Institution of Code Neurointervention and Its Impact on Reaction and

Treatment Times

Spozhmy Panezai, MD , Sanket Meghpara, MD , Ashish Kulhari, MD , Jaskiran Brar, MD ,

Laura Suhan, NP-C¹, Amrinder Singh, MD¹, Siddhart Mehta, MD¹, Haralabous Zacharatos, MD¹,

Sara Strauss, MD¹, and Jawad Kirmani, MD¹

¹JFK Stroke and Neurovascular Center, Hackensack Meridian Health-JFK Medical Center, Edison, NJ USA

²Tripler Army Medical Center, HI 96859

³Surrey Memorial Hospital, B.C, Canada

Abstract

Background/Objective—Various strategies have been implemented to reduce acute stroke treatment

times. Recent studies have shown a significant benefit of acute endovascular therapy. The JFK Comprehen‐

sive Stroke Center instituted Code Neurointervention (NI) on May 1, 2014 for the purpose of rapidly

assembling the NI team and rapidly providing acute endovascular therapy.

Design/Methods—We performed a retrospective analysis of all patients who had Code NI (Code NI

group) called from May 1, 2014 to July 30, 2018 and compared them to patients who underwent acute

endovascular treatment prior to initiation of the code (pre-Code NI group) between January 2012 and April

30, 2014. The following parameters were compared: door to puncture (DTP) and door to recanalization

(DTR) times, as well as preprocedure NIHSS, 24-hour postprocedure NIHSS, and 90-day modified Rankin

scores.

Results—There were 67 pre-Code NI patients compared to 193 Code NI patients. Mean and median DTP

times for pre-code NI vs Code NI patients were 161 minutes(mins) vs 115mins (p<0.0001, 31.76-58.86)

and 153mins vs 112mins (p <0.0001), respectively. Mean and median DTR times were 220 mins vs

167mins (p <0.0001, 37.76-69.97) and 225mins vs 171mins (p <0.0001). Mean pre-procedure NIHSS was

16 for both groups while 24 hours post procedure NIHSS was 10.6 vs 10.8 (p =.078, 1.8-2.38). Mean 90

day mRS was 2.15 vs 1.65 (p=0.036, 0.32-0.96).

Conclusion—Institution of Code NI significantly improved DTP and DTR times as well as mRS at 3-

months postprocedure. Rapid assembly of the NI team, rapid availability of imaging and angiography suite,

and streamlining of processes, likely contribute to these differences. These lessons and more widespread

institution of such codes will further aid in improving acute stroke care for patients.

Introduction

Stroke is a leading cause of serious long-term disability Although stroke continues to impact the population

and the fifth leading cause of death in the United States heavily, stroke care overall has improved in many ways.

[1]. Ischemic strokes, in which blood flow to the brain is This is likely due to many factors including better pri‐

blocked, account for about 87% of all strokes [2]. The mary and secondary prevention and more rapid and

longer neuronal tissue is without adequate blood flow, effective acute stroke treatments [4]. Intravenous alte‐

the greater the extent of damage to the brain [3]. Thus, plase (IV tPA) continues to be the only FDA approved

time plays an important role in predicting clinical out‐ medical treatment of acute ischemic stroke; however,

comes and treatment effect in cerebral ischemia and fur‐ outcomes with treatment are time-dependent. A large

ther supports the need for emergent assessment and meta-analysis of individual patient data from random‐

ized clinical trials showed that the odds ratio (OR) for a

good outcome was 1.75 for treatment within 3 hours of

treatment.

Vol. 11, No. 1, pp. 1–5. Published January, 2020.

*Corresponding Author: Spozhmy Panezai MD, JFK Stroke and Neurovascular Center, Hackensack Meridian Health-JFK Medical Center, 65

James St, Edison, NJ 08820, USA. Tel:(732)744-5805. spozhmy.panezai@hackensackmeridian.org

stroke onset and 1.26 for treatment between 3 and 4.5 mendation. If it was felt that the patient may benefit

from a procedure, then the entire neurointerventional

team (physicians, technicians, and nurses) would per‐

sonally be notified by the stroke team and called in after

hours. Delays to treatment in this paradigm included

extra time needed for acquisition and interpretation of

advanced imaging, discussion with the neurointerven‐

tionalist, and notification of the individual members of

the team, as well as travel time if the team was not in

hours; the absolute benefit decreased from 9.8% to 4.2%

in these time windows [5].

Various strategies have been undertaken to reduce acute

stroke treatment times, including institution of a Code

Stroke alert and improvement of door to CT and door to

needle times [6,7]. In contrast to the IMS III, MR RES‐

CUE, and Synthesis Expansion trials, which failed to

show improved outcomes with endovascular therapy, house after hours and on weekends, and patient prepara‐

more recent studies (MR CLEAN, EXTEND IA, tion prior to groin puncture. Time metrics, including

door to decision for NI, DTP, and DTR were reviewed in

early 2014. It was determined that improvements needed

to be made in order to make the process more efficient

and timely.

ESCAPE, and SWIFT PRIME) have shown a significant

benefit of endovascular therapy in acute stroke treatment

[8–12]. Earlier reperfusion (within a 6-hour window) of

large vessel occlusions (LVOs) via intraarterial treat‐

ment has been shown to correlate with improved out‐

comes [13–15]. In fact, with the use of advanced neuroi‐

maging techniques and careful patient selection, acute

endovascular thrombectomy has been shown to be feasi‐

ble and results in better patient outcomes when per‐

formed up to 24 hours of last known well time [16]. In

addition, a meta-analysis by the HERMES Collaborators

has shown that shorter emergency department (ER)

arrival to groin puncture time period was associated with

higher recanalization rates of occluded vessels and better

clinical outcomes [17,18].

A process improvement project was undertaken by the

multidisciplinary stroke team in early 2014 and a Code

NI alert and policy were created for the purpose of rapid

activation of the NI Team. Under this new policy, the

stroke team made the determination as to whether a

patient would be a candidate for NI and the team would

activate the Code NI prior to speaking with the neuroin‐

terventionalist. The NI team members were provided

with pagers through which they would be alerted simul‐

taneously. The patient was prepared for the procedure in

the emergency room and was brought to the neurointer‐

ventional suite as soon as the room was available and a

technician arrived. The emergency room nurse would

care for the patient and would remain to start the proce‐

dure until handoff was given to the interventional nurse.

The patient’s groin was prepared and draped and the

neurointerventionalist would puncture upon arrival.

Education was given to the various staff that would be

involved in this process (including the ED, radiology,

neurology, stroke, and ICU staff) and an official hospi‐

tal-wide policy was created and approved by administra‐

tion. On May 1, 2014, this alert was officially instituted

and time parameters were collected.

In May 2014, the Hackensack Meridian JFK Compre‐

hensive Stroke Center instituted a Code Neurointerven‐

tion (NI) process for the purpose of rapidly assembling

the NI team and rapidly providing acute endovascular

treatment. This alert was set up in addition to the already

existent Code Stroke alert. Door to puncture (DTP) and

door to recanalization (DTR) were compared to corre‐

sponding times from the years prior to institution of

Code NI. Preprocedure and 24 hours postprocedure

NIHSS Scores were compared as well as 90-day mRS.

These time measures will continue to be looked at in

more detail to see where further improvements in the

process can be made.

We performed a retrospective analysis of all patients

who had Code NI called from May 1, 2014 to July 30,

2018 and compared them to patients who underwent

acute endovascular treatment from January 1, 2012 to

April 29, 2014, the years prior to initiation of the new

code(pre-Code NI). The following time parameters were

compared: DTP and DTR times. Preprocedure and 24-

hour postprocedure NIHSS and 3-month postprocedure

Modified Rankin Scores were also compared between

the groups to see if institution of the new process resul‐

ted in better outcomes.

Method

A Code Stroke alert was already in place to activate the

stroke team for the purpose of rapid patient assessment

and stabilization, imaging acquisition, and administra‐

tion of IV tPA to eligible patients. Prior to institution of

Code NI, the acute stroke team would first have a dis‐

cussion with the neurointerventionalist on call as to

whether a patient would be a candidate for neurointer‐

ventional treatment. This was based on the patient’s clin‐

ical presentation, advanced imaging modalities (CT, CT

Statistical analysis was performed using the GraphPad

angiography, and CT perfusion), and physician recom‐ QuickCalcs Web site. A two-tailed t-test was performed.

Panezai et al.

Table 1. Pre-Code NI versus Post-Code NI data

Pre-Code NI

Post-Code NI

Door to groin puncture

No. of patients

Mean

161

153

193

115

112

Median

P-value, 95% confidence interval (CI) <0.0001 (32.06–58.55)

DTR

No. of patients

Mean

220

225

193

167

171

Median

P-value, 95% CI

mRS on discharge

No. of patients

Mean

<0.0001 (38.15–69.58)

3.98

193

3.91

Median

P-value, 95% CI

3-month mRS

No. of patients

Mean

0.7238 (–0.29 to 0.42)

2.15

193

1.65

Median

P-value, 95% CI

Initial NIH

No. of patients

Mean

0.0361 ( 0.032–0.95)

193

16.08854167

15.70149254

15.5

Median

24-hour NIH

No. of patients

Mean

10.6

193

10.8

Median

NIH change

No. of patients

Mean

5.45

193

Median

P-value, 95% CI

0.6621 (−1.59 to 2.5)

ded vessel. Major criticisms of the IMS III, MR RES‐

CUE, and Synthesis expansion trials included not only

the usage of older devices but also the prolonged dura‐

tion of time between stroke onset and initiation of endo‐

vascular therapy. Median time from stroke onset to groin

puncture in MR RESCUE, IMS III, and Synthesis

expansion was 330, 212, and 245 minutes, respectively

[8,19,20]. As a result, recanalization rates were lower

and endovascular therapy was concluded to be inferior

to IV thrombolysis. Although a big portion of such time

delays includes stroke recognition and ED presentation,

a large amount of time is also spent between ED arrival

to initiation of endovascular therapy.

Results

There were 1008 total ischemic stroke patients admitted

to the hospital during the pre-Code NI period versus

2255 total ischemic stroke patients in Code NI time

frame. Of these, there were 67 patients who underwent

NI in the pre-Code NI period compared to 193 NI

patients in the Code NI time frame (Table 1). Mean and

median DTP times for pre-Code NI versus Code NI

patients were 161 mins versus 115 mins (p < 0.0001,

31.76–58.86) and 153 mins versus 112 mins (p <

0.0001), respectively. Mean and median DTR times

were 220 mins versus 167 mins (P < 0.0001, 37.76–

69.97) and 220 mins versus 171 (p < 0.0001). These

reductions in response and treatment times were statisti‐

cally significant. Mean preprocedure NIHSS was 16 for

both groups while 24 hours postprocedure NIHSS was

10.6 versus 10.8 (p = 0.078, 1.8–2.38). This was similar

in both groups. The change in NIHSS preprocedure and

24 hours postprocedure in both groups was the same as

well and was not significant. Mean 90-day mRS was

2.15 versus 1.65 (p = 0.036, 0.32–0.96) which was stat‐

istically significant.

The meta-analysis by the HERMES Collaborators

showed that the time between stroke onset to ED arrival

did not significantly effect clinical outcomes post throm‐

bectomy. However, pronounced treatment effect modifi‐

cation was observed with various time metrics begin‐

ning from ER arrival [17]. One possible explanation for

this includes imprecise determination or documentation

of stroke onset time compared to more accurate ED

arrival time [21]. A sigmoid trajectory of cerebral injury

following ischemia, with most of the damage happening

in the intermediate time period after stroke symptom

onset rather than early after stroke onset may also

explain such findings [3,22].

Discussion

The outcomes of patients with LVOs heavily depend on

the time from stroke onset to recanalization of the occlu‐

The HERMES Collaborators concluded that for every

1000 LVO patients achieving substantial endovascular

reperfusion and for every 15-minute more rapid ED door Our study looked to see if faster decision-making and

to reperfusion times, an estimated 39 patients would assembly of our NI team via institution of the Code NI

have better outcomes at 3 months. This included 25 alert system would improve DTP and recanalization

more patients who would achieve functional independ‐ times, which in turn may be associated with better out‐

ence (mRS 0–2) without any significant difference in comes. We did show significant improvement in all time

rates of mortality, symptomatic intracranial hemorrhage, parameters between the pre-Code NI group and Code NI

and major parenchymal hematoma [17]. Rates of func‐ group. This was likely the result of changes in multiple

tional independence at 3 months declined with delays in subprocesses which were streamlined and occurred in

symptom onset to reperfusion time same as: age, base‐ parallel. The more rapid availability and communication

line stroke severity, clot location, initial extent of cere‐ between stroke team attending, fellow, and resident

bral infarction (ASPECTS), patient arrival directly or by reduced the decision time to call Code NI. The pre-call‐

transfer, and time from symptom onset to initiation of IV

tPA.

ing of a Code NI prior to discussing the patient’s case

with the neurointerventionalist saved time as well

because NI team members were already activated simul‐

taneously through the operator, as opposed to personal

phone calls. After hours, the preparation of the patient

by the ER staff for the NI procedure saved time for the

NI team so that groin puncture could be done as soon as

the patient was on the table.

The meta-analysis also showed that stroke patients who

were transferred for endovascular treatment had signifi‐

cantly longer symptom onset to endovascular hospital

arrival time but significantly shorter endovascular hospi‐

tal arrival to arterial puncture time when compared with

direct arrival patients [17].

Limitations

Rates of vessel recanalization are significantly effected

by ED arrival to arterial puncture and Imaging to arterial

puncture. Every additional hour between ED arrival to

arterial puncture is associated with a 22% reduction in

the odds of TICI 2b/3 reperfusion. Similarly, every addi‐

tional hour between imaging and arterial puncture is

associated with 26% reduction in the odds of TICI 2b/3

reperfusion [18]. The most likely explanation for this

includes thrombus modification (higher fibrin content

and more organized configuration of old thrombus com‐

pared to fresh thrombus) and stronger adhesion of the

thrombus within the vessel wall over time which makes

entrapment and retrieval of the thrombus more difficult

[23,24].

There was a big difference in the number and data avail‐

able for the pre-Code NI patients compared to Code NI

patients. There was not adequate and consistent data

available on patients who underwent a neuroendovascu‐

lar procedure prior to 2012. This discrepancy effects the

power of our study.

Our Code NI process had a number of limitations early

on that required frequent regrouping and discussion. In

the months following institution of Code NI, we found

that staff required continued education with regards to

the process despite initial education being given. We

also found initially that despite creating an automatic

paging system for the NI team, there were times that

various team members did not receive their pages and so

we had to have a secondary system where the operator

would call the on call team members to confirm receipt

of their page. Another area that needed readdressing

included the ED nurses comfort with preparing the

patient and in many cases, especially after hours, start‐

ing the neurointerventional procedure with the available

team and remaining with the patient until the interven‐

tional nurse was available to receive handoff. To handle

this issue, we created an NI kit for the ED nurse which

contained pertinent supplies that the nurse may need to

prepare that patient. The ED nurses were also given ori‐

entation to the biplanar angiography suite. These were

just a few issues that contributed to some of the delays

we found in the earlier phase of instituting Code NI.

There has been a lot of emphasis on reducing the time

from stroke onset to recanalization of the occluded ves‐

sel. Recommendations have been put forth with regards

to improving stroke care that starts from community

education and rapid recognition of stroke symptoms, to

pre-hospital assessment and care, creation of stroke cen‐

ters, emergency room evaluation and stabilization, use

of imaging modalities, consideration for IV thromboly‐

sis and endovascular therapies, Get with the Guidelines

(GWTG) time metrics for CT scan and IV tPA [4,25,26].

There are currently no GWTG time measures for DTP or

DTR because there are many confounding variables

including the availability of well-trained ED nurses,

preparation of the patient for endovascular therapy (IV

access, Foley catheter), rapid assembly of the endovas‐

cular team, etc. Median DTP and DTR times in SWIFT

PRIME, EXTEND IA, and PENUMBRA 3D trials were Patient characteristics were not analyzed in this study to

90/118; 113/156; 103/147 minutes, respectively [27–29]. see if delays were confounded by individual differences

Panezai et al.

with perfusion-imaging selection. N Engl J Med 2015;372:1009–

1018.

in presentation. This review was conducted purely for

process improvement purposes. A follow-up study can

be done to look at such factors and include additional

changes to the process.

12. Saver J. Solitaire FR as primary treatment for acute ischemic

stroke (SWIFT PRIME). Invited Presentation. International Stroke

Conference (ISC)February 12–15, 2015Nashville, TN

13. Fransen PSS, et al. Time to reperfusion and treatment effect for

acute ischemic stroke: a randomized clinical trial. JAMA Neurol

2016;73(2):190–196.10.1001/jamaneurol.2015.3886

Conclusions

As stroke treatments continue to be evaluated for utility

and resultant improvements in patients’ outcomes, indi‐

vidual hospitals and stroke teams will have to look

closer at their current processes and identify areas where

they can make improvements. We were able to formalize

and streamline our existing process for the activation of

our neurointerventional team. Our next steps include

using an algorithm for rapidly identifying LVO patients

to improve decision times and a further look at the indi‐

vidual components of our process to see where further

time may be saved.

14. Khatri P, et al. IMS III trialists. Time to angiographic reperfusion

and clinical outcome after acute ischaemic stroke: an analysis of

data from the Interventional Management of Stroke (IMS III) phase

3 trial. Lancet Neurol 2014;13:567–574.

15. Khatri P, et al. IMS I and II investigators. Good clinical outcome

after ischemic stroke with successful revascularization is time-

dependent. Neurology 2009;73:1066–1072.

16. Nogueira RG, et al. DAWN trial investigators thrombectomy 6 to

24 hours after stroke with a mismatch between deficit and infarct. N

Engl J Med 2018;378:11–21.10.1056/NEJMoa1706442

17. Saver JL, et al. Time to treatment with endovascular thrombectomy

and outcomes from ischemic stroke: a meta-analysis. <Hyper‐

link>Jama. </HYPERLINK> 2016;316(12):1279–1288.10.1001/

jama.2016.13647

Acknowledgments:

18. Bourcier R, et al. Association of time from stroke onset to groin

puncture with quality of reperfusion after mechanical thrombec‐

None.

tomy.

JAMA

Neurol

2019;6:405–411.10.1001/jamaneurol.

2018.4510

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