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Page 6 of 9 Linger et al. Vessel Plus 2020;4:36 I http://dx.doi.org/10.20517/2574-1209.2020.51

TIME TO TREATMENT IS STILL CRUCIAL: IMPROVING DOOR-TO-REPERFUSION TIMES
The critically time-dependent benefits of reperfusion therapies are well understood, and streamlining
workflow to reduce treatment delays remains central to optimizing patient outcomes. Even though
individual patients with excellent collateral flow may have slower infarct progression, there is an overall
decrease in the proportion of patients eligible for extended-window thrombectomy on the basis of
favorable perfusion imaging as time elapses. This corresponds to the time-dependent cerebral blood flow
thresholds for infarction and failure of collateral cerebral circulation over time. A meta-analysis looking
at time to effective reperfusion demonstrated that for every 4-min delay from emergency department
arrival to substantial endovascular reperfusion time, 1 of every 100 treated patients had a worse disability
[15]
score (higher score by 1 or more on the mRS) . Minimizing time from onset of symptoms to reperfusion
therapy is therefore crucial in maximizing the number of patients eligible for reperfusion therapy.

[15]
The largest delay in reperfusion therapy is in the pre-hospital setting . Several advances have been made
in both the pre-hospital and emergency department settings. Paramedic stroke recognition and pre-
hospital notification, whereby stroke centers are notified of a potential stroke patient prior to arrival, have
been shown to decrease door-to-imaging, door-to-thrombolysis and onset-to-thrombolysis times, while
also increasing eligibility for thrombolysis [41-43] . In addition, screening tools have been developed to identify
suspected LVOs in the pre-hospital setting [44-46] . These tools allow patients with suspected LVOs to be
transferred directly to thrombectomy-capable centers, bypassing hospitals not capable of providing this
service and subsequently improving time to reperfusion. One study investigating an ambulance pre-hospital
clinical triage tool demonstrated high sensitivity (85.7%), specificity (93.5%), and positive predictive value
[46]
(80%) for the recognition of thrombectomy-eligible LVOs . Future studies are investigating the application
of these tools to accelerate patient delivery to thrombectomy-capable centers by bypassing hospitals not
capable of providing this service [Direct Transfer to an Endovascular Center Compared to Transfer to
Closest Stroke Center in Acute Stroke with Suspected Large Vessel Occlusion (RACECAT), NCT02795962
and Treatment Strategy In Acute Ischemic large Vessel STROKE: Prioritize Thrombolysis or Endovascular
Treatment (TRIAGE), NCT03542188].

There is evidence for the benefit of mobile stroke units (MSUs) in reducing time to reperfusion and
subsequent disability. An MSU is an ambulance with on-board CT-scanner and a specialized stroke team
capable of assessing and treating patients in the community and directing those eligible to thrombectomy-
capable centers. A study from Melbourne, Australia demonstrated that the MSU model resulted in an
overall time saving from first ambulance dispatch to thrombolysis of 42.5 min (95%CI: 36.0-49.0) and a
median time saving from first ambulance dispatch to the start of thrombectomy (arterial puncture) of 51 min
[47]
in those with LVO (95%CI: 30.1-71.9) . The estimated disability reduction, based on time saved, was 20.9
disability-adjusted life years for 100 patients in the thrombolysis group and 24.6 disability-adjusted life
[47]
years in the thrombectomy group . Berlin has three MSU and results presented in abstract form indicated
[48]
improved functional outcomes compared to standard in-hospital care .
Workflow efficiencies in the movement of stroke patients in and between hospitals have decreased time
to reperfusion therapy in stroke centers around the world. Universal features of efficient systems include
emergency department and stroke team prenotification of suspected stroke patients by ambulance, direct
transfer of patients from triage to CT table on the ambulance stretcher and the delivery of thrombolysis,
if eligible, on the CT table. These interventions have been shown to reduce door-to-thrombolysis to 20-
[52]
34 min [49-51] . Repeated imaging after transfer is a major cause of delays . A time saving of 59 min from
door-to-groin access (at a thrombectomy center) is possible if patients diagnosed with LVOs at an external
site are transferred directly to the neuro-angiography suite rather than being admitted via the emergency
[53]
department . Another strategy to achieve time savings that is currently under investigation is to transfer
patients with suspected LVO (NIHSS score > 10 on arrival) directly from triage to the neuro-angiography