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The mission lifeline severity-based stroke treatment algorithm: We need more time
  1. J Mocco1,
  2. David Fiorella2,
  3. Felipe C Albuquerque3
  1. 1Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, USA
  2. 2Department of Neurosurgery, State University of New York at Stony Brook, Stony Brook University Medical Center, Stony Brook, NY, USA
  3. 3Division of Neurological Surgery, Barrow Neurological Institute, Phoenix, AZ, USA
  1. Correspondence to Dr J Mocco, The Mount Sinai Health System, 1450 Madison Ave, KCC-1 North New York, NY 10029, USA; j.mocco{at}

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On March 10th, 2017 the American Heart Association presented their Mission Lifeline Severity-Based Stroke Treatment Algorithm For EMS. This document consisted of single page algorithm written to provide guidance to EMS providers regarding the triage and transport of suspected stroke patients, as well as a single explanatory page ( Specifically, patients with suspected emergent large vessel occlusion (ELVO) (based on pre-hospital stroke assessment), who were last know well within 6 hours, are to be considered for direct transfer to an endovascular capable center if such a direct transfer will not delay arrival at a stroke center by more than 15 minutes.

The AHA acknowledges that level I data are lacking to support a firm recommendation on the acceptable delay in arrival at a stroke center when considering re-routing patients. They therefore state that the committee felt it “was best to err on the side of caution and initially set the additional transport delay to 15 minutes”.

The JNIS applauds the AHA's effort to further the important conversation of stroke patient triage and transfer. We also recognize that the document's authors acknowledge fallability of any algorithm, and clearly state that this algorithm is not a final or comprehensive answer to the many problems currently relevent to communities struggling to provide timely care for stroke patients. However, we feel that there are a number of critical limitiations to the document that should be addressed and discussed in the broader community. It is our hope to engender a constructive conversation, which will ultimately lead to a revised recommendation and the best possible care for stroke patients.

In 2015 and 2016, seven concordant randomized controlled trials powerfully and unequivocally demonstrated that for ELVO, thrombectomy results in markedly better patient outcomes than does treatment with IV-tPA alone.1–7 The differences between treatment groups were massive, with numbers needed to treat as low as 2–4 for one additional independent outcome. The benefits of thrombectomy were observed in studies that included patients randomized up to 12 hours after the onset of symptoms.2 Correspondingly, these same studies confirmed that most ELVO patients receiving IV tPA alone had poor clinical outcomes. Prior studies have shown that IV tPA is ineffective in achieving timely revascularization in the majority of patients with ELVO.8 At the same time, modern thrombectomy techniques were shown capable of achieving efficient revascularization in more than 70–80% of patients.9 ,10 In meta-analysis, clinical outcomes in thrombectomy patients remained superior to best medical management for more than 7 hours after the onset of stroke symptoms.11

Thus, modern thrombectomy has been established as the standard of care for ELVO and is far superior to IV tPA. However, it has not been precisely established how great a time delay is acceptable to transport a patient to facility that can provide this overwhelmingly effective interventional therapy over one that is potentially capable of more rapidly delivering a far less effective alternative. We would argue that, despite the highly critical component played by time in acute stroke treatment, 15 minutes is far too short of a time allowance.

This is especially true when one considers the “real world” implications of a now obselete policy that still mandates the transport of patients with severe stroke to the nearest primary stroke center. First, it is important to consider that many smaller “IV-tPA only” centers are relatively inefficient with respect to the delivery of the drug to eligible stroke patients when they are compared to larger advanced stroke centers. Thus transfer times to a larger center may be largely offset by greater efficiencies in triage, diagnosis and IV tPA delivery. Second, one must consider the tremendous inherent time delay (typically hours) that is inevitably imposed upon endovascular therapy by a policy that mandates stopping at a geographically closer “IV-tPA only” hospital prior to subsequent transfer to an interventional center. In the majority of patients with ELVO and severe stroke, who will not revascularize efficiently with IV tPA, these substantial delays can be devastating and in many cases lethal.

The likelihood that many primary stroke centers are not meeting current IV tPA target times is supported by the Get With The Guidelines: Target Stroke Initiative data reporting a median door-to-needle time of 67 minutes, despite a long-established AHA door to needle target time of 60 minutes.12 It is notable that these prolonged door-to-needle times have persisted despite decades of emphasis on physician education, infrastructural investment and regulatory monitoring specifically designed to reduce delays. As such, these times are unlikely to substantially improve. This contention is also supported by a recent regional stroke center survey that reported major multifactorial logistical barriers to rapid IV tPA administration are prevalent in many designated primary stroke centers.13

Recently, the AHA journal Stroke published two separate studies performing sophisticated mathematical modeling deisgned to compare the “drip and ship” to “mothership” (i.e., direct bypass to an endovascular capable center) models. The models were designed to account for the screening power of pre-hospital stroke scales, the decay curve of success/benefit for both endovascular therapy and IV tPA (taken from quality real world data), travel time across multiple geographic regions, and in-hospital door to needle times.14 ,15 In these analyses, unless the non-endovascular stroke center was able to provide IV tPA in 30 min or less – clearly the exception rather than the rule – the modelling favored bypass directly to an endovascular center over a “drip and ship” strategy in all but the most remotely located and sparesly populated areas.14 The closer the thrombectomy center was to the non-endovascular center, the more dramatic the benefit was for the “mothership” model. An efficient “drip and ship center” model did not start to become favorable until the travel times exceeded 45 minutes.15 Thus, under the current circumstances, in most suburban and urban areas, the available models would predict that primary transfer to a thrombectomy center would be beneficial for patient outcomes. On the basis of these analyses the authors conclude that the American Heart Association's time recommendations for bypass “may be too conservative”.

There are also “real world” clinical data that have corroborated this hypothesis. In 2016, Zaidi et al. published an observational cohort study performed across an entire county of Ohio.16 In this study, they compared outcomes of all stroke patients seen at their hospital both before and after the institution of a broad bypass protocol targeting arrival at an endovascular center within 30 minutes. They observed that with the bypass model, despite potentially longer transport times, a much higher percentage of patients received IV tPA (26% versus 13%) and that door to needle times for IV tPA were significantly reduced by the bypass model. Further support for a longer threshold for bypass was recently presented at the AHA's 2017 International Stroke Conference in Houston by Froehler et al. who used STRATIS registry data, as well as supplementary real world data, to statistically model bypass systems.15 The investigators found no significant detrimental effect on 90-day independence rates for patients that missed IV tPA administration due to bypass. Furthermore, the data supported the hypothesis that endovasular capable centers, often with higher volumes of stroke patients, broader physician teams, and more stringent certification requirements may demonstrate faster door to IV tPA times, which again, could offset or altogether overcome differences in pre-hospital travel time.

Similarly, a bypass program for suspected EVLO patients instituted in Central Denmark resulted in marked reductions in average times to endovascular treatment (approximately 1 hour) and resulted in substantial improvements in good patient outcomes (62 vs. 43%). Moreover, the benefits associated with the bypass program were achieved without increasing the average times to the initiation of IV-tPA therapy for patients in the region – again reflecting the superior efficiency of endovascular stroke centers with respect to the administration of medical therapy relative to non-endovascular centers.16

It is our belief that the AHA has a broad reach in the stroke community and a justifiably powerful impact on EMS practice across the nation. As such, they bear an onus to ensure that their recommendations are not only a “consensus algorithm… subsequently reviewed by numerous stroke committees within the organization” but rather an evidence-based algorithm (using the best evidence available, even if it is not from RCTs) that has recieved broad stakeholder endorsement for the betterment of stroke patients everywhere. We look forward to the eventual results of the RACECAT trial in Spain, which is specifically designed to evaluate the question of bypass (NCT 02795962). However, until that time, we believe that the available data favor a substantially expanded travel-time threshold of 45 minutes for the bypass of severe acute stroke patients directly to thrombectomy centers. Such a policy will directly and dramatically reduce times to thrombectomy, and for most patients, time to effective reperfusion, relative to the largely antiquated “drip and ship” model. Also, the existing data would suggest that much of the delay incurred in longer transfer times would be offset or compeltely overcome by greater efficiencies in regard to the delivery of IV-tPA at larger, endovascular capable centers.


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