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 K LLL 2012 #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 0O<&E 101 K 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 0O<&E 101 K LLL 2012 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 or late in ac"te #ancreatitisS ;nt , 'ancreatol 2000325%=1G@4 ??4 ,ohnson C(, Ab":)ilal &4 'ersistent organ fail"re $"ring the first /eeB as a marBer of fatal o"tcome in ac"te #ancreatitis4 G"t 20013@3% 1310G14 ?54 ytras (, &anes Q* Trianto#o"lo" C et al. 'ersistent early organ fail"re% $efining the high risB gro"# of #atients /ith se2ere ac"te #ancreatitis4 'ancreas 200533>%21=G@14 ?=4 Qerner T* 0ollmar -, &enger &( et al. (eterminants of #ancreatic micro: circ"lation in ac"te #ancreatitis in rats4 , S"rg Res 1==>3>2%1>@G?14 504 -assi (, Qollias N* +ernan$eA:$el Castillo C et al. ;m#airment of #ancre: atic microcirc"lation correlates /ith the se2erity of ac"te eD#erimental #ancreatitis4 , Am Coll S"rg 1==131?=%2@?G>34 514 ;no"e Q* )irota &* -e##" T et al. Angiogra#hicfeat"res in ac"te #ancrea: titis% the se2erity of ab$ominal 2essel ischemic change reflects the se2erity of ac"te #ancreatitis4 ,O' 200331%20?G134 524 -iAe '* 'laton A* -ecBer C4 'erf"sion meas"rement in ac"te #ancreatitis "sing $ynamic #erf"sion &( CT. Am , Ra$iol 200>315>%111G54 534 ." -<, )/ang ,V, Gar$ner T) et al. actate$ RingerMs sol"tion re$"ces systemic inflammation com#are$ /ith saline in #atients /ith ac"te #ancreatitis4 Clin Gastroenterol )e#atol 20113=%?10G?4 514 TaBe$a Q* &iBami !, +"B"yama S et al. 'ancreatic ischemia associate$ /ith 2asos#asm in the early #hase of h"man ac"te necrotiAing #ancreati: tis4 'ancreas 200@330%10G=4 5@4 Gar$ner T-, 0ege SS* Chari ST et al. +aster rate of initial fl"i$ res"scita: tion in se2ere ac"te #ancreatitis $iminishes in:hos#ital mortality. 'ancrea: tology 200=3=%??0G>4 5>4 .arn$orf &G* Q"rtAman ,T, -artel &, et al. Early fl"i$ res"scitation re$"ces morbi$ity among #atients /ith ac"te #ancreatitis4 Clin Gastro: enterol )e#atol 20113=%?0@G=4 5?4 &ao EV* +ei ,, 'eng !- et al. Ra#i$ hemo$il"tion is associate$ /ith increase$ se#sis an$ mortality among #atients /ith se2ere ac"te #ancreatitis4 Chin &e$ , 8Engl9 20103123%1>3=G114 554 $e:&a$aria E* Soler:Sala G* SWncheA:'aya , et al. ;nfl"ence of fl"i$ thera#y on the #rognosis of ac"te #ancreatitis% a #ros#ecti2e cohort st"$y4 Am , Gastroenterol 2011310>%1513G@04 5=4 Qha7a2i &R, EteAa$i +, &oharari RS et al. Effects of normal saline 2s4 lactate$ RingerMs $"ring renal trans#lantation4 Renal +ail 2005330%@3@G=4 =04 Cho !S* im )* Qim S)4 Com#arison of lactate$ RingerMs sol"tion an$ 04=N saline in the treatment of rhab$omyolysis in$"ce$ by $oDylamine intoDication4 Emerg &e$ , 200?321%2?>G504 =14 EcBer/all G* Olin )* An$ersson - et al. +l"i$ res"scitation an$ n"tritional s"##ort $"ring se2ere ac"te #ancreatitis in the #ast% /hat ha2e /e learne$ an$ ho/ can /e $o betterS Clin N"tr 200>32@%1=?G@014 =24 Acosta ,&* e$esma C4 Gallstone migration as a ca"se of ac"te #ancreatitis4 N Engl , &e$ 1=?132=0%151G?4 =34 Neo#tolemos ,', on$on N,, ,ames ( et al. Controlle$ trail of "rgent en$osco#ic retrogra$e cholangio#ancreatogra#hy an$ en$osco#ic s#hinc: terotomy 2ers"s conser2ati2e management for ac"te #ancreatitis $"e to gallstones4 ancet 1=5533%=?=G534 =14 +an ST, ai EC* &oB +' et al. Early treatment of ac"te biliary #ancreatitis by en$osco#ic #a#illotomy. Ne/ Engl , &e$ 1==33325%225G324 =@4 +olsch <R, Nitsche R, "$tBe R et al. Early ERC' an$ #a#illotomy com#are$ /ith conser2ati2e treatment for ac"te biliary #ancreatitis4 N Engl , &e$ 1==?333>%23?G124 =>4 Arg"e$as &R, ("#ont A., .ilcoD C&4 .here $o ERC', en$osco#ic "ltraso"n$* magnetic resonance cholangio#ancreatogra#hy, an$ intra: o#erati2e cholangiogra#hy fit in the management of ac"te biliary #ancrea: titisS A $ecision analysis mo$el. Am , Gastroenterol 20013=>%25=2G=4 =?4 &oretti A* 'a#i C* Aratari A et al. ;s early en$osco#ic retrogra$e cholangio#ancreatogra#hy "sef"l in the management of ac"te biliary #ancreatitisS A meta:analysis of ran$omiAe$ controlle$ trials4 (i2 i2er (is 2005310%3?=G5@4 =54 +reeman &* (iSario ,A* Nelson (- et al. RisB factors for #ost:ERC' #ancreatitis% a #ros#ecti2e, m"lticenter st"$y. Gastrointest En$osc 20013@1%12@G314 ==4 &ehta SN, 'a2one E, -arB"n ,S et al. 're$ictors of #ost:ERC' com#lications in #atients /ith s"s#ecte$ chole$ocholithiasis. En$osco#y 1==5330%1@?G>3. 1004 ella +, -agnolo +, Colombo E et al. A sim#le /ay of a2oi$ing #ost: ERC' #ancreatitis4 Gastrointest En$osc 20013@=%530G14 1014 Artifon E* SaBai '* C"nha ,E et al. G"i$e/ire cann"lation re$"ces risB of #ost:ERC' #ancreatitis an$ facilitates bile $"ct cann"lation4 Am , Gastroenterol 200?3102%211?G@34 1024 &ariani A* Gi"ssani A* (i eo & et al. G"i$e/ire biliary cann"lation $oes not re$"ce #ost:ERC' #ancreatitis com#are$ /ith the contrast in7ec: tion techniF"e in lo/:risB an$ high:risB #atients4 Gastrointest En$osc 20123?@%33=G1>4 1034 Che"ng ,, Tsoi QQ* V"an . et al. G"i$e/ire 2ers"s con2entional contrast cann"lation of the common bile $"ct for the #re2ention of #ost: ERC' #ancreatitis% a systematic re2ie/ an$ meta:analysis4 Gastrointest En$osc 200=3?0%1211G=4 1014 A$ler (G* 0erma (, )il$en Q et al. (ye:free /ire:g"i$e$ cann"lation of the biliary tree $"ring ERC' is associate$ /ith high s"ccess an$ lo/ com#lication rates% o"tcomes in a single o#erator eD#erience of 522 cases4 , Clin Gastroenterol 2010311%e@?G>24 10@4 An$ri"lli A* +orlano R, Na#olitano G et al. 'ancreatic $"ct stents in the #ro#hylaDis of #ancreatic $amage after en$osco#ic retrogra$e cholangio: #ancreatogra#hy% a systematic analysis of benefits an$ associate$ risBs4 (igestion 200?3?@%1@>G>34 10>4 Rash$an A* +ogel E* &c)enry ,r et al. ;m#ro2e$ stent characteristics for #ro#hylaDis of #ost:ERC' #ancreatitis4 Clin Gastroenterol )e#atol 200132%322G=4 10?4 (as A* Singh '* Si2aB ,r &0 et al. 'ancreatic:stent #lacement for #re2ention of #ost:ERC' #ancreatitis% a cost effecti2eness analysis4 Gastrointest En$osc 200?3>@%=>0G54 1054 +reeman &4 'ancreatic stents for #re2ention of #osten$osco#ic retro: gra$e cholangio#ancreatogra#hy #ancreatitis4 Clin Gastroenterol )e#atol 200?3@%13@1G>@4 10=4 Soto"$ehmanesh R, Qhatibian &* Qolah$ooAan S et al. ;n$omethacin may re$"ce the inci$ence an$ se2erity of ac"te #ancreatitis after ERC'. Am , Gastroenterog 200?3102%=?5G534 1104 Elm"nAer -,, .al7ee AQ* Elta G) et al. A meta:analysis of rectal NSA;(s in the #re2ention of #ost:ERC' #ancreatitis4 G"t 20053@?%12>2G ?4 1114 &"rray -, Carter R, ;mrie C et al. (iclofenac re$"ces the inci$ence of ac"te #ancreatitis after en$osco#ic retrogra$e cholangio#ancreatogra#hy4 Gastroenterology 20033121%1?5>G=14 1124 Qhoshbaten &* Qhorram )* &a$a$ et al. Role of $iclofenac in re$"cing #ost:en$osco#icretrogra$e cholangio#ancreatogra#hy #ancreatitis. , Gastroenterol )e#atol 2005323%11G>4 1134 Elm"nAer -,, Scheiman ,&* ehman GA et al. A ran$omiAe$ trial of rectal in$omethacin to #re2ent #ost:ERC' #ancreatitis4 N Engl , &e$ 201233>>%1111G224 1114 -aril N-, Ralls '., .ren S& et al. (oes an infecte$ #eri#ancreatic fl"i$ collection or abscess man$ate o#erationS Ann S"rg 20003231%3>1G ?4 11@4 -eger )G* Ra" -, ;senmann R. Nat"ral history of necrotiAing #ancreatitis. 'ancreatology 200333%=3G1014 11>4 -eger )G* -ittner R, -locB S et al. -acterial contamination of #ancreatic necrosis% a #ers#ecti2e clinical st"$y. Gastroenterology 1=5>3=1%133G54 11?4 'etro2 &S* Q"Bosh &0, Emelyano2 N0. A ran$omiAe$ controlle$ trial of enteral 2ers"s #arenteral fee$ing in #atients /ith #re$icte$ se2ere ac"te #ancreatitis sho/s a significant re$"ction in mortality an$ in infecte$ #ancreatic com#lications /ith total enteral n"trition4 (ig S"rg 200>323%33>G1@4 1154 -esselinB &G* -er/er T,, ShoenmaecBers E, et al. Timing of s"rgical inter2ention in necrotiAing #ancreatitis4 Arch S"rg 200?3112%11=1G 2014 11=4 'e$erAoli '* -assi C* 0esontini S et al. A ran$omiAe$ m"lticenter clinical trial of antibiotic #ro#hylaDis of se#tic com#lications in ac"te necrotiAing #ancreatitis /ith imi#enem4 S"rg Gynecol Obstet 1==331?>%150G34 1204 Saino 0, Qem##ainem E* '"olaBBainen ' et al. Early antibiotic treatment in ac"te necrotiAing #ancreatitis4 ancet 1==@331>%>>3G?4 1214 (ellinger E', Tella$o ,&* Soto NE et al. Early antibiotic treatment for se2ere ac"te necrotiAing #ancreatitis% a ran$omiAe$* $o"ble blin$, #lacebo controlle$ st"$y. Ann S"rg 200?321@%>?1G534 1224 ;senmann R, R"nAi &* Qron & et al. 'ro#hylactic antibiotic treatment in #atients /ith #re$icte$ se2ere ac"te #ancreatitis% a #lacebo: controlle$* $o"ble:blin$ trial. Gastroenterology 2001312>%==?G10014 1234 0illatoro E* -assi C* ar2in &4 Antibiotic thera#y for #ro#hylaDis against infection of #ancreatic necrosis in ac"te #ancreatitis4 Cochrane (atabase Syst Re2%C(002=114 1214 (e 0ries A* -esselinB &G* -"sBens E et al. Ran$omiAe$ controlle$ trials of antibiotic #ro#hylaDis in se2ere ac"te #ancreatitis% relationshi# bet/een metho$ologic F"ality an$ o"tcome. 'ancreatology 200?3?%@31G 54 12@4 ,afri NS* &ahi$ SS* ;$stein SR et al. Antibiotic #ro#hylaDis is not #rotec: ti2e in se2ere ac"te #ancreatitis% a systemic re2ie/ an$ meta: analysis4 Am , S"rg 200=31=?%50>G134 12>4 ,iang Q* )"ang ., !ang LN et al. 'resent an$ f"t"re of #ro#hylactic antibiotics for se2ere ac"te #ancreatitis4 .orl$ , Gastroenterol 2012315% 2?=G514 12?4 TriB"$anathan G* NA2aneethan <, 0ege SS4 ;ntra:ab$ominal f"ngal infections com#licating ac"te #ancreatitis% a re2ie/. Am , Gastroenterol 2011310>%1155G=24 1254 "iten E,, )o# .C* ange ,+ et al. Controlle$ clinical trial of selecti2e $econtamination for the treatment of se2ere ac"te #ancreatitis4 Ann S"rg 1==@3222%@?G>@4 12=4 -esselinB &G* 2an Sant2oort )C* -"sBens E et al. 'robiotic #ro#hylaDis in #re$icte$ se2ere ac"te #ancreatitis% a ran$omise$* $o"ble:blin$* #lacebo:controlle$ trial. ancet 200533?1%>@1G=4 1304 S"n S* !ang Q* )e L et al. angenbecBs 'robiotics in #atients /ith se2ere ac"te #ancreatitis% a meta:analysis4 Arch S"rg 200=33=1%1?1G?4 1314 )art/ig ., &aBsan S&* +oitAiB T et al. Re$"ction in mortality /ith $elaye$ s"rgical thera#y of se2ere #ancreatitis4 , Gastrointest S"rg 20023>%151G?4 1324 ("bner )* Steinberg ., )ill & et al. ;nfecte$ #ancreatic necrosis an$ #eri#ancreatic fl"i$ collections% seren$i#ito"s res#onse to antibiotics an$ me$ical thera#y in three #atients4 'ancreas 1232=5%1==>4 1334 R"nAi &* Niebel ., Goebell ) et al. Se2ere ac"te #ancreatitis% non s"rgical treatment of infecte$ necrosis4 'ancreas 200@330%1=@G=4 1314 Garg 'Q* Sharma &* &a$an Q et al. 'rimary conser2ati2e treatment res"lts in mortality com#arable to s"rgery in #atients /ith infecte$ #ancreatic necrosis4 Clin Gastroenterol )e#atol 201035%105=G=14 13@4 &o"li 0', 0ishn"bhatla S* Garg 'Q4 Efficacy of conser2ati2e treatment* /itho"t necrosectomy, for infecte$ #ancreatic necrosis% a systematic re2ie/ an$ meta:analysis4 Gastroenterology 20133111%333G104 13>4 -"chler &., Gloor -, &"sller CA et al. Ac"te necrotiAing #ancreati: tis% treatment strategy accor$ing to the stat"s of infection4 Ann S"rg 20003232%>1=G2>4 13?4 Tenner S&* +eng S* Noer$ooB S et al. The relationshi# of organ fail"re to #ancreatic necrosis4 Gastroenterology 1==?3113%5==G=034 1354 'a##as T4 ;s CT g"i$e$ fine nee$le as#iration hel#f"l in #atients /ith infecte$ necrosis4 Am , Gastroenterol 200@3100%23?1G14 13=4 EcBer/all GE* Tingste$t --, -ergenAa"n 'E et al. ;mme$iate oral fee$ing in #atients /ith ac"te #ancreatitis is safe an$ may accelerate reco2ery::a ran$omiAe$ clinical st"$y. Clin N"tr 200?32>%?@5G>34 1104 o"ie -E* Nose/orthy T* )ailey ( et al. 2001 &acean:&"eller 'riAe enteral or #arenteral n"trition for se2ere #ancreatitis% a ran$omiAe$ controlle$ trial an$ health technology assessment. Can , S"rg 200@315%2=5G30>. 1114 Casas &* &ora ,, +ort E et al. Total enteral n"trition 2s4 total #arenteral n"trition in #atients /ith se2ere ac"te #ancreatitis4 Re2 Es# Enferm (ig 200?3==%2>1G=4 1124 G"#ta R, 'atel Q* Cal$er 'C et al. A ran$omise$ clinical trial to assess the effect of total enteral an$ total #arenteral n"tritional s"##ort on metabolic* inflammatory an$ oDi$ati2e marBers in #atients /ith #re$icte$ se2ere ac"te #ancreatitis ;; 8A'AC)E X>94 'ancreatology 200333% 10>G134 1134 !i +, Ge * Yhao , et al. &eta:analysis% total #arenteral n"trition 2ers"s total enteral n"trition in #re$icte$ se2ere ac"te #ancreatitis4 ;ntern &e$ 20123@1%@23G304 1114 ,acobson -C* 0an$r 0liet &-, )"ghes &( et al. A #ros#ecti2e, ran$o: miAe$ trial of clear liF"i$s 2ers"s lo/:fat soli$ $iet as the initial meal in mil$ ac"te #ancreatitis4 Clin Gastroenterol )e#atol 200?3@%=1>G@14 11@4 Sathiara7 E* &"rthy S* &ansar$ &, et al. Clinical trial3 oral fee$ing /ith a soft $iet com#are$ /ith clear liF"i$ $iet as initial meal in mil$ ac"te #ancreatitis4 Aliment 'harmacol 2005325%???G514 11>4 &oraes ,&* +elga GE* Chebli A et al. A f"ll soli$ $iet as the initial meal in mil$ ac"te #ancreatitis is safe an$ res"lt in a shorter length of hos#itali: Aation3 res"lts from a #ros#ecti2e, ran$omiAe$* controlle$, $o"ble:blin$ clinical trial. , Clin Gastroenterol 2010311%@1?G224 11?4 Singh N* Sharma -, Sharma & et al. E2al"ation of early enteral fee$ing thro"gh nasogastric an$ naso7e7"nal t"be in se2ere ac"te #ancreatitis4 A non:inferiority ran$omiAe$ controlle$ trial. 'ancreas 2012311% 1@3G=. 1154 arson S(, Nealson .)* E2ers -&4 &anagement of gallstone #ancreatitis. A$2 S"rg 200>310%2>@G514 11=4 <hl ., &"ller CA* Qrahenb"hl et al. Ac"te gallstone #ancreatitis% timing of cholecystectomy in mil$ an$ se2ere $isease4 S"rg En$osc 1===311%10?0G>4 1@04 Trna ,, 0ege SS* 'ribramsBa 0 et al. acB of significant li2er enAyme ele2ation an$ gallstones an$6or sl"$ge on "ltraso"n$ on $ay 1 of ac"te #ancreatitis is associate$ /ith rec"rrence after cholecystectomy% a #o#"la: tion:base$ st"$y. S"rgery 210231@1%1==G20@4 1@14 Ay"b Q* ;ma$a R, Sla2in ,. ERC' in gallstone associate$ ac"te #ancreatitis. Cochrane (atabase Syst Re2 2001%C(003>304 1@24 A$ler (G* Chari ST, (ahl T, et al. Conser2ati2e management of infecte$ necrosis com#licating se2ere ac"te #ancreatitis4 Am , Gastroenterol 20033=5%=5G1034 1@34 2an -aal &C* 2an Sant2oort )C* -ollen T et al. Systematic re2ie/ of #erc"taneo"s catheter $rainage as #rimary treatment for necrotiAing #ancreatitis4 -r , S"rg 20113=5%15G2?4 1@14 -aBBer O,, 2an Sant2oort )C* 2an -r"nschott S et al. En$osco#ic trans: gastric 2s s"rgical necrosectomy for infecte$ necrotiAing #ancreatitis3 a ran$omiAe$ trial. ,A&A 2012330?%10@3G>14 1@@4 0ege SS* -aron T)4 &anagement of #ancreatic necrosis in se2ere ac"te #ancreatitis4 Clin Gastroenterol )e#atol 20013==%215=G=14 1@>4 2an Sant2oort )C* -aBBer O,, -ollen T et al. A conser2ati2e an$ mini: mally in2asi2e a##roach to necrotiAing #ancreatitis im#ro2es the o"tcome4 Gastroenterology 20113111%12@1G>34 1@?4 )ong S* Vi/en -, !ing , et al. -o$y mass in$eD an$ the risB an$ #rog: nosis of ac"te #ancreatitis% a meta:analysis4 E"r , Gastroenterol )e#atol 2011312%13>G134 0O<&E 101 K LLL 2012