REVIEW

CURRENT
OPINION Is there a role for adrenaline during
cardiopulmonary resuscitation?
Jerry P. Nolan a and Gavin D. Perkins b

Purpose of review
To critically evaluate the recent data on the influence adrenaline has on outcome from cardiopulmonary
resuscitation.
Recent findings
Two prospective controlled trials in out-of-hospital cardiac arrest (OHCA) have indicated that adrenaline
increases the rate of return of spontaneous circulation (ROSC), but neither was sufficiently powered to
determine the long-term outcomes. Several observational studies document higher ROSC rates in patients
receiving adrenaline after OHCA, but these also document an association between receiving adrenaline
and worse long-term outcomes.
Summary
Appropriately powered prospective, placebo-controlled trials of adrenaline in cardiac arrest are essential if
the role of this drug is to be defined reliably.
Keywords
adrenaline, cardiopulmonary resuscitation, epinephrine, outcome, return of spontaneous circulation

INTRODUCTION Liaison Committee on Resuscitation stated:

Adrenaline has been an integral component of
advanced life support from the birth of modern
cardiopulmonary resuscitation (CPR) in the early
1960s. In guidelines written originally in 1961, Safar
[1] recommended the use of very large doses of
adrenaline: 10 mg intravenously or 0.5 mg intra-
cardiac. When injected during cardiac arrest, adre-
naline increases aortic relaxation (diastolic) pressure
and, in animal studies, thereby augments coronary
and cerebral blood flow [2,3]. In contrast, another
animal study has shown that although adrenaline
improves myocardial blood flow during ventricular
fibrillation cardiac arrest, it does not improve the
myocardial oxygen balance (measured by determin-
ing intramyocardial adenosine triphosphate and
lactate values) [4]. Recent prospective, randomized
& &&
trials [5,6 ] and observational studies [7 ,8,9] have
challenged the value of using adrenaline in cardiac
arrest, and this view is supported by the findings
from systematic reviews of vasopressors in cardiac
&&
arrest [10 ,11]. These and other relevant studies are
discussed in detail in this review.
CURRENT GUIDELINES
The treatment recommendation on the use of
vasopressors published in 2010 by the International
Although there is evidence that vasopressors (adre-
naline or vasopressin) may improve return of spon-
taneous circulation (ROSC) and short-term survival,
there is insufficient evidence to suggest that vaso-
pressors improve survival to discharge and neuro-
logical outcome. There is insufficient evidence to
suggest the optimal dosage of any vasopressor in the
treatment of adult cardiac arrest. Given the observed
benefit in short-term outcomes, the use of adrena-
line or vasopressin may be considered in adult car-
diac arrest [12].
The 2010 European Resuscitation Council (ERC)
guidelines for ventricular fibrillation/pulseless ven-
tricular tachycardia cardiac arrest stated: give adre-
naline after the third shock once chest compressions
have resumed, and then repeat every 35 min
during cardiac arrest (alternate cycles) [13]. If the
initial monitored rhythm is pulseless electrical
a
Royal United Hospital, Bath and bUniversity of Warwick, Heart of
England NHS Foundation Trust, Coventry, UK
Correspondence to Jerry P. Nolan, FRCA, FCEM, FRCP, FFICM, Con-
sultant in Anaesthesia and Intensive Care Medicine, Royal United Hos-
pital, Combe Park, Bath, BA1 3NG, UK. Tel: +44 1225 825056; e-mail:
jerry.nolan@nhs.net
Curr Opin Crit Care 2013, 19:169174
DOI:10.1097/MCC.0b013e328360ec51

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 Cardiopulmonary resuscitation
KEY POINTS

When given during cardiac arrest, adrenaline
increases aortic relaxation pressure and increases
coronary and cerebral perfusion pressure.

Adrenaline increases the chances of achieving return of
spontaneous circulation.

There is no evidence of long-term benefit for adrenaline
in cardiac arrest and observational studies suggest that
its long-term outcomes may be worse.

Large, placebo-controlled clinical trials are essential.
activity (PEA) or asystole, give adrenaline 1 mg as
soon as venous access is achieved. These guidelines
are followed by healthcare professionals throughout
most of Europe and in many other countries.
RANDOMIZED CONTROLLED TRIALS OF
ADRENALINE COMPARED TO PLACEBO
A trial published in 1995 compared adrenaline
10 mg with placebo in 194 cardiac arrest patients
[14]. Although the trial was conducted in hospital, it
included in-hospital and out-of-hospital cardiac
arrests. An additional 145 patients who were eligible
but not randomized received adrenaline 1 mg and
were included in the analysis. There was no differ-
ence in the immediate survival or survival to hos-
pital discharge between those receiving adrenaline
1 or 10 mg, or placebo, but the poor quality of the
study design makes it impossible to draw any
reliable conclusions.
In a study undertaken in Oslo, Norway, 851
patients with out-of-hospital nontraumatic cardiac
arrest (all rhythms) were randomized to intravenous
cannulation with injection of drugs (including adre-
naline) vs. no intravenous cannula or drugs until
after ROSC had been achieved [5]. The patients in
the intravenous group had a higher rate of ROSC
(40 vs. 25%; P < 0.001), hospital admission (43 vs.
29%; P < 0.001) and admission to the intensive care
unit (ICU) (30 vs. 20%; P 0.002). The higher rate of
ROSC was seen only in the patients with initial
nonshockable rhythms (asystole and PEA): 29 vs.
11% (P < 0.001); the rate of ROSC was 59 vs. 53%
(P 0.35) in those patients with an initial rhythm
of ventricular fibrillation/ventricular tachycardia.
There was no significant difference in survival to
hospital discharge between the intravenous and no
intravenous groups (10.5 vs. 9.2%; P 0.61). The
survival with favourable outcome [cerebral perform-
ance category (CPC) 12: 9.8 vs. 8.1%; P 0.45] and
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the survival at 1 year (10 vs. 8%; P 0.53) did not
differ significantly between the groups. There was
no difference between the groups in the quality of
CPR (hands-off ratio, median: 15 vs. 14%; P 0.16)
and, importantly, in both groups therapeutic
hypothermia was used in just over 70% of those
admitted to the ICU. These results were based,
correctly, on an intention-to-treat analysis, and
many patients allocated to the intravenous drug
group did not actually receive adrenaline. Further-
more, the study included the use of all drugs vs. no
drugs it was not simply an adrenaline vs. no
adrenaline trial.
In a post hoc analysis of this Norwegian study,
outcomes were examined according to whether the
&
patient had actually received adrenaline [15 ]. Treat-
ment with adrenaline (n 367) was associated
with a greater chance of being admitted to hospital
[odds ratio (OR) 2.5; 95% confidence interval (CI)
1.93.4]. However, the chance of survival to hospi-
tal discharge was reduced by half in those given
adrenaline [24 of 367 (7%) vs. 60 of 481 (13%);
OR 0.5; 95% CI 0.30.8] as were the number of
neurologically intact (CPC 1 or 2) survivors [19 of
367 (5%) vs. 57 of 481 (11%); OR 0.4; 95% CI 0.2
0.7]. These effects persisted after adjustment for con-
founding factors (ventricular fibrillation, response
interval, witnessed arrest, sex, age and tracheal intu-
bation). Although these results are of interest, a per
protocol analysis is likely to introduce unmeasured
bias, making reliable interpretation difficult.
The only double-blind, randomized placebo-
controlled trial of adrenaline in out-of-hospital car-
diac arrest (OHCA) was undertaken in Western Aus-
&
tralia [6 ]. The primary endpoint of this study was
survival to hospital discharge and the investigators
had planned originally to enrol 5000 patients
based on the power calculation using this endpoint.
Unfortunately, several ambulance services were
unable to participate and ultimately only 601 out
of 4103 patients screened for inclusion underwent
randomization and, of these, 534 were included in
the final analysis. The rate of ROSC was three times
higher in those receiving adrenaline [64 of 272
(23.5%) vs. 22 of 262 (8.4%); OR 3.4; 95% CI 2.0
5.6]. Survival to hospital discharge was no different
between the groups: adrenaline 11 (4.0%) vs.
placebo 5 (1.9%; OR 2.2; 95% CI 0.76.3). Unlike
the Norwegian study, this Australian study docu-
mented higher ROSC rates with adrenaline in both
shockable and nonshockable rhythms. This study
ended up being grossly underpowered for the
primary outcome (survival to hospital discharge)
and it leaves the resuscitation community uncertain
about the role of adrenaline in the treatment of
cardiac arrest.
Volume 19
Number 3
June 2013

OBSERVATIONAL TRIALS OF ADRENALINE
IN CARDIOPULMONARY RESUSCITATION
Prehospital randomized placebo-controlled trials
are challenging to undertake as evidenced by the
&
experience of Jacobs et al. [6 ]. Observational studies
enable large quantities of data to be collected, but
they rely on statistical risk adjustment to remove the
inherent biases. The Swedish ambulance cardiac
arrest registry was started in 1990. A multivariate
analysis (including age, sex, place of arrest,
bystander CPR, initial arrhythmia, witnessed and
cause) of this registry (n 10 966) published in
2002 documented a lower 1-month survival
amongst the 42.4% of patients who received adrena-
line (OR 0.43; 95% CI 0.270.66) [16]. The impact of
adrenaline on survival to discharge after OHCA was
evaluated in a before-and-after study undertaken
during 20022004 in Singapore [9]. There was no
significant difference in survival to discharge in the
preadrenaline phase compared with the adrenaline
phase (1.0 vs. 1.6%; OR 1.7; 95% CI 0.64.5). In
contrast to many other studies, in this study, there
was also no difference in the rate of ROSC between
the two phases (preadrenaline 17.9% vs. adrenaline
15.7%; OR 0.9; 95% CI 0.61.2). One of several
limitations of this study was that only 44.2% of
patients actually received adrenaline in the adrena-
line phase. The Ontario Prehospital Advanced Life
Support (OPALS) study also used a before-and-after
design to evaluate the impact of adding tracheal
intubation and drug administration to an optimized
rapid defibrillation programme [17]. The rate of
admission to hospital increased significantly in
the advanced life support (ALS) phase [152 of
1391 (10.9%) vs. 621 of 4247 (14.6%); P < 0.001],
but the rate of survival to hospital discharge was
Table 1. Outcome based on multivariate analyses of patients with out-of-hospital cardiac arrest according to
adrenaline administration, 20052008, Japan
Adrenaline
Outcome Total cases n (%)
ROSC
Unadjusted 417 155 2786 (18.5)
Adjusteda 391 046 2556 (18.6)
1-Month survival
Unadjusted 417 186 805 (5.4)
a
Adjusted 391 046 733 (5.3)
CPC 1 or 2
Unadjusted 417 187 205 (1.4)
Adjusteda 391 046 187 (1.4)
CPC, cerebral performance category; ROSC, return of spontaneous circulation. Data from [7 ].
a
Adjusted for age, sex, bystander witnessed, cause, bystander CPR (by type), presence of emergency life-saving technician, presence of physician in ambulance,
advanced life support performed by physician, intervals, first documented rhythm, defibrillation, advanced airway, intravenous cannulation.
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Role for adrenaline Nolan and Perkins
unchanged [69 (5.0%) vs. 217 (5.1%); P 0.83].
During the ALS phase, 95.8% of patients received
adrenaline. Given that other drugs and tracheal
intubation were also included in the ALS phase, it
is difficult to make firm conclusions about the
impact of adrenaline, but the results are notably
similar to those documented in the later prospective
controlled studies.
In a single-centre study from Fukuoka, Japan,
492 patients with OHCA were analysed retrospec-
tively and divided into those receiving adrenaline
(n 49) and those not receiving adrenaline (n 443)
before arrival at hospital [8]. There was no difference
in the rates of ROSC or survival to hospital dis-
charge, but given the very few patients receiving
adrenaline before hospital arrival, the study is
grossly underpowered to determine any meaningful
outcomes.
The largest observational study to date on the
use of adrenaline in cardiac arrest involves 417 188
&&
OHCAs in Japan (Table 1) [7 ]. In propensity-
matched (statistical adjustment for potential con-
founders) patients, use of adrenaline was associated
with a ROSC rate 2.5 times higher (adjusted OR 2.51;
95% CI 2.242.80; P < 0.001), but a 1-month sur-
vival rate approximately half of that achieved in
those not given adrenaline (adjusted OR 0.54; 95%
CI 0.430.68; P < 0.001). Although this is a very large
study and the authors have made great efforts to
eliminate bias by using multiple and comprehensive
statistical analyses, there is still a strong possibility
that hidden confounders account for their findings.
Another limitation is that generalizability is limited
by the fact that in both groups the rate of survival
with good neurological outcome is much lower than
those reported from most other countries [18].
No adrenaline Odds ratio
n (%) (95% CI)
23 042 (5.7) 3.75 (3.593.91)
21 629 (5.7) 2.36 (2.222.50)
18 906 (4.7) 1.15 (1.071.23)
17 677 (4.7) 0.46 (0.420.51)
8903 (2.2) 0.61 (0.530.70)
8329 (2.2) 0.31 (0.260.36)
&&
www.co-criticalcare.com 171
 Cardiopulmonary resuscitation
The Resuscitation Outcomes Consortium (ROC)
Investigators analysed drug use amongst 16 221
OHCAs attended by 74 emergency medical services
(EMS) agencies [19]. Adrenaline was used in approxi-
mately 80% of ALS-treated cardiac arrests and there
was an inverse association between adrenaline dose
and survival to discharge; however, this finding was
unadjusted for confounders.
In another observational study from the Osaka
group in Japan, investigators studied the impact of
timing of adrenaline administration in OHCA [20].
Of 3161 patients analysed, 1013 (32.0%) received
adrenaline. Those receiving adrenaline had a signifi-
cantly lower rate of neurologically intact (CPC 1 or
2) 1-month survival than those not receiving adre-
naline (4.1 vs. 6.1%, P 0.028). In patients with an
initial rhythm of ventricular fibrillation, those
receiving adrenaline within 10 min of the call time
had a higher rate of neurologically intact 1-month
survival compared with those not receiving adre-
naline [6 of 9 (66.7%) vs. 75 of 301 (24.9%); OR
6.03; 95% CI 1.524.7], but there are so few
patients receiving early adrenaline that it is
impossible to draw reliable conclusions about the
timing of adrenaline administration and its impact
on outcome.
RATIONALIZING THE FINDINGS FROM
RANDOMIZED CONTROLLED TRIALS AND
OBSERVATIONAL STUDIES
Taken together, the findings from randomized trials
and observational studies indicate that giving adre-
naline in OHCA increases the rate of ROSC, but that
longer term outcomes (survival to hospital dis-
charge and neurologically favourable survival) are
either worse or, at best, neutral. The observational
studies showing worse long-term outcome after
adrenaline administration may be misleading if
there are confounders that have not been fully
adjusted for in the statistical analyses. For example,
most of these studies do not adjust for the duration
of the resuscitation attempt; yet, patients who
respond rapidly to initial treatment (e.g. defibrilla-
tion) will have the best outcomes. In general, only
those with longer resuscitation attempts might be
expected to receive adrenaline.
Alternatively, it is entirely possible that adrena-
line is genuinely harmful when given in cardiac
arrest. Of those patients who reach hospital alive
after OHCA, but who subsequently die before hos-
pital discharge, the majority die from neurological
&
injury [21,22 ]. Although adrenaline helps in
achieving ROSC, it may have adverse effects,
particularly on the brain, heart and immune system
that outweigh any of its short-term benefits.
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Reduced microvascular blood flow and
exacerbating cerebral injury
In a pig model of cardiac arrest, although adrenaline
increased mean aortic pressure during CPR, through
its alpha1-agonist action, it reduced cerebral micro-
circulatory blood flow and increased cerebral ischae-
mia (as determined by reduced cerebral oxygen
tension and increased cerebral carbon dioxide ten-
sion) [23]. Impaired microvascular blood flow was
seen to persist for several minutes after adrenaline
administration in a further animal study [24]. In
another pig study involving active compression
decompression CPR in combination with an impe-
dance threshold device, adrenaline increased coron-
ary perfusion pressure and cerebral perfusion
pressure, but carotid blood flow was decreased
[25]. Adrenaline was also associated with a decrease
in end-tidal carbon dioxide values, which the
authors ascribed to reductions in tissue perfusion.
Cardiovascular toxicity
Adrenaline also has adverse effects on the myo-
cardium mediated by b-receptor stimulation. In a
further analysis of the Norwegian intravenous vs. no
intravenous trial, ECG downloads were analysed
from 101 patients who received adrenaline and
73 who did not; all of these patients had an initial
&
rhythm of PEA [26 ]. Adrenaline increased the
frequency of transitions from PEA to ROSC and
extended the time window for ROSC to develop.
However, this was at a cost of greater cardiovas-
cular instability after ROSC, with a higher rate of
re-arresting. These observations are consistent with
other studies that link adrenaline with ventricular
arrhythmias and increased post-ROSC myocardial
dysfunction [27]. In human studies with patients
with sepsis [28] or acute lung injury [29], b-agonist
stimulation is similarly linked to cardiovascular
instability and reduced survival [30]. A systematic
review of b-blocker treatment in animal models of
cardiac arrest found fewer shocks were required for
defibrillation, myocardial oxygen demand was
reduced and postresuscitation myocardial stability
improved with fewer arrhythmias and improved
&
survival [31 ]. The same review identified several
case reports and two small prospective trials point
towards a beneficial effect of b-blockade in patients
presenting with cardiac arrest because of ventricular
fibrillation/ventricular tachycardia.
Metabolic effects
Adrenaline is associated with the development of
lactic acidosis [32]. High concentrations of lactate
and slow lactate clearance after ROSC are associated
Volume 19
Number 3
June 2013

with poor outcomes [33,34]. Adrenaline also indu-
ces stress hyperglycaemia which is associated with
poorer outcomes following cardiac arrest [35,36].
Immunomodulation and predisposition to
infection
Infective complications, especially early-onset pneu-
monia, are common after OHCA and associated with
worse outcomes [37]. In a single-centre observational
study, investigators carefully reviewed the case notes,
charts, laboratory and imaging results amongst
138 consecutive patients admitted to intensive care
&
following OHCA for evidence of infection [38 ]. Of
the 138 patients, 135 (97.8%) had at least one positive
marker of infection. Microbiological samples were
taken from 78 patients (56.5%), of which 43
(55.1%; 95% CI 44.165.7) were positive. Patients
treated with early antibiotics had better outcomes
[mortality rate 56.6% (30 of 53) compared with 75.3%
(64 of 85); P 0.025].
The use of therapeutic hypothermia has been
linked to an increased risk of infection [37]. There
is also a well recognized association between the
sympathetic nervous system and immune response.
b-Adrenoceptors are present on many of the cells
that contribute to innate immunity including
macrophages, T lymphocytes and neutrophils
[39]. Animal and human studies have documented
reductions in neutrophil chemotaxis [40], oxidative
burst, and degranulation in response to b-agonist
stimulation [41]. In addition, downregulation of
inflammatory cytokines (e.g. TNF-a, IL-8, IL-8 and
IL-1b) and increased release of anti-inflammatory
cytokines (e.g. IL-10) may reduce the host defence to
infection. It is possible these effects may contribute
to an increased susceptibility to postresuscitation
sepsis.
EFFECT OF DOSE
Another factor to be considered is the dose of
adrenaline. The current 1-mg bolus dose of adrena-
line was derived from animal studies in the 1960s
[4244]. Several studies have documented harm
from using higher doses of adrenaline [45], but there
have been no investigations of smaller doses (e.g.
1 mg/kg) or infusions of adrenaline in clinical studies
& during out-of-hospital cardiac arrest: a randomized trial. JAMA 2009; 302:
[26 ].
THE NEED FOR FUTURE TRIALS
The accumulating evidence highlights the urgent
need for further appropriately powered high-quality
randomized controlled trials. The emerging data
suggest several experimental strategies could be
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Role for adrenaline Nolan and Perkins
considered, including comparing adrenaline to
alpha2 agonists, adrenaline with b-blockade, lower
dose adrenaline or adrenaline as a continuous infu-
sion. We suggest the most pressing need is for a
definitive trial comparing standard dose adrenaline
(1 mg every 35 min) to placebo. Until there is
clarity about the effect of adrenaline on long-term
outcomes, the best comparator (placebo or standard
dose adrenaline) for future trials remains unknown.
CONCLUSION
Use of adrenaline in cardiac arrest increases the
chance of achieving ROSC, but randomized con-
trolled trials have failed to show that this is translated
into increased rates of survival to hospital discharge
and observational studies show an association
between adrenaline and worse long-term survival.
Appropriately powered placebo-controlled clinical
trials of adrenaline in cardiac arrest are essential to
determine whether patients benefit from being given
this drug [30,42]. In the mean time, current guide-
lines dictate that most patients with cardiac arrest
will continue to be given adrenaline.
Acknowledgements
None.
Conflicts of interest
J.P.N. and G.D.P. receive an honorarium as editor-in-
chief and editor of the journal Resuscitation.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 265).
1. Safar P. Community-wide cardiopulmonary resuscitation. J Iowa Med Soc
1964; 54:629635.
2. Michael JR, Guerci AD, Koehler RC, et al. Mechanisms by which epinephrine
augments cerebral and myocardial perfusion during cardiopulmonary resus-
citation in dogs. Circulation 1984; 69:822835.
3. Brown CG, Werman HA, Davis EA, et al. The effects of graded doses
of epinephrine on regional myocardial blood flow during cardiopulmonary
resuscitation in swine. Circulation 1987; 75:491497.
4. Ditchey RV, Lindenfeld J. Failure of epinephrine to improve the balance
between myocardial oxygen supply and demand during closed-chest resus-
citation in dogs. Circulation 1988; 78:382389.
5. Olasveengen TM, Sunde K, Brunborg C, et al. Intravenous drug administration
22222229.
6. Jacobs IG, Finn JC, Jelinek GA, et al. Effect of adrenaline on survival in out-of-
& hospital cardiac arrest: a randomised double-blind placebo-controlled trial.
Resuscitation 2011; 82:11381143.
To date, the only randomized, double-blind, placebo-controlled trial of adrenaline in
OHCA. It shows clearly that rates of ROSC are increased with adrenaline.
7. Hagihara A, Hasegawa M, Abe T, et al. Prehospital epinephrine use and
&& survival among patients with out-of-hospital cardiac arrest. JAMA 2012;
307:11611168.
A very large observational study with extensive statistical analyses showing
improved short-term outcomes, but worse long-term outcome with adrenaline.
www.co-criticalcare.com 173
 Cardiopulmonary resuscitation
8. Machida M, Miura S, Matsuo K, et al. Effect of intravenous adrenaline before
arrival at the hospital in out-of-hospital cardiac arrest. J Cardiol 2012;
60:503507.
9. Ong ME, Tan EH, Ng FS, et al. Survival outcomes with the introduction of
intravenous epinephrine in the management of out-of-hospital cardiac arrest.
Ann Emerg Med 2007; 50:635642.
10. Larabee TM, Liu KY, Campbell JA, Little CM. Vasopressors in cardiac arrest: a
&& systematic review. Resuscitation 2012; 83:932939.
A very useful systematic review of all vasopressors in cardiac arrest.
11. BET 1: the use of adrenaline and long-term survival in cardiopulmonary
resuscitation following cardiac arrest. Emerg Med J 2013; 30:249250.
12. Deakin CD, Morrison LJ, Morley PT, et al. Part 8. Advanced life support. 2010
International Consensus on Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care Science with Treatment Recommendations. Resuscita-
tion 2010; 81 (Suppl. 1):e93e174.
13. Deakin CD, Nolan JP, Soar J, et al. European Resuscitation Council Guide-
lines for resuscitation 2010 Section 4. Adult advanced life support. Resusci-
tation 2010; 81:13051352.
14. Woodhouse SP, Cox S, Boyd P, et al. High dose and standard dose
adrenaline do not alter survival, compared with placebo, in cardiac arrest.
Resuscitation 1995; 30:243249.
15. Olasveengen TM, Wik L, Sunde K, Steen PA. Outcome when adrenaline
& (epinephrine) was actually given vs. not given post hoc analysis of a
randomized clinical trial. Resuscitation 2012; 83:327332.
A post hoc analysis which shows increased rates of ROSC with adrenaline in OHCA.
16. Holmberg M, Holmberg S, Herlitz J. Low chance of survival among patients
requiring adrenaline (epinephrine) or intubation after out-of-hospital cardiac
arrest in Sweden. Resuscitation 2002; 54:3745.
17. Stiell IG, Wells GA, Field B, et al. Advanced cardiac life support in out-of-
hospital cardiac arrest. N Engl J Med 2004; 351:647656.
18. Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of out-of-
hospital cardiac arrest and survival rates: systematic review of 67 prospective
studies. Resuscitation 2010; 81:14791487.
19. Glover BM, Brown SP, Morrison L, et al. Wide variability in drug use in out-of-
hospital cardiac arrest: a report from the Resuscitation Outcomes Consor-
tium. Resuscitation 2012; 83:13241330.
20. Hayashi Y, Iwami T, Kitamura T, et al. Impact of early intravenous epinephrine
administration on outcomes following out-of-hospital cardiac arrest. Circ J
2012; 76:16391645.
21. Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an
intensive care unit following cardiac arrest. Intensive Care Med 2004;
30:21262128.
22. Dragancea I, Rundgren M, Englund E, et al. The influence of induced
& hypothermia and delayed prognostication on the mode of death after cardiac
arrest. Resuscitation 2013; 84:337342.
This study confirms the previous studies that brain injury is the commonest mode of
death amongst those admitted to hospital after OHCA.
23. Ristagno G, Tang W, Huang L, et al. Epinephrine reduces cerebral perfusion
during cardiopulmonary resuscitation. Crit Care Med 2009; 37:14081415.
24. Fries M, Weil MH, Chang YT, et al. Microcirculation during cardiac arrest and
resuscitation. Crit Care Med 2006; 34:S454S457.
25. Burnett AM, Segal N, Salzman JG, et al. Potential negative effects of
epinephrine on carotid blood flow and ETCO2 during active compression-
decompression CPR utilizing an impedance threshold device. Resuscitation
2012; 83:10211024.
26. Nordseth T, Olasveengen TM, Kvaloy JT, et al. Dynamic effects of adrenaline
& (epinephrine) in out-of-hospital cardiac arrest with initial pulseless electrical
activity (PEA). Resuscitation 2012; 83:946952.
An interesting re-analysis of data from a previous reported study that clarifies the
precise impact of adrenaline on cardiac rhythm during cardiac arrest.
174 www.co-criticalcare.com
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
27. Sun S, Tang W, Song F, et al. The effects of epinephrine on outcomes of
normothermic and therapeutic hypothermic cardiopulmonary resuscitation.
Crit Care Med 2010; 38:21752180.
28. Schmittinger CA, Torgersen C, Luckner G, et al. Adverse cardiac events
during catecholamine vasopressor therapy: a prospective observational
study. Intensive Care Med 2012; 38:950958.
29. Gao Smith F, Perkins GD, Gates S, et al. Effect of intravenous beta-2 agonist
treatment on clinical outcomes in acute respiratory distress syndrome
(BALTI-2): a multicentre, randomised controlled trial. Lancet 2012; 379:
229235.
30. McQueen C, Gates S, Perkins GD. Adrenaline for the pharmacological
treatment of cardiac arrest... going, going, gone? Resuscitation 2012; 83:
921922.
31. De Oliveira FC, Feitosa-Filho GS, Ritt LE. Use of beta-blockers for
& the treatment of cardiac arrest due to ventricular fibrillation/pulseless
ventricular tachycardia: a systematic review. Resuscitation 2012; 83:674
683.
A useful systematic review highlighting the potential benefits of beta-blockers for
ventricular fibrillation/ventricular tachycardia cardiac arrest.
32. Stratakos G, Kalomenidis J, Routsi C, et al. Transient lactic acidosis as a side
effect of inhaled salbutamol. Chest 2002; 122:385386.
33. Cocchi MN, Miller J, Hunziker S, et al. The association of lactate and
vasopressor need for mortality prediction in survivors of cardiac arrest.
Minerva Anestesiol 2011; 77:10631071.
34. Shinozaki K, Oda S, Sadahiro T, et al. Blood ammonia and lactate levels on
hospital arrival as a predictive biomarker in patients with out-of-hospital
cardiac arrest. Resuscitation 2011; 82:404409.
35. Beiser DG, Carr GE, Edelson DP, et al. Derangements in blood glucose
following initial resuscitation from in-hospital cardiac arrest: a report from the
national registry of cardiopulmonary resuscitation. Resuscitation 2009; 80:
624630.
36. Nolan JP, Laver SR, Welch CA, et al. Outcome following admission to
UK intensive care units after cardiac arrest: a secondary analysis of the
ICNARC Case Mix Programme Database. Anaesthesia 2007; 62:1207
1216.
37. Perbet S, Mongardon N, Dumas F, et al. Early-onset pneumonia after cardiac
arrest: characteristics, risk factors and influence on prognosis. Am J Respir
Crit Care Med 2011; 184:10481054.
38. Davies KJ, Walters JH, Kerslake IM, et al. Early antibiotics improve
& survival following out-of hospital cardiac arrest. Resuscitation 2013;
84.
This observational study evaluates the impact of antibiotics on outcome after
OHCA. It raises an important research question: should we give prophylactic
antibiotics after OHCA?
39. Bassford CR, Thickett DR, Perkins GD. The rise and fall of beta-agonists in the
treatment of ARDS. Crit Care 2012; 16:208.
40. Perkins GD, Nathani N, McAuley DF, et al. In vitro and in vivo effects of
salbutamol on neutrophil function in acute lung injury. Thorax 2007; 62:36
42.
41. Perkins GD, McAuley DF, Richter A, et al. Bench-to-bedside review: beta2-
agonists and the acute respiratory distress syndrome. Crit Care 2004; 8:25
32.
42. Callaway CW. Questioning the use of epinephrine to treat cardiac arrest.
JAMA 2012; 307:11981200.
43. Redding JS, Pearson JW. Resuscitation from ventricular fibrillation: drug
therapy. JAMA 1968; 203:255260.
44. Redding JS, Pearson JW. Resuscitation from asphyxia. JAMA 1962;
182:283286.
45. Vandycke C, Martens P. High dose versus standard dose epinephrine in
cardiac arrest a meta-analysis. Resuscitation 2000; 45:161166.
Volume 19
Number 3
June 2013