Editorial
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References
1 Roizen MF. More preoperative
assessment by physicians and less by
laboratory tests. New England Journal of
Medicine 2000; 342: 204–5.
2 Association of Anaesthetists of Great
Britain and Ireland. Pre-operative
Assessment and Patient Preparation – The
Role of the Anaesthetist. London:
AAGBI, 2010. http://www.aagbi.
org/publications/guidelines/docs/
preop2010.pdf (accessed 30 ⁄ 07 ⁄
2010).
3 National Collaborating Centre for
Acute Care. Preoperative Tests, the Use of
Routine Preoperative Tests for Elective
Surgery – Evidence, Methods and Guidance.
London: National Institute for Clinical
Excellence, 2003. http://www.nice.
org.uk/nicemedia/pdf/CG3NICE
guideline.pdf (accessed 30 ⁄ 07 ⁄ 2010).
4 Arrowsmith JE. Preoperative investi-
gation of the surgical patient. Surgery
2005; 23: 447–8.
Editorial
ARDS, acronyms and the
Pinocchio effect
How can there be a biomarker for what is
imaginary?
– well-known intensivist, 2010
A speciality should, by definition, have
a special interest, a distinguishing
feature or a characteristic that sets it
apart. The concept of Intensive Care
was derived from the polio epidemic
where ventilation was used to support a
paralysed respiratory system, allowing
time for muscle function to recover.
Organ support characterised the speci-
ality. It was inevitable that, when
patients were regularly presenting with
failing lungs or kidneys, the common
clinical and physiological patterns
would be recognised, and called syn-
dromes (‘syndrome’ literally meaning
‘running together’). In 1967, Ashbaugh
et al. described a severe chest syndrome
with a classic X-ray appearance associ-
ated with a time of onset between 1 and
976
Anaesthesia, 2010, 65, pages 971–979
5 Smetana GW, Macpherson DS. The preoperative testing in ambulatory
case against routine preoperative surgery. Anesthesia and Analgesia 2009;
laboratory testing. Medical Clinics of 108: 467–75.
North America 2003; 87: 7–40. 10 Chung F, Mezei G, Tong D. Preex-
6 Olson RP, Stone A, Lubarsky D. The isting medical conditions as predictors
prevalence and significance of low of adverse events in day-case surgery.
preoperative haemoglobin in ASA 1 British Journal of Anaesthesia 1999; 83:
or 2 outpatient surgery candidates. 262–70.
Anesthesia and Analgesia 2005; 101: 11 NHS Modernisation Agency. High
1337–40. Impact Changes for Service Improvement
7 Liu LL, Dzankic S, Leung JM. and Delivery. London: Department of
Preoperative electrocardiogram Health, 2004. http://www.ogc.gov.
abnormalities do not predict postoper- uk/documents/Health_High_
ative cardiac complications in geriatric Impact_Changes.pdf (accessed
surgical patients. Journal of the American 30 ⁄ 07 ⁄ 2010).
Geriatrics Society 2002; 50: 1186–91. 12 Carlisle J, Langham J, Thoms G.
8 Schein OD, Katz J, Bass EB, et al. The Guidelines for routine preoperative
value of routine preoperative medical testing. British Journal of Anaesthesia
testing before cataract surgery. Study 2004; 93: 495–7.
of Medical Testing for Cataract Sur-
gery. New England Journal of Medicine doi:10.1111/j.1365-2044.2010.06503.x
2000; 342: 168–75.
9 Chung F, Yuan H, Yin L, Vairava-
nathan S, Wong DT. Elimination of
96 h [1]. It was secondary to a collec- ‘treatment’ that could target this path-
tion of very disparate primary illnesses, way. A recognisable common pattern
mainly direct chest trauma but also effectively homogenised the wide range
infection and others including pancrea- of causes of lung failure and allowed
titis. It was called adult respiratory far easier recruitment of large numbers
distress syndrome, ARDS. Life-threat- of patients to studies. Those studies
ening and necessitating ventilation, it involved methods ranging from basic
immediately fell under the auspices of science techniques, exploring inflam-
an emerging speciality, Intensive Care, mation in the ARDS-affected lung,
which had the capability to ventilate. through epidemiology, to the assess-
Over several years the syndrome was ment of clinical supportive measures
defined and refined radiologically, clin- such as ventilation. It became a fruitful
ically and physiologically, so that by source of funding. The syndrome
1994 a consensus conference issued became central to the capability, com-
criteria for both ARDS and its milder petence and credibility of the emerging
form, acute lung injury (ALI). The speciality. ‘ARDS’ became synonymous
syndrome now had a recognisable and with Intensive Care. The raison d’etre
measurable spectrum of severity [2]. of Intensive Care Medicine remained
Now it could be readily identified in organ support, but the speciality no
clinical practice, ARDS was a focal longer merely supported failing organs,
point for teaching and was accessible to it became acknowledged as expert in
research. By defining the syndrome recognising conditions, such as ARDS.
more physiologically, it could be stud- Furthermore, ARDS provided an
ied as a single entity and the common excellent model for a way around the
pathways in lung injury could be problem of studying ‘organ failure’ –
identified. This raised the prospect of a which encompasses a broad range of
 2010 The Authors
Anaesthesia  2010 The Association of Anaesthetists of Great Britain and Ireland
Anaesthesia, 2010, 65, pages 971–979
. ....................................................................................................................................................................................................................
causative conditions, the heterogeneity
of which hampers research and hence
advances in the speciality. By defining
the syndrome, a single quantifiable
entity emerged, and by implication this
could be linked to the common final
pathway. Add a numerical scale for the
spectrum of severity of ALI and ARDS,
and a convincingly robust research
model evolves.
The techniques of defining and
quantifying a homogenous endpoint of
an organ failure could be easily applied
elsewhere. Acute renal failure (ARF) is
now defined by the degree of organ
failure. It was a small step to apply this
more broadly to other common patterns
such as sepsis and the systemic inflam-
matory response syndrome (SIRS), that
predispose to organ failure [3, 4].
Pattern definition allows ‘lumping’
together of all comers that meet the
criteria for that pattern or syndrome.
The common diagnosis then opens the
door to discussion, teaching and
research in terms of diagnostics, mech-
anisms and therapeutics. These patterns
of symptoms, signs and numerical indi-
ces are now indispensible to Intensive
Care Medicine.
The results have been impressive.
These syndromes are established in
common parlance, are part of teaching
and a central theme at almost every
meeting. They are the core feature of
the speciality and attract both prestige
and – more pragmatically – funding.
The explosion in basic science knowl-
edge of the response of the lung to
injury is phenomenal, and this also
follows for the other syndromes.
Equally impressive is the development
of support techniques and evaluation of
their efficacy as well as other effects.
These ‘new’ conditions now sit centre
stage in Intensive Care Medicine.
It would appear that this is all
positive. An emerging speciality has
defined new conditions that it is recog-
nised as being expert in identifying,
treating, researching and teaching, and
is hence characterised by these condi-
tions.
The clue that there is a problem is the
relatively consistent failure of the num-
ber of syndrome-related ‘magic bullet’
trials. And ARDS leads the way –
 2010 The Authors
Anaesthesia  2010 The Association of Anaesthetists of Great Britain and Ireland
nothing works but the results are better
anyway. Curiously, the epidemiology is
changing. Sepsis follows closely but to
date only activated protein C has been
positive [5] So wherein lies the prob-
lem?
The flaw is fundamental. A syndrome
(and its acronym) is not a disease and the
pattern does not acknowledge a cause.
Rather, the syndrome allows tacit
acceptance of the probable existence of
a common pathway and an unspoken
understanding that its cause is immate-
rial. The exception was the eloquent
description by Pelosi et al. of the
different natural histories of intrinsic
and extrinsic ARDS, the implication
being that the mechanistic differences
are dependent on the cause [6]. This
should have challenged the status quo,
but rather than looking more closely at
the range of causes of ARDS and their
natural history, recognition of two
common pathways was incorporated
into the default position.
The clinical risk with ARDS and
other acronyms is that the real emphasis
shifts to the syndrome and its supportive
management, often dismissing the
importance of the underlying cause.
The treatments are ventilation for lung
failure, dialysis for renal failure, and
correction of the haemodynamic prob-
lems in sepsis or septic shock. In each,
the cause is quietly divorced from the
syndrome, is relegated to being one of a
list of known causes of the syndrome
and hence becomes irrelevant. But
surely the cause and its management
help define the natural history of the
illness? For example, the type of pneu-
monia and its specific treatment will
affect the impact on the lung. Compare
pneumococcus, swine flu, mycoplasma
and tuberculosis, and then add in age,
immunocompromise and fluid shifts. All
can produce ARDS and each poten-
tially has a very different natural history
that is quite different from trauma, fat
embolism, aspiration and pancreatitis –
all of which were included by Ashbaugh
et al. [1]. In acute renal failure, acute
glomerulonephritis, myoglobinuria and
non-steroidal inflammatory drug toxic-
ity have different natural histories.
Curiously, the RIFLE classification,
geared to make sense of acute renal
Editorial
failure, fails at the first hurdle by being
disease independent [7, 8]. At present,
acute liver failure is still defined by cause
and no one would seriously consider the
cause unimportant, yet it would be
temptingly easy to create a single syn-
drome with a catchy acronym. Are
these so different from hypoxaemia
associated with non-specific X-ray
changes? Even these acronyms are rel-
atively focused compared with SIRS
and sepsis. These terms ‘lump’ together
such disparate conditions as meningo-
coccal infection in a fit 18-year-old,
faecal peritonitis in an unfit 80-year-
old, urosepsis in general and necrotising
fasciitis, on the basis of a collection of
relatively non-specific symptoms and
signs. There is no acknowledgement of
the wide range of exo- and endotoxins
that all have very different and some-
times very specific effects. At least
‘sepsis’ acknowledges that infection,
albeit in many guises, must be part of
the cause, and ‘source control’ recog-
nises that there is a cause. ‘SIRS’ does
not even have that to recommend it and
is just a cluster of non-specific signs of
general inflammation [9, 10].
Conditions like ARDS, ALI, ARF,
sepsis, SIRS and others are central to
Intensive Care Medicine as a speciality.
They are not specific illnesses and there
is no direct link to their own causation.
They are convenient collective terms,
so why are they so important?
This could be described as the
‘Pinocchio effect’. Geppetto, a toymaker
eager to fill a void in his life, created a toy
to be his little boy. With some magic, the
toy was so lifelike it behaved like a boy,
but no matter how much he wished it be
otherwise, in reality it was always a toy
[11]. So it is with Intensive Care Med-
icine, where the desire to produce
diagnoses that can be used clinically
and scientifically has resulted in harness-
ing syndromes and giving them real
disease status. If any confirmation was
needed, it is the eagerness to find
biomarkers for these acronyms as if they
were real diseases. Hence the quotation
at the top of this Editorial.
Does this matter? Several generations of
intensivists have grown up with ARDS,
ARF, SIRS, sepsis and now possibly
posterior reversible encephalopathy
977
Editorial
. ....................................................................................................................................................................................................................
syndrome (PRES). They pervade the
science and hence the literature of
the speciality. They are the flagship
conditions of Intensive Care Medicine
and the speciality owes much of its
recognition to the exploration, dissem-
ination and proliferation of these
syndromes.
The Pinocchio effect, whereby these
syndromes are treated as real diseases,
makes this an unfortunate and poten-
tially compromising reality, both at the
bedside and in research. The acronym
acquires diagnostic status and the mantra
of ‘treat the cause’ is of only secondary
interest. Management and treatment of
the syndrome are to the detriment of
the search for the cause. Frequently, the
argument is that the cause is no longer
relevant, engendering the acronym with
the potential to become its own cause.
In clinical practice, cause and effect blur
but even the potential benefits to
research pose problems. The acronyms
transform population heterogeneity
magically into syndrome homogeneity
and readily give the numbers needed.
The homogeneity of the syndromes is
comforting but imaginary, so it is hardly
surprising that specific treatments given
to non-specific conditions consistently
fail to reverse the syndromes. To suc-
ceed would confirm the transition of
syndrome to a real disease state, and that
therefore there is an identical pathway
for all comers and specific interventions
are possible. It would confirm that cause
is genuinely unimportant. Pinocchio
would be a real flesh and blood boy
and no longer a toy. Paradoxically, a
positive finding from a magic bullet
trial, without a clear defined mecha-
nism, should be a cause for concern
rather than a relief.
There have been positive aspects of
the rise of the acronym. Organ failure
syndromes have allowed support
modalities to be examined. The syn-
drome provides a population requiring
specific support and can be used to test
the efficacy and iatrogenicity of that
support. Support reverses effects not
causes. The now classic ARDSnet trial
seems to have identified that ventilation
causes iatrogenic problems and that
some modes cause fewer problems than
others [12]. This approach can be used
978
Anaesthesia, 2010, 65, pages 971–979
with other modes of support such previous generation of clinicians has had
as dialysis, or the pharmacological sup- to come to terms with the redundancy
port of the cardiovascular system. The of concepts that were popular but
research focus is on the method of unhelpful. The renaissance taught us
support, not the condition, and in this that old ideas were not always great
scenario less detriment is not the same as ideas. Textbooks can be rewritten and
treatment benefit. The other benefit of will be less repetitive.
acronyms is in basic science research, Will Geppetto relinquish Pinocchio?
where syndromes have generated inter- I doubt it, and while the world is
est and funding to unravel the mecha- convinced that Pinocchio is a little boy
nisms of injury, such as that affecting the all will be well, but when the puppet is
lung. It is interesting that basic sciences recognised as a puppet, damage limita-
models of injury invariably use a single, tion could be a problem. It is time that
specific, reproducible mechanism to Intensive Care Medicine acknowledges
mimic a syndrome of many different the Pinocchio effect before everyone
causes. else does.
Geppetto was as attached to his In the story it takes a magic fairy to
marionette as Intensive Care Medicine transform Pinocchio into a real boy.
is to its syndromes. Impressive driving Now, where can we find one of
forces maintain the status of these them…?
acronyms. They produce big numbers
for the randomised trials on which Competing interests
modern evidence based medicine is No external funding and no competing
fixated. Unfortunately, the erroneous interests declared.
assumption that the heterogeneity of
causation is very much secondary to the N. Soni
homogeneity of the syndrome is both Consultant in Critical Care and
self-sustaining and defeating, but at Anaesthesia
present it does not seem open to debate. Magill Department of Anaesthesia, Pain
Funding is attracted to track record and and Intensive Care
to populist topics such as ARDS and Chelsea and Westminster Hospital
sepsis. Abandon acronyms and this London, UK
infrastructure fails. Email: n.soni@imperial.ac.uk
Tradition is powerful and these acro-
nyms are the foundation of the special- References
ity and have helped build and establish 1 Ashbaugh D, Bigelow D, Petty T,
credibility. The textbooks are full of Levine B. Acute respiratory distress in
acronyms and their definitions, diagno- adults. Lancet 1967; 2: 319–23.
sis and management, as is the world of 2 Bernard GR, Artigas A, Brigham KL,
evidence based medicine. Many intens- et al. The American-European
ivists (acronymists) have spent their Consensus Conference on ARDS.
careers working with acronyms and Definitions, mechanisms, relevant
are deeply attached to them. Could outcomes, and clinical trial coordina-
Geppetto have forsaken his puppet? tion. American Journal of Respiratory
ARDS, ALI, sepsis, SIRS and ARF and Critical Care Medicine 1994; 149:
are now more of a problem than a 818–24.
benefit. Unless Intensive Care Medicine 3 American College of Chest Physi-
comes to terms with acronyms and what cians ⁄ Society of Critical Care Medi-
they really mean, clinical management cine Consensus Conference.
will stumble on, hamstrung by these Definitions for sepsis and organ failure
syndromes, and clinical trials will con- and guidelines for the use of innova-
tinue to be a futile waste of money. tive therapies in sepsis. Critical Care
True, the current infrastructure may fail Medicine 1992; 20: 864–74.
if acronyms are relegated to history, but 4 Bone RC, Balk RA, Cerra FB, et al.
the speciality will recover and will be Definitions for sepsis and organ failure
empowered by the makeover. There and guidelines for the use of
may even be progress. Almost every innovative therapies in sepsis.
 2010 The Authors
Anaesthesia  2010 The Association of Anaesthetists of Great Britain and Ireland
Anaesthesia, 2010, 65, pages 971–979 Editorial
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The ACCP ⁄ SCCM Consensus 7 Bagshaw SM, George C, Bellomo R. 10 Robertson CM, Coopersmith CM.
Conference Committee. American A comparison of the RIFLE and The systemic inflammatory response
College of Chest Physicians ⁄ Society AKIN criteria for acute kidney injury syndrome. Microbes and Infection 2006;
of Critical Care Medicine. Chest 1992; in critically ill patients. Nephrology 8: 1382–9.
101: 1644–55. Dialysis Transplantation 2008; 23: 11 Collodi C. Le Avventure di Pinocchio:
5 Bernard GR, Vincent JL, Laterre PF, 1569–74. Storia di un Burattino. Florence: Felice
et al. Efficacy and safety of re- 8 Venkataraman R, Kellum JA. Defin- Paggi, 1883.
combinant human activated protein C ing acute renal failure: the RIFLE 12 The Acute Respiratory Distress Syn-
for severe sepsis. New England Journal of criteria. Journal of Intensive Care drome Network. Ventilation with
Medicine 2001; 344: 699–709. Medicine 2007; 22: 187–93. lower tidal volumes as compared with
6 Pelosi P, Caironi P, Gattinoni L. 9 Bone RC. Toward a theory regarding traditional tidal volumes for acute lung
Pulmonary and extrapulmonary the pathogenesis of the systemic injury and the acute respiratory distress
forms of acute respiratory distress inflammatory response syndrome: syndrome. New England Journal of
syndrome. Seminars in Respiratory what we do and do not know about Medicine 2000; 342: 1301–8.
and Critical Care Medicine 2001; 22: cytokine regulation. Critical Care
259–68. Medicine 1996; 24: 163–72. doi:10.1111/j.1365-2044.2010.06508.x

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