Monday, March 25, 2019

Thrombolysis, Thrombectomy and Acute Stroke Therapy. Series. Part 3

In series 3, our panel of experts, reporting from the 14th International Symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy has a very interesting and in-depth look into the drip and ship model of treating with thrombolytics, the treatment landscape in Finland  and performance and training standards set by a multi-society consensus (CAST) for neurointerventional training recommendations.

A summary of this meeting, and an extended report are available in the International Journal of Stroke, the flagship publication of the World Stroke Organization.  

Structuring Stroke Systems of Care


Drip and ship—safety, what is an acceptable time delay, what imaging should be done and where?

Atte Meretoja, Sheryl Martin-Schild, Heinrich Audebert 

The drip-and-ship model of treating with thrombolytics facilitates access to time-sensitive proven intervention to more patients with suspected stroke.  One consequence of this model is that patients treated with thrombolytics are vulnerable to complications while in transit via ground or air ambulance. While remote guidance provides access to otherwise unavailable neurological expertise for decision making on ischemic stroke thrombolysis, the dripping sites usually have lower volume of acute strokes and may be less efficient in treating with thrombolytic than the hubs.  This complicates the analysis of whether there is advantage for patients with suspected stroke stopping at a thrombolytic capable spoke versus bypassing in favor of access to the hub, where definitive care can be provided, particularly for patients who are candidates for thrombectomy. Reducing the door-in-door- out times for sites who do not keep post-thrombolytic patients and for those patients who have emergent large vessel occlusion is a major opportunity for process improvement.  In most ischemic stroke patients, the only imaging test necessary for decision-making is the non-contrast head CT. In our new world of treatment for stroke due to large vessel occlusion, access to and appropriate utilization of endovascular resources is critical.  Vascular and penumbral imaging may evolve, particularly when thrombolytic is given.  The “want to know” must be balanced with the “need to know” and is most relevant for sites who keep post-thrombolytic patients who do not require thrombectomy for a large vessel occlusion. Depending on hub priorities and tolerance of limitations, clinical tools for identifying patients with large vessel occlusion may substitute vascular imaging and reduce the need for repeating studies upon arrival at the hub.

Successful networks in resource rich and poor, urban and rural regions

Lee Schwamm, Markku Kaste, Tsong-Hai Lee 

Finland is presented as an example of a successful European network. After organizing acute stroke care and stroke unit care in Helsinki University Hospital, Dr. Kaste and the leadership team in Helsinki encouraged other Finnish university hospitals to follow their example. To ensure equal access to high-quality acute stroke care including thrombolysis for the entire population of Finland, the Helsinki team developed a telestroke program to support rural hospitals with low resources. These hospitals now have equally good results from thrombolysis as those observed in Helsinki University Hospital. Through telestroke, assistance to rural hospitals in recognizing thrombectomy candidates is given, and when appropriate, patients are transferred to the nearest university hospital applying the drip-and-ship method.  The ways in which other European countries have done the same differ by country, but high-quality stroke care is ensured over much of Western Europe.

In Asia, the resource-rich areas, mainly high-income countries, have sufficient support for acute stroke treatment networks in urban areas. However, in some rural areas where resources are limited, there are still problems of lack of public awareness of stroke and limited access to mechanical thrombectomy. The establishment of stroke centers should be helpful in public and provider education, and the diagnosis and treatment of stroke.

Key components to implementing an effective Stroke System of Care include the need to factor in the nature of the First Responders (e.g., fire/police/volunteer, BLS, ALS, Paramedic, Flight Nurse) and how they can bring to bear various levels of education and training into a more standard approach to prehospital diagnosis (Figure 2). This includes incorporating EMS assets effectively, taking into account EMS by ground and air, and Mobile Stroke Units as available to provide the greatest coverage without depleting critical resources from a community for too long. It also means creating regionalized point of entry routing plans for suspected stroke destination so that the region fairly allocates suspected stroke patients to a level of capability that fits the resources. It will be important to maintain a strong PSC network while developing a broader plan for rapid access to EVT at TSC and CSC facilities, and to standardize stroke alert pre-arrival notification and severity scale use so that each community or state becomes comfortable in the use of a single scale and can thereby communicate more effectively. Also needed is a tiered accreditation or designation of stroke centers that includes the recommended levels of Basic, Acute Stroke Ready, Primary and Comprehensive centers. All these activities should ideally be done by national organizations, since national organizations provide greater transparency and uniformity, and potentially better outcomes. These systems should encourage high levels of participation in National QI programs with recognition for performance to ensure that systems are based on infrastructure and performance. 

Discussion Panel

George Tsvigoulis, Michael Lerario, Nate Bornstein, Claude Nguyen  

Traditional hub and spoke networks for acute stroke treatment were developed to balance resource allocation in urbanized, resource rich regions and improve access to care in rural, resource poor regions.  However, as the need for thrombectomy services expands and technology is increasingly used to improve triaging decisions, newer stroke systems have developed and compete with hub and spoke networks utilizing drip and ship protocols in both resource rich and poor regions.  

Examples of stroke system innovations disrupting current drip-and-ship networks include those where field triage is performed to bypass suspected LVO patients directly to a hospital with thrombectomy services.  Field triage can be accomplished through standard emergency medical services staffing,(1) through telehealth,(2) or through the use of mobile applications (3) and may improve time efficiency and outcomes in time-sensitive stroke care.  Mobile stroke units offer comparable services to PSCs and can assist in the triaging of suspected LVO patients directly to endovascular centers without delaying thrombolysis times.(4) Prospective studies are underway to ascertain if these newer methods of stroke triaging will continue to supplement or even replace drip and ship networks.

Drip-and-ship networks alone cannot optimize resource utilization since false positive screens may occur up to 40-50% of the time if only clinical scores are used for LVO assessment,(5)and recanalization of an identified LVO may occur in 10-20% of patients during transport to the hub facility as a result of intravenous thrombolysis. (6,7) These factors generate confusion as to whether vessel imaging should occur at the hub or spoke facility and may result in overtriage of stoke patients to endovascular centers, when a primary stroke center may have been sufficient. Overtriage to advanced stroke centers could theoretically burden hub hospitals with unnecessary transfers and decrease volumes at spoke centers where competencies may be more difficult to maintain if patient numbers diminish.  

Key Points:

  1. Stroke systems of care will need to be restructured to improve patient access to EVT. Key elements include reducing door-in-door-out times, determining whether clinical tools for evaluating for LVO may substitute for imaging, and improving access to subspecialty care with technology including telemedicine and mobile stroke units.
  2. Standardization of pre-hospital notifications and pre-hospital routing changes to avoid over-triage to comprehensive centers will be important.


Who is carrying out thrombolysis and who should do it in the future?

Andrew Demchuk, Steven R. Levine, Elizabeth Jones  

Thrombolysis is carried out in hospitals, emergency departments and in the field with the help of mobile stroke units. Intravenous alteplase can be administered by non-vascular and vascular neurologists, emergency medicine physicians, residents and fellows in the training programs, physician assistants and advanced nurse practitioners. Telemedicine has allowed for more patients, especially in the rural networks, to get access to thrombolysis and for neurology expertise to become readily available for decision-making. In controlled trials, telemedicine stroke consultations within an organized system of care have demonstrated improved and safe intravenous alteplase use and better patient outcomes than without telemedicine coverage. Many networks, including hub and spokes, have developed telestroke coverage for their patients, including some rural networks. 

Data from a recent study (8)show that approximately 40% of emergency department physicians are uncomfortable treating acute stroke patients. The lack of expertise in interpreting CT imaging and the limited follow up of the patient after a code stroke is activated leaves the physician uncertain and unprepared to treat future stroke patients. On the other hand, physicians tend to exclude patients from receiving thrombolysis, as they often overestimate the risks of administering intravenous alteplase, especially the risk of hemorrhagic transformation. There is a higher number of emergency medicine doctors than neurologists in the US, and despite the clear advance in stroke care systems, emergency physicians need to be qualified and equipped to determine whether a patient is a candidate for thrombolysis. Implementation of pathways for stroke care and neurology training in emergency medicine residency programs will help physicians to be familiar with thrombolytic therapy.
In the near future, proper support for health providers from vascular neurologists should allow expanding and improvement of stroke patient care, empowering the autonomy of providers in the decision-making of thrombolysis. Guidance by a vascular neurologist, either on the field or through telemedicine, will lead to more patients getting the proper treatment, at the right time and the right place.   

Who is carrying out thrombectomy and who should do it in the future?

Arthur Day, Marc Ribo, Reza Jahan
Almost all stroke programs across the United States are now led by neurologically-trained subspecialist practitioners being either neuroradiologists, neurologists, or neurosurgeons who are doing intracranial thrombectomy, with only a small number of non-neurologic subspecialists with catheter skills due to their training and routine practice that are now venturing into the intracranial circuit, which may include vascular surgeons, cardiologists and interventional radiologists. (Table 1) The existing dichotomy on who should be doing thrombectomy in the future has on one side the scenario where more subspecialties should be able to deliver intracranial thrombectomy as the number of practitioners does not meet the needs of stroke care, while on the other hand, it is not a matter of available providers but a lack of an equally distributed and available expertise in small or rural communities.

The reason of a more restricted delivery of thrombectomy between providers is the complex access to the delicate intracranial vasculature which has a higher risk of perforation or distal embolization than the extracranial circulation, the need of a more comprehensive knowledge of the anatomical variants and functional anatomy of the collateral circulation, as well as the awareness of the physiology and pathophysiology of the disease which is entirely different from other organ systems suffering from infarction. This organ-specific expertise is what limits, to say, a neurosurgeon or radiologist from performing an arteriography and stenting in the management of a myocardial infarction. Future safe practice of intracranial thrombectomy requires a practitioner highly skilled with intracranial catheter-based vascular techniques, with a firm knowledge base of the anatomy, pathophysiology, and treatment alternatives of the various cerebrovascular conditions that may arise during the evolution of a thrombotic stroke. (Figure 3) Further research will be needed to ascertain the number of trained physicians to meet the demands of stroke intervention, distribution of these physicians across the nation and better understanding of access of populations to stroke centers to help on planning regional stroke programs.

Current guidelines for training for thrombolysis and thrombectomy; appropriateness of current guidelines

Sunil Sheth, Don Heck, Diogo Hausen, James Grotta 

Performance and training standards set by a multi-society consensus (CAST) for neurointerventional training demands a proper 1-year minimum training under direction of multiple neurointerventionists at a high-volume center. Pre-requisites to training include neuroscience-based residency training. A distribution of diagnostic and interventional procedures, covering the breadth of neurointerventional diseases including cerebral aneurysms, cerebral arteriovenous malformations as well as spinal diseases is required. Final certification is obtained following the completion of such a training program as well as a review of two years of subsequent practice data, to ensure high quality outcomes after training.

Should the standards for stroke thrombectomy be different? On the one hand, there is a clear and present need to expand patient access to the therapy. This treatment is highly time sensitive – perhaps one of the most time sensitive in medicine – and as such delays in treatment such as those created by prolonged pre-hospital transports or inter-hospital transfers are costly. On the other hand, all the data supporting the efficacy of EVT at improving clinical outcomes after LVO stroke were derived from high volume hospitals and high volume neurointerventionalists. As such, treatment outside these specialized centers could be considered unproven.

Would it be beneficial then to train a group of neurointerventionalists for EVT alone, and forgo the remainder of neurointerventional training? Insisting that all providers to treat stroke also be proficient in aneurysm treatments, for example, would likely be mathematically impossible. But would a model in which some providers perform only EVT be even possible, whereby one can learn to effectively perform delicate and intricate intra-cranial thrombectomy without exposure to other cerebrovascular disorders? 

Ultimately, these discussions should be framed in the context of what is best for patients, and not along specialty or “turf” considerations. As such, this topic is one that will need to be addressed with data, particularly from lower volume centers and lower volume physician practices, which are notoriously absent from traditional data generating mechanisms including clinical trials and clinical registries.

Discussion Panel

Mike Frankel, Gary Spiegel, Hen Hallevi, Jonathan Zhang 

Since the FDA approval of alteplase (recombinant tissue plasminogen activator - rtPA) for acute ischemic stroke in 1996 and the publication of consensus guidelines, the acceptance by the medical community has been mixed. Although vascular neurologists have fully embraced the robust nature of the data supporting the benefit of alteplase there has been reluctance to treat by general neurologists and emergency medicine physicians in large part due to fear of causing harm. As such, it is imperative that vascular neurologists work together to create more opportunities for clinical coverage through telestroke and education of general neurologists and emergency medicine physicians. 
In the case of thrombectomy, adoption of the procedure has not been a problem. However, a strategy to equally distribute neurological expertise for thrombolysis and thrombectomy in both urban and rural areas may lead to certification of centers and physicians not fully competent to be involved in stroke care. Expanding certification of centers to deliver treatment to all population is only part of the solution, as more expertise from first responders and ways to reduce onset-to-door time play an important role in patient care. On the other hand, certifying non-neuroscience-based physicians, such as cardiologists or interventional radiologists, to perform thrombectomy requires a thorough review of training requirements and experience. It is clear that extracranial vessels differ enormously from intracranial vessels. Hence a singular set of technical and cognitive expertise, as well as catheter-based skills and knowledge is necessary to better perform the thrombectomy procedure. 

Key Points:
  1. There is a need for an expansion of providers able to oversee thrombolysis treatments. Advanced practice providers including nurse practitioners, telemedicine, and MSUs may help address this issue.
  2. With the magnitude of benefit EVT confers on patients with AIS, and the resulting increase in need for proficient providers and suitable hospitals, there is a need to rethink hospital certification and training standards for Neurointervention. These standards, however, must be determined with the patients’ best interest in mind.



1. Schlemm L, Ebinger M, Nolte CH, Endres M. Impact of Prehospital Triage Scales to Detect Large Vessel Occlusion on Resource Utilization and Time to Treatment. Stroke. 2018;49:439–446. 
2. Belt GH, Felberg RA, Rubin J, Halperin JJ. In-Transit Telemedicine Speeds Ischemic Stroke Treatment: Preliminary Results. Stroke. 2016;47:2413–2415. 
3. Nogueira RG, Silva GS, Lima FO, Yeh Y-C, Fleming C, Branco D, Yancey AH, Ratcliff JJ, Wages RK, Doss E, Bouslama M, Grossberg JA, Haussen DC, Sakano T, Frankel MR. The FAST-ED App: A Smartphone Platform for the Field Triage of Patients With Stroke. Stroke. 2017;48:1278–1284. 
4. Kettner M, Helwig SA, Ragoschke-Schumm A, Schwindling L, Roumia S, Keller I, Martens D, Kulikovski J, Manitz M, Lesmeister M, Walter S, Grunwald IQ, Schlechtriemen T, Reith W, Fassbender K. Prehospital Computed Tomography Angiography in Acute Stroke Management. Cerebrovasc Dis. 2017;44:338–343. 
5. Smith EE, Kent DM, Bulsara KR, Leung LY, Lichtman JH, Reeves MJ, Towfighi A, Whiteley WN, Zahuranec DB, American Heart Association Stroke Council. Accuracy of Prediction Instruments for Diagnosing Large Vessel Occlusion in Individuals With Suspected Stroke: A Systematic Review for the 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 2018;49:e111–e122. 
6. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater L-A, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378:1573–1582. 
7. Tsivgoulis G, Katsanos AH, Schellinger PD, Köhrmann M, Varelas P, Magoufis G, Paciaroni M, Caso V, Alexandrov AW, Gurol E, Alexandrov AV. Successful Reperfusion With Intravenous Thrombolysis Preceding Mechanical Thrombectomy in Large-Vessel Occlusions. Stroke. 2018;49:232–235. 
8. Scott PA, Xu Z, Meurer WJ, Frederiksen SM, Haan MN, Westfall MW, Kothari SU, Morgenstern LB, Kalbfleisch JD. Attitudes and Beliefs of Michigan Emergency Physicians Toward Tissue Plasminogen Activator Use in Stroke. Stroke. 2010;41:2026–2032.

About: International symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy 

The 14thInternational Symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy (TTST) took place in Houston, Texas on October 21stand 22nd, 2018. TTST meetings began in 1990 during the initial simultaneous clinical investigations into thrombolysis taking place in the United States, Europe, and Japan. Since then, TTST has brought together invited experts on reperfusion therapy for acute stroke every two years, and rotates among venues in Europe, North America, and Asia. TTST has provided opportunities for stimulating controversial discussions on data from recent clinical trials, the status of major ongoing studies, and priorities for future research. Initially focused on thrombolytic therapy, recent TTST conferences have helped lay the groundwork for the success of thrombectomy clinical research. 

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