Abstract
Introduction
The overarching goal in endovascular stroke treatment (EVT)1,2 is to open the occluded artery fast and completely. Reperfusion speed is a major determinant of outcome that can be influenced by the stroke intervention team.1,3 Faster treatment is strongly associated with better outcomes4–7 and lower overall costs of stroke treatment,8,9 and therefore, interval times are an important process measure outcome used to assess the quality of acute stroke care. Thus, stroke physicians and their medical teams have worked hard towards achieving faster treatment times, by introducing pre-notification tools, optimizing transport paradigms 10 and streamlining in-hospital workflows.11–14,15 Both the ESCAPE and ESCAPE-NA1 trials16,17 emphasized workflow speed. ESCAPE had the shortest workflow times compared to other EVT trials.18–22
We compared workflow interval times and endovascular reperfusion results from the ESCAPE trial (enrolment period February 2013 to October 2014), to ESCAPE-NA1 (enrolment period: March 2017 to August 2019) to compare interval times according to their modality of arrival (transfer vs. direct) and to evaluate improvement in workflow interval times.
Methods
Data are from the ESCAPE and the ESCAPE-NA1 trials. The ESCAPE trial (NCT01778335) was a multicenter randomized controlled trial comparing EVT in addition to the best medical treatment to the best medical treatment alone for AIS patients with LVO.
16
Patients were eligible for the trial if they presented within 12 h of symptom onset.
23
In total, 316 patients (
The two trials collected data on multiple workflow interval times. Hospital arrival was defined as arrival at the emergency department of the endovascular-capable hospital. Baseline imaging time was defined as the time of the first slice of non-contrast head CT of the qualifying imaging which was performed at the EVT-capable hospital. Reperfusion time was defined as the time of first modified treatment in cerebral infarction (mTICI) 3 score of 2b or higher, as seen on digital subtraction angiography. The first and final reperfusion results were assessed by an independent core lab. In the ESCAPE trial, transfer patients were defined as those who received intravenous alteplase prior to arrival at the EVT hospital. Mothership patients were those who arrived directly at the EVT hospital. In the ESCAPE-NA1 trial, patients were classified as ‘transfer’ or ‘mothership’ primarily, regardless of where intravenous alteplase was administered.
Statistical analysis
Data are summarized using descriptive statistics. Workflow metrics and reperfusion results were compared between the two trials using the Wilcoxon rank sum (Mann–Whitney U) test and Fisher's exact test. We investigated predictors of the summary in-hospital metric, door-to-puncture time using multiple linear regression. All tests were two-sided and conventional levels of significance (alpha = .05) were used for interpretation. Data analyses were performed in Stata 16.1.
Results
Baseline characteristics are shown in Table 1. Key differences between the two trials were the higher proportion of patients arriving by transfer from a primary hospital, higher general anaesthesia use and lower alteplase use in the ESCAPE-NA1 trial. Distributions for interval times are shown in Supplemental Figures I–III.
Baseline characteristics.
ESCAPE trial included 165 in the treatment group.
IQR = interquartile range.
Workflow interval times from both trials are shown in Table 2, and by mode of hospital arrival in Table 3. Except for onset-to-randomization time, all interval times were significantly shorter in ESCAPE-NA1, suggesting clear improvement in in-hospital workflows over 5 years (Table 2). In-hospital process times at the EVT-capable hospital were generally faster in transfer patients compared to direct arrival (mothership) patients (Table 3). A comparison of workflow times in transfer vs. mothership patients showed that the largest improvements were made in mothership patients, while the differences in interval times in transfer patients were less pronounced (Table 3). In fact, in transfer patients, some interval times were longer in ESCAPE-NA1 compared to ESCAPE (door-to-imaging time: median 12 [7–19] min in ESCAPE-NA1 vs. 9.5 [5–19] min in ESCAPE, door-to-puncture time: 48 [37–68] min vs. 46. [32–64] min, imaging-to-puncture time: 36 [26–53] min vs. 32 [24–48] min).
Workflow interval times in ESCAPE and ESCAPE-NA1 trials.
Note. Interpretation of interval times.
Door = arrival at ED of comprehensive (EVT) stroke centre; imaging = time of first slice of non-contrast CT of the qualifying imaging; alteplase = time of intravenous alteplase bolus dose (applies to patient receiving alteplase only); puncture = time of arterial access for EVT; reperfusion = time of reperfusion (eTICI 2b score or higher, patients who received EVT only); IQR = interquartile range; ED = emergency department; EVT = endovascular thrombectomy; CT = computed tomography; eTICI = expanded thrombolysis in cerebral ischemia score
Negative times here indicate the fact that alteplase was dosed at an outside hospital before transfer.
Workflow interval times in direct vs. transfer patients.
Note = interpretation of interval times
Door = arrival at ED of comprehensive (EVT) stroke centre; imaging = time of first slice of non-contrast CT of the qualifying imaging; alteplase = time of intravenous alteplase bolus dose (applies to patient receiving alteplase only); puncture = time of arterial access for EVT; reperfusion = time of reperfusion (eTICI 2b score or higher, patients who received EVT only); IQR = interquartile range; ED = emergency department; EVT = endovascular thrombectomy; CT = computed tomography; eTICI = expanded thrombolysis in cerebral ischemia score
Negative times here indicate the fact that alteplase was dosed at an outside hospital before transfer.
Predictors of improvement in door-to-puncture time are shown in Table 4. The marked difference between direct arrival and transfer patients, between the two studies over 5 years and among regions of the world, is evident. There was no effect of procedural sedation use, age, sex, stroke severity or evidence of a learning effect (change according to randomization order) over the duration of each trial.
Predictors of in-hospital door-to-puncture time.
Multiple linear regression analysis identifying predictors of door-to-puncture time in minutes, adjusted for age, sex, baseline NIHSS score, alteplase use, high volume (>30 patients enrolled) vs. low volume centre, procedural sedation type and randomization order. On average, door-to-puncture is 18 min slower with direct arrival to the EVT centre vs. transfer from a primary hospital; using Canadian sites as a benchmark, 19 min faster in Europe and 19 min slower in Australasia (Australian and South Korean sites), with no difference between the US and Canada; and 18 min faster in ESCAPE-NA1 compared to the ESCAPE trial. Clinical factors age, sex, baseline NIHSS score, alteplase use, high volume (>30 patients enrolled) vs. low volume centre, procedural sedation type and randomization order (as a surrogate marker for a protocol learning effect) were not predictive of door-to-puncture time.
Discussion
This study shows significant improvements in endovascular stroke treatment interval times over 5 years, particularly in patients directly admitted to an EVT-capable hospital.
Since 2015, pre-notification tools, one-stop-shop imaging (i.e. bypassing the CT scanner) and pre-prepared standardized thrombectomy kits (BRISK; Brisk Recanalization Ischemic Stroke Kit) for example have been introduced to minimize in-hospital delays.13,14,25 Our results suggest that these measures have indeed been successful in minimizing in-hospital workflow times, particularly in EVT-capable hospitals. All the in-hospital workflow interval times that were assessed in this study have improved over time, which resulted in a notable decrease of almost 20 min on average in door-to-reperfusion time (median 91 [69–120] min in ESCAPE-NA1 vs. 110 [89–143] min in ESCAPE), which is arguably the most meaningful in-hospital workflow interval time. Time efficiency of in-hospital workflows improved at all levels, with significantly shorter door-to-imaging, door-to-alteplase, imaging-to-puncture and puncture-to-reperfusion-times in the ESCAPE-NA1 trial. An important neutral finding is that the use of general anaesthesia or conscious sedation did not, on average, result in longer in-hospital treatment times.
Onset to randomization times were slightly longer in ESCAPE-NA1 compared to ESCAPE. We suspect that this was caused by secular changes in stroke care with more patients being treated and enrolled into the trial in later time windows.
Overall, in-hospital process times at the EVT-capable hospital are significantly faster for patients who are transferred, probably due to the opportunity to prepare for the patient's arrival while the patient is in transit. Once the EVT procedure has begun, interval times to reperfusion are very similar in transfer and mothership patients. Improvements in interval times for transfer patients were less pronounced, with door-to-imaging, door-to-puncture and imaging-to-puncture times having even slightly increased over time. One reason for this could be that workflows and protocols for transfer patients are less standardized and also depend on the local infrastructure and referring hospitals. Limited communication and imaging transmission between hospitals play a role in longer interval times for transfer patients. Alternately, we may have reached a ceiling where substantively faster treatment is simply not possible to achieve. It is important to note that most patients in both trials underwent imaging at the endovascular centre. Bypassing this step, especially in those situations where the imaging at the outside hospital is relatively recent and there is no change in the patient's clinical status, could potentially lead to further shortening of the overall times of transfer patients. On the other hand, the COVID-19 pandemic, which started after completion of the ESCAPE-NA1 trial, has slowed down acute stroke workflow times in some instances, 26 and the recent increase in endovascular treatment of large core and medium vessel occlusion patients may require a more nuanced approach to decision-making compared to the LVO stroke patient population with small-to-moderate core sizes that were included in the ESCAPE and ESCAPE-NA1 trials. This may cause slight treatment delays, and a workflow comparison that includes more recent workflow data from large core and medium vessel occlusion EVT trials would thus be of interest.
The current study benefits from two large, randomized datasets that allowed for patient-level comparison of a number of workflow metrics and reperfusion quality but is limited to the sites that contributed to both trials. The external validity of the results will necessarily depend upon site-specific factors. The distinction between mothership and transfer patients in the ESCAPE trial was based on the location of intravenous alteplase administration; patients who did not receive intravenous alteplase were classified as mothership patients, even if they might have initially been admitted to another hospital. Only the EVT arm of ESCAPE was used for the comparison of reperfusion time metrics and quality, which resulted in a relatively small sample number of ESCAPE patients that were included in the comparison.
In conclusion, workflow interval times in endovascular stroke treatment have significantly improved over time, particularly in patients directly presenting to an EVT-capable hospital.
Supplemental Material
sj-docx-1-ine-10.1177_15910199251330095 - Supplemental material for Improvements in endovascular stroke treatment workflow over 5 years: ESCAPE to ESCAPE-NA1
Supplemental material, sj-docx-1-ine-10.1177_15910199251330095 for Improvements in endovascular stroke treatment workflow over 5 years: ESCAPE to ESCAPE-NA1 by Johanna M Ospel, Mayank Goyal, Ryan McTaggart, Alexandre Y Poppe, Andrew M Demchuk, J Rempel, J Thornton, Ricardo A Hanel, Mohammed Almekhlafi, Bruce CV Campbell, René Chapot, Diogo Haussen, Mahesh Jayaraman, Joung-Ho Rha, Richard H Swartz, Michael Tymianski, Bijoy K Menon, Raul G Nogueira, Michael D Hill and in Interventional Neuroradiology
Footnotes
Declaration of conflicting interests
Funding
Supplemental material
References
Supplementary Material
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