clasificación de maxim petrov
TRANSCRIPT
The American Journal of GASTROENTEROLOGY VOLUME 105 | JANUARY 2010 www.amjgastro.com
nature publishing group74 R
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CLINICAL REVIEWS
“Crude classifi cations and false generalizations are the curse of organized life.”
— George Bernard Shaw
Th e Atlanta classifi cation, the most widely used classifi cation
of acute pancreatitis, was introduced in 1992 and defi ned mild
and severe categories of acute pancreatitis (1) . However, its
limitations have been highlighted in a number of publications
over the past 5 years and a call for its revision has been made
(2 – 4) . Th e major impetus to revision has been the recent signi-
fi cant advances in understanding the pathophysiology of acute
pancreatitis and especially the role of systemic complications.
Whereas the original Atlanta classifi cation assessed only the
presence or absence of organ failure (OF), it is now recognized
that the number of organs that fail, the timing of onset, the
change in OF in response to initial treatment, and the duration
of OF, all contribute to severity (5 – 7) . Given that OF lasting
for >48 h is associated with signifi cantly increased mortality in
patients with acute pancreatitis (8,9) , the proposed revision of
the Atlanta classifi cation suggests that patients with persistent
OF should be defi ned as having severe acute pancreatitis (10) .
Th is means that patients with transient OF are considered to
have mild acute pancreatitis, and that local (peri)pancreatic
complications are not considered to contribute to the defi ni-
tion of severity in patients with acute pancreatitis.
Since the fi rst attempt to classify the severity of acute pan-
creatitis by Fitz in 1889 and until the most recent Atlanta sym-
posium in 1992, a morphological component has always been
included (11) . Whereas Fitz believed that the morphological
features of severe disease were evidence of pancreatic hemor-
rhage and disseminated fat necrosis, the morphological features
of severe disease in the original Atlanta classifi cation were pan-
creatic necrosis, abscess, and pseudocyst. Since then, a number
of studies have demonstrated that infectious (peri)pancreatic
complications (IPCs), rather than the presence of necrosis
per se , are a key determinant of the high morbidity and morta-
lity in patients with acute pancreatitis (12 – 15) . It therefore
seems reasonable to consider local complications in classifying
the severity of acute pancreatitis.
A retrospective study from the Mayo Clinic (16) showed that
patients with local pancreatic complications (as defi ned by the
1992 Atlanta classifi cation) and no systemic complications at any
time during hospitalization had an almost negligible mortality
but an appreciable morbidity. Only 2 (2 % ) patients died among
99 patients with local complications and no OF, and this was
similar to those with mild acute pancreatitis. At the same time, it
was shown that these patients required an average stay in the ICU
of 5 days and a total hospital stay of 28 days, both of which are
more than expected for patients with mild acute pancreatitis. Th is
was recently confi rmed by the same research group in a prospec-
tive study of 82 patients (17), as well as in a prospective study of
135 patients from Spain (18) . On the basis of these fi ndings, the
revision to the Atlanta classifi cation should include a third cat-
egory, those with “ moderate ” acute pancreatitis, and these would
be those with local (peri)pancreatic complications but no persist-
ent systemic complications. Th ese patients would have previously
been classifi ed as having severe acute pancreatitis.
Th ere is another subgroup of patients among those who
would have previously been classifi ed as having severe acute
pancreatitis. Th is proposed category is at the severe end of
the spectrum and these patients have both local and systemic
complications during the course of acute pancreatitis. Th e rea-
son for defi ning this subgroup of patients as having extremely
severe (or “ critical ” ) acute pancreatitis stems from fi ndings of
several studies that demonstrated a marked diff erence in the
mortality rate of patients with OF depending on whether IPCs
are present or not. Th is was shown in a study from Switzerland
that prospectively enrolled 204 patients with acute pancreatitis,
Classifi cation of the Severity of Acute Pancreatitis: How Many Categories Make Sense ? Maxim S. Petrov , MD, MPH 1 and John A. Windsor , MBChB, MD, FRACS 1
There is an ongoing effort to revise the 1992 Atlanta classifi cation of acute pancreatitis in the light of emerging evidence. The categorization of the severity of acute pancreatitis is one of the key elements of the classifi cation. This paper aims to defi ne the optimal number of categories and provide their defi nitions on sound clinical grounds. Am J Gastroenterol 2010; 105:74–76; doi:10.1038/ajg.2009.597; published online 20 October 2009
1 Department of Surgery, The University of Auckland , Auckland , New Zealand . Correspondence: Maxim S. Petrov, MD, MPH , Department of Surgery, The University of Auckland , Private Bag 92019 , Auckalnd 1142 , New Zealand . E-mail: [email protected] Received 13 May 2009; accepted 11 September 2009
© 2010 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
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Classification of the Severity of Acute Pancreatitis
regardless of its severity (19) . Th ere were 74 patients who devel-
oped OF, of whom 9 (12 % ) died. Of these, 47 patients had OF
and no evidence of IPC, of whom 2 (4 % ) died. Th is is in con-
trast to the 27 patients who had both OF and IPC, of whom 7
(26 % ) died. In a further prospective study of 64 patients with
predicted severe acute pancreatitis in Greece, 33 developed OF,
of whom 8 (24 % ) died (20) . Th ere were 12 patients with both
OF and IPC, of whom 7 (58 % ) died. Th ere were 21 patients
with OF and no evidence of IPC, of whom only 1 (5 % ) died.
In a prospective study from France, there were 30 patients with
multiple OF, of whom 10 (33 % ) died (21) . When OF and IPC
were both present, 9 of 23 (39 % ) patients died, compared with
1 of 7 (14 % ) who died with OF and no IPC. Th ese studies dem-
onstrate that the presence of OF and IPC signifi cantly increases
mortality compared with OF alone. Although patients with
both OF and IPC are not common in routine clinical practice,
they are an important subgroup because of excessive mortality.
Th is provides a sound rationale for the introduction of a fourth
category, namely, “ critical ” acute pancreatitis.
It could be argued that patients with the most severe acute
pancreatitis are those with persistent OF in the early phase of
the disease, which is a time when IPCs are rare. Th is argument is
primarily based on two studies that demonstrated signifi cantly
worse outcomes, in terms of OF and mortality, for patients with
so-called “ early severe acute pancreatitis, ” defi ned as a failure of
at least one organ system at admission or within 72 h aft er onset
of symptoms (22,23) . But this seems to be a circular argument,
as the diagnosis of “ early severe acute pancreatitis ” required the
presence of OF, resulting in a higher rate of OF. Th is is a clini-
cal illustration of the phenomenon widely referred to in social
sciences as “ the Oedipus Eff ect. ” In relation to mortality, one
might suggest that early persistent OF has greater impact on the
mortality of acute pancreatitis than late IPCs, but such a sug-
gestion cannot be proven in the absence of treatments that have
been studied to the same extent and are equally eff ective for
both IPCs and OF in acute pancreatitis. Whereas the preven-
tion and treatment of IPCs by means of enteral tube feeding,
prophylactic antibiotics, and delayed necrosectomy have been
extensively studied in clinical studies, including several high-
quality randomized controlled trials (24 – 26) , there is relatively
poor evidence relating to the prevention and treatment of early
OF in patients with acute pancreatitis. Th ere have been only
some “ negative ” studies examining antiproteases and lexipafant
(27,28), whereas other strategies, such as goal-directed resusci-
tation, inhibition of cytokines, calcium antagonists, and decom-
pression for abdominal compartment syndrome, have not been
studied in prospective clinical studies, let alone in randomized
controlled trials. Th us, the less-established treatment strategies
for the early phase of acute pancreatitis, compared with those
for the late phase, may account for the higher mortality ascribed
to “ early ” severe acute pancreatitis and persistent OF.
Th e proposed revision of the Atlanta classifi cation is based on
the concept of a biphasic natural course of acute pancreatitis and
recommends that clinicians use a diff erent method of classifi cation
for the early phase and the late phase of acute pancreatitis (10) . In
the early phase of the disease, the classifi cation of severity is to be
based on the presence or absence of persistent OF and / or death.
In the late phase, the classifi cation of severity is to be based on the
need for “ active intervention (operative, endoscopic, laparoscopic,
or percutaneous) or other supportive measures (such as need for
respiratory ventilation, renal dialysis, or nasojejunal feeding), ” as
well as on the presence or absence of persistent OF and / or death.
Th is approach has some important limitations that make it subop-
timal. First, there is imprecision in the defi nition of the duration
of the early phase as “ within the fi rst 1 – 2 weeks of onset, ” which
probably refl ects the lack of consensus in the literature. Moreover,
a recent large population-based study of all deaths due to acute
pancreatitis in Scotland over a 6-year period does not support the
concept of a biphasic natural course of acute pancreatitis as it did
not reveal a bimodal distribution of mortality (6) . Second, it is not
appropriate to use mortality as both an indicator of the natural
course of the disease and as a part of the defi nition of severity, the
latter of which lacks clinical utility postmortem. Th ird, signifi cant
variance will result from a classifi cation of severity that is based
on the need for an intervention or supportive care. Th is is because
there is a lack of international standardization of management,
including indications for endoscopic procedures, enteral nutri-
tion, and criteria for admission to intensive care units. Finally, the
prognostic and clinical utility of many of the suggested new radio-
logical terms (e.g., “ acute peripancreatic fl uid collection, ” “ acute
postnecrotic collection, ” “ walled-off necrosis ” ) has not been dem-
onstrated, and these may require further revision. Furthermore,
there is no consensus on the use of this terminology even among
radiologists, and an alternative image-based classifi cation based
on retroperitoneal extension has been proposed (29) . Th erefore,
a suggestion that the radiologists should refi ne their imaging
criteria for the diagnosis of (peri)pancreatic complications and
that the clinicians should integrate them into a clinical classifi ca-
tion system seems to be reasonable and justifi ed (30) .
It is appreciated that an ideal classifi cation of the severity of
acute pancreatitis would refl ect, through its categories, clini-
cally relevant changes that occur in individual patients (31) . Th e
proposed revision to the Atlanta classifi cation (10) only refl ects
one clinically relevant variable — persistent OF. But there is a
large body of evidence that demonstrates a broader spectrum of
clinically relevant changes in acute pancreatitis. Th ese include
(peri)pancreatic complication (absence, sterile, infectious) and
OF (absence, transient, persistent). Th ese clinically relevant
variables provide the basis for a classifi cation of the severity of
acute pancreatitis comprising four categories ( Table 1 ). Th is
classifi cation of severity uses widely accepted and unambigu-
ous terms, can be applied in both early and late phases of acute
pancreatitis, and will prove to be useful in tracking individual
patients and comparing groups of patients.
We conclude that a classifi cation of the severity of acute pan-
creatitis that includes just two categories does not refl ect all the
clinically important changes in patients with acute pancreatitis.
Th ere are sound clinical grounds for introducing two additional
categories, namely, “ moderate ” and “ critical ” acute pancreati-
tis. Th e four categories will better accomplish the main objec-
The American Journal of GASTROENTEROLOGY VOLUME 105 | JANUARY 2010 www.amjgastro.com
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Petrov and Windsor
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tives of the revision of the Atlanta classifi cation, which are to
improve clinical assessment, facilitate communication between
treating physicians and promote standardization for reporting
clinical studies.
ACKNOWLEDGMENTS We are indebted to Professor Peter A. Banks (Brigham and
Women ’ s Hospital, Harvard Medical School, Boston, MA) for
helpful discussion. Dr. Maxim S. Petrov is supported by the
Kenneth Warren Foundation of the International
Hepato-Pancreato-Biliary Association.
CONFLICT OF INTEREST Guarantor of the article: Maxim S. Petrov, MD, MPH.
Specifi c author contributions: Planning, conducting, and
draft ing the manuscript: Maxim S. Petrov; draft ing and critical
reviewing of the manuscript: John A. Windsor.
Financial support: None.
Potential competing interests: None.
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4 . Pandol SJ , Saluja AK , Imrie CW et al. Acute pancreatitis: bench to the bedside . Gastroenterology 2007 ; 132 : 1127 – 51 .
5 . Flint R , Windsor JA . Early physiological response to intensive care as a clinically relevant approach to predicting the outcome in severe acute pancreatitis . Arch Surg 2004 ; 139 : 438 – 43 .
Table 1 . Classifi cation and defi nitions of four categories for the severity of acute pancreatitis
Severity category
Local complications Systemic complications
Mild No (peri)pancreatic complication
and No organ failure
Moderate a Sterile (peri)pancreatic complication
or Transient organ failure
Severe a Infectious (peri)pancreatic complication
or Persistent organ failure
Critical Infectious (peri)pancreatic complication
and Persistent organ failure
a Severity is graded on the basis of more severe local or systemic complication (e.g., sterile pancreatic necrosis without organ failure has to be graded as “ moderate ” ; sterile pancreatic necrosis with persistent organ failure has to be graded as “ severe ” ).