Острый панкреатит PDF

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СБОРНИК
МЕТОДИЧЕСКИХ МАТЕРИАЛОВ
«ШКОЛЫ ХИРУРГИИ РОХ»
ОСТРЫЙ ПАНКРЕАТИТ
Редакция 1
2015
г. МОСКВА
СБОРНИК
МЕТОДИЧЕСКИХ МАТЕРИАЛОВ
«ШКОЛЫ ХИРУРГИИ РОХ»
ОСТРЫЙ ПАНКРЕАТИТ
Редакция 1
2015
г. МОСКВА
2 ОСТРЫЙ ПАНКРЕАТИТ
УВАЖАЕМЫЕ КОЛЛЕГИ!
Представляем вашему вниманию сборник материалов к проекту

непрерывного медицинского образования Российского общества хирургов
«Школа хирургии».
Основная идея проекта — дать практикующему хирургу максимум
современной полезной информации, основанной на клинических
рекомендациях по основным хирургическим заболеваниям. Семинары
Школы хирургии будут проходить на постоянной основе во всех регионах
Российской Федерации.
Основные методические материалы Вы можете получить в электронном
виде. Для этого на сайте www.nmo-roh.ru в разделе «Школа хирургии» надо
ввести оригинальный код участника школы хирургии, который Вы получаете
при регистрации на мероприятие школы.
В данном сборнике мы постарались собрать наиболее достоверную
информацию по современным представлениям о лечении больных с острым
панкреатитом. Очень непростым было принятие отечественных клинических
рекомендаций по острому панкреатиту. Тем не менее, после неоднократных
обсуждений на разных научных площадках, удалось достичь консенсуса
в Санкт-Петербурге 30 октября 2014 года на Круглом столе: диагностика
и лечение острого панкреатита. Этот консенсусный документ открывает
этот сборник.
Остальную часть сборника, которую Вы можете получить в электронном
виде, представляют зарубежные клинические рекомендации с высоким
уровнем доказательности. Не могли мы обойти пересмотр классификации
острого панкреатита Atlanta 2012 года.
Координаторы Школы хирургии надеются, что в течение 5-летнего
периода на столе у каждого хирурга окажется небольшая библиотечка
методических материалов по каждой из тем, которые будут освещаться
на семинарах Школы хирургии Российского общества хирургов.
Правление Российского Общества Хирургов

СБОРНИК МЕТОДИЧЕСКИХ МАТЕРИАЛОВ «ШКОЛЫ ХИРУРГИИ РОХ» 3
ОГЛАВЛЕНИЕ
I. Диагностика и лечение острого панкреатита (Российские

клинические рекомендации) – рекомендации, принятые
на круглом столе в Санкт-Петербурге, 30 октября 2014 г. .......................... 4
II. Классификация острого панкреатита 2012: пересмотр
классификации Atlanta и определения на основе
международного консенсуса (Classification of acute
pancreatitis 2012: revision of the Atlanta classification
and definitions by international consensus) ................................................. ˇ22
III. Клинические рекомендации IAP/APA по лечению острого
панкреатита, основанные на доказательствах (IAP/APA
evidence-based guidelines for the management of acute
pancreatitis) – рекомендации по лечению острого
панкреатита 2013 года, разработанные международной
ассоциацией панкреатологов совместно с американской
панкреатологической ассоциацией ........................................................... 32
IV. Клинические рекомендации Американского колледжа
гастроэнтерологии: лечение острого панкреатита
(American College of Gastroenterology Guideline:
Management of Acute Pancreatitis) – американские
клинические рекомендации 2013 года ..................................................... ˇ48
V. Практические рекомендации по лечению острого панкреатита
(Practical Guidelines for Acute Pancreatitis) – итальянские
клинические рекомендации, 2010 года ..................................................... 64
VI. ACR критерии острого панкреатита (ACR Appropriateness
Criteria® acute pancreatitis) – клинические рекомендации 2013 г.
по инструментальной диагностике острого панкреатита,
разработанные Американским колледжем радиологии ......................... 78
Для получения электронной версии «Сборника методических

материалов «Школы хирургии РОХ» по теме введите Ваш
уникальный код из «Регистрационного свидетельства»
на странице «Школы хирургии» «Пройти тестирование
по программе школы» (http://www.nmo-roh.ru/testirovanie).
ДИАГНОСТИКА И ЛЕЧЕНИЕ ОСТРОГО код МКБ – 10 – К85
I ПАНКРЕАТИТА
Диагностика и лечение острого панкреатита
РОССИЙСКИЕ КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ
(Российские клинические рекомендации)
ВВЕДЕНИЕ
В последние десятилетия усилиями мировых и национальных профессиональных сообществ
создается огромное число клинических протоколов (рекомендаций) по проведению диагностических
исследований, лечебной помощи и профилактике заболеваний. Это новый шаг в организации меди-
цинской деятельности, потому что позволяет врачу использовать только достоверно проверенные,
научно доказанные методы, средства и технологии.
Такие доказательства базируются на многоцентровых исследованиях, проведенных по нормам

надлежащей клинической практики (GCP), метаанализах литературных данных. Поэтому те положения
клинических рекомендаций, которые имеют высокий уровень доказательности требуют неукосни-
тельного исполнения.
Они позволяют оптимизировать последовательность действий медицинского персонала на всех

этапах медицинской помощи, а также принятие решений в выборе методов диагностики, места и ха-
рактера лечения, назначения лекарственных средств исходя из научно обоснованных доказательств их
эффективности и безопасности для больных. В этом отношении клинические рекомендации можно
рассматривать как пошаговую инструкцию, выполнение которой должно обеспечивать наиболее высо-
кое качество лечебной помощи, независимо от того, где и кем она оказывается.
Практикующему врачу клинические рекомендации помогают не только делать выбор в пользу

наиболее эффективных методов или способов лечения, но и обратить внимание на методы с недока-
занной эффективностью, а также опасные или просто бесполезные методы или средства.
Клинические рекомендации – постоянно обновляемый документ и нуждаются в регулярном пе-
ресмотре, дополнениях, связанных с появлением новых знаний, доказательств, технологий и средств.
Поэтому они должны быть обязательным элементом учебных программ и непрерывного медицинского
образования.
ДИАГНОСТИКА И ЛЕЧЕНИЕ ОСТРОГО ПАНКРЕАТИТА 5
Определение и классификация
Острый панкреатит – это первоначально асептическое воспаление поджелудочной же-

лезы, при котором возможно поражение окружающих тканей и отдаленных органов, а также
систем.
Классификация острого панкреатита
Российского общества хирургов – 2014г.
Разработана с учётом классификации Атланта–92 и её модификаций, предложенных
в г. Кочин в 2011г (Международная Ассоциация Панкреатологов, International Association
of Pancreatology) и Международной рабочей группой по классификации острого панкреа-
тита (Acute Pancreatitis Classification Working Group) в 2012г.
1. Острый панкреатит лёгкой степени. Панкреонекроз при данной форме острого панкре-
атита не образуется (отёчный панкреатит) и органная недостаточность не развивается.
2. Острый панкреатит средней степени. Характеризуется наличием либо одного из мест-
ных проявлений заболевания: перипанкреатический инфильтрат, псевдокиста, отграни-
ченный инфицированный панкреонекроз (абсцесс), – или/и развитием общих проявлений в
виде транзиторной органной недостаточности (не более 48 часов).
3. Острый панкреатит тяжёлой степени. Характеризуется наличием либо неотграничен-
ного инфицированного панкреонекроза (гнойно-некротического парапанкреатита), или/и
развитием персистирующей органной недостаточности (более 48 часов).
Диагноз острого панкреатита лёгкой, средней или тяжёлой степени устанавливается по факту
законченного случая заболевания.
Этиологические формы острого панкреатита

1. Острый алкогольно-алиментарный панкреатит – 55% .
2. Острый билиарный панкреатит (возникает из-за желчного рефлюкса в панкреатические
протоки при билиарной гипертензии, которая возникает, как правило, вследствие холели-
тиаза, иногда – от других причин: дивертикул, папиллит, описторхоз и т.д.) – 35%.
3. Острый травматический панкреатит (вследствие травмы поджелудочной железы, в том
числе операционной или после ЭРХПГ) 2 – 4 %.
4. Другие этиологические формы причины: аутоиммунные процессы, сосудистая недостаточ-
ность, васкулиты, лекарственные препараты (гипотиазид, стероидные и нестероидные гор-
моны, меркаптопурин), инфекционные заболевания (вирусный паротит, гепатит, цитоме-
галовирус), аллергические факторы (лаки, краски, запахи строительных материалов, ана-
филактический шок), дисгормональные процессы при беременности и менопаузе, заболе-
вания близлежащих органов (гастродуоденит, пенетрирующая язва, опухоли гепатопан-
креатодуоденальной области) – 6 – 8%.
Патогенез
Ведущая роль в патогенезе токсемии при остром панкреатите принадлежит ферментам
поджелудочной железы: трипсин, липаза, фосфолипаза – А2, лизосомным ферментам, которые
вызывают окислительный стресс, липидный дистресс-синдром, тромбоз капилляров, гипо-
ксию, ацидоз, гиперметаболизм,повреждение мембран клеток и эндотелия.
Первичные факторы агрессии:
а) ферменты поджелудочной железы: трипсин, химотрипсин, вызывают протеолиз белков тка-
ней.
б) фосфолипаза А2 разрушает мембраны клеток
в) липаза гидролизует внутриклеточные триглицериды до жирных кислот и, соединяясь с
кальцием, приводит к липолитическому некрозу в поджелудочной железе, забрюшинной клет-
чатке и брыжейке тонкой и толстой кишки.
г) эластаза разрушает стенку сосудов и межтканевые соединительнотканные структуры, что

приводит к некрозу.
Вторичные факторы агрессии:
Ферменты поджелудочной железы активируют калликреин – кининовую системы с обра-
зованием биологически активных веществ: брадикинин, гистамин, серотонин, которые приво-
дят к увеличению сосудистой проницаемости, нарушениям микроциркуляции, отеку, повы-
шенной экссудации и микротромбозу, ишемии, гипоксии и ацидозу тканей.
Третичные факторы:
Макрофаги, мононуклеарные клетки, нейтрофилы на фоне нарушений микроциркуляции,
СВР, гипоксии продуцируют цитокины ( интерлейкин 1,6 и 8, фактор некроза опухоли, фак-
тор активации тромбоцитов, простагландинов, тромбоксана, лейкотриенов, оксида азота, угне-
тению иммунного статуса.
Факторы агрессии четвертого порядка:
Цитокины, ферменты, метаболиты различной природы, образующиеся в поджелудочной
железе, жировой клетчатке, стенке кишечника, брюшной полости увеличивают проницаемость
стенки кишки, происходит транслокация кишечной флоры, способствуют поступлению токси-
нов в портальный и системный кровоток и лимфатическое русло с поражением органов мише-
ней: печени, легких, почек, сердца, мозга, кишечника, слизистых желудка и кишечника.
Факторы агрессии и органные дисфункции создают синдром «взаимного отягощения».
Определение начала острого панкреатита

Типичный болевой синдром возникает при остром панкреатите всегда. Обычно он интен-
сивный, стойкий, не купируется спазмолитиками и анальгетиками. Начало острого панкреати-
та должно определяться по времени появления абдоминального болевого синдрома, а не по
времени поступления больного в стационар. Выявить момент начала заболевания можно при
тщательном сборе анамнеза. При переводе больного из одного стационара в другой (например,
из ЦРБ в областную больницу) началом заболевания следует считать время появления болево-
го синдрома при первичном обращении за медицинской помощью.
Фазы острого панкреатита

Отечный (интерстициальный) панкреатит по частоте занимает 80-85% в структуре забо-
левания. Характеризуется легкой степенью тяжести заболевания и редким развитием локаль-
ных осложнений или системных расстройств, фазового течения не имеет.
Некротический панкреатит (панкреонекроз) встречается у 15-20% больных, клинически
всегда проявляется средней или тяжёлой степенью заболевания, имеет фазовое течение забо-
левания с двумя пиками летальности – ранней и поздней. После ранней фазы, которая обыч-
но продолжается в течение первых двух недель, следует вторая или поздняя фаза, которая мо-
жет затягиваться на период от недель до месяцев. Целесообразно рассматривать эти две фазы
раздельно, так как каждой фазе соответствует определённая клиническая форма, и, следова-
тельно, определённый лечебно-диагностический алгоритм.
I фаза – ранняя, в свою очередь подразделяется на два периода:
- IА фаза, как правило, первая неделя заболевания. В этот период происходит формирование
очагов некроза в паренхиме поджелудочной железы или окружающей клетчатке различного
объёма и развитие эндотоксикоза. Эндотоксикоз проявляется легкими или глубокими систем-
ными нарушениями в виде органной (полиорганной) недостаточности. Максимальный срок
формирования некроза в поджелудочной железе обычно составляет трое суток, после этого
срока он в дальнейшем не прогрессирует. Однако при тяжёлом панкреатите период его фор-
мирования гораздо меньше (как правило, 24-36 часов). В брюшной полости происходит накоп-
ление ферментативного выпота (ферментативные перитонит и парапанкреатит), который явля-
ется одним из источников эндотоксикоза. Средняя степень тяжести течения заболевания про-
является преходящей дисфункцией отдельных органов или систем. При тяжёлых формах забо-
левания в клинической картине могут преобладать явления органной (полиорганной) недоста-
точности: сердечно-сосудистой, дыхательной, почечной, печеночной и др.
- IВ фаза, как правило, вторая неделя заболевания. Характеризуется реакцией организма
на сформировавшиеся очаги некроза (как в поджелудочной железе, так и в парапанкреальной
клетчатке). Клинически превалируют явления резорбтивной лихорадки, формируется пери-
панкреатический инфильтрат.
II фаза – поздняя, фаза секвестрации (начинается, как правило, с 3-ей недели заболева-
ния, может длиться несколько месяцев). Секвестры в поджелудочной железе и в забрюшинной
клетчатке обычно начинают формироваться с 14-х суток от начала заболевания. При отторже-
нии крупных крупных фрагментов некротизированной ткани поджелудочной железы может
происходить разгерметизация её протоковой системы и образование внутреннего панкреати-
ческого свища. От конфигурации панкреонекроза (локализации, глубины, отношения к глав-
ному панкреатическому протоку и др.) и объёма оставшейся жизнеспособной паренхимы под-
желудочной железы зависят: количество, масштабы и скорость распространённости жидкост-
ного образования в забрюшинном пространстве, риск инфицирования и развития других
осложнений. Возможно два варианта течения этой фазы:
• асептическая секвестрация – стерильный панкреонекроз характеризуется образовани-
ем изолированного скопления жидкости в области поджелудочной железы и постнекроти-
ческих псевдокист поджелудочной железы;
• септическая секвестрация возникает при инфицировании некроза паренхимы поджелу-
дочной железы и парапанкреальной клетчатки с дальнейшим развитием гнойных осложне-
ний. Клинической формой данной фазы заболевания является инфицированный панкре-
онекроз, который может быть отграниченным (абсцесс) или неотграниченным (гнойно-
некротический парапанкреатит). При прогрессировании гнойных осложнений инфици-
рованный панкреонекроз может иметь собственные осложнения (гнойно-некротические
затёки, абсцессы забрюшинного пространства и брюшной полости, гнойный перитонит,
аррозионные и желудочно-кишечные кровотечения, дигестивные свищи, сепсис и т.д.) с
развитием эндотоксикоза инфекционного генеза, органной (полиорганной) недостаточно-
сти.
Терминология
Отёчный панкреатит («interstitial oedematous pancreatitis») - характеризуется диффуз-
ным (или иногда локальным) увеличением поджелудочной железы из-за воспалительного оте-
ка.
Некротический панкреатит (панкреонекроз, «pancreatic necrosis») - диффузные или
очаговые зоны нежизнеспособной паренхимы поджелудочной железы, которые, как правило,
сочетаются с некрозом забрюшинной жировой клетчатки.
Стерильный панкреонекроз («sterile pancreatic necrosis») – панкреонекроз, который не
содержит патогенной микрофлоры и не сопровождается развитием гнойных осложнений.
Инфицированный панкреонекроз («infected pancreatic necrosis») - бактериально об-
семененный некроз ткани поджелудочной железы и забрюшинной клетчатки с гнойным их
расплавлением и секвестрацией. Инфицированный панкреонекроз, не имеющий отграничения
от здоровых тканей называется гнойно-некротический парапанкреатит. Инфицированный
панкреонекроз, имеющий отграничение от здоровых тканей, следует расценивать, как панкре-
атический абсцесс.
Перипанкреатический инфильтрат («acute fluid сollection», «аcute necrotic
collection») - это экссудативно-пролиферативный воспалительный процесс в поджелудочной
железе и окружающих тканях, который сопровождается острым скоплением жидкости (с пан-
креонекрозом или без панкреонекроза), располагающейся внутри или около поджелудочной
железы и не имеющей стенок из грануляционной или фиброзной ткани. Возникает в IB фазе
острого панкреатита, имеет следующие исходы: полное разрешение и рассасывание (чаще к 4-
ой неделе заболевания), образование псевдокисты поджелудочной железы, развитие гнойных
осложнений.
Псевдокиста поджелудочной железы («acute pseudocyst») - это скопление жидкости (с
секвестрами или без секвестров), отграниченное фиброзной или грануляционной тканью, воз-
никающее после приступа острого панкреатита. Возникает в сроки после 4-х недель от начала
заболевания, в фазе асептической секвестрации некротического панкреатита. Как правило, яв-
ляется исходом инфильтрата. Содержимое кисты может быть асептическим и инфицирован-
ным. Бактериальная контаминация содержимого кисты часто не имеет клинического проявле-
ния, но вероятность её инфицирования всегда выше при наличии секвестров. Инфицирован-
ную кисту более корректно называть панкреатическим абсцессом.
Гнойные осложнения (панкреатический абсцесс или гнойно-некротический парапанкре-
атит) определяются при наличии минимум одного из следующих признаков:
- пузырьки воздуха в зоне панкреонекроза, выявленные при компьютерной томогра-
фии;
- положительный бакпосев аспирата, полученного при тонкоигольной пункции;
- положительный бакпосев отделяемого, полученного при санирующей операции.
Органная недостаточность («organ failure») определяется по наихудшему показателю
одной из 3 органных систем (сердечно-сосудистой, почечной и дыхательной) за 24-часовой
период без предшествующей органной дисфункции. Определение производится по соответ-
ствующим показателям шкалы SOFA (Sepsis-related Organ Failure Assessment): превышение
порога в 2 балла является основанием для диагностирования органной недостаточности:
- сердечно-сосудистая недостаточность: необходимость инотропных препаратов
- почечная недостаточность: креатинин >171 μmol/L (>2.0 mg/dL)
- дыхательная недостаточность: Pa02/Fi02 < 300 mmHg (<40 kPa).
Персистирующая органная недостаточность («persistent organ failure») - недостаточ-
ность одной органной системы в течение 48 часов или более.
Транзиторная органная недостаточность («transient organ failure») - недостаточность
одной органной системы в течение менее 48 часов.
Полиорганная недостаточность («multiple organ failure») - недостаточность двух и бо-
лее органных систем.
Первичная медико-санитарная
помощь и скорая медицинская помощь
Основанием для диагностики острого панкреатита при первичном осмотре больного яв-
ляется классическая триада симптомов – выраженная боль в эпигастрии с иррадиацией в спину
или опоясывающего характера, многократная рвота и напряжение мышц в верхней половине
живота. Чаще всего появлению симптомов предшествует обильный прием пищи или алкоголя,
наличие желчнокаменной болезни. Больные с подозрением на острый панкреатит подлежат
экстренной госпитализации в хирургическое отделение многопрофильного стационара. При
выраженном болевом синдроме допустима инъекция спазмолитических и нестероидных про-
тивовоспалительных препаратов.
Ранняя фаза
Протоколы диагностики и лечения

острого панкреатита в IА фазе заболевания
I. Первичный протокол диагностики и тактики при остром панкреатите
Как правило, осуществляется в приёмном отделении или отделении экстренной помощи.

1) Основанием для установления диагноза острого панкреатита (после исключения дру-
гой хирургической патологии) является сочетание минимум двух из следующих вы-
явленных признаков:
а) типичная клиническая картина (интенсивные некупируемые спазмолитиками боли
опоясывающего характера, неукротимая рвота, вздутие живота; употребление алко-
голя, острой пищи или наличие ЖКБ в анамнезе и др.);
б) характерные признаки по данным УЗИ: увеличение размеров, снижение эхогенно-
сти, нечёткость контуров поджелудочной железы; наличие свободной жидкости в
брюшной полости;
в) гиперферментемия (гиперамилаземия или гиперлипаземия), превышающая верх-
нюю границу нормы в три раза и более.
Сила рекомендаций «В»
Если диагноз острого панкреатита устанавливается на основании методов а), б) и в), то

выполнение мультиспиральной компьютерно-томографической ангиографии (МСКТА)
или магнитно-резонансной томографии (МРТ) для постановки диагноза острого панкреа-
тита не требуется.
Сила рекомендаций «С»
2) Для оценки тяжести ОП и прогноза развития заболевания возможно применение шкалы

критериев первичной экспресс-оценки тяжести острого панкреатита (СПб НИИ
СП имени И.И. Джанелидзе – 2006г.):
- перитонеальный синдром;
- олигурия (менее 250 мл за последние 12 часов);
- кожные симптомы (гиперемия лица, «мраморность», цианоз);
- систолическое артериальное давление менее 100 мм.рт.ст;
- энцефалопатия;
- уровень гемоглобина более 160 г/л;
- количество лейкоцитов более 14 х109/л;
- уровень глюкозы крови более 10 ммоль/л;
- уровень мочевины более 12 ммоль/л;
- метаболические нарушения по данным ЭКГ;
- вишнёвый или коричнево-чёрный цвет ферментативного экссудата, получен-
ного при лапароскопии (лапароцентезе);
- выявление при лапароскопии распространённого ферментативного парапан-
креатита, выходящего за границы сальниковой сумки и распространяющийся
по фланкам;
- наличие распространённых стеатонекрозов, выявленных при лапароскопии;
- отсутствие эффекта от базисной терапии.
Оценка шкалы:
• Если у конкретного пациента имеется минимум 5 признаков из числа перечисленных,
то с 95% вероятностью у него имеется тяжёлая форма ОП.
• Если имеется 2-4 признака – ОП средней степени.

• Если нет ни одного признака или имеется максимум один из них – лёгкая форма ОП.
Наиболее важно раннее выявление тяжёлого панкреатита, результаты лечения которого

во многом обусловлены сроком его начала. Наличие хотя бы двух признаков, перечис-
ленных в шкале экспресс-оценки, позволяет диагностировать тяжёлый или средне-
тяжёлый ОП, который подлежит обязательному направлению в отделение реанимации и
интенсивной терапии. Остальным пациентам (лёгкий ОП) показана госпитализация в хи-
рургическое отделение.
3) Для оценки органных и полиорганных дисфункций наиболее целесообразно использовать

шкалу SOFA. При невозможности использовать многопараметрические шкалы для опреде-
ления тяжести ОП допустимо применение клинико-лабораторных критериев: признаки
синдрома системного воспалительного ответа (ССВО) ; гипокальциемия < 1,2 ммоль/л,
гемоконцентрация: гемоглобин крови > 160г/л или гематокрит > 40 Ед., гипергликемия >
10 ммоль/л; С – реактивный белок > 120мг/л; шок (систолическое АД < 90 мм.рт.ст.) дыха-
тельная недостаточность (РО2<60мм.рт.ст.); почечная недостаточность (олиго-анурия, кре-
атинин > 177 мкмоль/л); печеночная недостаточность (гиперферментемия); церебральная
недостаточность (делирий, сопор, кома); желудочно-кишечное кровотечение (более
500мл/сутки); коагулопатия (тромбоциты < 100 х 109/л, фибриноген < 1,0г/л).
4) Интенсивный болевой синдром, не купируемый наркотическими анальгетиками, быстро

прогрессирующая желтуха, отсутствие желчи в ДПК при ФГДС, признаки билиарной гипер-
тензии по данным УЗИ свидетельствуют о наличии вклиненного камня большого дуоденаль-
ного сосочка (БДС). В этом случае пациент нуждается в срочном (12-24 часов) восстановле-
нии пассажа желчи и панкреатического сока, оптимальным методом которого служит ЭПСТ с
литоэкстракцией, после которой, при наличии возможностей, желательно выполнять дрениро-
вание главного панкреатического протока. При вклиненном камне БДС и при остром панкреа-
тите ЭПСТ нежелательно и опасно производить контрастирование протоков.
Сила рекомендаций «D»
5) Оптимальным видом лечения ОП в IА фазе является интенсивная консервативная тера-

пия. Хирургическое вмешательство в виде лапаротомии показано лишь при развитии ослож-
нений хирургического профиля, которые невозможно устранить мининвазивными технологи-
ями.
Сила рекомендаций «A»
II Протокол лечения острого панкреатита лёгкой степени

1) Госпитализация больных ОП лёгкой степени производится в хирургическое отделение.
Для лечения лёгкого панкреатита достаточно проведения базисного лечебного комплек-
са:
- голод;
- зондирование и аспирация желудочного содержимого;
- местная гипотермия (холод на живот);
- анальгетики;
- спазмолитики;
- инфузионная терапия в объёме до 40 мл на 1 кг массы тела пациента с форси-
рованием диуреза в течение 24-48 часов.
Базисную терапию целесообразно усиливать ингибиторами панкреатической секреции.
2) При отсутствии эффекта от проводимой базисной терапии (п.1) в течение 6 часов и нали-
чии хотя бы одного из признаков тяжёлого панкреатита (шкала экспресс оценки протокол
I.2) следует констатировать тяжёлый/средне-тяжёлый панкреатит и перевести больного в
отделение реанимации и интенсивной терапии и проводить лечение, соответствующее
тяжёлому/средне-тяжёлому острому панкреатиту (протоколы III, IV).
III Протокол интенсивной терапии острого панкреатита средней степени
Основной вид лечения – консервативная терапия. Приведенный выше базисный лечеб-

ный комплекс при средне-тяжёлом ОП необходимо дополнять специализированным лечебным
комплексом (см. ниже). Эффективность последнего максимальна при раннем начале лечения
(первые 24часа от начала заболевания). При поступлении больных ОП средней степени необ-
ходимо госпитализировать в отделение реанимации и интенсивной терапии (ОРИТ). Для ис-
ключения диагностических ошибок дежурной службой больных ОП средней тяжести целесо-
образно наблюдать в течение суток в условиях ОРИТ. При отсутствии явлений органной недо-
статочности и прогрессирования заболевания в течение суток больных ОП средней степени
можно перевести в хирургическое отделение. При условии появления у больных ОП средней
тяжести, находящихся в хирургическом отделении, признаков органной дисфункции или недо-
статочности, что свидетельствует о прогрессирования заболевания – гипотонии
(АД<100мм.рт.ст.), дыхательной недостаточности (ЧД>30 в 1 минуту), делирия и др. (см. про-
токол I.2, I.3), – последних необходимо перевести в ОРИТ.
Специализированное лечениe
1) Ингибирование секреции поджелудочной железы (оптимальный срок – первые трое

суток заболевания).
2) Активная реологическая терапия.

3) Инфузионная терапия в общей сложности не менее 40 мл соответствующих инфузи-

онных средств на 1 кг массы тела с форсированием диуреза при наличии органной
дисфункции.
4) Антиоксидантная и антигипоксантная терапия.

5) Эвакуация токсических экссудатов по показаниям (см. стандарт V). При фермента-

тивном перитоните – санационная лапароскопия. Допустимо выполнение чрескожно-
го дренирования брюшной полости под УЗ-наведением или лапароцентеза.
6) Применение антибиотиков с профилактической целью не является обязательным.

IV Протокол интенсивной терапии острого панкреатита тяжёлой степени

Основной вид лечения – интенсивная терапия. Приведенный выше базисный лечебный
комплекс при тяжёлом ОП является недостаточно эффективным и должен быть дополнен спе-
циализированным лечебным комплексом (см. ниже). Эффективность последнего максимальна
при раннем начале лечения (первые 12 часов от начала заболевания). При поступлении боль-
ные ОП тяжёлой степени должны быть госпитализированы в отделение реанимации и интен-
сивной терапии. Лечебно-диагностический комплекс для больных ОП тяжёлой степени необ-
ходимо проводить в условиях ОРИТ, после купирования явлений органной недостаточности и
стабилизации состояния (купирование делирия, расстройств гемодинамики, дыхательной дея-
тельности и др.) возможен перевод пациентов в хирургическое отделение.
Специализированное лечениe
К протоколу II и III прибавляются:
1. Экстакорпоральные методы детоксикации – по показаниям:
а) плазмаферез;
б) гемофильтрация
2. Назогастральное зондирование для декомпрессии и, при возможности, назогастроинтести-

нальное зондирование – для ранней энтеральной поддержки.
3. Коррекция гиповолемических нарушений.

4. Целесообразно выполнение эпидуральной блокады.

5. Применение антибиотиков с профилактической целью в первые трое суток заболевания не

является обязательным.
6. Целесообразно назначение дезагрегантной антитромботической терапии.

V Протокол лапароскопической операции
Лапароскопия показана:
- пациентам с перитонеальным синдромом, в том числе при наличии УЗ-
признаков свободной жидкости в брюшной полости;
- при необходимости дифференциальной диагностики с другими заболева-

ниями органов брюшной полости.
Сила рекомендаций «C»
Задачи лапароскопической операции могут быть диагностическими, прогностическими и

лечебными. Возможно выполнение чрескожного дренирования брюшной полости под
УЗ-наведением или лапароцентеза.
Задачи лапароскопической операции:

а) подтверждение диагноза острого панкреатита (и, соответственно, исключение дру-
гих заболеваний брюшной полости, прежде всего острой хирургической патологии –
мезентериального тромбоза и др.); к признакам ОП относятся:
- наличие отёка корня брыжейки поперечной ободочной кишки;
- наличие выпота с высокой активностью амилазы (в 2-3 раза превышающей ак-
тивность амилазы крови);
- наличие стеатонекрозов;
б) выявление признаков тяжёлого панкреатита:

- геморрагический характер ферментативного выпота (розовый, малиновый,
вишнёвый, коричневый);
- распространённые очаги стеатонекрозов;
- обширное геморрагическое пропитывание забрюшинной клетчатки, выходя-
щее за пределы зоны поджелудочной железы;
Верификация серозного («стекловидного») отёка в первые часы заболевания

(особенно на фоне тяжёлого общего состояния пациента) не исключает
наличие тяжёлого панкреатита, так как при лапароскопии в ранние сроки
признаки тяжёлого панкреатита могут не выявляться, т.е. заболевание в
дальнейшем может прогрессировать.
в) лечебные задачи:
- удаление перитонеального экссудата и дренирование брюшной полости.
VI Компьютерная томография
Показаниями для ранней МСКТА (МРТ) являются:
1. Неясность диагноза и дифференциальная диагностика с другими заболеваниями.
2. Необходимость подтверждения тяжести по выявленным клиническим прогностиче-
ским признакам тяжёлого ОП.
3. Отсутствие эффекта от консервативного лечения.
Оптимальными сроками выполнения МСКТА (МРТ) для диагностики панкреонекроза (и оцен-

ки всего объема патологических изменений в грудной клетке, брюшной полости и забрюшин-
ной клетчатке) являются 4 – 14 сутки заболевания.
МСКТА (МРТ) целесообразно выполнять накануне инвазивного вмешательства.

Последующие МСКТА (МРТ) необходимо выполнять при прогрессировании заболевания, при

отсутствии эффекта от лечения и для локализации очагов нагноения перед выполнением дре-
нирующих вмешательств.
Использование в клинической практике КТ–индекса тяжести панкреатита по Бальтазару

не является обязательным диагностическим исследованием. Его желательно использовать для
прогноза тяжести заболевания.

острого панкреатита IВ фазе заболевания
I Протокол диагностики и мониторинга перипанкреатического инфильтрата
Вторая неделя заболевания характеризуется наступлением периода асептической воспа-
лительной реакции на очаги некроза в поджелудочной железе и окружающей клетчатке, кото-
рая клинически выражается появлением инфильтрата в эпигастральной области (местный
компонент) и резорбтивной лихорадкой (системный компонент воспаления). Перипанкреати-
ческий инфильтрат (ПИ) и резорбтивная лихорадка являются закономерными признаками тя-
жёлого или средне-тяжёлого панкреатита, тогда как при лёгком панкреатите эти признаки не
выявляются.
1. Помимо клинических признаков (перипанкреатический инфильтрат и лихорадка) вторая

неделя ранней фазы ОП характеризуется:
1.1 Лабораторными показателями синдрома системной воспалительной реакции (ССВР):
лейкоцитозом со сдвигом влево, лимфопенией, увеличенной СОЭ, повышением кон-
центрации фибриногена, С-реактивного белка и др.;
1.2 УЗ-признаками ПИ (сохраняющееся увеличение размеров поджелудочной железы, не-

чёткость её контуров и появление жидкости в парапанкреальной клетчатке).
2. Мониторинг перипанкреатического инфильтрата заключается в динамическом исследо-

вании клинико-лабораторных показателей и данных повторных УЗИ (не менее 2 ис-
следований на второй неделе заболевания).
3. В конце второй недели заболевания целесообразна компьютерная томография зоны под-

желудочной железы, так как к этому сроку у подавляющего большинства пациентов
наблюдается один из трёх возможных исходов IВ фазы:
3.1 Рассасывание, при котором наблюдается редукция местных и общих проявлений
острой воспалительной реакции.
3.2 Асептическая секвестрация панкреонекроза с возможным последующим исходом
в псевдокисту поджелудочной железы: сохранение размеров ПИ при нормализа-
ции самочувствия и стихании синдрома системной воспалительной реакции
(ССВР) на фоне сохраняющейся гиперамилаземии.
3.3 Септическая секвестрация (развитие гнойных осложнений).
II Протокол тактики лечения перипанкреатического инфильтрата

У подавляющего большинства пациентов лечение перипанкреатического инфильтрата
является консервативным. Лапаротомия на второй неделе ОП выполняется только при ослож-
нениях хирургического профиля (деструктивный холецистит, желудочно-кишечное кровоте-
чение, острая кишечная непроходимость и др.), которые невозможно устранить миниинвазив-
ными технологиями.
Состав лечебного комплекса:
1. Продолжение базисной инфузионно-трансфузионной терапии, направленной на вос-
полнение водно-электролитных, энергетических и белковых потерь по показаниям.
2. Лечебное питание: стол № 5 при среднетяжёлом ОП; нутриционная поддержка (перо-

ральная, энтеральная или парентеральная) при тяжёлом ОП.
3. Системная антибиотикопрофилактика (цефалоспорины III-IV поколений или фторхи-

нолоны II-III поколений в сочетании с метронидазолом, препараты резерва - карбапе-
немы).
4. Иммунотерапия (желательна коррекция клеточного и гуморального иммунитета).

Поздняя фаза (секвестрации)

острого панкреатита в фазе асептической секвестрации
I Протокол диагностики и мониторинга псевдокисты поджелудочной железы
Клинической формой острого панкреатита в фазе асептической секвестрации является

постнекротическая псевдокиста поджелудочной железы, срок формирования которой состав-
ляет от 4-х недель и в среднем до 6 месяцев.
Критерии верификации кисты поджелудочной железы:
1. Стихание синдрома системной воспалительной реакции на фоне сохраняющейся ги-
перамилаземии.
2. Увеличение к 5-ой неделе заболевания размеров жидкостного скопления в парапан-

креальной клетчатке и появление у него стенки по данным УЗИ, КТ.
3. При отсутствии осложнений (см. ниже) больного можно выписать на амбулаторное

лечение. Размеры кисты необходимо мониторировать по данным УЗИ (1 раз в 2-4 не-
дели).
Если при асептической секвестрации не происходит вскрытия протоковой системы под-

желудочной железы, то образование кисты не происходит. В данном случае, как правило,
наблюдается рассасывание перипанкреатического инфильтрата (редукция жидкостного скоп-
ления в области поджелудочной железы) в сроки до 4-х недель. Этот период больные должны
находиться под динамическим врачебным наблюдением (допустимо в амбулаторном порядке).
II Протокол лечения псевдокисты поджелудочной железы
Псевдокисты поджелудочной железы небольшого размера (менее 5см) оперировать не-

целесообразно, они подлежат динамическому наблюдению хирурга. Псевдокисты поджелу-
дочной железы большого размера (более 5см) подлежат оперативному лечению в плановом
порядке при отсутствии осложнений (см. ниже). Операцией выбора незрелой (несформиро-
вавшейся) псевдокисты (менее 6мес) является наружное дренирование. Зрелая (сформировав-

шаяся) псевдокиста (более 6мес) подлежит оперативному лечению в плановом порядке.
Осложнения псевдокисты поджелудочной железы:

1. Инфицирование.
2. Кровотечение в полость кисты.
3. Перфорация кисты с прорывом в свободную брюшную полость с развитием перито-
нита.
4. Сдавление соседних органов с развитием механической желтухи, стеноза желудка,
кишечной непроходимости и др.
Протоколы диагностики и лечения острого панкреатита

в фазе септической секвестрации
I Протокол диагностики гнойных осложнений острого панкреатита
Инфицирование очага панкреатогенной деструкции происходит, в среднем в конце 2-ой

– начале 3-ей недели от начала заболевания. Однако при позднем поступлении больного, не-
адекватном лечении, или после слишком ранней и поспешной операции, инфицирование зон
панкреонекроза и гнойно-деструктивные осложнения могут развиваться раньше, минуя период
асептической деструкции ("перекрест фаз"). Клинической формой острого панкреатита в фазе
септической секвестрации (третья неделя от начала заболевания и более) является инфициро-
ванный панкреонекроз: отграниченный – панкреатический абсцесс (ПА) или неотграниченный
– гнойно-некротический парапанкреатит (ГНПП) различной степени распространённости.
Важным моментом является своевременная диагностика инфицирования и верифицикация
клинико-морфологических форм панкреатогенной инфекции.
Критерии ПА и ГНПП:
1 Клинико-лабораторные проявления гнойного очага:
1.1 Прогрессирование клинико-лабораторных показателей острого воспаления на третьей
неделе ОП.
1.2 Маркеры острого воспаления (повышение фибриногена в 2 раза и более, высокие

«С»-реактивный белок, прокальцитонин и др.).
1.3 КТ, УЗИ (нарастание в процессе наблюдения жидкостных образований, выявление

девитализированных тканей и/или наличие пузырьков газа).
1.4 Положительные результаты бактериоскопии и бакпосева аспирата, полученного при

тонкоигольной пункции.
В случае, когда методами п.1.3 и п.1.4 не удаётся выявить признаки инфицирования, ре-
шение о наличии у пациентов гнойных осложнений и показаний к оперативному лечению
принимается на основании лабораторно-клинического минимума (п. 1.1).
II Протокол лечения гнойных осложнений острого панкреатита
1. При гнойных осложнениях ОП показано хирургическое вмешательство, целью которого

является санация поражённой забрюшинной клетчатки. Вмешательство включает раскры-
тие, санацию и дренирование поражённой забрюшинной клетчатки. Основным методом
санации гнойно-некротических очагов является некрсеквестрэктомия, которая может быть
как одномоментной, так и многоэтапной, и достигается как миниинвазивными, так и тра-
диционными методами.
2. При решении вопроса о первичном дренировании абсцесса поджелудочной железы или
гнойно-некротического парапанкреатита следует отдавать предпочтение миниинвазивным
вмешательствам (дренирование под УЗ-наведением, ретроперитонеоскопия, минилапаро-
томия с помощью набора «Мини-ассистент» и др.). При неэффективности миниинвазивно-
го дренирования операцией выбора является санационная лапаротомия с некрсеквестрэк-
томией. Дренирование предпочтительно осуществлять внебрюшинными доступами. Опти-
мальными сроками выполнения первой санационной лапаротомии с некрсеквестрэктомией
являются 4-5 недели заболевания. При развитии осложнений, которые невозможно купиро-
вать с помощью миниинвазивных вмешательств, необходимо выполнять открытую опера-
цию, в том числе из мини-доступа.
3. После операции у большинства больных формируется наружный панкреатический свищ,

который после купирования воспалительного процесса лечится консервативно и закрыва-
ется самостоятельно в среднем за 2-4 месяца. Стойкий панкреатический свищ, не закрыва-
ющийся более чем за 6 месяцев, как правило, связан с крупными протоками поджелудоч-
ной железы. Больной подлежит оперативному лечению в плановом порядке.
4. В послеоперационном периоде показана комплексная терапия:
• Парентеральная или энтеральная нутриционная поддержка (через зонд, заведенный в
тонкую кишку за связку Трейтца) при невозможности перорального питания.
• Системная антибиотикотерапия по показаниям (выбор антибактериального препарата
зависит от чувствительности выделенных микроорганизмов) в сочетании с профилак-
тикой дисбактериоза и других осложнений.
Сила рекомендаций «B»
• Иммуномокоррекция, варианты которой определяются индивидуально в зависимости
от клинико-лабораторных показателей.
МЕТОДОЛОГИЯ
Рейтинговая схема для оценки силы рекомендаций (схема 1)
Уровни Описание
доказательств
1++ Мета-анализы высокого качества, систематические обзоры

рандомизированных контролируемых исследований (РКИ), или РКИ с
очень низким риском систематических ошибок
1+ Качественно проведенные мета-анализы, систематические, или РКИ с

низким риском систематических ошибок
1- Мета-анализы, систематические, или РКИ с высоким риском

систематических ошибок
2++ Высококачественные систематические обзоры исследований случай-

контроль или когортных исследований. Высококачественные обзоры
исследований случай-контроль или когортных исследований с очень
низким риском эффектов смешивания или систематических ошибок и
средней вероятностью причинной взаимосвязи
2+ Хорошо проведенные исследования случай-контроль или когортные

исследования со средним риском эффектов смешивания или
систематических ошибок и средней вероятностью причинной
взаимосвязи
2- Исследования случай-контроль или когортные исследования с

высоким риском эффектов смешивания или систематических ошибок и
средней вероятностью причинной взаимосвязи
3 Не аналитические исследования (например: описания случаев, серий

случаев)
4 Мнения экспертов
Рейтинговая схема для оценки силы рекомендаций (схема 2)
Сила Описание
А По меньшей мере, один мета-анализ, систематический обзор, или

РКИ, оцененные, как 1++ , напрямую применимые к целевой
популяции и демонстрирующие устойчивость результатов или группа
доказательств, включающая результаты исследований, оцененные,
как 1+, напрямую применимые к целевой популяции и
демонстрирующие общую устойчивость результатов
В Группа доказательств, включающая результаты исследований,

оцененные, как 2++, напрямую применимые к целевой популяции
и демонстрирующие общую устойчивость результатов или
экстраполированные доказательства из исследований, оцененных, как
1++ или 1+
С Группа доказательств, включающая результаты исследований,

оцененные, как 2+, напрямую применимые к целевой популяции и
демонстрирующие общую устойчивость результатов или
экстраполированные доказательства из исследований, оцененных, как
2++
D Доказательства уровня 3 или 4 или экстраполированные

доказательства из исследований, оцененных, как 2+
Сила рекомендаций (А-D), уровни доказательств (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) приводятся
при изложении текста клинических рекомендаций (протоколов).
Литература
1. Протокол обследования и лечения больных острым панкреатитом. Методические рекомендации под редак-
цией Ю.Л. Шевченко ,М., 2010, 21с.
2. Савельев В.С., Филимонов М.И., Гельфанд Б.Р. и др. Панкреонекроз: актуальные вопросы классификации,
диагностики и лечения ( результаты анкетирования хирургических клиник РФ) Consilium Medicum – 2000, -
т.2 - №7. С. 34 – 39
3. Сахно В.Д., Майнулов А.М., Власова Н.В., Бочкарева И.В.Некротический панкреатит, протоколы лечения.
Анналы хирургической гепатологии, 2005, т.10, № 1, с. 107 – 112
4. Ермолов А.С., Иванов П.А., Благовестнов Д.А. и др. Диагностика и лечение острого панкреатита. М., 2013,
«ВИДР», с. 382
5. Прудков М.И. Клинические рекомендации по оказанию медицинской помощи населению Уральского Феде-
рального округа, Екатеринбург, 2013, с. 23 – 29
6. Багненко С.Ф., Толстой А.Д., Красногоров В.Б. и др. Острый панкреатит (Протоколы диагностики и лече-
ние) Анналы хирургической гепатологии, 2006, т.11, №1, с. 60 – 66
7. Приказ №320 Департамента здравоохранения г. Москвы от 13.04.2011. О единой тактике и лечении острых
хирургических заболеваний органов брюшной полости в лечебно – профилактических учреждениях Депар-
тамента здравоохранения г. Москвы.
8. Филимонов М.И., Бурневич С.З. Хирургия панкреонекроза. 80 лекций по хирургии под редакцией В.С. Саве-
льева. М., «Литтера», 2008, с. 447 – 455.
9. Савельев В.С., Филимонов М.И., Бурневич С.З. Острый панкреатит. Национальное руководство по хирур-
гии. 2009, т.2, с. 196 – 229.
10. Савельев В.С., Филимонов М.И., Бурневич С.З. Панкреонекрозы. МИА, 2008, с. 259
11. Мумладзе Р.Б., Чудных С.М., Сельцовский А.П., Соловьев Н.А. Новые аспекты лечения острого панкреати-
та. М., 2002, с. 223
12. Савельев В.С., Гельфанд Б.Р., Филимонов М.И. и др. Деструктивный панкреатит. Доказательные методы
диагностики и лечения. Методические рекомендации. М., 2008, с. 11
13. Затевахин И.И., Цициашвили М.Ш., Будурова М.Д., Алтунин А.И. Панкреонекроз. М., 2007, с.223
14. Дибиров М.Д., Юанов А.А. Панкреонекроз. Протокол диагностики и лечения. Учебно-методическое посо-
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15. Атланта-1992г (Bradley E.L. 3rd. A clinically based classification system for acute pancreatitis. Summary of the
international symposium on acute pancreatitis, Atlanta, 1992// Arch. Surg. – Vol. 128, 1993; Р. 586-590.).
16. Международная рабочая группа по классификации острого панкреатита (Американская коллегия гастроэн-
терологов) – 2012г. (Banks P.A., Bollen T.L., Dervenis C., Gooszen H.G., Johnson C.D., Sarr M.G., Tsiotos G.G.,
Vege S.S. Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis 2012: revision of the
Atlanta classification and definitions by international consensus. Gut. 2013; 62 (1): 102–111).
17. Международная Ассоциация Панкреатологов (Индия, г.Кочин) – 2012г (Dellinger E.P., Forsmark C.E., Layer
P., Levy P., Maravi-Poma E., Petrov M.S., Shimosegawa T., Siriwardena A.K., Uomo G.,Whitcomb D.C., Windsor
J.A. Determinant_based classification of acute pancreatitis severity: an international multidisciplinary consultation.
Ann. Surg. 2012; 256 (6): 875–880.).
18. Рабочая группа (Международная Ассоциация Панкреатологов/Американская Панкреатологическая Ассоци-

ация) – 2013 (IAP/APA evidence-based guidelines for the management of acute pancreatitis. Working Group
IAP/APA (International Association of Pancreatology /American Pancreatic Association) Acute Pancreatitis Guide-
lines // Pancreatology - №13,2013; Р. 1- 15).
CLASSIFICATION OF ACUTE PANCREATITIS

2012: REVISION OF THE ATLANTA
II CLASSIFICATION AND DEFINITIONS
BY INTERNATIONAL CONSENSUS
КЛАССИФИКАЦИЯ ОСТРОГО ПАНКРЕАТИТА 2012: ПЕРЕСМОТР КЛАССИФИКАЦИИ ATLANTA ИˇОПРЕДЕЛЕНИЯ
НА ОСНОВЕ МЕЖДУНАРОДНОГО КОНСЕНСУСА (CLASSIFICATION OF ACUTE PANCREATITIS 2012: REVISION OF THE 23
ATLANTA CLASSIFICATION AND DEFINITIONS BY INTERNATIONAL CONSENSUS)
Pancreatology 13 (2013) e1ee15
IAP/APA EVIDENCE-BASED GUIDELINES Contents lists available at SciVerse ScienceDirect
III FOR THE MANAGEMENT

Pancreatology OF ACUTE
PANCREATITIS journal homepage: www.elsevier.com/locate/pan
Original article
IAP/APA evidence-based guidelines for the management of acute

pancreatitis
Working Group IAP/APA Acute Pancreatitis Guidelinesa, b, *,1
a
International Association of Pancreatology, UNSW Clinical School Locked Bag 7103, Liverpool, BC NSW 1871, Australia
b
American Pancreatic Association, PO Box 14906, Minneapolis, MN 55414, USA
a r t i c l e i n f o a b s t r a c t
Article history: Background: There have been substantial improvements in the management of acute pancreatitis since
Received 5 June 2013 the publication of the International Association of Pancreatology (IAP) treatment guidelines in 2002. A
Received in revised form collaboration of the IAP and the American Pancreatic Association (APA) was undertaken to revise these
1 July 2013
guidelines using an evidence-based approach.
Accepted 5 July 2013
Methods: Twelve multidisciplinary review groups performed systematic literature reviews to answer 38
predefined clinical questions. Recommendations were graded using the Grading of Recommendations
Keywords:
Assessment, Development and Evaluation (GRADE) system. The review groups presented their recom-
Acute pancreatitis
Pancreas
mendations during the 2012 joint IAP/APA meeting. At this one-day, interactive conference, relevant
Guidelines remarks were voiced and overall agreement on each recommendation was quantified using plenary
Diagnosis voting.
Prediction Results: The 38 recommendations covered 12 topics related to the clinical management of acute
Prevention pancreatitis: A) diagnosis of acute pancreatitis and etiology, B) prognostication/predicting severity, C)
Treatment imaging, D) fluid therapy, E) intensive care management, F) preventing infectious complications, G)
Intervention nutritional support, H) biliary tract management, I) indications for intervention in necrotizing pancre-
Nutrition
atitis, J) timing of intervention in necrotizing pancreatitis, K) intervention strategies in necrotizing
Surgery
pancreatitis, and L) timing of cholecystectomy. Using the GRADE system, 21 of the 38 (55%) recom-
Radiology
Gastroenterology mendations, were rated as ‘strong’ and plenary voting revealed ‘strong agreement’ for 34 (89%)
recommendations.
Conclusions: The 2012 IAP/APA guidelines provide recommendations concerning key aspects of medical
and surgical management of acute pancreatitis based on the currently available evidence. These rec-
ommendations should serve as a reference standard for current management and guide future clinical
research on acute pancreatitis.
Copyright 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd.
Open access under CC BY-NC-ND license.
1. Introduction guidelines with broad support from the pancreatic community. A

recent systematic review has demonstrated the variable quality of
Acute pancreatitis is one of the most common gastrointestinal the 30 guidelines published since 1988 and has highlighted the
disorders requiring acute hospitalization worldwide, with a re- need for a high quality update [3]. Eleven years have passed since
ported annual incidence of 13e45 cases per 100,000 persons [1]. In the “Guidelines for the surgical management of acute pancreatitis” by
the U.S. alone, acute pancreatitis leads to 270,000 hospital admis- the International Association of Pancreatology (IAP) were pub-
sions annually and inpatient costs exceed 2.5 billion dollars [2]. It is lished in 2002 [4]. Since then, a large body of new evidence has
clear that such a common disease associated with mortality up to become available, not infrequently from randomized controlled
30% in severe cases, requires up-to-date evidence-based treatment trials (RCTs) and systematic reviews. This evidence has greatly
influenced many important aspects of the medical and surgical
management of acute pancreatitis.
The leadership of both the IAP and the American Pancreatic
* Corresponding author. International Association of Pancreatology, UNSW Clin- Association (APA) supported an initiative for an international
ical School Locked Bag 7103, Liverpool, BC NSW 1871, Australia and American multidisciplinary approach to update the evidence-based guide-
Pancreatic Association, PO Box 14906, Minneapolis, MN 55414, USA.
1
See Collaborator section (apa@umn.edu).
lines for the management of acute pancreatitis. To this end an
1424-3903 Copyright 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. Open access under CC BY-NC-ND license.
http://dx.doi.org/10.1016/j.pan.2013.07.063
КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ IAP/APA ПО ЛЕЧЕНИЮ ОСТРОГО ПАНКРЕАТИТА,
ОСНОВАННЫЕ НА ДОКАЗАТЕЛЬСТВАХ (IAP/APA EVIDENCE-BASED GUIDELINES 33
FOR THE MANAGEMENT OF ACUTE PANCREATITIS)
e2 Working Group IAP/APA Acute Pancreatitis Guidelines / Pancreatology 13 (2013) e1ee15
adapted version of the Grading of Recommendations Assessment, opportunity to suggest changes in clinical questions or suggest
Development and Evaluation (GRADE) approach [5] was used. Both additional questions to the steering committee. Over a five-month
the revised Atlanta classification for acute pancreatitis [6] and the period (JuneeOct 2012) the review groups performed systematic
outcome of a recent consensus conference on interventions for reviews according to the guidelines defined in the finalized work-
necrotizing pancreatitis [7] were taken into account. Systematic ing plan.
reviews on 12 main topics answered 38 predefined clinical ques-
tions which were presented and discussed during an interactive 2.4. Systematic review guidelines
symposium at the IAP/APA joint meeting in Miami on October 31,
2012. A systematic search for relevant articles was performed in the
PubMed, Embase, and Cochrane databases.
2. Methods Inclusion criteria were: (1) randomized or observational cohort
studies, including systematic reviews, on patients with acute
2.1. Scope and purpose pancreatitis focusing on the specific study questions with a sample
size of at least 20 patients, (2) studies published in English lan-
The overall objective of these guidelines is to provide evidence- guage, and (3) available in full text. If review groups were capable of
based recommendations for the medical and surgical management translating non-English publications they were encouraged to do
of patients with acute pancreatitis using clearly specified, clinically so.
relevant questions. Exclusion criteria were: (1) non-randomized studies with less
than 20 patients because of the likelihood of selection bias, (2)
2.2. Stakeholder involvement studies on patients with ‘acute on chronic pancreatitis’, and (3)
non-randomized studies prior to 1993 (i.e. publication of the initial
Individuals from all relevant professional groups involved with Atlanta classification). RCTs prior to 1993 could only be excluded if
acute pancreatitis were included. Target users of the guidelines are the reviewers felt that the generalizability to today’s practice was
all clinicians involved in the care of patients with acute pancreatitis. not appropriate.
2.3. General outline of the process 2.5. Grading of the evidence
2.3.1. First phase: drafting of the working plan All reviewers were asked to take a GRADE system tutorial (link
The IAP/APA leadership actively supported an initiative (MGB, on UpToDate: http://www.uptodate.com/home/grading-tutorial).
HCvS, JW) to develop the current guidelines and invited seven clini-
cians to form the steering committee and provided secretarial support
2.6. Outcome reporting
(EB). Three coordinators (MGB, HCvS, JW) wrote the initial version of
the working plan and proposed the 12 main topics and associated
The definitions of the revised Atlanta classification for acute
clinical questions per topic and suggested the reviewers for each topic.
pancreatitis were used [6].
This preliminary working plan was discussed via telephone confer-
The final outcomes of the systematic reviews were discussed
ences and e-mails within the full steering committee and the IAP/APA
amongst the members of the review group. The review groups
leadership, and then the document including the composition of re-
provided the following for each clinical question:
view groups was finalized. The IAP/APA leadership also invited nine
additional senior clinicians to form the executive committee in
a. Recommendation: the GRADE strength of recommendation
addition to the members of the steering committee.
(1 ¼ strong, 2 ¼ weak) and quality of evidence (A ¼ high,
Each review group consisted of at least one primary reviewer
B ¼ moderate, C ¼ low) are provided along with the strength of
chosen because of recent publications on a particular topic and
agreement during plenary voting (strong/weak) (see
several senior reviewers. An attempt was made to have multidis-
Appendix). In the absence of studies specifically addressing the
ciplinary input in each review group as well as representatives of at
question, this had to be stated and the recommendation was
least two continents. Each review group was also assigned a time
then based on related studies or expert opinion.
manager from the steering committee, whose primary task was to
b. Remarks: these remarks could discuss any relevant aspect
ensure the completion of the review within the agreed timeframe.
regarding the recommendation, such as important exceptions/
The working plan for the review groups provided a structured
contra-indications, availability, lack of evidence, risks, and costs.
format for the systematic reviews. It included instructions on how
c. A summary table of relevant studies was produced, including
to grade the level of evidence and the strength of the recommen-
columns on outcome assessed (e.g. mortality, infected necro-
dations regarding clarity of risk/benefit, quality of the supporting
sis), the total number of patients, the number of included
evidence, and clinical implications according to the GRADE guide-
studies per outcome, design of the study (e.g. retrospective
lines as adapted for ‘UpToDate’.
cohort, prospective cohort, RCT), and critical appraisal of
A group of ‘expert referees’ (see Collaborator section) was
methodology according to the GRADE system for each study as
identified based on relevant publications in the field of clinical
well as a summary of outcomes
acute pancreatitis and input during the IAP/APA meeting. This
group reviewed the guidelines in the final stages. After a last round
of discussion within the executive committee, the working plan 2.6.1. Third phase: IAP/APA joint meeting
was finalized to include 12 main topics and 38 clinical questions The review groups (see Collaborator section) presented their
concerning key aspects of medical and surgical management of work at the IAP/APA Joint Annual Meeting on October 31st, 2012 in
acute pancreatitis. Miami, Florida, USA using standardized PowerPoint templates. Each
clinical question was addressed in a similar manner in three slide
2.3.2. Second phase: Systematic literature reviews sections: (1) the question with the recommendation including the
The suggested reviewers were invited and given their respective GRADE score, (2) the remarks, and (3) a summary of the literature
topics and clinical questions. All 12 review groups had the studied. After each presentation, the 171 registered attendees (North
Working Group IAP/APA Acute Pancreatitis Guidelines / Pancreatology 13 (2013) e1ee15 e3
America, n ¼ 71; South America, n ¼ 7; Europe, n ¼ 54; Asia/Oceania, only report published work. This draft was discussed with the
n ¼ 39) were invited to comment. The general aim was not to alter steering and executive committees, the review groups, and finally
the recommendations, because these were based on systematic re- the expert referees. The review groups were specifically asked to
views but rather to obtain clinically relevant comments to be added judge whether the amended remarks section of their clinical ques-
to the ‘remarks’ section for that specific clinical question. Occasion- tion(s) still reflected the current state of the literature. The final
ally, in case of absence of studies or unclear phrasing of the recom- version was approved by the steering and executive committees.
mendation, its’ wording was amended. In order to assess the level of
support from the international pancreatologists objectively, an
electronic plenary vote was conducted for each recommendation. 2.7. Future aspects
The attendees voted on a five point Likert scale (‘definitely yes’,
‘probably yes’, ‘no specific recommendation’, ‘probably no’, ‘defi- These guidelines will be updated by an IAP/APA committee
nitely no’) on the recommendation and their GRADE score. These when these associations believe there is a need to do so [8], but no
answers were projected to the audience immediately after each longer than 10 years after publication of these guidelines.
round of voting. Before the meeting, it was defined that ‘strong
agreement’ would require at least 70% of votes to be either ‘definitely
yes’ or ‘probably yes’. For optimal transparency the meeting was 3. Results
filmed and these films are accessible via the APA office.
The 12 main topics (AeL) are presented consecutively, incor-
porating 38 clinical questions (Q1eQ38) and their answers. See
2.6.2. Fourth phase: drafting of the manuscript table 1 for a summary of the recommendations. The GRADE
Based on the recommendations with remarks and GRADE rating, strength of recommendation (1 ¼ strong, 2 ¼ weak) and quality of
the voting results, and the remarks provided during the meeting, the evidence (A ¼ high, B ¼ moderate, C ¼ low) are provided along with
coordinators drafted a first version of the guidelines. Although the strength of agreement during plenary voting (strong/weak). For
several relevant ongoing multicenter RCTs were identified in the each recommendation the remarks from the reviewers and at-
reviews (i.e. through published study protocols), it was decided to tendees at the meeting are listed.
Table 1
Summary of recommendations
A. Diagnosis of acute pancreatitis and etiology

1. The definition of acute pancreatitis is based on the fulfillment of ‘2 out of 3’ of the following criteria: clinical (upper abdominal pain), laboratory (serum amylase or lipase
>3x upper limit of normal) and/or imaging (CT, MRI, ultrasonography) criteria.(GRADE 1B, strong agreement)
2. On admission, the etiology of acute pancreatitis should be determined using detailed personal (i.e. previous acute pancreatitis, known gallstone disease, alcohol intake,
medication and drug intake, known hyperlipidemia, trauma, recent invasive procedures such as ERCP) and family history of pancreatic disease, physical examination,
laboratory serum tests (i.e. liver enzymes, calcium, triglycerides), and imaging (i.e. right upper quadrant ultrasonography).(GRADE 1B, strong agreement)
3. In patients considered to have idiopathic acute pancreatitis, after negative routine work-up for biliary etiology, endoscopic ultrasonography (EUS) is recommended as
the first step to assess for occult microlithiasis, neoplasms and chronic pancreatitis. If EUS is negative, (secretin-stimulated) MRCP is advised as a second step to identify
rare morphologic abnormalities. CT of the abdomen should be performed. If etiology remains unidentified, especially after a second attack of idiopathic pancreatitis,
genetic counseling (not necessarily genetic testing) should be considered.(GRADE 2C, weak agreement)
B. Prognostication/prediction of severity
4. Systemic inflammatory response syndrome (SIRS) is advised to predict severe acute pancreatitis at admission and persistent SIRS at 48 hours.(GRADE 2B, weak
agreement)
5. During admission, a 3-dimension approach is advised to predict outcome of acute pancreatitis combining host risk factors (e.g. age, co-morbidity, body mass index),
clinical risk stratification (e.g. persistent SIRS) and monitoring response to initial therapy (e.g. persistent SIRS, blood urea nitrogen, creatinine).(GRADE 2B, strong
agreement)
C. Imaging
6. The indication for initial CT assessment in acute pancreatitis can be: 1) diagnostic uncertainty, 2) confirmation of severity based on clinical predictors of severe acute
pancreatitis, or 3) failure to respond to conservative treatment or in the setting of clinical deterioration. Optimal timing for initial CT assessment is at least 72e96 hours
after onset of symptoms.(GRADE 1C, strong agreement)
7. Follow up CT or MR in acute pancreatitis is indicated when there is a lack of clinical improvement, clinical deterioration, or especially when invasive intervention is
considered.(GRADE 1C, strong agreement)
8. It is recommended to perform multidetector CT with thin collimation and slice thickness (i.e. 5mm or less), 100e150 ml of non-ionic intra-venous contrast material at a
rate of 3mL/s, during the pancreatic and/or portal venous phase (i.e. 50e70 seconds delay). During follow up only a portal venous phase (monophasic) is generally
sufficient. For MR, the recommendation is to perform axial FS-T2 and FS-T1 scanning before and after intravenous gadolinium contrast administration.(GRADE 1C,
strong agreement)
D. Fluid therapy
9. Ringer’s lactate is recommended for initial fluid resuscitation in acute pancreatitis.(GRADE 1B, strong agreement)
10a. Goal directed intravenous fluid therapy with 5e10 ml/kg/h should be used initially until resuscitation goals (see Q10b) are reached.(GRADE 1B, weak agreement)
10b. The preferred approach to assessing the response to fluid resuscitation should be based on one or more of the following: 1) non-invasive clinical targets of heart rate <
120/min, mean arterial pressure between 65-85 mmHg (8.7e11.3 kPa), and urinary output > 0.5e1ml/kg/h, 2) invasive clinical targets of stroke volume variation, and
intrathoracic blood volume determination, and 3) biochemical targets of hematocrit 35-44%.(GRADE 2B, weak agreement)
E. Intensive care management
11. Patients diagnosed with acute pancreatitis and one or more of the parameters identified at admission as defined by the guidelines of the Society of Critical Care
Medicine (SCCM). Furthermore, patients with severe acute pancreatitis as defined by the revised Atlanta Classification (i.e. persistent organ failure) should be treated in
an intensive care setting.(GRADE 1C, strong agreement)
12. Management in, or referral to, a specialist center is necessary for patients with severe acute pancreatitis and for those who may need interventional radiologic,
endoscopic, or surgical intervention.(GRADE 1C, strong agreement)
13. A specialist center in the management of acute pancreatitis is defined as a high volume center with up-to-date intensive care facilities including options for organ
replacement therapy, and with daily (i.e. 7 days per week) access to interventional radiology, interventional endoscopy with EUS and ERCP assistance as well as surgical
expertise in managing necrotizing pancreatitis. Patients should be enrolled in prospective audits for quality control issues and into clinical trials whenever
possible.(GRADE 2C, weak agreement)
14. Early fluid resuscitation within the first 24 hours of admission for acute pancreatitis is associated with decreased rates of persistent SIRS and organ failure.(GRADE 1C,
strong agreement)
(continued on next page)
Table 1 (continued )
15. Abdominal compartment syndrome (ACS) is defined as a sustained intra-abdominal pressure > 20 mmHg that is associated with new onset organ failure.(GRADE 2B,
strong agreement)
16. Medical treatment of ACS should target 1) hollow-viscera volume, 2) intra/extra vascular fluid and 3) abdominal wall expansion. Invasive treatment should only be
used after multidisciplinary discussion in patients with a sustained intra-abdominal pressure >25mmHg with new onset organ failure refractory to medical therapy and
nasogastric/ rectal decompression. Invasive treatment options include percutaneous catheter drainage of ascites, midline laparostomy, bilateral subcostal laparostomy,
or subcutaneous linea alba fasciotomy. In case of surgical decompression, the retroperitoneal cavity and the omental bursa should be left intact to reduce the risk of
infecting peripancreatic and pancreatic necrosis.(GRADE 2C, strong agreement)
F. Preventing infectious complications
17. Intravenous antibiotic prophylaxis is not recommended for the prevention of infectious complications in acute pancreatitis.(GRADE 1B, strong agreement)
18. Selective gut decontamination has shown some benefits in preventing infectious complications in acute pancreatitis, but further studies are needed.(GRADE 2B, weak
agreement)
19. Probiotic prophylaxis is not recommended for the prevention of infectious complications in acute pancreatitis.(GRADE 1B, strong agreement)
G. Nutritional support
20. Oral feeding in predicted mild pancreatitis can be restarted once abdominal pain is decreasing and inflammatory markers are improving.(GRADE 2B, strong agreement)
21. Enteral tube feeding should be the primary therapy in patients with predicted severe acute pancreatitis who require nutritional support.(GRADE 1B, strong agreement)
22. Either elemental or polymeric enteral nutrition formulations can be used in acute pancreatitis.(GRADE 2B, strong agreement)
23. Enteral nutrition in acute pancreatitis can be administered via either the nasojejunal or nasogastric route.(GRADE 2A, strong agreement)
24. Parenteral nutrition can be administered in acute pancreatitis as second-line therapy if nasojejunal tube feeding is not tolerated and nutritional support is
required.(GRADE 2C, strong agreement)
H. Biliary tract management
25. ERCP is not indicated in predicted mild biliary pancreatitis without cholangitis.(GRADE 1A, strong agreement). ERCP is probably not indicated in predicted severe
biliary pancreatitis without cholangitis (GRADE 1B, strong agreement). ERCP is probably indicated in biliary pancreatitis with common bile duct obstruction (GRADE 1C,
strong agreement) ERCP is indicated in patients with biliary pancreatitis and cholangitis (GRADE 1B, strong agreement)
26. Urgent ERCP (<24 hrs) is required in patients with acute cholangitis. Currently, there is no evidence regarding the optimal timing of ERCP in patients with biliary
pancreatitis without cholangitis.(GRADE 2C, strong agreement)
27. MRCP and EUS may prevent a proportion of ERCPs that would otherwise be performed for suspected common bile duct stones in patients with biliary pancreatitis who
do not have cholangitis, without influencing the clinical course. EUS is superior to MRCP in excluding the presence of small (<5mm) gallstones. MRCP is less invasive,
less operator-dependent and probably more widely available than EUS. Therefore, in clinical practice there is no clear superiority for either MRCP or EUS.(GRADE 2C,
strong agreement)
I. Indications for intervention in necrotizing pancreatitis
28. Common indications for intervention (either radiological, endoscopical or surgical) in necrotizing pancreatitis are: 1) Clinical suspicion of, or documented infected
necrotizing pancreatitis with clinical deterioration, preferably when the necrosis has become walled-off, 2) In the absence of documented infected necrotizing
pancreatitis, ongoing organ failure for several weeks after the onset of acute pancreatitis, preferably when the necrosis has become walled-off.(GRADE 1C, strong
agreement)
29. Routine percutaneous fine needle aspiration of peripancreatic collections to detect bacteria is not indicated, because clinical signs (i.e. persistent fever, increasing
inflammatory markers) and imaging signs (i.e. gas in peripancreatic collections) are accurate predictors of infected necrosis in the majority of patients. Although the
diagnosis of infection can be confirmed by fine needle aspiration (FNA), there is a risk of false-negative results.(GRADE 1C, strong agreement)
30. Indications for intervention (either radiological, endoscopical or surgical) in sterile necrotizing pancreatitis are: 1) Ongoing gastric outlet, intestinal, or biliary
obstruction due to mass effect of walled-off necrosis (i.e. arbitrarily >4-8 weeks after onset of acute pancreatitis), 2) Persistent symptoms (e.g. pain, ‘persistent
unwellness’) in patients with walled-off necrosis without signs of infection (i.e. arbitrarily >8 weeks after onset of acute pancreatitis), 3) Disconnected duct syndrome
(i.e. full transection of the pancreatic duct in the presence of pancreatic necrosis) with persisting symptomatic (e.g. pain, obstruction) collection(s) with necrosis without
signs of infections (i.e. arbitrarily >8 weeks after onset of acute pancreatitis).(GRADE 2C, strong agreement)
J. Timing of intervention in necrotizing pancreatitis
31. For patients with proven or suspected infected necrotizing pancreatitis, invasive intervention (i.e. percutaneous catheter drainage, endoscopic transluminal drainage/
necrosectomy, minimally invasive or open necrosectomy) should be delayed where possible until at least 4 weeks after initial presentation to allow the collection to
become ‘walled-off’.(GRADE 1C, strong agreement)
32. The best available evidence suggests that surgical necrosectomy should ideally be delayed until collections have become walled-off, typically 4 weeks after the onset of
pancreatitis, in all patients with complications of necrosis. No subgroups have been identified that might benefit from earlier or delayed intervention.(GRADE 1C, strong
agreement)
K. Intervention strategies in necrotizing pancreatitis
33. The optimal interventional strategy for patients with suspected or confirmed infected necrotizing pancreatitis is initial image-guided percutaneous (retroperitoneal)
catheter drainage or endoscopic transluminal drainage, followed, if necessary, by endoscopic or surgical necrosectomy.(GRADE 1A, strong agreement)
34. Percutaneous catheter or endoscopic transmural drainage should be the first step in the treatment of patients with suspected or confirmed (walled-off) infected
necrotizing pancreatitis.(GRADE 1A, strong agreement)
35. There are insufficient data to define subgroups of patients with suspected or confirmed infected necrotizing pancreatitis who would benefit from a different treatment
strategy.(GRADE 2C, strong agreement)
L. Timing of cholecystectomy (or endoscopic sphincterotomy)
36. Cholecystectomy during index admission for mild biliary pancreatitis appears safe and is recommended. Interval cholecystectomy after mild biliary pancreatitis is
associated with a substantial risk of readmission for recurrent biliary events, especially recurrent biliary pancreatitis.(GRADE 1C, strong agreement)
37. Cholecystectomy should be delayed in patients with peripancreatic collections until the collections either resolve or if they persist beyond 6 weeks, at which time
cholecystectomy can be performed safely.(GRADE 2C, strong agreement)
38. In patients with biliary pancreatitis who have undergone sphincterotomy and are fit for surgery, cholecystectomy is advised, because ERCP and sphincterotomy
prevent recurrence of biliary pancreatitis but not gallstone related gallbladder disease, i.e. biliary colic and cholecystitis.(GRADE 2B, strong agreement)
3.1. Diagnosis of acute pancreatitis and etiology (GRADE 1B, strong agreement)
Remarks: imaging studies (e.g. contrast-enhanced abdominal CT
Q1. What is the definition of acute pancreatitis (regardless of abdomen (CT)) may be useful but are usually not required to
etiology)? diagnose acute pancreatitis. Scenarios where cross-sectional im-
The definition of acute pancreatitis is based on the fulfillment of aging may be required to confirm the diagnosis include sedated
‘2 out of 3’ of the following criteria: clinical (upper abdominal patients, clinical suspicion of duodenal perforation, or a pro-
pain), laboratory (serum amylase or lipase >3 upper limit of longed period between onset of symptoms and presentation
normal) and/or imaging (computed tomography, magnetic (lipase and amylase may have normalized). Although the urinary
resonance (MR), ultrasonography) criteria. trypsinogen-2 dipstick test is a rapid and non-invasive bedside
test with adequate accuracy confirmed in a recent meta-analysis typically select patients based on the predicted severity of acute
(pooled sensitivity 82% and specificity 94%), it was not included pancreatitis.
because of its presumed limited availability [9]. SIRS is defined by the presence of two or more of the following four
Q2. On admission, what should be done to determine the criteria: (1) temperature < 36 C (96.8 F) or >38 C (100.4 F), (2)
etiology of acute pancreatitis? heart rate >90/min, (3) respiratory rate >20/min, and (4) white
On admission, the etiology of acute pancreatitis should be blood cells (<4 109/L (<4 K/mm3), >12 109(>12 K/mm3) or 10%
determined using detailed personal (i.e. previous acute bands [15].
pancreatitis, known gallstone disease, alcohol intake, medica- Persistent (>48 h) SIRS is associated with multi-organ failure
tion and drug intake, known hyperlipidemia, trauma, recent and mortality in acute pancreatitis. Persistent (>48 h) organ
invasive procedures such as endoscopic retrograde chol- failure is the key determinant of mortality in acute pancreatitis
angiopancreatography (ERCP)) and family history of pancreatic [16]. Persistent SIRS was associated with a mortality of 25%
disease, physical examination, laboratory serum tests (i.e. liver compared with 8% for transient SIRS [17]. The sensitivity of
enzymes, calcium, triglycerides), and imaging (i.e. right upper persistent SIRS for mortality is 77e89% and specificity 79e86%
quadrant ultrasonography). [17e19] and of SIRS at admission respectively 100% and 31% [18].
(GRADE 1B, strong agreement) Arguments to recommend (persistent) SIRS as a marker for
Remarks: as treatment and follow-up depend on the etiology of predicting severe acute pancreatitis over the other predictive
pancreatitis (e.g. cholecystectomy for biliary pancreatitis and scoring systems were highly pragmatic, taking into account the
dedicated follow-up visits after alcoholic pancreatitis to prevent widespread familiarity, simplicity, and the possibility for re-
recurrence [10]) transabdominal ultrasonography should be petitive measurements [17,19]. It is recognized that there are
performed on admission. Although several studies have many different predictive scoring systems for acute pancreatitis
demonstrated that a single biochemical parameter cannot be (e.g. APACHEII, Ranson and modified Glasgow score), including
recommended for reliable prediction of biliary etiology, it single serum markers (C-reactive protein, hematocrit, procalci-
should be noted that an alanine aminotransferase (ALT) level tonin, blood urea nitrogen), but none of these are clearly supe-
>150 U/L within 48 h after onset of symptoms discriminates rior or inferior to (persistent) SIRS [20].
biliary pancreatitis with a positive predictive value exceeding Q5. What is the best strategy to predict outcome of acute
85% [11e13]. pancreatitis during admission?
Q3. What further investigations are indicated in patients During admission, a 3-dimension approach is advised to predict
after a first or second attack of idiopathic acute pancreatitis? outcome of acute pancreatitis combining
In patients considered to have idiopathic acute pancreatitis, af- host risk factors (e.g. age, co-morbidity, body mass index [21])
ter negative routine work-up for biliary etiology (e.g. repeated clinical risk stratification (e.g. persistent SIRS)
right upper quadrant ultrasonography), endoscopic ultraso- monitoring response to initial therapy (e.g. persistent SIRS,
nography (EUS) is recommended as the first step to assess for blood urea nitrogen [22], creatinine)
occult microlithiasis, neoplasms and chronic pancreatitis. If EUS (GRADE 2B, strong agreement).
is negative, (secretin-stimulated) magnetic resonance chol- Remarks: this clinical approach links prognosis to patient’s
angiopancreatography (MRCP) is advised as a second step to characteristics and response to initial treatment (e.g. fluid
identify rare morphologic abnormalities. CT of the abdomen resuscitation) and places emphasis on reassessment to guide
should be performed (i.e. if not performed before). If etiology further management [23]. More accurate prognostication could
remains unidentified, especially after a second attack of idio- facilitate a more tailored approach to treatment of individual
pathic pancreatitis, genetic counseling (not necessarily genetic patients.
testing) should be considered.
(GRADE 2C, weak agreement) 3.3. Imaging
Remarks: a systematic review of 5 studies including 416 patients
with idiopathic acute pancreatitis, reported a 32e88% diag- Q6. What is the indication for and timing of the initial CT
nostic yield of EUS, detecting either biliary sludge or signs of assessment in acute pancreatitis?
chronic pancreatitis [14]. If etiology remains unidentified after The indication for initial CT assessment in acute pancreatitis can
EUS, thorough review and, if necessary, repeat (e.g. repeat lipid be: (1) diagnostic uncertainty, (2) confirmation of severity based
profile and calcium levels) or further investigations for other on clinical predictors of severe acute pancreatitis, or (3) failure
more uncommon causes should be performed, depending on to respond to conservative treatment or in the setting of clinical
the clinical scenario. It is recognized that several diagnostic tests deterioration. Optimal timing for initial CT assessment is at least
are not widely available and need specific expertise (e.g. 72e96 h after onset of symptoms.
secretin-stimulated MRCP, genetic counseling, ERCP with (GRADE 1C, strong agreement).
manometry, bile analysis). Their exact role in the diagnostic Remarks: in the majority of patients, CT is not required for the
algorithm has yet to be determined. diagnosis of acute pancreatitis. Routine early CT in acute
pancreatitis is not recommended for the following reasons: (1)
3.2. Prognostication/prediction of severity there is no evidence that early CT improves clinical outcome or
that early detection of necrosis will influence treatment; (2) CT
Q4. What is the best score/marker (including cut-off value) to scoring systems are not superior to clinical scoring systems in
predict severe acute pancreatitis on admission and at 48 h? predicting prognosis and severity of disease [24]; (3) there is
Systemic inflammatory response syndrome (SIRS) is advised to evidence to suggest that an early (inappropriate) CT may in-
predict severe acute pancreatitis at admission and persistent crease the duration of hospital stay [25], has low yield without
SIRS at 48 h. direct management implications [26], does not improve clinical
(GRADE 2B, weak agreement) outcomes [27], and poses risks of contrast allergy and nephro-
Remarks: a prediction of the course and outcome of the disease toxicity. Because the complete extent of pancreatic and peri-
on admission, although difficult, can help with tailoring obser- pancreatic necrosis may only become obvious 72 h after onset of
vations and initial treatment, using evidence from RCTs which acute pancreatitis, a CT to assess the severity of pancreatitis
using the CT severity index (CTSI) criteria [28], should be per- but not identical to Hartmann’s solution. While there
formed only thereafter. Early CT may be useful to rule out bowel is emerging evidence that addition of HES to fluid resuscita-
ischemia or intra-abdominal perforations in patients presenting tion in acute pancreatitis may be beneficial [31], its detri-
with both acute pancreatitis and acute abdomen. mental effects in severe sepsis provide enough caution at this
Q7. What is the indication for follow-up scanning (CT/MR)? stage that its use cannot be endorsed in the current
Follow-up CT or MR in acute pancreatitis is indicated when there guidelines.
is a lack of clinical improvement, clinical deterioration, or Q10. What is the optimal fluid infusion rate and response
especially when invasive intervention is considered. measurement for initial fluid resuscitation?
(GRADE 1C, strong agreement). Q10a. Optimal infusion rate for initial fluid resuscitation: goal
Remarks: although routine follow-up CT (e.g. weekly) in acute directed intravenous fluid therapy with 5e10 ml/kg/h should be
pancreatitis is advocated in several guidelines, evidence for this used initially until resuscitation goals (see Q10b) are reached.
practice is lacking. The present guidelines does not recommend (GRADE 1B, weak agreement).
routine CT for initial assessment, because the vast majority of Remarks: in most patients, a total infusion of 2500e4000 ml
complications can be suspected by clinical and biochemical will suffice to reach the resuscitation goals within the first
assessment. One important complication, namely arterial pseu- 24 h. There is moderate quality evidence from two RCTs, from
doaneurysm formation, may not become clinically evident until the same research group, that overly aggressive fluid therapy
bleeding occurs, but this complication of acute pancreatitis is so increases morbidity and mortality. In the first RCT, patients
rare that it does not justify a ‘routine’ follow-up CT. MR may be assigned to a fluid infusion rate of 5e10 ml/kg/h experienced
required to distinguish between pseudocysts and walled-off ne- less need for mechanic ventilation, abdominal compartment
crosis as defined by the revised Atlanta classification at least 4 syndrome, sepsis and mortality as compared to patients
weeks after the index episode of acute pancreatitis. CT is frequently assigned to 10e15 ml/kg/h infusion rates [33]. In a second
not able to detect necrosis in a fluid-predominant collection [29]. RCT, patients assigned to slow hemodilution, aiming at a
Q8. What is the optimal CT and MR protocol to detect hematocrit >35% within 48 h, had decreased rates of sepsis
necrosis? and mortality as compared to patients assigned to rapid
It is recommended to perform multidetector CT with thin hemodilution, aiming at a hematocrit <35% within 48 h [34].
collimation and slice thickness (i.e. 5 mm or less), 100e150 ml of Because age and comorbidities such as heart failure need an
non-ionic intravenous contrast material at a rate of 3 ml/s, individualization of the fluid management, the rate of in-
during the pancreatic and/or portal venous phase (i.e. 50e70 s fusions suggested in these guidelines must be interpreted
delay). During follow-up only a portal venous phase (mono- with caution and needs to be tailored to the condition of the
phasic) is generally sufficient. patient.
For MR, the recommendation is to perform axial FS-T2 and FS-T1 Q10b. Measuring the response to fluid resuscitation: the preferred
scanning before and after intravenous gadolinium contrast approach to assessing the response to fluid resuscitation should
administration. be based on one or more of the following: (1) non-invasive
(GRADE 1C, strong agreement). clinical targets of heart rate <120/min, mean arterial pressure
Remarks: there is a wide variation in the literature regarding between 65 and 85 mmHg (8.7e11.3 kPa), and urinary output
CT and MR protocols but there are no existing dedicated >0.5e1 ml/kg/h, (2) invasive clinical targets of stroke volume
radiological guidelines. For CT, both the pancreatic and portal variation, and intrathoracic blood volume determination, and
venous phase are sufficient for discriminating viable from (3) biochemical targets of hematocrit 35e44%.
non-viable pancreatic tissue. The following indications would (GRADE 2B, weak agreement).
require a multiphasic protocol: hemorrhage, arterial pseu- Remarks: non-invasive targets are useful on a regular ward,
doaneurysm and mesenteric infarction. An MR with T2- while invasive targets are more appropriate in the intensive
weighted images is advised when the differentiation be- care unit. It is unlikely that a single parameter will be as
tween pseudocysts and collections with necrosis (i.e. acute reliable as the assessment of multiple parameters. Recent
necrotic collection and walled-off necrosis) is clinically rele- studies have focused on blood urea nitrogen as a predictor of
vant and in young patients because of the radiation burden of outcome but not on its value as a response measurement [22].
CT. Contrast-enhanced CT is clearly preferable, although in For biochemical parameters (e.g. hematocrit, blood urea ni-
patients with impending renal failure an initial non-contrast trogen) not only the absolute level, but also the trend should
CT is an option. be noted. A recent study pointed out that central venous
pressure alone may be unreliable as a crude indicator of
3.4. Fluid therapy adequate resuscitation [35].
Q9. What is the best fluid to use for initial fluid resuscitation 3.5. Intensive care management
in acute pancreatitis?
Ringer’s lactate is recommended for initial fluid resuscitation in Q11. What are the indications for admission to an intensive
acute pancreatitis. care unit in acute pancreatitis?
(GRADE 1B, strong agreement). A patient diagnosed with acute pancreatitis and one or more of
Remarks: only very few studies have investigated the effect of the following parameters identified at admission as defined by
different fluid types on outcome of acute pancreatitis [29e31]. the guidelines of the Society of Critical Care Medicine (SCCM)
In a multicenter RCT in 40 patients with acute pancreatitis, [36] should be transferred immediately to an intensive care
resuscitation with Ringer’s lactate decreased the incidence of setting: (1) pulse <40 or >150 beats/min; (2) systolic arterial
SIRS when compared to resuscitation with normal saline [30]. pressure <80 mmHg (<10.7 kPa) or mean arterial pressure
The use of hydroxyethyl starch (HES) is discouraged since it <60 mmHg (<8.0 kPa) or diastolic arterial pressure >120 mmHg
increased the rates of renal failure and mortality, as compared (>16 kPa); (3) respiratory rate >35 breaths/min; (4) serum so-
to Ringer’s lactate in a multicenter RCT in patients with severe dium <110 mmol/l or >170 mmol/l; (5) serum potassium
sepsis in an intensive care [32]. Ringer’s lactate is very similar <2.0 mmol/l or >7.0 mmol/l; (6) paO2 <50 mmHg (<6.7 kPa);
(7) pH < 7.1 or >7.7; 8) serum glucose >800 mg/dl Q15. What is the definition of abdominal compartment
(>44.4 mmol/L); (9) serum calcium > 15 mg/dl (>3.75 mmol/L); syndrome?
(10) anuria, or (11) coma. Furthermore, a patient with severe Intra-abdominal pressure is the steady-state pressure within the
acute pancreatitis as defined by the revised Atlanta Classifica- abdominal cavity. Abdominal compartment syndrome (ACS) is
tion (i.e. persistent organ failure) [6] should be treated in an defined as a sustained intra-abdominal pressure > 20 mmHg
intensive care setting. (with or without abdominal arterial perfusion pressure <
(GRADE 1C, strong agreement). 60 mmHg) that is associated with new onset organ failure.
Remarks: every patient considered at high risk of rapid clinical (GRADE 2B, strong agreement).
deterioration, such as those with persistent SIRS, the elderly, Remarks: ACS cannot be diagnosed by physical examination and
the obese, patients requiring ongoing volume resuscitation, requires objective measurements of intra-abdominal pressure via
and patients with moderately severe acute pancreatitis as the bladder with a maximal instillation volume of 25 ml of sterile
defined by the revised Atlanta classification [6] should be saline, as described in a 2013 international guideline [43]. Mea-
assessed for admission to a high dependency unit (i.e. inter- surement of intra-abdominal pressure should be considered in
mediate care unit, level 2), if available. The routine use of mechanically ventilated patients with severe acute pancreatitis,
single markers, such as CRP, hematocrit, BUN or procalcitonin especially in case of clinical deterioration.
alone to triage patients to an intensive care setting is not Intra-abdominal hypertension (IAH) is defined by an ongoing or
recommended. repeated pathologic increase in intra-abdominal pressure
Q12. What are the indications for referral to a specialist >12 mmHg. IAH is reported to occur in 60e80% of patients with
center? severe acute pancreatitis, but only a subset of these patients de-
Management in, or referral to, a specialist center is necessary velops ACS [44]. IAH is graded as follows: grade I: intra-abdominal
for patients with severe acute pancreatitis and for those who may pressure 12e15 mmHg; grade II 16e20 mmHg; grade III 21e
need interventional radiologic, endoscopic, or surgical 25 mmHg; and grade IV >25 mmHg. In a small, prospective cohort
intervention. study, IAH and ACS in patients with severe acute pancreatitis
(GRADE 1C, strong agreement). contributed to gut barrier failure with significantly greater endo-
Remarks: a recent analysis of the United States Nationwide toxin levels [45].
Inpatient Sample suggested that treatment of patients with Q16. How should ACS be treated?
acute pancreatitis in high volume centers (upper third, >118 Medical interventions for ACS in acute pancreatitis: interventions
patients per year) resulted in a decreased risk of prolonged to decrease intra-abdominal pressure should target the most
hospital stay and mortality (adjusted hazard ratio 0.74) [37]. important contributors to IAH in acute pancreatitis:
Q13. What are the minimal requirements for a specialist 1) Hollow-viscera volume: nasogastric drainage, prokinetics,
center? rectal tubes, if necessary endoscopic decompression.
A specialist center in the management of acute pancreatitis is 2) Intra/extra vascular fluid: volume resuscitation on demand,
defined as a high volume center with up-to-date intensive if volume overloaded either ultrafiltration or diuretics can be
care facilities including options for organ replacement ther- employed.
apy, and with daily (i.e. 7 days per week) access to interven- 3) Abdominal wall expansion: adequate analgesia and sedation
tional radiology, interventional endoscopy with EUS and ERCP to decrease abdominal muscle tone, if necessary neuro-
assistance as well as surgical expertise in managing necro- muscular blockade.
tizing pancreatitis. Patients should be enrolled in prospective Invasive treatment for ACS in acute pancreatitis: invasive decom-
audits for quality control issues and into clinical trials when- pression should only be used after multidisciplinary discussion in
ever possible. patients with a sustained intra-abdominal pressure >25 mmHg
(GRADE 2C, weak agreement). with new onset organ failure refractory to medical therapy and
Remarks: as there are no studies comparing requirements for nasogastric/rectal decompression. Invasive treatment options
specialist centers, this recommendation can only be weak. As include percutaneous catheter drainage of ascites, midline lapa-
optimal treatment of severe acute pancreatitis is achieved by a rostomy, bilateral subcostal laparostomy, or subcutaneous linea
multidisciplinary team, high volume academic centers usually alba fasciotomy. In case of surgical decompression, the retroperi-
classify as specialist centers. A minimum of two specialists toneal cavity and the omental bursa should be left intact to reduce
should be available in all fields of expertise (interventional the risk of infecting peripancreatic and pancreatic necrosis.
radiology, interventional endoscopy, surgery, critical care med- (GRADE 2C, strong agreement).
icine) to allow for minimum coverage. Remarks: although the necessity of decompression of ACS is a
Q14. Can persistent SIRS/organ failure be prevented? rare event in severe acute pancreatitis, it may be lifesaving
Early fluid resuscitation within the first 24 h of admission for [46]. RCTs comparing surgical decompression of ACS to other
acute pancreatitis is associated with decreased rates of persis- treatment strategies are lacking. A 2013 international guide-
tent SIRS and organ failure. line discusses both the prevalence and etiologic factors for ACS
(GRADE 1C, strong agreement). in various conditions, including acute pancreatitis, and pro-
Remarks: persistent organ failure is the key determinant of vides an evidence-based approach to both diagnosis and
mortality in acute pancreatitis. Persistent SIRS resulted in a clinical management [43]. These guidelines state that because
mortality of 25% compared to 8% with transient SIRS [17,38]. of the obvious disadvantages of laparostomy/open abdomen,
Renal failure predicts mortality in severe acute pancreatitis. percutaneous catheter drainage should be considered in pa-
Fluid resuscitation cannot prevent necrosis formation, but early tients with ACS and abundant abdominal fluid on CT. Percu-
fluid resuscitation is associated with reduced SIRS, organ fail- taneous drainage should lead to immediate and sustained
ure and in-hospital mortality [39]. Enteral nutrition, as improvement, if not, surgical decompression should be per-
compared to parenteral nutrition, decreases infectious com- formed. To avoid an open abdomen and its negative effects of
plications, organ failure and mortality [40,41]. The literature is evisceration of intestines, fluid losses and contamination, a
unclear on the impact of early feeding on early SIRS/organ primary closure with Mesh-grafts can be considered after open
failure [42]. laparotomy.
3.6. Preventing infectious complications infections, multi-organ failure, need for surgical intervention,
and mortality [40,41]. The overwhelming majority of studies
Q17. Is systemic antibiotic prophylaxis effective in preventing were performed in patients with predicted severe acute
infectious complications in acute pancreatitis? pancreatitis. Patients who can eat do not require additional
Intravenous antibiotic prophylaxis is not recommended for the enteral nutrition via a feeding tube. A recent RCT in 60 patients
prevention of infectious complications in acute pancreatitis. with ‘severe acute pancreatitis’ found improved outcomes when
(GRADE 1B, strong agreement). enteral nutrition was started within 48 h as compared to after 7
Remarks: according to a recent meta-analysis of 14 RCTs, there is days of fasting [56].
no evidence to support the routine use of antibiotic prophylaxis Q22. What type of enteral nutrition should be used?
in patients with (predicted) severe acute pancreatitis [47]. Ef- Either elemental or polymeric enteral nutrition formulations
fects of antibiotics may vary between subgroups, but more ev- can be used in acute pancreatitis.
idence is needed [48]. A recent Cochrane meta-analysis (GRADE 2B, strong agreement).
suggested a reduction in pancreatic infection in the subgroup of Remarks: a recent meta-analysis including 20 RCTs concluded
patients who received imipenem, but the authors concluded that there is no specific type of enteral nutrition or immuno-
that more evidence is needed [49]. Prophylactic continuous nutrition that improves outcome in acute pancreatitis [57]. The
regional arterial infusion of antibiotics appears to be somewhat relatively inexpensive polymeric feeding formulations were
promising but further studies are warranted [50]. Intravenous associated with similar feeding tolerance and appeared as
antibiotics should be given in case of suspected infection of beneficial as the more expensive (semi)elemental formulations
necrotizing pancreatitis and further intervention considered in reducing the risks of infectious complications and mortality.
[50]. Q23. Should enteral nutrition be administered via a nasoje-
Q18. Is selective gut decontamination effective in preventing junal or nasogastric route?
infectious complications? Enteral nutrition in acute pancreatitis can be administered via
Selective gut decontamination has shown some benefits in either the nasojejunal or nasogastric route.
preventing infectious complications in acute pancreatitis, but (GRADE 2A, strong agreement).
further studies are needed. Remarks: two relatively small RCTs have suggested that naso-
(GRADE 2B, weak agreement). gastric tube feeding is feasible and safe [58,59]. Although
Remarks: evidence on selective decontamination in acute nasogastric tube feeding is probably easier than nasojejunal
pancreatitis is limited to one RCT [51]. The results of this trial tube feeding, a number of patients will not tolerate nasogastric
have to be interpreted with caution, because it also included feeding because of delayed gastric emptying.
non-randomized systemic antibiotic treatment. Q24. What is the role of parenteral nutrition?
Q19. Are probiotics effective in preventing infectious Parenteral nutrition can be administered in acute pancreatitis as
complications? second-line therapy if nasojejunal tube feeding is not tolerated
Probiotic prophylaxis is not recommended for the prevention of and nutritional support is required.
infectious complications in acute pancreatitis. (GRADE 2C, strong agreement).
(GRADE 1B, strong agreement). Remarks: parenteral nutrition should only be started if the nutri-
Remarks: there are abundant variations in type and dosage of tional goals cannot be reached with oral or enteral feeding [40,60].
probiotic preparations. In one RCT in patients with predicted A delay up to 5 days in initiation of parenteral nutrition may be
severe acute pancreatitis a particular combination of probiotic appropriate to allow for restarting of oral or enteral feeding.
strains (i.e. Ecologic 641) did not prevent infectious compli-
cations but increased mortality [52].
3.8. Biliary tract management
3.7. Nutritional support
Q25. What is the indication for ERCP and sphincterotomy
Q20. When should oral feeding be restarted in patients with early in the course of biliary pancreatitis?
predicted mild pancreatitis? ERCP is not indicated in predicted mild biliary pancreatitis
Oral feeding in predicted mild pancreatitis can be restarted once without cholangitis(GRADE 1A, strong agreement).
abdominal pain is decreasing and inflammatory markers are ERCP is probably not indicated in predicted severe
improving. biliary pancreatitis without cholangitis (GRADE 1B, strong
(GRADE 2B, strong agreement). agreement).
Remark: it is not necessary to wait until pain or laboratory ab- ERCP is probably indicated in biliary pancreatitis with
normalities completely resolve before restarting oral feeding. common bile duct obstruction.
One RCT showed that immediate oral refeeding with a normal (GRADE 1C, strong agreement).
diet is safe in predicted mild pancreatitis and leads to a shorter ERCP is indicated in patients with biliary pancreatitis and
hospital stay (4 vs 6 days) [53]. A second RCT demonstrated that cholangitis (GRADE 1B, strong agreement).
feeding can be started with a full solid diet without a need to Remarks: a recent meta-analysis of 7 RCTs including 757 patients
first start with a liquid or soft diet [54]. A third RCT showed that found no evidence that early routine ERCP significantly affects
there is no need to wait for normalization of lipase levels before mortality or local/systemic complications, regardless of the
restarting oral feeding [55]. predicted severity of biliary pancreatitis [61]. The meta-analysis
Q21. What is the indication for enteral tube feeding? did support ERCP in patients with cholangitis or co-existing
Enteral tube feeding should be the primary therapy in patients biliary obstruction. It should be noted that predicting the pres-
with predicted severe acute pancreatitis who require nutritional ence of CBD stones in the early stages of biliary pancreatitis with
support. laboratory findings, transabdominal ultrasonography or CT is
(GRADE 1B, strong agreement). unreliable [62]. The individual trials, and even the pooled data in
Remarks: two meta-analyses demonstrated that enteral nutri- the meta-analyses, did not include enough patients with ‘pre-
tion, as compared with parenteral nutrition, decreases systemic dicted severe biliary pancreatitis without cholangitis’ to study
the hard clinical endpoints such as mortality (possible type-2 gas in peripancreatic collections on CT is considered evidence of
statistical error). infected necrotizing pancreatitis, irrespective of the source of
Q26. If indicated, what is the optimal timing for ERCP in the gas (i.e. loss of integrity of the gastrointestinal tract or
biliary pancreatitis? through gas-forming bacteria). In patients who are operated on
Urgent ERCP (<24 h) is required in patients with acute cholangitis. because of ‘persistent unwellness’ (also known as ‘failure to
Currently, there is no evidence regarding the optimal timing of thrive’) approximately 40% will have infected necrotizing
ERCP in patients with biliary pancreatitis without cholangitis. pancreatitis [66]. A small proportion of patients with docu-
(GRADE 2C, strong agreement). mented infected necrosis who remain clinically stable can be
Remarks: the recent meta-analysis found no statistically signif- managed with antibiotics alone, without the need for percuta-
icant effect of the timing of ERCP (<24 vs. <72 h) on mortality neous catheter drainage or necrosectomy. Future studies should
[61]. However, no studies were specifically designed to study compare (initial) antibiotic treatment of infected necrosis with
timing of ERCP in biliary pancreatitis. Because it is unclear what other, more invasive, strategies [67e70]. During surgical in-
the exact timing of early ERCP should be (24e72 h), it is terventions for ACS, acute bleeding, or bowel ischemia in sterile
reasonable to await spontaneous improvement of biliary necrotizing pancreatitis, drainage or necrosectomy is not indi-
obstruction for 24e48 h. It is important, that ERCP is performed cated because these procedures may increase the risk of
as soon as possible in patients with cholangitis. developing infected necrosis. Spontaneous fistula formation
Q27. What is the role of MRCP and EUS in biliary pancreatitis? between the gastrointestinal tract and necrosis may occur in the
MRCP and EUS may prevent a proportion of ERCPs that would absence of documented bowel ischemia. In cases of clinical
otherwise be performed for suspected common bile duct suspicion, without evidence on imaging, bowel ischemia can be
stones in patients with biliary pancreatitis who do not have diagnosed by colonoscopy or, if negative, laparoscopy. Finally,
cholangitis, without influencing the clinical course. EUS is very rare complications requiring (non-surgical) intervention
superior to MRCP in excluding the presence of small (<5 mm) include pancreaticopleural fistula, pancreatic ascites, obstruc-
gallstones. MRCP is less invasive, less operator-dependent and tive jaundice due to the enlargement of the pancreatic head, and
probably more widely available than EUS. Therefore, in clin- ongoing symptoms (i.e. pain, gastric outlet obstruction) from a
ical practice there is no clear superiority for either MRCP or ‘true’ pseudocyst (i.e. confirmed absence of necrosis in the
EUS. collection on MR or ultrasonography).
(GRADE 2C, strong agreement). Q29. What is the role of fine needle aspiration to diagnose
Remarks: MRCP, EUS and ERCP are generally not indicated in infected necrotizing pancreatitis?
patients with mild biliary pancreatitis without clinical evidence Routine percutaneous fine needle aspiration of peripancreatic
of persistent common bile duct obstruction, as that can be collections to detect bacteria is not indicated, because clinical signs
treated with (early) cholecystectomy with/without intra- (i.e. persistent fever, increasing inflammatory markers) and im-
operative cholangiography. One RCT found that EUS could safely aging signs (i.e. gas in peripancreatic collections) are accurate
replace diagnostic ERCP in patients with biliary pancreatitis predictors of infected necrosis in the majority of patients. Although
[63]. It should be noted that access to urgent MRCP and EUS is the diagnosis of infection can be confirmed by fine needle aspi-
likely to be limited in most hospitals. A negative MRCP does not ration (FNA), there is a risk of false-negative results [66].
exclude the presence of small (<5 mm) common bile duct (GRADE 1C, strong agreement).
stones [64]. This is especially relevant because small stones are Remarks: false-negative FNA results in patients with infected
known to cause biliary pancreatitis [65]. necrotizing pancreatitis have been reported in 12e25% of pa-
tients [66,71]. FNA is indicated in patients without clinical
improvement for several weeks after onset of necrotizing
3.9. Indications for intervention in necrotizing pancreatitis pancreatitis in the absence of clear clinical and imaging signs of
infected necrotizing pancreatitis. There is no evidence that the
Q28. What are the indications for intervention in necrotizing theoretical benefits of FNA, shortening the period to diagnosis of
pancreatitis? infected necrosis and tailoring antibiotic treatment, improve
Common indications for intervention (either radiological, outcome.
endoscopical or surgical) in necrotizing pancreatitis are: Q30. What are the indications for intervention in sterile
Clinical suspicion of, or documented, infected necrotizing necrotizing pancreatitis?
pancreatitis with clinical deterioration, preferably when the Indications for intervention (either radiological, endoscopical or
necrosis has become walled-off. surgical) in sterile necrotizing pancreatitis are:
In the absence of documented infected necrotizing pancre- Ongoing gastric outlet, intestinal, or biliary obstruction due
atitis, ongoing organ failure for several weeks after the onset to mass effect of walled-off necrosis (i.e. arbitrarily >4e8
of acute pancreatitis, preferably when the necrosis has weeks after onset of acute pancreatitis).
become walled-off. Persistent symptoms (e.g. pain, ‘persistent unwellness’) in
Less common indications for intervention are: patients with walled-off necrosis without signs of infection
Abdominal compartment syndrome (i.e. arbitrarily >8 weeks after onset of acute pancreatitis).
Ongoing acute bleeding Disconnected duct syndrome (i.e. full transection of the
Bowel ischemia pancreatic duct in the presence of pancreatic necrosis) with
Ongoing gastric outlet, intestinal, or biliary obstruction due to persisting symptomatic (e.g. pain, obstruction) collection(s)
mass effect from large walled-off necrosis (arbitrarily >4e8 with necrosis without signs of infections (i.e. arbitrarily >8
weeks after onset of pancreatitis) weeks after onset of acute pancreatitis).
(GRADE 1C, strong agreement). (GRADE 2C, strong agreement).
Remarks: the vast majority of patients with sterile necrotizing Remarks: according to one observational study in 639 patients,
pancreatitis can be managed without intervention (i.e. catheter approximately 1% of patients with necrotizing pancreatitis will
drainage or necrosectomy). Walled-off necrosis usually occurs have symptoms of obstruction during the initial hospital
>4 weeks after onset of acute pancreatitis [6]. The presence of admission necessitating intervention [67]. A recent study of
197 patients with follow-up after necrotizing pancreatitis guided percutaneous (retroperitoneal) catheter drainage or
found a disconnected duct syndrome in 40% of patients and endoscopic transluminal drainage, followed, if necessary, by
about half of these patients required an intervention more than endoscopic or surgical necrosectomy.
8 weeks after surviving necrotizing pancreatitis [72]. Further (GRADE 1A, strong agreement).
data are needed on the indication, timing, and type of inter- Remarks: a multicenter RCT in 88 patients with (suspected)
vention in the months after an episode of necrotizing pancre- infected necrotizing pancreatitis showed that a step-up
atitis. Rare complications requiring (non-surgical) intervention approach of percutaneous (retroperitoneal) catheter
in the follow-up after sterile necrotizing pancreatitis are pan- drainage, followed, if needed, by minimally invasive
creaticopleural fistula, pancreatic ascites, and a ‘true’ (no ne- necrosectomy decreased major short-term complications such
crosis found in the collection on MR or ultrasonography) as new onset multi-organ failure and long-term complications
symptomatic pseudocyst. Prospective cohort studies suggest such as endocrine insufficiency, and decreased costs as
that patients with ‘persistent unwellness’ and necrotizing compared to primary open necrosectomy [77]. Left retroperi-
pancreatitis should probably undergo intervention 6e8 weeks toneal catheter drainage can facilitate minimally invasive
after onset of the disease [66,73]. retroperitoneal necrosectomy. If catheter drainage fails [78],
the optimal method of necrosectomy (i.e. minimally invasive
3.10. Timing of intervention in necrotizing pancreatitis or open surgery or endoscopic transluminal) is unclear.
Minimally invasive necrosectomy may be associated with a
Q31. What is the optimal timing of intervention for suspected decreased risk of complications and death as compared to
or confirmed infected necrosis? open necrosectomy [79]. Several series from centers both in
For patients with proven or suspected infected necrotizing Europe and in the US have confirmed the efficacy of endo-
pancreatitis, invasive intervention (i.e. percutaneous catheter scopic transluminal necrosectomy [80,81]. A pilot multicenter
drainage, endoscopic transluminal drainage/necrosectomy, RCT in 22 patients suggested that endoscopic transluminal
minimally invasive or open necrosectomy) should be delayed necrosectomy may be superior to surgical necrosectomy in
where possible until at least 4 weeks after initial presentation to terms of risk of new onset multiple organ failure and overall
allow the collection to become ‘walled-off’. complications [82]. There is however a large variance in
(GRADE 1C, strong agreement). expertise with the various techniques between centers which
Remarks: open necrosectomy is associated with poor outcomes has to be taken into account.
when performed early [67,73e76]. In a subset of patients it will Q34. Should catheter drainage (percutaneous or endoscopic
not be feasible to delay intervention until 4 weeks. Even if transluminal) always be the first step for suspected or
initial percutaneous catheter drainage is undertaken early, confirmed infected necrotizing pancreatitis?
necrosectomy should ideally still be delayed until the collection Percutaneous catheter or endoscopic transmural drainage should
has become walled-off. The timing for repeat interventions (e.g. be the first step in the treatment of patients with suspected or
repeat percutaneous drainage, repeat endoscopic necrosec- confirmed (walled-off) infected necrotizing pancreatitis.
tomy, or crossover to surgery) should be based on clinical and (GRADE 1A, strong agreement).
imaging criteria, and no strict guidelines can be recommended. Remarks: percutaneous catheter drainage alone will prevent
Consultation with a specialist center before interventional 23e50% of necrosectomies in patients with infected necrotizing
treatment is advisable. pancreatitis [75,77,78,83,84]. Percutaneous catheter drainage is
Q32. Can subgroups of patients with necrotizing pancreatitis technically feasible in >95% of patients with infected necrosis
be defined that require early or late intervention? [77]. One prospective, observational multicenter study of 40
The best available evidence suggests that surgical necrosectomy patients found that a decrease in the size of the collection of at
should ideally be delayed until collections have become walled- least 75% after the first 10e14 days of percutaneous drainage
off, typically 4 weeks after the onset of pancreatitis, in all pa- (n ¼ 9, 23%) correctly predicts successful percutaneous treat-
tients with complications of necrosis. No subgroups have been ment [75] but more data are needed to confirm this finding.
identified that might benefit from earlier or delayed intervention. After catheter drainage, it is imperative that the patient is fol-
(GRADE 1C, strong agreement). lowed by an experienced clinician, who in the absence of clinical
Remarks: regardless of the presence of necrosis, patients with improvement can direct the next appropriate therapeutic step
intra-abdominal catastrophes (hemorrhage, perforation, (i.e. surgical or endoscopic necrosectomy). Although the use of
abdominal compartment syndrome) require immediate larger bore drains are sometimes claimed to yield better results,
intervention. Minimally invasive methods to address these data are lacking. Overall, there is currently less experience with
problems such as angioembolization/-stenting or percuta- endoscopic transluminal drainage than with percutaneous
neous catheter drainage of ascites should be considered in a drainage.
multidisciplinary team including at least interventional radi- Q35. Can subgroups of patients with infected necrotizing
ologists, endoscopists, and surgeons. Loop ileostomy may be pancreatitis be defined who require different strategies
considered for patients with a colonic fistula secondary to (including conservative treatment)?
(infected) necrotizing pancreatitis, in the absence of bowel There are insufficient data to define subgroups of patients with
ischemia. suspected or confirmed infected necrotizing pancreatitis who
would benefit from a different treatment strategy.
3.11. Intervention strategies in necrotizing pancreatitis (GRADE 2C, strong agreement).
Remarks: in a predefined subgroup analysis on severity in a
Q33. What is the optimal interventional strategy (percuta- multicenter RCT, the effect of the step-up approach was
neous catheter drainage, endoscopic transluminal drainage/ beneficial in patients with and without multiple organ failure
necrosectomy, minimally invasive or open necrosectomy) for [77]. No other prospective studies were specifically designed
suspected or confirmed infected necrotizing pancreatitis? to assess the efficacy of certain treatment strategies in specific
The optimal interventional strategy for patients with suspected subgroups. Although several small cohort studies have
or confirmed infected necrotizing pancreatitis is initial image- reported success of conservative treatment (i.e. antibiotics
alone) for infected necrosis the exact subgroup in which this available literature and the opinion of leading pancreatologists
strategy may be successful has not accurately been defined. worldwide.
Focus should now shift to optimal dissemination and imple-
mentation of these guidelines [90]. Several studies have indicated
3.12. Timing of cholecystectomy (or endoscopic sphincterotomy)
that guideline implementation in acute pancreatitis is frequently
suboptimal [91e94] and hence a structured, ongoing effort is
Q36. What is the optimal timing of cholecystectomy after
required. Dissemination will be facilitated by free online access to
mild biliary pancreatitis?
these guidelines. Although there is no optimal strategy to ensure
Cholecystectomy during index admission for mild biliary
good implementation of a guideline [95], there is clearly a role for
pancreatitis appears safe and is recommended. Interval chole-
pancreatologists in this process. By informing specialist and non-
cystectomy after mild biliary pancreatitis is associated with a
specialist colleagues and encouraging them to use these guide-
substantial risk of readmission for recurrent biliary events,
lines, by presenting the guidelines in local or national meetings and
especially recurrent biliary pancreatitis.
by writing about and referring to these guidelines in (inter-)na-
(GRADE 1C, strong agreement).
tional journals, pancreatologists can optimize implementation of
Remarks: a systematic review of nine studies including 998 pa-
these guidelines. Some evidence also suggests that auditing could
tients found an 18% readmission rate for recurrent biliary events a
increase awareness and improve guideline implementation [96].
median of 6 weeks after index admission for mild biliary
These guidelines will also be useful when designing future studies
pancreatitis [85]. Although cholecystectomy during index
as they reflect the current ‘benchmark’ of treating acute pancreatitis.
admission appeared safe, selection bias could not be excluded
The existence of evidence-based guidelines obviously does not
[85]. ERCP with sphincterotomy before cholecystectomy
relieve clinicians from the professional obligation to keep up-to-date
decreased the rate of recurrent biliary pancreatitis but not of other
with new developments in acute pancreatitis. Especially, the results
biliary events [86]. It should be noted that ERCP is rarely indicated
of currently ongoing randomized controlled trials (http://apps.who.
in mild biliary pancreatitis, except in the case of cholangitis (see
int/trialsearch/) should be taking into account. How than to decide
Q25). Alternatively, preoperative MRCP or EUS, or intraoperative
when to update these guidelines? Some have argued that a clinical
cholangiography can be performed during cholecystectomy to
guideline should be updated continuously. Although appealing this is
select out those patients with common bile duct stones who
clearly impractical. The Working group will use a published frame-
should be treated either by operative bile duct exploration or
work on how to decide when to update these guidelines [8].
endoscopic sphincterotomy. In unfit elderly (i.e. arbitrarily
These guidelines on the management of acute pancreatitis
>80 yrs) patients one could refrain from cholecystectomy, espe-
should result in reduced variation in practice and an improvement
cially if sphincterotomy was already performed, although a subset
in patient outcome. The challenge now is to ensure high compli-
of these patients will develop recurrent biliary colics [87].
ance in clinical practice and trial design.
Q37. What is the optimal timing of cholecystectomy after
severe biliary pancreatitis?
Funding
Cholecystectomy should be delayed in patients with peri-
pancreatic collections until the collections either resolve or if
The IAP/APA provided organizational support for the develop-
they persist beyond 6 weeks, at which time cholecystectomy can
ment of these guidelines. No external funding was provided, and
be performed safely.
there was no financial support for anyone involved with the
(GRADE 2C, strong agreement).
development of these guidelines.
Remarks: one retrospective study of 151 patients found an
increased incidence of infected collections in patients who un-
Acknowledgements
derwent early cholecystectomy after severe pancreatitis [88]. A
second retrospective study of 30 patients reported no episodes of
The leadership of both the IAP (especially 2012 president, Ashok
recurrent biliary pancreatitis during the waiting period for inter-
Saluja, PhD) and the APA (especially 2012 president Rodger Liddle,
val cholecystectomy after routine ERCP and sphincterotomy [89].
MD) are acknowledged for their support in developing these
Q38. What is the role of cholecystectomy after endoscopic
guidelines. A special expression of appreciation goes to Erin Brud-
sphincterotomy in biliary pancreatitis?
vik, administrator of the APA, for her excellent work, which
In patients with biliary pancreatitis who have undergone
included organizing all telephone/email correspondence and the
sphincterotomy and are fit for surgery, cholecystectomy is
interactive IAP/APA joint meeting.
advised, because ERCP and sphincterotomy prevent recurrence
No conflicts of interest were reported.
of biliary pancreatitis but not gallstone related gallbladder dis-
ease, i.e. biliary colic and cholecystitis.
Collaborators
(GRADE 2B, strong agreement).
Remarks: one meta-analysis reported a 10% readmission rate
The ‘Working group IAP/APA acute pancreatitis guidelines’
after ERCP for mild biliary pancreatitis because of biliary colic
consisted of a Steering committee, Executive Committee, the 2012
and acute cholecystitis [85]. Studies on this topic in severe
IAP and APA presidents, Review groups and Expert referees, all of
biliary pancreatitis are lacking. In severe biliary pancreatitis,
whom are listed below.
cholecystectomy should be postponed for 6 weeks.
Steering committee
4. Conclusion
Marc Besselink, AMC Amsterdam, Amsterdam (MGB, m.g.
The IAP/APA guidelines on the management of acute besselink@amc.nl)
pancreatitis are the result of an international, multidisciplinary, Hjalmar van Santvoort, University Medical Center Utrecht,
evidence-based approach. These guidelines provide recommen- Utrecht (HCvS, h.vansantvoort@umcutrecht.nl)
dations to key aspects of medical and surgical management Martin Freeman, University of Minnesota, Minneapolis
of acute pancreatitis combined with remarks based on the Timothy Gardner, Dartmouth Hitchcock Medical Center, Lebanon
Julia Mayerle, Ernst-Moritz-Arndt-University, Greifswald Greifswald (presenter).

Santhi Swaroop Vege, Mayo Clinic, Rochester Time manager: Timothy Gardner, Lebanon
Jens Werner, University of Heidelberg, Heidelberg (JW, jens. G. Nutritional support (Q20e24)
werner@med.uni-heidelberg.de) Reviewers: Maxim Petrov, Auckland; Roland Anderson,
Marc Besselink, Hjalmar van Santvoort, Jens Werner: co- Lund; Stephen McClave, Louisville.
ordinators, writing of working plan and current guidelines, prepa- Time manager: Timothy Gardner, Lebanon (presenter)
rations for IAP/APA meeting, time managers; Marc Besselink wrote H. Biliary tract management (Q25e27)
the first versions of the working plan and these guidelines, integrated Reviewers: Werner Hartwig, Heidelberg; Hjalmar van Sant-
comments from reviewers and referees in both the working plan and voort, Utrecht (presenter); Martin Freeman, Minneapolis;
in these guidelines. Martin Freeman, Timothy Gardner, Julia Mayerle, Marco Bruno, Rotterdam; Alejandro Oria, Buenos Aires; Peter
Santhi Swaroop Vege: discussions on working plan, guidelines and Banks, Boston.
meeting, critical review and co-authors of working plan and guide- Time manager: Julia Mayerle, Greifswald
lines, time managers. I. Indication for intervention in necrotizing pancreatitis (Q28e30)
Reviewers: Marc Besselink, Amsterdam (presenter); Timothy
Executive committee Gardner, Lebanon; Hein Gooszen, Nijmegen; Todd Baron,
Rochester; Carlos Fernandez-del Castillo, Boston;
Peter Banks, Brigham & Womens Hospital, Boston Time manager: Jens Werner, Heidelberg
Colin McKay, Glasgow Royal Infirmary, Glasgow J. Timing of intervention in necrotizing pancreatitis (Q31e32)
Carlos Fernandez-del Castillo, Massachussets General Hospital, Reviewers: Peter Fagenholz, Boston (presenter); Santhi
Boston Swaroop Vege, Rochester; Marc Besselink, Amsterdam; Jens
Jeremy French, Freeman Hospital, Newcastle upon Tyne Werner, Heidelberg; Carlos Fernandez-del Castillo, Boston.
Hein Gooszen, University Medical Centre St Radboud, Nijmegen Time manager: Hjalmar van Santvoort, Utrecht
Colin Johnson, Southampton General Hospital, Southampton K. Intervention strategy in necrotizing pancreatitis (Q33e35)
Mike Sarr, Mayo Clinic, Rochester Reviewers: Hjalmar van Santvoort, Utrecht (presenter);
Tadahiro Takada, Teikyo University School of Medicine, Tokyo Carlos Fernandez-del Castillo, Boston; Todd Baron, Roches-
John Windsor, The University of Auckland, Auckland ter; Karen Horvath, Seattle; Thomas Bollen, Nieuwegein;
and the members of the Steering committee. Koenraad Mortele, Boston; Jens Werner, Heidelberg.
Time manager: Martin Freeman, Minneapolis
L. Timing of cholecystectomy (or endoscopic sphincerotomy)
IAP/APA presidents 2012: (Q36e38)
Reviewers: Mark van Baal, Nijmegen; William Nealon,
Ashok Saluja, IAP president. Nashville; Timothy Gardner, Lebanon; Julia Mayerle, Greifs-
Rodger Liddle, APA president. wald (presenter).
Ashok Saluja provided secretarial support and provided, with Roger Time manager: Santhi Swaroop Vege, Rochester.
Liddle, facilities for the one-day interactive meeting at the IAP/APA
2012 meeting in Miami. Both were involved in the development of Expert referees (alphabetical order)
the working plan and guidelines.
Ake Andren-Sandberg, Stockholm.
Reviewers and time managers Olaf Bakker, Utrecht.
Claudio Bassi, Verona.
A. Diagnosis of acute pancreatitis and etiology (Q1e3) Markus Buchler, Heidelberg.
Reviewers: Georgios Papachristou, Pittsburgh; Vijay Singh, Marja Boermeester, Amsterdam.
Pittsburgh (presenter); Michael Rünzi, Essen. Ed Bradley, Tallahassee.
Time manager: Julia Mayerle, Greifswald Suresh Chari, Rochester.
B. Prognostication/predicting severity (Q4e5) Richard Charnley, Newcastle upon Tyne.
Reviewers: Bechien Wu, Los Angeles (presenter); Vikesh Saxon Connor, Christchurch.
Singh, Baltimore; John Windsor, Auckland; Peter Banks, Christos Dervenis, Athens.
Boston; Georgios Papachristou, Pittsburgh. Jacques Deviere, Brussels.
Time manager: Santhi Swaroop Vege, Rochester Vikas Dudeja, Minneapolis.
C. Imaging (Q6e8) Paul Fockens, Amsterdam.
Reviewers: Thomas Bollen, Nieuwegein (presenter); Desiree Chris Forsmark, Gainesville.
Morgan, Birmingham; Koenraad Mortele, Boston. Helmut Friess, Munich.
Time manager: Santhi Swaroop Vege, Rochester Shuji Isaji, Mie
D. Fluid therapy (Q9e10) Rainer Isenmann, Ellwangen
Reviewers: Anubhav Mittal, Auckland (presenter); John Ernst Klar, Rostock.
Windsor, Auckland; Mao En-qiang, Shanghai, Timothy Philippe Lévy, Clichy.
Gardner, Lebanon; Julia Mayerle, Greifswald. Keith Lillemoe, Boston.
Time manager: Santhi Swaroop Vege, Rochester Xubao Liu, Chengdu Matthias Löhr, Stockholm.
E. Intensive care management (Q11e16) Toshihiko Mayumi, KitaKyushu.
Reviewers: Julia Mayerle, Greifswald (presenter); Colin Joachim Mossner, Leipzig.
Johnson, Southampton; Jan de Waele, Gent. John Neoptolemos, Liverpool.
Time manager: Hjalmar van Santvoort, Utrecht Isto Nordback, Tampere.
F. Preventing infectious complications (Q17e19) Attila Olah, Gyor.
Reviewers: Maxim Petrov, Auckland; Patchen Dellinger, Roy Padbury, Adelaide.
Seattle; Marc Besselink; Amsterdam; Markus M. Lerch, Rowan Parks, Edinburgh.
Dejan Radenkovic, Belgrade. GRADE system: step 1, grade the evidence.

Bettina Rau, Rostock.
Vinciane Rebours, Clichy. A ¼ high quality evidence.
Stefan Seewald, Hamburg. B ¼ moderate quality evidence.
Hans Seifert, Oldenburg. C ¼ low quality evidence.
Tooru Shimosegawa, Sendai.
Ajith Siriwardena, Manchester. If RCTs, start by assuming high quality (grade A), but then grade
William Steinberg, Rockville down for:
Robert Sutton, Liverpool.
Masao Tanaka, Fukuoka. � Serious methodologic limitations.
Kazunori Takeda, Sendai. � Indirectness in population, intervention, or outcome.
Francis Tse, Hamilton. � Inconsistent results.
Harry van Goor, Nijmegen. � Imprecision in estimates.
Andrew Warshaw, Boston. � High likelihood of publication bias.
Chunyou Wang, Wuhan.
David Whitcomb, Pittsburgh. If no RCTs, start by assuming low quality (grade C), but then
Yupei Zhao, Beijing. grade up for:
Nicholas Zyromski, Indianapolis.
The expert referees reviewed the final version of these guidelines. � Large or very large treatment effects.
� All plausible biases would diminish the effect of the intervention.
� Doseeresponse gradient.
Appendix. GRADE system
GRADE system, step 2, grade the recommendation.
http://www.uptodate.com/home/about/tutorial/index.html
(30 min tutorial). 1 ¼ strong recommendation
http://www.uptodate.com/home/about/policies/grade.html. 2 ¼ weak recommendation
Grade of recommendation Clarity of risk/benefit Quality of supporting evidence Implications
1A Strong recommendation. Benefits clearly outweigh risk Consistent evidence from well performed Strong recommendation, can
and burdens, or vice versa randomized, controlled trials or overwhelming apply to most patients in most
High quality evidence
evidence of some other form. Further research circumstances without reservation
is unlikely to change our confidence in the
estimate of benefit and risk.
1B Strong recommendation. Benefits clearly outweigh risk Evidence from randomized, controlled trials Strong recommendation, likely
and burdens, or vice versa with important limitations (inconsistent results, to apply to most patients
Moderate quality evidence
methodologic flaws, indirect or imprecise),
or very strong evidence of some other form.
Further research (if performed) is likely to
have an impact on our confidence in the
estimate of benefit and risk and may change
the estimate.
1C Strong recommendation. Benefits appear to outweigh Evidence from observational studies, Relatively strong recommendation;
risk and burdens, or vice versa unsystematic clinical experience, or from might change when higher quality
Low quality evidence
randomized, controlled trials with evidence becomes available
serious flaws. Any estimate of effect
is uncertain.
2A Weak recommendation. Benefits closely balanced with Consistent evidence from well performed Weak recommendation, best
risks and burdens randomized, controlled trials or overwhelming action may differ depending on
High quality evidence
evidence of some other form. Further research circumstances or patients or
is unlikely to change our confidence in the societal values
estimate of benefit and risk.
2B Weak recommendation. Benefits closely balanced with Evidence from randomized, controlled trials Weak recommendation, alternative
risks and burdens, some with important limitations (inconsistent results, approaches likely to be better for
Moderate quality evidence
uncertainly in the estimates methodologic flaws, indirect or imprecise), some patients under some
of benefits, risks and burdens or very strong evidence of some other form. circumstances
Further research (if performed) is likely to have
an impact on our confidence in the estimate
of benefit and risk and may change the estimate.
2C Weak recommendation. Uncertainty in the estimates Evidence from observational studies, unsystematic Very weak recommendation;
of benefits, risks, and burdens; clinical experience, or from randomized, controlled other alternatives may be equally
Low quality evidence
benefits may be closely balanced trials with serious flaws. Any estimate of effect reasonable.
with risks and burdens is uncertain.
Please note: the abovementioned guideline for grading evidence is specifically for therapeutic studies. For studies on diagnostic accuracy, the GRADE system suggests different
criteria. Valid diagnostic accuracy studies e cross-sectional or cohort studies in patients with diagnostic uncertainty and direct comparison of test results with an appropriate
reference standard e provide high quality evidence. However, they often are downgraded to lower quality evidence based on an assessment of limitations, particularly
indirectness of outcomes, i.e. uncertainty about the link between the test accuracy and outcomes that are important to patients, inconsistency, imprecision and publication
bias. For background and specific instructions on the GRADE system in evaluating diagnostic question see Ref. [5].
[28] Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of
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nature publishing group PRACTICE GUIDELINES 1
AMERICAN COLLEGE OF
IV GASTROENTEROLOGY GUIDELINE:
American College of Gastroenterology Guideline:
MANAGEMENT OF ACUTE PANCREATITIS
Management of Acute Pancreatitis
Scott Tenner, MD, MPH, FACG1, John Baillie, MB, ChB, FRCP, FACG2, John DeWitt, MD, FACG3 and Santhi Swaroop Vege, MD, FACG4
This guideline presents recommendations for the management of patients with acute pancreatitis (AP). During
the past decade, there have been new understandings and developments in the diagnosis, etiology, and early
and late management of the disease. As the diagnosis of AP is most often established by clinical symptoms and
laboratory testing, contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI) of
the pancreas should be reserved for patients in whom the diagnosis is unclear or who fail to improve clinically.
Hemodynamic status should be assessed immediately upon presentation and resuscitative measures begun
as needed. Patients with organ failure and/or the systemic inflammatory response syndrome (SIRS) should be
admitted to an intensive care unit or intermediary care setting whenever possible. Aggressive hydration should be
provided to all patients, unless cardiovascular and/or renal comorbidites preclude it. Early aggressive intravenous
hydration is most beneficial within the first 12–24 h, and may have little benefit beyond. Patients with AP and
concurrent acute cholangitis should undergo endoscopic retrograde cholangiopancreatography (ERCP) within 24 h
of admission. Pancreatic duct stents and/or postprocedure rectal nonsteroidal anti-inflammatory drug (NSAID)
suppositories should be utilized to lower the risk of severe post-ERCP pancreatitis in high-risk patients. Routine use
of prophylactic antibiotics in patients with severe AP and/or sterile necrosis is not recommended. In patients with
infected necrosis, antibiotics known to penetrate pancreatic necrosis may be useful in delaying intervention, thus
decreasing morbidity and mortality. In mild AP, oral feedings can be started immediately if there is no nausea and
vomiting. In severe AP, enteral nutrition is recommended to prevent infectious complications, whereas parenteral
nutrition should be avoided. Asymptomatic pancreatic and/or extrapancreatic necrosis and/or pseudocysts do not
warrant intervention regardless of size, location, and/or extension. In stable patients with infected necrosis, surgical,
radiologic, and/or endoscopic drainage should be delayed, preferably for 4 weeks, to allow the development of a wall
around the necrosis.
Am J Gastroenterol advance online publication, 30 July 2013; doi:10.1038/ajg.2013.218
Acute pancreatitis (AP) is one of the most common diseases There have been important changes in the definitions and
of the gastrointestinal tract, leading to tremendous emotion- classification of AP since the Atlanta classification from 1992
al, physical, and financial human burden (1,2). In the United (5). During the past decade, several limitations have been rec-
States, in 2009, AP was the most common gastroenterology ognized that led to a working group and web-based consensus
discharge diagnosis with a cost of 2.6 billion dollars (2). revision (6). Two distinct phases of AP have now been identified:
Recent studies show the incidence of AP varies between 4.9 (i) early (within 1 week), characterized by the systemic inflam-
and 73.4 cases per 100,000 worldwide (3,4). An increase in matory response syndrome (SIRS) and/or organ failure; and
the annual incidence for AP has been observed in most recent (ii) late ( > 1 week), characterized by local complications. It is
studies. Epidemiologic review data from the 1988 to 2003 critical to recognize the paramount importance of organ failure
National Hospital Discharge Survey showed that hospital in determining disease severity. Local complications are defined
admissions for AP increased from 40 per 100,000 in 1998 to as peripancreatic fluid collections, pancreatic and peripancreatic
70 per 100,000 in 2002. Although the case fatality rate for AP necrosis (sterile or infected), pseudocysts, and walled-off necro-
has decreased over time, the overall population mortality rate sis (sterile or infected). Isolated extrapancreatic necrosis is
for AP has remained unchanged (1). also included under the term necrotizing pancreatitis; although
1
State University of New York, Downstate Medical Center, Brooklyn, New York, USA; 2Carteret Medical Group, Morehead City, North Carolina, USA; 3Indiana
University Medical Center, Indianapolis, Indiana, USA; 4Mayo Clinic, Rochester, Minnesota, USA. Correspondence: Santhi Swaroop Vege, MD, FACG, Division of
Gastroenterology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. E-mail: vege.santhi@mayo.edu
Received 23 December 2012; accepted 18 June 2013
© 2013 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY

КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ АМЕРИКАНСКОГО КОЛЛЕДЖАˇГАСТРОЭНТЕРОЛОГИИ:
ЛЕЧЕНИЕ ОСТРОГО ПАНКРЕАТИТА (AMERICAN COLLEGE OF GASTROENTEROLOGY 49
2 Tenner et al.
GUIDELINE: MANAGEMENT OF ACUTE PANCREATITIS)
Table 1. GRADE system of quality of evidence and strength of (iii) characteristic findings from abdominal imaging (strong
recommendation recommendation, moderate quality of evidence).
2. Contrast-enhanced computed tomography (CECT) and/or
High Further research is very unlikely to change our confidence in
the estimate of effect. magnetic resonance imaging (MRI) of the pancreas should
Moderate Further research is likely to have an important impact on
be reserved for patients in whom the diagnosis is unclear or
our confidence in the estimate of effect and may change the who fail to improve clinically within the first 48–72 h after
estimate. hospital admission or to evaluate complications (strong
Low Further research is very likely to have an important impact on recommendation, low quality of evidence).
our confidence in the estimate of effect and is likely to change
the estimate.
Very low Any estimate of the effect is very uncertain. DIAGNOSIS: CLINICAL PRESENTATION
Patients with AP typically present with epigastric or left upper
quadrant pain. The pain is usually described as constant with
radiation to the back, chest, or flanks, but this description is non-
outcomes like persistent organ failure, infected necrosis, and mor- specific. The intensity of the pain is usually severe, but can be vari-
tality of this entity are more often seen when compared to inter- able. The intensity and location of the pain do not correlate with
stitial pancreatitis, these complications are more commonly seen severity. Pain described as dull, colicky, or located in the lower
in patients with pancreatic parenchymal necrosis (7). There is now abdominal region is not consistent with AP and suggests an alter-
a third intermediate grade of severity, moderately severe AP, that native etiology. Abdominal imaging may be helpful to determine
is characterized by local complications in the absence of persistent the diagnosis of AP in patients with atypical presentations.
organ failure. Patients with moderately severe AP may have tran-
sient organ failure, lasting < 48 h. Moderately severe AP may also
exacerbate underlying comorbid disease but is associated with a DIAGNOSIS: LABORATORY PARAMETERS
low mortality. Severe AP is now defined entirely on the presence of Because of limitations in sensitivity, specificity, and positive and
persistent organ failure (defined by a modified Marshall Score) (8). negative predictive value, serum amylase alone cannot be used
We first discuss the diagnosis, etiology, and severity of AP. We reliably for the diagnosis of AP and serum lipase is preferred.
then focus on the early medical management of AP followed by a Serum amylase in AP patients generally rises within a few hours
discussion of the management of complicated disease, most nota- after the onset of symptoms and returns to normal values within
bly pancreatic necrosis. Early management focuses on advance- 3–5 days; however, it may remain within the normal range on
ments in our understanding of aggressive intravenous hydration, admission in as many as one-fifth of patients (12,13). Compared
which when applied early appears to decrease morbidity and with lipase, serum amylase returns more quickly to values below
mortality (9,10). The evolving issues of antibiotics, nutrition, and the upper limit of normal. Serum amylase concentrations may
endoscopic, radiologic, surgical, and other minimally invasive be normal in alcohol-induced AP and hypertriglyceridemia.
interventions will be addressed. Serum amylase concentrations might be high in the absence
A search of MEDLINE via the OVID interface using the MeSH of AP in macroamylasaemia (a syndrome characterized by
term “acute pancreatitis” limited to clinical trials, reviews, guide- the formation of large molecular complexes between amylase
lines, and meta-analysis for the years 1966–2012 was undertaken and abnormal immunoglobulins), in patients with decreased
without language restriction, as well as a review of clinical trials glomerular filtration rate, in diseases of the salivary glands,
and reviews known to the authors were performed for the prepara- and in extrapancreatic abdominal diseases associated with
tion of this document. The GRADE system was used to grade the inflammation, including acute appendicitis, cholecystitis, intes-
strength of recommendations and the quality of evidence (11). An tinal obstruction or ischemia, peptic ulcer, and gynecological
explanation of the quality of evidence and strength of the recom- diseases.
mendations is shown in Table 1. Each section of the document Serum lipase appears to be more specific and remains ele-
presents the key recommendations related to the section topic, vated longer than amylase after disease presentation. Despite
followed by a summary of the supporting evidence. A summary of recommendations of previous investigators (14) and guidelines
recommendations is provided in Table 2. for the management of AP (15) that emphasize the advantage
of serum lipase, similar problems with the predictive value
remain in certain patient populations, including the existence
DIAGNOSIS of macrolipasemia. Lipase is also found to be elevated in a vari-
ety of nonpancreatic diseases, such as renal disease, appen-
Recommendations dicitis, cholecystitis, and so on. In addition, an upper limit of
1. The diagnosis of AP is most often established by the normal greater than 3–5 times may be needed in diabetics who
presence of 2 of the 3 following criteria: (i) abdominal pain appear to have higher median lipase compared with nondiabetic
consistent with the disease, (ii) serum amylase and/or lipase patients for unclear reasons (16,17). A Japanese consensus con-
greater than three times the upper limit of normal, and/or ference to determine appropriate “cutoff ” values for amylase and
The American Journal of GASTROENTEROLOGY VOLUME 104 | XXX 2012 www.amjgastro.com

Management of Acute Pancreatitis 3
Table 2. Summary of recommendations

Diagnosis
1. The diagnosis of AP is most often established by the presence of two of the three following criteria: (i) abdominal pain consistent with the disease,
(ii) serum amylase and/or lipase greater than three times the upper limit of normal, and/or (iii) characteristic findings from abdominal imaging
(strong recommendation, moderate quality of evidence).
2. Contrast-enhanced computed tomographic (CECT) and/or magnetic resonance imaging (MRI) of the pancreas should be reserved for patients in
whom the diagnosis is unclear or who fail to improve clinically within the first 48–72 h after hospital admission (strong recommendation, low quality of
evidence).
Etiology
3. Transabdominal ultrasound should be performed in all patients with acute pancreatitis (strong recommendation, low quality of evidence).
4. In the absence of gallstones and/or history of significant history of alcohol use, a serum triglyceride should be obtained and considered the etiology
if > 1,000 mg/dl (conditional recommendation, moderate quality of evidence).
5. In a patient older than 40 years, a pancreatic tumor should be considered as a possible cause of acute pancreatitis (conditional recommendation,
low quality of evidence).
6. Endoscopic investigation in patients with acute idiopathic pancreatitis should be limited, as the risks and benefits of investigation in these patients are
unclear (conditional recommendation, low quality of evidence).
7. Patients with idiopathic pancreatitis should be referred to centers of expertise (conditional recommendation, low quality of evidence).
8. Genetic testing may be considered in young patients ( < 30 years old) if no cause is evident and a family history of pancreatic disease is present
(conditional recommendation, low quality of evidence).
Initial assessment and risk stratification
9. Hemodynamic status should be assessed immediately upon presentation and resuscitative measures begun as needed (strong recommendation,
moderate quality of evidence).
10. Risk assessment should be performed to stratify patients into higher- and lower-risk categories to assist triage, such as admission to an intensive care
setting (conditional recommendation, moderate quality of evidence).
11. Patients with organ failure should be admitted to an intensive care unit or intermediary care setting whenever possible (strong recommendation,
low quality of evidence).
Initial management
12. Aggressive hydration, defined as 250-500 ml per hour of isotonic crystalloid solution should be provided to all patients, unless cardiovascular
and/or renal comorbidites exist. Early aggressive intravenous hydration is most beneficial the first 12–24 h, and may have little benefit beyond
(strong recommendation, moderate quality of evidence).
13. In a patient with severe volume depletion, manifest as hypotension and tachycardia, more rapid repletion (bolus) may be needed (conditional
recommendation, moderate quality of evidence).
14. Lactated Ringer’s solution may be the preferred isotonic crystalloid replacement fluid (conditional recommendation, moderate quality of evidence).
15. Fluid requirements should be reassessed at frequent intervals within 6 h of admission and for the next 24–48 h. The goal of aggressive hydration
should be to decrease the blood urea nitrogen (strong recommendation, moderate quality of evidence).
ERCP in acute pancreatitis
16. Patients with acute pancreatitis and concurrent acute cholangitis should undergo ERCP within 24 h of admission (strong recommendation, moderate
quality of evidence).
17. ERCP is not needed in most patients with gallstone pancreatitis who lack laboratory or clinical evidence of ongoing biliary obstruction (strong
recommendation, low quality of evidence).
18. In the absence of cholangitis and/or jaundice, MRCP or endoscopic ultrasound (EUS) rather than diagnostic ERCP should be used to screen for
choledocholithiasis if highly suspected (conditional recommendation, low quality of evidence).
19. Pancreatic duct stents and/or postprocedure rectal nonsteroidal anti-inflammatory drug (NSAID) suppositories should be utilized to prevent severe
post-ERCP pancreatitis in high-risk patients (conditional recommendation, moderate quality of evidence).
The role of antibiotics in acute pancreatitis
20. Antibiotics should be given for an extrapancreatic infection, such as cholangitis, catheter-acquired infections, bacteremia, urinary tract infections,
pneumonia (strong recommendation, high quality of evidence).
21. Routine use of prophylactic antibiotics in patients with severe acute pancreatitis is not recommended (strong recommendation, moderate quality of
evidence).
22. The use of antibiotics in patients with sterile necrosis to prevent the development of infected necrosis is not recommended (strong recommendation,
23. Infected necrosis should be considered in patients with pancreatic or extrapancreatic necrosis who deteriorate or fail to improve after 7–10 days
of hospitalization. In these patients, either (i) initial CT-guided fine needle aspiration (FNA) for Gram stain and culture to guide use of appropriate
antibiotics or (ii) empiric use of antibiotics without CT FNA should be given (strong recommendation, low quality of evidence).
Table 2 continued on the following page

4 Tenner et al.
Table 2. Continued
24. In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis, such as carbapenems, quinolones, and metronidazole, may
be useful in delaying or sometimes totally avoiding intervention, thus decreasing morbidity and mortality (conditional recommendation, low quality of
evidence).
25. Routine administration of antifungal agents along with prophylactic or therapeutic antibiotics is not recommended (conditional recommendation, low
Nutrition in acute pancreatitis
26. In mild AP, oral feedings can be started immediately if there is no nausea and vomiting, and abdominal pain has resolved (conditional recommenda-
tion, moderate quality of evidence).
27. In mild AP, initiation of feeding with a low-fat solid diet appears as safe as a clear liquid diet (conditional recommendations, moderate quality of
evidence).
28. In severe AP, enteral nutrition is recommended to prevent infectious complications. Parenteral nutrition should be avoided unless the enteral route is
not available, not tolerated, or not meeting caloric requirements (strong recommendation, high quality of evidence).
29. Nasogastric delivery and nasojejunal delivery of enteral feeding appear comparable in efficacy and safety (strong recommendation, moderate quality
of evidence).
The role of surgery in acute pancreatitis
30. In patients with mild AP, found to have gallstones in the gallbladder, a cholecystectomy should be performed before discharge to prevent a recurrence
of AP (strong recommendation, moderate quality of evidence).
31. In a patient with necrotizing biliary AP, in order to prevent infection, cholecystectomy is to be deferred until active inflammation subsides and fluid
collections resolve or stabilize (strong recommendation, moderate quality of evidence).
32. The presence of asymptomatic pseudocysts and pancreatic and/or extrapancreatic necrosis do not warrant intervention, regardless of size, location,
and/or extension (strong recommendation, moderate quality of evidence).
33. In stable patients with infected necrosis, surgical, radiologic, and/or endoscopic drainage should be delayed preferably for more than 4 weeks to allow
liquefication of the contents and the development of a fibrous wall around the necrosis (walled-off necrosis) (strong recommendation, low quality of
evidence).
34. In symptomatic patients with infected necrosis, minimally invasive methods of necrosectomy are preferred to open necrosectomy (strong recommen-
dation, low quality of evidence).
AP, acute pancreatitis; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; MRCP, magnetic resonance cholangiopancreatography.
lipase could not reach consensus on appropriate upper limits of of detecting choledocholithiasis down to 3 mm diameter and pan-
normal (18). Assays of many other pancreatic enzymes have creatic duct disruption while providing high-quality imaging for
been assessed during the past 15 years, but none seems to diagnostic and/or severity purposes. MRI is helpful in patients
offer better diagnostic value than those of serum amylase and with a contrast allergy and renal insufficiency where T2-weighted
lipase (19). Although most studies show a diagnostic efficacy of images without gadolinium contrast can diagnose pancreatic
greater than 3–5 times the upper limit of normal, clinicians must necrosis (24).
consider the clinical condition of the patient when evaluat-
ing amylase and lipase elevations. When a doubt regarding the
diagnosis of AP exists, abdominal imaging, such as CECT, is ETIOLOGY
recommended.
Recommendations
1. Transabdominal ultrasound should be performed in all patients
DIAGNOSIS: ABDOMINAL IMAGING with AP (strong recommendation, low quality of evidence).
Abdominal imaging is useful to confirm the diagnosis of AP. 2. In the absence of gallstones and/or history of significant
CECT provides over 90% sensitivity and specificity for the diag- history of alcohol use, a serum triglyceride should be
nosis of AP (20). Routine use of CECT in patients with AP is obtained and considered the etiology if > 1,000 mg/dl.
unwarranted, as the diagnosis is apparent in many patients and (conditional recommendation, moderate quality of evidence).
most have a mild, uncomplicated course. However, in a patient 3. In a patient > 40 years old, a pancreatic tumor should be
failing to improve after 48–72 (e.g., persistent pain, fever, nausea, considered as a possible cause of AP (conditional recommen-
unable to begin oral feeding), CECT or MRI imaging is recom- dation, low quality of evidence).
mended to assess local complications such as pancreatic necrosis 4. Endoscopic investigation of an elusive etiology in patients
(21–23). Computed tomography (CT) and MRI are comparable with AP should be limited, as the risks and benefits of
in the early assessment of AP (24). MRI, by employing magnetic investigation in these patients are unclear (conditional
resonance cholangiopancreatography (MRCP), has the advantage recommendation, low quality of evidence).

5. Patients with idiopathic AP (IAP) should be referred to recurrent course (27,44,45). Thus, a contrast-enhanced CT scan
centers of expertise (conditional recommendation, low or MRI is needed in these patients. A more extensive evaluation
quality of evidence). including endoscopic ultrasound (EUS) and/or MRCP may be
6. Genetic testing may be considered in young patients needed initially or after a recurrent episode of IAP (46).
( < 30 years old) if no cause is evident and a family history of
pancreatic disease is present (conditional recommendation,
low quality of evidence). IDIOPATHIC AP
IAP is defined as pancreatitis with no etiology established after
initial laboratory (including lipid and calcium level) and imag-
ETIOLOGY: GALLSTONES AND ALCOHOL ing tests (transabdominal ultrasound and CT in the appropri-
The etiology of AP can be readily established in most patients. ate patient) (47). In some patients an etiology may eventually be
The most common cause of AP is gallstones (40–70%) and alco- found, yet in others no definite cause is ever established. Patients
hol (25–35%) (25–27). Because of the high prevalence and impor- with IAP should be evaluated at centers of excellence focusing on
tance of preventing recurrent disease, abdominal ultrasound to pancreatic disease, providing advanced endoscopy services and a
evaluate for cholelithiasis should be performed on all patients combined multidisciplinary approach.
with AP (28–30). Identification of gallstones as the etiology Anatomic and physiologic anomalies of the pancreas occur
should prompt referral for cholecystectomy to prevent recurrent in 10–15% of the population, including pancreas divisum and
attacks and potential biliary sepsis (29,30). Gallstone pancreatitis sphincter of Oddi dysfunction (48). It remains controversial if
is usually an acute event and resolves when the stone is removed these disorders alone cause AP (49). There may be a combination
or passes spontaneously. of factors, including anatomic and genetic, that predispose to the
Alcohol-induced pancreatitis often manifests as a spectrum, development of AP in susceptible individuals (48). Endoscopic
ranging from discrete episodes of AP to chronic irreversible silent therapy, focusing on treating pancreas divisum and/or sphincter of
changes. The diagnosis should not be entertained unless a person Oddi dysfunction, carries a significant risk of precipitating AP and
has a history of over 5 years of heavy alcohol consumption (31). should be performed only in specialized units (50,51). The influ-
“Heavy” alcohol consumption is generally considered to be > 50 g ence of genetic defects, such as cationic trypsinogen mutations,
per day, but is often much higher (32). Clinically evident AP SPINK, or CFTR mutations, in causing AP is being increasingly
occurs in < 5% of heavy drinkers (33); thus, there are likely other recognized. These defects, furthermore, may also increase the
factors that sensitize individuals to the effects of alcohol, such as risk of AP in patients with anatomic anomalies, such as pancreas
genetic factors and tobacco use (27,33,34). divisum (48). However, the role of genetic testing in AP has yet to
be determined, but may be useful in patients with more than one
family member with pancreatic disease (34). Individuals with IAP
OTHER CAUSES OF AP and a family history of pancreatic diseases should be referred for
In the absence of alcohol or gallstones, caution must be exercised formal genetic counseling.
when attributing a possible etiology for AP to another agent or
condition. Medications, infectious agents, and metabolic causes
such as hypercalcemia and hyperparathyroidism are rare causes, INITIAL ASSESSMENT AND RISK STRATIFICATION
often falsely identified as causing AP (35–37). Although some
drugs such as 6-mercaptopurine, azathioprine, and DDI (2′,3′- Recommendations
dideoxyinosine) can clearly cause AP, there are limited data sup- 1. Hemodynamic status should be assessed immediately upon
porting most medications as causative agents (35). Primary and presentation and resuscitative measures begun as needed
secondary hypertriglyceridemia can cause AP; however, these (strong recommendation, moderate quality of evidence).
account for only 1–4% of cases (36). Serum triglycerides should 2. Risk assessment should be performed to stratify patients
rise above 1,000 mg/dl to be considered the cause of AP (38,39). A into higher- and lower-risk categories to assist triage, such
lactescent (milky) serum has been observed in as many as 20% of as admission to an intensive care setting (conditional
patients with AP, and therefore a fasting triglyceride level should be recommendation, low to moderate quality of evidence).
re-evaluated 1 month after discharge when hypertriglyceridemia 3. Patients with organ failure should be admitted to an
is suspected (40). Although most do not, any benign or malignant intensive care unit or intermediary care setting whenever
mass that obstructs the main pancreatic can result in AP. It has possible (strong recommendation, low quality of evidence).
been estimated that 5–14% of patients with benign or malignant
pancreatobiliary tumors present with apparent IAP (41–43). His-
torically, adenocarcinoma of the pancreas was considered a dis- SUMMARY OF EVIDENCE
ease of old age. However, increasingly patients in their 40s—and Definition of severe AP
occasionally younger—are presenting with pancreatic cancer. Most episodes of AP are mild and self-limiting, needing only brief
This entity should be suspected in any patient > 40 years of age hospitalization. Mild AP is defined by the absence of organ failure
with idiopathic pancreatitis, especially those with a prolonged or and/or pancreatic necrosis (5,6). By 48 h after admission, these

6 Tenner et al.
patients typically would have substantially improved and begun

Table 3. Definitions of severity in acute pancreatitis: comparison
refeeding. In patients with severe disease, two phases of AP are
of Atlanta and recent revision
recognized: early (within the first week) and late. Local compli-
cations include peripancreatic fluid collections and pancreatic Atlanta criteria (1993) Atlanta Revision (2013)
and peripancreatic necrosis (sterile or infected). Most patients Mild acute pancreatitis Mild acute pancreatitis
with severe disease present to the emergency room with no organ Absence of organ failure Absence of organ failure
failure or pancreatic necrosis; unfortunately, this has led to many
Absence of local complications Absence of local complications
errors in clinical management of this disease (52). These errors
include failure to provide adequate hydration, failure to diagnose Severe acute pancreatitis Moderately severe acute pancreatitis
and treat cholangitis, and failure to treat early organ failure. For 1. Local complications AND/OR 1. Local complications AND/OR
this reason, it is critical for the clinician to recognize the impor- 2. Organ failure 2. Transient organ failure ( < 48 h)
tance of not falsely labeling a patient with mild disease within the
GI bleeding (> 500 cc/24 hr) Severe acute pancreatitis
first 48 h of admission for AP.
Shock – SBP � 90 mm Hg Persistent organ failure > 48 ha
Severe AP occurs in 15–20% of patients (53). Severe AP is
defined by the presence of persistent (fails to resolve within PaO 2 � 60 %
48 h) organ failure and/or death (6). Historically, in the absence Creatinine � 2 mg/dl
of organ failure, local complications from pancreatitis, such as GI, gastrointestinal; SBP, systolic blood pressure.
pancreatic necrosis, were also considered severe disease (5,6,53). Persistent organ failure is now defined by a Modified Marshal Score (6,8)
a
However, these local complications (including pancreatic necro-

sis with or without transient organ failure) define moderately
severe AP (see Table 3). Moderately severe acute pancreatitis is
characterized by the presence of transient organ failure or local Isolated extrapancreatic necrosis is also included under the term
or systematic complications in the absence of persistent organ necrotizing pancreatitis. This entity, initially thought to be a non-
failure (6). An example of a patient with moderately severe acute specific anatomic finding with no clinical significance, has become
pancreatitis is one who has peripancreatic fluid collections and better characterized and is associated with adverse outcomes, such
prolonged abdominal pain, leukocytosis and, fever, causing the as organ failure and persistent organ failure, but these outcomes are
patient to remain hospitalized for 7-10 days. In the absence of per- less frequent. Extrapancreatic necrosis is more often appreciated
sistent organ failure, mortality in patients with this entity is less during surgery than being identified on imaging studies. Although
than severe acute pancreatitis. If persistent organ failure develops most radiologists can easily identify pancreatic parenchymal
in a patient with necrotizing pancreatitis, it is then considered necrosis, in the absence of surgical intervention, extrapancreatic
severe disease. necrosis is appreciated less often (7).
Organ failure had previously been defined as shock (systolic
blood pressure < 90 mm Hg), pulmonary insufficiency (PaO2 Predicting severe AP
< 60 mm Hg), renal failure (creatinine > 2 mg/dl after rehydration), Clinicians have been largely unable to predict which patients
and/or gastrointestinal bleeding ( > 500 ml of blood loss/24 h) (53). with AP will develop severe disease. Uniformly, severity scoring
The Revised Atlanta Criteria now define organ failure as a score systems are cumbersome, typically require 48 h to become accu-
of 2 or more for one of these organ systems using the modified rate, and when the score demonstrates severe disease, the patient’s
Marshall scoring system (6,8). The authors feel that rather than condition is obvious regardless of the score (52,57,58). The new
calculate a Marshal score (which may be complex for the busy scoring systems, such as the BISAP (59), have not shown to be
clinician), relying on the older Atlanta definitions would be as more accurate than the other scoring systems (60,61). In general,
useful. Further study is needed to validate the need for using the AP-specific scoring systems have a limited value, as they provide
Marshal score. little additional information to the clinician in the evaluation of
Pancreatic necrosis is defined as diffuse or focal areas of non- patients and may delay appropriate management (52).
viable pancreatic parenchyma > 3 cm in size or > 30% of the pan- Although laboratory testing such as the hematocrit and blood
creas (53). Pancreatic necrosis can be sterile or infected (discussed urea nitrogen (BUN) can assist clinicians (52,62,63), no laboratory
below). In the absence of pancreatic necrosis, in mild disease the test is practically available or consistently accurate to predict sever-
edematous pancreas is defined as interstitial pancreatitis. Although ity in patients with AP (64–66). Even the acute-phase reactant
there is some correlation between infection, pancreatic necrosis, C-reactive protein (CRP), the most widely studied inflammatory
hospital length of stay, and organ failure, both patients with sterile marker in AP, is not practical as it takes 72 h to become accurate
necrosis and infected necrosis may develop organ failure (55,56). (54). CT and/or MRI imaging also cannot reliably determine
The presence of infection within the necrosis probably does not severity early in the course of AP, as necrosis usually is not present
increase the likelihood of present or future organ failure. Patients on admission and may develop after 24–48 h (24,67). Thus, in the
with sterile necrosis can suffer from organ failure and appear as ill absence of any available test to determine severity, close examina-
clinically as those patients with infected necrosis. Persistent organ tion to assess early fluid losses, hypovolemic shock, and symptoms
failure is now defined by a Modified Marshal Score (6,8). suggestive of organ dysfunction is crucial.

patients with persistent SIRS, particularly those who are tachypnic

Table 4. Clinical findings associated with a severe course for
and/or tachycardic, should be admitted to an intensive care unit
initial risk assessmenta
or similar unit for aggressive intravenous hydration and close
Patient characteristics monitoring.
Age > 55 years (53,57)
Obesity (BMI > 30 kg/m2) (68)
INITIAL MANAGEMENT
Altered mental status (69)
Comorbid disease (53) Recommendations
The systemic inflammatory response syndrome (SIRS) (6,53,54,70,71) 1. Aggressive hydration, defined as 250–500 ml per hour of iso-
Presence of > 2 of the following criteria: tonic crystalloid solution should be provided to all patients,
– pulse > 90 beats/min unless cardiovascular, renal, or other related comorbid
– respirations > 20/min or PaCO2 > 32 mm Hg factors exist. Early aggressive intravenous hydration is most
– temperature > 38 °C or < 36 °C
beneficial during the first 12–24 h, and may have little benefit
beyond this time period (strong recommendation, moderate
–WBC count > 12,000 or < 4,000 cells/mm3 or > 10% immature
neutrophils (bands)
2. In a patient with severe volume depletion, manifest as hypo-
Laboratory findings
tension and tachycardia, more rapid repletion (bolus) may be
BUN > 20 mg/dl (63) needed (conditional recommendation, moderate quality of
Rising BUN (63) evidence).
HCT > 44% (62) 3. Lactated Ringer’s solution may be the preferred isotonic
crystalloid replacement fluid (conditional recommendation,
Rising HCT (62)
Elevated creatinine (72)
4. Fluid requirements should be reassessed at frequent intervals
Radiology findings within 6 h of admission and for the next 24–48 h. The goal of
Pleural effusions (73) aggressive hydration should be to decrease the BUN (strong
Pulmonary infiltrates (53)
recommendation, moderate quality of evidence).
Multiple or extensive extrapancreatic collections (67)
BMI, body mass index; BUN, blood urea nitrogen; HCT, hematocrit; WBC, EARLY AGGRESSIVE INTRAVENOUS HYDRATION
white blood cell.
a
The presence of organ failure and/or pancreatic necrosis defines severe acute
Despite dozens of randomized trials, no medication has been
pancreatitis. shown to be effective in treating AP (32,53). However, an effective
intervention has been well described: early aggressive intravenous
hydration. Recommendations regarding aggressive hydration
are based on expert opinion (10,52,53), laboratory experiments
Rather than depending on a scoring system to predict severity (79,80), indirect clinical evidence (62,63,81,82), epidemiologic
of AP, clinicians need to be aware of intrinsic patient-related risk studies (59), and both retrospective and prospective clinical
factors, including laboratory and imaging risk factors, for the devel- trials (9,83).
opment of severe disease (Table 4). These include: a patient’s age, The rationale for early aggressive hydration in AP arises from
comorbid health problems, body mass index (74), the presence of observation of the frequent hypovolemia that occurs from multiple
SIRS (70,71), signs of hypovolemia such as an elevated BUN (63) factors affecting patients with AP, including vomiting, reduced oral
and an elevated hematocrit (62), presence of pleural effusions intake, third spacing of fluids, increased respiratory losses, and dia-
and/or infiltrates (73), altered mental status (69), and other factors phoresis. In addition, researchers hypothesize that a combination
(54,72) (Table 3). of microangiopathic effects and edema of the inflamed pancreas
During the early phase of the disease (within the first week), decreases blood flow, leading to increased cellular death, necro-
death occurs as a result of the development, persistence, and pro- sis, and ongoing release of pancreatic enzymes activating numer-
gressive nature of organ dysfunction (75,76). The development of ous cascades. Inflammation also increases vascular permeability,
organ failure appears to be related to the development and per- leading to increased third space fluid losses and worsening of
sistence of SIRS. The reversal of and early organ failure has been pancreatic hypoperfusion that leads to increased pancreatic
shown to be important in preventing morbidity and mortality in parenchymal necrosis and cell death (84). Early aggressive intra-
patients with AP (77,78). Although the presence of SIRS during venous fluid resuscitation provides micro- and macrocirculatory
the initial 24 h has a high sensitivity for predicting organ failure support to prevent serious complications such as pancreatic
and mortality, the presence of SIRS lacks specificity for severe dis- necrosis (10).
ease (41%). The lack of specificity is due to the fact that the pres- Although there are limited prospective data that aggressive
ence of SIRS is not as important as its persistence. For this reason, intravenous hydration can be monitored and/or guided by

8 Tenner et al.
laboratory markers, the use of hematocrit (62), BUN (63,83), ERCP IN AP

and creatinine (72) as surrogate markers for successful hydration The role of ERCP in AP is related to the management of choledo-
has been widely recommended (10,15,52,53). Although no firm cholithiasis. Although ERCP can be used to identify pancreatic
recommendations regarding absolute numbers can be made at ductal disruption in patients with severe AP, possibly leading
this time, the goal to decrease hematocrit (demonstrating hemo- to interventions for the so-called dislocated duct syndrome,
dilution) and BUN (increasing renal perfusion) and maintain a a consensus has never emerged that ERCP should be performed
normal creatinine during the first day of hospitalization cannot routinely for this purpose (52).
be overemphasized.
Although some human trials have shown a clear benefit to Recommendations
aggressive hydration (9,85,86), other studies have suggested 1. Patients with AP and concurrent acute cholangitis should
that aggressive hydration may be associated with an increased undergo ERCP within 24 h of admission (strong recommen-
morbidity and mortality (87,88). These variable study findings dation, moderate quality of evidence).
may be partly explained by critical differences in study design. 2. ERCP is not needed early in most patients with gallstone
Although these studies raise concerns about the continuous pancreatitis who lack laboratory or clinical evidence of
use of aggressive hydration over 48 h, the role of early hydra- ongoing biliary obstruction (strong recommendation,
tion (within the first 6–12 h) was not addressed in these nega- moderate quality of evidence).
tive studies. In addition, these negative studies included sicker 3. In the absence of cholangitis and/or jaundice, MRCP or
patients who would have required large volumes of hydration EUS rather than diagnostic ERCP should be used to screen
by the 48 h time point (87,88). Consistently, the human stud- for choledocholithiasis if highly suspected (conditional
ies in AP that focused on the initial rate of hydration early in recommendation, moderate quality of evidence).
the course of treatment (within the first 24 h) demonstrated a 4. Pancreatic duct stents and/or postprocedure rectal non-
decrease in both morbidity and mortality (9,85,86). Although steroidal anti-inflammatory drug (NSAID) suppositories
the total volume of hydration at 48 h after admission appears should be utilized to lower the risk of severe post-ERCP
to have little or no impact on patient outcome, early aggressive pancreatitis in high-risk patients (conditional recommenda-
intravenous hydration, during the first 12–24 h, with close moni- tion, moderate quality of evidence).
toring is of paramount importance.
In a well-designed prospective randomized trial, hydration
with a lactated Ringer’s solution appears to be more beneficial, THE ROLE OF ERCP IN AP
resulting in fewer patients developing SIRS as compared with Fortunately, most gallstones that cause AP readily pass to the
patients receiving normal (0.9%) saline (83). The benefit of duodenum and are lost in the stool (92). However in a minority
using lactated Ringer’s solution in large-volume resuscitation of patients, persistent choledocholithiasis can lead to ongoing
has been shown in other disease states to lead to better electro- pancreatic duct and/or biliary tree obstruction, leading to severe
lyte balance and improved outcomes (89,90). In AP, there are AP and/or cholangitis. Removal of obstructing gallstones from
additional theoretical benefits to using the more pH-balanced the biliary tree in patients with AP should reduce the risk of
lactated Ringer’s solution for fluid resuscitation compared with developing these complications.
normal saline. Low pH activates the trypsinogen, makes the There have been several clinical trials performed to answer the
acinar cells more susceptible to injury and increases the severity question: does early ERCP (within 24–72 h of onset) in acute bil-
of established AP in experimental studies. Although both are iary pancreatitis reduces the risk of progression of AP to severe
isotonic crystalloid solutions, normal saline given in large vol- disease (organ failure and/or necrosis)? Neoptolemos et al. (93)
umes may lead to the development of a non-anion gap, hyper- studied 121 patients with probable acute biliary pancreatitis, strati-
chloremic metabolic acidosis (83). fied for severity according to the modified Glasgow criteria. The
It is important to recognize that aggressive early hydration will trial was performed in a single center in the United Kingdom.
require caution for certain groups of patients, such as the elderly, Patients with predicted severe AP had fewer complications if they
or those with a history of cardiac and/or renal disease in order to underwent ERCP within 72 h of admission (24% vs. 61%, P < 0.05).
avoid complications such as volume overload, pulmonary edema, When patients with concurrent acute cholangitis (who would
and abdominal compartment syndrome (91). Measurement of obviously benefit from early ERCP) were excluded, the difference
the central venous pressure via a centrally placed catheter is most remained significant (15% vs. 61%, P = 0.003). Mortality was not
commonly used to determine volume status in this setting. How- significantly different in the two groups. Fan et al. (94) reported
ever, data indicate that the intrathoracic blood volume index may a study of 195 patients with suspected biliary pancreatitis strati-
have a better correlation with cardiac index than central venous fied for severity according to Ranson’s criteria. Patients in the study
pressure. Measurement of intrathoracic blood volume index may group underwent ERCP within 24 h of admission and those in the
therefore allow more accurate assessment of volume status for control group were offered conservative management. The control
patients managed in the intensive care unit. Patients not respond- group was offered ERCP if acute cholangitis developed. Those who
ing to intravenous hydration early (within 6–12 h) may not benefit underwent early ERCP had fewer complications (13% vs. 54%,
from continued aggressive hydration. P = 0.002).

Based on these studies, it was unclear whether patients with (ii) pancreatic duct stents, and (iii) rectal NSAIDs. Guidewire
severe AP in the absence of acute cholangitis benefit from early cannulation (cannulation of the bile duct and pancreatic duct
ERCP. Therefore, Folsch et al. (95) organized a multicenter study by a guidewire inserted through a catheter) decreases the risk of
of ERCP in acute biliary pancreatitis that excluded patients most pancreatitis (100) by avoiding hydrostatic injury to the pancreas
likely to benefit, namely those with a serum bilirubin > 5 mg/dl. that may occur with the use of radiocontrast agents. In a study
Thus, patients with acute cholangitis and/or obvious biliary of 400 consecutive patients randomized to contrast or guidewire
tree obstruction underwent early ERCP and were not included cannulation, there were no cases of AP in the guidewire group
in the study. This study focused on determining the benefit of as compared with 8 cases in the contrast group (P < 0.001).
early ERCP in preventing severe AP in the absence of biliary A more recent study in 300 patients prospectively randomized
obstruction. Although this study has been widely criticized for to guidewire cannulation compared with conventional contrast
design flaws and the unusually high mortality of patients with injection also found a decrease in post-ERCP pancreatitis in the
mild disease (8% compared with an expected 1%), no benefit in guidewire group (101). However, the reduction in post-ERCP
morbidity and/or mortality was seen in patients who underwent pancreatitis may not be entirely related to guidewire cannula-
early ERCP. From this study, it appears that the benefit of early tion (102) and may have been related to less need for precut
ERCP is seen in patients with AP complicated by acute cholangitis sphincterotomy in patients undergoing guidewire cannulation.
and biliary tree obstruction, but not severe AP in the absence Regardless, guidewire cannulation compared with conventional
of acute cholangitis. contrast cannulation appears to decrease the risk of severe post-
More recent studies have confirmed that early ERCP within 24 h ERCP AP (103,104).
of admission decreases morbidity and mortality in patients with Placement of a pancreatic duct stent decreases the risk of
AP complicated by biliary sepsis (96,97). A dilated biliary tree in severe post-ERCP pancreatitis in high-risk patients, such as
the absence of an elevated bilirubin and other signs of sepsis should those undergoing ampullectomy, endoscopic sphincter of Oddi
not be confused with cholangitis, but may indicate the presence manometry, or pancreatic interventions during ERCP. A 2007
of a common bile duct stone. In patients with biliary pancreatitis meta-analysis published by Andriulli et al. (105), which evalu-
who have mild disease, and in patients who improve, ERCP before ated 4 randomized, prospective trials including 268 patients,
cholecystectomy has been shown to be of limited value and may showed that pancreatic duct stent placement affords a two-
be harmful. Noninvasive imaging studies are the preferred diag- fold drop in the incidence of post-ERCP pancreatitis (24.1%
nostic modalities in these patients (EUS and/or MRCP). However, vs. 12%; P = 0.009; odds ratio: 0.44, 95% confidence interval:
it is not clear if any testing needs to be performed in patients who 0.24–0.81). Although further study is needed, smaller 3 French
improve. (Fr) unflanged pancreatic stents appear to lower the risk of
post-ERCP pancreatitis (P = 0.0043), pass more spontaneously
(P = 0.0001), and cause less pancreatic ductal changes (24% vs.
PREVENTING POST-ERCP PANCREATITIS 80%) as compared with larger 4 Fr, 5 Fr, or 6 Fr stents (106).
AP remains the most common complication of ERCP. Histori- However, 3 Fr pancreatic stent placement is more technically
cally, this complication was seen in 5–10% of cases and in 20–40% demanding because of the need to use a very floppy (0.018-inch
of certain high-risk procedures (50,98). Over the past 15 years, diameter) guidewire. Although prophylactic pancreatic duct
the risk of post-ERCP pancreatitis has decreased to 2–4% and the stenting is a cost-effective strategy for the prevention of post-
risk of severe AP to < 1/500 (50,98). In general, the decrease in ERCP pancreatitis for high-risk patients (107), a higher inci-
post-ERCP AP and severe AP is related to increased recognition dence of severe pancreatitis has been reported in patients with
of high-risk patients and high-risk procedures in which ERCP failed pancreatic duct stenting (108). Pancreatic duct stenting is
should be avoided and the application of appropriate interven- not always technically feasible, with reported failure rates rang-
tions to prevent AP and severe AP (50). ing from 4 to 10% (108). In addition, long-term complications
Patients with normal or near-normal bile duct and liver tests from pancreatic duct stenting, such as chronic pancreatitis, may
have a lower likelihood of a common bile duct stone and/or occur and further study is needed (49).
other pathology (stricture, tumor). In these patients, diagnostic Although a large number of pharmacologic interventions for
ERCP has largely been replaced by EUS or MRCP as the prophylaxis against post-ERCP pancreatitis have been studied
risk of post-ERCP pancreatitis is greater in a patient with (50), the results of the studies have been largely disappointing.
normal caliber bile duct and normal bilirubin (odds ratio 3.4 The most promising group of drugs to attenuate the inflamma-
for post-ERCP pancreatitis) as compared with a patient who tory response of AP are NSAIDs (109,110). Two clinical trials
is jaundiced with a dilated common bile duct (odds ratio 0.2 have shown that a 100 mg rectal suppository of diclofenac reduces
for post-ERCP pancreatitis) (99). Furthermore, MRCP and the incidence of post-ERCP pancreatitis (111,112). In addi-
EUS are as accurate as diagnostic ERCP and pose no risk of tion, a recent multicenter, double-blind, randomized placebo
pancreatitis (98). controlled trial of 602 patients undergoing a high-risk ERCP
For patients undergoing a therapeutic ERCP, three well-stud- demonstrated a significant reduction of post-ERCP pancreati-
ied interventions to decrease the risk of post-ERCP pancreatitis in patients given postprocedure rectal indomethacin (113).
tis, especially severe disease, include: (i) guidewire cannulation, It is important to note that this study included only patients at a

10 Tenner et al.
high risk of developing post-ERCP pancreatitis and severe AP, that may occur early in the course of AP may be indistinguishable
which is the population that would benefit the most. When from sepsis syndrome. When an infection is suspected, antibiotics
considering the costs, risks, and potential benefits reviewed should be given while the source of the infection is being inves-
in the published literature, rectal diclofenac and/or indo- tigated (53). However, once blood and other cultures are found
methacin should be considered before ERCP, especially in to be negative and no source of infection is identified, antibiotics
high-risk patients. Although further study is needed to define should be discontinued.
the optimal dose, at present it is reasonable to consider place-
ment of two indomethacin 50 mg suppositories (total 100 mg)
after ERCP in patients at a high risk of developing post-ERCP PREVENTING THE INFECTION OF STERILE
AP. However, until further study is performed, the placement of NECROSIS
rectal NSAIDs does not replace the need for a pancreatic duct The paradigm shift and controversy over using antibiotics in
stent in the appropriate high-risk patient. AP has centered on pancreatic necrosis. When compared with
patients with sterile necrosis, patients with infected pancreatic
necrosis have a higher mortality rate (mean 30%, range 14–69%)
THE ROLE OF ANTIBIOTICS IN AP (53). For this reason, preventing infection of pancreatic necrosis
is important. Although it was previously believed that infectious
Recommendations complications occur late in the course of the disease (115,116),
1. Antibiotics should be given for an extrapancreatic infection, a recent review found that 27% of all cases of infected
such as cholangitis, catheter-acquired infections, bacteremia, necrosis occur within the first 14 days (117); in another study,
urinary tract infections, pneumonia (strong recommenda- nearly half of all infections appear to occur within 7 days of
tion, moderate quality of evidence). admission (118).
2. Routine use of prophylactic antibiotics in patients with severe Although early unblinded trials suggested that administration of
AP is not recommended (strong recommendation, moderate antibiotics may prevent infectious complications in patients with
quality of evidence). sterile necrosis (119,120), subsequent, better-designed trials have
3. The use of antibiotics in patients with sterile necrosis consistently failed to confirm an advantage (121–125). Because of
to prevent the development of infected necrosis is not the consistency of pancreatic necrosis, few antibiotics penetrate
recommended (strong recommendation, moderate quality when given intravenously. The antibiotics shown to penetrate and
of evidence). used in clinical trials include carbapenems, quinolones, metro-
4. Infected necrosis should be considered in patients with nidazole, and high-dose cephalosporins (52,116,123). Since 1993,
pancreatic or extrapancreatic necrosis who deteriorate or there have been 11 prospective, randomized trials with proper
fail to improve after 7–10 days of hospitalization. In these study design, participants, and outcome measures that evaluated
patients, either (i) initial CT-guided fine-needle aspiration the use of prophylactic antibiotics in severe AP (126). From this
(FNA) for Gram stain and culture to guide use of appropriate meta-analysis, the number needed to treat was 1,429 for one patient
antibiotics or (ii) empiric use of antibiotics after obtaining to benefit. It remains uncertain if a subgroup of patients with severe
necessary cultures for infectious agents, without CT FNA, AP (such as extensive necrosis with organ failure) may benefit from
should be given (strong recommendation, moderate antibiotics, but large studies required to determine whether any
evidence). benefit exists will be difficult to perform. Based on the current liter-
5. In patients with infected necrosis, antibiotics known to pene- ature, use of prophylactic antibiotics to prevent infection in patients
trate pancreatic necrosis, such as carbapenems, quinolones, with sterile necrosis (even predicted as having severe disease) is not
and metronidazole, may be useful in delaying or sometimes recommended.
totally avoiding intervention, thus decreasing morbidity and Prevention of fungal infections in these patients is also not
mortality (conditional recommendation, moderate quality of recommended. Although it was suggested that fungal infection
evidence). may be a more common cause of mortality in AP, further study
6. Routine administration of antifungal agents along with has not confirmed this finding (127). There is one successful
prophylactic or therapeutic antibiotics is not recommended randomized controlled, clinical trial that used selective
(conditional recommendation, low quality of evidence). decontamination of the bowel, targeting both bacteria and
fungi, in order to prevent infected necrosis (128). Because of
the decreased morbidity and mortality in this trial in patients
Infectious complications with severe AP who had undergone selective decontamina-
Infectious complications, both pancreatic (infected necrosis) tion, further study in this area is needed. Finally, probiotics
and extrapancreatic (pneumonia, cholangitis, bacteremia, uri- should not be given in severe AP. Although earlier trials
nary tract infections, and so on), are a major cause of morbidity suggested a benefit, a very well-conducted, randomized con-
and mortality in patients with AP. Many infections are hospital- trolled clinical trial demonstrated increased mortality (129).
acquired and may have a major impact on mortality (114). Fever, This lack of benefit has also been shown in a recent meta-
tachycardia, tachypnea, and leukocytosis associated with SIRS analysis (130).

Infected necrosis accurate in distinguishing infected and sterile necrosis

Rather than preventing infection, the role of antibiotics in patients (53,136). As patients with infected necrosis and sterile necrosis
with necrotizing AP is now to treat established infected necro- may appear similar with leukocytosis, fever, and organ failure
sis. The concept that infected pancreatic necrosis requires prompt (137), it is impossible to separate these entities without
surgical debridement has also been challenged by multiple reports needle aspiration. Historically, the use of antibiotics is best
and case series showing that antibiotics alone can lead to resolu- established in clinically proven pancreatic or extrapancre-
tion of infection and, in select patients, avoid surgery altogether atic infection, and therefore CT FNA should be considered
(131–134). Garg et al. (134) reported 47/80 patients with infected when an infection is suspected. An immediate review of the
necrosis over a 10-year period who were successfully treated Gram stain will often establish a diagnosis. However, it may be
conservatively with antibiotics alone (134). The mortality in the prudent to begin antibiotics while awaiting microbiologic
conservative group was 23% as compared with 54% in the surgi- confirmation. If culture reports are negative, the antibiotics
cal group. The same group published a meta-analysis of 8 studies can be discontinued.
involving 409 patients with infected necrosis of whom 324 were There is some controversy as to whether a CT FNA is neces-
successfully treated with antibiotics alone (135). Overall, 64% of sary in all patients (Figure 1). In many patients, the CT FNA
the patients with infected necrosis in this meta-analysis could would not influence the management (138). Increased use of
be managed by conservative antibiotic treatment with 12% mor- conservative management and minimally invasive drainage
tality, and only 26% underwent surgery. Thus, a select group of have decreased the use of FNA for the diagnosis of infected
relatively stable patients with infected pancreatic necrosis could necrosis (54). Many patients with sterile or infected necrosis
be managed by antibiotics alone without requiring percutane- either improve quickly or become unstable, and decisions on
ous drainage. However, it should be cautioned that these patients intervention via a minimally invasive route will not be influenced
require close supervision and percutaneous or endoscopic or by the results of the aspiration. A consensus conference con-
necrosectomy should be considered if the patient fails to improve cluded that FNA should only be used in select situations where
or deteriorates clinically. there is no clinical response to antibiotics, such as when a fungal
infection is suspected (54).
THE ROLE OF CT FNA

The technique of computed tomography guided fine needle NUTRITION IN AP
aspiration (CT FNA) has proven to be safe, effective, and
Recommendations
1. In mild AP, oral feedings can be started immediately if there
Pancreatic necrosis: suspected of infection is no nausea and vomiting, and the abdominal pain has
resolved (conditional recommendation, moderate quality of
evidence).
Obtain CT-guided FNA Empiric use of necrosis 2. In mild AP, initiation of feeding with a low-fat solid diet
penetrating antibiotics
Negative gram stain
appears as safe as a clear liquid diet (conditional recommen-
and culture Positive gram dations, moderate quality of evidence).
stain and/or culture
3. In severe AP, enteral nutrition is recommended to prevent
STERILE NECROSIS: supportive
care, consider repeat FNA every 5–7 infectious complications. Parenteral nutrition should
Infected necrosis
days if clinically indicated be avoided, unless the enteral route is not available,
not tolerated, or not meeting caloric requirements
Clinically stable (strong recommendation, high quality of evidence).
Clinically unstable
Continue antibiotics and observe… 4. Nasogastric delivery and nasojejunal delivery of enteral
Prompt surgical
delayed minimally invasive surgical,
debridement
feeding appear comparable in efficacy and safety (strong
endoscopic, or radiologic debridement.
if asymptomatic: consider no debridement recommendation, moderate quality of evidence).
Figure 1. Management of pancreatic necrosis when infection is suspected.

Infected necrosis should be considered in patients with pancreatic or
SUMMARY OF EVIDENCE
extrapancreatic necrosis who deteriorate or fail to improve after 7–10 days
of hospitalization. In these patients, either (i) initial computed tomography-
Nutrition in mild AP
guided fine needle aspiration (CT FNA) for Gram stain and culture to guide Historically, despite the absence of clinical data, patients with AP
use of appropriate antibiotics or (ii) empiric use of antibiotics without CT were kept NPO (nothing by mouth) to rest the pancreas (32).
FNA should be given. In patients with infected necrosis, antibiotics known Most guidelines in the past recommended NPO until resolution
to penetrate pancreatic necrosis may be useful in delaying intervention,
of pain and some suggested awaiting normalization of pancre-
thus decreasing morbidity and mortality. In stable patients with infected
necrosis, surgical, radiologic, and/or endoscopic drainage should be
atic enzymes or even imaging evidence of resolution of inflam-
delayed by preferably 4 weeks to allow the development of a wall around mation before resuming oral feedings (53). The need to place
the necrosis (walled-off pancreatic necrosis). the pancreas at rest until complete resolution of AP no longer

12 Tenner et al.
seems imperative. The long-held assumption that the inflamed patients because of significant experimental and some human
pancreas requires prolonged rest by fasting does not appear to evidence of superiority of distal jejunal feeding in AP.
be supported by laboratory and clinical observation (139). Clini-
cal and experimental studies showed that bowel rest is associated
with intestinal mucosal atrophy and increased infectious compli- THE ROLE OF SURGERY IN AP
cations because of bacterial translocation from the gut. Multiple
studies have shown that patients provided oral feeding early in Recommendations
the course of AP have a shorter hospital stay, decreased infec- 1. In patients with mild AP, found to have gallstones in the
tious complications, decreased morbidity, and decreased mortal- gallbladder, a cholecystectomy should be performed
ity (117,140–143). before discharge to prevent a recurrence of AP (moderate
In mild AP, oral intake is usually restored quickly and no nutri- recommendation, moderate quality of evidence).
tional intervention is needed. Although the timing of refeeding 2. In a patient with necrotizing biliary AP, in order to prevent
remains controversial, recent studies have shown that immediate infection, cholecystectomy is to be deferred until active
oral feeding in patients with mild AP appears safe (139). In addi- inflammation subsides and fluid collections resolve or
tion, a low-fat solid diet has been shown to be safe compared with stabilize (strong recommendation, moderate evidence).
clear liquids, providing more calories (144). Similarly, in other 3. Asymptomatic pseudocysts and pancreatic and/or extra-
randomized trials, oral feeding with a soft diet has been found to pancreatic necrosis do not warrant intervention regardless of
be safe compared with clear liquids and it shortens the hospital size, location, and/or extension (moderate recommendation,
stay (145,146). Early refeeding also appears to result in a shorter high quality of evidence).
hospital stay. Based on these studies, oral feedings introduced in 4. In stable patients with infected necrosis, surgical, radiologic,
mild AP do not need to begin with clear liquids and increase in a and/or endoscopic drainage should be delayed preferably
stepwise manner, but may begin as a low-residue, low-fat, soft diet for more than 4 weeks to allow liquefication of the contents
when the patient appears to be improving. and the development of a fibrous wall around the necrosis
Total parenteral nutrition should be avoided in patients with (walled-off necrosis) (strong recommendation, low quality
mild and severe AP. There have been multiple randomized trials of evidence).
showing that total parenteral nutrition is associated with infectious 5. In symptomatic patients with infected necrosis, minimally
and other line-related complications (53). As enteral feeding main- invasive methods of necrosectomy are preferred to open necro-
tains the gut mucosal barrier, prevents disruption, and prevents sectomy (strong recommendation, low quality of evidence).
the translocation of bacteria that seed pancreatic necrosis, enteral
nutrition may prevent infected necrosis (142,143). A recent meta-
analysis describing 8 randomized controlled clinical trials involv- SUMMARY OF EVIDENCE
ing 381 patients found a decrease in infectious complications, Cholecystectomy
organ failure, and mortality in patients with severe AP who were In patients with mild gallstone pancreatitis, cholecystectomy
provided enteral nutrition as compared with total parenteral nutri- should be performed during the index hospitalization. The cur-
tion (143). Although further study is needed, continuous infusion rent literature, which includes 8 cohort studies and one rando-
is preferred over cyclic or bolus administration. mized trial describing 998 patients who had and who had not
Although the use of a nasojejunal route has been traditionally undergone cholecystectomy for biliary pancreatitis, 95 (18%)
preferred to avoid the gastric phase of stimulation, nasogastric were readmitted for recurrent biliary events within 90 days of
enteral nutrition appears as safe. A systematic review describ- discharge (0% vs. 18%, P < 0.0001), including recurrent biliary
ing 92 patients from 4 studies on nasogastric tube feeding found pancreatitis (n = 43, 8%) (148). Some of the cases were found
that nasogastric feeding was safe and well tolerated in patients to be severe. Based on this experience, there is a need for early
with predicted severe AP (117). There have been some reports of cholecystectomy during the same hospitalization, if the attack
nasogastric feeding slightly increasing the risk of aspiration. For is mild. Patients who have severe AP, especially with pancre-
this reason, patients with AP undergoing enteral nutrition should atic necrosis, will require complex decision making between the
be placed in a more upright position and be placed on aspiration surgeon and gastroenterologist. In these patients, cholecystec-
precautions. Although further study is needed, evaluating for tomy is typically delayed until (i) a later time in the typically
“residuals,” retained volume in the stomach, is not likely to be help- prolonged hospitalization, (ii) as part of the management of the
ful. Compared with nasojejunal feeding, nasogastric tube place- pancreatic necrosis if present, or (iii) after discharge (148,149).
ment is far easier, which is important in patients with AP, especially Earlier guidelines recommended a cholecystectomy after 2 attacks
in the intensive care setting. Nasojejunal tube placement requires of IAP, with a presumption that many such cases might be because
interventional radiology or endoscopy and thus can be expensive. of microlithiasis. However, a population-based study found that
For these reasons, nasogastric tube feeding should be preferred cholecystectomy performed for recurrent attacks of AP with
(147). A large multicenter trial sponsored by the National Insti- no stones/sludge on ultrasound and no significant elevation of
tutes of Health (NIH) is currently being performed to investigate liver tests during the attack of AP was associated with a > 50%
whether nasogastric or nasojejunal feedings are preferred in these recurrence of AP (150).

In the majority of patients with gallstone pancreatitis, the If the patient remains ill and the infected necrosis has not resolved,
common bile duct stone passes to the duodenum. Routine ERCP minimally invasive necrosectomy by endoscopic, radiologic,
is not appropriate unless there is a high suspicion of a persis- video-assisted retroperitoneal, laparoscopic approach, or com-
tent common bile duct stone, manifested by an elevation in the bination thereof, or open surgery is recommended once the
bilirubin (151). Patients with mild AP, with normal bilirubin, necrosis is walled-off (54,153–156).
can undergo laproscopic cholecystectomy with intraoperative
cholangiography, and any remaining bile duct stones can be dealt
with by postoperative or intraoperative ERCP. In patients with MINIMALLY INVASIVE MANAGEMENT OF
low to moderate risk, MRCP or EUS can be used preoperatively, PANCREATIC NECROSIS
but routine use of MRCP is unnecessary. In patients with mild Minimally invasive approaches to pancreatic necrosectomy
AP who cannot undergo surgery, such as the frail elderly and/or including laproscopic surgery either from an anterior or retro-
those with severe comorbid disease, biliary sphincterotomy alone peritoneal approach, percutaneous, radiologic catheter drain-
may be an effective way to reduce further attacks of AP, although age or debridement, video-assisted or small incision-based left
attacks of cholecystitis may still occur (53). retroperitoneal debridement, and endoscopy are increasingly
becoming the standard of care. Percutaneous drainage without
necrosectomy may be the most frequently used minimally inva-
DEBRIDEMENT OF NECROSIS sive method for managing fluid collections complicating necro-
Historically, open necrosectomy/debridement was the treatment tizing AP (54,68,148,152–157). The overall success appears to be
of choice for infected necrosis and symptomatic sterile necrosis. ~50% in avoiding open surgery. In addition, endoscopic drainage
Decades ago, patients with sterile necrosis underwent early debri- of necrotic collections and/or direct endoscopic necrosectomy
dement that resulted in increased mortality. For this reason, early has been reported in several large series to be equally successful
open debridement for sterile necrosis was abandoned (32). How- (53,54,155). Sometimes these modalities can be combined at the
ever, debridement for sterile necrosis is recommended if associ- same time or sequentially, for example, combined percutaneous
ated with gastric outlet obstruction and/or bile duct obstruction. and endoscopic methods. Recently, a well-designed study from
In patients with infected necrosis, it was falsely believed that the Netherlands using a step-up approach (percutaneous catheter
mortality of infected necrosis was nearly 100% if debridement drainage followed by video-assisted retroperitoneal debridement)
was not performed urgently (53,152). In a retrospective review (68,156) demonstrated the superiority of the step-up approach
of 53 patients with infected necrosis treated operatively (median as reflected by lower morbidity (less multiple organ failure and
time to surgery of 28 days) mortality fell to 22% when necrosec- surgical complications) and lower costs compared with open
tomy necrosis was delayed (118). After reviewing 11 studies that surgical necrosectomy.
included 1,136 patients, the authors found that postponing necro- Although these guidelines cannot discuss in detail the various
sectomy in stable patients treated with antibiotics alone until 30 methods of debridement, or the comparative effectiveness of each,
days after initial hospital admission is associated with a decreased because of limitations in available data and the focus of this review,
mortality (131). several generalizations are important. Regardless of the method
The concept that infected pancreatic necrosis requires prompt employed, minimally invasive approaches require the pancreatic
surgical debridement has also been challenged by multiple reports necrosis to become organized (54,68,154–157). Whereas early in
and case series showing that antibiotics alone can lead to resolu- the course of the disease (within the first 7–10 days) pancreatic
tion of infection and, in select patients, avoid surgery altogether necrosis is a diffuse solid and/or semisolid inflammatory mass,
(6,54). In one report (133) of 28 patients given antibiotics for the after ~4 weeks a fibrous wall develops around the necrosis that
management of infected pancreatic necrosis, 16 avoided surgery. makes removal more amenable to open and laproscopic surgery,
There were two deaths in the patients who underwent surgery and percutaneous radiologic catheter drainage, and/or endoscopic
two deaths in the patients who were treated with antibiotics alone. drainage.
Thus, in this report, more than half the patients were successfully Currently, a multidisciplinary consensus favors minimally inva-
treated with antibiotics and the mortality rate in both the surgi- sive methods over open surgery for the management of pancreatic
cal and nonsurgical groups was similar. The concept that urgent necrosis (54). A recent randomized controlled trial clearly dem-
surgery is required in patients found to have infected necrosis is onstrated the superiority of endoscopic debridement over surgery
no longer valid. Asymptomatic pancreatic and/or extrapancreatic (154). Although advances in surgical, radiologic, and endoscopic
necrosis does not mandate intervention regardless of size, location, techniques exist and are in development, it must be stressed that
and extension. It will likely resolve over time, even in some cases of many patients with sterile pancreatic necrosis, and select patients
infected necrosis (54). with infected necrosis, clinically improve to a point where no
Although unstable patients with infected necrosis should intervention is necessary (54,134). The management of patients
undergo urgent debridement, current consensus is that the initial with pancreatic necrosis should be individualized, requiring con-
management of infected necrosis for patients who are clinically sideration of all the available data (clinical, radiologic, laboratory)
stable should be a course of antibiotics before intervention to and using available expertise. Early referral to a center of excel-
allow the inflammatory reaction to become better organized (54). lence is of paramount importance, as delaying intervention with

14 Tenner et al.
maximal supportive care and using a minimally invasive approach 25. Lankisch PG, Assmus C, Lehnick D et al. Acute pancreatitis: does gender
matter? Dig Dis Sci 2001;46:2470–4.
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countries: etiology and mortality. Pancreas 2002;24:223–7.
CONFLICT OF INTEREST 27. Lowenfels AB, Maisonneuve P, Sullivan T. The changing character of acute
pancreatitis: epidemiology, etiology, and prognosis. Curr Gastroenterol Rep
Guarantor of the article: Scott Tenner, MD, MPH, FACG.
2009;11:97–103.
Specific author contributions: All four authors shared equally in 28. Johnson C, Lévy P. Detection of gallstones in acute pancreatitis: when and
conceiving, initiating, and writing the manuscript. how? Pancreatology 2010;10:27–32.
29. Moreau JA, Zinsmeister AR, Melton LJ et al. Gallstone pancreatitis and the
Financial support: None.
effect of cholecystectomy. Mayo Clin Proc 63;466:1988.
Potential competing interests: None. 30. Yadav D, O’Connell M, Papachristou GI. Natural history following the first
attack of acute pancreatitis. Am J Gastroenterol 2012;107:1096–103.
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PRACTICAL GUIDELINES
V FOR ACUTE
PANCREATITIS
ПРАКТИЧЕСКИЕ РЕКОМЕНДАЦИИ ПО ЛЕЧЕНИЮ ОСТРОГО ПАНКРЕАТИТА
65
(PRACTICAL GUIDELINES FOR ACUTE PANCREATITIS)
67
69
71
73
75
ACR APPROPRIATENESS
VI CRITERIA® ACUTE
PANCREATITIS
Guideline Summary NGC-10143
Guideline Title
Guideline Summary NGC-10143
ACR Appropriateness Criteria® acute pancreatitis.
Bibliographic
Guideline TitleSource(s)
ACR Appropriateness
Baker ME, Nelson RC, Criteria®
Rosenacute
MP, pancreatitis.
Blake MA, Cash BD, Hindman NM, Kamel IR, Kaur H,
Piorkowski RJ, Qayyum A, Yarmish GM, Expert Panel on Gastrointestinal Imaging. ACR
Bibliographic Source(s)
Appropriateness Criteria® acute pancreatitis. [online publication]. Reston (VA): American College
of Radiology (ACR);
Baker ME, Nelson RC, 2013.Rosen
11 p. [45
MP,references]
Blake MA, Cash BD, Hindman NM, Kamel IR, Kaur H,
Piorkowski
Guideline RJ, Qayyum A, Yarmish GM, Expert Panel on Gastrointestinal Imaging. ACR
Status
Appropriateness Criteria®
This is the current release acute
of the pancreatitis. [online publication]. Reston (VA): American College
guideline.
of Radiology (ACR); 2013. 11 p. [45 references]
This guideline updates a previous version: Macari M, Rosen MP, Blake MA, Baker ME, Cash BD,
Guideline Status FL, Jones B, Katz DS, Lalani T, Miller FH, Small WC, Sudakoff GS, Yee J, Expert
Fidler JL, Greene
This
Panel on current
is the release of the
Gastrointestinal guideline.
Imaging. ACR Appropriateness Criteria® acute pancreatitis. [online
publication]. Reston (VA): American College
This guideline updates a previous version: Macari of Radiology (ACR);
M, Rosen MP,2010.
Blake6 p.
MA, Baker ME, Cash BD,
Fidler JL, Greene FL, Jones B, Katz DS, Lalani T, Miller FH, Small WC, Sudakoff GS, Yee J, Expert
Panel on Gastrointestinal Imaging. ACR Appropriateness Criteria® acute pancreatitis. [online
Scope
publication]. Reston (VA): American College of Radiology (ACR); 2010. 6 p.
Disease/Condition(s)
Acute pancreatitis
Scope
Guideline Category
Disease/Condition(s)
Diagnosis
Acute pancreatitis
Evaluation
Guideline Category
Clinical Specialty
Diagnosis
Emergency Medicine
Evaluation
Family Practice
Clinical Specialty
Gastroenterology
Internal
Emergency Medicine
Medicine
Radiology
Family Practice
Surgery
Gastroenterology
Intended
Internal Users
Medicine
Radiology
Health Plans
Surgery
Hospitals
Intended
Managed Users
Care Organizations
Physicians
Health Plans
Utilization
Hospitals Management
Managed Care Organizations
Physicians
Utilization Management
ACR КРИТЕРИИ ОСТРОГО ПАНКРЕАТИТА
79
(ACR APPROPRIATENESS CRITERIA® ACUTE PANCREATITIS)
Guideline Objective(s)
To evaluate the appropriateness of initial radiologic examinations for patients with suspected or known
acute pancreatitis
Target Population
Patients with suspected or known acute pancreatitis
Interventions and Practices Considered
1. Ultrasound (US) abdomen
2. Computed tomography (CT) abdomen
• With contrast
• Without contrast
• Without and with contrast
3. Magnetic resonance imaging (MRI) abdomen
• Without contrast with magnetic resonance cholangiopancreatography (MRCP)
• Without (including MRCP) and with contrast
Major Outcomes Considered
• Morbidity
• Mortality
• Utility of radiologic examinations in differential diagnosis
Methodology
Methods Used to Collect/Select the Evidence
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence
Literature Search Procedure
Staff will search in PubMed only for peer reviewed medical literature for routine searches. Any article or
guideline may be used by the author in the narrative but those materials may have been identified
outside of the routine literature search process.
The Medline literature search is based on keywords provided by the topic author. The two general
classes of keywords are those related to the condition (e.g., ankle pain, fever) and those that describe the
diagnostic or therapeutic intervention of interest (e.g., mammography, MRI).
The search terms and parameters are manipulated to produce the most relevant, current evidence to
address the American College of Radiology Appropriateness Criteria (ACR AC) topic being reviewed or
developed. Combining the clinical conditions and diagnostic modalities or therapeutic procedures
narrows the search to be relevant to the topic. Exploding the term "diagnostic imaging" captures relevant
results for diagnostic topics.
The following criteria/limits are used in the searches.
1. Articles that have abstracts available and are concerned with humans.
2. Restrict the search to the year prior to the last topic update or in some cases the author of the topic
may specify which year range to use in the search. For new topics, the year range is restricted to the
last 10 years unless the topic author provides other instructions.
3. May restrict the search to Adults only or Pediatrics only.
4. Articles consisting of only summaries or case reports are often excluded from final results.
5. The search strategy may be revised to improve the output as needed.
Number of Source Documents

The total number of source documents identified as the result of the literature search is not known.
Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence
Strength of Evidence Key
Category 1 - The conclusions of the study are valid and strongly supported by study design, analysis and
results.
Category 2 - The conclusions of the study are likely valid, but study design does not permit certainty.
Category 3 - The conclusions of the study may be valid but the evidence supporting the conclusions is
inconclusive or equivocal.
Category 4 - The conclusions of the study may not be valid because the evidence may not be reliable
given the study design or analysis.
Methods Used to Analyze the Evidence
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence
The topic author drafts or revises the narrative text summarizing the evidence found in the literature.
American College of Radiology (ACR) staff draft an evidence table based on the analysis of the selected
literature. These tables rate the strength of the evidence (study quality) for each article included in the
narrative text.
The expert panel reviews the narrative text, evidence table, and the supporting literature for each of the
topic-variant combinations and assigns an appropriateness rating for each procedure listed in the table.
Each individual panel member assigns a rating based on his/her interpretation of the available evidence.
More information about the evidence table development process can be found in the ACR
Appropriateness Criteria® Evidence Table Development document (see the "Availability of Companion
Documents" field).
Methods Used to Formulate the Recommendations
Expert Consensus (Delphi)
Description of Methods Used to Formulate the Recommendations
Rating Appropriateness
The appropriateness ratings for each of the procedures included in the Appropriateness Criteria topics
are determined using a modified Delphi methodology. A series of surveys are conducted to elicit each
panelist's expert interpretation of the evidence, based on the available data, regarding the appropriateness
of an imaging or therapeutic procedure for a specific clinical scenario. American College of Radiology
(ACR) staff distribute surveys to the panelists along with the evidence table and narrative. Each panelist
interprets the available evidence and rates each procedure. The surveys are completed by panelists
without consulting other panelists. The appropriateness rating scale is an ordinal scale that uses integers
from 1 to 9 grouped into three categories: 1, 2, or 3 are in the category "usually not appropriate"; 4, 5, or
6 are in the category "may be appropriate"; and 7, 8, or 9 are in the category "usually appropriate." Each
panel member assigns one rating for each procedure for a clinical scenario. The ratings assigned by each
panel member are presented in a table displaying the frequency distribution of the ratings without
identifying which members provided any particular rating.
If consensus is reached, the median rating is assigned as the panel's final recommendation/rating.
Consensus is defined as eighty percent (80%) agreement within a rating category. A maximum of three
81
rounds may be conducted to reach consensus. Consensus among the panel members must be achieved to
determine the final rating for each procedure.
If consensus is not reached, the panel is convened by conference call. The strengths and weaknesses of
each imaging procedure that has not reached consensus are discussed and a final rating is proposed. If
the panelists on the call agree, the rating is proposed as the panel's consensus. The document is
circulated to all the panelists to make the final determination. If consensus cannot be reached on the call
or when the document is circulated, "No consensus" appears in the rating column and the reasons for this
decision are added to the comment sections.
This modified Delphi method enables each panelist to express individual interpretations of the evidence
and his or her expert opinion without excessive influence from fellow panelists in a simple, standardized
and economical process. A more detailed explanation of the complete process can be found in additional
methodology documents found on the ACR Web site (see also the "Availability of Companion
Documents" field).
Rating Scheme for the Strength of the Recommendations
Not applicable
Cost Analysis
A formal cost analysis was not performed and published cost analyses were not reviewed.
Method of Guideline Validation
Internal Peer Review
Description of Method of Guideline Validation
Criteria developed by the Expert Panels are reviewed by the American College of Radiology (ACR)
Committee on Appropriateness Criteria.
Recommendations
Major Recommendations
ACR Appropriateness Criteria®
Clinical Condition: Acute Pancreatitis
Variant 1: First time presentation, typical abdominal pain, and increased amylase and lipase with
high clinical certainty of diagnosis; <48–72 hours after onset of symptoms; clinical score
irrelevant; unknown cause.
Radiologic Procedure Rating Comments RRL*

US abdomen 9 This is essential to assess for O
gallstones with the first episode of
acute pancreatitis; secondarily, it can
be used to assess for
choledocholithiasis.
CT abdomen with contrast 4 Select this only if US is nondiagnostic
because of obesity, gas, etc. See
variant 4 for use in equivocal or
uncertain cases; results generally do
not alter initial management; it can
miss or underestimate necrosis.
MRI abdomen without 4 This is useful if US is nondiagnostic or O
contrast with MRCP choledocholithiasis is suspected;

generally, it is not used at initial
presentation.
MRI abdomen without 4 O
(including MRCP) and with
contrast
CT abdomen without 3 Select this only if iodinated contrast
contrast cannot be administered and if MR is
not possible.
CT abdomen without and 3

with contrast
Rating Scale: 1,2,3 Usually not appropriate; 4,5,6 May be appropriate; 7,8,9 Usually *Relative
appropriate Radiation
Level
Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.
Variant 2: Critically ill, SIRS, severe clinical scores (e.g., acute physiology and chronic health
evaluation [APACHE], bedside index of severity in acute pancreatitis score [BISAPS], and/or
Marshall); >48–72 hours after onset of symptoms.

CT abdomen with contrast 8 This is the single best, most practical
examination.
MRI abdomen without 7 This is a reasonable alternative to CT O

(including MRCP) and with abdomen with contrast, but it is not as
contrast practical or easy to perform in
critically ill patients.
MRI abdomen without 6 If AKI exists, this is preferred over CT O
contrast with MRCP abdomen without contrast.
US abdomen 6 O
CT abdomen without 5 Select this only if rapid examination is
contrast needed, if MR is not practical or
possible, and if iodinated contrast is
contraindicated.
CT abdomen without and 4 Without contrast portion of
with contrast examination, this is generally not
necessary.
Level
83
Variant 3: Continued SIRS, severe clinical scores, leukocytosis, and fever; >7–21 days after onset
of symptoms.

CT abdomen with contrast 9
CT abdomen without and 7 There may be reasons for a

with contrast noncontrast portion of examination,
but it is generally not necessary.
MRI abdomen without 7 This is a reasonable alternative to CT O

(including MRCP) and with but not as practical or easy to perform
contrast on acutely ill patients.
CT abdomen without 6 Select this only if rapid examination is
contrast needed, if MR is not practical or
possible, and if iodinated contrast is
contraindicated.
MRI abdomen without 6 O
contrast with MRCP
US abdomen 5 O
Level
Variant 4: Initial presentation with atypical signs and symptoms, including equivocal amylase and
lipase values (possibly confounded by AKI or chronic kidney disease) and when diagnoses other
than pancreatitis may be possible (bowel perforation, bowel ischemia, etc).

CT abdomen with contrast 8 This is overall the best survey for
equivocal or uncertain presentations
when other diagnoses are possible.
CT abdomen without 7 This is a reasonable, rapid examination

contrast if contrast administration is not
possible or safe.
MRI abdomen without 6 This may not be as efficacious as CT, O

(including MRCP) and with especially if bowel ischemia is in the
contrast differential diagnosis.
with contrast
MRI abdomen without 5 The addition of contrast is preferred; O

contrast with MRCP this has a limited role in equivocal
cases without contrast.
US abdomen 5 This is not a generalized survey; it is O
more focused on the right upper
quadrant.
Level
Variant 5: Known necrotizing pancreatic and peripancreatic pancreatitis, significant deterioration
in clinical status, including abrupt decrease in hemoglobin/hematocrit, hypotension, tachycardia,
tachypnea, abrupt change in fever curve, or increase in white blood cells; time after symptom
onset irrelevant.

CT abdomen with contrast 9 This is the single best, most practical
examination.
CT abdomen without 7 This is a reasonable, rapid examination

contrast if contrast administration is not
possible or safe.
MRI abdomen without 6 This is not as rapid or practical as CT; O

(including MRCP) and with it is more difficult to perform in
contrast acutely ill patients.
MRI abdomen without 6 This examination is more limited O
contrast with MRCP without intravenous contrast
enhancement.
with contrast
US abdomen 5 O
Level
Summary of Literature Review
Introduction/Background
The focus of this document is on the diagnosis and subsequent assessment of patients with suspected or
85
known acute pancreatitis. The proposed guidelines are based on the severity, timing, and natural history
of the disease and emphasize the role of imaging in patients with this disease. Although the document
does not focus on image-guided intervention or the specifics of the imaging findings, these aspects are
mentioned as they are essential in the image-centric approach to the disease.
An estimated 210,000 admissions for acute pancreatitis occur each year in the United States. Acute
pancreatitis is clinically described as nonsevere (or mild) and severe. Nonsevere pancreatitis is generally
seen only in interstitial edematous pancreatitis, and severe pancreatitis is generally seen only in
necrotizing pancreatitis, including glandular and peripancreatic fat necrosis. Interstitial edematous
pancreatitis is severe in only 1% to 3% of patients.
The Atlanta Classification by the Acute Pancreatitis Classification Working Group recently modified the
terminology for the clinical course and the morphologic changes identified on imaging, primarily
contrast-enhanced multidetector computed tomography (MDCT). The 2 distinct clinical courses of the
disease are classified as (1) early phase, which lasts approximately 1 week, and (2) late phase, which
starts after the first week and can last for months after the initial episode. The timing of imaging,
primarily contrast-enhanced MDCT, is based on the clinical phases and is, therefore, important for these
imaging guidelines. During the early phase of the disease, patient care is supportive and independent of
imaging findings. Clinical scoring methods that can be easily performed and validated are used to
facilitate patient care independent of imaging (as referenced). The modified terminology is based on
changes in the pancreatic parenchyma vis-à-vis enhancement as well as fluid collections associated with
pancreatitis. The reclassification of the clinical course and terminology for the morphological changes
emphasizes both the timing and importance of imaging.
Determinants of the natural course of acute pancreatitis are multisystem organ failure, pancreatic
parenchymal necrosis, extrapancreatic mesenteric and/or peripancreatic, retroperitoneal fatty tissue
necrosis, biologically active compounds in pancreatic ascites, infection of necrosis, and clinical factors
including age and obesity. Early in the course of acute pancreatitis, multiple organ failure can result
from inflammatory mediators released in the inflammatory process from activated leukocytes attracted
by pancreatic injury; this is also known as systemic inflammatory response syndrome (SIRS). Local and
systemic septic complications can occur at least 1 week after presentation.
Pancreatic inflammation may result in enlargement of the pancreas, peripancreatic inflammation with or
without fluid, solitary or loculated fluid collections, vascular compromise of adjacent arteries and veins,
necrosis of pancreatic parenchyma, necrosis of peripancreatic fat, and subsequent infection in any of
these inflammation sites. Distant organ complications can lead to organ failure, protracted course, and
death. Clinical scoring systems and imaging findings are used to predict these complications in patients.
Clinical scoring systems are very useful in assessing SIRS and organ failure, especially in patients with
early presentation of acute pancreatitis. SIRS is defined by a pulse >90 beats per minute, respiration >20
per minute or partial pressure of arterial carbon dioxide (PaCO2) <32 mm Hg, temperature >100.4ºF or
<96.8ºF, and a white blood cell count >12,000 or <4,000 cells/mm3. Commonly used scoring systems
include acute physiology and chronic health evaluation (APACHE), Marshall, and the bedside index of
severity in acute pancreatitis, which evaluates blood urea nitrogen, impaired mental status, SIRS, age,
and pleural effusion (BISAP). Systemic complications contribute substantially to early morbidity and
mortality associated with acute severe pancreatitis. Other laboratory values have been helpful in
assessing the severity of pancreatitis, including the hemoglobin level. High levels suggest
hemoconcentration and have been associated with third spacing of fluids and adverse outcomes.
Acute pancreatitis is suspected in patients presenting with epigastric and acute-onset upper abdominal
pain that increases rapidly in severity and persists without relief. The intensity of the pain almost always
results in the patient seeking medical attention. Differential diagnosis includes mesenteric ischemia,
perforated ulcer, intestinal obstruction, biliary colic, and myocardial infarction, among others. Serum
amylase and/or lipase are used in diagnosing acute pancreatitis; levels are considered diagnostic when
the reported value(s) is ≥3 times normal. The serum lipase level tends to remain elevated longer than the
amylase level does, however both levels tend to normalize over time. Serum enzyme levels do not
correlate with the severity of the disease. Consequently, clinical scoring systems and imaging tests have
been advocated to classify patients in terms of severity. Furthermore, the diagnosis may be overlooked if
the typical enzyme elevation is absent. Some patients with acute pancreatitis have no enzyme
abnormalities. As a result, there is growing acceptance that a diagnosis of acute pancreatitis now
requires 2 of the following 3 features: (1) abdominal pain characteristic of pancreatitis, (2) serum
amylase and/or lipase level ≥3 times normal, and (3) characteristic imaging findings on CT. In many
cases of acute pancreatitis, presenting with characteristic abdominal pain and appropriately elevated
amylase and/or lipase, early enhanced CT is performed, regardless of whether the criteria for diagnosis
have been met (see information for timing of imaging as follows). The justification for early scanning in
these cases is weak and should be questioned (again, see as follows).
An important aspect of imaging patients with acute pancreatitis is to consider causes other than
gallstones and alcohol. When patients have presented with idiopathic acute pancreatitis, the differential
diagnosis should include ductal adenocarcinoma and intraductal, papillary mucinous neoplasms, both
main ductal and side-branch. This is particularly important in patients who have had multiple episodes of
idiopathic, acute pancreatitis. Assessing for these entities is often reserved for follow-up imaging after
the pancreatic and peripancreatic changes have resolved. Nonetheless, neoplastic causes of acute
pancreatitis must be considered in the initial evaluation, even when gallstones and alcohol are not
etiologic agents.
Overview of Imaging Modalities
MDCT and scoring systems related to CT have been the most studied imaging tests used for evaluating
patients with acute pancreatitis. However, other imaging tests can be used, including transabdominal
ultrasound (US), endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and magnetic
resonance cholangiopancreatography (MRCP). In patients with pancreatitis, imaging tests are performed
for various reasons, including the detection of gallstones, detection of biliary obstruction, diagnosis of
pancreatitis when the clinical situation is unclear, and detection and classification of the severity of the
process and its complications.
Computed Tomography
MDCT is the primary imaging technique used to determine the extent of disease in patients suspected of
having acute pancreatitis to determine the extent of disease. CT can demonstrate morphological changes
in the pancreas, confirm pancreatitis, and assess the severity of the disease. It is the only imaging
modality that has consistently shown clinical value in predicting the severity of the disease as well as
clinical outcomes. The CT severity index (CTSI), in conjunction with other clinical scoring systems, is
the basis for decision making related to patient care. Patients with low CTSI have low morbidity and
mortality rates and can be safely triaged out of intensive care. The CTSI is based on (1) assessed
changes in the pancreas, (2) associated acute fluid collections, and (3) the presence and amount of
pancreatic necrosis (see Table 1 in the original guideline document).
Patients receive an overall score based on the CT grade and a score based on the presence and amount of
necrosis. Scores ranging from 0–10 are possible. Patients with increased CTSI scores have been shown
to have increased morbidity and mortality. Multiple studies have confirmed the use of CTSI in assessing
patient outcomes.
A modified CTSI has been proposed. This scoring system adds extrapancreatic findings (i.e., pleural
effusions, ascites, etc); reduces the classification of necrosis to none, <30% and >30%; and simplifies
the scoring of peripancreatic changes. A recent investigation showed no significant differences between
the modified CT index and CTSI in assessing acute pancreatitis severity. It also reported that both
indexes detect clinically severe disease more accurately, when compared with APACHE II.
Pancreatic necrosis is defined as focal or diffuse areas of hypoenhancing or nonenhancing pancreatic
parenchyma after the administration of intravenous (IV) contrast material. The degree of necrosis is
87
generally graded qualitatively as <30%, 30% to 50%, and >50%. To assess for possible pancreatic
necrosis, IV contrast needs to be administered. There has been some controversy about IV contrast
because it has been shown to impair microcirculation of the pancreas in rats that have acute necrotizing
pancreatitis and to increase the severity of the disease. These results, however, could not be reproduced
in the opossum. No prospective human trials have been published to date. Most experts believe the
benefits of detecting necrosis outweigh any theoretical risk. An advantage of CT over clinical scoring
systems (e.g., Ranson and APACHE II) is its direct visualization of the pancreas and the damage to the
pancreas. In addition, with CT it is easy to see the retroperitoneum and associated fluid collections.
Many factors contribute to determining the best time to perform CT in patients with acute pancreatitis.
In patients presenting with abdominal pain and elevated pancreatic enzymes, the pancreas may be
entirely normal, a so-called Balthazar Grade A. In these patients, the course of the disease tends to be
very mild, with little morbidity and no mortality, and CT will have no effect on patient management or
outcome. If CT is performed immediately after the initial event, pancreatic necrosis could be
underestimated or missed entirely. Thus, the initial CT will not accurately assess the presence or extent
of the most important finding: glandular or peripancreatic fat necrosis.
However, in patients presenting with severe abdominal pain atypical for acute pancreatitis and/or when
the amylase and lipase levels are equivocal, such as with acute kidney injury (AKI) or chronic kidney
disease (CKD), an immediate CT may be useful in detecting the disease or alternative diagnoses, such as
bowel ischemia.
In a recent study of a relatively large cohort of patients with acute pancreatitis, in whom enhanced CT
was performed on admission, while the Balthazar grading system (any CT technique) and CTSI system
were highly accurate for predicting the severity of disease, there were no statistical differences between
the predictive accuracies of CT and clinical scoring systems. The authors did not recommend CT on
admission for severity assessment only. A recent Dutch investigation showed that early (<1 week after
the onset of symptoms) scanning did not significantly alter patient management. Furthermore, in these
early CTs, the number of examinations, the timing of the examinations, and the Balthazar CT score of
these early CTs were not significantly different for mild and severe disease. Other investigations have
shown that patients with acute pancreatitis often have multiple CT examinations, depending on the
severity of the disease, without dramatic influence on clinical outcomes. These multiple scans lead to a
relatively high radiation dose with only infrequent changes in clinical management.
There is growing evidence, and it is the Expert Panel's opinion, that a CT is not indicated in the first 48
to 72 hours after the onset of symptoms in patients with an unequivocal clinical presentation and
appropriately elevated amylase and lipase; it could lead to inappropriate conclusions. Further, because
renal function is often compromised in patients with severe acute pancreatitis, enhanced CT should be
reserved for times in the disease process when the findings will have a significant impact. Some
advocate delaying initial contrast-enhanced CT for at least 7 to 21 days, even in critically ill patients, as
it does not alter patient management. During the first phase of the disease (7–10 days after the onset of
symptoms), treatment can be supported in the intensive care unit (ICU).
Follow-up Computed Tomography
Another important issue is the timing for follow-up CT in patients with acute pancreatitis, especially in
those with necrotizing pancreatitis. In the second phase of the disease, patients, especially those with
necrosis, can have persistent leukocytosis, fever, multiorgan system dysfunction or failure, and SIRS. It
is important to rescan these patients after 7 to 10 days to assess the size, extent, and character of the
postnecrotic fluid collections and to plan for aspiration. In many institutions, in consultation with the
gastroenterologist or surgeon caring for the patient, contrast-enhanced MDCT is used to examine
patients with necrotizing pancreatitis and continued leukocytosis, fever, SIRS, and organ dysfunction or
failure. In these cases, 1 or several of the identified postnecrotic fluid collections is aspirated for culture.
Although image-guided aspiration and drainage of pancreatic and peripancreatic collections are an
integral part of the image-centric approach to this disease, a discussion of their use is beyond the scope
of these guidelines. Another reason for using contrast-enhanced MDCT to re-examine patients is to
evaluate those who have had significant decreases in hemoglobin or hematocrit or an abrupt
deterioration in clinical status. In these patients, the identification of new, hemorrhagic components can
explain the acute anemia and identify the cause, commonly a ruptured pseudoaneurysm. Lastly, there are
uncommon to rare instances of bowel perforation in acute pancreatitis.
A potential limitation of MDCT in assessing acute pancreatitis is that it has only moderate sensitivity for
detecting stones in the gallbladder and bile duct. However, the biliary tree should be carefully inspected,
and, if biliary dilation is present, isoattenuating stones should be suspected.
Ultrasound
Because of its high sensitivity for detecting gallstones, US is often performed when evaluating patients
with acute pancreatitis. This examination is indicated early in the disease in patients who present with
acute pancreatitis for the first time, even when alcohol is the suspected cause. The purpose of the
examination is primarily to identify gallstones and secondarily to identify biliary ductal dilation and/or
choledocholithiasis. However, patients may have gallstones or another etiology of their pancreatitis.
Moreover, stones in the distal common bile duct may be difficult to visualize with US. Finally, portions
of the pancreas are often obscured by overlying bowel gas, which limits the effectiveness of US in
assessing the severity of the pancreatitis and determining the presence and amount of necrosis.
Some centers have used contrast-enhanced US to evaluate patients with acute pancreatitis and found the
technique equivalent to contrast-enhanced CT and clinical scoring. However, the technique is operator-
dependent, and US contrast agents are approved in the US for echocardiology only. Thus, this would be
an off-label use.
Magnetic Resonance Imaging
The use of MRI in evaluating patients with acute pancreatitis is gaining acceptance. Compared with
other noninvasive imaging modalities, it offers several advantages, especially with heavily T2-weighted
sequences for assessing biliary and pancreatic ducts. These advantages are as follows: (1) bile duct
stones and gallstones can be seen easily, the pancreatic duct can be followed in its entirety, and duct
disruption can often be assessed easily; and (2) its effectiveness for evaluating morphologic changes to
the pancreas and peripancreatic regions is similar to that of MDCT. An advantage of MRI, relative to
MDCT, in evaluating peripancreatic fluid collections is that solid debris is more easily appreciated with
MRI. This finding can help distinguish pancreatitis-induced fluid collections from other cystic lesions
and aid in the use of appropriate drainage techniques. Another advantage of MRI is that it does not use
ionizing radiation.
When IV contrast cannot be administered (primarily because of AKI), the use of T2-weighted sequences
can be very helpful in assessing the pancreatic duct and evaluating the presence of high-signal fluid that
would suggest necrosis in the pancreatic parenchyma.
The disadvantages of MRI are as follows: (1) it is often not readily available in an acute setting; (2) it is
more difficult to perform in acutely ill patients; and (3) the acquisition times are considerably longer
than with MDCT. Further, percutaneous intervention cannot be as easily performed simultaneously with
MRI as it can be with CT. However, MRI appears to offer diagnostic capabilities similar to MDCT, with
a better depiction of the stones and the pancreatico-biliary ductal system.
Other Modalities
Endoscopic US and endoscopic retrograde cholangiopancreatography in the evaluation of acute
pancreatitis are primarily used to assess and confirm choledocholithiasis and subsequent stone removal
in patients with gallstone pancreatitis as well as to identify other anatomic abnormalities (e.g., pancreas
divisum, malignancy) that can lead to acute pancreatitis.
Summary
89
• In the acute setting (<48–72 hours after the onset of symptoms), an enhanced CT should not be
performed when a typical clinical presentation and unequivocal elevations of amylase and lipase are
present.
• In the acute setting, an enhanced CT should be performed if the clinical presentation and amylase
and lipase levels are equivocal.
• Early (within the first 72 hours) imaging with CT may underestimate the full severity of the disease.
• Enhanced CT after 48 to 72 hours will detect pancreatic and peripancreatic necrosis as well as acute
pancreatic fluid collections.
• Delayed enhanced CT (>7–21 days after the onset of symptoms) is very effective in assessing
severity and will guide management, including image-guided aspiration and/or drainage as well as
other forms of minimally invasive drainage.
• Enhanced CT should be performed when there is a significant deterioration of the patient's
condition, including an acute drop in hemoglobin and hematocrit, tachycardia, and hypotension, an
abrupt change in fever, or leukocytosis.
• CT with IV contrast provides the best overall assessment of the pancreas and complications related
to pancreatitis.
• US is primarily used to assess for gallstones and should be performed early in patients who present
for the first time and in whom the cause is uncertain.
• MRI with IV contrast and MRCP have the potential to be an all-inclusive examination for assessing
pancreatitis; however, use may be limited in the acute setting.
Anticipated Exceptions
Nephrogenic systemic fibrosis (NSF) is a disorder with a scleroderma-like presentation and a spectrum
of manifestations that can range from limited clinical sequelae to fatality. It appears to be related to both
underlying severe renal dysfunction and the administration of gadolinium-based contrast agents. It has
occurred primarily in patients on dialysis, rarely in patients with very limited glomerular filtration rate
(GFR) (i.e., <30 mL/min/1.73 m2), and almost never in other patients. There is growing literature
regarding NSF. Although some controversy and lack of clarity remain, there is a consensus that it is
advisable to avoid all gadolinium-based contrast agents in dialysis-dependent patients unless the possible
benefits clearly outweigh the risk, and to limit the type and amount in patients with estimated GFR rates
<30 mL/min/1.73 m2. For more information, see the American College of Radiology (ACR) Manual on
Contrast Media (see the "Availability of Companion Documents" field).
Abbreviations
• AKI, acute kidney injury
• CT, computed tomography
• MRI, magnetic resonance imaging
• MRCP, magnetic resonance cholangiopancreatography
• SIRS, systemic inflammatory response syndrome
• US, ultrasound
Relative Radiation Level Designations
Relative Adult Pediatric

Radiation Effective Dose Effective Dose
Level* Estimate Estimate
Range Range
O 0 mSv 0 mSv
<0.1 mSv <0.03 mSv
0.1-1 mSv 0.03-0.3 mSv
1-10 mSv 0.3-3 mSv
10-30 mSv 3-10 mSv
30-100 mSv 10-30 mSv
*RRL assignments for some of the examinations

cannot be made, because the actual patient doses
in these procedures vary as a function of a
number of factors (e.g., region of the body
exposed to ionizing radiation, the imaging
guidance that is used). The RRLs for these
examinations are designated as "Varies".
Clinical Algorithm(s)
Algorithms were not developed from criteria guidelines.
Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations
The recommendations are based on analysis of the current literature and expert panel consensus.
Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits
Selection of appropriate radiologic imaging procedures for acute pancreatitis.
Potential Harms
Gadolinium-based Contrast Agents
Nephrogenic systemic fibrosis (NSF) is a disorder with a scleroderma-like presentation and a spectrum
of manifestations that can range from limited clinical sequelae to fatality. It appears to be related to both
underlying severe renal dysfunction and the administration of gadolinium-based contrast agents. It has
occurred primarily in patients on dialysis, rarely in patients with very limited glomerular filtration rate
(GFR) (i.e., <30 mL/min/1.73 m2), and almost never in other patients. Although some controversy and
lack of clarity remain, there is a consensus that it is advisable to avoid all gadolinium-based contrast
agents in dialysis-dependent patients unless the possible benefits clearly outweigh the risk, and to limit
the type and amount in patients with estimated GFR rates <30 mL/min/1.73 m2. For more information,
please see the American College of Radiology (ACR) Manual on Contrast Media (see the "Availability
of Companion Documents" field).
91
Relative Radiation Level (RRL)

Potential adverse health effects associated with radiation exposure are an important factor to consider
when selecting the appropriate imaging procedure. Because there is a wide range of radiation exposures
associated with different diagnostic procedures, a relative radiation level indication has been included
for each imaging examination. The RRLs are based on effective dose, which is a radiation dose quantity
that is used to estimate population total radiation risk associated with an imaging procedure. Patients in
the pediatric age group are at inherently higher risk from exposure, both because of organ sensitivity and
longer life expectancy (relevant to the long latency that appears to accompany radiation exposure). For
these reasons, the RRL dose estimate ranges for pediatric examinations are low as compared to those
specified for adults. Additional information regarding radiation dose assessment for imaging
examinations can be found in the ACR Appropriateness Criteria® Radiation Dose Assessment
Introduction document (see the "Availability of Companion Documents" field).
Qualifying Statements
Qualifying Statements
The American College of Radiology (ACR) Committee on Appropriateness Criteria and its expert
panels have developed criteria for determining appropriate imaging examinations for diagnosis and
treatment of specified medical condition(s). These criteria are intended to guide radiologists, radiation
oncologists, and referring physicians in making decisions regarding radiologic imaging and treatment.
Generally, the complexity and severity of a patient's clinical condition should dictate the selection of
appropriate imaging procedures or treatments. Only those examinations generally used for evaluation of
the patient's condition are ranked. Other imaging studies necessary to evaluate other co-existent diseases
or other medical consequences of this condition are not considered in this document. The availability of
equipment or personnel may influence the selection of appropriate imaging procedures or treatments.
Imaging techniques classified as investigational by the U.S. Food and Drug Administration (FDA) have
not been considered in developing these criteria; however, study of new equipment and applications
should be encouraged. The ultimate decision regarding the appropriateness of any specific radiologic
examination or treatment must be made by the referring physician and radiologist in light of all the
circumstances presented in an individual examination.
Implementation of the Guideline

Description of Implementation Strategy
An implementation strategy was not provided.
Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
IOM Domain
Effectiveness
Patient-centeredness
Identifying Information and Availability

Bibliographic Source(s)
Baker ME, Nelson RC, Rosen MP, Blake MA, Cash BD, Hindman NM, Kamel IR, Kaur H,
Piorkowski RJ, Qayyum A, Yarmish GM, Expert Panel on Gastrointestinal Imaging. ACR
Appropriateness Criteria® acute pancreatitis. [online publication]. Reston (VA): American College
of Radiology (ACR); 2013. 11 p. [45 references]
Adaptation
Not applicable: The guideline was not adapted from another source.
Date Released
1998 (revised 2013)
Guideline Developer(s)
American College of Radiology - Medical Specialty Society
Source(s) of Funding
The American College of Radiology (ACR) provided the funding and the resources for these ACR
Appropriateness Criteria®.
Guideline Committee
Committee on Appropriateness Criteria, Expert Panel on Gastrointestinal Imaging
Composition of Group That Authored the Guideline
Panel Members: Mark E. Baker, MD (Principal Author and Panel Vice-chair); Rendon C. Nelson, MD
(Co-Author); Max P. Rosen, MD, MPH (Panel Chair); Michael A. Blake, MB, BCh; Brooks D. Cash,
MD; Nicole M. Hindman, MD; Ihab R. Kamel, MD, PhD; Harmeet Kaur, MD; Robert J. Piorkowski,
MD; Aliya Qayyum, MD; Gail M. Yarmish, MD
Financial Disclosures/Conflicts of Interest
Not stated
Guideline Status
This is the current release of the guideline.
This guideline updates a previous version: Macari M, Rosen MP, Blake MA, Baker ME, Cash BD,
Fidler JL, Greene FL, Jones B, Katz DS, Lalani T, Miller FH, Small WC, Sudakoff GS, Yee J, Expert
Panel on Gastrointestinal Imaging. ACR Appropriateness Criteria® acute pancreatitis. [online
publication]. Reston (VA): American College of Radiology (ACR); 2010. 6 p.
Guideline Availability
Electronic copies: Available from the American College of Radiology (ACR) Web site.
Print copies: Available from the American College of Radiology, 1891 Preston White Drive, Reston,
VA 20191. Telephone: (703) 648-8900.
Availability of Companion Documents
The following are available:
• ACR Appropriateness Criteria®. Overview. Reston (VA): American College of Radiology; 2013
Nov. 3 p. Electronic copies: Available in Portable Document Format (PDF) from the American
College of Radiology (ACR) Web site.
• ACR Appropriateness Criteria®. Literature search process. Reston (VA): American College of
Radiology; 2013 Apr. 1 p. Electronic copies: Available in PDF from the ACR Web site.
• ACR Appropriateness Criteria®. Evidence table development – diagnostic studies. Reston (VA):
American College of Radiology; 2013 Nov. 3 p. Electronic copies: Available in PDF from the ACR
Web site.
• ACR Appropriateness Criteria®. Radiation dose assessment introduction. Reston (VA): American
College of Radiology; 2013 Nov. 2 p. Electronic copies: Available in PDF from the ACR Web site.
• ACR Appropriateness Criteria®. Manual on contrast media. Reston (VA): American College of
Radiology; 90 p. Electronic copies: Available in PDF from the ACR Web site.
• ACR Appropriateness Criteria®. Procedure information. Reston (VA): American College of
Radiology; 2013 Nov. 1 p. Electronic copies: Available in PDF from the ACR Web site.
• ACR Appropriateness Criteria® acute pancreatitis. Evidence table. Reston (VA): American College
93
of Radiology; 2013. 18 p. Electronic copies: Available in PDF from the ACR Web site.
Patient Resources
None available
NGC Status
This summary was completed by ECRI on March 19, 2001. The information was verified by the
guideline developer on March 29, 2001. This summary was updated by ECRI on July 31, 2002. The
updated information was verified by the guideline developer on October 1, 2002. This summary was
updated by ECRI on August 11, 2006. This summary was updated by ECRI Institute on May 17, 2007
following the U.S. Food and Drug Administration (FDA) advisory on Gadolinium-based contrast agents.
This summary was updated by ECRI Institute on June 20, 2007 following the U.S. Food and Drug
Administration (FDA) advisory on gadolinium-based contrast agents. This summary was updated by
ECRI Institute on January 13, 2011 following the U.S. Food and Drug Administration (FDA) advisory
on gadolinium-based contrast agents. This summary was updated by ECRI Institute on June 27, 2011.
This NGC summary was updated by ECRI Institute on February 27, 2014.
Copyright Statement
Instructions for downloading, use, and reproduction of the American College of Radiology (ACR)
Appropriateness Criteria® may be found on the ACR Web site.
Disclaimer
NGC Disclaimer
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guidelines represented on this site.
All guidelines summarized by NGC and hosted on our site are produced under the auspices of medical
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Guidelines represented on the NGC Web site are submitted by guideline developers, and are screened
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NGC, AHRQ, and its contractor ECRI Institute make no warranties concerning the content or clinical
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Readers with questions regarding guideline content are directed to contact the guideline developer.
ИСТОЧНИКИ МАТЕРИАЛОВ
1. Диагностика и лечение острого панкреатита (Российские клинические рекомендации) –

рекомендации, принятые на круглом столе в Санкт-Петербурге, 30 октября 2014 г.
2. Классификация острого панкреатита 2012: пересмотр классификации Atlanta и определения
на основе международного консенсуса (Classification of acute pancreatitis 2012: revision of the
Atlanta classification and definitions by international consensus)
3. Клинические рекомендации IAP/APA по лечению острого панкреатита, основанные
на доказательствах (IAP/APA evidence-based guidelines for the management of acute pancreatitis)
– рекомендации по лечению острого панкреатита 2013 года, разработанные международной
ассоциацией панкреатологов совместно с американской панкреатологической ассоциацией
4. Клинические рекомендации Американского колледжа гастроэнтерологии: лечение острого
панкреатита (American College of Gastroenterology Guideline: Management of Acute Pancreatitis)
– американские клинические рекомендации 2013 года
5. Практические рекомендации по лечению острого панкреатита (Practical Guidelines for Acute
Pancreatitis) – итальянские клинические рекомендации, 2010 года
6. ACR критерии острого панкреатита (ACR Appropriateness Criteria® acute pancreatitis) –
клинические рекомендации 2013 г. по инструментальной диагностике острого панкреатита,
разработанные Американским колледжем радиологии
Общероссийская общественная организация
«Российское Общество Хирургов»
Свидетельство о государственной регистрации некоммерческой
организации № 0012011430, выдано 20.07.2007 г. Министерством юстиции
Российской Федерации
ОГРН 1077799013764
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Р/с 40703810338250001491 в ОАО «Сбербанк России» г. Москва
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Тел.: +7 (499) 237-11-38, +7 (495) 954-08-99
www.общество-хирургов.рф E-mail: pravlenie@surgeons.ru
Фонд содействия развитию хирургии

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Свидетельство о государственной регистрации некоммерческой
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Изготовлено по заказу Фонда содействия развитию хирургии «Развитие Отечественной Хирургии»

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Правление Российского Общества Хирургов

I. Диагностика и лечение острого панкреатита (Российские

Для получения электронной версии «Сборника методических

ДИАГНОСТИКА И ЛЕЧЕНИЕ ОСТРОГО код МКБ – 10 – К85

Такие доказательства базируются на многоцентровых исследованиях, проведенных по нормам

Они позволяют оптимизировать последовательность действий медицинского персонала на всех

Практикующему врачу клинические рекомендации помогают не только делать выбор в пользу

Острый панкреатит – это первоначально асептическое воспаление поджелудочной же-

Этиологические формы острого панкреатита

г) эластаза разрушает стенку сосудов и межтканевые соединительнотканные структуры, что

Определение начала острого панкреатита

Фазы острого панкреатита

Протоколы диагностики и лечения

I. Первичный протокол диагностики и тактики при остром панкреатите

Как правило, осуществляется в приёмном отделении или отделении экстренной помощи.

Если диагноз острого панкреатита устанавливается на основании методов а), б) и в), то

2) Для оценки тяжести ОП и прогноза развития заболевания возможно применение шкалы

• Если имеется 2-4 признака – ОП средней степени.

Наиболее важно раннее выявление тяжёлого панкреатита, результаты лечения которого

3) Для оценки органных и полиорганных дисфункций наиболее целесообразно использовать

4) Интенсивный болевой синдром, не купируемый наркотическими анальгетиками, быстро

5) Оптимальным видом лечения ОП в IА фазе является интенсивная консервативная тера-

II Протокол лечения острого панкреатита лёгкой степени

III Протокол интенсивной терапии острого панкреатита средней степени

Основной вид лечения – консервативная терапия. Приведенный выше базисный лечеб-

1) Ингибирование секреции поджелудочной железы (оптимальный срок – первые трое

2) Активная реологическая терапия.

3) Инфузионная терапия в общей сложности не менее 40 мл соответствующих инфузи-

4) Антиоксидантная и антигипоксантная терапия.

5) Эвакуация токсических экссудатов по показаниям (см. стандарт V). При фермента-

6) Применение антибиотиков с профилактической целью не является обязательным.

IV Протокол интенсивной терапии острого панкреатита тяжёлой степени

2. Назогастральное зондирование для декомпрессии и, при возможности, назогастроинтести-

3. Коррекция гиповолемических нарушений.

4. Целесообразно выполнение эпидуральной блокады.

5. Применение антибиотиков с профилактической целью в первые трое суток заболевания не

6. Целесообразно назначение дезагрегантной антитромботической терапии.

V Протокол лапароскопической операции

- при необходимости дифференциальной диагностики с другими заболева-

Задачи лапароскопической операции могут быть диагностическими, прогностическими и

Задачи лапароскопической операции:

б) выявление признаков тяжёлого панкреатита:

Верификация серозного («стекловидного») отёка в первые часы заболевания

Оптимальными сроками выполнения МСКТА (МРТ) для диагностики панкреонекроза (и оцен-

МСКТА (МРТ) целесообразно выполнять накануне инвазивного вмешательства.

Последующие МСКТА (МРТ) необходимо выполнять при прогрессировании заболевания, при

Использование в клинической практике КТ–индекса тяжести панкреатита по Бальтазару

Протоколы диагностики и лечения

1. Помимо клинических признаков (перипанкреатический инфильтрат и лихорадка) вторая

1.2 УЗ-признаками ПИ (сохраняющееся увеличение размеров поджелудочной железы, не-

2. Мониторинг перипанкреатического инфильтрата заключается в динамическом исследо-

3. В конце второй недели заболевания целесообразна компьютерная томография зоны под-

II Протокол тактики лечения перипанкреатического инфильтрата

2. Лечебное питание: стол № 5 при среднетяжёлом ОП; нутриционная поддержка (перо-

3. Системная антибиотикопрофилактика (цефалоспорины III-IV поколений или фторхи-

4. Иммунотерапия (желательна коррекция клеточного и гуморального иммунитета).

Поздняя фаза (секвестрации)

Клинической формой острого панкреатита в фазе асептической секвестрации является

2. Увеличение к 5-ой неделе заболевания размеров жидкостного скопления в парапан-

3. При отсутствии осложнений (см. ниже) больного можно выписать на амбулаторное