Articles

Public-access defibrillation and neurological outcomes in

patients with out-of-hospital cardiac arrest in Japan:
a population-based cohort study
Takahiro Nakashima, Teruo Noguchi, Yoshio Tahara, Kunihiro Nishimura, Satoshi Yasuda, Daisuke Onozuka, Taku Iwami, Naohiro Yonemoto,
Ken Nagao, Hiroshi Nonogi, Takanori Ikeda, Naoki Sato, Hiroyuki Tsutsui, for the Japanese Circulation Society with Resuscitation Science Study
Group*

Summary
Background More than 80% of public-access defibrillation attempts do not result in sustained return of spontaneous Lancet 2019; 394: 2255–62
circulation in patients who have had an out-of-hospital cardiac arrest (OHCA) and a shockable heart rhythm before Published Online
arrival of emergency medical service (EMS) personnel. Neurological and survival outcomes in such patients have not December 17, 2019
https://doi.org/10.1016/
been evaluated. We aimed to assess the neurological status and survival outcomes in such patients.
S0140-6736(19)32488-2
See Comment page 2204
Methods This is a retropective analysis of a cohort study from a prospective, nationwide, population-based registry of
*Members listed in the appendix
1 299 784 patients who had an OHCA event between Jan 1, 2005, and Dec 31, 2015 in Japan. The primary outcome was
Department of Cardiovascular
favourable neurological outcome (Cerebral Performance Category of 1 or 2) at 30 days after the OHCA and the
Medicine, National Cerebral
secondary outcome was survival at 30 days following the OHCA. This study is registered with the University Hospital and Cardiovascular Centre,
Medical Information Network Clinical Trials Registry, UMIN000009918. Suita, Japan (T Nakashima MD,
T Noguchi MD, Y Tahara MD,
K Nishimura MD, S Yasuda MD,
Findings We identified 28 019 patients with bystander-witnessed OHCA and shockable heart rhythm who had received
D Onozuka PhD); Department
CPR from a bystander. Of these, 2242 (8·0%) patients did not achieve return of spontaneous circulation with CPR of Health Communication,
plus public-access defibrillation, and 25 087 (89·5%) patients did not achieve return of spontaneous circulation with Kyushu University Graduate
CPR alone before EMS arrival. The proportion of patients with a favourable neurological outcome was significantly School of Medical Sciences,
Fukuoka, Japan (D Onozuka);
higher in those who received public-access defibrillation than those who did not (845 [37·7%] vs 5676 [22·6%]; Kyoto University Health
adjusted odds ratio [OR] after propensity score-matching, 1·45 [95% CI 1·24–1·69], p<0·0001). The proportion of Service, Kyoto, Japan
patients who survived at 30 days after the OHCA was also significantly higher in those who received public-access (Prof T Iwami MD); Department
defibrillation than those who did not (987 [44·0%] vs 7976 [31·8%]; adjusted OR after propensity score-matching, of Biostatistics, Kyoto
University School of Public
1·31 [95% CI 1·13–1·52], p<0·0001). Health, Kyoto, Japan
(N Yonemoto PhD);
Interpretation Our findings support the benefits of public-access defibrillation and greater accessibility and availability Cardiovascular Centre, Nihon
of automated external defibrillators in the community. University Hospital, Tokyo,
Japan (K Nagao MD); Intensive
Care Centre, Shizuoka General
Funding None. Hospital, Shizuoka, Japan
(H Nonogi MD); Department of
Copyright © 2019 Elsevier Ltd. All rights reserved. Cardiovascular Medicine,
Toho University Faculty of
Medicine, Tokyo, Japan
Introduction with OHCA who do not achieve return of spontaneous (Prof T Ikeda MD); Cardiology
In developed countries, public access to automated circulation through cardiopulmonary resuscitation (CPR) and Intensive Care Unit,
external defibril­lators (AEDs) has led to an increase in the combined with public-access defibrillation have a poorer Nippon Medical School,
Musashi-Kosugi Hospital,
survival of patients who have a shockable heart rhythm prognosis than those who do not achieve return of Kawasaki, Japan (N Sato MD);
after an out-of-hospital cardiac arrest (OHCA).1,2 However, spontaneous circulation through CPR alone. and Department of
in Japan, the pro­ portion of patients with a favourable To investigate this hypothesis, we aimed to assess Cardiovascular Medicine,
Kyushu University, Fukuoka,
neurological outcome after a bystander-witnessed ventric­ whether public-access defibrillation affected the neuro­
Japan (Prof H Tsutsui MD)
ular fibrillation OHCA was approximately 20% in 2009.3 logical outcome of patients with OHCA who did not
Correspondence to:
A population-based study in Japan1 showed that 10% of achieve return of spontaneous circulation before arrival Dr Yoshio Tahara, Department of
patients with OHCA who had a shockable heart rhythm of EMS personnel. Cardiovascular Medicine,
received public-access defibrilla­tion by a bystander, and National Cerebral and
return of spontaneous circulation before arrival of an Methods Cardiovascular Centre, Suita,
Osaka 564-8565, Japan
emergency medical service (EMS) occurs in only 18% of Study design and participants tahara@ncvc.go.jp
patients.4 Use of public-access AEDs by a bystander could This cohort study is a retrospective analysis of patients See Online for appendix
lead to potential problems with patient survival by from the All-Japan Utstein Registry of the Fire and
interrupting chest compressions or by delaying arrival to Disaster Management Agency), which is a prospective,
hospital.5,6 Public-access AEDs are not as widely accessible population-based, nationwide registry of patients who
as they could be. Therefore, we hypothesised that patients have had an OHCA (appendix p 4).1,4,7–10 Data were

www.thelancet.com Vol 394 December 21/28, 2019 2255

 Articles
Research in context
Evidence before this study
Previous studies in industrialised countries have shown that the
dissemination of public-access automated external defibrillators
has increased the survival of patients after they have an
out-of-hospital cardiac arrest (OHCA) with an initial shockable
heart rhythm on the electrocardiogram. However, more than
80% of public-access defibrillation attempts do not result in
sustained return of spontaneous circulation before initiation of
an emergency medical service (EMS) response in patients with a
shockable heart rhythm after the OHCA event. It remains
unknown whether patients with a bystander-witnessed OHCA
and an initial shockable heart rhythm, who do not achieve return
of spontaneous circulation before initiation of EMS response,
have a better prognosis if they receive public-access defibrillation
than those who do not.
Added value of this study
This nationwide, retrospective analysis of a prospective,
population-based registry of patients who have had an OHCA in
Japan showed that a significantly higher proportion of patients
recorded by use of the internationally standardised
Utstein template.11,12 Details of the registry have been
described previously.4 The FDMA established the registry
cohort and collected and verified the quality of the data.
In patients with a bystander-witnessed OHCA and a
shockable heart rhythm who did not achieve return of
spontaneous circulation before arrival of EMS personnel,
we compared the proportion of patients with a favourable
neurological outcome at 30 days after the OHCA event
between those who received public access defibrillation
and those who did not. In both groups of patients, a
shockable heart rhythm was defined as ventricular
fibrillation or ventricular tachycardia without a pulse, as
determined by the EMS provider upon arrival.
Eligibility criteria for inclusion and recruitment of
patients to the study were as follows: participants had to
have had an OHCA of cardiac origin and a shockable
heart rhythm that was witnessed by a bystander, be
resuscitated by a bystander, not have achieved return of
spontaneous circulation before arrival of an EMS, and
then have been transported to a medical institution in
Japan between Jan 1, 2005, and Dec 31, 2015. Cardiac
arrest was defined as the cessation of cardiac mechanical
activity, as confirmed by the absence of signs of
circulation.12 An OHCA of cardiac or non-cardiac origin
was diagnosed clinically by the physician in charge, in
collaboration with EMS personnel.1,4,7–10
The study was approved by the ethics committee of
Surugadai Nihon University Hospital10 and the National
Cerebral and Cardiovascular Centre (M29–088–2). The
requirement of written informed consent from recruited
For more on the Japanese
patients was waived. A resuscitation science subcommittee
Circulation Society see of the Japanese Circulation Society was provided with the
http://www.j-circ.or.jp/english/ trial registry data after the prescribed governmental legal
2256 www.thelancet.com Vol 394 December 21/28, 2019
who received cardiopulmonary resuscitation combined with
public-access defibrillation before initiation of an EMS response
achieved a favourable neurological outcome at 30 days after the
OHCA than did those who received cardiopulmonary
resuscitation alone, even if return of spontaneous circulation
was not achieved at time of public-access defibrillation.
Moreover, logistic regression analysis showed that, regardless of
EMS response time, a significantly higher proportion of patients
who received public-access defibrillation achieved a favourable
neurological outcome at 30 days after the OHCA event than did
those who did not receive public-access defibrillation.
Implications of all the available evidence
This novel finding supports proactive cardiopulmonary
resuscitation combined with public-access defibrillation for all
patients with OHCA, despite the potential risk of delaying
hospital arrival. In addition, our study supports further
extending the implementation of public-access defibrillation
programmes in the community.
procedures were followed. We analysed only de-identified
(anonymised) data. This study is registered with the
University Hospital Medical Information Network Clinical
Trials Registry, UMIN000009918.
Procedures
In Japan, there are 802 municipally governed fire stations
with dispatch centres operating for 24 h every day and that
follow uniform guideline-based resus­citation protocols.7
All EMS personnel are municipal government employees
who have been trained to perform CPR according to
Japan Resuscitation Council guidelines, which are based
on the 2005 and 2010 International Liaison Committee On
Resuscitation guidelines.4,7 EMS personnel are instructed
to transport patients with an OHCA to the nearest high-
quality emergency centre in the region. Every ambulance
has three EMS providers, including at least one emer­
gency lifesaving technician with a national certification
for inserting intravenous lines, airway adjuncts, and
tracheal tubes, as well as for administering intravenous
epinephrine. All patients who have an OHCA and receive
resuscitation by EMS personnel are transported to a
hospital because EMS personnel in Japan are not
permitted to terminate resuscitation in the field.
Data were collected prospectively by the FDMA from
Jan 1, 2005, according to the Utstein guidelines.11,12 The
following patient information was collected and analysed
on Sept 26, 2017: aetiology of arrest (ie, cardiac or non-
cardiac), sex, age, whether the arrest was witnessed by a
bystander, relationship of the bystander to the patient
(ie, family member or other), first documented cardiac
rhythm, type of bystander-initiated CPR (ie, CPR with
chest compressions only or CPR with chest com­pressions
and assisted breathing), whether CPR was assisted by an

EMS dispatcher, whether public-access defibrillation was
delivered by a bystander, and the return of spon­taneous
circulation status of the patient before they arrived in
hospital. The time between patient collapse and initiation
of bystander CPR or public-access defibrillation was
obtained from interviews of the bystander by an EMS
provider or from public-access defibrillation records. All
patients who received bystander-delivered public-access
defibrillation were considered to have had a shockable
heart rhythm. Return of spontaneous circu­lation before
hospital arrival was defined as detection of any spon­
taneous palpable pulse, as confirmed by cardiac rhythm
monitoring by elec­trocardiography before hospital arrival.
All survivors were followed up for up to 30 days after the
OHCA by EMS providers who provided their emergency
care. The neurological outcome of patients was assessed
by the attending physician 30 days after successful
resuscitation and was based on a follow-up interview and
the Cerebral Performance Category scale.11–13 A study data
form of questions about neuro­logical status and survival
was completed by EMS personnel in cooperation with the
attending physician. Collected data were stored on the
FDMA registry data­ base server and were checked for
missing or repeated data by the FDMA using an Utstein-
style online statistical survey system. If a study data form
was incomplete, the FDMA returned it to the respective
fire station for completion.
Outcomes
The primary outcome was favourable neurological
outcome in patients at 30 days after the OHCA. A
favourable neurological outcome was defined as a
Cerebral Performance Category score of 1 (good cerebral
performance) or 2 (moderate cerebral disability).11–13 The
secondary outcome was survival of patients at 30 days
after the OHCA. The outcomes in this study were pre-
specified.
Statistical analysis
For baseline patient characteristics and outcomes from
bystander use of public-access AEDs before EMS arrival,
we compared normally distributed variables using a
t test and Mann-Whitney U test and the results are
presented as the mean (SD). We compared non-
normally distributed variables using the Mann-Whitney
U test. Categorical variables were compared by use of
the Fisher’s exact test or χ² test, as appropriate. A p value
of less than 0·05 was considered to indicate a significant
difference.
Patients with an OHCA who did and did not receive
public-access defibrillation before EMS arrival were
pro­pensity score-matched on the basis of age, sex,
relationship of bystander to patient (ie, family member
or other), assistance of CPR by the EMS dispatcher, type
of bystander-initiated CPR (ie, CPR with chest compres­
sions only or CPR with chest compressions and assisted
breathing), CPR protocol (ie, from version 2005 or 2010
www.thelancet.com Vol 394 December 21/28, 2019 2257
Articles
Japan Resuscitation Council guidelines), time from
collapse to initiation of bystander CPR, time from
emergency call to arrival of EMS (EMS response time),
and district of Japan (appendix p 3). The propensity
score was estimated by use of probit regression analysis.
Propensity score matching was done for patients who
had an OHCA and received public-access defibrillation
and those who did not at a 1:1 ratio, and we used the
nearest-neighbour matching method within a calliper of
0·01 of the propensity score with the psmatch2 proce­
dure in the Stata software programme (StataCorp,
Stata Statistical Software: Release 14; College Station,
1 299 784 with an out-of-hospital cardiac arrest event
25 851 did not have attempted resuscitation
1 273 933 had attempted resuscitation
547 908 had arrest of non-cardiac origin
726 025 had arrest of cardiac origin
490 673 excluded
431 480 did not have arrest witnessed by a bystander
56 658 had arrest witnessed by EMS personnel
2535 had unknown witness status
235 352 had cardiac arrest witnessed by a citizen
119 946 did not receive CPR from a bystander
115 406 received CPR from a bystander
87 387 excluded because they did not have an initial shockable
heart rhythm
28 019 had an initial shockable heart rhythm
2568 received public-access defibrillation by a 25 451 did not receive public-access defibrillation
citizen before arrival of emergency medical by a citizen before arrival of emergency
service personnel medical service personnel
326 achieved return of spontaneous 364 achieved return of spontaneous
circulation before arrival of emergency circulation before arrival of emergency
medical service personnel medical service personnel
2242 did not achieve return of spontaneous 25 087 did not achieve return of spontaneous
circulation before arrival of emergency circulation before arrival of emergency
medical service personnel medical service personnel
Figure 1: Participant flow chart
CPR=cardiopulmonary resuscitation. EMS=emergency medical service.
 Articles

TX, USA). For sensi­ tivity analysis, we used logistic
regression for subgroup analysis to evaluate the
association between public-access defibrillation before
arrival of the EMS and a favourable neurological
outcome by quartiles of EMS response time in the
overall study population.
We compared baseline characteristics of patients in the
group of people who received public-access defibrillation
with those who did not using JMP version 11.0
(SAS Institute, Cary, NC, USA). Univariate and multi­
variate logistic regression and propensity score-matched
analyses were done with Stata version 14 (StataCorp,
Stata Statistical Software: Release 14).
Role of the funding source
There was no funding source for this study. The
implementation working group for the All-Japan Utstein
registry of the FDMA designed the study protocol, and
the FDMA collected and managed the data. The FDMA
had no role in the analysis or interpretation of the data,
nor the writing of this report. All authors had full access
to all data from the All-Japan Utstein Registry, which is a
publicly accessible open database. The corresponding
author had the ultimate responsibility for the decision to
submit the study for publication.
Results
Study population
In total, 1 299 784 patients were confirmed to have had
an OHCA between Jan 1, 2005, and Dec 31, 2015
(figure 1). Of the 1 273 933 patients with a confirmed
OHCA and in whom resuscitation was attempted,
115 406 patients had a cardiac that was witnessed by a
citizen and received bystander CPR. 28 019 (24·3%) of
these patients had an initial shockable heart rhythm of
whom 2568 (9·2%) received public-access defibrillation
before arrival of EMS. Patients who achieved return
of spontaneous circulation with (n=326) or without

Total (n=27 329) Unadjusted Propensity score-matched population*

Public-access No public-access p value Public-access No public-access
defibrillation defibrillation defibrillation defibrillation
(n=2242) (n=25 087) (n=1483) (n=1483)
Age, years 64 (17) 60 (17) 64 (16) <0·0001 61 (17) 61 (17)
Men 21 780 (80%) 1907 (85%) 19 873 (79%) <0·0001 1251 (84%) 1248 (84%)
Relationship of bystander to patient ·· ·· ·· <0·0001 ·· ··
Family member 14 772 (54%) 221 (10%) 14 551 (58%) ·· 189 (13%) 201 (14%)
Other 12 557 (46%) 2021 (90%) 10 536 (42%) ·· 1294 (87%) 1282 (86%)
Dispatcher-assisted CPR 17 197 (63%) 906 (40%) 16 291 (65%) <0·0001 663 (45%) 820 (55%)
Type of bystander-initiated CPR ·· ·· ·· <0·0001 ·· ··
Chest compressions only 19 534 (71%) 1217 (54%) 18 317 (73%) ·· 895 (60%) 903 (60%)
Chest compressions with rescue breathing 7717 (28%) 966 (43%) 6751 (26%) ·· 584 (39%) 576 (39%)
Unknown 78 (1%) 59 (3%) 19 (1%) ·· 4 (1%) 4 (1%)
CPR protocol based on Japan Resuscitation ·· ·· ·· <0·0001 ·· ··
Council guidelines
2005 13 715 (50%) 719 (32%) 12 996 (52%) ·· 542 (37%) 520 (35%)
2010 14 424 (50%) 1523 (68%) 12 901 (48%) ·· 941 (63%) 963 (65%)
Time between patient collapse and initiation 2 (0–4) 1 (0–4) 2 (0–4) <0·0001 1 (0–4) 1 (0–4)
of bystander CPR, mins
Time between placing of emergency call and 8 (6–10) 8 (6–10) 8 (6–10) 0·0033 8 (6–10) 8 (6–10)
arrival of emergency medical service, mins
Number of patients stratified by district† ·· ·· ·· <0·0001 ·· ··
Hokkaido 1183 (4%) 74 (3%) 1109 (4%) ·· 47 (3%) 69 (5%)
Tohoku 2656 (10%) 127 (6%) 2529 (10%) ·· 78 (5%) 151 (10%)
Kanto 8536 (31%) 1049 (47%) 7487 (30%) ·· 655 (44%) 521 (35%)
Chubu 5263 (19%) 344 (15%) 4919 (20%) ·· 249 (17%) 249 (17%)
Kinki 4449 (16%) 342 (15%) 4107 (16%) ·· 237 (16%) 247 (17%)
Chugoku 146 (5%) 87 (4%) 1373 (5%) ·· 64 (4%) 79 (5%)
Shikoku 736 (3%) 46 (2%) 690 (3%) ·· 33 (2%) 45 (3%)
Kyushu 3046 (11%) 173 (8%) 2873 (11%) ·· 120 (8%) 122 (8%)
Data are n (%), mean (SD), or median (IQR). Data include patients with bystander-witnessed out-of-hospital cardiac arrest and a shockable rhythm who did not achieve return of
spontaneous circulation before arrival of emergency medical service. CPR=cardiopulmonary resuscitation. *Adjusted for age, sex, relationship of bystander to patient, dispatcher
provision of CPR instructions, type of bystander-initiated CPR, CPR protocol based on Japan Resuscitation Council guidelines, time from collapse to initiation of bystander CPR,
time from emergency call to emergency medical service contact with the patient, and by the districts of Japan. †See appendix p 3 for more information.

Table 1: Baseline characteristics

2258 www.thelancet.com Vol 394 December 21/28, 2019

 Articles

(n=364) public-access defibrillation before arrival of
EMS response were excluded from the study. Ultimately,
27 329 patients who did not achieve return of spon­
taneous circulation and who received (n=2242) or did
not receive (n=25 087) public-access defibrillation were
eligible and were included in the analysis.
Table 1 shows the baseline charac­teristics of study par­
ticipants, stratified by public-access defibrillation status.
Propensity score matching on the nine variables matched
1483 (66·1%) of 2242 patients who received public-access
defibrillation to 1483 (5·9%) of 25 087 patients who did
not receive public-access defibrillation (table 1).
Figure 2 presents the neurological and survival out­
comes of patients who received public-access defibrillation
compared with those who did not. The proportion of
patients who survived and had a favourable neurological
outcome at 30 days after the OHCA was significantly
higher in those who received public-access defibrillation
than in those who did not (845 [37·7%] vs 5676 [22·6%];
OR 2·07 [95% CI 1·89–2·26], p<0·0001). Consistent with
these results, propensity score matching showed that a
significantly higher proportion of patients who received
Public-access defibrillation
No public-access defibrillation
50
p<0·0001
40
Proportion of patients (%)
public-access defibrillation had a favourable neurological
outcome at 30 days after the OHCA than did patients who
did not receive public-access defibrillation (table 2).
Table 3 shows the amount of time between patient
collapse and the placing of an emergency call by a
bystander, administration of the first shock, and hospital
arrival, and stratifies the results by the type of procedure
given by EMS personnel to the patient before arrival
at the hospital. The median time from patient collapse
to first shock by a citizen or EMS per­ sonnel was
significantly shorter in patients who received public-
access defibrillation than in patients who did not
(table 3). However, the median time from patient
collapse and placing of an emergency call by a bystander
was significantly longer for patients who received
public-access defibrillation than for those who did not.
Similarly, the median time from patient collapse to
hospital arrival was significantly longer in patients who
received public-access defibrillation than in those who
did not. No significant difference in the number of
shocks administered by EMS personnel between
patients who received public-access defibrillation and
those who did not was observed. Similar associations
were observed after propensity score matching (table 3).
The median time between the emergency call and
p<0·0001 initiation of an EMS response to the patient in the overall
study population was 8 min (IQR 6–10). Figure 3 shows
the effect of public-access defibrillation on the primary

outcome. The proportion of patients with a favourable

30
44%
20 38%
10 23%
0
Favourable neurological outcome
at 30 days
Figure 2: Primary and secondary outcomes
Data include patients who had a bystander-witnessed out-of-hospital cardiac
arrest event and an initial shockable heart rhythm, and who did not achieve
return of spontaneous circulation before initiation of an emergency medical
service response, stratified by public-access defibrillation. The primary outcome
was favourable neurological outcome at 30 days after the out-of-hospital
cardiac event. The secondary outcome was survival at 30 days after the
out-of-hospital cardiac arrest.
neurological outcome at 30 days after the OHCA was
significantly higher in those who received public-access
defibrillation than in those who did not regardless of
32%
EMS response time (<6 min, OR 1·41 [95% CI 1·09–1·84];
6–10 min, OR 1·71 [1·51–1·94]; >10 min, OR 1·84
[1·43–2·36]).
Survival Sensitivity analysis showed that, regardless of age, sex,
at 30 days type of dispatcher-assisted CPR, and type of bystander-
initiated CPR, a significantly higher proportion of
patients who received public-access defibrillation had a
favourable neurological outcome than those who did not
(appendix p 5). However, in patients who had an OHCA
witnessed by family member, AED use was not
associated with a favourable neurological outcome
com­pared with patients who had an OHCA that was

Unadjusted Propensity score-matched*

Public-access No public-access Odds ratio (95% CI) p value Public-access No public-access Odds ratio (95% CI) p value
defibrillation defibrillation defibrillation defibrillation
(n=2242) (n=25 087) (n=1483) (n=1483)
Favourable neurological 845 (38%) 5676 (23%) 2·07 (1·89–2·26) <0·0001 546 (37%) 425 (29%) 1·45 (1·24–1·69) <0·0001
outcome at 30 days
Survival at 30 days 987 (44%) 7976 (32%) 1·69 (1·55–1·84) <0·0001 650 (44%) 553 (37%) 1·31 (1·13–1·52) <0·0001
Data are n (%) unless otherwise specified. Includes patients with bystander-witnessed out-of-hospital cardiac arrest and a shockable rhythm who did not achieve return of
spontaneous circulation before arrival of emergency medical service. *Adjusted for age, sex, relationship of bystander to patient, dispatcher provision of CPR instructions, type of
bystander-initiated CPR, CPR protocol based on Japan Resuscitation Council guidelines, time from collapse to arrival of emergency medical service, and by the districts of Japan.

Table 2: Effect of public-access defibrillation contact on primary and secondary outcomes

www.thelancet.com Vol 394 December 21/28, 2019 2259

 Articles

Total (n=27 319) Unadjusted Propensity score-matched*

Public-access No public-access p value Public-access No public-access p value
defibrillation defibrillation defibrillation defibrillation
(n=2242) (n=25 087) (n=1483) (n=1483)
Time interval after placing of emergency call
Time interval between collapse and 2 (0–4) 2 (0–4) 2 (0–4) <0·0001 2 (0–4) 1 (0–3) <0·0001
placing of emergency call, min
Time interval between collapse and first 11 (8–15) 1 (0–4) 12 (9–15) <0·0001 1 (0–4) 12 (9–15) <0·0001
shock, min†
Time interval between collapse and 33 (26–41) 34 (27–43) 32 (26–41) <0·0001 33 (26–42) 32 (26–40) 0·0085
hospital arrival, min
Procedure by emergency medical service personnel
Advanced airway management 11 348 (42%) 639 (29%) 10 709 (44%) <0·0001 433 (30%) 535 (37%) <0·0001
Supraglottic airway 9997 (37%) 555 (25%) 9442 (38%) <0·0001 376 (25%) 484 (33%) 0·0012
Endotracheal intubation 1454 (5%) 91 (4%) 1510 (6%) 0·003 63 (5%) 64 (4%) 0·2128
Insertion of an intravenous line 9330 (34%) 670 (30%) 8660 (35%) <0·0001 455 (31%) 524 (35%) 0·0071
Administration of epinephrine 5498 (20%) 455 (20%) 5043 (20%) 0·9332 310 (21%) 324 (22%) 0·5312
Number of shocks administered by 2 (1–3) 2 (1–3) 2 (1–3) 0·2280 2 (1–4) 2 (1–3) 0·0017
emergency medical service personnel
Number of patients who received 10 123 (38%) 761 (37%) 9362 (38%) 0·6020 198 (22%) 242 (21%) 0·6141
three shocks
Data are n (%) or median (IQR) unless otherwise specified. CPR=cardiopulmonary resuscitation. *Adjusted for age, sex, relationship of bystander to patient, dispatcher
provision of CPR instructions, type of bystander-initiated CPR, CPR protocol based on Japan Resuscitation Council guidelines, time from collapse to initiation of bystander
CPR, time from emergency call to emergency medical service arrival with patient, and by the districts of Japan. †For the group with public-access defibrillation, this was the
interval from collapse of the patient to the first shock by a bystander; for the group without public-access defibrillation, this was the interval from collapse of the patient to
the first shock by emergency medical service personnel.

Table 3: Time intervals and pre-hospital resuscitation care after placing of the emergency call by a bystander

Public-access defibrillation No public-access defibrillation Odds ratio than in those who did not. To our knowledge, our study is
(n/N) (n/N) (95% CI) the first to show that public-access defi­brillation has a
Emergency medical service response time (mins)
positive effect on the neurological outcome status of
<6 139/289 1212/3582 1·41 (1·09–1·84)
patients who did not achieve return of spontaneous
6–10 578/1431 3811/16 188 1·71 (1·51–1·94) circulation at the time of public-access defibrillation. In
>10 128/522 653/5317 1·84 (1·43–2·36) addition, as our study included all cases of OHCA in
Japan, which therefore excludes the possibility of selection
0 1 2 3 4 bias, it satisfies the assumptions of a natural experiment
Favours no public-access defibrillation Favours public-access defibrillation observational study.
Early defibrillation plays a key role in improving
Figure 3: Association between public-access defibrillation and favourable neurological outcome by emergency the survival of patients with an initial shockable heart
medical service response time
EMS response time is defined as the time between the emergency call and initiation of emergency medical service
rhythm after an OHCA.14–16 According to Kitamura and
response to the patient. colleagues,1 public-access defibrillation has signifi­cantly
increased the proportion of patients with a favourable
witnessed by a bystander (appendix p 5). In patients who neuro­logical outcome over a 9-year period after public-
were older than 65 years, female, and who had had an access AEDs were legally authorised in Japan in
OHCA witnessed by a family member, AED use was not July, 2004. In general, we attribute this positive effect
associated with increased survival when compared with to the number of sur­ vivors who achieve return of
patients who were younger than 65 years, male, and who spontaneous circulation through public-access defibril­
had an OHCA witnessed by a bystander. lation,4 however more than 80% of patients with a
bystander-witnessed OHCA and a shockable heart
Discussion rhythm do not achieve return of spontaneous circulation.
Our analysis shows that among patients with a bystander- One study in the UK17 reported that only 5% of people
witnessed OHCA and an initial shockable heart rhythm, knew the location of the nearest public-access AED, and
who did not achieve return of spontaneous circulation retrieval of public-access AEDs might have the potential
before arrival of an EMS personnel, the proportion of disadvantage of interrupting chest compressions or
those who achieved a favourable neurological outcome could delay arrival of the patient at hospital.5,6
at 30 days after the OHCA was significantly higher in Our study focused on patients who did not achieve
participants who received public-access defibrillation return of spontaneous circulation before arrival of

2260 www.thelancet.com Vol 394 December 21/28, 2019


EMS. Therefore, we adjusted for prognostic factors
that might affect the neurological status of patients
between the OHCA event and initiation of the EMS
response, including the time between patient collapse and
initiation of bystander CPR and the time between the
emergency call and initiation of an EMS response to the
patient (EMS response time).18 Patients who received
public-access defibrillation had a significantly shorter
median time from collapse to first shock and a significantly
longer mean time from collapse to emergency call and
hospital arrival than patients who did not receive public-
access defibrillation. However, no significant difference in
the number of shocks admin­istered by EMS personnel
was observed between patients who did and those who did
not receive public-access defibrillation. Thus, the pro­
portion of patients with refractory ventricular fibrillation
was similar between the two groups. These results
indicate that earlier delivery of the first shock by a citizen
using a public-access AED might be more advantageous
for a favourable neurological outcome than a later delivery
of the first shock by the EMS personnel, despite the delay
in hospital arrival for patients who do not achieve return
of spontaneous circulation at the time of public-access
defibrillation.
This unanticipated result could be due to differences
in the quality of CPR administered by the bystander, or
due to the transient return of spontaneous circulation in
the patient as a result of citizen-administered public-
access defibrillation. Citizens who were familiar with the
use of public-access AEDs might have received CPR
training, and could therefore have delivered better quality
CPR than citizens who did not use a public-access AED.19
Moreover, assistance from the visual and audio CPR
prompts from public-access AEDs might also have had a
positive effect on the resuscitation efforts of the bystander.
A previous study20 showed that audio prompts from
public-access AEDs are associated with the delivery of
significantly better quality CPR by untrained individuals
than untrained individuals who do not use a public-access
AED. In addition, dispatcher-assisted CPR is associated
with significantly better survival and neurological out­
comes after an OHCA than unassisted CPR.21 In our study,
citizens who delivered shocks using public-access AEDs
might have therefore provided higher quality CPR than
those who did not deliver shocks using public-access
AEDs. Transient return of spontaneous circulation
through public-access defibrillation can increase coro­
nary and cerebral blood flow in the short period of time
between shock delivery and initiation of an EMS response.
A previous study22 investigating extracorporeal membrane
oxygenation in patients with OHCA showed that transient
return of spontaneous circulation before hospital arrival
is an inde­ pendent predictor of Cerebral Performance
Category 1 or 2 status. Even though return of spontaneous
circulation is transient, earlier coronary reperfusion might
supply oxygen and energy substrates to the myocardium
and reduce reperfusion injury by delaying mitochondrial
www.thelancet.com Vol 394 December 21/28, 2019 2261
Articles
permeability transition pore opening.23,24 Earlier cerebral
reperfusion might also reduce brain damage.25
Our study has some limitations. First, this study is not
a randomised controlled trial and is therefore subject to
the inherent weaknesses of an epidemiological study
(in terms of data integrity and validity). However,
uniform data were collected according to the Utstein-
style guidelines for the reporting of cardiac arrest in a
large sample size and with a population-based design.
To address this limitation in study design, we adjusted
for prognostic factors associated with pre-EMS contact
that could affect neurological status using propensity
score matching. Nevertheless, this approach cannot fully
control for factors actually measured and cannot account
for variables that were not recorded, including the
quality of CPR provided. Therefore, bias due to latent
variables might remain even after propensity score
matching. Second, our results do not address the
potential variability caused by pre-existing medical
conditions of the patients. A severe pre-existing medical
condition could cause refractory cardiac arrest and
decrease survival. Third, we have no information
about the number of bystanders participating in the
CPR efforts and about the duration of CPR before the
emergency call was placed. For example, it was not
known how long CPR was given before an emergency
call was placed in cases involving a single bystander.
Fourth, no information about the type and duration of
return of spontaneous circulation that might have occur­
red before initiation of an EMS response was available.
Further studies are needed to collect this type of
information in the future. Fifth, we did not adjust
for pre-hospital resuscitation care by EMS personnel.
However, bias introduced by variations in regional
treatment quality was minimised by adjusting for
district. Sixth, no information about post-resuscitation
electrocardiography findings and post-cardiac arrest
care, such as extracorporeal CPR, targeted temperature
management, coronary angiography, and percutaneous
coronary intervention were available. Finally, neuro­
logical outcomes were measured at 30 days after the
OHCA. A consensus statement from the American
Heart Association26 acknowledges that a 3-month post-
discharge period would balance the opportunity for
recovery and minimise the loss of patients to follow-up
when standardising assessment of neurological out­
comes in patients after cardiac arrest.
In conclusion, the results of our study showed that a
significantly higher proportion of patients with OHCA
achieved a favourable neurological outcome if they
received public-access defibrillation before initiation of
an EMS response than those who did not, even if return
of spontaneous circulation was not achieved at the time
of public-access defibrillation. Our findings support
proactive CPR combined with public-access defibrillation
in all patients who have an OHCA, despite the potential
risks of delaying hospital arrival. The results also support
 Articles
further extending the implementation of public-access
defibrillation programmes in the community.
Contributors
TNa, TNo, YT, KNi, SY, and DO were involved in the study design,
data analysis, and interpretation of the results, and contributed to the
writing of the final report. TIw, NY, KNa, and HN were the principal
investigators involved in study design, study completion, data collection,
and data management, and these authors contributed to formulation of the
concept of the All-Japan Utstein Registry. TIk, NS, and HT were involved in
formulating the concept of the study and were involved in the study design,
study completion, data collection, data management, and interpretation of
the results. All authors approved the final version of the Article.
Declaration of interests
We declare no competing interests.
Acknowledgments
We thank all the emergency medical service personnel, the staff of the
Fire and Disaster Management Agency, and the staff of the Institute for
Fire Safety and Disaster Preparedness of Japan for their cooperation in
establishing and maintaining the Utstein database.
References
1 Kitamura T, Kiyohara K, Sakai T, et al. Public-access defibrillation and
out-of-hospital cardiac arrest in Japan. N Engl J Med 2016; 375: 1649–59.
2 Claesson A, Herlitz J, Svensson L, et al. Defibrillation before EMS
arrival in western Sweden. Am J Emerg Med 2017; 35: 1043–48.
3 Kitamura T, Iwami T, Kawamura T, et al. Nationwide improvements
in survival from out-of-hospital cardiac arrest in Japan. Circulation
2012; 126: 2834–43.
4 Kitamura T, Iwami T, Kawamura T, et al. Nationwide public-access
defibrillation in Japan. N Engl J Med 2010; 362: 994–1004.
5 Eilevstjonn J, Kramer-Johansen J, Sunde K. Shock outcome is
related to prior rhythm and duration of ventricular fibrillation.
Resuscitation 2007; 75: 60–67.
6 Berdowski J, ten Haaf M, Tijssen JG, Chapman FW, Koster RW.
Time in recurrent ventricular fibrillation and survival after
out-of-hospital cardiac arrest. Circulation 2010; 122: 1101–08.
7 Nagao K, Nonogi H, Yonemoto N, et al. Duration of prehospital
resuscitation efforts after out-of-hospital cardiac arrest. Circulation
2016; 133: 1386–96.
8 Hasegawa M, Abe T, Nagata T, Onozuka D, Hagihara A. The number
of prehospital defibrillation shocks and 1-month survival in patients
with out-of-hospital cardiac arrest. Scand J Trauma Resusc Emerg Med
2015; 23: 34.
9 Izawa J, Komukai S, Gibo K, et al. Pre-hospital advanced airway
management for adults with out-of-hospital cardiac arrest:
nationwide cohort study. BMJ 2019; 364: l430.
10 Japanese Circulation Society Resuscitation Science Study Group.
Chest-compression-only bystander cardiopulmonary resuscitation
in the 30:2 compression-to-ventilation ratio era. Nationwide
observational study. Circ J 2013; 77: 2742–50.
11 Perkins GD, Jacobs IG, Nadkarni VM, et al. Cardiac arrest and
cardiopulmonary resuscitation outcome reports: update of the Utstein
Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest:
a statement for healthcare professionals from a task force of the
International Liaison Committee on Resuscitation (American Heart
Association, European Resuscitation Council, Australian and
New Zealand Council on Resuscitation, Heart and Stroke Foundation
of Canada, InterAmerican Heart Foundation, Resuscitation Council
of Southern Africa, Resuscitation Council of Asia); and the American
Heart Association Emergency Cardiovascular Care Committee and
the Council on Cardiopulmonary, Critical Care, Perioperative and
Resuscitation. Circulation 2015; 132: 1286–300.
2262 www.thelancet.com Vol 394 December 21/28, 2019
12 Jacobs I, Nadkarni V, Bahr J, et al. Cardiac arrest and
cardiopulmonary resuscitation outcome reports: update and
simplification of the Utstein templates for resuscitation registries:
a statement for healthcare professionals from a task force of the
International Liaison Committee on Resuscitation (American
Heart Association, European Resuscitation Council, Australian
Resuscitation Council, New Zealand Resuscitation Council,
Heart and Stroke Foundation of Canada, InterAmerican Heart
Foundation, Resuscitation Councils of Southern Africa). Circulation
2004; 110: 3385–97.
13 Cummins RO, Chamberlain DA, Abramson NS, et al.
Recommended guidelines for uniform reporting of data from
out-of-hospital cardiac arrest: the Utstein Style. A statement for
health professionals from a task force of the American Heart
Association, the European Resuscitation Council, the Heart and
Stroke Foundation of Canada, and the Australian Resuscitation
Council. Circulation 1991; 84: 960–75.
14 Hasselqvist-Ax I, Riva G, Herlitz J, et al. Early cardiopulmonary
resuscitation in out-of-hospital cardiac arrest. N Engl J Med 2015;
372: 2307–15.
15 Malta Hansen C, Kragholm K, Pearson DA, et al. Association of
bystander and first-responder intervention with survival after
out-of-hospital cardiac arrest in North Carolina, 2010–2013. JAMA
2015; 314: 255–64.
16 Wissenberg M, Lippert FK, Folke F, et al. Association of national
initiatives to improve cardiac arrest management with rates of
bystander intervention and patient survival after out-of-hospital
cardiac arrest. JAMA 2013; 310: 1377–84.
17 Brooks B, Chan S, Lander P, Adamson R, Hodgetts GA, Deakin CD.
Public knowledge and confidence in the use of public access
defibrillation. Heart 2015; 101: 967–71.
18 Kronick SL, Kurz MC, Lin S, et al. Part 4: systems of care and
continuous quality improvement: 2015 American heart association
guidelines update for cardiopulmonary resuscitation and
emergency cardiovascular care. Circulation 2015; 132: S397–413.
19 Kuramoto N, Morimoto T, Kubota Y, et al. Public perception of and
willingness to perform bystander CPR in Japan. Resuscitation 2008;
79: 475–81.
20 Williamson LJ, Larsen PD, Tzeng YC, Galletly DC. Effect of
automatic external defibrillator audio prompts on cardiopulmonary
resuscitation performance. Emerg Med J 2005; 22: 140–43.
21 Song KJ, Shin SD, Park CB, et al. Dispatcher-assisted bystander
cardiopulmonary resuscitation in a metropolitan city: a before-after
population-based study. Resuscitation 2014; 85: 34–41.
22 Yukawa T, Kashiura M, Sugiyama K, Tanabe T, Hamabe Y.
Neurological outcomes and duration from cardiac arrest to the
initiation of extracorporeal membrane oxygenation in patients with
out-of-hospital cardiac arrest: a retrospective study.
Scand J Trauma Resusc Emerg Med 2017; 25: 95.
23 Shanmuganathan S, Hausenloy DJ, Duchen MR, Yellon DM.
Mitochondrial permeability transition pore as a target for
cardioprotection in the human heart. Am J Physiol Heart Circ Physiol
2005; 289: H237–42.
24 Assaly R, de Tassigny A, Paradis S, Jacquin S, Berdeaux A, Morin D.
Oxidative stress, mitochondrial permeability transition pore
opening and cell death during hypoxia-reoxygenation in adult
cardiomyocytes. Eur J Pharmacol 2012; 675: 6–14.
25 Kastrup A, Engelhorn T, Beaulieu C, de Crespigny A, Moseley ME.
Dynamics of cerebral injury, perfusion, and blood-brain barrier
changes after temporary and permanent middle cerebral artery
occlusion in the rat. J Neurol Sci 1999; 166: 91–99.
26 Becker LB, Aufderheide TP, Geocadin RG, et al. Primary outcomes
for resuscitation science studies: a consensus statement from the
American Heart Association. Circulation 2011; 124: 2158–77.