico agudo e estudos que apresentassem resultados sobre a efetividade da implantação de protocolos no tempo de atendimento. A pesquisa bibliográfica foi realizada em junho de 2020 nas bases de dados LILACS, MEDLINE, Embase, Scopus, CINAHL, Academic Search Premier e SocINDEX. A seleção dos artigos e a extração dos dados foram feitas por dois revisores independentes; a síntese dos resultados foi feita de forma narrativa. A qualidade metodológica dos artigos foi avaliada por meio de instrumentos do Joanna Briggs Institute.

Resultados

Foram encontradas 11.226 publicações, das quais 35 foram incluídas no estudo. Apenas um estudo relatou melhora no tempo início dos sintomas-porta após a implementação do protocolo, no entanto, foi efetiva na melhora dos tempos porta-imagem, imagem-agulha, porta-agulha e início dos sintomas-agulha. A principal limitação encontrada nos artigos diz respeito à falta de clareza quanto à população de estudo.

Conclusões

Vários avanços foram identificados no atendimento intra-hospitalar com implantação de protocolo; porém, é necessário melhorar o tempo de reconhecimento dos sintomas do AVC entre aqueles que têm o primeiro contato com a pessoa acometida e entre os profissionais envolvidos com o atendimento pré-hospitalar.

Palavras-chave:
AVC Isquêmico; Doença Aguda; Protocolos Clínicos; Tratamento de Emergência; Avaliação de Programas e Projetos de Saúde

Authors/Journal/Year/Country	Study design*	Objective(s)	Population(n)
Ye et al.¹²12 Ye S, Hu S, Lei Z, et al. Shenzhen stroke emergency map improves access to rt-PA for patients with acute ischaemic stroke. Stroke Vasc Neurol 2019;4(03):115–122. Doi: 10.1136/svn-2018-000212 https://doi.org/10.1136/svn-2018-000212... /StrokeVasc Neurol/201 9/ China	Before-after cohort	Evaluate the effectiveness of the Shenzhen stroke emergency map to optimize access to thrombolysis for patients with acute ischemic stroke.	6,843 patients before and 8,268 after; 568 had thrombolysis before and 802 after
Madhok et al.¹³13 Madhok DY, Keenan KJ, Cole SB, Martin C, Hemphill JC III. Prehospital and Emergency Department-Focused Mission Protocol Improves Thrombolysis Metrics for Suspected Acute Stroke Patients. J Stroke Cerebrovasc Dis 2019;28(12):104423. Doi: 10.1016/j.jstrokecerebrovasdis.2019.104423 https://doi.org/10.1016/j.jstrokecerebro... /J Stroke Cerebrovasc Dis/2019/USA	Retrospective cross-sectional	To assess whether the implanted protocol for prehospital and emergency care increases the percentage of patients treated with thrombolysis in a door-to-needle time of up to 45 minutes.	112 patients before and 236 after; 45 patients underwent thrombolysis before and 50 after.
Ajmi et al.¹⁴14 Ajmi SC, Advani R, Fjetland L, et al. Reducing door-to-needle times in stroke thrombolysis to 13 min through protocol revision and simulation training: a quality improvement project in a Norwegian stroke centre. BMJ Qual Saf 2019;28(11):939-948. Doi: 10.1016/j.jstrokecerebrovasdis.2019.104423 https://doi.org/10.1016/j.jstrokecerebro... /BMJ Qual Saf/2019/Norway	Cohort	To describe quality improvement project with the objective of reducing door-to-needle time and improving patient results.	446 patients before and 204 after
Vanhoucke et al.¹⁵15 VanhouckeJ, Hemelsoet D, Achten E, et al. Impact of a code stroke protocol on the door-to-needle time for IV thrombolysis: a feasibility study. Acta Clin Belg 2020;75(04):267-274. Doi: 10.1080/17843286.2019.1607991 https://doi.org/10.1080/17843286.2019.16... /Acta Clin Belg/2019/Belgium	Before-after cohort	To evaluate the impact of a stroke code protocol on the door-to-needle time for the use of thrombolysis.	110 patients before and 71 after
Silsby et al.¹⁶16 Silsby M, Duma SR, Fois AF, et al. Time to acute stroke treatment in-hours was more than halved after the introduction of the Helsinki Model at Westmead Hospital. Intern Med J 2019;49(11): 1386-1392. Doi: 10.1111/imj.14290 https://doi.org/10.1111/imj.14290... /lntern Med J/2019/Australia	Retrospective	To assess whether simple and cost-free changes of a protocol could improve treatment time for acute ischemic stroke cases in a tertiary hospital.	143 patients before and 134 after; 30 received thrombolysis before and 14 after
Kansagra et al.¹⁷17 Kansagra AP, Wallace AN, Curfman DR, et al. Streamlined triage and transfer protocols improve door-to-puncture time for endovascular thrombectomy in acute ischemic stroke. Clin Neurol Neurosurg 2018;166:71-75. Doi: 10.1016/j.clineuro.2018.01.026 https://doi.org/10.1016/j.clineuro.2018.... /Clin Neurol Neurosurg/2018/USA	Retrospective	To evaluate improvements in the prethrombectomy process in a multihospital network and report the puncture time in patients undergoing mechanical thrombectomy.	104 patients underwent thrombolysis /78 underwent thrombectomy**
Nguyen-Huynh et al.¹⁸18 Nguyen-Huynh MN, Klingman JG, Avins AL, et al; KPNC Stroke FORCE Team. Novel Telestroke Program Improves Thrombolysis for Acute Stroke Across 21 Hospitals of an Integrated Healthcare System. Stroke 2018;49(01):133-139. Doi: 10.1161/stro-keaha.117.018413 https://doi.org/10.1161/stro-keaha.117.0... /Stroke/2018/USA	Before-after cohort	To present the results of the Kaiser Permanente Northern California stroke protocol, which combines the modified Helsinki protocol and telemedicine, according to the door-to-needle time, use of thrombolysis and symptomatic intracranial hemorrhage rates.	310 patients before and 557 after
Koge et al.¹⁹19 Koge J, Matsumoto S, Nakahara I, et al. Improving treatment times for patients with in-hospital stroke using a standardized protocol. J Neurol Sci 2017;381:68-73. Doi: 10.1016/j.nrleng.2018.03.009 https://doi.org/10.1016/j.nrleng.2018.03... /J Neurol Sci/ 2017/Japan	Retrospective	To assess the effectiveness and safety of our standardized protocol for intrahospital stroke	25 patients before and 30 after
Psychogios et al.²⁰20 Psychogios M-N, Behme D, Schregel K, et al. One-Stop Management of Acute Stroke Patients: Minimizing Door-to-Reperfusion Times. Stroke 2017;48(11):3152-3155. Doi: 10.1161/strokeaha.117.018077 https://doi.org/10.1161/strokeaha.117.01... / Stroke/ 2017/Germany	Retrospective observational	To determine whether centralized treatment can reduce intrahospital treatment times for patients with acute occlusion of large vessels.	44 patients**
Kalnins et al.²¹21 Kalnins A, Mickelsen LJ, Marsh D, et al. Decreasing Stroke Code to CT Time in Patients Presenting with Stroke Symptoms. Radiographics 2017;37(05):1559-1568. Doi: 10.1148/rg.2017160190 https://doi.org/10.1148/rg.2017160190... / Radiographics/2017/USA	Cohort	To decrease stroke code time to CT for patients with non-prenotified stroke code from a reference mean of 20 minutes to 1 5 minutes or less.	107 patients before and 298 after
Caputo et al.²²22 Caputo LM, Jensen J, Whaley M, et al. How a CT-Direct Protocol at an American Comprehensive Stroke Center Led to Door-to-Needle Times Less Than 30 Minutes. Neurohospitalist 2017;7 (02):70-73/ Neurohospitalist/2017/USA	Prospective cohort	To describe the process of developing and implementing a protocol and comparing the door-to-needle times and rates of symptomatic intracranial hemorrhage before and after the implementation of the protocol.	295 patients**
Zinkstok et al.²³23 Zinkstok SM, Beenen LF, Luitse JS, Majoie CB, Nederkoorn PJ, Roos YB. Thrombolysis in Stroke within 30 Minutes: Results of the Acute Brain Care Intervention Study. PLoS One 2016;11(11): e0166668. Doi: 10.1371/journal.pone.0166668 https://doi.org/10.1371/journal.pone.016... / PLoS One/ 2016/Netherlands	Before-after cohort	To reduce the door-to-needle time to 30 minutes or less with the optimization of intrahospital stroke treatment.	373 patients**
Busby et al.²⁴24 Busby L, Owada K, Dhungana S, et al. CODE FAST: a quality improvement initiative to reduce door-to-needle times. J Neurointerv Surg 2016;8(07):661-664. Doi: 10.1136/neurintsurg-2015-011806 https://doi.org/10.1136/neurintsurg-2015... / J Neurointerv Surg/2016/USA	Retrospective	To initiate a quality improvement project called CODE FAST to reduce the door-to-needle time in the institution.	41 patients before and 52 after
Liang et al.²⁵25 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 (04):987-996. Doi: 10.1007/s13246-016-0442-1 https://doi.org/10.1007/s13246-016-0442-... / Australasian Physical and Engineering Sciences in Medicine/ 2016/ China	Prospective	To determine whether the application of lean principles for flow optimization could accelerate the start of thrombolysis.	13 patients before and 20 after
Moran et al.²⁶26 Moran JL, Nakagawa K, Asai SM, Koenig MA. 24/7 Neurocritical Care Nurse Practitioner Coverage Reduced Door-to-Needle Time in Stroke Patients Treated with Tissue Plasminogen Activator. J Stroke Cerebrovasc Dis 2016;25(05):1148-1152. Doi: 10.1016/j.jstrokecerebrovasdis.2016.01.033 https://doi.org/10.1016/j.jstrokecerebro... / Journal of Stroke and Cerebrovascular Diseases/ 2016/USA	Retrospective Cohort	To assess the impact of the provision of neurocritical nursing care 24 hours a day, 7 days a week, according to the first aid coverage in the "stroke code" on delays in the treatment of patients with acute stroke who received thrombolysis.	44 patients before and 122 after
Marto et al.²⁷27 Marto JP, Borbinha C, Calado S, Viana-Baptista M. The Stroke Chronometer-A New Strategy to Reduce Door-to-Needle Time. J Stroke Cerebrovasc Dis 2016;25(09):2305-2307. Doi: 10.1016/j.jstrokecerebrovasdis.2016.05.023 https://doi.org/10.1016/j.jstrokecerebro... / J Stroke Cerebrovasc Dis/ 2016/ Portugal	Retrospective	To evaluate the effect of implementing a regressive timer in the acute stroke emergency room, in the door-to-CT and door-to-needle times.	30 patients before and 41 after
Ibrahim et al.²⁸28 Ibrahim F, Akhtar N, Salam A, et al. Stroke Thrombolysis Protocol Shortens “Door-to-Needle Time” and Improves Outcomes-Experience at a Tertiary Care Center in Qatar. J Stroke Cerebrovasc Dis 2016;25(08):2043-2046. Doi: 10.1016/j.jstrokecerebrovasdis.2016.03.047 https://doi.org/10.1016/j.jstrokecerebro... / J Stroke Cerebrovasc Dis/ 2016/ Qatar	Retrospective	To assess the effect of the acute thrombolysis protocol on "door-to-needle time" and on the prognosis of acute stroke cases.	102 patients before and 102 after
Heikkilä et al.²⁹29 Heikkilä I, Kuusisto H, Stolberg A, Palomäki A. Stroke thrombolysis given by emergency physicians cuts in-hospital delays significantly immediately after implementing a new treatment protocol. Scand J Trauma Resusc Emerg Med 2016;24:46. Doi: 10.1186/s13049-016-0237-0 https://doi.org/10.1186/s13049-016-0237-... / Scand J Trauma Resusc Emerg Med/ 2016/ Finland	Retrospective	To describe a new protocol for patients with acute ischemic stroke and thrombolysis administered by emergency physicians in the Emergency Department - the so-called Hämeenlinna model and present preliminary results regarding the door-to-needle and treatment initiation times.	31 patients before and 33 after
Rai et al.³⁰30 Rai AT, Smith MS, Boo S, Tarabishy AR, Hobbs GR, Carpenter JS. The ‘pit-crew’ model for improving door-to-needle times in endovascular stroke therapy: a Six-Sigma project. J Neurointerv Surg 2016;8(05):447-452. Doi: 10.1136/neurintsurg-2015-012219 https://doi.org/10.1136/neurintsurg-2015... / J Neurointerv Surg/2016/ USA	Prospective	To present the results of a quality improvement process aimed at reducing stroke treatment time in a tertiary academic medical center.	64 patients before and 30 after
Zuckerman et al.³¹31 Zuckerman SL, Magarik JA, Espaillat KB, et al. Implementation of an institution-wide acute stroke algorithm: Improving stroke quality metrics. Surg Neurol Int 2016;7(Suppl 41):S1041-S1048. Doi: 10.4103/2152-7806.196366 https://doi.org/10.4103/2152-7806.196366... / Surg Neurol Int/2016/ USA	Retrospective	To describe the process of implementing a new stroke algorithm, compare the pre- and postalgorithm quality improvement metrics, specifically door-to-CT, door-to-neurologist, and door-to-needle times.	Not described**
Kendall et al.³²32 Kendall J, Dutta D, Brown E. Reducing delay to stroke thrombolysis-lessons learnt from the Stroke 90 Project. Emerg Med J 2015; 32(02):100-104. Doi: 10.1136/emermed-2013-202993 https://doi.org/10.1136/emermed-2013-202... / Emerg Med J/ 2015/England	Before-after	To describe how the Stroke 90 project was configured and what interventions were implemented, report the results and discuss lessons learned from it.	136 patients before and 215 after
Atsumi et al.³³33 Atsumi C, Hasegawa Y, Tsumura K, et al. Quality assurance monitoring of a citywide transportation protocol improves clinical indicators of intravenous tissue plasminogen activator therapy: a community-based, longitudinal study. J Stroke Cerebrovasc Dis 2015;24(01):183-188. Doi: 10.1016/j.jstrokecerebrovasdis.2014.08.013 https://doi.org/10.1016/j.jstrokecerebro... / J Stroke Cerebrovasc Dis/ 2015/ Japan	Prospective	To investigate whether prehospital and hospital thrombolysis indicators improved after using a single prehospital scale in a municipal transport protocol, and examine whether a deleterious effect of admission on weekends was observed.	2,049 patients**
Van Schaik et al.³⁴34 Van Schaik SM, Van der Veen B, Van den Berg-Vos RM, Weinstein HC, Bosboom WMJ. Achieving a door-to-needle time of 25 minutes in thrombolysis for acute ischemic stroke: a quality improvement project. J Stroke Cerebrovasc Dis 2014;23(10): 2900-2906. Doi: 10.1016/j.jstrokecerebrovasdis.2014.07.025 https://doi.org/10.1016/j.jstrokecerebro... / J Stroke Cerebrovasc Dis/ 2014/ Netherlands	Before-after	To reduce the delay in intrahospital treatment of patients with acute ischemic stroke through the implementation of a standard operating procedure and the creation of a greater and sustained awareness of the importance of this time-oriented protocol among all health professionals involved in the process.	41 patients before and 185 after
Advani et al.³⁵35 Advani R, Naess H, Kurz MW. Evaluation of the implementation of a rapid response treatment protocol for patients with acute onset stroke: can we increase the number of patients treated and shorten the time needed? Cerebrovasc Dis Extra 2014;4(02): 115-121. Doi: 10.1159/000363050 https://doi.org/10.1159/000363050... / Cerebrovasc Dis Extra/ 2014/ Norway	Retrospective	To retrospectively evaluate the importance of streamlining the treatment chain for patients with acute ischemic stroke, reviewing and improving the pre- and intrahospital routines around the treatment of these patients in the procedure in relation to the number of patients treated with thrombolysis. The secondary objective of the study was to assess changes in door-to-needle times and onset of symptoms-to-needle resulting from changes in pre- and intrahospital routines.	320 patients**
Chen et al.³⁶36 Chen C-H, Tang S-C, Tsai L-K, et al. Stroke code improves intravenous thrombolysis administration in acute ischemic stroke. PLoS One 2014;9(08):e104862. Doi: 10.1371/journal.pone.0104862 https://doi.org/10.1371/journal.pone.010... / PLoS One/ 2014/China	Prospective	To investigate the impact of the stroke code on the performance of thrombolytic therapy and functional results for patients with acute ischemic stroke.	91 patients before and 216 after
Fonarow et al.³⁷37 Fonarow GC, Zhao X, Smith EE, et al. Door-to-needle times for tissue plasminogen activator administration and clinical outcomes in acute ischemic stroke before and after a quality improvement initiative. JAMA 2014;311(16):1632-1640. Doi: 10.1001/jama.2014.3203 https://doi.org/10.1001/jama.2014.3203... / JAMA/ 2014/ USA	Before-after	To analyze the time trend of the door-to-needle time for the administration of thrombolysis and determine the proportion of patients with a time of 60 minutes or less before and after the beginning of the program; to evaluate whether improvement in the door-to-needle time was associated with improved clinical results, including hospital mortality, destination of discharge, ambulatory status, the presence of symptomatic intracranial hemorrhage 36 hours after thrombolysis and complications of thrombolysis.	27,319 patients before and 43,850 after
Ruff et al.³⁸38 Ruff IM, Ali SF, Goldstein JN, et al. Improving door-to-needle times: a single center validation of the target stroke hypothesis. Stroke 2014;45(02):504-508. Doi: 10.1161/strokeaha.113.004073 https://doi.org/10.1161/strokeaha.113.00... / Stroke/ 2014/ USA	Retrospective	To assess whether the incorporation of a stroke protocol into the Target Stroke initiative significantly changed the mean door-to-CT and door-to-needle times.	1,413 patients before and 925 after
Ford et al.³⁹39 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(12):3395-3398. Doi: 10.1161/strokeaha.112.670687 https://doi.org/10.1161/strokeaha.112.67... / Stroke/ 2012/ USA	Prospective	The "current state analysis" mapped operations with waste and those that added value. A "future state analysis" removed useless steps and retained value-added steps. An "action plan" was created to implement the simplified protocol and provide feedback for continuous improvement. The efficiency and safety metrics of the protocol were compared before and after implementation.	132 patients before and 87 after
Lin et al.⁴⁰40 Lin CB, Peterson ED, Smith EE, et al. Emergency medical service hospital prenotification is associated with improved evaluation and treatment of acute ischemic stroke. Circ Cardiovasc Qual Outcomes 2012;5(04):514-522. Doi: 10.1161/CIRCOUT-COMES.112.965210 https://doi.org/10.1161/CIRCOUT-COMES.11... / Circ Cardiovasc Qual Outcomes/2012/ USA	Retrospective	To assess the association of prenotification of the emergency medical service with assessment and treatment of acute ischemic stroke, including door-to-CT and door-to-needle times, symptoms-door onset and thrombolytic treatment rates in eligible patients.	249,197 patients before and 122,791 after
Tai et al.⁴¹41 Tai YJ, Weir L, Hand P, Davis S, Yan B. Does a ‘code stroke’ rapid access protocol decrease door-to-needle time for thrombolysis? Intern Med J 2012;42(12):1316-1324. Doi: 10.1111/j.14455994.2011.02709.x https://doi.org/10.1111/j.14455994.2011.... / Intern Med J/ 2012/ Australia	Retrospective	To perform a comprehensive qualitative analysis of the stroke code service at a Melbourne hospital to determine whether it had resulted in a reduction in door-to-needle and door-to-CT times, and increased the percentage of patients treated with thrombolysis.	96 patients before and 189 after
O'Brien et al.⁴²42 O’Brien W, Crimmins D, Donaldson W, et al. FASTER (Face, Arm, Speech, Time, Emergency Response): experience of Central Coast Stroke Services implementation of a pre-hospital notification system for expedient management of acute stroke. J Clin Neurosci 2012;19(02):241-245. Doi: 10.1016/j.jocn.2011.06.009 https://doi.org/10.1016/j.jocn.2011.06.0... / J Clin Neurosci/2012/ Australia	Prospective cohort pre- and postintervention	To determine whether the introduction of a prehospital notification scheme based on an ambulance stroke service (FASTER) reduces the assessment time for thrombolysis and increases the use of thrombolysis in a health service in the Central Coast area.	42 patients before and 67 after
Sung et al.⁴³43 Sung S-F, Huang Y-C, Ong C-T, Chen Y-W. A Parallel Thrombolysis Protocol with Nurse Practitioners As Coordinators Minimized Door-to-Needle Time for Acute Ischemic Stroke. Stroke Res Treat 2011;2011:198518. Doi: 10.4061/2011/198518 https://doi.org/10.4061/2011/198518... / Stroke Res Treat/2011/ China	Before-after	To determine whether modifying the protocol shortened intrahospital delay and facilitated thrombolytic therapy.	338 patients before and 139 after
Hoegerl et al.⁴⁴44 Hoegerl C, Goldstein FJ, Sartorius J. Implementation of a stroke alert protocol in the emergency department: a pilot study. J Am Osteopath Assoc 2011;111(01):21-27/ Journal of the American Osteopathic Association/2011/ USA	Prospective	To determine whether implementing a stroke alert protocol, in conjunction with a limited education program, will reduce the arrival time for CT and the treatment time for stroke patients in the emergency department.	132 patients before and 101 after
Kamal et al.⁴⁵45 Kamal N, Holodinsky JK, Stephenson C, et al. Improving Door-to-Needle Times for Acute Ischemic Stroke: Effect of Rapid Patient Registration, Moving Directly to Computed Tomography, and Giving Alteplase at the Computed Tomography Scanner. Circ Cardiovasc Qual Outcomes 2017;10(01):e003242. Doi: 10.1161/CIRCOUTCOMES.116.003242 https://doi.org/10.1161/CIRCOUTCOMES.116... / Circulation/ 2017/USA	Prospective cohort	To analyze the impact of four specific strategies (a new call activation system; registering the patient with suspected stroke as unknown on admission until laboratory confirmation/image; sending direct patient to CT in emergency services; applying thrombolysis on the CT table scan or imaging) to reduce the door-to-needle time in a single center.	350 patients**
Iglesias Mohedano et al.⁴⁶46 Iglesias Mohedano AM, García Pastor A, Díaz Otero F, et al. A new protocol reduces median door-to-needle time to the benchmark of 30minutes in acute stroke treatment. Neurologia (Engl Ed) 2021;36(07):487–494. Doi: 10.1016/j.nrleng.2018.03.009 https://doi.org/10.1016/j.nrleng.2018.03... / Neurologia/ 2020/ Spain	Before-after cohort	To determine whether a new intra-hospital intravenous thrombolysis protocol is effective in reducing the door-to-needle time and correcting previously identified factors associated with delays.	239 patients before and 222 after

References / methodological quality appraisal	Symptoms onset-to-door time	Door-to-image time	Image-to-needle time	Door-to-needle time	Symptoms onset-to-needle time
References / methodological quality appraisal	Before-After (min) p-value	Before-After (min) p-value	Before-After (min) p-value	Before-After (min) p-value	Before-After (min) p-value
Ye et al.¹²12 Ye S, Hu S, Lei Z, et al. Shenzhen stroke emergency map improves access to rt-PA for patients with acute ischaemic stroke. Stroke Vasc Neurol 2019;4(03):115–122. Doi: 10.1136/svn-2018-000212 https://doi.org/10.1136/svn-2018-000212... 8/11	DNM	DNM	DNM	Mdn 71.5–51.5 p < 0.001	Mdn 175.5–149.5 p = 0.039
Madhok et al.¹³13 Madhok DY, Keenan KJ, Cole SB, Martin C, Hemphill JC III. Prehospital and Emergency Department-Focused Mission Protocol Improves Thrombolysis Metrics for Suspected Acute Stroke Patients. J Stroke Cerebrovasc Dis 2019;28(12):104423. Doi: 10.1016/j.jstrokecerebrovasdis.2019.104423 https://doi.org/10.1016/j.jstrokecerebro... 4/8	DNM	Mdn 19(IQR 14–23)–9(9–11) p < 0.01	DNM	Mdn 35(IQR 32–57)–29 (22–36) p < 0.01	DNM
Ajmi et al.¹⁴14 Ajmi SC, Advani R, Fjetland L, et al. Reducing door-to-needle times in stroke thrombolysis to 13 min through protocol revision and simulation training: a quality improvement project in a Norwegian stroke centre. BMJ Qual Saf 2019;28(11):939-948. Doi: 10.1016/j.jstrokecerebrovasdis.2019.104423 https://doi.org/10.1016/j.jstrokecerebro... 8/11	Mdn 38(IQR 27–54)–37 (25–50) p = 0.2	DNM	DNM	Mdn 27(IQR 19–41)–13(9–23)*	Mdn 110(IQR 77–168)–96(68–146)*
Vanhoucke et al.¹⁵15 VanhouckeJ, Hemelsoet D, Achten E, et al. Impact of a code stroke protocol on the door-to-needle time for IV thrombolysis: a feasibility study. Acta Clin Belg 2020;75(04):267-274. Doi: 10.1080/17843286.2019.1607991 https://doi.org/10.1080/17843286.2019.16... 8/11	DNM	DNM	Mdn 24(IQR 13–42)–15 (10–21) p = 0.009	Mdn 57 (IQR 43–69)–33 (25–45) p < 0.001	DNM
Silsby et al.¹⁶16 Silsby M, Duma SR, Fois AF, et al. Time to acute stroke treatment in-hours was more than halved after the introduction of the Helsinki Model at Westmead Hospital. Intern Med J 2019;49(11): 1386-1392. Doi: 10.1111/imj.14290 https://doi.org/10.1111/imj.14290... 5/11	Mdn 90(IQR 65–130)–93 (64–154) p = 0.66	Mdn 23(IQR 14–55)–22(9–49) p = 0.11 Reduced from Mdn 16 (IQR 9–22) to 8(4–14) min (p < 0.01) in patients prenotified by the ambulance	Mdn 55 (IQR 39–67)–26 (23–27) p < 0.01	76(54–91)–33(27–44) p < 0.01	DNM
Kansagra et al.¹⁷17 Kansagra AP, Wallace AN, Curfman DR, et al. Streamlined triage and transfer protocols improve door-to-puncture time for endovascular thrombectomy in acute ischemic stroke. Clin Neurol Neurosurg 2018;166:71-75. Doi: 10.1016/j.clineuro.2018.01.026 https://doi.org/10.1016/j.clineuro.2018.... 6/11	DNM	DNM	DNM	Mdn 147–39 minutes p < 0.001	Mdn 290–212 p = 0.05
Nguyen-Huynh et al.¹⁸18 Nguyen-Huynh MN, Klingman JG, Avins AL, et al; KPNC Stroke FORCE Team. Novel Telestroke Program Improves Thrombolysis for Acute Stroke Across 21 Hospitals of an Integrated Healthcare System. Stroke 2018;49(01):133-139. Doi: 10.1161/stro-keaha.117.018413 https://doi.org/10.1161/stro-keaha.117.0... 8/11	DNM	DNM	DNM	Mdn 53.5(IQR 42–73)–34 (26–45) p < 0.001	DNM
Koge et al.¹⁹19 Koge J, Matsumoto S, Nakahara I, et al. Improving treatment times for patients with in-hospital stroke using a standardized protocol. J Neurol Sci 2017;381:68-73. Doi: 10.1016/j.nrleng.2018.03.009 https://doi.org/10.1016/j.nrleng.2018.03... 5/11	DNM	DNM	Mdn 45(IQR 20–58)–16 (13–40) for thrombolysis p = 0.02 Mdn 75(IQR 45–90)–53 (45–73) for thrombectomy p = 0.08	DNM	DNM
Psychogios et al.²⁰20 Psychogios M-N, Behme D, Schregel K, et al. One-Stop Management of Acute Stroke Patients: Minimizing Door-to-Reperfusion Times. Stroke 2017;48(11):3152-3155. Doi: 10.1161/strokeaha.117.018077 https://doi.org/10.1161/strokeaha.117.01... 6/11	DNM	DNM	DNM	M 54.5(95% CI 47–61)–20.5 (95% CI 17–26)	DNM
Kalnins et al.²¹21 Kalnins A, Mickelsen LJ, Marsh D, et al. Decreasing Stroke Code to CT Time in Patients Presenting with Stroke Symptoms. Radiographics 2017;37(05):1559-1568. Doi: 10.1148/rg.2017160190 https://doi.org/10.1148/rg.2017160190... 7/11	DNM	DNM	DNM	M 98–65 p = 0.08	M 186–130 p = 0.02
Caputo et al.²²22 Caputo LM, Jensen J, Whaley M, et al. How a CT-Direct Protocol at an American Comprehensive Stroke Center Led to Door-to-Needle Times Less Than 30 Minutes. Neurohospitalist 2017;7 (02):70-73 7/11	DNM	DNM	DNM	Mdn 38–28 p < 0.001	DNM
Zinkstok et al.²³23 Zinkstok SM, Beenen LF, Luitse JS, Majoie CB, Nederkoorn PJ, Roos YB. Thrombolysis in Stroke within 30 Minutes: Results of the Acute Brain Care Intervention Study. PLoS One 2016;11(11): e0166668. Doi: 10.1371/journal.pone.0166668 https://doi.org/10.1371/journal.pone.016... 7/11	Mdn 65(IQR 50–90)–71 (48–120) p < 0.156	Mdn 35(IQR 27–47)–6(4–10) p < 0.001	Mdn 40(IQR 31–55)–20 (15–28) p < 0.001	Mdn 75(IQR 60–105)–28 (20–37) p < 0.001	Mdn 158(IQR 135–177)–105(75–160) p < 0.001
Busby et al.²⁴24 Busby L, Owada K, Dhungana S, et al. CODE FAST: a quality improvement initiative to reduce door-to-needle times. J Neurointerv Surg 2016;8(07):661-664. Doi: 10.1136/neurintsurg-2015-011806 https://doi.org/10.1136/neurintsurg-2015... 6/11	DNM	Mdn 16(IQR 11–25)–8(5–11) p < 0.0001	DNM	Mdn 62(IQR 49–77)–25 (18–36) p < 0.0001	DNM
Liang et al.²⁵25 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 (04):987-996. Doi: 10.1007/s13246-016-0442-1 https://doi.org/10.1007/s13246-016-0442-... 8/11	DNM	Mdn 37(IQR 26–40)–22 (13–27) p = 0.003	Mdn 33(IQR 30–47)–25 (18–29) p < 0.001	Mdn 90(IQR 60–125)–47 (40–61) p = 0.004	Mdn 163(IQR 140–180)–170(133–205) p = 0.625
Moran et al.²⁶26 Moran JL, Nakagawa K, Asai SM, Koenig MA. 24/7 Neurocritical Care Nurse Practitioner Coverage Reduced Door-to-Needle Time in Stroke Patients Treated with Tissue Plasminogen Activator. J Stroke Cerebrovasc Dis 2016;25(05):1148-1152. Doi: 10.1016/j.jstrokecerebrovasdis.2016.01.033 https://doi.org/10.1016/j.jstrokecerebro... 5/11	DNM	DNM	Mdn 36(IQR 28–64)–21 (16–31) p < 0.0001	Mdn 53(IQR 45–43)–45 (35–58) p = 0.001	Mdn 118(IQR 96–157)–110(80–141) p = 0.13
Marto et al.²⁷27 Marto JP, Borbinha C, Calado S, Viana-Baptista M. The Stroke Chronometer-A New Strategy to Reduce Door-to-Needle Time. J Stroke Cerebrovasc Dis 2016;25(09):2305-2307. Doi: 10.1016/j.jstrokecerebrovasdis.2016.05.023 https://doi.org/10.1016/j.jstrokecerebro... 6/11	M 91.5(SD 51.6)–90.7(SD 42.8) p = 0.943	M 24–16.5 p = 0.004	DNM	M 47–39 p = 0.016	DNM
Ibrahim et al.²⁸28 Ibrahim F, Akhtar N, Salam A, et al. Stroke Thrombolysis Protocol Shortens “Door-to-Needle Time” and Improves Outcomes-Experience at a Tertiary Care Center in Qatar. J Stroke Cerebrovasc Dis 2016;25(08):2043-2046. Doi: 10.1016/j.jstrokecerebrovasdis.2016.03.047 https://doi.org/10.1016/j.jstrokecerebro... 5/11	DNM	M 42.5(SD 42.1)–27.1(SD 26.4) p < 0.001	DNM	M 83.3(SD 47.7)–47.1(SD 25.7) p < 0.001	DNM
Heikkilä et al.²⁹29 Heikkilä I, Kuusisto H, Stolberg A, Palomäki A. Stroke thrombolysis given by emergency physicians cuts in-hospital delays significantly immediately after implementing a new treatment protocol. Scand J Trauma Resusc Emerg Med 2016;24:46. Doi: 10.1186/s13049-016-0237-0 https://doi.org/10.1186/s13049-016-0237-... 6/11	DNM	DNM	DNM	Mdn 54–28 p < 0.001	Mdn 139–101 p < 0.001
Rai et al.³⁰30 Rai AT, Smith MS, Boo S, Tarabishy AR, Hobbs GR, Carpenter JS. The ‘pit-crew’ model for improving door-to-needle times in endovascular stroke therapy: a Six-Sigma project. J Neurointerv Surg 2016;8(05):447-452. Doi: 10.1136/neurintsurg-2015-012219 https://doi.org/10.1136/neurintsurg-2015... 8/11	M 180(SD 128)-183(SD 244) p = 0.2	M 40(SD 29)-26(SD 15) p = 0.008	M 111–66 for thrombectomy p < 0.0001 M 111(SD 49)–67(SD 33) for thombolysis p < 0.0001	M 151(SD 51)–93(SD 37) P < 0.0001	DNM
Zuckerman et al.³¹31 Zuckerman SL, Magarik JA, Espaillat KB, et al. Implementation of an institution-wide acute stroke algorithm: Improving stroke quality metrics. Surg Neurol Int 2016;7(Suppl 41):S1041-S1048. Doi: 10.4103/2152-7806.196366 https://doi.org/10.4103/2152-7806.196366... 6/11	DNM	M 39.9–12.8 p < 0.001	DNM	M 62.5 (SD 44.9)–43.5 (SD 21.5) p = 0.169	DNM
Kendall et al.³²32 Kendall J, Dutta D, Brown E. Reducing delay to stroke thrombolysis-lessons learnt from the Stroke 90 Project. Emerg Med J 2015; 32(02):100-104. Doi: 10.1136/emermed-2013-202993 https://doi.org/10.1136/emermed-2013-202... 8/11	DNM	M 32(SD 22.6)–23.5(SD 21.8) p < 0.001	M 43.8(SD 27.3)–42.1(SD 26.1) p = 0.57	M 76.2(SD 32.3)–65.6(SD 33.7) p = 0.004	M 164.9(SD 50.1)–154.1 (SD 51.7) p = 0.053
Atsumi et al.³³33 Atsumi C, Hasegawa Y, Tsumura K, et al. Quality assurance monitoring of a citywide transportation protocol improves clinical indicators of intravenous tissue plasminogen activator therapy: a community-based, longitudinal study. J Stroke Cerebrovasc Dis 2015;24(01):183-188. Doi: 10.1016/j.jstrokecerebrovasdis.2014.08.013 https://doi.org/10.1016/j.jstrokecerebro... 8/11	DNM	DNM	DNM	M 75.3(SD 23.8)–78.1(SD 31.6) p = 0.457	M 132.4(SD 27.4)–117.4 (SD 59.0) p = 0.168
Van Schaik et al.³⁴34 Van Schaik SM, Van der Veen B, Van den Berg-Vos RM, Weinstein HC, Bosboom WMJ. Achieving a door-to-needle time of 25 minutes in thrombolysis for acute ischemic stroke: a quality improvement project. J Stroke Cerebrovasc Dis 2014;23(10): 2900-2906. Doi: 10.1016/j.jstrokecerebrovasdis.2014.07.025 https://doi.org/10.1016/j.jstrokecerebro... 8/11	DNM	DNM	DNM	Mdn 60(IQR 41–65)–25 (20–37) p < 0.001	DNM
Advani et al.³⁵35 Advani R, Naess H, Kurz MW. Evaluation of the implementation of a rapid response treatment protocol for patients with acute onset stroke: can we increase the number of patients treated and shorten the time needed? Cerebrovasc Dis Extra 2014;4(02): 115-121. Doi: 10.1159/000363050 https://doi.org/10.1159/000363050... 5/11	DNM	DNM	DNM	Mdn 73–31 p < 0.001	Mdn 135–119 minute p < 0.44
Chen et al.³⁶36 Chen C-H, Tang S-C, Tsai L-K, et al. Stroke code improves intravenous thrombolysis administration in acute ischemic stroke. PLoS One 2014;9(08):e104862. Doi: 10.1371/journal.pone.0104862 https://doi.org/10.1371/journal.pone.010... 7/11	Mdn 45(IQR 30–65)–58 (32–94.5) p = 0.009	Mdn 24(IQR 19–38.5)–11 (9–13) p < 0.001	Mdn 61(IQR 44–79)–40 (32–51) p < 0.001	Mdn 88(IQR 67–107)–51 (43–64) p < 0.001	Mdn 145(IQR 122–163)–125(90.3–157) p < 0.001
Fonarow et al.³⁷37 Fonarow GC, Zhao X, Smith EE, et al. Door-to-needle times for tissue plasminogen activator administration and clinical outcomes in acute ischemic stroke before and after a quality improvement initiative. JAMA 2014;311(16):1632-1640. Doi: 10.1001/jama.2014.3203 https://doi.org/10.1001/jama.2014.3203... 7/11	Mdn 50(IQR 35–70)–52 (36–73)*	DNM	DNM	Mdn 77(IQR 60–98)–67 (51–87) p < 0.001	Mdn 137(IQR 113–160)–128(103–154) p < 0.001
Ruff et al.³⁸38 Ruff IM, Ali SF, Goldstein JN, et al. Improving door-to-needle times: a single center validation of the target stroke hypothesis. Stroke 2014;45(02):504-508. Doi: 10.1161/strokeaha.113.004073 https://doi.org/10.1161/strokeaha.113.00... 6/11	Med 576 (180–2, 166)–498 (120–1,578) p = 0.001	Med 71 (IQR 37–156)–59 (24–142) p < 0.001	DNM	Mdn 70(IQR 56–85)–47 (32–62) p < 0.001	Mdn 124(IQR 100–162)–105(75–148) p = 0.002
Ford et al.³⁹39 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(12):3395-3398. Doi: 10.1161/strokeaha.112.670687 https://doi.org/10.1161/strokeaha.112.67... 7/11	Mdn 62(IQR 43–93)–67 (38–91) p = 0.75	Mdn 16(IQR 10–22)–1(0–4) p < 0.001	DNM	Mdn 60 (IQR 46–73)–39 (28–56) p < 0.0001	Mdn 131(IQR 105–165)–11(80–158) p = 0.0161
Lin et al.⁴⁰40 Lin CB, Peterson ED, Smith EE, et al. Emergency medical service hospital prenotification is associated with improved evaluation and treatment of acute ischemic stroke. Circ Cardiovasc Qual Outcomes 2012;5(04):514-522. Doi: 10.1161/CIRCOUT-COMES.112.965210 https://doi.org/10.1161/CIRCOUT-COMES.11... 5/11	Mdn 113(IQR 55–340)–150 (60–445) p < 0.0001	Mdn 55(IQR 28–103)–42 (22–83) p < 0.0001	DNM	Mdn 80(IQR 60–103)–78 (60–100) p < 0.0001	Mdn 145(IQR 116–170)–141(115–169) p < 0.0001
Tai et al.⁴¹41 Tai YJ, Weir L, Hand P, Davis S, Yan B. Does a ‘code stroke’ rapid access protocol decrease door-to-needle time for thrombolysis? Intern Med J 2012;42(12):1316-1324. Doi: 10.1111/j.14455994.2011.02709.x https://doi.org/10.1111/j.14455994.2011.... 5/11	Mdn 61.5 (IQR 49.0–73.8)–72.0 (56.0–111.5) p < 0.001	Mdn 42 (IQR 29–56)–23 (16–39) p < 0.001	Mdn 48.5 (IQR 32.8–67.3)–39.0 (25.0–62.0) p = 0.044	Mdn 90 (IQR 77.3–111)–72 (50.5–93.5) p < 0.001	Mdn 160 (IQR 133–175)–160 (128–195) (p < 0.339)
O'Brien et al.⁴²42 O’Brien W, Crimmins D, Donaldson W, et al. FASTER (Face, Arm, Speech, Time, Emergency Response): experience of Central Coast Stroke Services implementation of a pre-hospital notification system for expedient management of acute stroke. J Clin Neurosci 2012;19(02):241-245. Doi: 10.1016/j.jocn.2011.06.009 https://doi.org/10.1016/j.jocn.2011.06.0... 8/11	M 59–76 minutes p = 0.180	M 49–19 minutes p = 0.004	DNM	M 102–56 minute p = 0.001	M 157–125 minutes p = 0.005
Sung et al.⁴³43 Sung S-F, Huang Y-C, Ong C-T, Chen Y-W. A Parallel Thrombolysis Protocol with Nurse Practitioners As Coordinators Minimized Door-to-Needle Time for Acute Ischemic Stroke. Stroke Res Treat 2011;2011:198518. Doi: 10.4061/2011/198518 https://doi.org/10.4061/2011/198518... 7/11	Mdn 65(IQR 34–108)–66 (IQR 36–117) p = 0.217	Mdn 29(IQR 19–50)–20 (13–38) p < 0.001	DNM	Mdn 68.5 (IQR 57–83)–58 (54–69) p = 0.035	DNM
Hoegerl et al.⁴⁴44 Hoegerl C, Goldstein FJ, Sartorius J. Implementation of a stroke alert protocol in the emergency department: a pilot study. J Am Osteopath Assoc 2011;111(01):21-27 8/11	DNM	Mdn 65.5(IQR 41.0–101.0)–54.0(33.1–55.3) (p < 0.004)	Mdn 23.0–16.3*	Mdn 85.5–48.9*	DNM
Kamal et al.⁴⁵45 Kamal N, Holodinsky JK, Stephenson C, et al. Improving Door-to-Needle Times for Acute Ischemic Stroke: Effect of Rapid Patient Registration, Moving Directly to Computed Tomography, and Giving Alteplase at the Computed Tomography Scanner. Circ Cardiovasc Qual Outcomes 2017;10(01):e003242. Doi: 10.1161/CIRCOUTCOMES.116.003242 https://doi.org/10.1161/CIRCOUTCOMES.116... 8/11	DNM	DNM	DNM	Mdn 53–35 p = 0.0002	DNM
Iglesias Mohedano et al.⁴⁶46 Iglesias Mohedano AM, García Pastor A, Díaz Otero F, et al. A new protocol reduces median door-to-needle time to the benchmark of 30minutes in acute stroke treatment. Neurologia (Engl Ed) 2021;36(07):487–494. Doi: 10.1016/j.nrleng.2018.03.009 https://doi.org/10.1016/j.nrleng.2018.03... 8/11	Mdn 84(IQR 60–120)–82.5 (57.7–116.2) p = 0.90	Mdn 17(IQR 13–24.8)–15 (11.7–20) p < 0.001	Mdn 34(IQR 26–47)–18 (13–25) p < 0.001	Mdn 52(IQR 43–70)–34 (28–45) p < 0.001	Mdn 145(IQR 120–180)–119(93–155.2) p < 0.001

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[1] Address for correspondence Rubia Laine de Paula Andrade (e-mail: rubia@eerp.usp.br).