The American Journal of GASTROENTEROLOGY VOLUME 105 | JANUARY 2010 www.amjgastro.com

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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: max.petrov@gmail.com 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-

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Petrov and Windsor

6 . Mole DJ , Olabi B , Robinson V et al. Incidence of individual organ dysfunction in fatal acute pancreatitis: analysis of 1024 death records . HPB 2009 ; 11 : 166 – 70 .

7 . Lankisch PG . Natural course of acute pancreatitis: what we know today and what we ought to know for tomorrow . Pancreas 2009 ; 38 : 494 – 8 .

8 . Buter A , Imrie CW , Carter CR et al. Dynamic nature of early organ dysfunction determines outcome in acute pancreatitis . Br J Surg 2002 ; 89 : 298 – 302 .

9 . Johnson CD , Abu-Hilal M . Persistent organ failure during the fi rst week as a marker of fatal outcome in acute pancreatitis . Gut 2004 ; 53 : 1340 – 4 .

10 . Acute Pancreatitis Classifi cation Working Group . Revision of the Atlanta classifi cation of acute pancreatitis (3rd revision) . www. pancreasclub.com/resources/AtlantaClassifi cation.pdf Accessed 1 April 2009 .

11 . Pannala R , Kidd M , Modlin IM . Acute pancreatitis: a historical perspective . Pancreas 2009 ; 38 : 355 – 66 .

12 . Gloor B , M ü ller CA , Worni M et al. Late mortality in patients with severe acute pancreatitis . Br J Surg 2001 ; 88 : 975 – 9 .

13 . Garg PK , Madan K , Pande GK et al. Association of extent and infection of pancreatic necrosis with organ failure and death in acute necrotizing pancreatitis . Clin Gastroenterol Hepatol 2005 ; 3 : 159 – 66 .

14 . Beger HG , Rau BM . Severe acute pancreatitis: clinical course and manage-ment . World J Gastroenterol 2007 ; 13 : 5043 – 51 .

15 . Xue P , Deng LH , Zhang ZD et al. Infectious complications in patients with severe acute pancreatitis . Dig Dis Sci 2008 ; [e-pub ahead of print] .

16 . Vege SS , Gardner TB , Chari ST et al. Low mortality and high morbidity in severe acute pancreatitis without organ failure: a case for revising the Atlanta classifi cation to include “ moderately severe acute pancreatitis ” . Am J Gastroenterol 2009 ; 104 : 710 – 5 .

17 . Talukdar R , Vege SS , Chari ST et al. Moderately severe acute pancreatitis: a prospective validation study of this new subgroup of acute pancreatitis . Pancreatology 2009 ; 9 : 434 .

18 . De-Madaria E , Soler G , Martinez J et al. Update of the Atlanta classifi cation of severity of acute pancreatitis: should a moderate category be included? Pancreatology 2009 ; 9 : 433 – 4 .

19 . B ü chler MW , Gloor B , M ü ller CA et al. Acute necrotizing pancreatitis: treat-ment strategy according to the status of infection . Ann Surg 2000 ; 232 : 619 – 26 .

20 . Lytras D , Manes K , Triantopoulou C et al. Persistent early organ failure: defi ning the high-risk group of patients with severe acute pancreatitis? Pancreas 2008 ; 36 : 249 – 54 .

21 . Le M é e J , Paye F , Sauvanet A et al. Incidence and reversibility of organ fail-ure in the course of sterile or infected necrotizing pancreatitis . Arch Surg 2001 ; 136 : 1386 – 90 .

22 . Isenmann R , Rau B , Beger HG . Early severe acute pancreatitis: characteris-tics of a new subgroup . Pancreas 2001 ; 22 : 274 – 8 .

23 . Tao HQ , Zhang JX , Zou SC . Clinical characteristics and management of patients with early acute severe pancreatitis: experience from a medical center in China . World J Gastroenterol 2004 ; 10 : 919 – 21 .

24 . Petrov MS , van Santvoort HC , Besselink MG et al. Enteral nutrition and the risk of mortality and infectious complications in patients with severe acute pancreatitis: a meta-analysis of randomized trials . Arch Surg 2008 ; 143 : 1111 – 7 .

25 . Windsor JA . Minimally invasive pancreatic necrosectomy . Br J Surg 2007 ; 94 : 132 – 3 .

26 . Petrov MS . Meta-analyses on the prophylactic use of antibiotics in acute pancreatitis: many are called but few are chosen . Am J Gastroenterol 2008 ; 103 : 1837 – 8 .

27 . Cavallini G , Frulloni L . Somatostatin and octreotide in acute pancreatitis: the never-ending story . Dig Liver Dis 2001 ; 33 : 192 – 201 .

28 . Abu-Zidan FM , Windsor JA . Lexipafant and acute pancreatitis: a critical appraisal of the clinical trials . Eur J Surg 2002 ; 168 : 215 – 9 .

29 . Ishikawa K , Idoguchi K , Tanaka H et al. Classifi cation of acute pancreatitis based on retroperitoneal extension: application of the concept of interfascial planes . Eur J Radiol 2006 ; 60 : 445 – 52 .

30 . Bradley EL III . Confusion in the imaging ranks: time for a change? Pancreas 2006 ; 33 : 321 – 2 .

31 . Frey CF . Classifi cation of pancreatitis: state-of-the-art, 1986 . Pancreas 1986 ; 1 : 62 – 8 .

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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titis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992 . Arch Surg 1993 ; 128 : 586 – 90 .

2 . Vege SS , Chari ST . Organ failure as an indicator of severity of acute pancreatitis: time to revisit the Atlanta classifi cation . Gastroenterology 2005 ; 128 : 1133 – 5 .

3 . Banks PA , Freeman ML . Practice guidelines in acute pancreatitis . Am J Gastroenterol 2006 ; 101 : 2379 – 400 .

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 ” ).