Management of delays in stroke management

1. How can we manage delays
in stroke treatment ?
Jacek Staszewski, MD, PhD
ACUTE STROKE EXPERT WORKSHOP
Almaty, KAZAKHSTAN

2. Disclosures
• Honoraria from Boehringer Ingelheim, Polfarma
• Not currently involved in any thrombolytic studies

3. What has not changed
since i.v. rt-PA is on the stroke scene

4. • Thrombolysis in ischaemic stroke
Population-based studies & meta-analyses
• Thrombectomy
– better functional outcome with shorter OTT
REVASCAT trial
• Rapid restore of coagulation in anticoagulation-related ICH
• Early intensive BP reduction may be beneficial
Guidelines for management of ICH
ESO 2014, AHA/ASA 2010
Time is still brain
OTT = onset to treatment time, ICH = intracranial haemorrhage, BP = blood pressure
Gumbinger C et al. BMJ 2014; Jovin TG et al. 2015; Ray B et al. Crit Care 2014
Odds ratio
OTT /min/

5. • Stroke is the most common disease worldwide
– incidence (M/F): 101–239 / 63–158 per 100,000
– 243,000 hospitalizations in Germany (2010); 92,500 in Poland (2013)
• Incidence of stroke will double in the next 20 years
• 20–40% of EU hospitals treating stroke patients
do not perform rt-PA!
Thrombolysis is still underused
Sentinel Stroke National Audit Programme 2014; Schwamm LH et al. Circulation 2013; 6
Scholten et al. Implement Science 2015; Ferrari J et al. J Neurol 2013
11.8%
8.9%
7% 7%
18.3%
UK Germany US Poland Austria
rt-PA rates

6. Ongoing effort to overcome delays
• ~50% stroke patients arrive to ER
outside the time window
• The majority of those who receive rt-
PA have a DTN time ≥60 min
• Only 11% of patients receive rt-PA
within 90 min of symptoms onset
• Reducing rt-PA treatment times is the
single most important modifiable
factor to improve patient outcomes
from hyperacute stroke care
rt-PA = recombinant tissue plasminogen activator; DTN = door-to-needle, ER = emergency room
Swartz RH et al. Int J Stroke 2014

7. Stroke thrombolysis: Every minute counts!
• Each 1 min saved of OTT time = a mean 1.8 days of DALY
– 0.6 day in old severe stroke patients (age, 80 yrs, NIHSS 20 p)
– 0.9 day in old mild (80 yrs, NIHSS 4 p)
– 2.7 days in young mild (50 yrs, NIHSS 4 p)
– 3.5 days in young severe (50 yrs, NIHSS 20 p)
• Each 15 min decrease = 1 month of additional disability-free
life
Helsinki Stroke Thrombolysis Registry; SITS-Australia
• Every 15 minute reduction in DTN time = 5% lower odds of in-
hospital mortality, 4% greater odds of walking independently
Get with the Guidelines-Stroke (US)
OTT = onset-to-treatment; DALY = disability-adjusted life year;
NIHSS = National Institutes of Health Stroke Scale; DTN = door-to-needle
Meretoja A et al. Stroke 2014;45:1053-8; Fonarow GC et al. Circulation 2011;123:750-8; Saver JL et al. JAMA
2013;309:2480-8

8. Chain of survival
Stroke is an emergency
Jauch et al. Stroke 2013; AHA/ASA Circulation 2005; Deng et al. Neurology 2006
• Public campaigns (knowledge of stroke symptoms & avoid delayed seeking medical attention)
• Centralised emergency number (triage prior to dispatch of emergency team)
• Standardised protocols & instruments for early stroke recognition (e.g. FAST, LAPSS)
• Emergency and direct transfer to hospitals with stroke / endovascular expertise
AHA/ASA 2013 Class I; Level of Evidence B
Quick recognition
Reaction to stroke signs
Rapid dispatch Priority transport ER triage Rapid in-hospital
diagnosis and
treatment
Patient EMS Transport CT/MRI Treatment
50-80% of delays
Collaboration between pre- and in-hospital stroke care providers!

9. Pre-hospital notification
Code Stroke
• Mobilisation of appropriate hospital
resources
• Bypassing administrative admission
• Activation of Code Stroke
– decreases time to stroke team arrival & CT
scan interpretation
• Shortens door-to-needle time
– 41 min vs. 57 min (Lille, FR)
• Increases likelihood of rt-PA treatment
– 22% vs. 5%
Abdulah AR et al. Prehosp Emerg Care 2008; Casolla B et al. J Neurol 2012; Patel MD et al. Stroke 2011;

10. Advanced pre-hospital stroke management
• Telemedicine
– supply 24/7 access to specialist stroke
expertise
– patient relevant data to the receiving site
• Pre-hospital thrombolysis
– call–to-needle time: 51 vs. 76 min
in routine care
– OTT≤ 90 min: 58% vs 37%
– rt-PA rates: 33% vs. 21%
– no difference in ICH, mortality rates
– can be integrated into the service chain
Ebinger M et al. JAMA 2014; Weber EJ et al. Neurology 2013

11. Hospital delays
Factors associated with increased DTN times
Fonarow GC et al. Circulation 2011; Nyika D et al. Stroke 2013; Bhatt A et al. Neurohospitalist 2012
1. Arrival to ED
2. Emergency assessment
3. Stroke team notified
4. Priority CT scan
5. Blood tests
6. Stroke team assessment
7. CT report obtained
8. Patient informed and consent
obtained
9. Reconstitution/ drawing up rt-PA
10. tPA is initiated
Logistics
Incorrect triage
No neurologist availability 24/7
Difficulties with weighting the pt
CT scan occupied
Lab result delayed
No medication available
Waiting for consent from family
Patient
Unknown symptoms duration
Unknown medical history
• anticoagulants?
Self-transport
Uncontrolled BP
Fluctuating neurological deficit
Hospital
High annual number of stroke
admissions
Low annual volume of rt-PA
Personnel
Lack of tPA experience
• non-neurohospitalists
• uncertain if rt-PA eligible
• fear of tPA safety
• unrecognised stroke
Tendency to delay treatment

12. National and hospital variation in DTN times
Tai YJ et al. Int Med J 2013; Fonarow GC et al. Circulation 2011
2008-2012

13. Single interventions to reduce
rt-PA delays
Eissa A et al. J Clin Pharm Ther 2012;37:399-409; Tai YJ et al. Int Med J 2013;43:1176-82
% rt-PA
2% 11%
Only the assessment of blood glucose must precede the initiation of intravenous rtPA
AHA/ASA 2013 Class I; Level of Evidence B

14. Strategies of in-hospital acute stroke management
Tai YJ et al. Int Med J 2013; Fonarow GC et al. Circulation 2011
Streamlined (Helsinki model)
Stroke
physician
ED
physician
Emergency department
Stroke team
CT
scanner
DTN (median): 20 min vs. 105 min
DTN ≤ 60 min: 94%
Triage
POC tests
iv rt-PA
Parallelprocessing
Pre-notification
History taking
Pre-registration
“Do as little as possible
after the patient has arrived
at the ER and as much as
possible before the patient
is being transported”
Meretoja A et al.
CT/testsrequests

15. Aggregation of marginal gains
Adapted from Meretoja A et al. Neurology 2012
EMS involvement
Hospital pre-notification
Code stroke
rt-PA prepared and administered in CT
CT relocated to ER
Direct to CT
Examination on CT table
Pre-acquisition of history, POC test,
Advanced imaging only in unclear case
Learning by doing

16. Having time: the decision takes time
“Three-hour effect”
Strbian D et al. Stroke 2013;44:2808-13; Kobayashi A et al. Acta Neurol Scand 2010;122:229-36; Kohrmann M et al. Int J Stroke 2011;6:493-7
0-4.5h 0-3h
3-4.5h
Pooled analysis of 10 European dedicated stroke centers: n=7106
rt-PA ≤ 3h Post-ECASS III (rt-PA 3-4.5h)
min
SITS
Poland

17. Get with the Guidelines Target:
Stroke
• A national quality improvement initiative from the AHA/ASA
• Aim: to ensure that as many patients as possible with AIS
achieve a DTN time ≤60 min
• 10 key best practice strategies, associated with faster DTN
AIS = acute ischaemic stroke; DTN = door-to-needle; EMS = emergency medical service;
POC = point-of-care; rt-PA = recombinant tissue plasminogen activator
Fonarow GC et al. Stroke 2011;42:2983-9
1. EMS pre-notification
2. Rapid triage protocol and stroke
team notification
3. Single call to active stroke team
4. Stroke tools
5. Rapid imaging and interpretation
6. Rapid laboratory testing and
POC test
7. Premixing rt-PA
8. Rapid access to rt-PA
9. Team-based approach
10. Rapid data feedback

18. DTN = door-to-needle; rt-PA = recombinant tissue plasminogen activator
Fonarow GC et al. JAMA. 2014;311:1632-1640
Before and after “Target: Stroke”
DTN times ≤ 60 min
International Stroke Conference 2014
Pre- Post-intervention
Median DTN (min) 77 67
rt-PA DTN ≤ 60min (%) 26.5% 41.3%
53.3%
29.6%

19. Before and after “Target: Stroke”
Results
Outcome* Before
Target: Stroke
(n=27,319)
After
Target: Stroke
(n=43,850)
Difference
(before/after)
P Value
In-hospital
mortality
9.93% 8.25% -1.68% <0.0001
Discharge
home
37.6% 42.7% +5.1% <0.0001
Ambulatory
status
independent
42.2% 45.4% +3.2% <0.0001
Symptomatic
ICH
5.68% 4.68% -1.00% <0.0001
Any rt-PA
complications
6.68% 5.50% -1.18% <0.0001
* Significant after adjustment for potential confounders (age, baseline stroke severity, hospital characteristics)
International Stroke Conference 2014
AIS = acute ischaemic stroke; DTN = door-to-needle; rt-PA = recombinant tissue plasminogen activator
Fonarow GC et al. JAMA 2014;311:1632-40

20. Stroke thrombolysis rates in Poland
Mikulik R et al. Stroke 2012; Kobayashi A et al. Acta Neurol Scand 2010; Mapa statystyk NFZ. http://www.sga.waw.pl
686
1204
2285
3182
5200
0
1000
2000
3000
4000
5000
6000
YR 2009 YR 2010 YR 2011 YR 2012 YR 2013
No. of rt-PA procedures according to National Health Service (NFZ)
4% AIS
7% AIS
AIS – all ischaemic strokes
No. of stroke units 105 110 124 171 173

21. The QUICK Stroke Initiative
Making Every Second Count Towards Stroke Recovery
Objective of the QUICK Stroke Project:
Reduce the delays in the stroke management
process of participating hospitals
 By measuring the delays in the stroke management
 Pre-hospital phase
 Hospitalization phase
 Specialized care phase
 By identifying the points of improvement in each step
 By implementing a specific action plan
 By preparation of the comparative analysis
1
Y
E
A
R
1st snapshot
2nd snapshot
www.quick-initiative.com

22. Successful pilot in France:
More patients in the golden hour
Caumette D et al. SFNV, November 22-23, 2012, Paris, France, Poster 67
ASA goals
1st
snapshot
2nd
snapshot
DTN: 60 min
Scan results / therapeutic decision: 45 min
50% of patients ≤ 60 min
Decision to
treatment
DTN: 75 min
Scan results: 55 min 12 min
27% ≤ 60 min
DTN: 65 min
Scan results: 50 min 12 min
40% ≤ 60 min
Total of 780 patients
EMS contact to stroke clinicians  11% improvement
Symptoms onset to hospital arrival  19 min reduction
15 min

23. QUICK launched in ≈100 centres all over the world
RUSSIA 11 centres
POLAND 25 centres
RCV 10 centres
RCV new 12 centres
RCV total 58 centres

24. QUICK project progress overview
Recruitment
1st diagnostic
audit
Action plan
implementation
2nd diagnostic
audit
Final report
Number of
participating
hospitals
1 4
11
Main
phases
Participating
countries
1
11 hospitals
10 22 hospitalsRCV
countries
8 hospitals
25 hospitals
12 hospitals1 132
9
2
10
2
37 hospitals*205
*Note: In France, 5 hospitals have stopped whereas some of
the participating centres decided to run a 3rd snapshot
MENA
3 9 3 15 hospitals
1 1
6
12

25. The QUICK initiative in Poland
Main actions taken
 Actions aiming at improving the hospital delays and the alert phase:
• Procedures
– implementation/re-evaluation of stroke alert procedure (in 10 hospitals)
– new patient card to fill in ambulance during transport (2)
• Training
– neurology personnel (10) & ER staff, lab/CT technicians training (4)
– training for ambulance service – “Load and go strategy” (2)
• Communication
– regular “stroke team” (10) & ER, CT, Lab meetings (3)
– display of the stroke alert procedure in the ER (4)
– site visits of centres by stroke experts for good practice sharing (2)
– local patient awareness campaign (10)
 10 Hospitals with primary or comprehensive stroke centres
 Conventional model of stroke management, 510 patients

26. Main delays:
Overall delay to medical decision
0
50
100
150
200
250
300
350
400
450
500
First symptoms to medical
decision
Median:
- 50 min
Med=225 Med=175
Snapshot 1
Sep 2012
Snapshot 2
Apr 2013
50-min reduction (22%)
Alert phase: Onset of symptoms - to arrival at hospital
• median ↓ 40 min (137 vs. 97 min)
First symptoms to call to ambulance: ↓ 36 min (60 vs. 24 min)
Call to ambulance to arrival at hospital: ↓ 8 min (50 vs. 42 min)
Hospital phase: Arrival at the hospital - to medical decision
• median ↓ 11 min (71 vs. 60 min)
Arrival to laboratory results: ↓ 13 min (82 vs. 69 min)
Arrival to consultation with neurologist : ↓ 2 min (7 vs. 5 min)
Door-to-CT:  30 min

27. Main delays
Hospital phase
9-min reduction (11%)
Med=89 Med=80
Snapshot 1 Snapshot 2
Median:
-9 min
rt-PA rate (2012 vs 2013)
12.6%  16.6%
7/10 sites improved rates
Door to medical decision ≤60 min: 31% vs 50%

28. Military Institute of Medicine Warsaw
• Specialty tertiary care hospital
• Covers ½ million population
• 1100 beds
• 40,000/yr inpatient admissions
• ≈ 800 strokes/yr
• Regional Priority Trauma Centre
Emergency Department
• 45,000 /yr outpatient visits
• ≈ 35/d neurological consultations
• 75% “stroke suspicion”
• On-hours: 1 neurologist (ED based)
• Out of hours: 1 neurology resident
on call (hospital / ED consultations)

29. Every single day at ED…
Identification of
rt-PA candidate?
Fast track?

30. Two-way EMS communication, stroke triage and strict
monitoring selected as possible gains
Diagnosis
1st snapshot
(pre-implementation)
IX – X 2012
22 IS (16 rt-PA)
Action plan
2nd snapshot
(post-implementation)
II - IV 2013
23 IS (11 rt-PA)
• Insufficient communication with EMS
• General non-stroke triage
• Stroke suspicion triaged by ED physician out of hours
• ER staff insufficiently educated in stroke
• Target times not monitored and not obligatory
• 2-way communication with EMS / dedicated phoneline
• Obligatory stroke triage protocol: “Priority patient” 24/7
• ER staff/ paramedics training & regular meetings
• Obligatory monitoring of key-time intervals in real-time
• Prehospital notification
• Preregistration
• Parallel processing

31. Main delays: hospital phase (1/2)
20
40
60
80
100
120
140
160
180
Minutes
Door-to-medical decision
Median:
- 33 min
Med=120 Med=87
Snapshot 1 Snapshot 2
33-min reduction (28%)
Arrival to blood draw: ↓ 15 min (30 vs 15 min)
Door to CT: ↓ 9 min (41 vs 32 min)
Access to imaging results: ↓ 18 min (43 vs 25 min)
Medical decision to therapy: ↓5 min (10 vs 5 min)
Improved communication in ED
Better understanding of procedures
by staff at all levels
Oct 2012 Feb 2013

32. Main delays: hospital phase (2/2)
Median:
-35 min
Med=128 Med=93
In-hours: Med = 92 Med = 69
Snapshot 1 Snapshot 2
35-min reduction (27%)
Arrival- to consultation with neurologist :
↓ 11 min (28 vs 17 min)
rt-PA not delayed for lab results :
75%  25%
rt-PA not delayed for CT reports/ MRI:
50%  25%
rt-PA rate (2012 vs 2013)
9%  14%

33. *American Heart Association/American Stroke Association
A value of simple external assessment
AHA/ASA*
objectives
Door to CT25 min
Arrival at hospital – imaging results / medical decision45 min 15 min
Door to needle60 min
41 min
100 min 20 min
128 min
32 min
71 min 16 min
93 min
1st vs 2nd
diagnostic
snapshot
35-min
gain
9-min
gain
33-min
gain
• Quick identification and simple changes support
• Gains achieved with minimal resources
• Quick improvements seen < 6/12
• Ongoing process

34. Main goal: quick reperfusion therapy
How can we do better ?
• See the need
• Identify obstacles
• Implement best strategies focused on local needs
• Decrease variation
• Track delays and progress
• Multidisciplinary communication & regular trainings / meetings
• Out-of-hours & ED walk-in patients arrangements
• Learn by doing
• Share experience

35. New strategies to improve stroke management:
ESO-EAST
• ESO initiative to support Eastern European
countries to optimise & implement best stroke
care practice locally
• AIM: to improve stroke treatment, research and education
– developing a strategy to optimize and implement best practices
– annual workshops over 5 years from 2015
– leading stroke specialists from 15 countries
– facilitate interactions with government agencies, collaboration
– unrestricted grants from industry (EVER, Boehringer Ingelheim)

36. The angels initiative is a project sponsored by
Boehringer Ingelheim, aimed at optimising and
setting up acute stroke networks in low- and
middle-income countries with the support of
local and international stroke societies.
The angels initiative is only available in Africa,
Brazil, China, Eastern Europe, India, Mexico,
Middle East and South East Asia.

37. Steering committee
Patrick
Goldstein
France
Thorsten
Steiner
Germany
David
Hargroves
UK
Werner
Hacke
Germany
Peter
Schellinger
Germany
Kennedy
Lees
UK
President
of ESO
Stephen
Davis
Australia
President
of WSO
Mark
Cooke
Australia
Suhail Al-
Rukn
Dubai
Jacek
Staszewski
Poland
The angels initiative is only available in Africa, Brazil,
China, Eastern Europe, India, Mexico, Middle East
and South East Asia.

38. The angels initiative “start-up kit” for registered
hospitals will contain…
Checklists
and scoring
tools
Standard
forms &
protocols
Stroke
treatment
process flow
Slide kits &
training sets
ePatCare®
patient case
study tool
Body
Interact
simulations
QUICK
initiative
quality
control
FAQ & tips
and tricks
International
guidelines
Motivational
materials
The angels initiative is only available in Africa, Brazil,
China, Eastern Europe, India, Mexico, Middle East
and South East Asia.

39. Summary

40. Thank you for your attention