Best Practice & Research Clinical Anaesthesiology 27 (2013) 317–325

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Anaesthesiology
journal homepage: www.elsevier.com/locate/bean

International CPR guidelines – Perspectives

in CPR
Jerry P. Nolan, FRCA, FRCP, FCEM, FFICM, Consultant in
Anaesthesia and Intensive Care Medicine *
Royal United Hospital, Combe Park, Bath BA1 3NG, United Kingdom

Keywords:
The International Liaison Committee on Resuscitation (ILCOR) co-
cardiopulmonary resuscitation ordinates regular reviews of cardiopulmonary resuscitation (CPR)
science science and publishes consensus on science statements and
guidelines treatment recommendations. These outputs are used by interna-
implementation tional resuscitation organisations to generate clinical guidelines.
This review will outline the history behind the development of
international CPR guidelines and will provide a detailed descrip-
tion of the current guideline generating process. A perspective is
provided on the future of this process and the prospects for
completely unified international CPR guidelines.
Ó 2013 Elsevier Ltd. All rights reserved.

Introduction

In recent years there has been a strong drive to ensure that all clinical guidelines are evidence-based
and that the process involved in their development is completely transparent [1]. For the last two
decades the International Liaison Committee on Resuscitation (ILCOR) has been responsible for co-
ordinating a regular review of the science underpinning cardiopulmonary resuscitation (CPR).
Regional resuscitation organisations have used the ILCOR consensus on science statements and
treatment recommendations to formulate their own clinical guidelines. This has resulted in global CPR
guidelines that are based on a common evaluation of the science but with some local adaptation to suit
the prevailing culture and economy. The steps involved in the process for developing evidence-based
guidelines have been outlined by the Grades of Recommendation Assessment, Development and
Evaluation (GRADE) Working Group (Table 1) [2–4].

* Tel.: þ44 1225 825056; Fax: þ44 1225 825061.

E-mail address: jerry.nolan@btinternet.com.

1521-6896/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bpa.2013.07.006
318 J.P. Nolan / Best Practice & Research Clinical Anaesthesiology 27 (2013) 317–325

Table 1
Steps in involved in translating science into clinical guidelines according to the GRADE process (adapted from Brozek JL et al. [2]).

 Establish the guideline development group

 Define the scope of the guidelines
 Prioritise the problems
 Ask precise clinical questions using the Population–Intervention–Comparator–Outcome (PICO) format
 Decide on the relative importance of outcomes
 Identify the existing evidence for every clinical question
 Develop evidence profiles
 Grade the quality of existing evidence for each outcome separately
 Determine the overall quality of available evidence across outcomes
 Decide on the balance between desirable and undesirable consequences
 Decide on the strength of recommendation
 Formulate the recommendation reflecting its strength
 Write the guideline
 Disseminate the guideline

The history of international CPR science reviews and guideline development

Modern CPR was described in the late 1950s and early 1960s [5,6]. But it was several years before
the technique was fully implemented into clinical practice. Dissemination of information interna-
tionally was helped by a series of conferences. The National Academy of Sciences’ National Research
Council held a conference on CPR in 1966 and this involved more than 30 national organisations [7]. An
International Symposium on Emergency Resuscitation took place in Oslo, Norway, the following year.
The American Heart Association (AHA) sponsored subsequent conferences in 1973 and 1979 [8,9].
Resuscitation organisations in other countries also faced a growing demand for CPR training and the
first European Resuscitation Council (ERC) guidelines, for example, were published in 1992 [10]. Un-
surprisingly, variations in resuscitation techniques and training methods began to emerge from indi-
vidual countries and regions of the world; awareness of this fact stimulated thoughts about gathering
international experts at a single location with the aim of achieving consensus in CPR techniques. The
AHA had invited resuscitation experts and opinion-makers from many countries to observe its 1985
review of standards and guidelines for CPR and emergency cardiovascular care (ECC) [11]. Although
these international delegates participated in discussions and disseminated the findings and recom-
mendations to their own countries, this was not strictly an international ‘consensus’.
In June 1990, representatives from the AHA, ERC, Heart and Stroke Foundation of Canada (HSFC),
and the Australian Resuscitation Council (ARC) held a meeting at Utstein Abbey on the island of
Mosterøy, Norway. The primary purpose of this meeting was to establish uniform terms and defini-
tions for out-of-hospital resuscitation. At a follow-up meeting in December 1990 in Surrey, England,
the term ‘Utstein-style’ was adopted for the uniform reporting of data from out-of-hospital cardiac
arrests (OHCAs) [12]. Many ‘Utstein-style’ international consensus statements have since been pub-
lished, including the uniform reporting of paediatric advanced life support [13], laboratory CPR
research [14], in-hospital resuscitation [15], neonatal life support [16], drowning [17], post-
resuscitation care [18], medical emergency teams [19], and dispatch [20]. The Utstein statements on
OHCA and in-hospital cardiac arrest (IHCA) were updated in 2004 [21]. More recently, meetings have
been held in Vienna in 2012 and Melbourne in 2013; the output from these will be an update of the
2004 Utstein document.
The Fifth National Conference on CPR was held in Dallas in 1992. More than 40% of the participants
were from outside the United States and represented 25 countries and 53 international organisations
[11]. At this meeting there were discussions about the creation of an international CPR organisation,
along with the possibility of common international guidelines and an international conference on CPR.

The International Liaison Committee on Resuscitation (ILCOR)

The first international conference held by the ERC took place in Brighton, England in 1992 [22]. At
the end of the conference, representatives from the AHA, ERC, HSFC, ARC, and the Resuscitation Council
 J.P. Nolan / Best Practice & Research Clinical Anaesthesiology 27 (2013) 317–325 319

of Southern Africa (RCSA) held the first meeting of the International Liaison Committee [23]. The name
International Liaison Committee on Resuscitation (ILCOR) was proposed by Dr Walter Kloeck and
formally adopted in May 1996 – this was a deliberate play on the words sick heart – ‘ill cor’. The
founding member organisations of ILCOR were later joined by the Consejo Latino-Americano de
Resuscitatión (CLAR) – now part of the Inter-American Heart Foundation, the New Zealand Resusci-
tation Council (which now forms part of the Australia and New Zealand Committee on Resuscitation
(ANZCOR)) and the Resuscitation Council of Asia (RCA).
ILCOR co-ordinates international systematic reviews of the evidence to support resuscitation
standards and guideline and has published 23 scientific advisory statements, which enable interna-
tional resuscitation organisations to update their guidelines [12,14,17,24–43]. While some regional
differences in guidelines are inevitable because of varying cultures and available resources [44], the
ultimate goal of ILCOR is to provide a unified consensus on the science of resuscitation and issues
relating to education and implementation [45]. The first major meeting coordinated by ILCOR was the
2000 Guidelines Conference [46]. Leading up to this meeting, a sophisticated process for gathering and
assessing evidence was adopted. This process of resuscitation science review evolved further in 2005
[47] and 2010 [48].
Broad consensus on resuscitation science has been reached, but local variations in treatment rec-
ommendations persist because of differences in epidemiology, healthcare systems, implementation,
culture or economic factors. These variations will be reflected by some subtle differences in regional
and national resuscitation guidelines. Reasons for failure to achieve truly universal guidelines include:

1. High-level evidence (randomised clinical trials) is not available for many interventions.
2. The evidence may be inconsistent, imprecise or contradictory. Much of the evidence for resusci-
tation relies on extrapolation from animal models or from studies that are not focused on a cardiac
arrest cohort.
3. Resuscitation has evolved over 50 years and many of the practices originally recommended were
based on expert opinion and other low-level evidence.

The 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency

Cardiovascular Care Science with Treatment Recommendations (2010 CoSTR)

The 2010 International Consensus Conference was attended by experts from 30 countries [43].
Worksheet authors who had reviewed thousands of peer-reviewed papers addressed 300 PICO-format
resuscitation questions. Many of these worksheets were presented and discussed at monthly task force
international web conferences. The evidence reviews and worksheet author conflict of interest (COI)
statements were posted on the ILCOR Website (www.ilcor.org). Public comments were sought via
journal advertisements and emails and were sent to the appropriate ILCOR task force chair and
worksheet author for consideration.

The evidence evaluation process

The evidence evaluation process used for the 2010 International Consensus on CPR and ECC Science
with Treatment Recommendations (2010 CoSTR) was an update of the process used in 2005 and has
been described in detail [48].
The questions for systematic review were devised by each of six ILCOR task forces (Table 2), from
the ILCOR member resuscitation councils, and from the knowledge gaps that had been identified after
the 2005 conference [49]. PICO-format questions were allocated to worksheet authors by the task
force cochairs. Each author completed a conflict of interest (COI) declaration [50]; this aspect of the
process was assigned considerable priority and is discussed in further detail below. Instructions were
provided on the search strategy and the databases to be searched. The minimum electronic databases
to be searched included the Cochrane database for systematic reviews and the Central Register of
Controlled Trials [http://www.cochrane.org/], MEDLINE [http://www.ncbi.nlm.nih.gov/PubMed/],
EMBASE (www.embase.com), and the EndNote (www.endnote.com) reference library collated by
the AHA.
320 J.P. Nolan / Best Practice & Research Clinical Anaesthesiology 27 (2013) 317–325

Table 2
The International Liaison Committee on Resuscitation (ILCOR) 2010 Task Forces.

 Basic Life Support (BLS)

 Advanced Life Support (ALS)
 Acute coronary syndromes (ACS)
 Paediatric Life Support (PLS)
 Neonatal Life Support (NLS)
 Education, implementation and teams (EIT)

Abstracts obtained from the search were reviewed and all relevant articles identified. The
2010 process used a simplified list of five levels of evidence (LOE). Levels of evidence-based
on the likelihood for bias were developed for therapeutic interventions, diagnostic questions,
and prognosis (Table 3). Allocation of LOE for studies related to therapeutic interventions were
based on the likelihood of eliminating bias in the control group: true randomisation (LOE 1),
concurrent (LOE 2) versus historic (LOE 3) controls, absence of controls (LOE 4), or studies that were
related to the worksheet question but that did not directly answer it (LOE 5). Level of evidence 5
studies included those from related populations, animal studies, and bench and mathematical
models [48].
Reviewers classified the quality of each study as good, fair, or poor based on predefined criteria.
Studies were designated as good if they had most or all of the relevant quality items, fair if they had
some of the quality items, and poor if they had only a few of the quality items but sufficient quality to
include for further review [48]. The evidence was summarised using three tables: supportive, neutral
or opposing. Authors formulated a ‘consensus on science statement’, which summarised the relevant
evidence, and drafted a treatment recommendation. The science statements and treatment recom-
mendations were reviewed, debated and edited by the task forces and then posted online for public
comment. The treatment recommendations were relatively broad and lacked the detail that would be
required for use in clinical practice. The generation of detailed guidelines for clinical practice, the final
step in the process, was the responsibility of regional resuscitation organisations such as the AHA and
the ERC [51,52].

Table 3
Levels of evidence used in the 2010 Consensus on CPR Science (reproduced from Ref. [48]).

2A. Levels of evidence for studies of therapeutic interventions

LOE 1: Randomised Controlled Trials (or meta-analyses of RCTs)
LOE 2: Studies using concurrent controls without true randomisation (e.g. pseudo-randomised)
LOE 3: Studies using retrospective controls
LOE 4: Studies without a control group (e.g. case series)
LOE 5: Studies not directly related to the specific patient/population (e.g. different patient/population, animal models,
mechanical models etc.)
2B. Levels of evidence for prognostic studies
LOE P1: Inception (prospective) cohort studies (or meta-analyses of inception cohort studies), or validation of Clinical
Decision Rule (CDR)
LOE P2: Follow-up of untreated control groups in RCTs (or meta-analyses of follow-up studies), or derivation of CDR, or
validated on split-sample only
LOE P3: Retrospective cohort studies
LOE P4: Case series
LOE P5: Studies not directly related to the specific patient/population (e.g. different patient/population, animal models,
mechanical models etc.)
2C. Levels of evidence for diagnostic studies
LOE D1: Validating cohort studies (or meta-analyses of validating cohort studies), or validation of Clinical Decision Rule
(CDR)
LOE D2: Exploratory cohort study (or meta-analyses of follow-up studies), or derivation of CDR, or a CDR validated on a split-
sample only
LOE D3: Diagnostic case control study
LOE D4: Study of diagnostic yield (no reference standard)
LOE D5: Studies not directly related to the specific patient/population (e.g. different patient/population, animal models,
mechanical models etc.)
 J.P. Nolan / Best Practice & Research Clinical Anaesthesiology 27 (2013) 317–325 321

Controversies arising from the 2010 CoSTR

The 2010 CoSTR is a very valuable resource for guideline writers, clinicians and academics world-
wide but it can still be improved. The process was time consuming and expensive. Some authors failed
to deliver their reviews on time and some failed to complete them at all. There was failure to reach
consensus for several topics, usually because data were lacking or there was disagreement on inter-
pretation. Incorporation of late-breaking science into the consensus process is challenging – there is a
desire to include important science but it should be subject to the same level of scrutiny as the other
published evidence.

Potential conflict of interest and clinical guidelines

Those who write guidelines for clinical practice must be free from conflicts of interest (COI). In-
ternational clinical guidelines will influence the treatment of patients throughout the world and in
some cases may involve considerable resources being directed at specific drugs or equipment.
Although, a potential COI is usually considered to be financial in nature, intellectual COIs are just as
likely to cause bias: an individual who has invested significant time and effort in researching a
particular drug or intervention is likely to want to see it included in clinical guidelines. It has been
suggested that an information scientist directed by questions defined by clinical experts does literature
searches and that the final responsibility for recommendations should be placed in the hands of
unconflicted methodologists [1]. ILCOR has yet to adopt this idealist approach but does use the AHA’s
COI process for all those producing evidence reviews and treatment recommendations [50].

Cardiopulmonary resuscitation guidelines throughout the world

The AHA and the ERC both publish CPR guidelines based on the ILCOR CoSTR [51,52]. These are
probably the most widely adopted guidelines internationally, but several other organisations also
publish their own guidelines based on the ILCOR process; these include the Japanese Resuscitation
Council (http://jrc.umin.ac.jp/english.html) and the Australian Resuscitation Council (http://www.
resus.org.au). Survival rates are increasing after both IHCA [53] and OHCA [54] and it seems likely
that changes in guidelines are at least partly responsible for these better outcomes. Key changes
incorporated into recent guidelines have included:

 More focus on the delivery of uninterrupted high-quality chest compressions [55].

 The delivery of chest compression-only CPR by bystanders who are untrained or unwilling to
provide standard CPR [56].
 Increased emphasis on the prevention of IHCA by increased implementation of track-and-trigger
systems and do-not-attempt cardiopulmonary resuscitation (DNACPR) decisions.
 Greater emphasis on a protocolised approach to post-resuscitation care [57].
 Increased use of percutaneous coronary intervention (PCI) after OHCA, irrespective of the ECG
appearances [58].

The AHA and ERC guidelines both include these important advances and can be downloaded at
www.erc.edu and http://circ.ahajournals.org/content/122/18_suppl_3.toc respectively. The two sets of
guidelines are broadly consistent in the recommendations given to healthcare providers. Subtle dif-
ferences include the option to use vasopressin instead of, or addition to, adrenaline in the AHA
guidelines but not in the ERC guidelines, and the injection of adrenaline after the 2nd shock in the AHA
guidelines but after the 3rd shock in the ERC guidelines.

Implementing guidelines

Translation of research findings into clinical practice is frequently problematic [59,60]. Passive
methods of disseminating and implementing guidelines (e.g. publication in journals) are unlikely to
322 J.P. Nolan / Best Practice & Research Clinical Anaesthesiology 27 (2013) 317–325

change professional behaviour [61]. Resuscitation organisations have a primary responsibility for
disseminating and implementing resuscitation guidelines. Resuscitation guidelines can be dissemi-
nated effectively through national scientific meetings and by meetings held locally in hospitals and in
the community. Resuscitation training materials require frequent updating so that they reflect the new
guidelines; however, continually changing guidelines may make delivery and implementation more
difficult – an optimal updating interval is probably about 5 years. The updating of training materials
requires considerable resources and often involves many of the individuals who have been involved in
the guideline process.

The formula for survival

The ILCOR Advisory Statement on Education and Resuscitation (2003) introduced the concept of the
‘formula for survival (FfS)’, a hypothetical formula involving three interactive factors: guideline quality
(science), efficient education of patient caregivers (education), and a well-functioning chain of survival
at a local level (local implementation); these form multiplicands in determining survival from resus-
citation (Fig. 1) [37]. A symposium held in May 2006 enabled invited experts to discuss the validity of
the formula for survival hypothesis and to investigate the influence of each of the multiplicands on
survival. There was a particular focus on implementation, which was thought to involve the following
important components:

 A local champion and effective team to facilitate the implementation process [62,63].
 A simple protocol approved by all involved disciplines [64].
 Identification of local barriers to routine implementation (political, legislative, cultural or pro-
fessional) [65].
 Personal, group and organisational ownership to enhance acceptance locally.
 Goal-directed benchmarking to enable continuous feedback and measurement of quality and
outcome.

The future of international resuscitation guidelines

The science of resuscitation is evolving rapidly and it requires continual review. If important new
research is published it may be appropriate for ILCOR to publish interim consensus advisory statements
to enable treatment guidelines to be updated. Members of ILCOR are currently designing a process that
enables continual review and updating online. Ultimately, the resource for resuscitation evidence
reviews, consensus science statements and treatment recommendations will be a website instead of
conventional journal publications. The 2015 evidence review is following the GRADE process [2–4],
which will make ILCOR consistent with most other international guideline-producing organisations.
The GRADE process places the body of evidence into one of four quality categories: high, moderate, low
and very low [66]. Randomised trials begin as high quality evidence but are downgraded on the basis of
risk of bias, imprecision, inconsistency, indirectness and publication bias. Observational studies begin
as low quality evidence but may be upgraded if the effect size is large, there is evidence of a dose
response, and if all plausible confounders would reduce a demonstrated effect. One of the advantages
of the GRADE system is that it is possible to make a ‘strong’ recommendation (most clinicians would
use the intervention in most circumstances and most well-informed patients would accept it) even if

Fig. 1. The formula for survival.

 J.P. Nolan / Best Practice & Research Clinical Anaesthesiology 27 (2013) 317–325 323

the quality of the evidence is low [67]. Another advantage of the GRADE system is that a GRADE grid
has been proposed to enable recording of panellists’ views in the development of guidelines [68]. The
use of such a grid would enhance transparency in the guideline process because it enables docu-
mentation of the range of views when consensus has been difficult to achieve.

Summary

The process for generating CPR guidelines has evolved over several decades. There has been
extensive international collaboration for the last two decades and there are now only subtle differences
in the guidelines published in different regions of the globe. Adoption of the GRADE process will bring
CPR guidelines inline with the standards accepted by the majority of healthcare organisations. In the
future, the review of the evidence underpinning CPR will probably be a continuous process supported
by online tools.

Conflict of interest statement

JPN is Editor-in-Chief of Resuscitation and Immediate Past Co-Chair of the International Liaison
Committee on Resuscitation.

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