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2013 by the American College of Gastroenterology The American Journal of GASTROENTEROOG!

nat"re #"blishing gro"# PRACTICE GUIDELINES 1


American College of Gastroenterology G"i$eline%
&anagement of Ac"te 'ancreatitis
Scott Tenner, &(, &')* +ACG
1
, ,ohn -aillie* &-, Ch-, +RC', +ACG
2
, ,ohn (e.itt* &(, +ACG
3
an$ Santhi S/aroo# 0ege, &(, +ACG
1
This guideline resen!s recommenda!ions for !he managemen! of a!ien!s "i!h acu!e ancrea!i!is #AP$% During
!he as! decade& !here ha'e (een ne" unders!andings and de'elomen!s in !he diagnosis, e!iolog), and earl)
and la!e managemen! of !he disease% As !he diagnosis of AP is mos! of!en es!a(lished () clinical s)m!oms and
la(ora!or) !es!ing, con!ras!*enhanced comu!ed !omograh) #CECT$ and+or magne!ic resonance imaging #,RI$ of
!he ancreas should (e reser'ed for a!ien!s in "hom !he diagnosis is unclear or "ho fail !o imro'e clinicall)%
-emod)namic s!a!us should (e assessed immedia!el) uon resen!a!ion and resusci!a!i'e measures (egun
as needed% Pa!ien!s "i!h organ failure and+or !he s)s!emic inflamma!or) resonse s)ndrome #SIRS$ should (e
admi!!ed !o an in!ensi'e care uni! or in!ermediar) care se!!ing "hene'er ossi(le% Aggressi'e h)dra!ion should (e
ro'ided !o all a!ien!s, unless cardio'ascular and+or renal comor(idi!es reclude i!. Earl) aggressi'e in!ra'enous
h)dra!ion is mos! (eneficial "i!hin !he firs! 1./.0 h, and ma) ha'e li!!le (enefi! (e)ond. Pa!ien!s "i!h AP and
concurren! acu!e cholangi!is should undergo endoscoic re!rograde cholangioancrea!ograh) #ERCP$ "i!hin .0 h
of admission. Pancrea!ic duc! s!en!s and+or os!rocedure rec!al nons!eroidal an!i*inflamma!or) drug #NSAID$
suosi!ories should (e u!ili1ed !o lo"er !he ris2 of se'ere os!*ERCP ancrea!i!is in high*ris2 a!ien!s. Rou!ine use
of roh)lac!ic an!i(io!ics in a!ien!s "i!h se'ere AP and+or s!erile necrosis is no! recommended. In a!ien!s "i!h
infec!ed necrosis, an!i(io!ics 2no"n !o ene!ra!e ancrea!ic necrosis ma) (e useful in dela)ing in!er'en!ion, !hus
decreasing mor(idi!) and mor!ali!). In mild AP, oral feedings can (e s!ar!ed immedia!el) if !here is no nausea and
'omi!ing. In se'ere AP, en!eral nu!ri!ion is recommended !o re'en! infec!ious comlica!ions, "hereas aren!eral
nu!ri!ion should (e a'oided. As)m!oma!ic ancrea!ic and+or e3!raancrea!ic necrosis and+or seudoc)s!s do no!
"arran! in!er'en!ion regardless of si1e, loca!ion, and+or e3!ension. In s!a(le a!ien!s "i!h infec!ed necrosis,
surgical& radiologic, and+or endoscoic drainage should (e dela)ed, refera(l) for 0 "ee2s, !o allo" !he
de'elomen! of a "all around !he necrosis%
Am J Gastroenterol a$2ance online #"blication* 30 ,"ly 20133 $oi%10410356a7g420134215
Ac"te #ancreatitis 8A'9 is one of the most common $iseases
of the gastrointestinal tract, lea$ing to tremen$o"s emotion:
al, #hysical, an$ financial h"man b"r$en 81*29. ;n the <nite$
States, in 200=, A' /as the most common gastroenterology
$ischarge $iagnosis /ith a cost of 24> billion $ollars 8294
Recent st"$ies sho/ the inci$ence of A' 2aries bet/een 14=
an$ ?341 cases #er 100*000 /orl$/i$e 83*19. An increase in
the ann"al inci$ence for A' has been obser2e$ in most recent
st"$ies4 E#i$emiologic re2ie/ $ata from the 1=55 to 2003
National )os#ital (ischarge S"r2ey sho/e$ that hos#ital
a$missions for A' increase$ from 10 #er 100*000 in 1==5
to
?0 #er 100*000 in 2002. Altho"gh the case fatality rate for
A' has $ecrease$ o2er time, the o2erall #o#"lation mortality
rate for A' has remaine$ "nchange$ 8194
There ha2e been im#ortant changes in the $efinitions an$
classification of A' since the Atlanta classification from 1==2
8@9. ("ring the #ast $eca$e, se2eral limitations ha2e been rec:
ogniAe$ that le$ to a /orBing gro"# an$ /eb:base$ consens"s
re2ision 8>9. T/o $istinct #hases of A' ha2e no/ been
i$entifie$% 8i9 early 8/ithin 1 /eeB9, characteriAe$ by the
systemic inflam: matory res#onse syn$rome 8S;RS9 an$6or
organ fail"re3 an$ 8ii9 late 8 C 1 /eeB9, characteriAe$ by local
com#lications. ;t is critical to recogniAe the #aramo"nt
im#ortance of organ fail"re in $etermining $isease se2erity.
ocal com#lications are $efine$ as #eri#ancreatic fl"i$
collections* #ancreatic an$ #eri#ancreatic necrosis 8sterile or
infecte$9, #se"$ocysts, an$ /alle$:off necro: sis 8sterile or
infecte$94 ;solate$ eDtra#ancreatic necrosis is also incl"$e$
"n$er the term necrotiAing #ancreatitis3 altho"gh
1
State <ni2ersity of Ne/ !orB* (o/nstate &e$ical Center, -rooBlyn* Ne/ !orB, <SA3
2
Carteret &e$ical Gro"#* &orehea$ City, North Carolina* <SA3
3
;n$iana
<ni2ersity &e$ical Center, ;n$iana#olis* ;n$iana* <SA3
1
&ayo Clinic* Rochester, &innesota* <SA4 Corresondence4 Santhi S/aroo# 0ege* &(* +ACG* (i2ision
of Gastroenterology, &ayo Clinic* 200 +irst Street S., Rochester, &innesota @@=0@* <SA4 E:mail% 2ege4santhiEmayo4e$"
Recei'ed .5 Decem(er .61.7 acce!ed 18 June .615
. Tenner et al.
8iii9 characteristic fin$ings from ab$ominal imaging 8strong
recommen$ation* mo$erate F"ality of e2i$ence94
24 Contrast:enhance$ com#"te$ tomogra#hy 8CECT9 an$6or
magnetic resonance imaging 8&R;9 of the #ancreas sho"l$
be reser2e$ for #atients in /hom the $iagnosis is "nclear
or /ho fail to im#ro2e clinically /ithin the first 15G?2 h
after hos#ital a$mission or to e2al"ate com#lications
8strong recommen$ation* lo/ F"ality of e2i$ence94
o"tcomes liBe #ersistent organ fail"re, infecte$ necrosis, an$
mor: tality of this entity are more often seen /hen com#are$ to
inter: stitial #ancreatitis, these com#lications are more
commonly seen in #atients /ith #ancreatic #arenchymal necrosis
8?9. There is no/ a thir$ interme$iate gra$e of se2erity,
mo$erately se2ere A'* that is characteriAe$ by local
com#lications in the absence of #ersistent organ fail"re. 'atients
/ith mo$erately se2ere A' may ha2e tran: sient organ fail"re,
lasting H 15 h. &o$erately se2ere A' may also eDacerbate
"n$erlying comorbi$ $isease b"t is associate$ /ith a lo/
mortality. Se2ere A' is no/ $efine$ entirely on the #resence of
#ersistent organ fail"re 8$efine$ by a mo$ifie$ &arshall Score9
8594 .e first $isc"ss the $iagnosis* etiology, an$ se2erity of A'.
.e then foc"s on the early me$ical management of A' follo/e$
by a $isc"ssion of the management of com#licate$ $isease, most
nota: bly #ancreatic necrosis. Early management foc"ses on
a$2ance: ments in o"r "n$erstan$ing of aggressi2e intra2eno"s
hy$ration* /hich /hen a##lie$ early a##ears to $ecrease
morbi$ity an$ mortality 8=*109. The e2ol2ing iss"es of
antibiotics, n"trition, an$ en$osco#ic, ra$iologic, s"rgical, an$
other minimally in2asi2e
inter2entions /ill be a$$resse$.
A search of &E(;NE 2ia the O0;( interface "sing the
&eS) term Iac"te #ancreatitisJ limite$ to clinical trials,
re2ie/s, g"i$e: lines, an$ meta:analysis for the years 1=>>G2012
/as "n$ertaBen /itho"t lang"age restriction, as /ell as a
re2ie/ of clinical trials an$ re2ie/s Bno/n to the a"thors /ere
#erforme$ for the #re#ara: tion of this $oc"ment. The GRA(E
system /as "se$ to gra$e the strength of recommen$ations an$
the F"ality of e2i$ence 8119. An eD#lanation of the F"ality of
e2i$ence an$ strength of the recom: men$ations is sho/n in
Ta(le 1. Each section of the $oc"ment #resents the Bey
recommen$ations relate$ to the section to#ic* follo/e$ by a
s"mmary of the s"##orting e2i$ence. A s"mmary of
recommen$ations is #ro2i$e$ in Ta(le ..
(;AGNOS;S
Recommendations
14 The $iagnosis of A' is most often establishe$ by the
#resence of 2 of the 3 follo/ing criteria% 8i9 ab$ominal #ain
consistent /ith the $isease, 8ii9 ser"m amylase an$6or
li#ase greater than three times the "##er limit of normal,
an$6or
Ta(le 1% GRADE s)s!em of 9uali!) of e'idence and s!reng!h of
recommenda!ion
)igh +"rther research is 2ery "nliBely to change o"r confi$ence in
the estimate of effect4
&o$erate +"rther research is liBely to ha2e an im#ortant im#act on
o"r confi$ence in the estimate of effect an$ may change the
estimate4
o/ +"rther research is 2ery liBely to ha2e an im#ortant im#act on
o"r confi$ence in the estimate of effect an$ is liBely to change
the estimate4
0ery lo/ Any estimate of the effect is 2ery "ncertain4
,anagemen! of Acu!e Pancrea!i!is 5
(;AGNOS;S% C;N;CA 'RESENTAT;ON
'atients /ith A' ty#ically #resent /ith e#igastric or left "##er
F"a$rant #ain4 The #ain is "s"ally $escribe$ as constant /ith
ra$iation to the bacB* chest* or flanBs* b"t this $escri#tion is non:
s#ecific4 The intensity of the #ain is "s"ally se2ere, b"t can be 2ari:
able. The intensity an$ location of the #ain $o not correlate /ith
se2erity. 'ain $escribe$ as $"ll, colicBy, or locate$ in the lo/er
ab$ominal region is not consistent /ith A' an$ s"ggests an alter:
nati2e etiology. Ab$ominal imaging may be hel#f"l to $etermine the
$iagnosis of A' in #atients /ith aty#ical #resentations4
(;AGNOS;S% A-ORATOR! 'ARA&ETERS
-eca"se of limitations in sensiti2ity, s#ecificity, an$ #ositi2e an$
negati2e #re$icti2e 2al"e, ser"m amylase alone cannot be "se$
reliably for the $iagnosis of A' an$ ser"m li#ase is #referre$4
Ser"m amylase in A' #atients generally rises /ithin a fe/ ho"rs
after the onset of sym#toms an$ ret"rns to normal 2al"es /ithin
3G@ $ays3 ho/e2er* it may remain /ithin the normal range on
a$mission in as many as one:fifth of #atients 812*139. Com#are$
/ith li#ase, ser"m amylase ret"rns more F"icBly to 2al"es belo/ the
"##er limit of normal. Ser"m amylase concentrations may be
normal in alcohol:in$"ce$ A' an$ hy#ertriglyceri$emia4 Ser"m
amylase concentrations might be high in the absence of A'
in macroamylasaemia 8a syn$rome characteriAe$ by the
formation of large molec"lar com#leDes bet/een amylase an$
abnormal imm"noglob"lins9* in #atients /ith $ecrease$
glomer"lar filtration rate, in $iseases of the sali2ary glan$s*
an$ in eDtra#ancreatic ab$ominal $iseases associate$ /ith
inflammation, incl"$ing ac"te a##en$icitis, cholecystitis, intes:
tinal obstr"ction or ischemia, #e#tic "lcer, an$
gynecological $iseases4
Ser"m li#ase a##ears to be more s#ecific an$ remains ele:
2ate$ longer than amylase after $isease #resentation4 (es#ite
recommen$ations of #re2io"s in2estigators 8119 an$ g"i$elines
for the management of A' 81@9 that em#hasiAe the a$2antage
of ser"m li#ase, similar #roblems /ith the #re$icti2e 2al"e
remain in certain #atient #o#"lations, incl"$ing the eDistence
of macroli#asemia. i#ase is also fo"n$ to be ele2ate$ in a 2ari:
ety of non#ancreatic $iseases, s"ch as renal $isease, a##en:
$icitis, cholecystitis, an$ so on. ;n a$$ition, an "##er limit
of normal greater than 3G@ times may be nee$e$ in $iabetics
/ho a##ear to ha2e higher me$ian li#ase com#are$ /ith
non$iabetic #atients for "nclear reasons 81>*1?9. A ,a#anese
consens"s con: ference to $etermine a##ro#riate Ic"toff J
2al"es for amylase an$
0O<&E 101
K
LLL 2012
Ta(le .% Summar) of recommenda!ions
(iagnosis
14 The $iagnosis of A' is most often establishe$ by the #resence of t/o of the three follo/ing criteria% 8i9 ab$ominal #ain consistent /ith the $isease*
8ii9 ser"m amylase an$6or li#ase greater than three times the "##er limit of normal* an$6or 8iii9 characteristic fin$ings from ab$ominal imaging
8strong recommen$ation* mo$erate F"ality of e2i$ence94
24 Contrast:enhance$ com#"te$ tomogra#hic 8CECT9 an$6or magnetic resonance imaging 8&R;9 of the #ancreas sho"l$ be reser2e$ for #atients in
/hom the $iagnosis is "nclear or /ho fail to im#ro2e clinically /ithin the first 15G?2 h after hos#ital a$mission 8strong recommen$ation* lo/ F"ality of
e2i$ence94
Etiology
34 Transab$ominal "ltraso"n$ sho"l$ be #erforme$ in all #atients /ith ac"te #ancreatitis 8strong recommen$ation* lo/ F"ality of e2i$ence94
14 ;n the absence of gallstones an$6or history of significant history of alcohol "se* a ser"m triglyceri$e sho"l$ be obtaine$ an$ consi$ere$ the etiology
if C 1*000 mg6$l 8con$itional recommen$ation* mo$erate F"ality of e2i$ence94
@4 ;n a #atient ol$er than 10 years* a #ancreatic t"mor sho"l$ be consi$ere$ as a #ossible ca"se of ac"te #ancreatitis 8con$itional recommen$ation*
lo/ F"ality of e2i$ence94
>4 En$osco#ic in2estigation in #atients /ith ac"te i$io#athic #ancreatitis sho"l$ be limite$* as the risBs an$ benefits of in2estigation in these #atients are
"nclear 8con$itional recommen$ation* lo/ F"ality of e2i$ence94
?4 'atients /ith i$io#athic #ancreatitis sho"l$ be referre$ to centers of eD#ertise 8con$itional recommen$ation* lo/ F"ality of e2i$ence94
54 Genetic testing may be consi$ere$ in yo"ng #atients 8 H 30 years ol$9 if no ca"se is e2i$ent an$ a family history of #ancreatic $isease is #resent
8con$itional recommen$ation* lo/ F"ality of e2i$ence94
;nitial assessment an$ risB stratification
=4 )emo$ynamic stat"s sho"l$ be assesse$ imme$iately "#on #resentation an$ res"scitati2e meas"res beg"n as nee$e$ 8strong recommen$ation*
mo$erate F"ality of e2i$ence94
104 RisB assessment sho"l$ be #erforme$ to stratify #atients into higher- an$ lo/er:risB categories to assist triage* s"ch as a$mission to an intensi2e care
setting 8con$itional recommen$ation* mo$erate F"ality of e2i$ence94
114 'atients /ith organ fail"re sho"l$ be a$mitte$ to an intensi2e care "nit or interme$iary care setting /hene2er #ossible 8strong recommen$ation*
lo/ F"ality of e2i$ence94
;nitial management
124 Aggressi2e hy$ration* $efine$ as 2@0:@00 ml #er ho"r of isotonic crystalloi$ sol"tion sho"l$ be #ro2i$e$ to all #atients* "nless car$io2asc"lar
an$6or renal comorbi$ites eDist4 Early aggressi2e intra2eno"s hy$ration is most beneficial the first 12G21 h* an$ may ha2e little benefit beyon$
8strong recommen$ation* mo$erate F"ality of e2i$ence94
134 ;n a #atient /ith se2ere 2ol"me $e#letion, manifest as hy#otension an$ tachycar$ia* more ra#i$ re#letion 8bol"s9 may be nee$e$ 8con$itional
recommen$ation, mo$erate F"ality of e2i$ence94
114 actate$ RingerMs sol"tion may be the #referre$ isotonic crystalloi$ re#lacement fl"i$ 8con$itional recommen$ation* mo$erate F"ality of e2i$ence94
1@4 +l"i$ reF"irements sho"l$ be reassesse$ at freF"ent inter2als /ithin > h of a$mission an$ for the neDt 21G15 h4 The goal of aggressi2e hy$ration
sho"l$ be to $ecrease the bloo$ "rea nitrogen 8strong recommen$ation* mo$erate F"ality of e2i$ence94
ERC' in ac"te #ancreatitis
1>4 'atients /ith ac"te #ancreatitis an$ conc"rrent ac"te cholangitis sho"l$ "n$ergo ERC' /ithin 21 h of a$mission 8strong recommen$ation* mo$erate
F"ality of e2i$ence94
1?4 ERC' is not nee$e$ in most #atients /ith gallstone #ancreatitis /ho lacB laboratory or clinical e2i$ence of ongoing biliary obstr"ction 8strong
recommen$ation* lo/ F"ality of e2i$ence94
154 ;n the absence of cholangitis an$6or 7a"n$ice* &RC' or en$osco#ic "ltraso"n$ 8E<S9 rather than $iagnostic ERC' sho"l$ be "se$ to screen for
chole$ocholithiasis if highly s"s#ecte$ 8con$itional recommen$ation* lo/ F"ality of e2i$ence94
1=4 'ancreatic $"ct stents an$6or #ost#roce$"re rectal nonsteroi$al anti:inflammatory $r"g 8NSA;(9 s"##ositories sho"l$ be "tiliAe$ to #re2ent se2ere
#ost:ERC' #ancreatitis in high:risB #atients 8con$itional recommen$ation* mo$erate F"ality of e2i$ence94
The role of antibiotics in ac"te #ancreatitis
204 Antibiotics sho"l$ be gi2en for an eDtra#ancreatic infection* s"ch as cholangitis* catheter:acF"ire$ infections* bacteremia* "rinary tract infections*
#ne"monia 8strong recommen$ation* high F"ality of e2i$ence94
214 Ro"tine "se of #ro#hylactic antibiotics in #atients /ith se2ere ac"te #ancreatitis is not recommen$e$ 8strong recommen$ation* mo$erate F"ality of
e2i$ence94
224 The "se of antibiotics in #atients /ith sterile necrosis to #re2ent the $e2elo#ment of infecte$ necrosis is not recommen$e$ 8strong recommen$ation*
mo$erate F"ality of e2i$ence94
234 ;nfecte$ necrosis sho"l$ be consi$ere$ in #atients /ith #ancreatic or eDtra#ancreatic necrosis /ho $eteriorate or fail to im#ro2e after ?G10 $ays
of hos#italiAation4 ;n these #atients* either 8i9 initial CT:g"i$e$ fine nee$le as#iration 8+NA9 for Gram stain an$ c"lt"re to g"i$e "se of a##ro#riate
antibiotics or 8ii9 em#iric "se of antibiotics /itho"t CT +NA sho"l$ be gi2en 8strong recommen$ation* lo/ F"ality of e2i$ence94
Table 2 contin"e$ on the follo/ing #age
Ta(le .% Con!inued
214 ;n #atients /ith infecte$ necrosis* antibiotics Bno/n to #enetrate #ancreatic necrosis* s"ch as carba#enems* F"inolones* an$ metroni$aAole* may
be "sef"l in $elaying or sometimes totally a2oi$ing inter2ention* th"s $ecreasing morbi$ity an$ mortality 8con$itional recommen$ation* lo/ F"ality of
e2i$ence94
2@4 Ro"tine a$ministration of antif"ngal agents along /ith #ro#hylactic or thera#e"tic antibiotics is not recommen$e$ 8con$itional recommen$ation* lo/ F"ality
of e2i$ence94
N"trition in ac"te #ancreatitis
2>4 ;n mil$ A', oral fee$ings can be starte$ imme$iately if there is no na"sea an$ 2omiting* an$ ab$ominal #ain has resol2e$ 8con$itional recommen$a: tion*
mo$erate F"ality of e2i$ence94
2?4 ;n mil$ A', initiation of fee$ing /ith a lo/:fat soli$ $iet a##ears as safe as a clear liF"i$ $iet 8con$itional recommen$ations* mo$erate F"ality of
e2i$ence94
254 ;n se2ere A', enteral n"trition is recommen$e$ to #re2ent infectio"s com#lications4 'arenteral n"trition sho"l$ be a2oi$e$ "nless the enteral ro"te is not
a2ailable* not tolerate$* or not meeting caloric reF"irements 8strong recommen$ation* high F"ality of e2i$ence94
2=4 Nasogastric $eli2ery an$ naso7e7"nal $eli2ery of enteral fee$ing a##ear com#arable in efficacy an$ safety 8strong recommen$ation* mo$erate F"ality of
e2i$ence94
The role of s"rgery in ac"te #ancreatitis
304 ;n #atients /ith mil$ A', fo"n$ to ha2e gallstones in the gallbla$$er, a cholecystectomy sho"l$ be #erforme$ before $ischarge to #re2ent a rec"rrence of A'
8strong recommen$ation* mo$erate F"ality of e2i$ence94
314 ;n a #atient /ith necrotiAing biliary A', in or$er to #re2ent infection* cholecystectomy is to be $eferre$ "ntil acti2e inflammation s"bsi$es an$ fl"i$
collections resol2e or stabiliAe 8strong recommen$ation* mo$erate F"ality of e2i$ence94
324 The #resence of asym#tomatic #se"$ocysts an$ #ancreatic an$6or eDtra#ancreatic necrosis $o not /arrant inter2ention* regar$less of siAe* location* an$6or
eDtension 8strong recommen$ation* mo$erate F"ality of e2i$ence94
334 ;n stable #atients /ith infecte$ necrosis* s"rgical* ra$iologic* an$6or en$osco#ic $rainage sho"l$ be $elaye$ #referably for more than 1 /eeBs to allo/
liF"efication of the contents an$ the $e2elo#ment of a fibro"s /all aro"n$ the necrosis 8/alle$:off necrosis9 8strong recommen$ation* lo/ F"ality of
e2i$ence94
314 ;n sym#tomatic #atients /ith infecte$ necrosis* minimally in2asi2e metho$s of necrosectomy are #referre$ to o#en necrosectomy 8strong recommen: $ation*
lo/ F"ality of e2i$ence94
A', ac"te #ancreatitis3 CT* com#"te$ tomogra#hy3 ERC', en$osco#ic retrogra$e cholangio#ancreatogra#hy3 &RC', magnetic resonance cholangio#ancreatogra#hy.
li#ase co"l$ not reach consens"s on a##ro#riate "##er limits of
normal 8159. Assays of many other #ancreatic enAymes ha2e
been assesse$ $"ring the #ast 1@ years, b"t none seems to
offer better $iagnostic 2al"e than those of ser"m amylase an$
li#ase 81=9. Altho"gh most st"$ies sho/ a $iagnostic efficacy of
greater than 3G@ times the "##er limit of normal, clinicians
m"st consi$er the clinical con$ition of the #atient /hen
e2al"at: ing amylase an$ li#ase ele2ations. .hen a $o"bt
regar$ing the $iagnosis of A' eDists* ab$ominal imaging, s"ch
as CECT, is recommen$e$.
(;AGNOS;S% A-(O&;NA ;&AG;NG
Ab$ominal imaging is "sef"l to confirm the $iagnosis of A'4
CECT #ro2i$es o2er =0N sensiti2ity an$ s#ecificity for the
$iag: nosis of A' 82094 Ro"tine "se of CECT in #atients /ith
A' is "n/arrante$, as the $iagnosis is a##arent in many
#atients an$ most ha2e a mil$, "ncom#licate$ co"rse.
)o/e2er* in a #atient failing to im#ro2e after 15G?2 8e4g4*
#ersistent #ain* fe2er, na"sea* "nable to begin oral fee$ing9*
CECT or &R; imaging is recom: men$e$ to assess local
com#lications s"ch as #ancreatic necrosis 821G2394 Com#"te$
tomogra#hy 8CT9 an$ &R; are com#arable in the early
assessment of A' 82194 &R;* by em#loying magnetic resonance
cholangio#ancreatogra#hy 8&RC'9* has the a$2antage
of $etecting chole$ocholithiasis $o/n to 3 mm $iameter an$
#an: creatic $"ct $isr"#tion /hile #ro2i$ing high:F"ality
imaging for $iagnostic an$6or se2erity #"r#oses4 &R; is hel#f"l
in #atients /ith a contrast allergy an$ renal ins"fficiency /here
T2:/eighte$ images /itho"t ga$olini"m contrast can
$iagnose #ancreatic necrosis 82194
ET;OOG!
Recommendations
14 Transab$ominal "ltraso"n$ sho"l$ be #erforme$ in all
#atients /ith A' 8strong recommen$ation, lo/ F"ality of
e2i$ence94
24 ;n the absence of gallstones an$6or history of
significant history of alcohol "se, a ser"m triglyceri$e
sho"l$ be obtaine$ an$ consi$ere$ the etiology if C
1*000 mg6$l.
8con$itional recommen$ation* mo$erate F"ality of e2i$ence94
34 ;n a #atient C 10 years ol$, a #ancreatic t"mor sho"l$ be
consi$ere$ as a #ossible ca"se of A' 8con$itional
recommen: $ation* lo/ F"ality of e2i$ence94
14 En$osco#ic in2estigation of an el"si2e etiology in #atients
/ith A' sho"l$ be limite$, as the risBs an$ benefits of
in2estigation in these #atients are "nclear 8con$itional
recommen$ation* lo/ F"ality of e2i$ence94
0O<&E 101
K
LLL 2012
@4 'atients /ith i$io#athic A' 8;A'9 sho"l$ be referre$
to centers of eD#ertise 8con$itional recommen$ation*
lo/ F"ality of e2i$ence94
>4 Genetic testing may be consi$ere$ in yo"ng
#atients
8 H 30 years ol$9 if no ca"se is e2i$ent an$ a family history
of #ancreatic $isease is #resent 8con$itional
recommen$ation* lo/ F"ality of e2i$ence94
ET;OOG!% GASTONES AN( ACO)O
The etiology of A' can be rea$ily establishe$ in most #atients4
The most common ca"se of A' is gallstones 810G?0N9 an$ alco:
hol 82@G3@N9 82@G2?94 -eca"se of the high #re2alence an$
im#or: tance of #re2enting rec"rrent $isease, ab$ominal
"ltraso"n$ to e2al"ate for cholelithiasis sho"l$ be #erforme$
on all #atients /ith A' 825G3094 ;$entification of gallstones
as the etiology sho"l$ #rom#t referral for cholecystectomy to
#re2ent rec"rrent attacBs an$ #otential biliary se#sis 82=*3094
Gallstone #ancreatitis is "s"ally an ac"te e2ent an$ resol2es
/hen the stone is remo2e$ or #asses s#ontaneo"sly.
Alcohol:in$"ce$ #ancreatitis often manifests as a s#ectr"m*
ranging from $iscrete e#iso$es of A' to chronic irre2ersible
silent changes. The $iagnosis sho"l$ not be entertaine$ "nless a
#erson has a history of o2er @ years of hea2y alcohol
cons"m#tion 83194 I)ea2yJ alcohol cons"m#tion is generally
consi$ere$ to be C @0 g #er $ay, b"t is often m"ch higher
8329. Clinically e2i$ent A' occ"rs in H @N of hea2y $rinBers
83393 th"s, there are liBely other factors that sensitiAe in$i2i$"als
to the effects of alcohol, s"ch as genetic factors an$ tobacco "se
82?*33*3194
OT)ER CA<SES O+ A'
;n the absence of alcohol or gallstones* ca"tion m"st be
eDercise$ /hen attrib"ting a #ossible etiology for A' to
another agent or con$ition4 &e$ications* infectio"s agents* an$
metabolic ca"ses s"ch as hy#ercalcemia an$
hy#er#arathyroi$ism are rare ca"ses* often falsely i$entifie$ as
ca"sing A' 83@G3?94 Altho"gh some $r"gs s"ch as >:
merca#to#"rine* aAathio#rine, an$ ((; 82O*3O: $i$eoDyinosine9
can clearly ca"se A', there are limite$ $ata s"#: #orting most
me$ications as ca"sati2e agents 83@94 'rimary an$ secon$ary
hy#ertriglyceri$emia can ca"se A'3 ho/e2er* these acco"nt for
only 1G1N of cases 83>94 Ser"m triglyceri$es sho"l$ rise abo2e
1*000 mg6$l to be consi$ere$ the ca"se of A' 835*3=94 A
lactescent 8milBy9 ser"m has been obser2e$ in as many as 20N
of #atients /ith A', an$ therefore a fasting triglyceri$e le2el
sho"l$ be re:e2al"ate$ 1 month after $ischarge /hen
hy#ertriglyceri$emia is s"s#ecte$ 81094 Altho"gh most $o not*
any benign or malignant mass that obstr"cts the main
#ancreatic can res"lt in A'4 ;t has been estimate$ that @G11N
of #atients /ith benign or malignant #ancreatobiliary t"mors
#resent /ith a##arent ;A' 811G1394 )is: torically,
a$enocarcinoma of the #ancreas /as consi$ere$ a $is: ease of
ol$ age. )o/e2er, increasingly #atients in their 10sPan$
occasionally yo"ngerPare #resenting /ith #ancreatic cancer4
This entity sho"l$ be s"s#ecte$ in any #atient C 10 years of
age /ith i$io#athic #ancreatitis* es#ecially those /ith a #rolonge$ or
rec"rrent co"rse 82?*11*1@94 Th"s* a contrast:enhance$ CT
scan or &R; is nee$e$ in these #atients4 A more eDtensi2e
e2al"ation incl"$ing en$osco#ic "ltraso"n$ 8E<S9 an$6or
&RC' may be nee$e$ initially or after a rec"rrent e#iso$e
of ;A' 81>94
;(;O'AT);
C A'
;A' is $efine$ as #ancreatitis /ith no etiology establishe$
after initial laboratory 8incl"$ing li#i$ an$ calci"m le2el9
an$ imag: ing tests 8transab$ominal "ltraso"n$ an$ CT
in the a##ro#ri: ate #atient9 81?94 ;n some #atients an
etiology may e2ent"ally be fo"n$, yet in others no $efinite
ca"se is e2er establishe$. 'atients /ith ;A' sho"l$ be
e2al"ate$ at centers of eDcellence foc"sing on #ancreatic
$isease, #ro2i$ing a$2ance$ en$osco#y ser2ices an$ a
combine$ m"lti$isci#linary a##roach.
Anatomic an$ #hysiologic anomalies of the #ancreas
occ"r in 10G1@N of the #o#"lation* incl"$ing #ancreas
$i2is"m an$ s#hincter of O$$i $ysf"nction 8159. ;t
remains contro2ersial if these $isor$ers alone ca"se A'
81=9. There may be a combination of factors, incl"$ing
anatomic an$ genetic, that #re$is#ose to the $e2elo#ment
of A' in s"sce#tible in$i2i$"als 8159. En$osco#ic thera#y,
foc"sing on treating #ancreas $i2is"m an$6or s#hincter of
O$$i $ysf"nction, carries a significant risB of #reci#itating
A' an$ sho"l$ be #erforme$ only in s#ecialiAe$ "nits
8@0*@19. The infl": ence of genetic $efects* s"ch as cationic
try#sinogen m"tations* S';NQ, or C+TR m"tations, in
ca"sing A' is being increasingly recogniAe$. These $efects,
f"rthermore* may also increase the risB of A' in #atients
/ith anatomic anomalies, s"ch as #ancreas $i2is"m 8159.
)o/e2er, the role of genetic testing in A' has yet to be
$etermine$, b"t may be "sef"l in #atients /ith more than one
family member /ith #ancreatic $isease 8319. ;n$i2i$"als /ith
;A' an$ a family history of #ancreatic $iseases sho"l$ be
referre$ for formal genetic co"nseling4
;N;T;A ASSESS&ENT AN( R;SQ STRAT;+;CAT;ON
Recommendations
14 )emo$ynamic stat"s sho"l$ be assesse$ imme$iately "#on
#resentation an$ res"scitati2e meas"res beg"n as nee$e$
8strong recommen$ation* mo$erate F"ality of e2i$ence94
24 RisB assessment sho"l$ be #erforme$ to stratify #atients
into higher- an$ lo/er-risB categories to assist triage,
s"ch as a$mission to an intensi2e care setting
8con$itional recommen$ation* lo/ to mo$erate F"ality of
e2i$ence94
34 'atients /ith organ fail"re sho"l$ be a$mitte$ to an
intensi2e care "nit or interme$iary care setting /hene2er
#ossible 8strong recommen$ation* lo/ F"ality of
e2i$ence94
S<&&AR! O+ E0;(ENCE
Defini!ion of se'ere AP
&ost e#iso$es of A' are mil$ an$ self:limiting, nee$ing only
brief hos#italiAation4 &il$ A' is $efine$ by the absence of organ
fail"re an$6or #ancreatic necrosis 8@*>94 -y 15 h after
a$mission* these
#atients ty#ically /o"l$ ha2e s"bstantially im#ro2e$ an$ beg"n
refee$ing4 ;n #atients /ith se2ere $isease, t/o #hases of A'
are recogniAe$% early 8/ithin the first /eeB9 an$ late. ocal
com#li: cations incl"$e #eri#ancreatic fl"i$ collections an$
#ancreatic an$ #eri#ancreatic necrosis 8sterile or infecte$94 &ost
#atients /ith se2ere $isease #resent to the emergency room /ith
no organ fail"re or #ancreatic necrosis3 "nfort"nately, this has
le$ to many errors in clinical management of this $isease 8@294
These errors incl"$e fail"re to #ro2i$e a$eF"ate hy$ration*
fail"re to $iagnose an$ treat cholangitis* an$ fail"re to treat
early organ fail"re. +or this reason* it is critical for the clinician
to recogniAe the im#or: tance of not falsely labeling a #atient
/ith mil$ $isease /ithin the first 15 h of a$mission for A'.
Se2ere A' occ"rs in 1@G20N of #atients 8@39. Se2ere A' is
$efine$ by the #resence of #ersistent 8fails to resol2e /ithin
15 h9 organ fail"re an$6or $eath 8>9. )istorically, in the
absence of organ fail"re, local com#lications from #ancreatitis,
s"ch as #ancreatic necrosis, /ere also consi$ere$ se2ere $isease
8@*>*@394 )o/e2er, these local com#lications 8incl"$ing
#ancreatic necro: sis /ith or /itho"t transient organ fail"re9
$efine mo$erately se2ere A' 8see Ta(le 59. &o$erately se2ere
ac"te #ancreatitis is characteriAe$ by the #resence of transient
organ fail"re or local or systematic com#lications in the
absence of #ersistent organ fail"re 8>9. An eDam#le of a #atient
/ith mo$erately se2ere ac"te #ancreatitis is one /ho has
#eri#ancreatic fl"i$ collections an$ #rolonge$ ab$ominal #ain,
le"Bocytosis an$, fe2er* ca"sing the #atient to remain
hos#italiAe$ for ?:10 $ays. ;n the absence of #er: sistent organ
fail"re* mortality in #atients /ith this entity is less than se2ere
ac"te #ancreatitis. ;f #ersistent organ fail"re $e2elo#s in a
#atient /ith necrotiAing #ancreatitis, it is then consi$ere$ se2ere
$isease.
Organ fail"re ha$ #re2io"sly been $efine$ as shocB 8systolic
bloo$ #ress"re H =0 mm )g9* #"lmonary ins"fficiency
8'aO
2
H >0 mm )g9, renal fail"re 8creatinine C 2 mg6$l after
rehy$ration9*
an$6or gastrointestinal blee$ing 8 C @00 ml of bloo$ loss621 h9
8@394 The Re2ise$ Atlanta Criteria no/ $efine organ fail"re as a
score of 2 or more for one of these organ systems "sing the
mo$ifie$ &arshall scoring system 8>*59. The a"thors feel that
rather than calc"late a &arshal score 8/hich may be com#leD
for the b"sy clinician9, relying on the ol$er Atlanta $efinitions
/o"l$ be as "sef"l. +"rther st"$y is nee$e$ to 2ali$ate the nee$
for "sing the &arshal score4
'ancreatic necrosis is $efine$ as $iff"se or focal areas of non:
2iable #ancreatic #arenchyma C 3 cm in siAe or C 30N of the
#an: creas 8@394 'ancreatic necrosis can be sterile or infecte$
8$isc"sse$ belo/94 ;n the absence of #ancreatic necrosis* in mil$
$isease the e$emato"s #ancreas is $efine$ as interstitial
#ancreatitis4 Altho"gh there is some correlation bet/een
infection* #ancreatic necrosis* hos#ital length of stay, an$ organ
fail"re, both #atients /ith sterile necrosis an$ infecte$ necrosis
may $e2elo# organ fail"re 8@@*@>94 The #resence of infection
/ithin the necrosis #robably $oes not increase the liBelihoo$ of
#resent or f"t"re organ fail"re. 'atients /ith sterile necrosis can
s"ffer from organ fail"re an$ a##ear as ill clinically as those
#atients /ith infecte$ necrosis4 'ersistent organ fail"re is no/
$efine$ by a &o$ifie$ &arshal Score 8>*594
Ta(le 5% Defini!ions of se'eri!) in acu!e ancrea!i!is4 comarison
of A!lan!a and recen! re'ision
A!lan!a cri!eria #1::5$ A!lan!a Re'ision #.615$
,ild acu!e ancrea!i!is ,ild acu!e ancrea!i!is
Absence of organ fail"re Absence of organ fail"re
Absence of local com#lications Absence of local com#lications
Se'ere acu!e ancrea!i!is &o$erately se2ere ac"te #ancreatitis
14 ocal com#lications AND+;R 14 ocal com#lications AND+;R
24 Organ fail"re 2. Transient organ fail"re 8 H 15 h9
G; blee$ing 8C @00 cc621 hr9 Se'ere acu!e ancrea!i!is
ShocB G S-' =0 mm )g 'ersistent organ fail"re C 15 h
a
'aO 2 >0 N
Creatinine 2 mg6$l
G;* gastrointestinal3 S-', systolic bloo$ #ress"re4
a
'ersistent organ fail"re is no/ $efine$ by a &o$ifie$ &arshal Score 8>*59
;solate$ eDtra#ancreatic necrosis is also incl"$e$ "n$er the term
necrotiAing #ancreatitis. This entity, initially tho"ght to be a non:
s#ecific anatomic fin$ing /ith no clinical significance, has become
better characteriAe$ an$ is associate$ /ith a$2erse o"tcomes, s"ch as
organ fail"re an$ #ersistent organ fail"re, b"t these o"tcomes are less
freF"ent. EDtra#ancreatic necrosis is more often a##reciate$ $"ring
s"rgery than being i$entifie$ on imaging st"$ies. Altho"gh most
ra$iologists can easily i$entify #ancreatic #arenchymal necrosis,
in the absence of s"rgical inter2ention, eDtra#ancreatic necrosis
is a##reciate$ less often 8?94
Predic!ing se'ere AP
Clinicians ha2e been largely "nable to #re$ict /hich #atients
/ith A' /ill $e2elo# se2ere $isease. <niformly, se2erity
scoring systems are c"mbersome, ty#ically reF"ire 15 h to
become acc": rate, an$ /hen the score $emonstrates se2ere
$isease, the #atientMs con$ition is ob2io"s regar$less of the score
8@2*@?*@594 The ne/ scoring systems* s"ch as the -;SA' 8@=9*
ha2e not sho/n to be more acc"rate than the other scoring
systems 8>0*>194 ;n general* A':s#ecific scoring systems ha2e a
limite$ 2al"e, as they #ro2i$e little a$$itional information to the
clinician in the e2al"ation of #atients an$ may $elay a##ro#riate
management 8@294
Altho"gh laboratory testing s"ch as the hematocrit an$ bloo$
"rea nitrogen 8-<N9 can assist clinicians 8@2*>2*>39, no
laboratory test is #ractically a2ailable or consistently acc"rate to
#re$ict se2er: ity in #atients /ith A' 8>1G>>9. E2en the ac"te:
#hase reactant C:reacti2e #rotein 8CR'9, the most /i$ely
st"$ie$ inflammatory marBer in A', is not #ractical as it taBes
?2 h to become acc"rate 8@19. CT an$6or &R; imaging also
cannot reliably $etermine se2erity early in the co"rse of A', as
necrosis "s"ally is not #resent on a$mission an$ may $e2elo#
after 21G15 h 821*>?9. Th"s, in the absence of any a2ailable test
to $etermine se2erity, close eDamina: tion to assess early fl"i$
losses, hy#o2olemic shocB, an$ sym#toms s"ggesti2e of organ
$ysf"nction is cr"cial.
0O<&E 101
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#atients /ith #ersistent S;RS, #artic"larly those /ho are
tachy#nic an$6or tachycar$ic, sho"l$ be a$mitte$ to an
intensi2e care "nit or similar "nit for aggressi2e intra2eno"s
hy$ration an$ close monitoring.
;N;T;A &ANAGE&ENT
&"lti#le or eDtensi2e eDtra#ancreatic collections 8>?9
-&;* bo$y mass in$eD3 -<N* bloo$ "rea nitrogen3 )CT, hematocrit3
.-C* /hite bloo$ cell4
a
The #resence of organ fail"re an$6or #ancreatic necrosis $efines se2ere ac"te
#ancreatitis.
Rather than $e#en$ing on a scoring system to #re$ict
se2erity of A', clinicians nee$ to be a/are of intrinsic #atient:
relate$ risB factors, incl"$ing laboratory an$ imaging risB
factors, for the $e2el: o#ment of se2ere $isease 8Ta(le 09. These
incl"$e% a #atientMs age* comorbi$ health #roblems, bo$y mass
in$eD 8?19, the #resence of S;RS 8?0*?19, signs of hy#o2olemia
s"ch as an ele2ate$ -<N 8>39 an$ an ele2ate$ hematocrit 8>29,
#resence of #le"ral eff"sions an$6or infiltrates 8?39, altere$
mental stat"s 8>=9, an$ other factors 8@1*?29 8Ta(le 594
("ring the early #hase of the $isease 8/ithin the first /eeB9*
$eath occ"rs as a res"lt of the $e2elo#ment, #ersistence, an$
#ro: gressi2e nat"re of organ $ysf"nction 8?@*?>9. The
$e2elo#ment of organ fail"re a##ears to be relate$ to the
$e2elo#ment an$ #er: sistence of S;RS. The re2ersal of an$
early organ fail"re has been sho/n to be im#ortant in
#re2enting morbi$ity an$ mortality in #atients /ith A' 8??*?59.
Altho"gh the #resence of S;RS $"ring the initial 21 h has a
high sensiti2ity for #re$icting organ fail"re an$ mortality, the
#resence of S;RS lacBs s#ecificity for se2ere $is: ease 811N9. The
lacB of s#ecificity is $"e to the fact that the #res: ence of S;RS is
not as im#ortant as its #ersistence. +or this reason,
Recommendations
14 Aggressi2e hy$ration* $efine$ as 2@0G@00 ml #er ho"r of
iso: tonic crystalloi$ sol"tion sho"l$ be #ro2i$e$ to all
#atients* "nless car$io2asc"lar, renal, or other relate$
comorbi$ factors eDist4 Early aggressi2e intra2eno"s
hy$ration is most
beneficial $"ring the first 12G21 h* an$ may ha2e little
benefit beyon$ this time #erio$ 8strong recommen$ation*
mo$erate F"ality of e2i$ence94
24 ;n a #atient /ith se2ere 2ol"me $e#letion* manifest as hy#o:
tension an$ tachycar$ia* more ra#i$ re#letion 8bol"s9 may
be nee$e$ 8con$itional recommen$ation* mo$erate F"ality
of e2i$ence94
34 actate$ RingerMs sol"tion may be the #referre$ isotonic
crystalloi$ re#lacement fl"i$ 8con$itional recommen$ation*
mo$erate F"ality of e2i$ence94
14 +l"i$ reF"irements sho"l$ be reassesse$ at freF"ent inter2als
/ithin > h of a$mission an$ for the neDt 21G15 h4 The goal
of aggressi2e hy$ration sho"l$ be to $ecrease the -<N
8strong recommen$ation* mo$erate F"ality of e2i$ence94
EAR! AGGRESS;0E ;NTRA0ENO<S )!(RAT;ON
(es#ite $oAens of ran$omiAe$ trials* no me$ication has been
sho/n to be effecti2e in treating A' 832*@394 )o/e2er, an
effecti2e inter2ention has been /ell $escribe$% early aggressi2e
intra2eno"s hy$ration4 Recommen$ations regar$ing
aggressi2e hy$ration are base$ on eD#ert o#inion 810*@2*@39*
laboratory eD#eriments 8?=*509* in$irect clinical e2i$ence
8>2*>3*51*529* e#i$emiologic st"$ies 8@=9* an$ both
retros#ecti2e an$ #ros#ecti2e clinical trials 8=*5394
The rationale for early aggressi2e hy$ration in A' arises
from obser2ation of the freF"ent hy#o2olemia that occ"rs from
m"lti#le factors affecting #atients /ith A', incl"$ing 2omiting*
re$"ce$ oral intaBe, thir$ s#acing of fl"i$s, increase$ res#iratory
losses, an$ $ia: #horesis. ;n a$$ition, researchers hy#othesiAe
that a combination of microangio#athic effects an$ e$ema of the
inflame$ #ancreas $ecreases bloo$ flo/, lea$ing to increase$
cell"lar $eath, necro: sis, an$ ongoing release of #ancreatic
enAymes acti2ating n"mer: o"s casca$es. ;nflammation also
increases 2asc"lar #ermeability* lea$ing to increase$ thir$
s#ace fl"i$ losses an$ /orsening of #ancreatic hy#o#erf"sion
that lea$s to increase$ #ancreatic #arenchymal necrosis an$ cell
$eath 8519. Early aggressi2e intra: 2eno"s fl"i$ res"scitation
#ro2i$es micro- an$ macrocirc"latory s"##ort to #re2ent
serio"s com#lications s"ch as #ancreatic necrosis 81094
Altho"gh there are limite$ #ros#ecti2e $ata that
aggressi2e intra2eno"s hy$ration can be monitore$ an$6or
g"i$e$ by
Ta(le 0% Clinical findings associa!ed "i!h a se'ere course for
ini!ial ris2 assessmen!
a
Patient characteristics
Age C @@ years 8@3*@?9
Obesity 8-&; C 30 Bg6m
2
9 8>59
Altere$ mental stat"s 8>=9
Comorbi$ $isease 8@39
The systemic inflammatory response syndrome (SIRS) 8>*@3*@1*?0*?19
'resence of C 2 of the follo/ing criteria%
G #"lse C =0 beats6min
G res#irations C 206min or 'aCO C 32 mm )g
2
G tem#erat"re C 35 RC or H 3> RC
G.-C co"nt C 12*000 or H 1*000 cells6mm
3
or C 10N immat"re
ne"tro#hils 8ban$s9
Laboratory findings
-<N C 20 mg6$l 8>39
Rising -<N 8>39
)CT C 11N 8>29
Rising )CT 8>29
Ele2ate$ creatinine 8?29
Radiology findings
'le"ral eff"sions 8?39
'"lmonary infiltrates 8@39
laboratory marBers* the "se of hematocrit 8>29* -<N
8>3*539* an$ creatinine 8?29 as s"rrogate marBers for s"ccessf"l
hy$ration has been /i$ely recommen$e$ 810*1@*@2*@394
Altho"gh no firm recommen$ations regar$ing absol"te
n"mbers can be ma$e at this time, the goal to $ecrease
hematocrit 8$emonstrating hemo: $il"tion9 an$ -<N
8increasing renal #erf"sion9 an$ maintain a normal creatinine
$"ring the first $ay of hos#italiAation cannot be
o2erem#hasiAe$.
Altho"gh some h"man trials ha2e sho/n a clear benefit to
aggressi2e hy$ration 8=*5@*5>9, other st"$ies ha2e s"ggeste$
that aggressi2e hy$ration may be associate$ /ith an increase$
morbi$ity an$ mortality 85?*559. These 2ariable st"$y fin$ings
may be #artly eD#laine$ by critical $ifferences in st"$y $esign4
Altho"gh these st"$ies raise concerns abo"t the contin"o"s
"se of aggressi2e hy$ration o2er 15 h, the role of early
hy$ra: tion 8/ithin the first >G12 h9 /as not a$$resse$ in
these nega: ti2e st"$ies. ;n a$$ition, these negati2e st"$ies
incl"$e$ sicBer #atients /ho /o"l$ ha2e reF"ire$ large
2ol"mes of hy$ration by the 15 h time #oint 85?*559.
Consistently, the h"man st"$: ies in A' that foc"se$ on the
initial rate of hy$ration early in the co"rse of treatment
8/ithin the first 21 h9 $emonstrate$ a $ecrease in both
morbi$ity an$ mortality 8=*5@*5>9. Altho"gh the total 2ol"me
of hy$ration at 15 h after a$mission a##ears to ha2e little or
no im#act on #atient o"tcome, early aggressi2e intra2eno"s
hy$ration, $"ring the first 12G21 h, /ith close moni: toring is
of #aramo"nt im#ortance.
;n a /ell:$esigne$ #ros#ecti2e ran$omiAe$ trial, hy$ration
/ith a lactate$ RingerMs sol"tion a##ears to be more beneficial*
res"lting in fe/er #atients $e2elo#ing S;RS as com#are$ /ith
#atients recei2ing normal 804=N9 saline 8539. The benefit of
"sing lactate$ RingerMs sol"tion in large:2ol"me res"scitation
has been sho/n in other $isease states to lea$ to better electro:
lyte balance an$ im#ro2e$ o"tcomes 85=*=09. ;n A', there
are a$$itional theoretical benefits to "sing the more #):
balance$ lactate$ RingerMs sol"tion for fl"i$ res"scitation
com#are$ /ith normal saline. o/ #) acti2ates the
try#sinogen, maBes the acinar cells more s"sce#tible to in7"ry
an$ increases the se2erity of establishe$ A' in eD#erimental
st"$ies. Altho"gh both are isotonic crystalloi$ sol"tions,
normal saline gi2en in large 2ol: "mes may lea$ to the
$e2elo#ment of a non:anion ga#* hy#er: chloremic metabolic
aci$osis 85394
;t is im#ortant to recogniAe that aggressi2e early hy$ration
/ill reF"ire ca"tion for certain gro"#s of #atients, s"ch as the
el$erly* or those /ith a history of car$iac an$6or renal $isease in
or$er to a2oi$ com#lications s"ch as 2ol"me o2erloa$,
#"lmonary e$ema* an$ ab$ominal com#artment syn$rome
8=19. &eas"rement of the central 2eno"s #ress"re 2ia a
centrally #lace$ catheter is most commonly "se$ to $etermine
2ol"me stat"s in this setting. )o/: e2er, $ata in$icate that the
intrathoracic bloo$ 2ol"me in$eD may ha2e a better correlation
/ith car$iac in$eD than central 2eno"s #ress"re. &eas"rement
of intrathoracic bloo$ 2ol"me in$eD may therefore allo/ more
acc"rate assessment of 2ol"me stat"s for #atients manage$ in
the intensi2e care "nit. 'atients not res#on$: ing to intra2eno"s
hy$ration early 8/ithin >G12 h9 may not benefit from contin"e$
aggressi2e hy$ration.
ERC' ;N A'
The role of ERC' in A' is relate$ to the management of chole$o:
cholithiasis4 Altho"gh ERC' can be "se$ to i$entify #ancreatic
$"ctal $isr"#tion in #atients /ith se2ere A', #ossibly lea$ing to
inter2entions for the so:calle$ $islocate$ $"ct syn$rome* a
consens"s has ne2er emerge$ that ERC' sho"l$ be #erforme$
ro"tinely for this #"r#ose 8@294
Recommendations
14 'atients /ith A' an$ conc"rrent ac"te cholangitis sho"l$
"n$ergo ERC' /ithin 21 h of a$mission 8strong recommen:
$ation* mo$erate F"ality of e2i$ence94
24 ERC' is not nee$e$ early in most #atients /ith gallstone
#ancreatitis /ho lacB laboratory or clinical e2i$ence of
ongoing biliary obstr"ction 8strong recommen$ation*
mo$erate F"ality of e2i$ence94
34 ;n the absence of cholangitis an$6or 7a"n$ice, &RC' or E<S
rather than $iagnostic ERC' sho"l$ be "se$ to screen for
chole$ocholithiasis if highly s"s#ecte$ 8con$itional
recommen$ation* mo$erate F"ality of e2i$ence94
14 'ancreatic $"ct stents an$6or #ost#roce$"re rectal non: steroi$al
anti:inflammatory $r"g 8NSA;(9 s"##ositories sho"l$ be
"tiliAe$ to lo/er the risB of se2ere #ost:ERC' #ancreatitis in
high:risB #atients 8con$itional recommen$a: tion* mo$erate
F"ality of e2i$ence94
T)E ROE O+ ERC' ;N A'
+ort"nately, most gallstones that ca"se A' rea$ily #ass to the
$"o$en"m an$ are lost in the stool 8=294 )o/e2er in a minority
of #atients* #ersistent chole$ocholithiasis can lea$ to ongoing
#ancreatic $"ct an$6or biliary tree obstr"ction* lea$ing to se2ere
A' an$6or cholangitis4 Remo2al of obstr"cting gallstones from
the biliary tree in #atients /ith A' sho"l$ re$"ce the risB of
$e2elo#ing these com#lications4
There ha2e been se2eral clinical trials #erforme$ to ans/er
the F"estion% $oes early ERC' 8/ithin 21G?2 h of onset9 in
ac"te bil: iary #ancreatitis re$"ces the risB of #rogression of A'
to se2ere $isease 8organ fail"re an$6or necrosis9S Neo#tolemos
et al. 8=39 st"$ie$ 121 #atients /ith #robable ac"te biliary
#ancreatitis, strati: fie$ for se2erity accor$ing to the mo$ifie$
Glasgo/ criteria. The trial /as #erforme$ in a single center in
the <nite$ Qing$om4 'atients /ith #re$icte$ se2ere A' ha$
fe/er com#lications if they "n$er/ent ERC' /ithin ?2 h of
a$mission 821N 2s. >1N, P H 040@94 .hen #atients /ith
conc"rrent ac"te cholangitis 8/ho /o"l$ ob2io"sly benefit
from early ERC'9 /ere eDcl"$e$, the $ifference remaine$
significant 81@N 2s. >1N, P T 040039. &ortality /as not
significantly $ifferent in the t/o gro"#s. +an et al. 8=19
re#orte$ a st"$y of 1=@ #atients /ith s"s#ecte$ biliary
#ancreatitis strati: fie$ for se2erity accor$ing to RansonMs criteria.
'atients in the st"$y gro"# "n$er/ent ERC' /ithin 21 h of
a$mission an$ those in the control gro"# /ere offere$
conser2ati2e management. The control gro"# /as offere$ ERC'
if ac"te cholangitis $e2elo#e$. Those /ho "n$er/ent early
ERC' ha$ fe/er com#lications 813N 2s. @1N* P T 0400294
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LLL 2012
-ase$ on these st"$ies* it /as "nclear /hether #atients /ith
se2ere A' in the absence of ac"te cholangitis benefit from early
ERC'. Therefore, +olsch et al. 8=@9 organiAe$ a m"lticenter
st"$y of ERC' in ac"te biliary #ancreatitis that eDcl"$e$
#atients most liBely to benefit* namely those /ith a ser"m
bilir"bin C @ mg6$l4 Th"s* #atients /ith ac"te cholangitis
an$6or ob2io"s biliary tree obstr"ction "n$er/ent early
ERC' an$ /ere not incl"$e$ in the st"$y. This st"$y foc"se$
on $etermining the benefit of early ERC' in #re2enting se2ere
A' in the absence of biliary obstr"ction4 Altho"gh this st"$y
has been /i$ely criticiAe$ for $esign fla/s an$ the "n"s"ally
high mortality of #atients /ith mil$ $isease 85N com#are$
/ith an eD#ecte$ 1N9* no benefit in morbi$ity an$6or mortality
/as seen in #atients /ho "n$er/ent early ERC'. +rom this
st"$y, it a##ears that the benefit of early ERC' is seen in
#atients /ith A' com#licate$ by ac"te cholangitis an$ biliary
tree obstr"ction* b"t not se2ere A' in the absence of ac"te
cholangitis4
&ore recent st"$ies ha2e confirme$ that early ERC' /ithin 21
h of a$mission $ecreases morbi$ity an$ mortality in #atients
/ith A' com#licate$ by biliary se#sis 8=>*=?9. A $ilate$ biliary
tree in the absence of an ele2ate$ bilir"bin an$ other signs of
se#sis sho"l$ not be conf"se$ /ith cholangitis, b"t may
in$icate the #resence of a common bile $"ct stone. ;n #atients
/ith biliary #ancreatitis /ho ha2e mil$ $isease, an$ in #atients
/ho im#ro2e, ERC' before cholecystectomy has been sho/n to
be of limite$ 2al"e an$ may be harmf"l. Nonin2asi2e imaging
st"$ies are the #referre$ $iag: nostic mo$alities in these #atients
8E<S an$6or &RC'9. )o/e2er* it is not clear if any testing
nee$s to be #erforme$ in #atients /ho im#ro2e.
'RE0ENT;NG 'OST:ERC'
'ANCREAT;T;S
A' remains the most common com#lication of ERC'4
)istori: cally, this com#lication /as seen in @G10N of cases an$
in 20G10N of certain high:risB #roce$"res 8@0*=594 O2er the
#ast 1@ years* the risB of #ost:ERC' #ancreatitis has $ecrease$
to 2G1N an$ the risB of se2ere A' to H 16@00 8@0*=594 ;n
general, the $ecrease in #ost:ERC' A' an$ se2ere A' is relate$
to increase$ recognition of high:risB #atients an$ high:risB
#roce$"res in /hich ERC' sho"l$ be a2oi$e$ an$ the
a##lication of a##ro#riate inter2en: tions to #re2ent A' an$
se2ere A' 8@094
'atients /ith normal or near:normal bile $"ct an$ li2er tests
ha2e a lo/er liBelihoo$ of a common bile $"ct stone an$6or
other #athology 8strict"re, t"mor9. ;n these #atients,
$iagnostic ERC' has largely been re#lace$ by E<S or
&RC' as the risB of #ost:ERC' #ancreatitis is greater in
a #atient /ith normal caliber bile $"ct an$ normal bilir"bin
8o$$s ratio 341 for #ost:ERC' #ancreatitis9 as com#are$ /ith
a #atient /ho is 7a"n$ice$ /ith a $ilate$ common bile $"ct
8o$$s ratio 042 for #ost:ERC' #ancreatitis9 8==9.
+"rthermore* &RC' an$ E<S are as acc"rate as $iagnostic
ERC' an$ #ose no risB of #ancreatitis 8=594
+or #atients "n$ergoing a thera#e"tic ERC', three /ell:
st"$: ie$ inter2entions to $ecrease the risB of #ost:ERC'
#ancreati: tis, es#ecially se2ere $isease* incl"$e% 8i9 g"i$e/ire
cann"lation*
8ii9 #ancreatic $"ct stents, an$ 8iii9 rectal NSA;(s.
G"i$e/ire cann"lation 8cann"lation of the bile $"ct an$
#ancreatic $"ct by a g"i$e/ire inserte$ thro"gh a catheter9
$ecreases the risB of #ancreatitis 81009 by a2oi$ing
hy$rostatic in7"ry to the #ancreas that may occ"r /ith the
"se of ra$iocontrast agents. ;n a st"$y of 100 consec"ti2e
#atients ran$omiAe$ to contrast or g"i$e/ire cann"lation,
there /ere no cases of A' in the g"i$e/ire gro"# as
com#are$ /ith 5 cases in the contrast gro"# 8P H
0400194 A more recent st"$y in 300 #atients #ros#ecti2ely
ran$omiAe$ to g"i$e/ire cann"lation com#are$ /ith
con2entional contrast in7ection also fo"n$ a $ecrease in
#ost:ERC' #ancreatitis in the g"i$e/ire gro"# 81019.
)o/e2er, the re$"ction in #ost:ERC' #ancreatitis may
not be entirely relate$ to g"i$e/ire cann"la: tion 81029
an$ may ha2e been relate$ to less nee$ for #rec"t
s#hincterotomy in #atients "n$ergoing g"i$e/ire
cann"lation4 Regar$less, g"i$e/ire cann"lation com#are$
/ith con2entional contrast cann"lation a##ears to $ecrease
the risB of se2ere #ost: ERC' A' 8103*10194
'lacement of a #ancreatic $"ct stent $ecreases the
risB of se2ere #ost:ERC' #ancreatitis in high:risB
#atients* s"ch as those "n$ergoing am#"llectomy,
en$osco#ic s#hincter of O$$i manometry, or #ancreatic
inter2entions $"ring ERC'4 A 200? meta:analysis
#"blishe$ by An$ri"lli et al. 810@9* /hich e2al": ate$ 1
ran$omiAe$* #ros#ecti2e trials incl"$ing 2>5 #atients*
sho/e$ that #ancreatic $"ct stent #lacement affor$s a
t/o: fol$ $ro# in the inci$ence of #ost:ERC'
#ancreatitis 82141N 2s. 12N3 P T 0400=3 o$$s ratio% 0411,
=@N confi$ence inter2al%
0421G04519. Altho"gh f"rther st"$y is nee$e$, smaller 3 +rench
8+r9 "nflange$ #ancreatic stents a##ear to lo/er the risB of
#ost:ERC' #ancreatitis 8P T 0400139, #ass more s#ontaneo"sly
8P T 0400019, an$ ca"se less #ancreatic $"ctal changes 821N
2s4
50N9 as com#are$ /ith larger 1 +r, @ +r, or > +r stents 810>94
)o/e2er* 3 +r #ancreatic stent #lacement is more technically
$eman$ing beca"se of the nee$ to "se a 2ery flo##y 804015:inch
$iameter9 g"i$e/ire. Altho"gh #ro#hylactic #ancreatic $"ct
stenting is a cost:effecti2e strategy for the #re2ention of #ost:
ERC' #ancreatitis for high:risB #atients 810?9, a higher inci:
$ence of se2ere #ancreatitis has been re#orte$ in #atients /ith
faile$ #ancreatic $"ct stenting 81059. 'ancreatic $"ct stenting is
not al/ays technically feasible, /ith re#orte$ fail"re rates rang:
ing from 1 to 10N 81059. ;n a$$ition, long:term com#lications
from #ancreatic $"ct stenting, s"ch as chronic #ancreatitis, may
occ"r an$ f"rther st"$y is nee$e$ 81=94
Altho"gh a large n"mber of #harmacologic inter2entions for
#ro#hylaDis against #ost:ERC' #ancreatitis ha2e been st"$ie$
8@09, the res"lts of the st"$ies ha2e been largely $isa##ointing4
The most #romising gro"# of $r"gs to atten"ate the inflamma:
tory res#onse of A' are NSA;(s 810=*1109. T/o clinical trials
ha2e sho/n that a 100 mg rectal s"##ository of $iclofenac
re$"ces the inci$ence of #ost:ERC' #ancreatitis 8111*1129.
;n a$$i: tion, a recent m"lticenter* $o"ble:blin$* ran$omiAe$
#lacebo controlle$ trial of >02 #atients "n$ergoing a high:
risB ERC' $emonstrate$ a significant re$"ction of #ost:ERC'
#ancreati: tis in #atients gi2en #ost#roce$"re rectal
in$omethacin 811394 ;t is im#ortant to note that this st"$y
incl"$e$ only #atients at a
high risB of $e2elo#ing #ost:ERC' #ancreatitis an$ se2ere A'*
/hich is the #o#"lation that /o"l$ benefit the most. .hen
consi$ering the costs, risBs, an$ #otential benefits
re2ie/e$ in the #"blishe$ literat"re, rectal $iclofenac an$6or
in$o: methacin sho"l$ be consi$ere$ before ERC',
es#ecially in high:risB #atients. Altho"gh f"rther st"$y is
nee$e$ to $efine the o#timal $ose* at #resent it is reasonable to
consi$er #lace: ment of t/o in$omethacin @0 mg
s"##ositories 8total 100 mg9 after ERC' in #atients at a high
risB of $e2elo#ing #ost:ERC' A'. )o/e2er, "ntil f"rther
st"$y is #erforme$, the #lacement of rectal NSA;(s $oes not
re#lace the nee$ for a #ancreatic $"ct stent in the a##ro#riate
high:risB #atient4
T)E ROE O+ ANT;-;OT;CS ;N A'
Recommendations
14 Antibiotics sho"l$ be gi2en for an eDtra#ancreatic infection*
s"ch as cholangitis* catheter:acF"ire$ infections*
bacteremia* "rinary tract infections* #ne"monia 8strong
recommen$a: tion* mo$erate F"ality of e2i$ence94
24 Ro"tine "se of #ro#hylactic antibiotics in #atients /ith
se2ere A' is not recommen$e$ 8strong recommen$ation*
mo$erate F"ality of e2i$ence94
34 The "se of antibiotics in #atients /ith sterile necrosis to
#re2ent the $e2elo#ment of infecte$ necrosis is not
recommen$e$ 8strong recommen$ation* mo$erate F"ality
of e2i$ence94
14 ;nfecte$ necrosis sho"l$ be consi$ere$ in #atients /ith
#ancreatic or eDtra#ancreatic necrosis /ho $eteriorate or
fail to im#ro2e after ?G10 $ays of hos#italiAation. ;n
these #atients, either 8i9 initial CT:g"i$e$ fine:nee$le
as#iration
8+NA9 for Gram stain an$ c"lt"re to g"i$e "se of
a##ro#riate antibiotics or 8ii9 em#iric "se of antibiotics after
obtaining necessary c"lt"res for infectio"s agents, /itho"t
CT +NA* sho"l$ be gi2en 8strong recommen$ation,
mo$erate e2i$ence94
@4 ;n #atients /ith infecte$ necrosis* antibiotics Bno/n to
#ene: trate #ancreatic necrosis* s"ch as carba#enems*
F"inolones* an$ metroni$aAole, may be "sef"l in $elaying or
sometimes totally a2oi$ing inter2ention* th"s $ecreasing
morbi$ity an$ mortality 8con$itional recommen$ation*
mo$erate F"ality of e2i$ence94
>4 Ro"tine a$ministration of antif"ngal agents along /ith
#ro#hylactic or thera#e"tic antibiotics is not recommen$e$
8con$itional recommen$ation* lo/ F"ality of e2i$ence94
Infec!ious comlica!ions
;nfectio"s com#lications* both #ancreatic 8infecte$ necrosis9
an$ eDtra#ancreatic 8#ne"monia* cholangitis* bacteremia* "ri:
nary tract infections* an$ so on9* are a ma7or ca"se of morbi$ity
an$ mortality in #atients /ith A'. &any infections are
hos#ital: acF"ire$ an$ may ha2e a ma7or im#act on mortality
811194 +e2er* tachycar$ia* tachy#nea* an$ le"Bocytosis
associate$ /ith S;RS
that may occ"r early in the co"rse of A' may be
in$isting"ishable from se#sis syn$rome. .hen an infection is
s"s#ecte$, antibiotics sho"l$ be gi2en /hile the so"rce of the
infection is being in2es: tigate$ 8@394 )o/e2er, once bloo$ an$
other c"lt"res are fo"n$ to be negati2e an$ no so"rce of
infection is i$entifie$, antibiotics sho"l$ be $iscontin"e$.
'RE0ENT;NG T)E ;N+ECT;ON O+ STER;E
NECROS;S
The #ara$igm shift an$ contro2ersy o2er "sing antibiotics in
A' has centere$ on #ancreatic necrosis4 .hen com#are$ /ith
#atients /ith sterile necrosis* #atients /ith infecte$ #ancreatic
necrosis ha2e a higher mortality rate 8mean 30N* range 11G>=N9
8@394 +or this reason* #re2enting infection of #ancreatic necrosis
is im#ortant4 Altho"gh it /as #re2io"sly belie2e$ that
infectio"s com#lications occ"r late in the co"rse of the $isease
811@*11>9* a recent re2ie/ fo"n$ that 2?N of all cases
of infecte$ necrosis occ"r /ithin the first 11 $ays 811?93 in
another st"$y* nearly half of all infections a##ear to occ"r
/ithin ? $ays of a$mission 811594
Altho"gh early "nblin$e$ trials s"ggeste$ that a$ministration
of antibiotics may #re2ent infectio"s com#lications in #atients
/ith sterile necrosis 811=*1209, s"bseF"ent, better:$esigne$
trials ha2e consistently faile$ to confirm an a$2antage 8121G
12@9. -eca"se of the consistency of #ancreatic necrosis, fe/
antibiotics #enetrate /hen gi2en intra2eno"sly. The antibiotics
sho/n to #enetrate an$ "se$ in clinical trials incl"$e
carba#enems, F"inolones, metro: ni$aAole, an$ high:$ose
ce#halos#orins 8@2*11>*1239. Since 1==3* there ha2e been 11
#ros#ecti2e, ran$omiAe$ trials /ith #ro#er st"$y $esign*
#artici#ants, an$ o"tcome meas"res that e2al"ate$ the "se of
#ro#hylactic antibiotics in se2ere A' 812>9. +rom this meta:
analysis, the n"mber nee$e$ to treat /as 1*12= for one #atient to
benefit. ;t remains "ncertain if a s"bgro"# of #atients /ith se2ere
A' 8s"ch as eDtensi2e necrosis /ith organ fail"re9 may benefit
from antibiotics, b"t large st"$ies reF"ire$ to $etermine
/hether any benefit eDists /ill be $iffic"lt to #erform. -ase$ on
the c"rrent liter: at"re, "se of #ro#hylactic antibiotics to #re2ent
infection in #atients /ith sterile necrosis 8e2en #re$icte$ as
ha2ing se2ere $isease9 is not recommen$e$.
're2ention of f"ngal infections in these #atients is also not
recommen$e$. Altho"gh it /as s"ggeste$ that f"ngal infection
may be a more common ca"se of mortality in A', f"rther
st"$y has not confirme$ this fin$ing 812?94 There is one
s"ccessf"l ran$omiAe$ controlle$, clinical trial that "se$
selecti2e $econtamination of the bo/el, targeting both
bacteria an$ f"ngi, in or$er to #re2ent infecte$ necrosis
81259. -eca"se of the $ecrease$ morbi$ity an$ mortality in
this trial in #atients /ith se2ere A' /ho ha$ "n$ergone
selecti2e $econtamina: tion, f"rther st"$y in this area is
nee$e$. +inally* #robiotics sho"l$ not be gi2en in se2ere
A'. Altho"gh earlier trials s"ggeste$ a benefit, a 2ery /ell:
con$"cte$, ran$omiAe$ con: trolle$ clinical trial
$emonstrate$ increase$ mortality 812=94 This lacB of benefit
has also been sho/n in a recent meta: analysis 813094
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Infec!ed necrosis
Rather than #re2enting infection* the role of antibiotics in
#atients /ith necrotiAing A' is no/ to treat establishe$ infecte$
necro: sis4 The conce#t that infecte$ #ancreatic necrosis reF"ires
#rom#t s"rgical $ebri$ement has also been challenge$ by
m"lti#le re#orts an$ case series sho/ing that antibiotics alone
can lea$ to resol": tion of infection an$, in select #atients*
a2oi$ s"rgery altogether 8131G13194 Garg et al. 81319 re#orte$
1?650 #atients /ith infecte$ necrosis o2er a 10:year #erio$
/ho /ere s"ccessf"lly treate$ conser2ati2ely /ith antibiotics
alone 813194 The mortality in the conser2ati2e gro"# /as 23N
as com#are$ /ith @1N in the s"rgi: cal gro"#. The same gro"#
#"blishe$ a meta:analysis of 5 st"$ies in2ol2ing 10= #atients
/ith infecte$ necrosis of /hom 321 /ere s"ccessf"lly treate$
/ith antibiotics alone 813@94 O2erall, >1N of the #atients /ith
infecte$ necrosis in this meta:analysis co"l$ be manage$ by
conser2ati2e antibiotic treatment /ith 12N mor: tality, an$
only 2>N "n$er/ent s"rgery. Th"s* a select gro"# of relati2ely
stable #atients /ith infecte$ #ancreatic necrosis co"l$ be
manage$ by antibiotics alone /itho"t reF"iring #erc"tane:
o"s $rainage4 )o/e2er, it sho"l$ be ca"tione$ that these
#atients reF"ire close s"#er2ision an$ #erc"taneo"s or
en$osco#ic or necrosectomy sho"l$ be consi$ere$ if the #atient
fails to im#ro2e or $eteriorates clinically.
T)E ROE O+ CT
+NA
The techniF"e of com#"te$ tomogra#hy g"i$e$ fine nee$le
as#iration 8CT +NA9 has #ro2en to be safe, effecti2e, an$
Pancreatic necrosis: suspected of infection
acc"rate in $isting"ishing infecte$ an$ sterile necrosis
8@3*13>9. As #atients /ith infecte$ necrosis an$ sterile necrosis
may a##ear similar /ith le"Bocytosis, fe2er, an$ organ fail"re
813?9* it is im#ossible to se#arate these entities /itho"t
nee$le as#iration. )istorically* the "se of antibiotics is best
establishe$ in clinically #ro2en #ancreatic or eDtra#ancre:
atic infection, an$ therefore CT +NA sho"l$ be consi$ere$
/hen an infection is s"s#ecte$. An imme$iate re2ie/ of the
Gram stain /ill often establish a $iagnosis. )o/e2er, it may
be #r"$ent to begin antibiotics /hile a/aiting microbiologic
confirmation4 ;f c"lt"re re#orts are negati2e, the antibiotics
can be $iscontin"e$.
There is some contro2ersy as to /hether a CT +NA is neces:
sary in all #atients 8<igure 194 ;n many #atients* the CT +NA
/o"l$ not infl"ence the management 813594 ;ncrease$ "se of
conser2ati2e management an$ minimally in2asi2e $rainage
ha2e $ecrease$ the "se of +NA for the $iagnosis of infecte$
necrosis 8@194 &any #atients /ith sterile or infecte$ necrosis
either im#ro2e F"icBly or become "nstable, an$ $ecisions on
inter2ention 2ia a minimally in2asi2e ro"te /ill not be infl"ence$
by the res"lts of the as#iration4 A consens"s conference con:
cl"$e$ that +NA sho"l$ only be "se$ in select sit"ations /here
there is no clinical res#onse to antibiotics* s"ch as /hen a f"ngal
infection is s"s#ecte$ 8@194
N<TR;T;ON ;N A'
Recommendations
14 ;n mil$ A', oral fee$ings can be starte$ imme$iately if
there is no na"sea an$ 2omiting, an$ the ab$ominal #ain
has resol2e$ 8con$itional recommen$ation* mo$erate
F"ality of e2i$ence94
Obtain CT-guided FNA
Negative gram stain
Empiric use of necrosis
penetrating antibiotics
24 ;n mil$ A', initiation of fee$ing /ith a lo/:fat soli$ $iet
a##ears as safe as a clear liF"i$ $iet 8con$itional
recommen:
and culture
Positive gram
stain and/or culture
$ations* mo$erate F"ality of e2i$ence94
34 ;n se2ere A', enteral n"trition is recommen$e$ to #re2ent
STE!"E NECOS!S: supportive
care# consider repeat FNA ever$ %&'
da$s if clinicall$ indicated
Clinicall$ stable
Continue antibiotics and observe(
dela$ed minimall$ invasive surgical#
endoscopic# or radiologic debridement)
if as$mptomatic: consider no debridement
!nfected necrosis
Clinicall$ unstable
Prompt surgical
debridement
infectio"s com#lications4 'arenteral n"trition sho"l$
be a2oi$e$, "nless the enteral ro"te is not a2ailable*
not tolerate$, or not meeting caloric reF"irements
8strong recommen$ation* high F"ality of e2i$ence94
14 Nasogastric $eli2ery an$ naso7e7"nal $eli2ery of enteral
fee$ing a##ear com#arable in efficacy an$ safety 8strong
recommen$ation* mo$erate F"ality of e2i$ence94
<igure 1% &anagement of #ancreatic necrosis /hen infection is s"s#ecte$4
;nfecte$ necrosis sho"l$ be consi$ere$ in #atients /ith #ancreatic or
eDtra#ancreatic necrosis /ho $eteriorate or fail to im#ro2e after ?G10 $ays
of hos#italiAation4 ;n these #atients* either 8i9 initial com#"te$ tomogra#hy:
g"i$e$ fine nee$le as#iration 8CT +NA9 for Gram stain an$ c"lt"re to g"i$e
"se of a##ro#riate antibiotics or 8ii9 em#iric "se of antibiotics /itho"t CT
+NA sho"l$ be gi2en4 ;n #atients /ith infecte$ necrosis* antibiotics Bno/n
to #enetrate #ancreatic necrosis may be "sef"l in $elaying inter2ention*
th"s $ecreasing morbi$ity an$ mortality. ;n stable #atients /ith infecte$
necrosis* s"rgical* ra$iologic* an$6or en$osco#ic $rainage sho"l$ be
$elaye$ by #referably 1 /eeBs to allo/ the $e2elo#ment of a /all aro"n$
the necrosis 8/alle$:off #ancreatic necrosis94
S<&&AR! O+
E0;(ENCE
Nu!ri!ion in
mild AP
)istorically, $es#ite the absence of clinical $ata, #atients
/ith A' /ere Be#t N'O 8nothing by mo"th9 to rest the
#ancreas 83294 &ost g"i$elines in the #ast recommen$e$ N'O
"ntil resol"tion of #ain an$ some s"ggeste$ a/aiting
normaliAation of #ancre: atic enAymes or e2en imaging
e2i$ence of resol"tion of inflam: mation before res"ming oral
fee$ings 8@39. The nee$ to #lace the #ancreas at rest "ntil
com#lete resol"tion of A' no longer
seems im#erati2e4 The long:hel$ ass"m#tion that the inflame$
#ancreas reF"ires #rolonge$ rest by fasting $oes not a##ear to
be s"##orte$ by laboratory an$ clinical obser2ation 813=9.
Clini: cal an$ eD#erimental st"$ies sho/e$ that bo/el rest is
associate$ /ith intestinal m"cosal atro#hy an$ increase$
infectio"s com#li: cations beca"se of bacterial translocation
from the g"t. &"lti#le st"$ies ha2e sho/n that #atients
#ro2i$e$ oral fee$ing early in the co"rse of A' ha2e a shorter
hos#ital stay* $ecrease$ infec: tio"s com#lications, $ecrease$
morbi$ity, an$ $ecrease$ mortal: ity 811?*110G11394
;n mil$ A', oral intaBe is "s"ally restore$ F"icBly an$ no
n"tri: tional inter2ention is nee$e$. Altho"gh the timing of
refee$ing remains contro2ersial, recent st"$ies ha2e sho/n that
imme$iate oral fee$ing in #atients /ith mil$ A' a##ears safe
813=9. ;n a$$i: tion, a lo/:fat soli$ $iet has been sho/n to be
safe com#are$ /ith clear liF"i$s, #ro2i$ing more calories
81119. Similarly* in other ran$omiAe$ trials, oral fee$ing /ith a
soft $iet has been fo"n$ to be safe com#are$ /ith clear liF"i$s
an$ it shortens the hos#ital stay 811@*11>9. Early refee$ing also
a##ears to res"lt in a shorter hos#ital stay. -ase$ on these
st"$ies, oral fee$ings intro$"ce$ in mil$ A' $o not nee$ to
begin /ith clear liF"i$s an$ increase in a ste#/ise manner, b"t
may begin as a lo/:resi$"e, lo/:fat, soft $iet /hen the #atient
a##ears to be im#ro2ing4
Total #arenteral n"trition sho"l$ be a2oi$e$ in #atients /ith
mil$ an$ se2ere A'. There ha2e been m"lti#le ran$omiAe$
trials sho/ing that total #arenteral n"trition is associate$ /ith
infectio"s an$ other line:relate$ com#lications 8@39. As enteral
fee$ing main: tains the g"t m"cosal barrier, #re2ents
$isr"#tion, an$ #re2ents the translocation of bacteria that see$
#ancreatic necrosis, enteral n"trition may #re2ent infecte$
necrosis 8112*1139. A recent meta: analysis $escribing 5
ran$omiAe$ controlle$ clinical trials in2ol2: ing 351 #atients
fo"n$ a $ecrease in infectio"s com#lications* organ fail"re,
an$ mortality in #atients /ith se2ere A' /ho /ere #ro2i$e$
enteral n"trition as com#are$ /ith total #arenteral n"tri: tion
81139. Altho"gh f"rther st"$y is nee$e$, contin"o"s inf"sion is
#referre$ o2er cyclic or bol"s a$ministration.
Altho"gh the "se of a naso7e7"nal ro"te has been tra$itionally
#referre$ to a2oi$ the gastric #hase of stim"lation, nasogastric
enteral n"trition a##ears as safe. A systematic re2ie/
$escrib: ing =2 #atients from 1 st"$ies on nasogastric t"be
fee$ing fo"n$ that nasogastric fee$ing /as safe an$ /ell
tolerate$ in #atients /ith #re$icte$ se2ere A' 811?9. There ha2e
been some re#orts of nasogastric fee$ing slightly increasing the
risB of as#iration. +or this reason, #atients /ith A' "n$ergoing
enteral n"trition sho"l$ be #lace$ in a more "#right #osition
an$ be #lace$ on as#iration #reca"tions4 Altho"gh f"rther
st"$y is nee$e$* e2al"ating for Iresi$"als,J retaine$ 2ol"me in
the stomach, is not liBely to be hel#: f"l. Com#are$ /ith
naso7e7"nal fee$ing* nasogastric t"be #lace: ment is far easier,
/hich is im#ortant in #atients /ith A', es#ecially in the
intensi2e care setting4 Naso7e7"nal t"be #lacement reF"ires
inter2entional ra$iology or en$osco#y an$ th"s can be
eD#ensi2e4 +or these reasons, nasogastric t"be fee$ing sho"l$
be #referre$ 811?94 A large m"lticenter trial s#onsore$ by the
National ;nsti: t"tes of )ealth 8N;)9 is c"rrently being
#erforme$ to in2estigate /hether nasogastric or naso7e7"nal
fee$ings are #referre$ in these
#atients beca"se of significant eD#erimental an$ some h"man
e2i$ence of s"#eriority of $istal 7e7"nal fee$ing in A'.
T)E ROE O+ S<RGER! ;N A'
Recommendations
14 ;n #atients /ith mil$ A', fo"n$ to ha2e gallstones in the
gallbla$$er, a cholecystectomy sho"l$ be #erforme$ before
$ischarge to #re2ent a rec"rrence of A' 8mo$erate
recommen$ation* mo$erate F"ality of e2i$ence94
24 ;n a #atient /ith necrotiAing biliary A', in or$er to #re2ent
infection* cholecystectomy is to be $eferre$ "ntil acti2e
inflammation s"bsi$es an$ fl"i$ collections resol2e or stabiliAe
8strong recommen$ation* mo$erate e2i$ence94
34 Asym#tomatic #se"$ocysts an$ #ancreatic an$6or eDtra:
#ancreatic necrosis $o not /arrant inter2ention regar$less of siAe*
location* an$6or eDtension 8mo$erate recommen$ation* high
F"ality of e2i$ence94
14 ;n stable #atients /ith infecte$ necrosis* s"rgical, ra$iologic*
an$6or en$osco#ic $rainage sho"l$ be $elaye$ #referably
for more than 1 /eeBs to allo/ liF"efication of the contents an$
the $e2elo#ment of a fibro"s /all aro"n$ the necrosis 8/alle$:off
necrosis9 8strong recommen$ation* lo/ F"ality of e2i$ence94
@4 ;n sym#tomatic #atients /ith infecte$ necrosis, minimally in2asi2e
metho$s of necrosectomy are #referre$ to o#en necro: sectomy
8strong recommen$ation, lo/ F"ality of e2i$ence94
S<&&AR! O+ E0;(ENCE
Cholec)s!ec!om)
;n #atients /ith mil$ gallstone #ancreatitis* cholecystectomy
sho"l$ be #erforme$ $"ring the in$eD hos#italiAation. The c"r:
rent literat"re* /hich incl"$es 5 cohort st"$ies an$ one ran$o:
miAe$ trial $escribing ==5 #atients /ho ha$ an$ /ho ha$ not
"n$ergone cholecystectomy for biliary #ancreatitis* =@ 815N9
/ere rea$mitte$ for rec"rrent biliary e2ents /ithin =0 $ays of
$ischarge 80N 2s. 15N, P H 0400019, incl"$ing rec"rrent
biliary #ancreatitis 8n T 13, 5N9 81159. Some of the cases
/ere fo"n$ to be se2ere4 -ase$ on this eD#erience* there is a
nee$ for early cholecystectomy $"ring the same
hos#italiAation, if the attacB is mil$4 'atients /ho ha2e
se2ere A', es#ecially /ith #ancre: atic necrosis, /ill reF"ire
com#leD $ecision maBing bet/een the s"rgeon an$
gastroenterologist. ;n these #atients, cholecystec: tomy is
ty#ically $elaye$ "ntil 8i9 a later time in the ty#ically
#rolonge$ hos#italiAation, 8ii9 as #art of the management of the
#ancreatic necrosis if #resent, or 8iii9 after $ischarge 8115*11=94
Earlier g"i$elines recommen$e$ a cholecystectomy after 2
attacBs of ;A', /ith a #res"m#tion that many s"ch cases might
be beca"se of microlithiasis. )o/e2er, a #o#"lation:base$
st"$y fo"n$ that cholecystectomy #erforme$ for rec"rrent
attacBs of A' /ith no stones6sl"$ge on "ltraso"n$ an$ no
significant ele2ation of li2er tests $"ring the attacB of A' /as
associate$ /ith a C @0N rec"rrence of A' 81@094
0O<&E 101
K
LLL 2012
;n the ma7ority of #atients /ith gallstone #ancreatitis*
the common bile $"ct stone #asses to the $"o$en"m. Ro"tine
ERC' is not a##ro#riate "nless there is a high s"s#icion of a
#ersis: tent common bile $"ct stone, manifeste$ by an ele2ation
in the bilir"bin 81@19. 'atients /ith mil$ A', /ith normal
bilir"bin* can "n$ergo la#rosco#ic cholecystectomy /ith
intrao#erati2e cholangiogra#hy, an$ any remaining bile $"ct
stones can be $ealt /ith by #osto#erati2e or intrao#erati2e
ERC'. ;n #atients /ith lo/ to mo$erate risB, &RC' or E<S
can be "se$ #reo#erati2ely* b"t ro"tine "se of &RC' is
"nnecessary. ;n #atients /ith mil$ A' /ho cannot "n$ergo
s"rgery, s"ch as the frail el$erly an$6or those /ith se2ere
comorbi$ $isease, biliary s#hincterotomy alone may be an
effecti2e /ay to re$"ce f"rther attacBs of A', altho"gh attacBs
of cholecystitis may still occ"r 8@394
(E-R;(E&ENT O+ NECROS;S
)istorically, o#en necrosectomy6$ebri$ement /as the
treatment of choice for infecte$ necrosis an$ sym#tomatic
sterile necrosis4 (eca$es ago, #atients /ith sterile necrosis
"n$er/ent early $ebri: $ement that res"lte$ in increase$
mortality. +or this reason* early o#en $ebri$ement for sterile
necrosis /as aban$one$ 83294 )o/: e2er, $ebri$ement for
sterile necrosis is recommen$e$ if associ: ate$ /ith gastric
o"tlet obstr"ction an$6or bile $"ct obstr"ction4 ;n #atients
/ith infecte$ necrosis* it /as falsely belie2e$ that mortality
of infecte$ necrosis /as nearly 100N if $ebri$ement /as not
#erforme$ "rgently 8@3*1@294 ;n a retros#ecti2e re2ie/ of @3
#atients /ith infecte$ necrosis treate$ o#erati2ely 8me$ian time
to s"rgery of 25 $ays9 mortality fell to 22N /hen necrosec:
tomy necrosis /as $elaye$ 811594 After re2ie/ing 11 st"$ies
that incl"$e$ 1*13> #atients* the a"thors fo"n$ that #ost#oning
necro: sectomy in stable #atients treate$ /ith antibiotics alone
"ntil 30 $ays after initial hos#ital a$mission is associate$ /ith a
$ecrease$ mortality 813194
The conce#t that infecte$ #ancreatic necrosis reF"ires
#rom#t s"rgical $ebri$ement has also been challenge$ by
m"lti#le re#orts an$ case series sho/ing that antibiotics alone
can lea$ to resol": tion of infection an$, in select #atients,
a2oi$ s"rgery altogether 8>*@19. ;n one re#ort 81339 of 25
#atients gi2en antibiotics for the management of infecte$
#ancreatic necrosis, 1> a2oi$e$ s"rgery4 There /ere t/o $eaths
in the #atients /ho "n$er/ent s"rgery an$ t/o $eaths in the
#atients /ho /ere treate$ /ith antibiotics alone4 Th"s, in this
re#ort, more than half the #atients /ere s"ccessf"lly treate$
/ith antibiotics an$ the mortality rate in both the s"rgi: cal
an$ nons"rgical gro"#s /as similar. The conce#t that "rgent
s"rgery is reF"ire$ in #atients fo"n$ to ha2e infecte$ necrosis is
no longer 2ali$. Asym#tomatic #ancreatic an$6or
eDtra#ancreatic necrosis $oes not man$ate inter2ention
regar$less of siAe, location* an$ eDtension. ;t /ill liBely resol2e
o2er time, e2en in some cases of infecte$ necrosis 8@194
Altho"gh "nstable #atients /ith infecte$ necrosis sho"l$
"n$ergo "rgent $ebri$ement, c"rrent consens"s is that the
initial management of infecte$ necrosis for #atients /ho are
clinically stable sho"l$ be a co"rse of antibiotics before
inter2ention to allo/ the inflammatory reaction to become
better organiAe$ 8@194
;f the #atient remains ill an$ the infecte$ necrosis has not
resol2e$* minimally in2asi2e necrosectomy by
en$osco#ic, ra$iologic* 2i$eo:assiste$ retro#eritoneal*
la#arosco#ic a##roach* or com: bination thereof, or o#en
s"rgery is recommen$e$ once the necrosis is /alle$:off
8@1*1@3G1@>94
&;N;&A! ;N0AS;0E
&ANAGE&ENT O+ 'ANCREAT;C
NECROS;S
&inimally in2asi2e a##roaches to #ancreatic
necrosectomy incl"$ing la#rosco#ic s"rgery either from
an anterior or retro: #eritoneal a##roach* #erc"taneo"s*
ra$iologic catheter $rain: age or $ebri$ement* 2i$eo:
assiste$ or small incision:base$ left retro#eritoneal
$ebri$ement* an$ en$osco#y are increasingly becoming
the stan$ar$ of care. 'erc"taneo"s $rainage /itho"t
necrosectomy may be the most freF"ently "se$ minimally
in2a: si2e metho$ for managing fl"i$ collections
com#licating necro: tiAing A' 8@1*>5*115*1@2G1@?94 The
o2erall s"ccess a##ears to be
U@0N in a2oi$ing o#en s"rgery. ;n a$$ition* en$osco#ic
$rainage of necrotic collections an$6or $irect en$osco#ic
necrosectomy has been re#orte$ in se2eral large series to
be eF"ally s"ccessf"l 8@3*@1*1@@94 Sometimes these
mo$alities can be combine$ at the same time or
seF"entially, for eDam#le, combine$ #erc"taneo"s an$
en$osco#ic metho$s4 Recently, a /ell:$esigne$ st"$y
from the Netherlan$s "sing a ste#:"# a##roach
8#erc"taneo"s catheter $rainage follo/e$ by 2i$eo:assiste$
retro#eritoneal $ebri$ement9 8>5*1@>9 $emonstrate$ the
s"#eriority of the ste#:"# a##roach as reflecte$ by lo/er
morbi$ity 8less m"lti#le organ fail"re an$ s"rgical
com#lications9 an$ lo/er costs com#are$ /ith o#en s"rgical
necrosectomy.
Altho"gh these g"i$elines cannot $isc"ss in $etail the 2ario"s
metho$s of $ebri$ement, or the com#arati2e effecti2eness of
each* beca"se of limitations in a2ailable $ata an$ the foc"s of this
re2ie/* se2eral generaliAations are im#ortant4 Regar$less of the
metho$ em#loye$, minimally in2asi2e a##roaches reF"ire the
#ancreatic necrosis to become organiAe$ 8@1*>5*1@1G1@?9.
.hereas early in the co"rse of the $isease 8/ithin the first ?G
10 $ays9 #ancreatic necrosis is a $iff"se soli$ an$6or semisoli$
inflammatory mass* after U1 /eeBs a fibro"s /all $e2elo#s
aro"n$ the necrosis that maBes remo2al more amenable to o#en
an$ la#rosco#ic s"rgery* #erc"taneo"s ra$iologic catheter
$rainage, an$6or en$osco#ic $rainage.
C"rrently, a m"lti$isci#linary consens"s fa2ors minimally
in2a: si2e metho$s o2er o#en s"rgery for the management of
#ancreatic necrosis 8@19. A recent ran$omiAe$ controlle$ trial
clearly $em: onstrate$ the s"#eriority of en$osco#ic $ebri$ement
o2er s"rgery 81@19. Altho"gh a$2ances in s"rgical, ra$iologic,
an$ en$osco#ic techniF"es eDist an$ are in $e2elo#ment, it m"st
be stresse$ that many #atients /ith sterile #ancreatic necrosis,
an$ select #atients /ith infecte$ necrosis, clinically im#ro2e to
a #oint /here no inter2ention is necessary 8@1*1319. The
management of #atients /ith #ancreatic necrosis sho"l$ be
in$i2i$"aliAe$, reF"iring con: si$eration of all the a2ailable $ata
8clinical, ra$iologic, laboratory9 an$ "sing a2ailable eD#ertise.
Early referral to a center of eDcel: lence is of #aramo"nt
im#ortance, as $elaying inter2ention /ith
maDimal s"##orti2e care an$ "sing a minimally in2asi2e
a##roach ha2e both been sho/n to re$"ce morbi$ity an$
mortality.
C;N<LICT ;< INTEREST
Guaran!or of !he ar!icle% Scott Tenner, &(, &')* +ACG4
Secific au!hor con!ri(u!ions% All fo"r a"thors share$
eF"ally in concei2ing, initiating* an$ /riting the
man"scri#t.
<inancial suor!% None.
Po!en!ial come!ing in!eres!s% None.
@?4 Ranson ,)* 'asternacB -S4 Statistical metho$s for F"antifying the
se2erity of clinical ac"te #ancreatitis4 , S"rg Res 1=??322%?=G=14
@54 Qna"s .A* (ra#er EA* .agner (' et al. A'AC)E ;;% a se2erity of
$isease classification system4 Crit Care &e$ 1=5@313%515G2=4
@=4 ." -<, ,ohannes RS* S"n L et al. The early #re$iction of mortality in
ac"te #ancreatitis% a large #o#"lation:base$ st"$y. G"t
20053@?%1>=5!1?034
>04 'a#achristo" G;* &"$$ana 0, !a$a2 ( et al. Com#arison of -;SA'*
RansonMs* A'AC)E:;;* an$ CTS; scores in #re$icting organ fail"re*
com#lications* an$ mortality in ac"te #ancreatitis4 Am ,
Gastroenterol
2010310@%13@G114
>14 ." -<, ,ohannes RS* S"n L et al. Early changes in bloo$ "rea nitrogen
#re$ict mortality in ac"te #ancreatitis4 Gastroenterology 200=313?%12=G
3@4
>24 &o"nAer R et al. Com#arison of eDisting clinical scoring systems to
#re$ict #ersistent organ fail"re in #atients /ith ac"te #ancreatitis4
Gastroentero: logy 20123112%11?>G524
>34 -ro/n A* Ora2 ,, -anBs 'A4 )emoconcentration is an early marBer
for organ fail"re an$ necrotiAing #ancreatitis4 'ancreas 2000320%3>?G
?24
>14 anBisch 'G* &ahlBe R, -l"m T et al. )emoconcentration% an early
marBer of se2ere an$6or necrotiAing #ancreatitisS A critical
a##raisal4 Am , Gastroenterol 20013=>%2051G@4
>@4 +rossar$ ,* )a$eng"e A* 'astor C&4 Ne/ ser"m marBers for the
$etection of se2ere ac"te #ancreatitis in h"mans4 Am , Res#ir Crit Care
&e$ 20013
1>1%1>2G?04
>>4 'a#achristo" G;* .hitcomb (C4 ;nflammatory marBers of $isease
se2er: ity in ac"te #ancreatitis4 Clin ab &e$ 200@32@%1?G3?4
>?4 -althaAar E,, Robinson (* &egibo/ A, et al. Ac"te #ancreatitis% 2al"e
of
CT in establishing #rognosis4 Ra$iology 1==031?1%331G>4
>54 2an Sant2oort )C* -esselinB &G* -aBBer O, et al. A ste#:"#
a##roach or o#en necrosectomy for necrotiAing #ancreatitis4 Ne/
Engl , &e$
201333>2%11=1G@024
>=4 Tran ((, C"esta &A4 E2al"ation of se2erity in #atients /ith ac"te
#an: creatitis4 Am , Gastroenterol 1==235?%>01G54
?04 &ofi$i R, ("ff &(, .igmore S, et al. Association bet/een early
systemic inflammatory res#onse, se2erity of m"ltiorgan $ysf"nction an$
$eath in ac"te #ancreatitis4 -r , S"rg 200>3=3%?35G114
?14 -"ter A* ;mrie C., Carter CR et al. (ynamic nat"re of early organ
$ysf"nction $etermines o"tcome in ac"te #ancreatitis4 -r , S"rg
200235=%
2=5G3024
?24 'a#achristo" G;* &"$$ana 0, !a$a2 ( et al. ;ncrease$ ser"m creatinine
is associate$ /ith #ancreatic necrosis in ac"te #ancreatitis4 Am , Gastro:
enterol 2010310@%11@1G24
?34 )eller S,, Noor$hoeB E* Tenner S& et al. 'le"ral eff"sion as a #re$ictor
of se2erity in ac"te #ancreatitis4 'ancreas 1==?31@%222G@4
?14 +"nnell ;C* -ornman 'C* .eaBley S' et al. Obesity% an im#ortant
#rog: nostic factor in ac"te #ancreatitis4 -r , S"rg 1==3350%151G>4
?@4 &ann (0, )ershman &,, )ittinger R et al. &"lticentre a"$it of
$eath from ac"te #ancreatitis4 -r , S"rg 1==1351%5=0G34
?>4 &"tinga &* Rosenbl"th A* Tenner S& et al. (oes mortality occ"r early
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