Fas P o ocol o T ea ing Acu e Ischemic S oke by
Eme gency Physicians
Ii o Heikkilä, MD*; Hanna Kuusis o, MD, PhD; Ma kus Holmbe g, MD; A i Palomäki, MD, PhD
*Co esponding Au ho . E-mail: ii o.heikkila@fimne .fio ii o.heikkila@khshp.fi.
S udy objec i e: Th ombolysis wi h issue plasminogen ac i a o should occu p omp ly a e ischemic s oke onse . Va ious
s a egies ha e a emp ed o imp o e doo - o-needle ime. Ou objec i e is o e alua e a s a egy ha uses an eme gency
physician–based p o ocol when no s oke neu ologis is a ailable.
Me hods: This was a e ospec i e be o e-a e in e en ion analysis in an u ban hospi al. Reo ganiza ion o he acu e ischemic
s oke ea men p ocess was ca ied ou in 2013. We e alua ed ime delay, symp oma ic in ace eb al hemo hage, and clinical
eco e y o pa ien s be o e and a e he eo ganiza ion. We used mul i a iable linea eg ession o es ima e he change in
doo - o-needle ime be o e and a e he eo ganiza ion.
Resul s: A o al o 107 pa ien s wi h compa able da a we e ea ed wi h issue plasminogen ac i a o in 2009 o 2012 (g oup 1) and
46 pa ien s we e ea ed du ing 12 mon hs in 2013 o 2014 (g oup 2). Median doo - o-needle ime was 54 minu es be o e he
eo ganiza ion and 20 minu es a e i (s a is ical es ima e o di e ence 32 minu es; 95% confidence in e al 26 o 38 minu es).
A e adjus ing o se e al po en ial co ounde s in mul i a iable eg ession analysis, he only ac o con ibu ing o a significan educ ion
in delay was g oup (a e eo ganiza ion e sus be o e). Median onse - o- ea men imes we e 135 and 119 minu es, espec i ely
(s a is ical es ima e o di e ence 23 minu es; 95% confidence in e al 6 o 39 minu es). The a es o symp oma ic in ace eb al
hemo hage we e 4.7% (5/107) and 2.2% (1/46), espec i ely (di e ence 2.5%;95% confidence in e al –8.7% o 9.2%). App oxima ely
70% o ea ed pa ien s we e unc ionally independen (modified Rankin Scale sco e 0 o 2) when ea ed a e he eo ganiza ion.
Conclusion: Implemen a ion o a s oke p o ocol wi h eme gency physician–di ec ed acu e ca e dec eased bo h doo - o-needle
ime and onse - o- ea men ime wi hou inc easing he a e o symp oma ic in ace eb al hemo hage. [Ann Eme g Med.
2019;73:105-112.]
Please see page 106 o he Edi o ’s Capsule Summa y o his a icle.
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h ps://doi.o g/10.1016/j.anneme gmed.2018.07.019
SEE EDITORIAL, P. 113.
INTRODUCTION
Backg ound
Th ombolysis wi h issue plasminogen ac i a o ( PA)
is a co ne s one in ea ing a pa ien wi h acu e ischemic
s oke.
1,2
This ea men should be gi en as soon as
possible, p e e ably wi hin 4.5 hou s a e symp om onse
and wi hin 60 minu es a e pa ien a i al a he hospi al.
1
P e ious s udies ha e shown ha a median doo - o-needle
(DNT) ime o 20 minu es is achie able.
3
Each minu e
sa ed om he ime o ea men can p oduce significan
imp o emen in a pa ien ’s pos s oke li e.
4
Va ious s a egies o imp o ing doo - o-needle ime
ha e been p esen ed p e iously.
5
A e ha ing begun
pos g adua e aining in he na ionally new special y o
eme gency medicine in ou hospi al,
6
we changed
he ea men o acu e ischemic s oke om he use
o eles oke o a model based on a s ong con ibu ion
o eme gency physicians. We ecen ly epo ed he
basic p inciples and p elimina y esul s o his new model.
7
The p ima y aim o his s udy was o analyze median
doo - o-needle ime oge he wi h sa e y da a o PA-
ea ed acu e ischemic s oke pa ien s du ing he fi s 12
mon hs o he eme gency physician–based p o ocol. These
esul s a e compa ed wi h hose in 2009 o 2012, p eceding
eo ganiza ion o he acu e ischemic s oke p o ocol.
Seconda ily, we aimed o e eal whe he onse - o- ea men
(OTT) ime was a ec ed a e he eo ganiza ion. Sa e y
da a a e compa ed wi h in e na ional da a as well.
Volume 73, no. 2 : Feb ua y 2019 Annals o Eme gency Medicine 105
NEUROLOGY/ORIGINAL RESEARCH
Edi o ’s Capsule Summa y
Wha is al eady known on his opic
Mos s oke eams a e led by neu ologis s, whe eas
eme gency physicians ypically a e he fi s o e alua e
and ea pa ien s wi h acu e neu ologic defici s.
Wha ques ion his s udy add essed
Wha was he e ec o a eo ganiza ion o he acu e
s oke p ocess o ocus on eme gency physicians
guiding acu e s oke ca e?
Wha his s udy adds o ou knowledge
S oke pa ien s we e ea ed as e a e he
eo ganiza ion. Al hough complica ions we e simila
be o e and a e he change, he s udy was no
powe ed o confi m hei equi alency.
How his is ele an o clinical p ac ice
Wi h aining and a well-defined p o ocol, eme gency
physicians quickly ea ed pa ien s wi h acu e s oke.
MATERIALS AND METHODS
This was a be o e-a e in e en ion analysis, and i s
design was app o ed by he local e hics commi ee. The
s udy included all pa ien s wi h acu e ischemic s oke who
we e ea ed wi h PA in ou eme gency depa men (ED)
in 2009 o 2012 (g oup 1, ie, “be o e”) and om Oc obe
1, 2013, o Sep embe 30, 2014 (g oup 2, ie, “a e ”). In
2009 o 2012, be o e he implemen a ion o he eme gency
medicine special y, he ea men p o ocol o pa ien s wi h
acu e ischemic s oke a ied sligh ly, as desc ibed in one o
ou ea lie s udies.
7
The ea e , s oke educa ion o
eme gency physician ainees ook place du ing he 9-
mon h eo ganiza ion pe iod p eceding Oc obe 1, 2013.
7
I consis ed o aining in he s oke uni a he neu ology
wa d, heo e ical eaching and p ac ical aining in
diagnosing and ea ing pa ien s wi h acu e ischemic s oke
(eg, diagnosis and di e en ial diagnosis o acu e ischemic
s oke, Na ional Ins i u es o Heal h S oke Scale [NIHSS]
sco ing wi h indica ions and con aindica ions o PA
adminis a ion), p epa a ion wi h he elec onic pa ien
eco d a e he p eno ifica ion gi en by eme gency medical
se ices (EMS), shadowing o an expe ienced neu ologis in
acu e neu ologic eme gencies, and finally wi h he diagnosis
and ea men o hei own pa ien s wi h clinical acu e
ischemic s oke, unde he supe ision o he specialis in
he ED. Radiologis s augh eme gency physicians he
e alua ion o head compu ed omog aphy (CT) o pa ien s
wi h acu e ischemic s oke. A e aining, adiologis s
emained on call and a ailable con inuously o e alua e
head CT images. Finally, we emphasized he impo ance o
he acu e ischemic s oke p ocess wi hou ex a delays in
ou ED.
7
Depending on he day o he week o he ime o day,
he physician on call aking ca e o pa ien s wi h acu e
ischemic s oke was ei he a neu ologis (o esiden ) o
in e nis esiden wo king wi h he aid o eles oke
be o e he eo ganiza ion. Since Oc obe 1, 2013, he
esponsible physician in he ED has been a s oke-educa ed
eme gency physician in 97.5% o all ou -o -hou shi s
du ing he fi s yea a e he eo ganiza ion.
7
The
neu ologis on call was always eachable by elephone i
needed. E e y eme gency physician ainee in ou ED
became s oke educa ed du ing he 9-mon h eo ganiza ion
pe iod be o e Oc obe 1, 2013 (ie, he o ficial s a o ou
p og am). Howe e , because o he ela i ely small numbe
(n¼9) o ou ainees, on a ew occasions we had o ely on
expe ienced physicians who we e no specifically s oke
educa ed. In hese si ua ions, he ole o he senio
neu ologis on call was emphasized.
The da a we e collec ed om pa ien files e ospec i ely
by using he ele an p ima y sou ce da a. The w i en
pa ien eco ds consis ed o 3 sou ces: he epo om
EMS by pa amedics; a pape o m filled ou in he ED by
nu ses, which con ained in o ma ion om he clinical ca e
deli e ed and desc ibed du ing he s oke ac i a ion ( ime
o a i al and ime o ini ia ion o PA); and he elec onic
pa ien eco d gene a ed by he esponsible physician.
The pape o m was conside ed a p ima y sou ce i he e
we e any conflic s conce ning he da a ha occu ed a e
pa ien a i al. Fo example, he ime o pa ien en ance
and ha o PA bolus a e p ima ily eco ded on his pape .
Physicians usually la e dic a e he same in o ma ion in o
he elec onic eco d. On he o he hand, he onse o
symp oms is usually confi med by a physician and s o ed in
he elec onic pa ien eco d. I he e was any disc epancy
in he ime o onse be ween da a sou ces, he no a ion o
he a ending physician in he ED was conside ed he ue
alue. The da a we e abs ac ed by he fi s au ho (I.H.).
He ead all pa ien eco ds o PA- ea ed pa ien s and
collec ed he nume ic in o ma ion in o he elec onic
abs ac ion o m. These da a included p ecisely defined
a iables such as sex, age, NIHSS sco e, in e als (doo - o-
needle and onse - o- ea men ime), and p esence o
in ace eb al hemo hages in bo h g oups (in ace eb al
hemo hage a his poin : yes o no). Missing da a we e
coded as such. Conflic ing o ambiguous cha elemen s
had o be discussed wi h he senio esea che . Howe e , in
ou se ing such da a did no exis . This in es iga o was
no blinded o he pe iod (p e- e sus pos in e en ion).
106 Annals o Eme gency Medicine Volume 73, no. 2 : Feb ua y 2019
Fas P o ocol o T ea ing Acu e Ischemic S oke Heikkilä e al
We calcula ed he annual p opo ion o s oke pa ien s
ea ed wi h h ombolysis. Then, he numbe s o ad e se
hospi al ou comes (inhospi al mo ali y o impai ed
eco e y leading he pa ien o become pe manen ly
bed idden) we e abs ac ed om he elec onic E fica
pa ien da abase ( e sion 1.5; Tie o Oy, Helsinki, Finland)
and o he hospi al sou ces by using he Web-based da abase
p og am Ex epo ( e sion 2.0; Neo ide Oy, Vaasa,
Finland). The c ucial da a o each hospi al s ay a e
na ionally coded uni o mly and can be accessed wi hou
en e ing confiden ial indi idual pa ien eco ds.
Fu he mo e, he calcula ion o he 30-day mo ali y o all
pa ien s wi h acu e ischemic s oke was based on da a
ob ained om he S a is ical O fice o Finland. The annual
esul s be o e he eo ganiza ion (ie, 2009 o 2012) a e
p esen ed as such, and he a e age mo ali y o hese 4 yea s
is compa ed wi h ha o 12 mon hs a e he eo ganiza ion.
Fo pa ien s who ecei ed PA ea men , we collec ed
indi idual da a, including sex, age, NIHSS sco e, in e als
(doo - o-needle and onse - o- ea men ime), and p esence
o in ace eb al hemo hages in bo h g oups.
The modified Rankin Scale is commonly used o
measu e disabili y in PA- ea ed pa ien s.
8
I is a 7-le el,
o dinal, nonin e al scale in which 0 co esponds o no
symp oms; 5, o se e e disabili y; and 6, o dea h.
E alua ion o clinical eco e y by using he modified
Rankin Scale was no ou ine p ac ice in ou hospi al un il
2013. Since hen, i has been used in all cases 3 mon hs
a e acu e ischemic s oke
9
by way o he modified Rankin
Scale–9Q ques ionnai e.
10
So in his s udy, he modified
Rankin Scale sco e was eco ded clinically in pa ien files
(only a e eo ganiza ion) a 3 mon hs a e he PA
ea men and collec ed om he pa ien files
e ospec i ely wi h he o he da a by in es iga o s.
All PA- ea ed pa ien s we e included in he analysis.
Exclusion c i e ia we e as ollows: symp oma ic s oke in an
inhospi al pa ien , symp om fluc ua ion (ie, no e iden
ime o he s a o index s oke symp oms), basila a e y
occlusion, discon inua ion o PA in usion be o e a ull
dose ( o example, because o low hemoglobin le el), and
missing da a on c ucial imes.
The sa e y o he new p o ocol was assessed by using he
Eu opean Coope a i e Acu e S oke S udy (ECASS II)
c i e ia.
11
Du ing he s udy pe iods, ou ine eimaging o
he b ain by way o CT was ca ied ou app oxima ely 24
hou s a e PA ea men i he e we e no pa ien - ela ed
easons o eimaging be o e ha . B ain hemo hages we e
classified by using sligh ly modified ECASS II c i e ia:
in ace eb al hemo hage was defined as symp oma ic i
he e was blood a any si e in he b ain on he CT scan
acco ding o he adiologis and significan clinical
wo sening o he si ua ion occu ed; o example,
d owsiness and deepening o hemipa esis o an inc ease in
NIHSS sco e by 4 o mo e poin s. O he findings
conce ning blood a any si e o he b ain bu wi hou
clinical e ec we e classified as asymp oma ic. This
p ac ical sligh modifica ion was ca ied ou because o he
e ospec i e se ing: adiologis s’ epo s p esen ed CT
eading panels and pa ien eco d no es indica ed
“documen a ion by he in es iga o .”
11
The in e a e
eliabili y assessmen was used when he in ace eb al
hemo hages we e classified as asymp oma ic and
symp oma ic hemo hages. This was accomplished in 2
phases. Fi s , I.H. classified he pa ien s wi hou blinding
acco ding o he in o ma ion ha was a ailable om he
pa ien eco ds (eg, he adiologis epo o he head CT,
he clinical si ua ion in he ED o in he s oke uni ).
ECASS II c i e ia we e used as desc ibed. The ea e , be o e
u he e alua ion, each pa ien file was blinded so ha he
g oup, da e, and name o he pa ien o physician could no
be iden ified. Finally, an expe ienced neu ologis (H.K.)
conduc ed he classifica ion o he same pa ien s, using he
iden ical bu blinded in o ma ion.
Me hods o Measu emen
S a is ical analyses we e pe o med by using IBM SPSS
S a is ics ( e sion 22; IBM, Chicago, IL). Di e ences o
dicho omous a iables wi h 95% confidence in e als (CIs)
wi h a co ec ion o con inui y we e analyzed by using
public s a is ical so wa e (h p:// assa s a s.ne /p op2_ind.
h ml) acco ding o a me hod desc ibed by Newcombe
12
and de i ed om he p ocedu e ou lined by Wilson.
13
Da a a e p esen ed as median (minimum–maximum) i no
men ioned o he wise. We made a p io i a sample size
calcula ion o he doo - o-needle ime (SD 40%), wi h he
p esumed sampling a io o 4:1. Fo he e ec o 30%
(a¼.05, 2 ailed), we would ha e needed app oxima ely 20
pa ien s in g oup 2 o yield powe o 80%.
Be o e we compa ed esul s be o e and a e he
eo ganiza ion, we es ed he homogenei y o he esul s
du ing 2009 o 2012. Dicho omous a iables such as
p opo ions o s oke pa ien s ea ed wi h PA and he 30-
day mo ali y o all pa ien s wi h acu e ischemic s oke
be o e and a e he eo ganiza ion we e compa ed by c
2
es . Because o small numbe s, compa isons o ad e se
hospi al ou come o all ischemic s oke pa ien s, all
in ace eb al hemo hages, and symp oma ic e sus
asymp oma ic in ace eb al hemo hages we e conduc ed
wi h Fishe ’s exac es . The es ima ed di e ences o doo -
o-needle ime and onse - o- ea men ime be o e and a e
eo ganiza ion, wi h 95% CIs, we e calcula ed by using he
Heikkilä e al Fas P o ocol o T ea ing Acu e Ischemic S oke
Volume 73, no. 2 : Feb ua y 2019 Annals o Eme gency Medicine 107
independen -samples Hodges-Lehman median di e ence
es . Di e ences in con inuous a iables we e assessed by
using he Mann-Whi ney U es .
To analyze whe he he eo ganiza ion as such had an
e ec on doo - o-needle ime, ou p eplanned analysis was
o pe o m mul i a iable eg ession analysis including
collinea i y s a is ics wi h he g oup and 9 well-known
biologically ele an a iables possibly a ec ing doo - o-
needle ime. Fac o s used in he analysis we e en e ed as
p edic o s as ollows: age in yea s, sex (male o emale),
yea ( om 2009 o 2014), home municipali y (3 g oups
based on he dis ance o he hospi al), p eno ifica ion
( om he EMS be o e pa ien a i al: yes o no), use o
eles oke consul a ion (yes o no), day o he week
(Sa u day/Sunday e sus o he , ie, weekend [yes o no]),
hou o he day (o fice hou s e sus ou -o -o fice hou s),
NIHSS sco e a pa ien a i al o he ED, and he g oup (1
e sus 2). He e, we we e in e es ed in he compa a i e
e ec s o hese ac o s on doo - o-needle ime ins ead o
conduc ing any es ima ion o gene al modeling based on
ou esul s.
In s a is ical analyses, P<.05 was conside ed significan .
RESULTS
Be o e he eo ganiza ion, 1,581 pa ien s wi h acu e
ischemic s oke we e ea ed in ou ED in 2009 o 2012.
Fu he mo e, 355 pa ien s we e ea ed du ing he 12
mon hs a e he eo ganiza ion. The p opo ions o
pa ien s ea ed yea ly wi h PA we e 7.9% (n¼29), 7.9%
(n¼33), 8.1% (n¼27), and 7.6% (n¼35) in 2009 o
2012, espec i ely. Taken oge he , he p opo ions o
PA- ea ed pa ien s wi h acu e ischemic s oke be o e and
a e he eo ganiza ion we e 7.8% (n¼124) and 14.4%
(n¼51), espec i ely (di e ence 6.5%; 95% CI 2.8% o
10.9%). O he 124 o pa ien s in g oup 1, 17 we e
excluded, 8 because o basila a e y occlusion o because o
an inhospi al s oke and 9 because o insu ficien ime da a.
In g oup 2, he o al numbe o pa ien s was 51. Fi e o
hem we e excluded, 1 because o missing da a, 1 because
PA was s a ed a e symp om fluc ua ion, 1 because he
PA in usion was discon inued because o low hemoglobin
le el, and 2 because o basila a e y occlusion.
When only PA- ea ed pa ien s wi hou exclusion
c i e ia we e coun ed, he yea ly numbe s we e 25, 30, 21,
and 31 in 2009 o 2012, espec i ely. Du ing hese 4 yea s,
he pe cen age o PA ea men a ied om 6.3% o 7.2%,
wi hou any empo al end. Hence, he mean p opo ion
o his pe iod could be compa ed wi h ha o he 12-
mon h pe iod a e he eo ganiza ion. As a esul , he o al
numbe s o pa ien s included in u he analyses we e 107
in g oup 1 (2009 o 2012) and 46 in g oup 2 (2013 o
2014) (Figu e 1). P opo ions o PA- ea ed pa ien s wi h
acu e ischemic s oke and wi hou exclusion c i e ia be o e
(g oup 1) and a e (g oup 2) he eo ganiza ion we e 6.8%
and 13.0%, espec i ely (di e ence 6.2%; 95% CI 2.7% o
10.4%). The cha ac e is ics o he g oups a e p esen ed in
he Table.
The median doo - o-needle ime was 54 minu es in
g oup 1 and 20 minu es in g oup 2 (s a is ical es ima e o
di e ence 32 minu es; 95% CI 26 o 38 minu es)
(Figu e 2Aand B). Acco ding o mul i a iable eg ession
analysis, he only ac o explaining doo - o-needle ime was
g oup. All assessed a iance infla ion ac o s we e less han
10, so we did no find e idence o mul icollinea i y. Resul s
o he model wi h all 10 o he po en ially biologically
ele an p edic o s a e gi en in Table E1, a ailable online a
h p://www.anneme gmed.com.
The median onse - o- ea men ime in g oup 1 was 135
minu es, whe eas i was 119 minu es in g oup 2 (s a is ical
es ima e o di e ence 23 minu es; 95% CI 6 o 39
minu es) (Figu e 3).
Figu e 1. The ial p ofile was a be o e-a e in e en ion analysis. G oup 1 (ie, “be o e”) ep esen s 2009 o 2012; and g oup 2, 1
yea ( om Oc obe 1, 2013, un il Sep embe 30, 2014).
Fas P o ocol o T ea ing Acu e Ischemic S oke Heikkilä e al
108 Annals o Eme gency Medicine Volume 73, no. 2 : Feb ua y 2019
In g oup 2, he median modified Rankin Scale sco e 3
mon hs a e ea men was 1.0 (mean 1.6; da a a ailable
om 44 pa ien s). Thi y- wo o he 46 pa ien s we e
unc ionally independen , wi h a modified Rankin Scale
sco e o 0 o 2. These da a we e no a ailable o g oup 1
because ou hospi al did no ha e a s anda d p ac ice o
sys ema ically assess ou comes a 90 days be o e he
eo ganiza ion.
Six cases o symp oma ic in ace eb al hemo hages a e
PA ea men we e de ec ed, 5 o 107 (4.7%) in g oup 1
and 1 o 46 (2.2%) in g oup 2 (di e ence 2.5%; 95% CI
–8.7% o 9.2%) (Table). Fo he assessmen o classi ying
he in ace eb al hemo hages as asymp oma ic and
symp oma ic, I.H. and H.K. ob ained he same esul s so
ha he ag eemen o he symp oma ic in ace eb al
hemo hages in bo h g oups was 100%.
O PA- ea ed pa ien s wi h acu e ischemic s oke, 4
(3.7%) in g oup 1 died du ing he hospi al s ay, whe eas
none did in g oup 2 (di e ence 3.7%; 95% CI –6.2% o
9.9%) (Table). A e he hospi al s ay, 57.9% (62 o 107)
and 63.0% (29 o 46) o pa ien s wi h acu e ischemic
s oke and PA ea men we e discha ged home in g oups
1 and 2, espec i ely (di e ence 5.1%; 95% CI –13.0% o
21.8%). The 30-day mo ali y o all ischemic s oke
pa ien s (bo h PA ea ed and un ea ed) was 8.1% be o e
and 7.5% a e he eo ganiza ion o he s oke p o ocol in
ou ED (di e ence 0.6%; 95% CI –0.4% o 1.6%). In
PA- ea ed pa ien s wi h acu e ischemic s oke, he 3-
mon h mo ali y a e in g oup 2 was 2.2% (ie, only 1
pa ien o 46 died a e ea men ) (Table). Because he e
we e no eliable da a on 3-mon h modified Rankin Scale
Table. S udy popula ion and he main findings.
S udy Popula ion and Main Findings G oup 1 G oup 2
Pa ien s included 107 46
Men (%) 50 (47) 28 (61)
NIHSS sco e, median (IQR) 7 (4–12) 5 (4–9)
DNT median, min 54 20
OTT median, min 135 119
Hospi al mo ali y, No. pa ien s 4 0
Mo ali y a 3 mo, No. pa ien s NA 1
mRS 3 mo, median (IQR) NA 1 (0–3)
sICH, No. pa ien s (%) 5 (4.7) 1 (2.2)
IQR, In e qua ile ange; OTT, onse - o- ea men ime; NA, no applicable be o e he
eo ganiza ion; mRS, modified Rankin Scale sco e; sICH, symp oma ic in ace eb al
hemo hage.
Figu e 2. A, Be o e he eo ganiza ion (g oup 1, 2009 o 2012), in median DNTs he e we e no ends ei he o dec ease o
inc ease (NS). B, In g oup 1 (ie, “be o e,”2009 o 2012), median DNT was 54 minu es. A e eo ganiza ion, i was 20 minu es
(g oup 2 [ie, “a e ,”12 mon hs om Oc obe 1, 2013]). The di e ence (s a is ical es ima e 32 minu es; 95% CI 26 o 38 minu es)
was significan . DNT as in A. Also shown is a back- o-back his og am ep esen ing same esul s. Box plo s ep esen medians and
in e qua ile ange. Whiske s and ou lie s (open ci cles) ep esen he whole ange o DNTs. In g oup 1, minimum and maximum
DNTs we e 20 minu es and 2 hou s, 11 minu es, espec i ely. In g oup 2, hey we e 8 and 60 minu es, espec i ely.
Figu e 3. Median OTT was 135 minu es be o e eo ganiza ion
(g oup 1). A e implemen a ion o he new s oke p o ocol, i
was 119 minu es (g oup 2). The di e ence (s a is ical es ima e
23 minu es; 95% CI 6 o 39 minu es) was significan (P¼.006).
Heikkilä e al Fas P o ocol o T ea ing Acu e Ischemic S oke
Volume 73, no. 2 : Feb ua y 2019 Annals o Eme gency Medicine 109

sco es a ailable in g oup 1, he mo ali y a e in his g oup
was una ailable.
The diagnosis a discha ge om he s oke uni in he
neu ology depa men was associa ed wi h acu e ischemic
s oke in all o he cases in g oup 2.
LIMITATIONS
A limi a ion o ou s udy is ha i was e ospec i e and
modified Rankin Scale sco e da a on pa ien s ea ed be o e
2013 we e a ailable only in a limi ed numbe o cases.
The e o e, we we e able o compa e ou modified Rankin
Scale sco e da a om g oup 2 only wi h in e na ional
findings.
14
Since 2013, modified Rankin Scale sco e
e alua ion using he modified Rankin Scale–9Q
10
has been
ou ine p ac ice. As is well known, he modified Rankin
Scale has i s own limi a ions,
15
bu i is s ill p obably he
mos ele an scale.
9
A u he limi a ion o his s udy is ha as a single-cen e
s udy ca ied ou in a medium-sized hospi al, he o al
numbe o PA- ea ed pa ien s was ela i ely low.
Howe e , he numbe o PA- ea ed pa ien s du ing he
12-mon h obse a ion pe iod was 51 (46 included in
he s udy) o 355 pa ien s wi h acu e ischemic s oke, so
he p opo ion o pa ien s wi h h ombolysis (14.4; 13.0%)
was ela i ely good compa ed wi h esul s published
ea lie .
16
A e he eo ganiza ion, no only did doo - o-
needle ime and onse - o- ea men ime dec ease bu also
he numbe o s oke pa ien s pe yea who we e ea ed
wi h PA inc eased compa ed wi h ha in p e ious yea s.
Because he median NIHSS sco e o he pa ien s dec eased
(Table) and simul aneously no s oke mimics we e ea ed,
ou s udy implies ha , o e all, eo ganiza ion o he s oke
p o ocol imp o ed he ea men o pa ien s wi h acu e
ischemic s oke.
An impo an me hodological limi a ion is simila o ha
o many o he s udies in he field o eme gency medicine.
17
Re ospec i e s udies a e always challenging and suscep ible
o biases. Especially he cha - e iewing p ocess in his s udy
was no pe ec because he da a abs ac ing and cha
e iewing we e conduc ed by he au ho s. Howe e ,
especially when e alua ing symp oma ic in ace eb al
hemo hages, we ied o a oid biases by using blinded
double-check a e an open e alua ion. The e was no
disc epancy be ween he open and blinded e alua ions in
ega d o symp oma ic o asymp oma ic in ace eb al
hemo hages. We did no find he e ospec i e na u e o his
s udy a majo p oblem because he mos impo an da a ( o
example, ime and mo ali y da a) a e nume ic and hus no
sensi i e o subjec i e biases. S ill, we a e well awa e o he
possibili y o ailu e o ain and moni o da a abs ac o s, as
desc ibed in a e iew a icle by Vassa and Holzmann
acco ding he conside a ions o e ospec i e cha e iew.
18
DISCUSSION
On he basis o ou esul s in his single-cen e s udy,
eme gency physicians we e able o ea acu e ischemic
s oke wi h PA apidly, wi hou inc easing in ace eb al
hemo hage, wi h he aid o neu ologis s on call o e he
elephone i needed. Sho ening o median doo - o-needle
ime o 20 minu es and onse - o- ea men ime o 119
minu es was s a is ically significan , and he e was no
inc ease in he a e o symp oma ic in ace eb al
hemo hages. Because we did no e alua e he subin e als
o doo - o-needle ime, we a e no able o exac ly show
whe e ime sa ing ac ually occu ed. One o he key poin s
is ha he ea men p o ocol is always he same, wi hou
any a ia ions, and ha he pa ien is examined
immedia ely a e en ance o he ED.
Pa ien selec ion was adequa e because no s oke mimics
we e ea ed wi h PA in g oup 1 no 2, al hough small
sample size limi s he gene aliza ion o ou esul s. Mo e
impo an , he e is no e idence ha any pa ien wi h acu e
ischemic s oke du ing he la e s udy pe iod would ha e
been le wi hou PA when indica ed: acco ding o he
sys ema ic quali y assu ance in he neu ology depa men
(including he s oke uni ), no pa ien was missed in he
la e pe iod (g oup 2). The use o he eles oke was
in e up ed on Sep embe 30, 2013, so ha i was no
a ailable in he la e pe iod (g oup 2).
The e a e ways o imp o e capaci y e ficiency in EDs
h ough, o example, op imizing wo k spaces; educa ion;
coope a ion o s a be ween EMS, EDs, and neu ology and
adiology depa men s; eo ganizing p ocesses; and
implemen a ion o bedside diagnos ics.
19-22
Ou acu e
ischemic s oke p ocess ep esen s a combina ion o hese
(Figu e 4).
7
The e is ma ked egional a ia ion in h ombolysis
ea men .
23
Some po en ial ex e nal and in e nal ba ie s
o he eme gency use o PA o acu e ischemic s oke has
been ecognized, including, o example, en i onmen al
ac o s and ou come expec ancy.
24
Sco e al
16
epo ed
he findings o an impo an Inc easing S oke T ea men
h ough In e en ional beha io al Change Tac ics
(INSTINCT) ial, in which hey made an in e en ion
designed o al e sys ems and beha io a an ins i u ional
le el and indi idual s a le el. In ha s udy, he use o PA
emained below 3% a e ha ing inc eased in bo h g oups,
and he in e en ion had no significan e ec on al eplase
use in pa ien s wi h acu e ischemic s oke. The o iginal aim
o ou new p o ocol was o dec ease he delay o ea men .
Fas P o ocol o T ea ing Acu e Ischemic S oke Heikkilä e al
110 Annals o Eme gency Medicine Volume 73, no. 2 : Feb ua y 2019
Simul aneously, we succeeded in significan ly inc easing
he p opo ion o PA- ea ed pa ien s wi h acu e ischemic
s oke.
Compa ison o he in ace eb al hemo hage and
eco e y da a wi h he Sa e Implemen a ion o
Th ombolysis in S oke-Moni o ing S udy (SITS-MOST)
shows ha ou p o ocol had compa able sa e y and e ficacy.
In ou s udy, symp oma ic in ace eb al hemo hage in
g oup 2 was ound in only 2.2% o he whole popula ion,
acco ding o ECASS II,
11
whe eas he pe cen age a ies
be ween 1.6% and 7.3% in SITS-MOST, depending on
he pa icula c i e ia.
14
Again, 70% o ou pa ien s had
modified Rankin Scale sco es o 0 o 2 a e 3 mon hs
compa ed wi h 54.8% o 56.0% in SITS-MOST.
14
To ou knowledge, his s udy is he fi s in which he
ole o eme gency physicians as impo an execu o s o a
s oke p o ocol wi h a e y sho median doo - o-needle
ime has been confi med. G eenbe g e al
25
p esen ed
esul s in which eme gency physicians ained in
neu oscience could achie e be e esul s han hei
colleagues wi hou such aining, wi h doo - o-needle imes
o 35 and 83 minu es, espec i ely. We ca ied ou a sea ch
in PubMed (2007 o No embe 2016; sea ch e ms
“Eme gency physician”[Ti le/Abs ac ] OR “Eme gency
physicians”[Ti le/Abs ac ] AND “s oke”[Ti le/Abs ac ]
AND “ h ombolysis”[Ti le/Abs ac ]) ha e ealed a o al
o 19 publica ions, including an ea lie s udy o ou s.
7
O
hese, 15 we e based on clinical s udies, bu only 2 epo ed
doo - o-needle o onse - o- ea men imes.
26,27
An a icle by Fe a i e al
26
ocused on Aus ian s oke
p o ocols and inhospi al delays. They ound ha doo - o-
needle imes anged be ween 30 and 78 minu es in
Aus ian s oke cen e s in Ap il 2004 o No embe 2012.
The s udy did no include eme gency physician–led
p o ocols because he special y o eme gency medicine does
no exis in he coun y. Ano he clinical s udy conce ned
h ombolysis o acu e ischemic s oke in a dis ic gene al
hospi al in he Uni ed Kingdom wi h an eme gency
physician–led s oke eam.
27
The main finding o his
s udy was ha h ombolysis is bo h sa e and possible in a
nonspecialis cen e led by eme gency physicians compa ed
wi h SITS-MOST egis e da a.
28
This s udy in ol ed no
doo - o-needle imes bu onse - o- ea men imes. Thei
finding o an onse - o- ea men ime o 142 minu es is in
line wi h ou esul s in g oup 1 (ie, be o e he
eo ganiza ion). In a hi d s udy, onse - o- ea men ime
was a ailable in only 4 cases, and i was ocused mainly on
CT angiog aphy in basila a e y occlusion wi h in uba ed
pa ien s.
29
One educa ional s udy e ealed ha he
Canadian sys em p o ided de ailed s oke p o ocol
educa ion o ainees in eme gency medicine.
30
To conclude, we ound ha implemen a ion o a s oke
p o ocol based on he cen al ole o eme gency physicians
dec eased bo h doo - o-needle ime and onse - o- ea men
ime. Eme gency physicians a e able o ea s oke pa ien s
quickly and e ficien ly once he acu e ischemic s oke
p o ocol has been c ea ed, wi h coope a ion be ween
neu ologis s, adiologis s, and eme gency physicians.
The au ho s acknowledge he p o essional echnical aid o
Nick Bol on, PhD; Roope Ki i an a, MA; bios a is ician
Mika Helminen, MSc; E ja Uo ila; and Alexand S olbe g,
MD, and he coope a ion o he medical and nu sing s a
wo king in he ED, as well as in he neu ologic and adiologic
wa ds o he hospi al.
Supe ising edi o : William J. Meu e , MD, MS
Au ho a filia ions: F om he Depa men o Eme gency Medicine
(Heikkilä, Holmbe g, Palomäki) and Depa men o Neu ology
(Kuusis o), Kan a-Häme Cen al Hospi al, Hämeenlinna, Finland;
and he Facul y o Medicine and Li e Sciences, Uni e si y o
Tampe e, Tampe e, Finland (Palomäki).
Figu e 4. Main p e equisi es and elemen s o he in e en ion. Modified om ou ea lie publica ion.
7
INR, In e na ional
no malized a io.
Heikkilä e al Fas P o ocol o T ea ing Acu e Ischemic S oke
Volume 73, no. 2 : Feb ua y 2019 Annals o Eme gency Medicine 111
Au ho con ibu ions: IH, HK, and AP designed he s udy. IH
o ganized he da a collec ion. HK, MH, and AP pa icipa ed
subs an ially in in e p e a ion o he da a. IH and AP ca ied ou
s a is ical analyses. All au ho s d a ed he a icle, c i ically e ised
i , and app o ed i . AP akes esponsibili y o he pape as a whole.
All au ho s a es o mee ing he ou ICMJE.o g au ho ship c i e ia:
(1) Subs an ial con ibu ions o he concep ion o design o he
wo k; o he acquisi ion, analysis, o in e p e a ion o da a o he
wo k; AND (2) D a ing he wo k o e ising i c i ically o impo an
in ellec ual con en ; AND (3) Final app o al o he e sion o be
published; AND (4) Ag eemen o be accoun able o all aspec s o
he wo k in ensu ing ha ques ions ela ed o he accu acy o
in eg i y o any pa o he wo k a e app op ia ely in es iga ed and
esol ed.
Funding and suppo : By Annals policy, all au ho s a e equi ed o
disclose any and all comme cial, financial, and o he ela ionships
in any way ela ed o he subjec o his a icle as pe ICMJE conflic
o in e es guidelines (see www.icmje.o g). The au ho s ha e s a ed
ha no such ela ionships exis . The s udy was unded by he
Finnish Cul u al Founda ion, Häme Regional Fund (a g an o Ii o
Heikkilä, MD), and he Minis y o Heal h and Social Wel a e in
Finland h ough he Medical Resea ch Fund o Kan a-Häme
Cen al Hospi al.
Publica ion da es: Recei ed o publica ion May 27, 2017.
Re isions ecei ed Sep embe 30, 2017; Feb ua y 10, 2018, and
June 1, 2018. Accep ed o publica ion June 25, 2018. A ailable
online Sep embe 17, 2018.
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