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Research Article

Vol. 20 No. 2 (2022): New Horizons: Innovation in Medicine

Thrombolytic Administration for Acute Ischemic Stroke: What Processes can be Optimized?

April 17, 2021


Background: The therapeutic benefit of tissue plasminogen activator (tPA) for acute ischemic stroke is provenbut extremely time-dependent. Current guidelines recommend a <60 minute door-to-needle time. We identify here factors affecting door-to-needle time of tPA administration for acute ischemic stroke.

Methods: We conducted a retrospective chart review of an emergency department from 2010 to 2013. Inclusion criteria were discharge diagnosis of acute ischemic stroke and tPA administration within 4.5 hours of onset. Exclusion criteria were non-ischemic strokes (transient ischemic attacks, subarachnoid hemorrhage, intracerebral hemorrhage) or those given tPA >4.5 hours. We used a linear regression model to quantify factor influence and compared tPA administration benchmark times to target benchmark times (median + quartiles).

Results: Among the 71 ischemic stroke patients included, 38 (54%) received tPA within ≤ 60 minutes. Female sex was associated with a door-to-needle time delay of 13.97 minutes (95% CI 3.412 to 27.111). Median benchmark times did not show evidence of delay in any benchmark in comparison with target benchmark times.

Conclusion: Female sex was associated with increased door-to-needle time. Further investigation of these areas may enable optimized workflow, decreased door-to-needle times, and improved patient outcomes.




  1. Writing Group Members, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C. Executive summary: heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010 Feb 23;121(7):948-54.
  2. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. stroke. 2018 Mar;49(3):e46-99.
  3. ATLANTIS T. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. The Lancet. 2004 Mar 6;363(9411):768-74.
  4. Lees KR, Bluhmki E, Von Kummer R, Brott TG, Toni D, Grotta JC, Albers GW, Kaste M, Marler JR, Hamilton SA, Tilley BC. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. The Lancet. 2010 May 15;375(9727):1695-703.
  5. Meretoja A, Keshtkaran M, Saver JL, Tatlisumak T, Parsons MW, Kaste M, Davis SM, Donnan GA, Churilov L. Stroke thrombolysis: save a minute, save a day. Stroke. 2014 Apr;45(4):1053-8.
  6. Fonarow GC, Smith EE, Saver JL, Reeves MJ, Hernandez AF, Peterson ED, Sacco RL, Schwamm LH. 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 Oct;42(10):2983-9.
  7. Target: Stroke Campaign Manual (PDF). American Heart Association; 2010.
  8. Jauch EC, Saver JL, Adams Jr HP, Bruno A, Connors JJ, Demaerschalk BM, Khatri P, McMullan Jr PW, Qureshi AI, Rosenfield K, Scott PA. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013 Mar;44(3):870-947.
  9. Kim SK, Lee SY, Bae HJ, Lee YS, Kim SY, Kang MJ, Cha JK. Pre‐hospital notification reduced the door‐to‐needle time for IV t‐PA in acute ischaemic stroke. European Journal of Neurology. 2009 Dec;16(12):1331-5.
  10. Mehdiratta M, Woolfenden AR, Chapman KM, Johnston DC, Schulzer M, Beckman J, Teal PA. Reduction in IV t-PA door to needle times using an Acute Stroke Triage Pathway. Canadian journal of neurological sciences. 2006 Jul;33(2):214-6. doi:10.1017/S031716710000500X
  11. McKinney JS, Mylavarapu K, Lane J, Roberts V, Ohman-Strickland P, Merlin MA. Hospital prenotification of stroke patients by emergency medical services improves stroke time targets. Journal of Stroke and Cerebrovascular Diseases. 2013 Feb 1;22(2):113-8. 2011.06.018
  12. Xian Y, Smith EE, Zhao X, Peterson ED, Olson DM, Hernandez AF, Bhatt DL, Saver JL, Schwamm LH, Fonarow GC. Strategies used by hospitals to improve speed of tissue-type plasminogen activator treatment in acute ischemic stroke. Stroke. 2014 May;45(5):1387-95.
  13. Fonarow GC, Smith EE, Saver JL, Reeves MJ, Bhatt DL, Grau-Sepulveda MV, Olson DM, Hernandez AF, Peterson ED, Schwamm LH. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. circulation. 2011 Feb 22;123(7):750-8.
  14. Gilbert EH, Lowenstein SR, Koziol-McLain J, Barta DC, Steiner J. Chart reviews in emergency medicine research: where are the methods?. Annals of emergency medicine. 1996 Mar 1;27(3):305-8.
  15. Worster A, Bledsoe RD, Cleve P, Fernandes CM, Upadhye S, Eva K. Reassessing the methods of medical record review studies in emergency medicine research. Annals of emergency medicine. 2005 Apr 1;45(4):448-51.
  16. Turrentine MA, Braems G, Ramirez MM. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstetrical & gynecological survey. 1995 Jul 1;50(7):534-41. DOI not available.
  17. Wiese KM, Talkad A, Mathews M, Wang D. Intravenous recombinant tissue plasminogen activator in a pregnant woman with cardioembolic stroke. Stroke. 2006 Aug 1;37(8):2168-9.
  18. Murugappan A, Coplin WM, Al-Sadat AN, McAllen KJ, Schwamm LH, Wechsler LR, Kidwell CS, Saver JL, Starkman S, Gobin YP, Duckwiler G. Thrombolytic therapy of acute ischemic stroke during pregnancy. Neurology. 2006 Mar 14;66(5):768-70. DOI:
  19. Leonhardt G, Gaul C, Nietsch HH, Buerke M, Schleussner E. Thrombolytic therapy in pregnancy. Journal of thrombosis and thrombolysis. 2006 Jun 1;21(3):271-6.
  20. Sousa Gomes M, Guimarães M, Montenegro N. Thrombolysis in pregnancy: a literature review. The Journal of Maternal-Fetal & Neonatal Medicine. 2019 Jul 18;32(14):2418-28.
  21. Watanabe TT, Ichijo M, Kamata T. Uneventful pregnancy and delivery after thrombolysis plus thrombectomy for acute ischemic stroke: case study and literature review. Journal of Stroke and Cerebrovascular Diseases. 2019 Jan 1;28(1):70-5.
  22. Van Alebeek ME, De Heus R, Tuladhar AM, de Leeuw FE. Pregnancy and ischemic stroke: a practical guide to management. Current opinion in neurology. 2018 Feb 1;31(1):44-51.
  23. Lazarenko GC, Dobson C, Enokson R, Brant R. Accuracy and speed of urine pregnancy tests done in the emergency department: a prospective study. Canadian Journal of Emergency Medicine. 2001 Oct;3(4):292-5. doi:10.1017/S1481803500005790
  24. Bushnell C, Howard VJ, Lisabeth L, Caso V, Gall S, Kleindorfer D, Chaturvedi S, Madsen TE, Demel SL, Lee SJ, Reeves M. Sex differences in the evaluation and treatment of acute ischaemic stroke. The Lancet Neurology. 2018 Jul 1;17(7):641-50.
  25. Amy YX, Penn AM, Lesperance ML, Croteau NS, Balshaw RF, Votova K, Bibok MB, Penn M, Saly V, Hegedus J, Zerna C. Sex differences in presentation and outcome after an acute transient or minor neurologic event. JAMA neurology. 2019 Aug 1;76(8):962-8.
  26. Reeves MJ, Bushnell CD, Howard G, Gargano JW, Duncan PW, Lynch G, Khatiwoda A, Lisabeth L. Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. The Lancet Neurology. 2008 Oct 1;7(10):915-26.
  27. Tong D, Reeves MJ, Hernandez AF, Zhao X, Olson DM, Fonarow GC, Schwamm LH, Smith EE. Times from symptom onset to hospital arrival in the Get with the Guidelines–Stroke Program 2002 to 2009: temporal trends and implications. Stroke. 2012 Jul;43(7):1912-7.
  28. Teo KC, Leung WC, Wong YK, Liu RK, Chan AH, Choi OM, Kwok WM, Leung KK, Tse MY, Cheung RT, Tsang AC. Delays in stroke onset to hospital arrival time during COVID-19. Stroke. 2020 Jul;51(7):2228-31.
  29. Meretoja A, Strbian D, Mustanoja S, Tatlisumak T, Lindsberg PJ, Kaste M. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology. 2012 Jul 24;79(4):306-13. DOI:
  30. Meretoja A, Weir L, Ugalde M, Yassi N, Yan B, Hand P, Truesdale M, Davis SM, Campbell BC. Helsinki model cut stroke thrombolysis delays to 25 minutes in Melbourne in only 4 months. Neurology. 2013 Sep 17;81(12):1071-6. DOI:
  31. Wu TY, Coleman E, Wright SL, Mason DF, Reimers J, Duncan R, Griffiths M, Hurrell M, Dixon D, Weaver J, Meretoja A. Helsinki stroke model is transferrable with “real-world” resources and reduced stroke thrombolysis delay to 34 min in Christchurch. Frontiers in neurology. 2018 Apr 30;9:290.
  32. Lindsberg PJ, Häppölä O, Kallela M, Valanne L, Kuisma M, Kaste M. Door to thrombolysis: ER reorganization and reduced delays to acute stroke treatment. Neurology. 2006 Jul 25;67(2):334-6. DOI:
  33. Lin CB, Peterson ED, Smith EE, Saver JL, Liang L, Xian Y, Olson DM, Shah BR, Hernandez AF, Schwamm LH, Fonarow GC. Emergency medical service hospital prenotification is associated with improved evaluation and treatment of acute ischemic stroke. Circulation: Cardiovascular quality and outcomes. 2012 Jul;5(4):514-22.
  34. Ekundayo OJ, Saver JL, Fonarow GC, Schwamm LH, Xian Y, Zhao X, Hernandez AF, Peterson ED, Cheng EM. Patterns of emergency medical services use and its association with timely stroke treatment: findings from Get With The Guidelines–Stroke. Circ Cardiovasc Qual Outcomes. 2013;6:262–269. doi: 10.1161/CIRCOUTCOMES.113.000089. Crossref. PubMed.
  35. Davis NW, Bailey M, Buchwald N, Farooqui A, Khanna A. Factors that Influence Door-to-Needle Administration for Acute Stroke Patients in the Emergency Department. Journal of Neuroscience Nursing. 2021 Jun 1;53(3):134-9.
  36. Xu H, Xian Y, Woon FP, Bettger JP, Laskowitz DT, Ng YY, Ong ME, Matchar DB, De Silva DA. Emergency medical services use and its association with acute ischaemic stroke evaluation and treatment in Singapore. Stroke and Vascular Neurology. 2020 Jun 1;5(2).
  37. Wang Y, Zhang C, Sun W, Hu X, Lyu Z, Liu W. Effect of prehospital intervention based on emergency medical services on door-to-needle time of thrombolysis in acute ischemic stroke. Zhonghua wei zhong bing ji jiu yi xue. 2018 Jul 1;30(7):667-70.
  38. Mikulík R, Kadlecová P, Czlonkowska A, Kobayashi A, Brozman M, Švigelj V, Csiba L, Fekete K, Korv J, Demarin V, Vilionskis A. Factors influencing in-hospital delay in treatment with intravenous thrombolysis. Stroke. 2012 Jun;43(6):1578-83.
  39. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-418.
  40. Target Stroke Phase II website STROKEORG/Professionals/TargetStroke/Target-Stroke-Phase-II_ UCM_469859_Article.jsp#.Wk1CBd-nF3g. Accessed December 08, 2021.
  41. Scott PA, Meurer WJ, Frederiksen SM, Kalbfleisch JD, Xu Z, Haan MN, Silbergleit R, Morgenstern LB; INSTINCT Investigators. A multilevel intervention to increase community hospital use of alteplase for acute stroke (INSTINCT): a cluster-randomised controlled trial. Lancet Neurol. 2013;12:139–148. doi: 10.1016/S1474-4422(12)70311-3.
  42. Saver JL, Fonarow GC, Smith EE, Reeves MJ, Grau-Sepulveda MV, Pan W, Olson DM, Hernandez AF, Peterson ED, Schwamm LH. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. Jama. 2013 Jun 19;309(23):2480-8.
  43. Saver JL. Time is brain—quantified. Stroke. 2006 Jan 1;37(1):263-6.


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