Stroke Systems of Care and Impact on Acute Stroke Treatment

Global Rates of Thrombolysis and Thrombectomy

Global use of thrombolysis and thrombectomy remain low relative to the clinical burden of stroke. ^, In the United States, the use of intravenous alteplase has increased over the past decade upon publication of trials such as the European Cooperative Acute Stroke Study (ECASS) III, which extended the treatment window. ^, Thrombolysis rates have increased from 4% in 2003–2005 to 7% in 2010–2011, particularly in the population subset arriving within 2 hours from symptom onset. Recently, the overall use of intravenous alteplase, regardless of time from symptom onset, has remained relatively constant and hovers around 8%–10% in the United States. ^{, ,} Single centers have reported rates as high as 19.4%–21%.

In comparison, treatment with thrombolysis is quite variable worldwide. In a survey, 64 of the 214 countries and independent territories (30%) reported use of intravenous alteplase, including 3% of low-income countries (1 of 36), 19% of lower middle-income countries (10 of 54), 33% of upper middle-income countries (18 of 54), and 50% of high-income countries (35 of 70). ^, In Europe, thrombolysis is administered, on average, in 7.3% of stroke patients, with countries reporting rates as low as 0.2% in Ukraine to as high as 17.5% in Germany, 18.4% in Austria, 19% in Denmark, and 20.6% in the Netherlands, with 13 countries’ rates higher than 10%. In a recent report of the Safe Implementation of Treatments in Stroke–Sociedad Iberoamericana de EnfermedadesCerebrovasculares (SITS-SIECV) Ibero-American Stroke Registry, intravenous thrombolysis rates in 14 countries averaged 7.7%. Thrombolysis rates can vary between and within a nation, and also depend on whether reported by population or by hospital. In Africa, only three countries, South Africa, Egypt, and Morocco, have reported experiences on thrombolysis. In Asia, data regarding the use of thrombolysis is scarce. Since 2007, there has been an increase in the use of thrombolysis in India. The Indo-US Collaborative Stroke Project reported administration of intravenous thrombolysis in 10% patients in India. The government has also approved use of tenecteplase, with more than 4800 patients having received it thus far. In Thailand, the proportion of patients receiving intravenous thrombolysis has increased from 0.38% in 2008 to 1.95% in 2012. An audit of Australian hospitals found that only 3% of eligible ischemic patients were treated with thrombolysis.

Urban areas exhibit increased use of thrombolysis in comparison to rural areas. Delays in transport contribute to the low rates of thrombolysis of 1%–6% for patients in rural areas worldwide. This trend is prevalent throughout low-, middle-, and high-income countries worldwide but can be overcome by using telemedicine. ^, In the United States, the Get With The Guidelines Stroke Registry identified arrival to a rural hospital as one factor associated with failure of thrombolytic administration.

Following the success of several trials, utilization rates of mechanical thrombectomy have significantly increased in patients arriving up to 6 hours from symptom onset with a National Institutes of Health Stroke Scale (NIHSS) greater than 5. In an analysis from Get With The Guidelines-Stroke (GWTG-S) hospitals from 2004 to 2016, utilization of thrombectomy increased upon publication of pivotal second generation endovascular trials in 2014 and 2015, from 0.13% more per year to 1.33%. By late 2016, after the publications of late time window trials, 7.5% of all ischemic stroke patients were treated with mechanical thrombectomy in centers providing endovascular thrombectomy (EVT), including 27.3% of eligible patients in such centers. In Europe, 1.9% of eligible patients overall received mechanical thrombectomy, with countries such as France, Germany, Switzerland, and Malta reporting rates of 5% or higher. The majority of cases were completed in high-volume centers with more than 25 cases/year, and more than 50% in centers with more than 100 patients/year. In comparison, lower thrombectomy rates have been reported from Asian countries. The treatment gap between urban and rural areas is even more pronounced with endovascular treatment.

Changing Stroke Demographics and Characteristics and Predicted Impact on Thrombolysis and Thrombectomy

Stroke epidemiology including incidence and prevalence is discussed in Chapter 14 . How will the expected changes affect stroke treatment and distribution of resources? Stroke prevention measures are increasingly effective in reducing stroke incidence and mortality in developed countries. This is particularly true for strokes due to atherosclerosis or cardioembolism, which are the main causes of large artery occlusions amenable to thrombectomy; however, the overall prevalence of stroke will continue to increase due to population growth and the aging of the population. Therefore the expected need for both thrombolysis and thrombectomy will continue to increase, although this is difficult to project accurately.

Existing and Projected Distribution of Thrombolysis Centers Worldwide

In the United States, 81% of the population is in reach of intravenous-capable hospitals within 60 minutes by ground and 97% are in reach by air. This data is based on analysis of the 2011 US Medicare Provider and Analysis Review (MEDPAR), which looked at facilities treating patients greater than 65 years that provided at least one case of intravenous alteplase for acute ischemic stroke ( Fig. 51.1 ). Similar access to thrombolysis can be assumed in Canada. In a 1996 census analysis of Geographic Information System (GIS), Scott et al. identified hospitals capable of delivering intravenous alteplase in addition to those with computed tomography (CT), a staff neurologist, and emergency medicine specialist. In this study, 67.3%, 78.2%, and 85.3% of the Canadian population were within 32, 64, and 105 km (60, 90, and 120 minutes) of a thrombolysis capable hospital, respectively.

In Europe, the network of Stroke Units capable of administering thrombolysis varies by country and region. Northern European countries demonstrate a dense network of Stroke Units; however, no such network exists for most of eastern and southern European countries. The European Brain Council estimated that only one in three stroke patients have access to acute Stroke Unit care in Europe. In Asia, the distribution of organized stroke programs capable of thrombolysis has been reported for India and Thailand. In India, approximately 100 centers are able to provide intravenous thrombolysis. In Thailand, only one-fourth of stroke patients were admitted to one of the 110 specialized stroke units, mostly in regional and provincial hospitals. While the quality of acute stroke management is unknown in South Korea, the government initiated 11 Regional Comprehensive Stroke Centers (CSCs) in 2008. Upon initiation, intravenous thrombolysis door-to-needle time was shortened to less than 30 minutes in CSCs.

Where Should Thrombolysis Be Done? Challenges in Thrombolysis Treatment and Development of Designated “Stroke Centers”

Use of thrombolytic therapy in patients with acute ischemic stroke requires recognition of neurologic symptoms, confirmation of diagnosis through history and physical examination, verification of eligibility, safe administration of thrombolytic therapy, and post-treatment follow-up. Initial prehospital recognition of signs or symptoms of stroke is critical to increasing the number of potential patients eligible for thrombolytic therapy. The public’s education in stroke as an emergency, utilization of a single emergency number (911 in the United States, 112 in the European Union), and targeted programs for emergency medical services (EMS), hospital personnel, and physicians speed healthcare access and increase thrombolytic treatment rates. Utilization of prehospital notification by EMS further reduces in-hospital delays to treatment.

Diagnostic confirmation of stroke requires a focused history and a thorough examination to rule out other causes of neurologic deficits. Blood pressure monitoring, blood glucose level, and non-contrast CT are the minimal workup required prior to administration of thrombolytics. In addition, CT angiogram (CTA) can identify patients with large vessel occlusions (LVOs) who may further benefit from EVT. Magnetic resonance imaging (MRI) in acute stroke is a valuable tool to discriminate between stroke and stroke mimics in patients with atypical or less-specific symptoms. Emerging technology, including machine processing and learning, and serum biomarkers may aid in the identification of stroke.

Eligibility for thrombolytic treatment is currently based on review of evidence-based inclusion and exclusion criteria. Physicians or healthcare personnel with stroke thrombolytic expertise can be utilized in the field, at the bedside, or remotely via telemedicine. As more data becomes available through clinical trials and experience in administration increases, certain exclusion criteria have changed from absolute to relative, increasing the number of potential patients eligible for treatment. ^, Further minimum requirements including drug cost, drug availability, physical drug stability, and delivery are important considerations in non-resource rich environments globally. Additional post treatment minimum requirements include monitoring of vital signs.

Delivery of thrombolytic therapy may occur in the pre-hospital setting through Mobile Stroke Units (MSUs) or in the emergency department (ED)/hospital setting. Pre-hospital MSU administration of intravenous alteplase in European and American stroke systems increases the number of patients treated within 60 minutes of symptom onset. Furthermore, pre-hospital administration of thrombolytics may lead to better outcomes in patients with and without pre-stroke dependency as compared to hospital administration. ^, Pre-hospital thrombolytic therapy, however, may be challenging for rural communities or for those with limited resources, and cost effectiveness is still being evaluated in prospective studies.

Most often, thrombolysis is started in the ED, where treatment is limited by the clinical expertise of the ED physician. Neurologic complaints account for 8% of ED consultations, with acute stroke comprising 3%. ^, It has been suggested the average ED physician treats two cases of ischemic stroke with thrombolysis per decade. Lack of experience for ED physicians as well as lack of availability for on-site neurologists therefore limit the use of thrombolysis. Multifaceted training programs for ED physicians, including organized protocols for emergency evaluation, have increased access to thrombolytics in the community setting. ^, Checklists have been proposed as a means to increase ED physician comfort and accuracy in selecting patients for thrombolysis. In addition, utilization of telemedicine as well as advanced practitioners has proven to be an essential tool to expanding the delivery of thrombolytics to hospitals where neurologic expertise is not available.

The current paradigm of excluding patients from thrombolytic treatment on the basis of time has led to the future paradigm of excluding patients based on tissue viability. Advances in the field of neuroimaging with CT or MR perfusion can be utilized to explore the efficacy and safety of thrombolytics in patients with unknown time of onset. ^, As further data become available, the most common barrier to thrombolytic treatment for the practicing clinician, namely, time from symptom onset, may become obsolete.

Owing to these complexities, in 2000, the Brain Attack Coalition (BAC) encouraged the development of primary stroke centers (PSCs) and CSCs to improve the quality and organization of evidence-based stroke care. ^, A PSC has the necessary personnel, infrastructure, and support to stabilize and treat the majority of stroke patients. A CSC is able to provide specialized testing and interventions to the most complex stroke patients, in addition to serving as resource centers for regional facilities.

In 2003, the American Heart Association/American Stroke Association (AHA/ASA) and The Joint Commission (TJC) proposed a stroke certification process through a Disease-Specific Certification program, involving voluntary evaluation of consistent clinical outcomes and minimal standards in stroke care centered around treatment with intravenous thrombolysis. BAC recommendations on the major elements of a PSC, later revised in 2011, were critical to the development of PSCs. ^, Major elements for a PSC included patient care areas (EMS, ED services, stroke unit, acute stroke teams, written protocols, neurosurgical services) and support services (parent medical organization, director of stroke center, neuroimaging, laboratory services, outcome and quality improvement committees, continuing medical education). In 2004, certification of PSCs began, and by 2011 there were more than 800 PSCs out of 4000–5000 facilities in the United States. By 2010, 16 states had adopted legislation for EMS to route acute stroke patients to PSCs, bypassing noncertified facilities, which covered 53% of the US population. Implementation of stroke performance measures, utilizing the AHA/ASA GWTG-S program, has been associated with further improvement in stroke care.

In 2005, the BAC provided recommendations for a new level of care: CSCs. These recommendations emphasized specialized personnel (vascular neurology, neurosurgery, critical care, rehabilitation medicine, stroke nurses, neuroradiology), diagnostic techniques (CTA, MRI with diffusion, conventional cerebral angiography, transesophageal echocardiography, and transcranial Doppler), availability of interventional and surgical therapies (intra-arterial reperfusion, brain hematoma evacuation, ventriculostomy, carotid endarterectomy), infrastructure (stroke unit, intensive care unit, operating and interventional coverage 24/7), and education and research programs (patient, community, and professional education). TJC launched a certification program for CSCs in 2012.

TJC, Der Norske Veritas and Germanischer Lloyd (DNV GL), and Healthcare Facilities Accreditation Program (HFAP) designate three levels of national certification programs: CSC, PSC, and acute stroke-ready hospital (ASRH). ASRH certification was created to recognize smaller, at times remote, community hospitals in areas without PSCs or CSCs, to optimize emergency stroke care, with the guidance of regional PSCs and CSCs. PSC certification was designed to meet BAC’s recommendations for stroke care through access to dedicated, specialized personnel and therapies in the context of a defined stroke unit. CSCs must meet all of the requirements for PSC certification, plus additional requirements to manage complex stroke cases including specified volumes of patients and procedures. To date in the United States, there are more than 1500 PSCs, 200 CSCs, and a growing number of ASRHs.

In 2013, the ASA published recommendations regarding stroke systems of care in light of changes in endovascular therapy, neurocritical care, stroke center certification, and use of telestroke and MSUs ( Table 51.1 ). These guidelines stress the importance of support mechanisms to assist communities as a whole, and patients and providers with a commitment to local and regional public awareness and education. Furthermore, these guidelines outline the key role of EMS, with use of prehospital stroke severity scales to identify LVOs and in agreement with the Mission: Lifeline algorithm, route patients to a CSC if travel time is less than 15 minutes, compared to the closest PSC or ASRH. Further research is warranted to address integration of MSUs into pre-hospital systems. Currently, “ideal” times have been proposed; however, uncertainty remains regarding the quality metric thresholds for pre-hospital recognition of patients with LVO and acceptable time metrics for patients initially triaged to non-thrombectomy centers. Additional opportunities to improve include establishment of best practices in low-volume, inexperienced centers regarding transport and training standardization of neurointerventionalists to ensure adequate supply and development of sharing processes.

Quality initiatives for stroke care also evolved worldwide, with TJC International certifying hospitals outside the United States. The European Stroke Organization (ESO) recommended the establishment of ESO Stroke Units and Stroke Centers as levels of certification in participating countries, a system that has been in use in Germany since the early 2000 decade.