Resuscitation 83 (2012) 327–332
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Resuscitation
journal homepage: www.elsevier.com/locate/resuscitation
Clinical Paper
Outcome when adrenaline (epinephrine) was actually given vs. not given – post
hoc analysis of a randomized clinical trial夽
Theresa M. Olasveengen a,∗ , Lars Wik b , Kjetil Sunde c , Petter A. Steen d
a
Department of Anaesthesiology and Institute for Experimental Medical Research, Oslo University Hospital, PB 4956 Nydalen, N-0424 Oslo, Norway
Department of Anaesthesiology and National Centre for Prehospital Emergency Medicine, Oslo University Hospital, PB 4956 Nydalen, N-0424 Oslo, Norway
Department of Anaesthesiology, Oslo University Hospital, PB 4956 Nydalen, N-0424 Oslo, Norway
d
University of Oslo, Faculty Division OUH and Ambulance Department, Oslo University Hospital, PB 4956 Nydalen, N-0424 Oslo, Norway
b
c
a r t i c l e
i n f o
Article history:
Received 29 August 2011
Received in revised form
15 November 2011
Accepted 15 November 2011
Keywords:
Advanced Life Support (ALS)
Cardiac arrest
Cardiopulmonary resuscitation (CPR)
Chest compression
Emergency medical services
Out-of-hospital CPR
Outcome
Drugs
a b s t r a c t
Purpose of the study: IV line insertion and drugs did not affect long-term survival in an out-of-hospital
cardiac arrest (OHCA) randomized clinical trial (RCT). In a previous large registry study adrenaline was
negatively associated with survival from OHCA. The present post hoc analysis on the RCT data compares
outcomes for patients actually receiving adrenaline to those not receiving adrenaline.
Materials and methods: : Patients from a RCT performed May 2003 to April 2008 were included. Three
patients from the original intention-to-treat analysis were excluded due to insufficient documentation
of adrenaline administration. Quality of cardiopulmonary resuscitation (CPR) and clinical outcomes were
compared.
Results: Clinical characteristics were similar and CPR quality comparable and within guideline recommendations for 367 patients receiving adrenaline and 481 patients not receiving adrenaline. Odds ratio
(OR) for being admitted to hospital, being discharged from hospital and surviving with favourable neurological outcome for the adrenaline vs. no-adrenaline group was 2.5 (CI 1.9, 3.4), 0.5 (CI 0.3, 0.8) and
0.4 (CI 0.2, 0.7), respectively. Ventricular fibrillation, response interval, witnessed arrest, gender, age and
endotracheal intubation were confounders in multivariate logistic regression analysis. OR for survival for
adrenaline vs. no-adrenaline adjusted for confounders was 0.52 (95% CI: 0.29, 0.92).
Conclusion: Receiving adrenaline was associated with improved short-term survival, but decreased survival to hospital discharge and survival with favourable neurological outcome after OHCA. This post hoc
survival analysis is in contrast to the previous intention-to-treat analysis of the same data, but agrees with
previous non-randomized registry data. This shows limitations of non-randomized or non-intention-totreat analyses.
© 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
Drugs like epinephrine and amiodarone are still recommended
in the current international guidelines of Advanced Life Support
(ALS) during cardiac arrest,1,2 although their outcome benefit on
survival to hospital discharge is debated. Especially, the use of
adrenaline is questioned.3 In intention-to-treat analysis in a randomized controlled out-of-hospital cardiac arrest (OHCA) study,
the intravenous line insertion and drug administration group had
improved short term outcome without improved survival rate to
夽 A Spanish translated version of the summary of this article appears as Appendix
in the final online version at doi:10.1016/j.resuscitation.2011.11.011.
∗ Corresponding author at: Department of Anaesthesiology, Oslo University Hospital, PB 4956 Nydalen, N-0424 Oslo, Norway. Tel.: +47 23016837/41419930;
fax: +47 23016799.
E-mail address: [email protected] (T.M. Olasveengen).
0300-9572/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.resuscitation.2011.11.011
hospital discharge.4 A before and after Canadian study of OHCA
similarly failed to find any change in outcome after introducing
intravenous drug administration and endotracheal intubation into
local resuscitation protocols.5 In a large Swedish OHCA registry
study, which included patients where some ambulance personnel were allowed to give adrenaline and some were not, patients
receiving adrenaline were 57% less likely to be alive after one
month in a multivariate logistic regression analysis adjusting for
all known confounders compared to those who had not received
adrenaline.6
This apparent contrast in results could be due to various factors. Non-randomized registry studies do not intend to prove
causality, and there might be unknown factors not adjusted
for in regression analysis. Patients with rapid return of spontaneous circulation (ROSC) such as those with ventricular fibrillation
(VF) and ROSC after the first defibrillation attempt might never
have had time for adrenaline injection. These patients, with
very good prognosis, would thereby end in the no-drug group
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T.M. Olasveengen et al. / Resuscitation 83 (2012) 327–332
impacting on the data interpretation. Our randomized study
was analyzed on an intention-to-treat basis.4 As expected; some
patients in the intravenous group had achieved ROSC before
adrenaline could be given, while some in the no-intravenous
group received adrenaline for different reasons. For example, it
was permitted to place the IV line 5 min after ROSC. If re-arrest
occurred, adrenaline could be administered if indicated by the CPR
guidelines.7
Non-randomized, observational registry data from before and
after studies are often used to explore therapeutic issues in cardiac arrest. These studies always compare when a certain therapy
was actually administered vs. when it was not. Although many
confounding factors may be identified in clinical registry data, significant unknown factors may exist. We have therefore performed
a post hoc analysis of our previously published data4 comparing
outcomes for patients who actually received adrenaline to those
who did not, and included a multivariate regression analysis as in
the Swedish registry study.6
2.3. Equipment and data collection
Standard LIFEPAK 12 defibrillators (Physio-Control, Medtronic,
Redmond, WA, USA) were used, and ECGs with transthoracic
impedance signals were transferred to a hospital server. Data were
documented according to Utstein style as abstracted from Utstein
cardiac arrest forms,11 ambulance run sheets and hospital records.
Automated, computer based dispatch centre time records supplement ambulance run sheets with regards to response intervals.
Administrations of all relevant intravenous drugs including
doses administered were documented on the ambulance run
sheets.
Primary end point was survival to hospital discharge. Secondary
endpoints were return of spontaneous circulation, survival to hospital admission, and neurologic outcome at hospital discharge for
survivors (using cerebral performance categories 1–4).11 The study
was externally monitored.
2.4. Data processing
2. Materials and methods
We conducted a prospective cohort study using clinical trial
population.4 The randomized trial was designed to evaluate the
effect of intravenous access and medication in cardiac arrest resuscitation.
2.1. Description of emergency medical services (EMS) and
in-hospital treatment
Until January 2006 the one-tiered Oslo EMS system with
paramedics and one physician-manned ambulance followed the
International ALS Guidelines 20008 with the modification that
patients with VF received 3 min of CPR before first shock and
between unsuccessful series of shocks.9 Guidelines 20057 were
implemented January 2006 with the same modification of 3 min
periods of CPR. Manual mode defibrillation and endotracheal intubation were standard procedures. Two ambulances are routinely
dispatched when cardiac arrest is suspected. The physician manned
ambulance is dispatched whenever available.
All hospitals in Oslo have goal directed post-resuscitation protocols including therapeutic hypothermia for all actively treated
patients.10 If coronary angiography is indicated from prehospital 12
lead electrocardiogram (ECG) for possible percutaneous coronary
intervention (PCI), patients are transported to one of two university
hospitals with this capacity 24 h/day.
Ventilations and chest compressions were determined from
changes in transthoracic impedance using CODE-STATTM 7.0
(Physio-Control, Redmond, WA, USA) and added to the written
information from patient report forms. Time without spontaneous circulation, time without compressions during time without
spontaneous circulation (hands-off time), pre-shock pauses, compression rate and actual number of compressions and ventilations
per minute were calculated for each episode. Hands-off ratio is
defined as hands-off time divided by total time without spontaneous circulation.
2.5. Statistical analysis
Demographic
and
clinical
data
are
presented
as
means ± standard deviation (SD), medians with 25 percentile
and 75 percentile (25p, 75p) or proportions. Crude associations
between the two trial arms and survival were quantified by
odds ratio (OR) with 95% confidence interval (CI). For continuous
variables, Student’s t test was used for normally distributed data
and Mann–Whitney U test for not normally distributed data.
Potential confounders were identified and adjusted for using
logistic regression. An investigation of the correlation between
potential confounders was performed. P-values less than 0.05 were
considered significant
3. Results
3.1. Patient allocation (Fig. 1).
2.2. Study design and recruitment
All patients older than 18 years with non-traumatic, nonambulance witnessed OHCA of all causes in Oslo between May
1st 2003 and April 28th 2008 were randomized to receive either
ALS with intravenous access and drugs (IV group) or ALS without
intravenous access and drugs (No-IV group). Intravenous access
was to be established 5 min after ROSC regardless of randomization, and drugs could then be given if indicated. In the present post
hoc study patients who actually received adrenaline were allocated
to the adrenaline group and those who did not receive adrenaline
were allocated to the no adrenaline group using information from
ambulance run sheets.
The original study was registered at clinicaltrials.gov
(NCT00121524) and approved by the regional ethics committee. Informed consent for inclusion was waived as decided by
this committee, but was required from survivors with 1-year
follow-up.
Resuscitation was attempted in 1183 patients, and 851 of 946
those eligible were successfully randomized. Thirty-seven of 433
patients randomized to the No-IV arm received adrenaline and 85
of 418 patients randomized to the IV arm did not receive adrenaline.
Three cases were excluded as we were unable to determine drug
administration, leaving 367 patients in the adrenaline group and
481 patients in the no-adrenaline group.
Table 1.
3.2. Baseline demographics and CPR quality (Table 1).
There was no difference in proportion of patients presenting
with VF between the two post hoc study groups, while fewer
patients presenting with asystole received adrenaline (OR 0.7 CI
0.6, 1.0 vs. the no-adrenaline group) and more patients presenting
with PEA tended to receive adrenaline (OR 1.4 CI 1.0, 2.0 vs. the noadrenaline group). Quality of CPR was similar and within guideline
T.M. Olasveengen et al. / Resuscitation 83 (2012) 327–332
329
Table 1
Demographics and quality of cardiopulmonary resuscitation (CPR).
No Adrenaline (n = 481)
Age (years)
Males (%)
Cardiac aetiology (%)
Location of arrest
Home
Public
Other
Bystander witnessed
Bystander BLS
Initial Rhythm
VF/VT
Asystole
PEA
Physician manned ambulance present
Response interval (min)
Intubation
Other IV drugs during resuscitation
-Atropine
-Amiodarone
Defibrillation
No. of Shocks
No. of Shocks when defibrillated
ECG available for analysis
-CPR duration (min)
-Hands off ratio
-Compression rate
-Compressions min−1
-Ventilations min−1
-Pre-shock pause (sec)
Adrenaline (n = 367)
Odds ratio (95% CI)
p-value
66 (54, 78)
337 (70)
337 (70)
66 (54, 78)
266 (73)
265 (72)
1.1 (0.8, 1.5)
1.1 (0.8, 1.5)
0.45
0.55
268 (56)
173 (36)
38 (8)
313 (65)
300 (62)
205 (56)
129 (35)
33 (9)
241 (66)
233 (64)
1.0 (0.8, 1.3)
1.0 (0.7, 1.3)
1.2 (0.7, 1.9)
1.0 (0.8, 1.4)
1.1 (0.8, 1.4)
1.00
0.86
0.66
0.91
0.79
156 (32)
253 (53)
72 (15)
171 (36)
9 (7, 12)
387 (81)
128 (35)
166 (46)
73 (20)
145 (40)
10 (7, 12)
341 (93)
1.1 (0.8, 1.5)
0.7 (0.6, 1.0)
1.4 (1.0, 2.0)
0.50
0.04
0.07
0.28
0.88
< 0.001
10 (2)
9 (2)
171 (36)
0 (0,1)
2 (1, 4)
352 (73)
16 (11, 21)
.16 (.09, .023)
117 (110, 122)
95 (86, 103)
11 (8, 13)
12 (3, 18)
204 (56)
77 (21)
182 (50)
1 (0, 3)
3 (2, 6)
288 (79)
25 (15, 31)
.17 (.09, .23)
118 (111, 124)
94 (87, 104)
11 (9, 14)
12 (3, 21)
3.2 (2.0, 5.0)
59.7 (30.9, 115.4)
14.0 (6.9, 28.4)
1.8 (1.4, 2.4)
<0.001
<0.001
<0.001
<0.001
<0.001
0.09
<0.001
0.91
0.33
0.84
0.004
0.35
VF = ventricular fibrillation. VT = pulseless ventricular tachycardia, PEA = pulseless electrical activity, IV = intravenous, ECG = electrocardiogram, Hands-off = proportion of time
without chest compressions during the resuscitation effort, compression rate = rate of compressions when delivered, compressions min−1 = average number of compressions
actually given per minute during resuscitation effort. All categorical variables given as numbers (percentages in parenthesis). Continuous variables are given as medians with
interquartile range. Differences between groups were analyzed using chi-squared with continuity correction and odds ratio with 95% confidence intervals for categorical
data, and Students t-tests or Mann–Whitney U-tests for continuous data as appropriate.
recommendations for both groups, but patients in the adrenaline
group were more likely to be intubated (OR 3.2 CI 2.0, 5.0) and
defibrillated (OR 1.8 CI 1.4, 2.4) and had longer resuscitation efforts
(25 vs. 16 min, p < 0.001) than those not receiving adrenaline.
3.3. In-hospital treatment and outcome (Tables 2–4).
Patients in the adrenaline group were more likely to be admitted to hospital and an intensive care unit compared to the
no-adrenaline group (OR 2.5 CI 1.9, 3.4 and OR 1.4 CI 1.0, 1.9,
respectively). In the adrenaline group only one patient was awake
on hospital admission compared to 13% in the no-adrenaline
group (p = 0.002). Patients in the adrenaline group received angiography/percutaneous coronary intervention less often than the
no-adrenaline group (OR 0.1 CI 0.0, 0.5 and OR 0.4 CI 0.2, 0.7, respectively). Regarding outcome, patients in the adrenaline group were
less likely to be discharged from hospital, less likely to be discharged with favourable neurological outcome and less likely to
be alive one year after cardiac arrest (odds ratios for adrenaline vs.
no-adrenaline groups were 0.5 CI 0.3; 0.8, 0.4 CI 0.2, 0.7; and 0.5 CI
0.3, 0.8, respectively). (Table 2)
Patients were divided into two predefined subgroups based on
their initial rhythms (Table 3). Patients in the adrenaline group presenting with VF or pulseless VT were less likely to be admitted to
intensive care (OR 0.6 CI 0.4, 1.0), discharged alive (OR 0.3, CI 0.2,
0.6), and discharged with favourable neurological outcome (OR 0.3,
CI 0.1, 0.5) compared to the no-adrenaline group. Patients in the
adrenaline group presenting with asystole or PEA were more likely
to achieve ROSC (OR 5.1 CI 3.2, 8.1) and be admitted to an intensive
care unit (OR 3.3 CI 2.0, 5.4), but were no more likely to be discharged alive compared to the no-adrenaline group (OR 0.9 CI 0.3,
3.2). (Table 3).
Ventricular fibrillation, response interval, witnessed arrest,
gender, age and endotracheal intubation were identified as confounding factors in the multivariate logistic regression analysis.
After adjusting for confounders, patients in the adrenaline group
had a 48% lower chance of survival with adjusted odds ratio 0.52
(CI 0.29, 0.92) compared to the no-adrenaline group. (Table 4).
4. Discussion
The results from our previously published randomized controlled trial of intravenous access and drugs administration during
OHCA would suggest that an EMS system opting to include intravenous drug administration in their cardiac arrest treatment
protocol could expect increased survival to hospital admission,
but no increase in survival to hospital discharge. In this post
hoc analysis the actual use of adrenaline was associated with
increased short-term survival, but with 48% less survival to hospital discharge. This negative association with survival is very
similar to the multivariate analysis of observational Swedish registry data where patients receiving adrenaline were 57% less
likely to be alive after one month.6 Our findings are also consistent with previous studies evaluating effects of amiodarone,12
atropine13 , adrenaline14 and high-dose adrenaline,15 all of which
indicated improved short term effects such as survival to hospital
or intensive care unit (ICU) admission without improved long-term
outcome.
An important lesson learned from the present analysis is the
limitations of such post hoc analysis when attempting to elucidate
causal relationships from non-randomized data, and even more
so in registry studies as appropriately discussed in the previous
Swedish paper.6 Some patients randomized to adrenaline never
received it as they had ROSC before the drug could be given, thus
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T.M. Olasveengen et al. / Resuscitation 83 (2012) 327–332
Table 2
In-hospital treatment and outcome.
Admitted to hospital
-with ROSC
-with ongoing CPR
Admitted to ICU
-Awake on admission ICU
-Therapeutic hypothermia
-Angiography/PCI
-No. of days in ICUa
Cause of death in ICU: b
-brain death
-cardiac death
-multi-organ failure
Discharged alive
Discharged with CPC 1–2
CPC 1
CPC 2
CPC 3
CPC 4
Discharged if admitted ICU
Alive 1 year after cardiac arrestc
No Adrenaline (n = 481)
Adrenaline (n = 367)
Odds ratio (95% CI)
p-value
128 (27)
115 (24)
13 (3)
108 (23)
14 (13)
74 (69)
58 (54)
5 (3, 9)
175 (48)
106 (29)
69 (19)
104 (28)
1 (1)
77 (74)
35 (33)
4 (2, 7)
2.5 (1.9, 3.4)
1.3 (0.9, 1.8)
8.3 (4.5, 15.3)
1.4 (1.0, 1.9)
0.1 (0.0, 0.5)
1.3 (0.7, 2.4)
0.4 (0.2, 0.7)
<0.001
0.12
<0.001
0.06
0.002
0.46
0.003
0.023
29 (71)
6 (15)
6 (15)
60 (13)
57 (11)
51
6
2
1
56%
56 (12)
52 (69)
14 (19)
9 (12)
24 (7)
19 (5)
16
3
4
1
23%
21 (6)
0.9 (0.4, 2.2)
1.3 (0.5, 3.8)
0.8 (0.3, 2.4)
0.5 (0.3, 0.8)
0.4 (0.2, 0.7)
1.00
0.77
0.91
0.006
0.001
0.2 (0.1, 0.4)
0.5 (0.3, 0.8)
<0001
0.004
IV = intravenous, ROSC = return of spontaneous circulation, CPR = cardiopulmonary resuscitation, ICU = intensive care unit, PCI = percutaneous coronary intervention,
CPC = cerebral performance score. CPC 1: good cerebral performance, CPC 2: moderate cerebral disability, CPC 3: severe cerebral disability, CPC 4: coma or vegetative
state. All categorical variables given as numbers (percentages in parenthesis). No. of days in ICU is not normally distributed, and is given as median interquartile range. Differences between groups were analyzed using chi-squared with continuity correction and odds ratio with 95% confidence intervals for categorical data, and Mann–Whitney
U-test for no. of days in ICU. Proportions of “awake on admission to ICU”,“therapeutic hypothermia”, “Angiography/PCI” and “number of days in ICU” are reported for patients
admitted ICU only. Proportions “brain death”, “cardiac death” and “multi-organ failure” reported for patients who died in ICU only.
a
Data missing for 6 patients, 2 in no-adrenaline and 4 in adrenaline group.
b
Data missing for 12 patients, 7 in no-adrenaline and 5 in adrenaline group.
c
3 patients lost to 1 year follow up, 2 patients in the no adrenaline group.
Table 3
Outcome for VF/pulseless VT (n = 284) and Non-VF/pulseless VT subgroups (n = 564).
First rhythm VF/pulseless VT
Admitted to hospital
Admitted to ICU
Discharged alive
Discharged with CPC 1–2
Discharged if admitted ICU
No adrenaline (n = 156)
Adrenaline (n = 128)
Odds ratio (95% CI)
p-value
92 (59)
82 (53)
53 (34)
51 (33)
65%
80 (63)
51 (40)
18 (14)
15 (12)
35%
1.2 (0.7, 1.9)
0.6 (0.4, 1.0)
0.3 (0.2, 0.6)
0.3 (0.1, 0.5)
0.3 (0.1, 0.6)
0.63
0.04
<0.001
<0.001
0.002
First rhythm asystole or pulseless electrical activity
Admitted to hospital
Admitted to ICU
Discharged alive
Discharged with CPC 1–2
Discharged if admitted ICU
No adrenaline (n = 325)
Adrenaline (n = 239)
Odds ratio (95% CI)
p-value
36 (11)
26 (8)
7 (2.2)
6 (1.8)
27%
95 (40)
53 (22)
6 (2.5)
4 (1.7)
11%
5.3 (3.4, 8.1)
3.3 (2.0, 5.4)
1.2 (0.4, 3.5)
0.9 (0.3, 3.2)
0.3 (0.1, 1.2)
<0.001
<0.001
1.00
1.00
0.15
VF = ventricular fibrillation, VT = pulseless ventricular tachycardia, IV = intravenous, ICU = intensive care Unit, CPC = cerebral performance score. All categorical variables given
as numbers (percentages in parenthesis). Differences between groups were analyzed using chi-squared with continuity corrections.
yielding a selection bias with the most easily resuscitated patients
in the post hoc no-adrenaline group. On the other hand, Fig. 1 illustrates that at least 1 of 5 patients randomized to receive IV access
and drugs did not receive adrenaline as it was regarded futile or it
was impossible to gain intravenous access. At the same time 1 of 10
patients randomized to not receive drugs received adrenaline after
they had regained spontaneous circulation for > 5 min.
In a single centre double blinded randomized study Jacobs et
al. recently reported increased rate of ROSC with adrenaline vs.
placebo (24% vs. 8%) with no difference in hospital discharge rate
Table 4
Multivariate logistic regression analysis: Adjusted effect on survival when controlling for confounders.
Initial VF/VT
Witnessed arrest
Male gender
Age (per increased year)
Response interval (per increased minute)
Adrenaline
Intubation
Odds Ratio Survival
95% CI
p-value
15.60
2.33
1.59
0.96
0.81
0.52
0.38
7.75, 31.41
1.08, 5.01
0.79, 3.20
0.95, 0.98
0.75, 0.88
0.29, 0.92
0.20, 0.72
<0.001
0.031
0.193
<0.001
<0.001
0.024
0.003
VF = ventricular fibrillation. VT = pulseless ventricular tachycardia. 95% CI = confidence interval.
T.M. Olasveengen et al. / Resuscitation 83 (2012) 327–332
331
Fig. 1. Patient allocation. IV = intravenous. ROSC = return of spontaneous circulation.
(4% vs. 2%). The low rates of ROSC (especially in the placebo group)
and survival in the Australian study with rates of initial shockable rhythm and ambulance response times relatively similar to the
present study makes a comparison difficult, and no data on quality
of CPR are reported.16
Quality of CPR is a known confounder when studying drug
effects during cardiac arrest in animal models.17 As quality was
similar and adequate for both groups, this is less likely to have
influences our results. Adrenaline is well known to facilitate return
of spontaneous circulation, but is also associated with increased
post-resuscitation myocardial dysfunction in animals.18 Negative
post-resuscitation effects of adrenaline are also reported to be
more prominent after longer, more clinically relevant arrest periods (4–6 min) than short arrest periods (2 min) in experimental
models.19 These experimental data might partly explain our clinical
observations.
We believe that intention-to-treat analysis of randomized
trials is the gold standard when creating clinical guidelines.
This does not implicate that continuous quality improvement
models cannot be extremely helpful as recently pointed out
by Sanders,20 or that large registry databases do not provide
helpful information. All approaches have advantages and limitations; the present report highlights some limitations of post hoc
analysis.
With the present post-ROSC treatment regimes, the general use
of adrenaline during CPR does not seem important for long-term
outcome. While more patients had improved short-term survival
with adrenaline both by intention-to-treat analysis and this post
hoc analysis of who actually received adrenaline, more patients did
not survive to hospital discharge. In fact, even among the patients
randomized to receive drugs, only 43% of the survivors received
adrenaline. The actual use of adrenaline may be a surrogate marker
for patients with bad prognosis, but that has previously only been
published from studies without a group randomized to not receiving drugs.21
Should patients presenting with initial shockable or nonshockable rhythms be treated differently? Effects of adrenaline
seem to vary between these groups, both in magnitude and direction. While there is no negative association between adrenaline and
short-term outcome in patients with shockable rhythms, long-term
survival was halved in those who received adrenaline compared
to those who did not. In a previous non-randomized study of
VF patients in Gothenburg, where only some ambulances were
allowed to use adrenaline, there was a higher rate of ROSC with
adrenaline, but no difference in long-term outcome.11 For nonshockable rhythms in the present study, there was a 2–3 fold
improvements in short-term outcome with no difference in longterm outcome. Several studies have identified dissimilar aetiologies
in shockable and non-shockable sub-groups,22–24 and it seems reasonable that differences in treatment strategies will emerge.25
As a limitation, we do not have reliable time points for IV line
establishment, adrenaline administration or ROSC. The first two
time points were not systematically registered, and we believe
the time points for spontaneous circulation to be too inaccurately
recorded. As the small ALS team is busy treating the patient, such
data are usually manually recorded with significant delay, and
defibrillator recordings were not synchronized with the automatic
dispatch and ambulance recordings. If such time points had been
accurate, we might have been able to adjust for more confounders
such as patients who did not receive IV drugs due to rapid establishment of ROSC. A subgroup study of patients who required more
than three defibrillation attempts would also be unreliable due to
the limited number of patients plus the change in defibrillation
strategy from guidelines 2000 to guidelines 2005 in the middle
of the study. Early administration of adrenaline, as recently advocated, 26,27 must be evaluated in systems with shorter ambulance
response times or other drug regimes and priorities than present
guidelines. Further, this is a single centre study and the results may
not be generalized to other EMS systems with different training,
infrastructure and treatment protocols.
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T.M. Olasveengen et al. / Resuscitation 83 (2012) 327–332
5. Conclusions
Receiving adrenaline was associated with improved shortterm survival, but decreased survival to hospital discharge
and survival with favourable neurological outcome after
OHCA. This post hoc survival analysis is in contrast to the
previous intention-to-treat analysis of the same data, but
agrees with previous non-randomized registry data. This
shows limitations of non-randomized or non-intention-to-treat
analyses.
Conflict of interest
Olasveengen and Sunde have no conflicts to declare. Steen is
a member of the board of directors for Laerdal Medical and The
Norwegian Air Ambulance. Wik is the principle investigator for
a multi-centre mechanical chest compression device study sponsored by Zoll.
Acknowledgements
We thank all physicians and paramedics working in the
Oslo EMS Service. The study was supported by grants from
South-Eastern Norway Regional Health Authority, Oslo University
Hospital, Norwegian Air Ambulance Foundation, Laerdal Foundation for Acute Medicine and Anders Jahres Fund.
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