Management of Acute Pancreatitis in the Pediatric ...pgnrc.sbmu.ac.ir/uploads/...Acute_Pancreatitis_in...Background: Although the incidence of acute pancreatitis (AP) in children is

SOCIETY PAPER

Management of Acute Pancreatitis in the Pediatric

Population: A Clinical Report From the North American

Society for Pediatric Gastroenterology, Hepatology and

Nutrition Pancreas Committee�Maisam Abu-El-Haija, ySoma Kumar, zJose Antonio Quiros, §Keshawadhana Balakrishnan,jjBradley Barth, �Samuel Bitton, #John F. Eisses, ��Elsie Jazmin Foglio, yyVictor Fox,

zzDenease Francis, §§Alvin Jay Freeman, jjjjTanja Gonska, yyAmit S. Grover, #Sohail Z. Husain,��Rakesh Kumar, ##Sameer Lapsia, �Tom Lin, ��Quin Y. Liu, yyyAsim Maqbool,

zzzZachary M. Sellers, §§§Flora Szabo, jjjjjjAliye Uc, ��Steven L. Werlin,and ###Veronique D. Morinville

ABSTRACT

Copyright © ESPGHAN and NASPGHAN. All ri

What Is Known

� Pediatric acute� A subset of ch

complications o� No guidelines

acute pancreat

What Is New

� Recommendatiacute pancreaincluding aggreful monitoring,and indicationprocedures.

� Evidence for usefor pediatric ac

Received March 29, 2017; accepted August 3, 2017.From the �Division of Gastroenterology Hepatology and Nutrition,

Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, theyDivision of Pediatric Gastroenterology, Hepatology and Nutrition,

Rady Children’s HoPediatric GastroenteroChildren’s Hospital,Gastroenterology, Ma

JPGN � Volume 66, Number 1, January 2018

pancreatitis incidence is increasing.ildren develop local and systemicf acute pancreatitis.exist for management of pediatric

itis in North America.

ons for management of pediatrictitis manifestations are provided,ssive early fluid administration, care-pain control, early enteral nutrition,s for endoscopic and surgical

of antibiotics and protease inhibitorsute pancreatitis is limited.

Background: Although the incidence of acute pancreatitis (AP) in children

is increasing, management recommendations rely on adult published guide-

lines. Pediatric-specific recommendations are needed.

Methods: The North American Society for Pediatric Gastroenterology,

Hepatology and Nutrition Pancreas committee performed a MEDLINE review

using several preselected key terms relating to management considerations in

adult and pediatric AP. The literature was summarized, quality of evidence

reviewed, and statements of recommendations developed. The authorship met

to discuss the evidence, statements, and voted on recommendations. A

consensus of at least 75% was required to approve a recommendation.

Results: The diagnosis of pediatric AP should follow the published

INternational Study Group of Pediatric Pancreatitis: In Search for a

CuRE definitions (by meeting at least 2 out of 3 criteria: (1) abdominal

pain compatible with AP, (2) serum amylase and/or lipase values �3 times

upper limits of normal, (3) imaging findings consistent with AP). Adequate

fluid resuscitation with crystalloid appears key especially within the first

24 hours. Analgesia may include opioid medications when opioid-sparing

measures are inadequate. Pulmonary, cardiovascular, and renal status should

be closely monitored particularly within the first 48 hours. Enteral nutrition

should be started as early as tolerated, whether through oral, gastric, or

jejunal route. Little evidence supports the use of prophylactic antibiotics,

antioxidants, probiotics, and protease inhibitors. Esophago-gastro-

duodenoscopy, endoscopic retrograde cholangiopancreatography, and

endoscopic ultrasonography have limited roles in diagnosis and

management. Children should be carefully followed for development of

early or late complications and recurrent attacks of AP.

Conclusions: This clinical report represents the first English-language

recommendations for the management of pediatric AP. Future aims

should include prospective multicenter pediatric studies to further

validate these recommendations and optimize care for children with AP.

Key Words: endoscopy, fluid management, nutrition, pain control,

protease inhibitors, surgery

(JPGN 2018;66: 159–176)

A cute pancreatitis (AP) has been increasingly diagnosed inchildren in recent decades (1–3). A variety of etiologies can

result in AP in children, including structural/anatomic, obstructive/biliary, trauma, infections, toxins, metabolic, systemic illness,inborn errors of metabolism, and genetic predispositions. Theseare a more prevalent compared with adult AP, when biliary andalcoholic causes are well recognized to be the 2 primary AP riskfactors (4).

Most of the literature regarding management of AP describesadult experience. Recommendations for fluid resuscitation, prog-nosis based on markers of severity/signs of multiorgan failure, andmanagement thereof are all based on adult criteria and experience,

ghts reserved.

spital, San Diego, CA, the zDivision oflogy, Medical University of South CarolinaCharleston, SC, the §Division of Pediatricria Fareri Children’s Hospital, Valhalla, NY,

159

Abu-El-Haija et al JPGN � Volume 66, Number 1, January 2018

and reflect experience with etiologies leading to AP in adults. Forthe reasons listed above, adult recommendations cannot be applieddirectly to the pediatric population diagnosed with AP.

Although pediatric pancreatologists may be consulted duringan AP hospitalization, a child will typically be initially and primar-ily handled by a pediatrician and/or a general pediatric gastroen-terologist at the first episode of AP. Thus, broader awareness ofavailable published evidence/gaps/recommendations for managingboth the early and later phases of AP in children are needed.

The aims of the current clinical report consist mainly toreview published evidence for management of AP in children,compare and contrast pediatric to adult literature, identify gapsand limitations in the available literature and knowledge, and makerecommendations for providers for a unified approach to help guideclinical management of children with AP.

METHODSThe working group involved in the development of this

NASPGHAN clinical report included members of the NASPGHANPancreas Committee in early 2016, under the leadership of thePancreas Committee chair (V.D.M.).

Three subgroups were created, headed by the 3 co-firstauthors (M.A.E.H., S.K., J.A.Q.), who provided guidance on themain topics of interest to be subdivided for thorough review of theavailable literature. Topics were selected ahead of time throughgroup discussions. Keywords included pediatrics, acute pancreati-tis, diagnosis, management, intravenous (IV) fluids, enteral nutri-tion (EN), parenteral nutrition (PN), pain management, antibiotics,probiotics, antioxidants, anti-proteases, endoscopy, endoscopycultrasonography (EUS), endoscopic retrograde cholangiopancrea-tography (ERCP), surgery, outcomes, and complications.

All available adult and pediatric publications were reviewedafter each subgroup conducted Medline searches using the abovekeywords to generate output to end date July 2016. All Englishliterature was reviewed, and 1 foreign language (5) document wastranslated and reviewed (5). Regular calls and e-mail correspon-dences were conducted between the subgroup leaders and commit-tee chair. Section paragraphs were written by subgroup members.Subsections were assembled by the subgroup leaders and seniorauthor. Tentative summary statements and recommendations werewritten. The first manuscript draft was circulated among all authorsin August to September 2016.

Copyright © ESPGHAN and NA

the jjUniversity of Texas Southwestern Medical School, Dallas, TX, the�Pediatric Gastroenterology and Nutrition, Steven & Alexandra CohenChildren’s Medical Center of New York, Hofstra Northwell School ofMedicine, Hempstead, NY, the #Division of Pediatric Gastroenterology,Hepatology and Nutrition, Children’ Hospital of Pittsburgh, University ofPittsburgh School of Medicine, Pittsburgh, PA, the ��Pediatric Gastro-enterology, The Children’s Hospital of New Jersey at Newark Beth IsraelMedical Center, Newark, NJ, the yyDivision of Gastroenterology, Hepa-tology and Nutrition, Boston Children’s Hospital, Harvard MedicalSchool, Boston, MA, the zzPediatric Gastroenterology, Stony BrookUniversity, NY, the §§Division of Gastroenterology, Hepatology andNutrition, Emory University School of Medicine, Atlanta, GA, thejjjjPediatric Gastroenterology, Toronto Hospital for Sick Children, Tor-onto, ON, Canada, the ��Division of Pediatric Gastroenterology, Hepa-tology and Nutrition, University of Oklahoma Health Sciences Centre,Oklahoma City, OK, the ##Gastroenterology, Hepatology and Nutrition,Children’s Hospital of the King’s Daughters, Norfolk, VA, the��Digestive Disease Center, Cedars-Sinai Medical Center, LosAngeles, CA, the yyyGastroenterology, Hepatology and Nutrition, TheChildren’s Hospital of Philadelphia, University of Pennsylvania Perel-man School of Medicine, Philadelphia, PA, the zzzDivision of PediatricGastroenterology, Hepatology, and Nutrition, Stanford University, Palo

160

A face-to-face meeting was held at the 2016 World Congressof Pediatric Gastroenterology, Hepatology and Nutrition in Mon-treal, Quebec, Canada in October 2016. Each subgroup presentedpertinent literature review, and proposed statements to vote upon foreach element being considered. The evidence presented and sum-mary statements/recommendations were discussed and modifiedbased on the feedback of attendees. Strength of scientific evidencewas reviewed.

It had been initially anticipated that the group would grade thequality of evidence to support each recommendation, utilizing theGrading of Recommendations, Assessment, Development, and Eval-uation system (6). Upon review of the literature by the group at theWorld Congress, it was, however, deemed that the overall quantityand quality of pediatric data were so limited that it was decided that allrecommendations could only be stated to have either (1) ‘‘low’’quality of evidence- meaning that further research is likely to impactour confidence in the estimate of effect and likely to change theestimate, or (2) ‘‘very low’’ quality of evidence so that any estimate ofeffect is uncertain. Hence, recommendations were not individuallylabeled with quality of evidence. Subsequent to group discussion,each summary statement was voted upon, using a 5-point scale (5—strongly agree; 4—agree; 3—neutral: neither agree nor disagree; 2—disagree; 1—strongly disagree). It had been agreed ahead of time thatconsensus could only be reached if at least 75% of the participantsvoted ‘‘4’’ (agree) or ‘‘5’’ (strongly agree) on a statement. Voting wasanonymous, and no justification was requested for what responsecategory was selected. Members that could not physically be presentwere encouraged to participate by phone/by Internet during theprocess. For those who could not participate via these methods,the manuscript draft and recommendations were re-circulated bye-mail, with request to vote upon each statement within 1-week.

Subsequent to the October 2016 face-to-face meeting, sub-group leaders re-edited their respective manuscript sections, sum-mary and statement wording was finalized, and the updated draftwas circulated amongst all authors for a second round of voting viaInternet in February 2017. The same 5-point scale was utilized, andauthors were instructed to answer within 14-days Twenty-fourauthors were eligible to vote. Results were tabulated and includedwithin the manuscript. The updated draft of the manuscript was re-circulated to all participating committee members for further reviewand editing until a final manuscript draft was agreed upon by allauthors. The final version was reviewed and approved by theNASPGHAN Council.

SPGHAN. All rights reserved.

Alto, CA, the §§§Division of Pediatric Gastroenterology, Hepatology andNutrition, Children’s Hospital, Richmond Virginia Commonwealth Med-ical Center, Richmond, VA, the jjjjjjUniversity of Iowa Carver College ofMedicine, Iowa City, IA, the ��Medical College of Wisconsin, Mil-waukee, WI, and the ###Division of Pediatric Gastroenterology andNutrition, Montreal Children’s Hospital, McGill University Health Cen-tre, Montreal, QC, Canada.

Address correspondence and reprint requests to Veronique D. Morinville,MDCM, FRCPC, Division of Pediatric Gastroenterology and Nutrition,Montreal Children’s Hospital, McGill University Health Centre,B04.2443, 1001 Blvd Decarie, Montreal, QC, Canada, H4A 3J1(e-mail: [email protected]).

This publication was supported by the North American Society for PediatricGastroenterology, Hepatology and Nutrition (NASPGHAN); M.A.E.H.by the National Institutes of Diabetes and Digestive and Kidney Diseases(NIDDK) under award number R43 DK105640-01.

Drs Abu-El-Haija, Kumar, and Quiros contributed equally to the article.The authors report no conflicts of interest.Copyright # 2017 by European Society for Pediatric Gastroenterology,

Hepatology, and Nutrition and North American Society for PediatricGastroenterology, Hepatology, and Nutrition

DOI: 10.1097/MPG.0000000000001715

www.jpgn.org

mailto:[email protected]

http://dx.doi.org/10.1097/MPG.0000000000001715

JPGN � Volume 66, Number 1, January 2018 Management of Acute Pancreatitis in the Pediatric Population

RESULTS

1. INITIAL EVALUATION AND DIAGNOSIS OFPEDIATRIC ACUTE PANCREATITIS

Recent studies estimate the incidence of acute pancreatitis(AP) at�1/10,000 children per year (2,7), an incidence approachingthat of adults. There are no evidence-based diagnostic guidelines forAP in children. The INSPPIRE (INternational Study Group ofPediatric Pancreatitis: In Search for a CuRE) definition of pediatricAP is an expert definition modeled after the Atlanta criteria in adults(8). As per INSPPIRE criteria, a diagnosis of AP requires at least 2of the following: (1) abdominal pain compatible with AP, (2) serumamylase and/or lipase values �3 times upper limits of normal, (3)imaging findings consistent with AP (9,10). INSPPIRE or othercriteria do not address phases (early or late) of AP in children ortypes (interstitial edematous pancreatitis, necrotizing pancreatitis,infected pancreatic necrosis) or severity of AP (mild, moderate orsevere AP with multisystem organ failure).

Pediatric AP diagnosis is typically suspected clinically withcompatible symptom presentations, and confirmed by laboratoryand/or radiological studies. Abdominal pain and/or irritability arethe most common findings of AP in children, followed by epigastrictenderness, nausea, and vomiting (11,12). In infants and toddlers,symptoms may be subtle; therefore, the diagnosis requires a highlevel of suspicion. Biliary/obstructive factors, medications andsystemic diseases are the main causes of childhood AP(1,4,9,12–23) and knowledge of these possible etiologies will guidethe initial investigations.

The percentage of children who develop ‘‘severe’’ acutepancreatitis is variable in published series (6–33), but children withAP in general have a mild course (11,16,24). In a subset of patients,AP may have a severe course (8), but no established clinical toolspredict this outcome. The scoring systems to assess severity of AP inadults (Ranson, Glasgow, modified Glasgow, Bedside Index ofSeverity in Acute Pancreatitis (BISAP) and Acute Physiology andChronic Health Evaluation II (APACHE II)) are not easily applicableto children for several reasons (25). DeBanto’s pediatric acutepancreatitis score (PAPS) (26) was assessed in children but haslow sensitivity and requires 48 hours for risk prediction. Likewise,the computed tomography severity index or Balthazar score (27),relies on radiologic appearance and thus not desirable in the pediatricage group due to radiation exposure. With its wide availability, lipaseis an attractive marker to identify severe cases of AP (24), but mayidentify many false positives because of its low positive predictivevalue and specificity. Coffey et al (24) found that serum lipase 7-foldabove the upper limit of normal within 24 hours of presentationhelped predict acute pancreatitis severity. This is a retrospectivestudy evaluating 211 children and has not been, however, validated inlarger study groups. Suzuki et al (28), in Japan, developed a pediatric-friendly severity scoring system using 9 parameters, but this was alsoa retrospective study that only evaluated 145 patients, and the authorsconcluded that results may not be broadly applicable to the pediatricpopulation. More recently, Szabo et al (29) reported that an earlyseverity prognostic model using serum albumin, lipase, and whiteblood cell count obtained within 24 hours demonstrated a positivepredictive value of 35% and negative predictive value of 91%.

Further prospective studies are necessary to determine theclinical utility of any of these tools. The above-mentioned studiesutilized various definitions of severity of AP, limiting the capacityto make comparisons across studies. A recent publication by theNASPGHAN Pancreas Committee addressed the need to have awell-defined classification of severity of AP by proposing defini-tions for mild, moderately severe, and severe AP to improvehomogeneity among studies (30).


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Serum Biomarkers

Acute pancreatitis is primarily a clinical diagnosis that relieson the presence of at least 2 of 3 criteria as published by theINSPPIRE and the Atlanta classification (8,9). Without 2 of these 3criteria fulfilled, it is difficult to make the diagnosis of AP. Themain biochemical markers used to diagnose AP include serumlipase and serum amylase. As a serum lipase or amylase level of atleast 3 times the upper limit of normal is considered consistent withpancreatitis, it is important to know a laboratory’s reference valuesto determine this threshold. Both amylase and lipase are usuallyelevated early in the disease course. Correlation of serum lipase oramylase levels and severity of disease is, however, poor (24,31,32).Lipase is primarily secreted from the pancreas, although othersources of lipase include gastric and lingual lipases. In AP, lipase isusually increased within 6 hours of symptoms; serum levels peak at24 to 30 hours and can remain elevated for more than 1 week (33).Some advocate that serum lipase without serum amylase is suffi-cient to diagnose AP, as lipase is a more sensitive and specificmarker of AP (87%–100% and 95%–100%, respectively) (34–37). Lipase, in addition, stays elevated longer than amylase, whichis useful in cases of delayed presentation (33,38,39). Lipase levelsare also less altered by etiology of AP in contrast to amylaseespecially in the case of ethanol (36,40) or hyperlipidemia (41,42).But caution in interpreting levels in children must be exercised,as normal lipase values have been demonstrated to relate to theage of a child, rising from newborn to child to adult (43,44).Amylase is secreted from several organs, primarily the salivaryglands and the pancreas. Most laboratories measure total amylaselevels, which contain both s-amylase (salivary) and p-amylase(pancreas) isoforms (45). Laboratory tests exist to fractionate p-and s-amylase, but this practice is less available. Amylase refer-ence values are different depending on the laboratory test used, butalso vary with age and gender (46,47). Serum amylase levels can bealtered by the etiology of pancreatitis as noted above. Amylaselevels rise faster than lipase levels and often can normalize by24 hours after onset of symptoms limiting usefulness in patientswith a delayed presentation to a medical facility (33). As thekidneys excrete amylase and lipase, nonpancreatic-based eleva-tions of these enzymes may be seen in patients with renal injury ordisease (45).

Several nonpancreatitis conditions cause elevations of pan-creatic serum amylase and/or lipase, including decompensated liverfailure, renal failure, intestinal inflammation (including celiacdisease and inflammatory bowel disease), abdominal trauma, dia-betic ketoacidosis, and head trauma (48). In addition to this, someindividuals produce large complexes of amylase or lipase withimmunoglobulins (termed macroamylase and macrolipase) that arepoorly filtered and excreted due to the large size, that will lead toelevated values if the enzyme level is measured in blood, despite notbeing related to inflammation of the pancreas (49).

Other biomarkers for diagnosis and management of pancre-atitis have been proposed and studied in animal models or smallclinical trials (reviewed in (45,50,51)). None has, however, gainedprominence and many have yet to be validated for generalclinical use.

Several laboratory tests are helpful for monitoring the courseof AP (52). In general, serum electrolytes, blood urea nitrogen(BUN) and creatinine and a complete blood cell count are importantto monitor fluid/hydration status and renal function. A hepaticenzyme panel is indicated to seek biliary or gallstone etiologyand to assess for organ involvement. Calcium and triglyceride levelsshould be considered baseline investigations (9). Monitoring respi-ratory status can alert the clinician to the progression from mild tomoderately severe or severe AP.


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Etiologies

As mentioned previously, anatomic, obstructive (includingbiliary), infectious, trauma, toxic, metabolic, systemic illness,inborn errors of metabolism, genetic predispositions, and idiopathichave all been described as potential etiologies in pediatric AP, acuterecurrent pancreatitis (ARP) and chronic pancreatitis (CP) (3,4,53).The review by Lowe and Morinville (3) summarized the top 6overall etiological categories in published reviews as being idio-pathic/other in 24%, trauma in 17%, systemic illness in 15%,structural abnormalities in 14%, drugs in 10%, and infections in8%. Considering more common etiologies and those for whichdirected therapies exist, a 2012 manuscript by Morinville et alpresented a survey of pediatric gastroenterologists providing pan-creatology care and proposed the following workup in first cases ofpancreatitis: serum liver enzymes, triglyceride and calcium levels,and abdominal ultrasound. They suggested reserving testing forgenetic causes/predispositions (which at the time consisted ofCFTR (cystic fibrosis transmembrane conductance regulator),SPINK1 (serine protease inhibitor Kazal type 1) and PRSS1(cationic trypsinogen)), sweat chloride, and more detailed imagingfor cases of ARP, CP, or first instances of AP with increasedconcern for underlying risk for recurrence based on presentation,medical history, or family history (9). As appropriate, a search canbe conducted for particular toxic-metabolic risk factors (54). Arecent publication by Gariepy et al (55) focused on the causalevaluation of ARP and CP in children, which tends to be moreexpansive due to the recurrent/chronic nature of the presentation.Autoimmune pancreatitis (AIP) types 1 and 2 are rarely diagnosedbut represent distinct types of pancreatitis with specific histologicalfindings in the context of suggestive symptoms, imaging, laboratoryresults, and response to therapy. Should AIP be suspected as theetiology of AP, further supportive evaluation is necessary. Inter-ested readers are directed to a recent publication on pediatric AIP byScheers et al (56).

Imaging

Imaging in the early phase of AP usually is not required ifhistory/presenting symptoms and biochemical serum markers arepresent to make a diagnosis. Imaging becomes relevant to documentpancreatic necrosis, complications of pancreatitis including fluidcollections, and etiology or pancreatitis such as gallstones/biliarydisease or anatomic abnormalities.

The criterion standard for diagnostic imaging remains thecontrast enhanced computed tomography (CECT) and several scor-ing systems have been developed (57). Despite CETC being theimaging criterion standard, it is, however, frequently not indicatednor necessary for the diagnosis or management of pediatric AP. Incases that are ambiguous for a diagnosis of AP, such as in a delayedpresentation when serum markers may be low, a CECT may berequired to confirm AP. IV contrast is key to distinguish necroticareas in the pancreas (58). As early imaging may underestimate extentof disease and because complications evolve over time and findingsmay not be present in the early phase of the disease, CETC ideallyshould be delayed at least 96 hours after onset of symptoms (8,59). Inmild cases, CECT may show homogenous organ enhancement,inflammatory changes of peripancreatic fat or fluid surroundingthe pancreas (58). In severe cases, CECT may show heterogeneousorgan enhancement, necrosis within the pancreas or in the surround-ing peripancreatic tissue. In addition, CECT can also identify peri-pancreatic fluid collections or pseudocysts. CECT should bereconsidered when the patient’s clinical condition deteriorates oris persistently severe (8). Lautz et al found that the computedtomography severity index (or Balthazar score) in pediatric patients


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gave a sensitivity, specificity, positive predictive value, and negativepredictive value of 81%, 76%, 62%, and 90%, respectively, forseverity, in a retrospective study evaluating 64 children (60).

Ultrasound is used extensively in cases when there is a highsuspicion of biliary pancreatitis, where it is useful early to deter-mine the need for therapeutic intervention (32,57). Ultrasound hasan excellent safety profile, is noninvasive and does not utilizeradiation. Ultrasound utility can, however, be limited in the assess-ment of the pancreas due to interfering structures, such as the bowelgas in the intestine and obesity, and has a lower sensitivity invisualizing the pancreas compared to CECT.

Magnetic resonance imaging (MRI) is typically not utilized asinitial imaging technique in AP but can be useful for late complica-tions (58). It can be particularly useful in young or pregnant patients(intent to limit radiation) and can allow alternative IV contrastmethods in patients with impaired renal function or allergies toiodinated contrast (59). MRI may also be more sensitive in evaluatingnecrotic tissue as compared to CECT (58,60). Magnetic resonancecholangiopancreatography (MRCP) in AP is most often employed indetecting distal common bile duct stones and diagnosing biliarycauses of AP. MRI/MRCP using secretin is helpful in examiningthe ductular system in the pancreas as well as common bile ductabnormalities including strictures or stones (61,62). To optimizedetection of ductal abnormalities, MRCP may be performed afteran attack of AP has resolved as acute edema may obscure thevisualization of the ducts. The use of secretin-enhanced MRCP inpediatric pancreatic disease has not been fully established (63) andaccess to secretin is not uniform across institutions and countries. Linet al (64) detail the use of MRI and MRCP in children requiringpancreatic imaging and overall imaging considerations in AP.

Recommendation 1a: Diagnosis of pediatric acute pan-creatitis should be as per previously published INSPPIREcriteria.

Diagnosis of AP in pediatric patients requires at least 2 ofthe following: (1) abdominal pain compatible with AP, (2)serum amylase and/or lipase values �3 times upper limits ofnormal, (3) imaging findings consistent with AP.

24/24 U 100% agreement with recommendation.

Voting results: Strongly agree¼ 22; agree¼ 2; neutral¼ 0;disagree¼ 0; strongly disagree¼ 0.

Recommendation 1b: Initial imaging may be accom-plished via transabdominal ultrasonography, with other imag-ing (CT, MRI) reserved for more complicated cases W tailoredto suspected etiology.



Recommendation 1c: Based on most frequent etiologiesand those for which therapeutic options exist, first-time attackof acute pancreatitis testing should include liver enzymes (ala-nine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin), triglyc-eride level, and calcium level.



2. MANAGEMENT CONSIDERATIONS INPEDIATRIC ACUTE PANCREATITIS

2a. Fluid Management in Acute PancreatitisIV fluid therapy is a mainstay of treatment during an episode

of AP. Fluid resuscitation maintains adequate fluid status and urine


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output, but recently attention has focused on the use of IV fluids toprevent potential complications in AP, such as necrosis and organfailure. The pathogenesis of AP and progression to severe forms isthought to be secondary to alteration in the microcirculation of thepancreas by events including hypovolemia, increased capillarypermeability and formation of microthrombi. Fluid resuscitationis thought not only to correct hypovolemia but to help preservepancreatic microcirculation by providing adequate perfusion andpreventing possible microthrombi formation and thus preventingcomplications and progression to severe disease (65).

Type of Fluid

Consensus is lacking regarding the ideal amount and type offluid to use during an episode of AP in adult practice, and even lessdata exist pertaining to fluids in the pediatric population. Crystal-loid has been the most recommended type of fluid in adult guide-lines (32,66–69). A major benefit of crystalloid is that it is readilyand quickly available. Normal saline (NS) has long been thecrystalloid of choice for initial fluid resuscitation in general butsome adult literature suggests Lactated Ringers (LR) as moreoptimal in AP. In a small randomized controlled trial (RCT) of40 adults with AP, Wu et al (70) showed that LR decreased theincidence of the systemic inflammatory response syndrome (SIRS)and C-reactive protein levels at 24 hours compared with NS. Bycontrast, a retrospective review of 103 patients failed to show anysignificant difference between LR and NS as the initial resuscitationfluid in adults with varying severities of pancreatitis (71). LR hasbeen recommended over NS in the International Association ofPancreatology/American Pancreatic Association (IAP/APA) guide-lines, but the American Gastroenterology Association (AGA)guidelines only state that LR may be a better choice but was nota strong recommendation (67,69). In pediatrics, it has been shownthat aggressive fluid management within the first 24 hours with NSwith dextrose 5% is a safe and well-tolerated option (72), but thiswas not compared to other types of IV fluids (such as LR).

Colloids (such as albumin, fresh frozen plasma, or packed redblood cells) have not been recommended as the initial resuscitationfluid in AP. Colloid components stay within the intravascular spacebecause of larger size and can draw fluid into the circulation fromthe interstitium secondary to osmotic effect. The guidelines fromthe AGA recommend colloid in specific situations when the hemat-ocrit is <25% or albumin is <2 g/dL (67), with another publicationrecommending a ratio of 3:1 of crystalloid to colloid (73).

Rate of Fluid Administration

The aggressiveness of fluid resuscitation in AP has also beendebated. The timing of intervention of aggressive fluid therapy maybe key. Adult studies in favor of early and aggressive fluids in APinclude several retrospective studies that utilized different strategiessuch as providing > versus <33% of total fluids within the first24 hours, and another providing 3.5 L versus 2.4 L IV within the first24 hours (74). In general, those receiving more aggressive IV fluidvolumes within the first 24 hours tend to have improved outcomesincluding mortality, but even within the various studies, findings areinconsistent as to whether higher early IV fluids reduced rates ofnecrosis, SIRS, and length of stay (LOS) (75). In contrast, Mao et al(76), reported an RCT of 76 patients with severe AP assigned to slowhemodilution (5–10 mL � kg�1 � h�1) or rapid hemodilution (10–15 mL � kg�1 � h�1) demonstrating that rapid aggressive early fluidadministration yielded higher sepsis rates and mortality. de-Madariaet al (77) conducted a prospective study of 247 patients dividingpatients based on the amount of fluid administered in the first


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24 hours. The group receiving the highest volume, >4.1 L, had anincreased rate of persistent organ failure. Weitz et al (78), reviewed391 cases of AP and found the use of aggressive fluids (approximately5 L) was associated with increased severity of disease and localcomplications. Concerns about this latter group of studies are thatthey have primarily involved sicker patients and fluid regimens werenot restricted to the first 24 hours of resuscitation.

Several experts and groups have since made recommenda-tions for the rate of fluid resuscitation in the first 24 to 48 hours inadults with AP. The IAP/APA guidelines recommend that patientsreceive 5 to 10 mL � kg�1 � h�1 until resuscitation goals are achievedwith regard to improvements in heart rate, urine output, meanarterial pressure and/or hematocrit (69). The American Collegeof Gastroenterology (ACG) recommends an initial rate of 250 to500 mL/h, in addition to boluses of fluid if hypotension or tachy-cardia is present, and using BUN to direct therapy (32). Similarrecommendations are made in a review by Whitcomb (79). Aggar-wal et al (80) advises 3 to 4 L of fluid in the first 24 hours (notto exceed 4 L) with an initial 1 L bolus and to follow with3 mL � kg�1 � h�1 for the first 24 to 48 hours. Nasr (81) recommend1 to 2 L boluses initially and 150 to 300 mL/h to follow. Subse-quently, they recommend 2 mL � kg�1 � h�1 if the patient responds tothe initial resuscitation, but otherwise to use 3 mL � kg�1 � h�1 (81).

Only 1 pediatric study evaluated different rates of maintenancefluid administration, involving 201 patients with AP (68). This studyshowed that a combination of early EN (<48 hours) and aggressivefluids (>1.5–2 times maintenance in the first 24 hours) decreased LOSand the occurrence of severe disease versus more conventional histori-cal management. Aggressive IV fluids did not adversely affect out-comes (primarily pulmonary complications or readmission rates). Nostudies specify the ideal rate of maintenance fluids in AP following theinitial resuscitation (>24–48 hours), although Szabo et al (72), sug-gested that 1.5 to 2 times maintenance was safe in their patientpopulation. No pediatric studies compare initial resuscitation volumes.

Summary: In the initial resuscitation phase of acute pan-creatitis, theoretical and potential clinical advantages favor LRabove NS based on adult data, but pediatric data are lacking.

Recommendation 2ai: Children with acute pancreatitisshould be initially resuscitated with crystalloids, either with LRor NS in the acute setting. Based on assessment of hydrationstatus/hemodynamic status, if evidence of hemodynamic com-promise, a bolus of 10 to 20 mL/kg is recommended.



Summary: Pediatric literature is sparse regarding fluidresuscitation and rate of fluid administration in acute pancrea-titis. The adult literature suggests boluses of 250 to 1000 mLinitially, and up to 3 to 4 L fluids within first 24 hours.

Recommendation 2aii: Children with diagnosis of acutepancreatitis should be provided 1.5 to 2 times maintenance IVfluids with monitoring of urine output over the next 24 to48 hours.



2b. Monitoring of Children Diagnosed WithAP/Extra-Pancreatic Manifestations of AcutePancreatitis

Although not well studied in pediatric patients, multiorgandisease in adult patients with AP is associated with worse clinical


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outcomes with over half of AP-related deaths occurring within1 week of the onset of multiorgan dysfunction (82). Cardiac,pulmonary and renal involvement comprise key components ofadult scoring systems used to predict severity of an AP episodeincluding the modified Atlanta Classification, Ranson criteria,Japanese Severity Assessment, Glasgow Score, BISAP, andAPACHE II (8,83–86). Pediatric models predicting severity ofAP have also placed importance on multiorgan involvement buthave proven to be less reliable (87) or have not yet been prospec-tively validated (28). Increased endothelial barrier permeability andprofound cytokine release associated with SIRS combined withaggressive hydration theoretically increases a patient’s risk forthird-spacing fluids and developing extrapancreatic manifestationsof AP. Appropriate monitoring is vital to balance appropriate fluidresuscitation while attempting to prevent cardiac, pulmonary, andrenal complications (88).

Cardiovascular Monitoring

Hypovolemia at admission is a strong predictor of morbidityand mortality among adults with AP and appears to be correlatedwith the magnitude of the SIRS (88). Tachycardia has been utilizedin both adult and pediatric scoring systems to predict severity of AP,and its improvement has been utilized to confirm adequate fluidresuscitation in addition to monitoring urine output and skin turgor(70,80). Routine adult cardiac monitoring for non-intensive careunit (ICU) patients includes routine vitals every 8 hours to accesscardiovascular status (70). In addition to this, rare cases of cardiactamponade and atrial fibrillation have been reported in AP andshould be considered during standard cardiac workup initiated inpatients with unexplained hypotension, shortness of breath and/orchest pain (89–92).

Pulmonary Monitoring

Both adult studies and animal models show acute respiratorydistress syndrome, pneumonia, and pulmonary edema/effusions asearly complications of AP, typically within the first 48 hours(15,93). As acute respiratory distress syndrome is the most commoncritical complication of severe AP associated with multiorgandysfunction in adults (94), abnormal PaO2 or abnormal pulmonaryimaging are components of all commonly used scoring systems topredict severity of an AP episode (8,28,83–86). Routine monitoringof oxygen saturation during aggressive hydration is typicallyimplemented, with some advocating patient beds be elevated at30-degree angle to decrease likelihood of pulmonary sequestration(70). Standard pulmonary workup and care should be considered inany patient with unexplained shortness of breath, worsening coughand/or difficulty breathing (93).

Renal Monitoring

Acute kidney injury (AKI) via abdominal compartmentsyndrome (82,95) or inflammatory-driven damage to the proximalconvoluted tubule (96) marked by elevation of BUN and creatinine,along with decreased urine output, is a known early complication ofAP in children and factors prominently in AP scoring systems topredict disease severity (8,15,28,83–86). BUN alone in some adultstudies has been shown to be as effective in predicting diseaseseverity as more advanced scoring systems (97) and AKI has beenassociated with a 10-fold increased risk of mortality in severe AP(98). Therefore, BUN and creatinine are considered importantmarkers to follow in assessing fluid management and to monitorfor AKI in adults during the first 48 hours and during aggressive


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hydration (70,80,97). Although no guidelines document the fre-quency of monitoring these parameters, 8 to 12 hours was used in 1study to determine responsiveness to fluid management (70).Guidelines from the ACG stress the importance in decreasingthe BUN and maintaining a normal creatinine within the first24 hours so early monitoring is essential (32). In rare cases,continuous veno-venous hemofiltration is required to preventfurther kidney damage, prevent abdominal compartment syn-drome, and/or removae inflammatory cytokines, but its use hasnot been studied in pediatric patients with AP (99). It may benecessary to install a urinary catheter to accurately documenturinary output, particularly in a sedated child within theICU setting.

Summary: Monitoring of patients with acute pancreatitiscan provide indicators of complications arising, including SIRSand organ dysfunction/failure. Cardiac, respiratory, and renalstatus should be followed particularly closely within the first48 hours after presentation as most complications will havetheir onset within that time frame. Urine output is animportant marker of adequate fluid resuscitation, with adultliterature suggesting benefit to aim for >0.5 to 1 mL �kgS1 �hS1

(IAP/APA guidelines).

Recommendation 2bi: In patients admitted to an inpa-tient ward, vitals should be obtained at least every 4 hoursduring the first 48 hours of admission and during periods ofaggressive hydration to monitor oxygen saturation, blood pres-sure, and respiratory rate. Frequency to be adjusted based onclinical status. Abnormalities of vital signs should promptspecialist assessment.



Recommendation 2bii: BUN, creatinine, and urine outputshould be monitored routinely during the first 48 hours asmarker of appropriate fluid management and to screen forAKI. Abnormalities should prompt nephrology assessment.

22/24 U 92% agreement with recommendation


2c. Pain Management in Acute Pancreatitis

Abdominal pain is the most common presenting symptom ofAP. In pediatric AP studies, 80% to 95% of patients presented withabdominal pain. Patients present with epigastric pain in 62% to 89%and diffusely in 12% to 20%. The ‘‘classic’’ presentation ofepigastric pain radiating to the back occurs in only 1.6% to5.6% of pediatric patients (15,16).

The pathophysiology of AP is characterized by a loss ofintracellular and extracellular compartmentalization, which couldresult from different mechanisms: obstruction of pancreatic secre-tory transport; activation of enzymes; or inability to stop theactivation cascade. AP occurs in genetically susceptible individu-als in whom the inflammatory reaction causes pancreatitis. This inturn stimulates visceral pancreatic and somatic peritoneal painreceptors (100). Other postulated mechanisms causing AP paininclude high pressures within the gland or pancreatic duct andsubsequent gland ischemia. Pain in AP is also likely related to therelease of tachykinin substance P and calcitonin-gene-relatedpeptide. Factors that stimulate primary sensory neurons includehydrogen ions, heat, leukotrienes, arachidonic acid metabolites,bradykinins and proteases, such as trypsin, released duringAP (101).


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Control of pain is an important therapeutic goal in themanagement of AP and commonly involves use of peripherallyand centrally acting analgesics. No data are published on optimalpain management in pediatric AP, and studies in adults have notidentified a single superior medication (66).

Opioid Analgesics

Because classic peripherally acting analgesics (such as acet-aminophen) often are insufficient in severe pancreatitis, opiates arerequired frequently to control pain. Morphine or related opioidswere utilized by 94% of respondents to manage children with APaccording to the 2012 INSPPIRE physician questionnaire (102).Morphine had been reported to cause sphincter of Oddi dysfunctionafter systemic administration (103). No clear evidence, however,supports this theory and morphine can be used safely in patientswith AP (104). Meperidine has been used in adults with AP butdrawbacks include its short half-life and potential of neurotoxicitythrough the buildup of toxic neurometabolites that can lead toseizures, myoclonus, and tremors (105). A review of narcotics andsphincter of Oddi function by Thompson (106), documents that nostudies to date directly compare the effects of meperidine andmorphine on sphincter of Oddi manometry and no comparativestudies exist in patients with AP. Furthermore, no studies orevidence exist to indicate morphine is contraindicated for use inAP. A Cochrane review from 2013 includes 5 studies with a total of227 subjects to assess the efficacy and safety of several opioids.Medications included were buprenorphine, pethidine, pentazocine,fentanyl and morphine. The overall conclusion is that opioids maybe an appropriate choice in the treatment of pain related to AP andthey may decrease the need for supplementary analgesia. In addi-tion to this, the risk of pancreatitis-associated complications orclinically serious adverse events is not different comparing opioidsand other analgesic agents (107).

Opioid-sparing Analgesics

NSAIDs have been hypothesized to be potential contributorsto the development of AP but have also shown benefit in AP painmanagement. Prophylactic NSAIDs including indomethacin anddiclofenac have been shown to be useful in several studies in theprevention of post-ERCP pancreatitis (108,109). With respect topain management post AP diagnosis, indomethacin has been foundto be superior to placebo and did not show an increased risk of GIbleeding in a small study (110). When compared with morphine,metamizole showed improved pain relief at 24 hours, but thedifference did not reach statistical significance (104).

Systemic administration of local anesthetics, mainly pro-caine, has been advocated as basic analgesia for AP. IV procaine isproposed to decrease pain and/or the necessity for auxiliary anal-gesic medication and possibly improve the clinical course of AP. In1 controlled trial, systemic administration of procaine in pancreati-tis improved and accelerated postoperative recovery after majorabdominal surgery, including diminished pain, improved cognitivefunction, and shortened duration of ileus as well as overall hospi-talization (111). But evidence is limited and there is lack of placebo-controlled data.

Epidural anesthesia (EA) widely used to induce analgesia inthe perioperative period and has also been used to decrease pain inpatients with AP. The mode of action has been attributed to asympathetic nerve blockade that redistributes splanchnic blood flowto nonperfused pancreatic regions. In a study of 35 patients withpredicted severe AP, EA was shown to significantly decrease painscores, improve pancreatic perfusion based on radiological


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perfusion studies, and improve clinical outcomes (decreasedrequirement for necrosectomy) (112). And, a prospective studyof 121 patients demonstrated good efficacy and safety of EA inadult AP (113).

Summary: No data provide guidance for optimal painmanagement in pediatric AP. Studies in adults have not identi-fied a single superior medication. No evidence exists supportingthe contention that morphine causes adverse events on thesphincter of Oddi.

Recommendations 2ci: IV morphine or other opioidshould be used for acute pancreatitis pain not responding toacetaminophen or NSAIDs.



Recommendation 2cii: Acute pain specialist servicesshould ideally be consulted in cases of more severe pain tooptimize pain management.



2d. Enteral and Parenteral Nutrition inPediatric Acute Pancreatitis

Oral and Enteral NutritionTraditionally, AP patients were managed by keeping nil per

os (114) and giving PN (115). It was hypothesized that by restingthe gut, the pancreas was allowed to ‘‘rest’’ and thus heal morerapidly. The rationale behind this theory was that presence offood in the intestines would stimulate cholecystokinin (CCK)release, which in turn would stimulate pancreatic enzyme secre-tion, which could lead to further activation of proteolytic enzymesand exaggerate the autodigestion process and worsen the injury(116,117).

In adults, a number of controlled studies, reviews and meta-analyses pertain to nutritional therapy in both severe and mild AP,including a review by the Dutch Pancreatitis Study Group andconsensus guidelines published by the International ConsensusGuideline Committee (118). Lodewijkx et al (119), support ENas being superior to PN, and an on-demand feeding strategy inpredicted severe AP. Mirtallo et al (118) reviewed 8 societal reportsin order to develop international consensus guidelines for nutritiontherapy in AP. They concluded that in adult AP, EN was preferableto PN and should be used first even in the presence of fistulas,ascites and pseudocysts.

The timing of EN initiation has been advocated to be as earlyas possible, especially as 1 of the goals of EN is to prevent bacterialtranslocation and thereby prevent the development of SIRS. Earlynutritional therapy is also purported to decrease cytokine responseand incidence of gastroparesis and intestinal ileus. Although somestudies (120) show no difference in outcomes when EN wasinitiated before or after 72 hours of presentation, a 2008 meta-analysis examining 11 RCTs demonstrated that EN started within48 hours of presentation significantly decreased rates of mortality,infections and multiorgan failure compared with PN (121). Theseeffects were diminished when EN was started after 48 hours. In a2011 review of nutritional support of adult AP, it was concludedthat early nutritional support, particularly EN, but also PN, reducedcomplications and improved survival (122). This review stated thatto be effective, nutritional support had to begin within 72 hours. Ithas been stated that EN should be considered ‘‘an active therapeuticintervention that improves the outcome of patients with pancreati-tis’’ (123).


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Clinical studies comparing the outcomes of PN and EN inpatients with AP report that the use of EN in severe acute pancrea-titis (SAP) or predicted SAP results in significantly lower rates ofcomplications (124–132). A recent meta-analysis demonstratedsuperiority of EN compared with PN with a lower incidence ofinfection and multiorgan failure, resulting in lower mortality ratesand a shorter hospital stay (133). Since full EN may not alwaysfeasible during AP because of increase in pain or feeding intoler-ance, some, however, have advocated a role for a combination ofEN and PN. In 1 study that randomized 100 patients to receive PNalone versus PN in combination of EN or EN alone, sepsis, intra-abdominal infection, and length of hospitalization declined whenEN was included in the management (134).

The routes of EN described have included gastric and jejunal.Two small studies found no difference in outcomes betweennasogastric and nasojejunal fed groups (135,136). A meta-analysisof 10 RCTs showed no differences in outcomes between groupsreceiving (semi)elemental and polymeric formulas (137).

No guidelines have been published relating to nutritionalsupport of children with AP. A recent study by Abu-El-Haija et al(138) demonstrated the feasibility of establishing enteral feeds inpediatric AP, without complicating the course or affecting the painscores of AP. From the same center, a retrospective study showedthat a combination of early enteral feeds in addition to greater than1.5 times maintenance IV fluids were associated with a shorterLOS and milder illness compared with those who remained nil peros for 48 hours and had lower rates of IV fluids than 1.5 timesmaintenance (72). Two children with severe AP are reported whowere treated successfully with nasojejunal feedings in a PICUand switched to oral feeding when discharged to the generalward (139).

Parenteral Nutrition

Parental nutrition provides the required calories and nutrientsto compensate for a catabolic state. Concern that PN could furtherstimulate the pancreas and result in exaggeration of the autodiges-tive process has not been supported by the literature (140,141). Dataindicate that infusion of protein does not stimulate pancreaticsecretions (142). When comparing different PN formulations, PNenhanced with glutamine has been reported to reduce overallcomplication rates, as well as reduce LOS (143–147). The admin-istration of IV glucose also does not appear to stimulate pancreassecretion (148,149). Infusion of glucose in critically ill patients maybe useful to provide an easily accessible energy source during acatabolic state and counteract gluconeogenesis from protein break-down. But glucose infusion must be monitored, as it may predisposeto hyperglycemia (150), as an inflamed pancreas may not mount anappropriate insulin response.

Hypertriglyceridemia is associated with severe AP (151–154), but the mechanism leading to SAP is not clear (155).Insufficient data exist to recommend or to discourage the use ofparenteral lipids in AP.

With respect to the timing of PN in AP, where the measuredoutcome was mortality, data suggest that early PN is significantlymore beneficial than bowel rest in adult severe AP (121). In all caseswhere EN is not possible for a prolonged time, such as in ileus,complex fistulae, and abdominal compartment syndrome, PN hasbeen advocated. In contrast, a recent study advocated for delayinginitiation of PN to 7 days in critically ill children due to increasedrisk of infection, and increased complication rates when PN wasinitiated within the first 24 hours of ICU stay. Early EN was allowedin both groups. The presence or percentage of AP patients specifi-cally was, however, not specified in that report (156).


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Summary: Adult literature supports early EN to reduceAP complications and improving survival. Pediatric literaturesupports early EN in mild AP cases, and small case report insevere AP.

Recommendation 2di: Except in the presence of directcontraindications to use the gut, children with mild acutepancreatitis may benefit from early (within 48–72 hours ofpresentation) oral/EN to decrease LOS and decrease risk oforgan dysfunction.



Recommendation 2dii: Parenteral nutrition (PN) shouldbe considered in cases where EN is not possible for a prolongedperiod (longer than 5–7 days) such as in ileus, complex fistulae,abdominal compartment syndrome, to reduce the catabolicstate of the body. Enteral nutrition should commence as soonas feasible, with a combination of EN and PN being superior tosole PN.


Voting results: Strongly agree¼ 15 agree¼ 7; neutral¼ 1;disagree¼ 0; strongly disagree¼ 1.

Recommendation 2diii: In cases of pancreatic laceration,fracture, or duct disruption, it is unclear whether oral/enteralfeedings may be detrimental in the acute phase. This must befurther studied.

21/24 U 88% agreement with recommendationVoting results: Strongly agree¼ 13; agree¼ 8; neutral¼ 2;

disagree¼ 0; strongly disagree¼ 0; no vote¼ 1.

2e. Use of Antibiotics in Pediatric AcutePancreatitis

The rationale for consideration of antibiotics in the manage-ment of AP relates to the concern for bacterial infection fromtranslocated intestinal microbiota. Antibiotics are not recom-mended for use in adult mild AP (69).

In the management of adult severe AP, antibiotics have beenstudied to prevent and manage infections. Imipenem and/or thirdgeneration cephalosporins have been most often used historically inan attempt to reduce morbidity and mortality. This prophylacticapproach is controversial, with prior studies suggesting benefit(157–159), whereas other studies did not demonstrate benefit fromroutine use (160) in the absence of documented infection. Prophylac-tic antibiotics have been used in the setting of sterile necrotizingpancreatitis to prevent infected necrotizing pancreatitis (161,162),particularly imipenem (162). Systematic reviews do not, however,support a benefit regarding mortality, for infections not involving thepancreas, or for the reduction of surgical interventions in adults (161).More recent meta-analyses support the use of antibiotics for infectednecrotizing pancreatitis but not for sterile necrosis (163–165). Currentadult AP recommendations are to use antibiotics only for infectednecrosis, or in patients with necrotizing pancreatitis who are hospi-talized and not improving clinically without antibiotic use (69).Infected necrosis should be suspected if the patient’s clinical statusis worsening with fevers, or with presence of gas within collections onimaging. In certain situations aspiration of the fluid by an endoscopic-guided technique or via interventional radiology and establishment ofappropriate drainage may be needed to guide management (8). Fornecrotizing pancreatitis, antibiotics known to penetrate necrotic tissueare recommended, such as carbapenems, quinolones, and metronida-zole, as antibiotic use in this setting has been demonstrated to delaysurgical interventions and decrease morbidity and mortality (31).


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Documented infections originating outside the pancreasshould be treated as indicated.

No studies have been published on the use of antibiotics inthe management of AP in children.

Summary: Antibiotics should not be used in the man-agement of AP, except in the presence of documented infectednecrosis, or in patients with necrotizing pancreatitis who arehospitalized and not improving clinically without antibioticuse. Antibiotics known to penetrate necrotic tissue should beused in management of infected pancreatic necrosis as thesemay delay surgical intervention and decrease morbidity andmortality.

Recommendations 2ei: Prophylactic antibiotics are notempirically recommended in severe acute pancreatitis.



Recommendation 2eii: Antibiotic use is indicated only incases of documented infected necrosis in acute pancreatitis.

16/24 U 67% agreement with recommendation. Recom-mendation not supported. This was identified as an area ofparticular controversy requiring further study.

Voting results: Strongly agree¼ 10; agree¼ 6; neutral¼ 2;disagree¼ 4; strongly disagree¼ 0; no vote¼ 2.

2f. Use of Protease inhibitors in Pediatric AcutePancreatitis

As AP is hypothesized to be a necroinflammatory processbegun through the acute, and inappropriate, activation of theprotease trypsin and pancreatic zymogens within the parenchyma,investigators have been keenly interested in blocking this inflam-matory process to limit extent of injury.

The 2 main compounds described in the literature to inhibit thisenzyme activation include the serine protease inhibitor gabexatemesilate and the trypsin inhibitor aprotinin. In 1993, Pederzoliet al (166) reported results of a randomized, double-blind multicenterclinical trial on use of gabexate mesilate versus aprotinin in APtherapy. In this study, gabexate mesilate appeared more favorable toaprotinin for the period 24 to 72 hours, but importantly, a placebocontrol arm is missing. Timing of treatment and mode of deliveryseem to be key factors in efficacy (166,167). Ino et al studied theefficacy of continuous regional artery infusion CRAI with gabexatemesilate and antibiotics for severe AP via a small prospective studyinvolving 9 patients receiving CRAI for 3 to 5 days and 9 othersreceiving systemic protease inhibitor therapy and antibiotics.Abdominal pain and SIRS disappeared quicker, LOS was signifi-cantly shorter in the CRAI group (167). CRAI of anti-proteases andantibiotics has been reported to reduce C-reactive protein andAPACHE II scores when initiated within 72 hours of onset of illness(168), an approach described in pediatric patients as well (169).

A 2007 review by Kitagawa and Hayakawa found no evi-dence to justify the routine use of anti-proteases in AP, and althoughthe use of continuous IV high-dose protease inhibitors and anti-biotics may be effective in preventing the exacerbation of severeAP, cost-effectiveness studies were necessary. Of importance, thesecompounds are not Food and Drug Administration (FDA)-approvedin the United States (170–172).

Summary: Certain adult studies support use of anti-proteases in the management of severe AP, but no definiterecommendations have ever been made for their use. Studiesare not randomized with placebo controls and only a few casesare described in pediatric patients.


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Recommendations 2f: Anti-proteases cannot be recom-mended in the management of acute pancreatitis in children atthis time.



2g. Use of Antioxidants in Pediatric AcutePancreatitis

Oxidative stress contributes to injury in AP, through forma-tion of oxygen free radicals that cause damage to the lipid pancre-atic cell membrane, depolarization of the mitochondrial membrane,and induction of DNA fragmentation (173). This contributes toedema, generation of pain and may also be involved with theprocess of necrosis. Antioxidants have thus been hypothesized tobe of potential benefit as adjunct management in AP by preventingthe formation of free radicals or scavenging existing oxygenfree radicals.

The agents most studied have been antioxidant vitamins(ascorbic acid, a-tocopherol, b-carotene), inorganic antioxidants(selenium) and glutamine. Two partially overlapping meta-anal-yses published in 2015 utilize different methodologies to assessbenefit of antioxidants in acute pancreatitis, 1 reviewing 11 andother 12 adults randomized controlled trials (168,169). Pederzoliet al (168), found that antioxidants reduce the number of APcomplications and shortened LOS, with glutamine reducing com-plications and mortality rates. Ino et al, reported that antioxidanttherapy shortens LOS, and decreases serum C-reactive protein, butonly after 10 days (169).

A significant limitation of published data of antioxidants inadult AP is that trials have included the entire spectrum of mild tosevere AP. In addition to this, different combinations of antiox-idants and timing of delivery have been utilized in trials. Largerandomized studies lack standardization of specific antioxidants aswell as timing and duration of treatment.

No data exist on antioxidant use in AP in the pediatricpopulation.

Summary: Pediatric data regarding the use of antioxi-dants in AP is lacking Adult publications display significantheterogeneity with respect to composition, timing, and durationof therapy. Despite potential benefits described in the adultseries, evidence is insufficient to support their use in pediatricsat this time.

Recommendation 2 g: Antioxidants should not be consid-ered standard therapy in the management of pediatric acutepancreatitis.



2h. Role of Probiotics in Pediatric AcutePancreatitis

Up to third of adult patients may develop severe AP,characterized by SIRS, organ failure and an increased risk ofinfection (174). In patients with infected peri-pancreatic and pan-creatic necrosis, the risk of mortality is significantly increased.Reduction of gut permeability and bacterial overgrowth during APis hypothesized to decrease the risk of infected pancreatic necrosisand thereby decrease the risk of mortality (175,176).

The World Health Organization defines probiotics as ‘‘livemicrobes which, when administered in adequate amounts, confer a


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health benefit to their host’’. Probiotics have been shown to play arole in maintaining gut microflora balance, inhibiting the growth ofharmful bacteria, and enhancing immune function (177). Of impor-tance, published studies have utilized different compositions anddosing regimens of probiotic bacteria.

Muftuoglu et al (177) demonstrated that lactobacillus aci-dophilus and bifidobacterium lactis decrease the severity of histo-logical damage in an experimental pancreatitis model. Early smalladult clinic trials suggested a beneficial role for probiotics in themanagement of AP. Olah et al (178) randomized 45 patients toreceive either 109 live or heat killed lactobacillus plantarum twicedaily together with enteral feeds. They found a statistically signifi-cant lower risk of infected pancreatic necrosis in the study groupcompared with control groups.

Subsequently, the PROPATRIA study, a double-blinded,placebo-controlled randomized, multicenter study on the role ofprobiotics in preventing infectious complications in AP) consistingof 298 adult patients with predicted severe AP, however, demon-strated a significantly higher risk of mortality in the multispeciesprobiotic group (179,180). Two small randomized trials sincecompleted did not demonstrate an increase in mortality(181,182), but the impact of the adverse findings of the PROPA-TRIA study has led to generalized caution in use of probiotics inadult AP.

No pediatric study has examined the role of probiotics inchildren with AP.

Summary: Subsequent to small case series suggesting apotential benefit of probiotics in adult AP, a large randomizedstudy demonstrated increased mortality in a probiotic group.No pediatric studies have been published.

Recommendation 2 h: Probiotics cannot be recom-mended in the management of pediatric acute pancreatitis atthis time. Highest-quality published adult evidence suggeststhey may not only be of no benefit, but increase mortality.



2i. Role of Endoscopy in Pediatric AcutePancreatitis

Various causes of duodenal mucosal inflammation have beenlinked to increased risk of AP. Celiac disease pancreatic-associatedmanifestations include endocrine and exocrine insufficiency, acuteand CP, malnutrition, papillary stenosis secondary to duodenitis, orimmunological disturbances and have all been hypothesized to beimplicated mechanistically (183–185). Gallstone disease has beenfound in up to 34% of Crohn patients and may manifest as AP (186).AIP and primary sclerosing cholangitis (187) can also be found inpatients with inflammatory bowel disease presenting with AP(188–190). Although IgG4 elevation is seen in Type I AIP in adultpatients, pediatric patients with AIP present commonly withoutIgG4 elevation, where biopsies from the duodenum or gastroduo-denal inflammatory lesions can be helpful in the diagnosis(191,192). Acute and CP have been uncommonly reported asmanifestations or associations of Helicobacter pylori infection(193,194). Exceedingly rare though possible causes of pancreatitisin children are tumors involving the ampulla or peri-ampullaryregion of the duodenum. Such lesions may be first identified byradiographic imaging, but can also be found at the time of endo-scopic assessment. From available case reports, the mechanism bywhich these patients develop recurrent pancreatitis is not fullyunderstood, but is likely related to tumor obstruction at the level


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of the ampulla (195,196). But in general, the role of esophagogas-troduodenoscopy in AP is limited.

No studies evaluate indications or benefits of esophagogas-troduodenoscopy in pediatric AP.

Summary: The role of endoscopy in the acute care ofchildren with AP is unclear. The potential for primary extra-pancreatic diseases resulting in the development of AP requiresthoughtful consideration.

Recommendation 2i: Esophagogastroduodenoscopy isnot considered a standard diagnostic tool in pediatric acutepancreatitis at this time. Indication for its use should be deter-mined on a case-by-case basis.



2j. Role of Endoscopic RetrogradeCholangiopancreatography in Pediatric AcutePancreatitis

The role for ERCP in AP has evolved with technologicalimprovements in the diagnostic capabilities of MRI/MRCP andwith increasing pediatric experience with EUS. With the availabil-ity of these latter diagnostic tools for pancreatic disorders, ERCP isincreasingly being used primarily for therapeutic interventions orfor unclear diagnoses following MRCP or EUS. ERCP is safe inchildren with the most common complication being mild post-ERCP pancreatitis, occurring at rates similar to those in adults(�3%–10%) when being done by experienced endoscopists (197–205). Biliary obstruction and CP are the most common indicationsfor ERCP in children. In pediatric AP, ERCP has a limited role,performed almost exclusively for biliary pancreatitis secondary tocholedocholithiasis or sludge. ERCP for choledocholithiasis with-out pancreatitis is safe and effective (206,207), but no specificrecommendations exist in pediatrics about the timing of ERCP incholedocholithiasis or acute biliary pancreatitis. In adults, a largemeta-analysis and the IAP evidence-based guidelines for manage-ment of acute biliary pancreatitis have recommended ERCP within48 hours of symptomatic onset if patient has obstructive jaundiceand/or cholangitis. Otherwise, ERCP can be done electively foruncomplicated choledocholithiasis and in other cases of biliarypancreatitis, regardless of severity (208,209).

Less common indications for ERCP in AP are pancreatic ductalstones, strictures, pseudocyst drainage, and pancreatic duct leaks(210). Pancreatic ductal stones and strictures are typically featuresof acute recurrent or CP, thus are relatively uncommon indications forERCP in AP. In rare circumstances when ductal obstruction preventsresolution of pancreatitis, therapeutic ERCP can be performed. Pan-creatic pseudocysts in children can occur from acute or CP, but themajority occurs following blunt trauma. Pancreatic pseudocysts, arehomogenous collection of pancreatic fluid enclosed by fibrous orgranulation tissue but lacking an epithelial lining (15,211), and candevelop from fluid collections persisting greater than 4 weeks (212).ERCP can be used to assess communication of the pseudocyst withpancreatic duct, where a transpapillary stent can be placed for drain-age. Otherwise, endoscopic cystagastrostomy (213–215) and EUS-guided drainage (216) are safe and effective ways to drain pancreaticpseudocysts in children and may be considered based on the location ofthe pseudocyst. Pancreatic duct injury and leak can also occurfrom trauma. Early endoscopic or surgical intervention may help tominimize ongoing morbidity from a ductal leak, as ERCP provides arapid and more definitive method to delineate the location and extentof injury than MRCP or CT and also provides the opportunity fortherapeutic stent placement across the injury (217,218).


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Summary: The role of ERCP in acute pancreatitis pri-marily relates to therapeutic management of biliary pancreati-tis secondary to choledocholithiasis or sludge. Adult literaturesuggests the performance of ERCP within 48 hours of symp-tomatic onset if patient has obstructive jaundice and/or cho-langitis. Less common indications for ERCP in acutepancreatitis are pancreatic ductal stones, strictures, pseudocystdrainage, and pancreatic duct leaks or ductal lacerations.

Recommendations 2ji and 2jii: (2ji) The role of ERCP islimited in acute pancreatitis and depends on local expertise.(2jii) ERCP is indicated in management of acute pancreatitisrelated to choledocholithiasis causing biliary pancreatitis, andfor pancreatic duct pathologies such as ductal stones or ductalleaks.



2k. Role of Endoscopic Ultrasonographyin Pediatric Acute Pancreatitis

EUS has been utilized to help determine the etiology of AP.EUS not only comprehensively evaluates the pancreatic paren-chyma and duct, but also the hepato-biliary anatomy. Biliarydisease such as choledocholithiasis can be evaluated with EUSespecially when transabdominal ultrasound does not visualize thedistal common bile duct. EUS can also determine the presence ofmicrolithiasis in the gallbladder that many times is not visualized ontransabdominal ultrasound or CT scan. Microlithiasis can lead toAP, and is treatable with cholecystectomy (219). Althoughextremely rare in children, pancreatic tumors, which could bedue to pancreatic neoplasm or AIP can present with AP and befurther evaluated with EUS with the possibility of pancreatic tissuesampling (220,221).

The therapeutic role of EUS in AP is mostly limited for thetreatment of complications of AP, namely pancreatic fluid collec-tions or WON. EUS has been shown to be useful in the managementof pancreatic fluid collections/or necrosis secondary to severe AP.Spontaneous resolution of pseudocysts is believed to occur morecommonly in children than adults, especially if < 5 cm in size(expert opinion). Thus, most collections of any type can be managedconservatively and therapeutic intervention is not necessary in theacute setting except with evidence of infection (222). If maturationoccurs (typically after 4–6 weeks), self-resolution is less likely, andthe patient may, however, need endoscopic drainage. Other indica-tions for EUS intervention and drainage include large size whencausing clinical symptoms, suspected infected collections or per-sistent symptoms from the pseudocyst. EUS-guided drainage andthe creation of a cystgastrostomy has been demonstrated to be aseffective and safe as surgical cystgastrostomy and has been shownto be successful even in children (223).

Summary: Based on adult literature, EUS may be usefulto determine the etiology of acute pancreatitis, which mayinclude diagnosis of distal common bile duct stones, pancreaticmasses, or AIP. Its role for therapy is mostly limited for thetreatment of complications of acute pancreatitis, namely pan-creatic fluid collections or WON secondary to severe AP.

Recommendation 2k: EUS is not considered a standarddiagnostic tool in pediatric acute pancreatitis at this time.Indication for its use should be determined on a case-by-casebasis.




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2l. Role of Surgery/Surgical Consultationin Pediatric Acute Pancreatitis

Surgical interventions are not part of the algorithm in themanagement of a typical episode of AP. Publications relate to adultexperience. An early indication for surgery includes management ofabdominal compartment syndrome. Management of pancreaticnecrosis with early necrosectomy within first 72 hours has, how-ever, been shown to lead to increased morbidity and mortalitycompared with those delayed at least to beyond 12 days (224).Guidelines by the International Association of Pancreatology from2002 suggest that delaying necrosectomy surgery for at least 3 to4 weeks after onset of disease leads to lower morbidity andmortality (209). The 2013 ACG guidelines on the managementof adult AP have commented on consideration of surgery in thecontext of gallstone pancreatitis, debridement of necrosis (infectedvs sterile), and minimally invasive management of pancreaticnecrosis (32). Recommendations included early cholecystectomyduring the same hospitalization for a mild attack of gallstonepancreatitis, and discussion between gastroenterology and surgeryfor timing of cholecystectomy versus other therapeutic options incases of severe AP, especially with necrosis. For patients withpersisting clinical instability and deterioration in the context ofpancreatic necrosis, drainage may be necessary to improve patientstatus and limit morbidity and mortality. The ACG guidelinespropose that debridement of necrosis should be delayed wheneverpossible, ideally to beyond 4 weeks from presentation, to allowinflammatory reactions to be better organized. Even in need ofnecrosectomy, less invasive methods including percutaneous radio-logic, or endoscopic drainage/debridement shouldbe consideredalong with laparoscopic surgical management as options to befavored above open surgery (32).

The 2015 pancreatitis of biliary origin, optimal timing ofcholecystectomy (PONCHO) trial involving 266 inpatients ran-domized to interval cholecystectomy or same-admission cholecys-tectomy also supported that same-admission cholecystectomyreduced the rate of recurrent gallstone-related complications inadult patients with mild gallstone pancreatitis with extremelylow risk of cholecystectomy-related complications (225).

In cases of severe abdominal trauma requiring emergentlaparotomy (including motor vehicle accidents), injury to thepancreas should be sought, including those involving the pancreaticduct. The severity of pancreatic trauma may be graded according tothe American Association for the Surgery of Trauma PancreasInjury Scale, wherein 5 grades of injury may be assigned (226).Higher-grade injuries to the pancreas from trauma typically alsoinclude associated duodenal injuries. Those with milder blunt gradeI and II injuries may be managed nonoperatively. In cases ofpancreatic trauma, a multidisciplinary approach involving themedical/gastroenterology and surgical teams is indicated.

The pediatric literature regarding the indications for surgery ismuch more limited. With regard to biliary pancreatitis, a retrospectivecase series of 19 children admitted with biliary pancreatitis reported 9children undergoing early cholecystectomy with no adverse events,and 4 of 10 children that had delayed surgery experiencing adverseclinical events (including recurrence of pancreatitis) (227).

Summary: Indications for acute surgical intervention inAP indications include abdominal trauma where patient insta-bility and/or search for associated injury to other organs isoccurring. In the context of biliary pancreatitis, cholecystec-tomy has been shown to not only be safe, but prevent recur-rences if occurring within the index hospitalization. Adultliterature suggests that early intervention in pancreatic necrosisleads to increased morbidity and mortality, and hence


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debridement of pancreatic necrosis causing patient instabilityshould preferably be delayed at least 4 weeks from presentationand ideally performed by endoscopic or percutaneous means.

Recommendation 2li: Cholecystectomy safely can andshould be performed before discharge in cases of mild uncom-plicated acute biliary pancreatitis.



Recommendation 2lii: In the management of acutenecrotic collections, interventions should be avoided anddelayed, even for infected necrosis, as outcomes are superiorwith delayed (>4 weeks) approach.



Recommendation 2liii: When drainage or necrosectomyis necessary, nonsurgical approaches including endoscopic(EUS, and ERCP-assisted) or percutaneous methods are pre-ferred over open necrosectomy or open pseudocyst drainage.



3. OUTCOMES OF PEDIATRIC ACUTEPANCREATITIS

Overall outcomes in AP in children are favorable compared toadults. The average length of hospitalization for children with APaverages 2.8 to 8 days, although infants/toddlers tend to be admittedfor a longer period (average 19.5 days) (12,15,72,228,229). Earlyinitiation of EN and aggressive fluid resuscitation has been linked toshorter hospital stay, fewer ICU admissions, and decreased rates ofsevere AP compared with patients who are kept nil per os (72). Thesefindings appear generally in line with most adult studies (230), butmay not have been applied to pediatric patients until recently. Highermortality in pediatric AP is associated with systemic disease but islow overall and is less than 5% in most cohorts, even including ICUadmissions (15,29,231,232).

Early-onset complications in AP include multiorgan dys-function or shock (15). Acute peripancreatic fluid collections areseen in the acute phase of pancreatitis and tend to resolve sponta-neously. The frequency of pseudocyst formation ranges from 8% to41% in children with pancreatitis, and higher rates are seen inpatients who present with pancreatitis related to abdominal trauma(15,211,233). Pseudocysts are often asymptomatic and can bemanaged conservatively or become larger and cause abdominalpain, vomiting, or fever. They can also become infected in 10% to15% of cases (234). Another late-onset complication relates topancreatic necrosis. Necrosis can manifest firstly as an acutenecrotic collection and then mature to WON (8). Managementoptions for drainage of pseudocysts and WON collections includeendoscopic (transpapillary or transmural) drainage, percutaneouscatheter drainage, or open/laparoscopic surgery. The modalitychosen depends on size, location, anatomy and the risks/benefitsof the procedure, although percutaneous and EUS-guided transgas-trointestinal drainage is now becoming more widely accepted (235).

Approximately 15% to 35% of children with acute pancrea-titis will have another bout of pancreatitis. Pediatric ARP isassociated with pancreatico-biliary anomalies, AIP, metabolic dis-orders, and hereditary pancreatitis (15).

Summary: Children need to be followed during theircourse of AP for local and systemic complications that may includeorgan dysfunction, acute fluid collections and subsequently WON


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or pseudocysts. Overall pediatric patients with acute pancreatitishave a good prognosis with extremely low rate of mortality, but upto 15–35% rate of recurrence is reported.

Recommendation 3: Children with acute pancreatitisshould receive close follow-up by a health care provider toidentify early or late complications, or recurrence.



4. SUMMARY OF RECOMMENDATIONSPlease refer to Table 1 for a summary of the above recom-

mendations for the management of pediatric AP accepted by at least75% of the voting group. Only 1 recommendation, relating toantibiotic use in documented infected necrosis (Recommendation2eii) did not reach sufficient level of agreement to be accepted, withonly 16/24 (67%) voters agreeing with the statement, and 2 votersbeing ‘‘neutral,’’ 4 voters disagreeing, and 2 voters abstaining. Asvoting was conducted in an anonymous fashion without requestingexplanation for voting category selected, the reason for the dis-agreement cannot be confirmed. This topic had, however, beendebated at the October 2016 face-to-face meeting, with certainmembers advocating for antibiotic prophylaxis for severe pancrea-titis episodes involving pancreatic necrosis without necessarilyinfected necrosis.

5. FUTURE DIRECTIONSThe differences in etiologies leading to adult versus pediat-

ric AP, the differences in physiology between children and adults,and the increased coexistence of extrapancreatic illnesses in manyadult patients would be anticipated to lead to different outcomes inchildren versus adults with AP. Findings from AP studies in adultpatients thus cannot be justified as appropriate surrogate formanaging children with AP. A 2014 manuscript by Abu-El-Haijaet al (4) highlighted areas in need of research within the realmof management of pediatric AP. Areas of note included the needfor robust studies that are prospectively designed to answerfundamental questions on optimizing imaging modalities, painmedications, rehydration strategies, route and timing of EN,surgical interventions, and prognostication scores in pediatricpancreatitis.

This current review of the available literature in pediatric APhighlights the ongoing lack of high-quality research focusing onpediatric AP in the great majority of spheres mentioned above.Some limited evidence has been published regarding fluid manage-ment and early introduction of EN in children with AP, andprognostication of severity in pediatric AP. Recommendations onmonitoring patients with AP relate to the care of sick children ingeneral, and are not specific to AP. Pain management similarly hasnot focused on children with AP. Other than 1 retrospective caseseries on biliary pancreatitis timing of cholecystectomy, surgicalrecommendations remain extrapolations from adult literature.Extremely few studies are published on use of protease inhibitors.Experience with ERCP and EUS in pediatric AP remains limited.No pediatric AP-specific data are published regarding use ofantibiotics, antioxidants, or probiotics. The lack of agreement onproposed recommendation 2eii relating to limiting use of antibioticsto only cases of documented infected pancreatic necrosis supportsthe need for further systematic research on use of antibiotics for AP.Certain authors stated monitoring recommendations were not suf-ficiently aggressive, leading to ‘‘neutral’’ votes cast. The authorswish to highlight the importance and necessity of supportingpediatric-specific research in the field of AP in all areas ofmanagement detailed within this manuscript.


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TABLE 1. Summary recommendations for management of acute pancreatitis in children

Topic Recommendation

Diagnosis AP Diagnosis of pediatric AP should be as per previously published INSPPIRE criteria. Diagnosis of AP in pediatric patients requires

at least 2 of the following: (1) abdominal pain compatible with AP, (2) serum amylase and/or lipase values�3 times upper limits

of normal, (3) imaging findings consistent with AP

Initial imaging may be accomplished via transabdominal ultrasonography, with other imaging (CT, MRI) reserved for more

complicated cases � tailored to suspected etiology

Based on most frequent etiologies and those for which therapeutic options exist, first attack of AP testing should include liver

enzymes (ALT, AST, GGT, ALP, bilirubin), triglyceride level, and calcium level

Fluid resuscitation Children with AP should be initially resuscitated with crystalloids, either with LR or NS in the acute setting. Based on assessment

of hydration status/hemodynamic status, if evidence of hemodynamic compromise, a bolus of 10 to 20 mL/kg is recommended

Children with diagnosis of AP should be provided 1.5 to 2 times maintenance IV fluids with monitoring of urine output over the

next 24 to 48 hours

Monitoring In patients admitted to an inpatient ward, vitals should be obtained at least every 4 hours during the first 48 hours of admission and

during periods of aggressive hydration to monitor oxygen saturation, blood pressure and respiratory rate. Frequency to be

adjusted based on clinical status. Abnormalities of vital signs should prompt specialist assessment

BUN, creatinine and urine output should be monitored routinely during the first 48 hours as marker of appropriate fluid

management and to screen for AKI. Abnormalities should prompt nephrology assessment

Pain management IV morphine or other opioid should be used for acute pancreatitis pain not responding to acetaminophen or NSAIDs

Acute pain specialist services should ideally be consulted in cases of more severe pain to optimize pain management

Nutrition Except in the presence of direct contraindications to use the gut, children with mild AP may benefit from early (within 48–72 hours

of presentation) oral/enteral nutrition (EN) to decrease LOS and decrease risk of organ dysfunction

Parenteral nutrition (PN) should be considered in cases when EN is not possible for a prolonged period (longer than 5–7 days) such

as in ileus, complex fistulae, abdominal compartment syndrome, to reduce the catabolic state of the body. Enteral nutrition

should commence as soon as feasible, with a combination of EN and PN being superior to sole PN.

In cases of pancreatic laceration, fracture, or duct disruption, it is unclear whether oral/enteral feedings may be detrimental in the

acute phase. This must be further studied.

Antibiotics Prophylactic antibiotics are not empirically recommended in severe AP

Antibiotic use is indicated only in cases of documented infected necrosis in AP

Proteases Anti-proteases cannot be recommended in the management of acute pancreatitis in children at this time

Antioxidants Antioxidants should not be considered standard therapy in the management of pediatric AP

Probiotics Probiotics cannot be recommended in the management of pediatric AP at this time. Highest-quality published adult evidence

suggests they may be not only of no benefit, but increase mortality

Endoscopy Esophago-gastroduodenoscopy is not considered a standard diagnostic tool in pediatric AP at this time. Indication for its use should

be determined on a case-by-case basis

ERCP The role of ERCP is limited in AP and depends on local expertise. ERCP is indicated in management of AP related to

choledocholithiasis causing biliary pancreatitis, and for pancreatic duct pathologies such as ductal stones or ductal leaks

EUS EUS is not considered a standard diagnostic tool in pediatric AP at this time. Indication for its use should be determined on a case-

by-case basis

Surgery Cholecystectomy safely can and should be performed before discharge in cases of mild uncomplicated acute biliary pancreatitis

In the management of acute necrotic collections, interventions should be avoided and delayed, even for infected necrosis, as

outcomes are superior with delayed (>4 weeks) approach

When drainage or necrosectomy is necessary, non-surgical approaches including endoscopic (EUS, and ERCP-assisted) or

percutaneous methods are preferred over open necrosectomy or open pseudocyst drainage

Outcomes/surveillance Children with AP should receive close follow-up by a health care provider to identify early or late complications, or recurrence

AKI¼ acute kidney injury; ALP¼ alkaline phosphatase; ALT¼ alanine aminotransferase; AP¼ acute pancreatitis; AST¼ aspartate aminotransferase;BUN¼ blood urea nitrogen; CT¼ computed tomography; ERCP¼Endoscopic Retrograde Cholangiopancreatography; EUS¼ endoscopic ultrasonography;GGT¼ gamma-glutamyl transferase; INSPPIRE¼ INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE; IV¼ intravenous; LOS¼ lengthof stay; MRI¼magnetic resonance imaging.


6. CONCLUDING REMARKSDue to the increased incidence of pediatric acute pan-

creatitis in recent years, pediatric specialists must be aware ofthe literature regarding its management. This clinical reportreviews published evidence and provides recommendations foroptimal management of AP in children, drawing upon adultliterature, the limited pediatric studies and expert opinion inareas where pediatric data are lacking. To optimize pediatricAP outcomes, it will be critical to revisit these topicsagain in the near future when more pediatric focused, prospectivestudies in all aspects of pancreatitis management becomeavailable.


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Acknowledgments: The authors wish to thank Ms MelissaDavis, intake coordinator at Cincinnati Children’s HospitalMedical Center for summarizing the second round of votingresults. We also wish to thank the NASPGHAN Council for theirreview of the manuscript.

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