J Thromb Thrombolysis (2011) 32:405–409
DOI 10.1007/s11239-011-0619-0
Impact of fibrinolysis on immediate prognosis of patients
with out-of-hospital cardiac arrest
Aurélien Renard • Catherine Verret • Daniel Jost • Jean-Baptiste Meynard
Julie Tricehreau • Olivier Hersan • David Fontaine •
Frédérique Briche • Patrick Benner • Olivier de Stabenrath •
Christophe Bartou • Nicolas Segal • Laurent Domanski
Published online: 27 July 2011
Ó Springer Science+Business Media, LLC 2011
Abstract Fibrinolytic therapy (FT) during out-of-hospital
cardiac arrest (OHCA) has been studied in several trials,
but they have produced unsatisfactory results even in the
most recent Thrombolysis in Cardiac Arrest (TROICA)
study. This study aimed to assess the impact of FT pro-
vided by an out-of-hospital emergency physician on the
immediate prognosis of patients with OHCA. We per-
formed a retrospective study in which the primary endpoint
was survival to hospital admission. Among 5,102 patients
with OHCA in Paris and the suburban area who received
medical care from the Fire Brigade of Paris, 1,261 met the
following inclusion criteria: age above 18 years with non-
traumatic OHCA. Among 107 patients who received FT,
51 (47.7%) survived to hospital admission whereas 272 out
of 1,154 (23.6%) patients who did not receive FT survived
to hospital admission. A matching process based on a
propensity score used to equalise potential prognosis fac-
tors in both groups demonstrated that FT was associated
with more frequent survival to hospital admission (OR
A. Renard (&)
D. Jost
O. Hersan
D. Fontaine
F. Briche

C. Bartou
N. Segal
L. Domanski
Service Médical de la Brigade de Sapeurs Pompiers de Paris,
1 Place Jules Renard, 75017 Paris, France
e-mail: aurelien.renard211@orange.fr
C. Verret
J.-B. Meynard
J. Tricehreau
CESPA Centre d’Epidémiologie et de Santé Publique des
Armées, ı̂lot Bégin 94163, Saint Mandé, France
P. Benner
Service Médical du Bataillon des Marins Pompiers de Marseille,
Marseille, France
O. de Stabenrath
Service d’accueil des Urgences, HIA Robert Picqué, Bordeaux,
France
•
adjusted: 1.7; CI 95% [1.09–2.68]). This result was
observed particularly in patients who were not initially
shocked by automatic electrical defibrillator (AED)
(ORa = 3.61; CI 95% [1.88–6.96]). This study showed that
fibrinolysis was associated with improved survival to
hospital admission, after performing a propensity analysis.
FT may be beneficial in out-of-hospital arrest patients.
However, any conclusions drawn are limited by the retro-
spective nature of the study.
Keywords Fibrinolysis
Resuscitation

Pre-hospital care
Cardiac arrest
Introduction
Out-of-hospital cardiac arrest (OHCA) remains a major
public health issue in France where its incidence is more
than 30,000 a year with a survival rate of less than 4% [1].
The management of OHCA is standardised and based on
the guidelines of the International Liaison Committee on
Resuscitation (ILCOR) 2005 [2]. Fibrinolytic therapy (FT)
is not included in the latest recommendations. Several
retrospective studies have evaluated the benefits of FT for
OHCA [3–5].
The results were promising, but a recent multicentre
randomised controlled trial did not show any benefits of
this therapy. However, after including 443 patients where
initial rhythm was not necessarily in ventricular fibrillation
(VF), the inclusion criteria were restricted to patients with
ventricular fibrillation refractory to three external electric
shocks (EES) [6].
The Fire Brigade of Paris (BSPP) is a military unit that
includes about 8,000 members. It provides first aid to about
6 million inhabitants and its emergency medical system
123
406
provides a two-tiered response system. This entails basic
life support (BLS) and EES by automated external defi-
brillators (AED), provided by 200 teams of 3 to 5 profes-
sional rescuers residing in 77 fire stations, and advanced
cardiac life support (ACLS) provided by 44 ambulances
each with an emergency physician, nurse and driver. These
medical ambulances are dispatched by the ‘‘Service d’Aide
Médicale Urgente’’ (SAMU) or BSPP, depending on the
location of the emergency.
This study aimed to assess the impact of FT provided by
an out-of-hospital emergency physician on the immediate
prognosis of patients with OHCA.
Materials and methods
This retrospective study included all consecutive patients
aged above 18 who presented a non-traumatic OHCA and
received medical care provided by the BSPP between 1st
September 2005 and 28th March 2007. Patients received
FT according to criteria that were not clearly identified by
the physicians. The fibrinolytic agents used were alteplase
(50 mg in a single bolus) or tenecteplase (100 UI/kg in a
single bolus).
Trial data were collected in accordance with the Utstein
style [7]. The available variables were: administration of
FT, age, gender, location of cardiac arrest, response time
(delay from alarm call to AED switch-on), bystander
presence, bystander action (cardiopulmonary resuscitation,
CPR or not), cardiac arrest etiology, shock administration
by first responder AED and survival to hospital admission.
Since patients were not randomised to receive FT, the
probability of receiving FT varied according to the baseline
Fig. 1 Flow diagram of patient
enrollment, considering
administration of FT and
outcome
123
A. Renard et al.
characteristics of the patients. Propensity-based matching
was used to select control patients who were similar to
patients receiving FT with respect to propensity score and
other covariates. The propensity score is the probability of
receiving treatment for a patient with these baseline char-
acteristics [8]. We estimated propensity scores for the
population included with a non-parsimonious multivariate
logistic regression model. We matched one patient
receiving FT with the two closest non-lytic patients whose
propensity score differed by less than 0.01. Absolute
standardised differences in baseline covariates were cal-
culated to assess pre-match imbalances estimated on a
simple random sampling of non-lytic patients and on the
sample of matched non-lytic patients on baseline covariates
(Love plot) [9].
The univariate description used the Mann–Whitney test
for continuous data and v2 test for categorical data. The
effects of FT on the endpoint (survival to hospital admis-
sion) were adjusted on baseline characteristics with a
multivariate logistic regression analysis and odds ratios
with 95% confidence intervals were calculated. The
threshold of significance was set at 0.05. All statistical
analyses were performed using STATA/SE 11.0 (Stata-
Corp, College Station, TX).
Results
Between 1st September 2005 and 28th March 2007, 5,102
patients were recorded to have had OHCA. A total of 1,261
consecutive patients were included in the final analysis
(Fig. 1). The baseline demographic characteristic vari-
ables (age, gender and location of cardiac arrest) and
Impact of fibrinolysis on immediate prognosis of patients 407

Table 1 Pre-hospital demographic and clinical characteristics of the 0% 40% 80% 120% 160% 200%
patients who did not receive FT (F-) and those who did (F?)
gender
F- F? P value
(n = 1154) (n = 107) age 50-75
n % n %
age 75+
Gender (male) 699 60.6 86 80.4 \0.001
Age (years)
bystander
\50 207 17.9 25 23.4 \0.001
50–75 437 37.9 68 63.5 CPR by bystander
[75 510 44.2 14 13.1
Cardiac arrest witnessed by 722 62.6 76 71.0 0.09 At home
bystander
CPR performed by bystander 150 12.9 17 15.8 0.37 Presumed cardiac
Location at home 874 75.7 85 79.4 0.48 etiology
Presumed cardiac etiology 389 33.7 45 42.0 0.09 delay alarm-switch on Post-match
8-11' Pre-match
Shock administered by AED 304 26.3 66 61.6 \0.001
Delay in ‘‘alarm—AED switch-on’’ delay alarm-switch on
11'+
\8 min 250 21.7 41 38.3
8–11 min 515 44.6 35 32.7 0.001 Shock by AED
[11 min 389 33.7 31 8.5
CPR cardiopulmonary resuscitation, AED automated external defi-
Fig. 2 Love plot for absolute standardised differences in baseline
brillator, F- patients who did not receive FT, F? patients who
covariates between patients receiving and not receiving FT, before
received FT
and after propensity score matching

intervention variables (response time, bystander presence,
bystander action and presumed OHCA etiology) are shown
in Table 1.
The 107 patients who received FT (F?) differed from
those who did not (F-) in terms of gender, age, response
time and EES administration by the fire fighters’ AEDs
before the arrival of the medical team. Both groups were
comparable for the other variables specified in Table 1.
Among the 107 patients who received FT, 51 (47.7%)
survived to hospital admission, while among the 1,154
‘‘F-’’ patients, only 272 (23.6%) survived to hospital
admission (P \ 0.001). Of the 107 patients who received
FT, only 101 could be matched (94.4%).
Figure 2 presents the absolute standardised differences
of baseline covariates in the pre-match analysis estimated
on 202 randomised (simple random sampling) non-lytic
patients and post-match balance estimated on 202 matched
non-lytic patients (Love plot). The differences were lower
in the matched analysis for all covariates (differences less
than 8%), except for CPR by bystanders, where the dif-
ference was nearly 23% in the matched analysis and 7% in
the other analysis.
Considering the matched analysis and after adjusting for
covariates, survival to hospital admission was more fre-
quent in patients who received FT (ORa: 1.7, CI 95%
[1.09–2.68]). Other factors associated with higher survival
to hospital admission were CAs that were witnessed, young
age, short delay in ‘‘call to AED switch-on’’ and shock
administration by AED. Factors that did not influence
survival to hospital admission were gender, location, CA
etiology and bystander action (Table 2).
Statistical analysis also showed a significant association
between the use of FT and administration of EES by AED
(Fig. 3). For non-shocked patients, FT was associated with
a higher survival to hospital admission (ORa: 3.61, CI 95%
[1.88–6.96]), while for shocked patients, survival to hos-
pital admission was not affected by fibrinolytic adminis-
tration (OR: 1.08, CI 95% [0.61–1.92]).
Considering the data after patient’s arrival at the hos-
pital, only 13 patients had an autopsy, from which we
concluded that there was no pulmonary embolism.
Discussion
This study showed that FT was associated with more fre-
quent survival to hospital admission (OR adjusted: 1.7 CI
95% [1.09–2.68]). Several retrospective studies have
reported results on the use of FT during OHCA resuscita-
tion. A meta-analysis showed that injection of a fibrinolytic
agent was associated with a higher rate of return of spon-
taneous circulation (ROSC), improved 24-h survival and
improved long-term survival without neurological impair-
ment [10]. These were the promising results that led to the

123
408 A. Renard et al.

Table 2 Factors associated with survival to hospital admission

Survival to Univariate Multivariatea
hospital
admission
n % OR 95% CI OR 95% CI

Fibrinolytic therapy
No 272 23.6 Ref. Ref.
Yes 51 47.7 2.9 1.9–4.4 1.7 1.09–2.68
Age
18–50 79 36.9 Ref. Ref.
Fig. 3 Survival of hospital admission comparing shocked or not
51–75 146 31.7 0.8 0.6–1.1 0.9 0.5–1.7 shocked by AED according to the administration of FT. *The
[75 75 14.3 0.3 0.2–0.4 0.4 0.1–0.9 adjustment was made on the variables: sex, age, presence of a witness,
Gender delay ‘‘emergency call ± AED’’ switch-on
Female 102 21.4 Ref. Ref.
Male 221 28.1 1.4 1.1–1.9 0.8 0.4–1.5
Bystander initial heart rhythm and the use of FT. An earlier pro-
Absent 98 20.8 Ref. Ref. spective study has shown that FT has no advantages for
Present but no 162 26.1 1.3 1.0–1.8 1.5 0.8–2.7 patients with pulseless electrical activity [11].
CRP initiated It seems clear that the low survival rate makes it difficult
Present and CPR 63 37.7 2.3 1.6–3.4 2.3 1.1–5.1 to consider a randomised controlled trial including non-VF
initiated patients. Survival to hospital discharge or to 1 year is an
Etiology presumed ambitious endpoint and we must accept that survival to
Unknown 161 27.9 Ref. Ref. hospital admission is currently a good endpoint that can be
Cardiological 103 23.7 0.8 0.6–1.1 0.9 0.5–1.5 used in this context.
Other 59 23.6 0.7 0.5–1.1 0.3 0.1–0.8 On the other hand, we do not know how the physician
Shock by AED selected patients who received FT in our study popula-
No 174 19.5 Ref. Ref. tion. We suppose that it was based on a suspicion of
Yes 149 40.3 2.8 2.1–3.6 2.2 0.9–5.2 pulmonary embolism, given the existence of specific
Delay in ‘‘alarm—AED switch on’’ guidelines for the management of OHCA with pulmonary
\8 min 102 35.1 Ref. Ref. embolism and the numerous reports on this subject [1,
8–11 min 125 22.7 0.5 0.4–0.7 0.2 0.1–0.9 11–17]. However, our hypothesis was wrong since no
[11 min 96 22.9 0.6 0.4–0.8 0.9 0.3–2.4 pulmonary embolism was found in the 13 patients whose
AED automated external defibrillator, CI confidence interval, OR etiology of cardiac arrest could be determined. Data from
odds ratio, Ref reference class the autopsies were rarely available and we could not
a
Adjusted for age, gender, bystander presence and action, etiology, determine the presence or absence of pulmonary embo-
AED shock administration, delay between alarm and AED switch on, lism in our whole population.
and propensity score matched (1 fibrinolytic patient with 2 non-lytic Finally, the decision to administer thrombolytics could
patients)
have been influenced by doctors choosing patients who had
a better chance of survival, probably those who were sus-
pected of having acute coronary syndrome, for whom FT
establishment of a multicentre double blinded study on a was recently shown to be beneficial for OHCA [18].
European scale (Thrombolysis in Cardiac Arrest, TRO-
ICA) [6]. However, this study, after including 443 patients,
restricted the inclusion criteria to OHCA with initial ven- Conclusion
tricular fibrillation. Therefore, TROICAs final results
included only a few patients who were not in VF, while Any conclusions drawn are limited by the retrospective
non-VF patients generally represented 80% of the cardiac nature of the study. Nevertheless, in our study population,
arrest victims. As a consequence, in our study, we focused the influence of shock administration by first responder
secondarily on patients with non-shockable rhythm and our AED, the variables that influence the doctor’s decision to
results appeared to show that non-VF patients benefitted administer fibrinolytics and the choice of a pragmatic
much more from FT than patients with VF shocked by endpoint are the three essential points that need further
AED. Few studies have focused on the association between research.

123
Impact of fibrinolysis on immediate prognosis of patients
References
1. Goldstein P (2002) L’arrêt cardiaque en 2002. Une nouvelle
course contre les morts évitables. Ann Fr Anesth Réanim 21:
547–549
2. 2005 American Heart Association Guidelines for Cardiopulmo-
nary Resuscitation and Emergency Cardiovascular Care. Circu-
lation 112(24 Suppl):IV1-203 (2005)
3. Lederer W, Lichtenberger C, Pechlaner C et al (2004) Long-term
survival and neurological outcome of patients who received
recombinant tissue plasminogen activator during out-of-hospital
cardiac arrest. Resuscitation 61(2):123–129
4. Böttiger BW, Bode C, Kern S et al (2001) Efficacy and safety of
thrombolytic therapy after initially unsuccessful cardiopulmonary
resuscitation: a prospective clinical trial. Lancet 357:1583–1585
5. Fatovich DM, Dobb GJ, Clugston RA (2004) A pilot randomized
trial of thrombolysis in cardiac arrest (the TICA trial). Resusci-
tation 61:309–313
6. Böttiger B, Arntz HR, Chamberlain DA et al (2008) Thrombol-
ysis during resuscitation for out-of-hospital cardiac arrest. N Engl
J Med 359(25):2651–2662
7. Jacobs I, Nadkarni V, Bahr J et al (2004) Cardiac arrest and
cardiopulmonary resuscitation outcome reports: update and sim-
plification of the Utstein templates for resuscitation registries. A
statement for healthcare professionals from a task force of the
international liaison committee on resuscitation. Resuscitation
63(3):233–249
8. D’Agostino RB Jr (1998) Propensity score methods for bias
reduction in the comparison of a treatment to a non-randomized
control group. Stat Med 17:2265–2281
9. Ahmed A, Zannad F, Love TE et al (2007) A propensity-matched
study of the association of the low serum potassium levels and
mortality in chronic heart failure. Eur Heart J 28:1334–1343
409
10. Li X, Fu QL, Jing XL et al (2006) A meta-analysis of cardio-
pulmonary resuscitation with and without the administration of
thrombolytic agents. Resuscitation 70:31–36
11. Abu-laban RB, Christenson JM, Innes GD et al (2002) Tissue
plasminogen activator in cardiac arrest with pulseless electrical
activity. N Engl J Med 346:1522–1528
12. Recommandations de la société française de médecine d’urgence
pour la prise en charge des arrets cardiaques extra hospitaliers.
Ann Fr Anesth Reanim 26:1008–1019 (2007)
13. Spöhr F, Böttiger BW (2008) Emergency medicine and myo-
cardial ischaemia thrombolysis during cardiopulmonary resusci-
tation available data and recommendations. Anasthesiol
Intensivmed Notfallmed Schmerzther 43:226–230
14. Spöhr F, Wenzel V, Böttiger BW (2008) Thrombolysis and other
drugs during cardiopulmonary resuscitation. Curr Opin Crit Care
14(3):292–298
15. Mysiak A, Nowicki P, Kobusiak-prokopowicz M (2007)
Thrombolysis during cardiopulmonary resuscitation: TROICA—
lost war or lost battle? Cardiol J 14(4):424–425
16. Goran KP (2008) Thrombolysis during cardiopulmonary resus-
citation should be addressed in guidelines for pulmonary embo-
lism. Eur Heart J 29(24):3066–3067
17. Cavallaro F, Sandroni C, Bocci MG, Marano C (2009) Good
neurological recovery after cardiopulmonary resuscitation and
thrombolysis in two old patients with pulmonary embolism. Acta
Anaesthesiol Scand 53:400–402
18. Arntz HR, Wenzel V, Dissmann R et al (2008) Out-of-hospital
thrombolysis during cardiopulmonary resuscitation in patients
with high likelihood of ST-elevation myocardial infarction.
Resuscitation 76:180–184
123