FEATURE ARTICLE

An Update on Pediatric Pancreatitis

Monica Shukla-Udawatta, MD; Shailender Madani, MD; and Deepak Kamat, MD, PhD, FAAP

such as fibrosis and necrosis, which may

ABSTRACT lead to pancreatic endocrine or exocrine
There has been a rise in the incidence and number of admissions of children with pancre- insufficiencies.3 ARP is defined as two
atitis over the past 20 years. Current management practices for pancreatitis in children are or more separate episodes of AP with
adapted from standards of care for adults, and there are a lack of multicenter, prospective interim return to baseline. The diagno-
research studies on pancreatitis in children. There are inherent differences in the clinical sis of CP requires recurrent episodes of
presentation and natural course of pancreatitis between adults and children. This review pancreatitis with exocrine or endocrine
focuses on the current understanding of the epidemiology, etiologies, evaluation, and man- insufficiency and characteristic imaging
agement of children with pancreatitis. [Pediatr Ann. 2017;46(5):e207-e211.] findings.4 These findings include pancre-
atic calcifications, ductal dilatation, fluid
collections, and, in advanced cases, pan-

P
ancreatitis in children has been dren among pediatric gastroenterologists, creatic fibrosis or atrophy.
diagnosed more frequently in the but all of them were extrapolated from
past few decades, possibly due to adult studies. Lack of a uniform classifi- CHANGING ETIOLOGIES
an increase in health care provider aware- cation system has impeded the compara- The leading causes of pancreatitis
ness and etiologies of pancreatitis being tive study of outcomes between various in adults are calculous gall bladder dis-
identified, as well as more thorough centers. The International Study Group ease and alcohol abuse. This contrasts
evaluations of children.1,2 In the United of Pediatric Pancreatitis: In Search for a with the leading causes of pancreatitis
States, the incidence of acute pancreati- Cure (INSPPIRE) consortium is the first in children, which are biliary system
tis over the past decade was estimated to global, multicenter collaboration estab- abnormalities, medications, systemic
be 13.2 cases per 100,000 people annu- lished to systematically define pediatric diseases (eg, sepsis, cystic fibrosis, in-
ally, meaning that approximately 11,000 pancreatitis and develop a standardized flammatory bowel disease, hemolytic
children were diagnosed each year.2 approach to diagnosis and management. uremic syndrome), and blunt abdomi-
This increase in pancreatitis in children Three categories of pancreatitis have nal trauma. Up to 30% of cases of AP in
has created a significant health and eco- been defined: acute pancreatitis (AP), children can be attributed to gallstones
nomic burden, with hospitalization costs acute recurrent pancreatitis (ARP), and that cause obstruction of the pancreatic
nearing approximately $200 million an- chronic pancreatitis (CP). AP is defined duct.5,6 Drug-induced pancreatitis (DIP)
nually.2 as a reversible inflammatory process of has been estimated to account for 13%
the pancreas that may be self-limited or of cases of pediatric AP.7 However, the
CLASSIFICATION SYSTEMS cause multisystemic organ dysfunction. actual incidence and prevalence of DIP
There are various proposed methods ARP and CP are characterized by irre- appears to be underestimated due to
of classification of pancreatitis in chil- versible damage to the pancreatic tissue, underreporting. The three drugs most
commonly associated with DIP include
valproic acid, L-aspariginase, and pred-
Monica Shukla-Udawatta, MD, is a Pediatric Resident, Children’s Hospital of Michigan. Shailender nisone.1,8 Both accidental and nonacci-
Madani, MD, is a Pediatric Gastroenterologist, Children’s Hospital of Michigan. Deepak Kamat, MD, PhD, dental trauma account for 10% to 40%
FAAP, is a Professor of Pediatrics, and the Director, Pediatric Academic Program, and a Designated Insti- of AP cases in children.1,2 Less common
tutional Official, Children’s Hospital of Michigan, Wayne State University School of Medicine. but other known causes of AP include
Address correspondence to Shailender Madani, MD, Children’s Hospital of Michigan, 3901 Beaubien infections and metabolic disorders
Boulevard, Detroit, MI 48201; email: Smadani@dmc.org. (Table 1). AP has also been reported as
Disclosure: The authors have no relevant financial relationships to disclose.
doi: 10.3928/19382359-20170420-01

PEDIATRIC ANNALS • Vol. 46, No. 5, 2017 e207

 FEATURE ARTICLE

TABLE 1. bilirubin, and triglycerides, as well as

white blood cell count, will help identify
Etiologies of Pancreatitis in Children the cause and possible complications of
Classification Common Etiologies pancreatitis. Immunoglobulin G4 (IgG4)
Biliary Choledochal cyst, cholecystitis, gall stones, pancreas divisum, pancrea- levels should be obtained in patients with
tobiliary malunion, and tumor CP, as autoimmune pancreatitis should
Systemic Shock, sepsis, systemic lupus erythematosus, juvenile idiopathic arthri- be considered in the differential diag-
tis, hemolytic uremic syndrome, Kawasaki disease, inflammatory bowel nosis. Hamano et al.12 reported that el-
disease, polyarteritis nodosa, organ transplantation, Henoch-Schonlein evated IgG4 is a characteristic finding in
purpura, chronic total parenteral nutrition use cases of autoimmune pancreatitis (sensi-
Medication Azathioprine, mercaptopurine, prednisone, mesalamine, cytarabine, tivity 95% and specificity 97%) but is not
salicylic acid, indomethacin, tetracycline, chlorothiazide, isoniazid,
diagnostic because elevation can also be
anticoagulants, estrogen use
observed in other autoimmune processes.
Trauma Abdominal trauma, post-ERCP, perforated gastric or duodenal ulcer
Ultrasound remains the most common
Infections Measles, mumps, coxsackievirus, echovirus, influenza, Epstein-Barr virus,
imaging modality to aid in the diagnosis
mycoplasma, Salmonella, hepatitis A, and Escherichia coli
of pancreatitis due to its accessibility and
Metabolic Hyperlipidemia, hypertriglyceridemia, cystic fibrosis, diabetes mellitus,
safety profile, but the sensitivity of ultra-
hypercalcemia, Reye’s syndrome, renal disease, propionic acidemia,
nutritional deficiency, and hereditary pancreatitis sound (70%) is limited when compared
to CT (90%).6 CT should be considered
Abbreviation: ERCP, endoscopic retrograde cholangiopancreatography.
Adapted from Werlin and Wilschanski.3 in patients when severe or complicated
pancreatitis is suspected, or in patients
with obese body habitus due to the limi-
a complication of diagnostic procedures two of the following three criteria: (1) tations of ultrasound in detecting pancre-
such as endoscopic retrograde cholangi- characteristic abdominal pain (epigastric atic tissue adequately beneath adipose
opancreatography (ERCP) and has been or right upper quadrant with or without tissue. In children, the greatest limitation
reported in 2.5% of children undergoing radiation to the back), (2) serum amylase of CT scans is radiation exposure.
this procedure.9 and/or lipase values 3 or more times the Magnetic resonance cholangiopan-
upper limit of normal, and (3) imaging creatography (MRCP) is a valuable non-
WHEN TO SUSPECT PANCREATITIS findings (ultrasound, magnetic reso- invasive imaging tool reserved to inves-
All children who present with ab- nance imaging, or computed tomography tigate etiologies of ARP and CP. MRCP
dominal pain, nausea, and/or vomiting [CT]) compatible with AP. In the case is used to diagnose intrahepatic and pan-
in combination or as isolated symptoms of imaging, the use of contrast greatly creatic ductal abnormalities, common
should be evaluated for pancreatitis enhances the diagnosis of pancreatitis, bile duct abnormalities, choledocholithi-
in conjunction with a comprehensive more clearly showing interstitial edema asis, strictures, pancreatic divisum, and
history and physical examination. It and areas of heterogeneous inflammation pancreatic or biliary tumors.13 MRCP is
is essential to inquire about history of or necrosis within the pancreas. When favored over ERCP because it eliminates
nonaccidental abdominal trauma, medi- pancreatitis is suspected, serum amylase the risks of contrast and radiation to the
cations, infections, gallstones, and di- and lipase should be measured, keep- patient. MRI/MRCP is a desirable imag-
etary history.10 AP may be the initial ex- ing in mind that lipase is more sensitive ing modality but access, cost, and time
traintestinal manifestation of a systemic and specific than amylase. Measuring are limitations.
illness such as inflammatory bowel dis- amylase level is useful when recurrent In cases of ARP, CP, or idiopathic
ease. A study conducted by Chen et al.11 pancreatic inflammation in the setting of pancreatitis (especially if the child is
found that AP preceded the diagnosis of an acute episode is considered because younger than age 3 years), certain he-
IBD in more than 2% of patients. amylase takes shorter time to reach a reditary disorders should be included in
peak and has a shorter half-life. Addi- the diagnostic evaluation, including cat-
HOW TO DIAGNOSE PANCREATITIS tionally, other laboratory studies such as ionic trypsinogen (PRSS1) gene muta-
The INSPPIRE initiative has estab- serum calcium, electrolytes, urea nitro- tion, serine protease inhibitor Kazal type
lished that a diagnosis of AP requires gen, creatinine, albumin, transaminases, 1 (SPINK1) gene mutation, cystic fibro-

e208 Copyright © SLACK Incorporated


sis transmembrane regulator gene abnor-
malities, chymotrypsin C, and calcium-
sensing receptor genes, to decrease the
proportion of cases labeled as “idiopath-
ic.”14 Patients with PRSS1 or SPINK1
gene mutations (hereditary pancreatitis)
are at higher risk of developing pancre-
atic exocrine insufficiency, diabetes mel-
litus type 1, and pancreatic cancer.
ASSESSING SEVERITY
The three most commonly used se-
verity predictor scores in adults are
Ranson’s Criteria for Pancreatitis Mor-
tality, Glasgow Acute Pancreatitis Se-
verity score, and Acute Physiology and
Chronic Health Examination score.
Unfortunately, none of these tests are
sensitive nor specific, and none of them
have been validated for use in children.
In 2002, DeBanto et al.15 established
a prognostic tool called the Pediatric
Acute Pancreatitis Severity score (PAPS)
for risk stratification. The parameters of
the score include three of the follow-
ing eight criteria: (1) age (<7 years), (2)
weight (<23 kg), (3) white blood cell
count at admission (>18,500 cells/mcL),
(4) lactate dehydrogenase at admission
(>2,000 U/L), (5) 48-hour trough calci-
um (<8.3 mg/dL), (6) 48-hour trough al-
bumin (<2.6 g/dL), (7) 48-hour fluid se-
questration (>75 mL/kg per 48 hours), and
(8) 48-hour rise in blood urea nitrogen
(>5 mg/dL). This study reported PAPS
sensitivity to be 70% compared to 30%
for Ranson’s criteria and 35% for the
Glasgow score.15 Current pancreatitis in-
vestigation practices vary due to a lack of
consensus in pediatric literature. Howev-
er, Coffey et al.16 recently proposed that
obtaining lipase values within the first 24
hours of admission makes it an optimal
marker of severity stratification early in
hospital course compared to PAPS, Ran-
son, and Glasgow scores, which include
markers identified at 48 hours of hospi-
talization. A lipase more than 7 times the
PEDIATRIC ANNALS • Vol. 46, No. 5, 2017
FEATURE ARTICLE
upper limit of normal was found to have
85% sensitivity and a negative predic-
tive value of 89% for predicting severe
pancreatitis. Another added benefit is the
availability and cost-effectiveness of ob-
taining this single parameter.16
COMPLICATIONS
Complications of AP can be divided
into early or late onset. Early systemic
complications such as respiratory dis-
tress syndrome, pneumonia, pulmonary
effusions, shock, or renal failure de-
velop in fewer than 6% of children with
AP.10 Fevers and signs of systemic ill-
ness presenting 2 weeks after the onset
of pancreatitis should prompt evaluation
for infectious complications. Late onset
complications include pancreatic necro-
sis or pseudocysts. Approximately 10%
to 20% of children, particularly those
with traumatic pancreatitis, develop pan-
creatic pseudocysts 4 weeks after the
onset of pancreatitis.17 Uncomplicated
pseudocysts can be managed conserva-
tively with serial monitoring by ultra-
sound. Complicated pseudocysts that
bleed or become infected may require
drainage and antibiotics. Approximately
15% to 35% of children with AP may
have recurrence of pancreatitis.18 These
patients should be assessed for biliary
tract anomalies, metabolic disorders,
hereditary pancreatitis, and hypertriglyc-
eridemia. Mortality rates among chil-
dren with pancreatitis range from 0% to
11%.10 The mortality rate remains lower
than in adult patients, in whom alcohol
is one of the leading causes of pancre-
atitis.10
CURRENT MANAGEMENT
STRATEGIES
Nutrition
Historically, management practices
of pediatric AP have been adopted from
adult literature, which emphasized pan-
creatic rest by maintaining patients nil
per os and the early use of parenteral nu-
trition to limit stimulation of the pancre-
atic secretions and prevent starvation.19
These practices have been challenged by
a systematic review of three randomized
control trials that showed early enteral
nutrition and avoidance of parenteral nu-
trition are associated with prevention of
bacterial stasis in the gut, lower rates of
infection, and decreased mortality.20
Early feeding and nutrition should be
a goal in management of AP. Unfortu-
nately, surveys of pediatric management
in AP estimated that only 3% of pedi-
atric patients are initially given enteral
feeds whereas 44% receive parenteral
nutrition, despite the available evidence
mentioned earlier.5 This staggering dif-
ference suggests possible unawareness
of pediatric clinicians regarding current
AP management.
Introduction of nutrition in mild AP
should be patient directed when good ap-
petite is achieved. If oral feeds are unsuc-
cessful, consider nasogastric or nasojeju-
nal semielemental feeds at one-fourth to
one-eighth of total calorie requirement at
a continuous slow rate, and then increase
as tolerated.4 Parenteral feeds should be
reserved for more severe cases of pancre-
atitis when enteric feeds are not tolerated
or total caloric intake is not sufficiently
met. Although there are no definitive
guidelines on duration of low-fat diet af-
ter an episode of pancreatitis in the cur-
rent pediatric literature, many clinicians
encourage patients to adhere to a low-fat
diet for 6 to 8 weeks after treatment.
Intravenous Fluid Therapy
Fluid resuscitation remains a critical
aspect of management of AP in chil-
dren. The inflammatory process in the
pancreas results in dilation of pancreatic
vasculature, promoting increased vascu-
lar permeability, extravasation of fluids
into extrapancreatic tissue, and potential
for ischemia and necrosis of the organ
e209
 FEATURE ARTICLE

TABLE 2. Antioxidants
Antioxidants (eg, selenium, ascorbic
Salient Points to Remember Regarding Pediatric acid, beta-carotene, alpha-tocopherol,
Pancreatitis and methionine) are frequently used as
• Diagnosis of pancreatitis in children requires inclusion of 2 of 3 of the following criteria supplements and complementary ther-
Classic clinical symptoms apy to provide pain relief and decrease
Serum lipase and/or amylase ≥3 times the upper limit of normal the need for analgesics in patients with
Radiographic evidence of AP ARP and CP. Antioxidants inhibit oxi-
• Pancreatitis must be suspected in children who present with symptoms of nausea, vomiting, dative and free radical stress caused to
and anorexia despite the absence of abdominal pain
tissues by reactive oxygen and nitrogen
• The initial imaging modality of choice is ultrasound of the abdomen. CT and MRI/MRCP are
released by inflamed pancreatic acinar
considered to screen for complications of pancreatitis, and if structural/anatomical causes are
suspected. Limiting factors are access and radiation exposure
cells. A recent study done by Bhardwaj
• Initial evaluation of AP should include liver function tests, triglycerides, calcium, urinalysis,
et al.25 showed a reduction in the num-
electrolytes, blood urea nitrogen, creatinine, and complete blood count with differential ber of painful days per month in chronic
• ARP and CP evaluation, especially if the child is younger than age 3 years, should include the pancreatitis patients by a mean of 4.15
AP testing, as well as MRI/MRCP, genetic testing, sweat test, and immunoglobulin G4 if there is days in the antioxidant group compared
an increased likelihood of anatomic, genetic, or autoimmune causes of pancreatitis to the placebo group.
• Early enteral nutrition should be instituted in severe AP
• Parenteral nutrition should be limited to cases when enteral feeds are not tolerated or contra- Pancreatic Enzyme Replacement
indicated Therapy
• Early aggressive fluid resuscitation in the first 24 hours of hospitalization followed by initiation In patients with CP, fibrosis and
of enteral nutrition between 24 and 48 hours after hospitalization are associated with better
destruction of acinar cells may lead
outcomes and decreased mortality
to exocrine pancreatic insufficiency
Abbreviations: AP, acute pancreatitis; ARP, acute recurrent pancreatitis; CP, chronic pancreatitis; CT, computed tomography;
MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging.
(when <10% of pancreatic function re-
mains intact) requiring pancreatic en-
zyme replacement therapy. Typically,
these patients present with features of
tissue causing “third-spacing” of fluids, 72-hour period within the first 24 hours steatorrhea, weight loss, and abdomi-
leading to hypovolemia and shock. Ag- of hospitalization to reduce the hospital nal discomfort due to abnormal lipid
gressive fluid resuscitation within the complication rate.22 digestion. Diagnosis of pancreatic exo-
first 24 hours of hospitalization is criti- crine insufficiency is made by 72-hour
cal to maintain pancreatic perfusion and Pain Management quantitative fecal fat test estimation,
reduce the rate of cell lysis and further There is no evidence in the pediatric low fecal elastase, or abnormal secre-
pancreatic enzyme diffusion into sur- literature that shows optimal analgesics tin pancreozymin-stimulated pancreatic
rounding tissue. There are limited data for control of abdominal pain in pediat- function tests during upper endoscopy.
in the pediatric literature to suggest an ric pancreatitis. Although the traditional A new study also suggests pancreatic
optimal fluid type and fluid rate. Crys- thought has been that morphine may enzyme replacement as a form of pain
talloid solutions such as normal saline cause paradoxical spasm of sphincter of control due to the negative feedback
(NS) and lactated ringer (LR) solution Oddi, more recent trials have clarified loop effect, by suppressing and down-
are more commonly used for initial that the sphincter of Oddi is equally sen- regulating the secretion of cholecys-
volume replacement. Studies in adults sitive to all opiates but morphine provides tokinin and, therefore, decreasing the
have recently reported that LR may lead more long-term relief than meperidine.23 pancreatic enzyme output.18 The results
to a greater reduction in inflammatory In patients age 17 years and older, there is of the studies are variable because of
response when compared to NS by cre- indication for treating moderate to severe the high rate of placebo response. Also,
ating a more optimal pH buffer.21 Cur- pain using tramadol, a centrally acting there is potential for the replacement
rent recommendations are to administer synthetic opioid analgesic that acts via in- enzymes to be inactivated by gastric
more than than one-third of the estimat- hibition of ascending pain pathways due acids before they effectively reach the
ed fluid volume requirement for the first to its higher efficacy than morphine.24 pancreas.

e210 Copyright © SLACK Incorporated


Monitoring
Prior to patient discharge, it is impor-
tant to ensure that dehydration and elec-
trolyte abnormalities have been duly cor-
rected, the patient has achieved adequate
pain control on oral medications, and is
tolerating an enteral diet. After discharge,
routine follow-up with the primary care
physician is needed to monitor for po-
tential complications such as pseudocyst.
If the patient presents with recurrent or
worsening abdominal pain approximately
4 to 6 weeks after the initial event, pseu-
docyst should be considered and repeat
lipase level and abdominal ultrasound
should be used to assess for peripancre-
atic fluid collection. Currently there is no
screening tool to detect the children who
are at risk for developing pancreatitis so
that primary prevention can be initiated.
Secondary prevention of pancreatitis is
specific to etiology. Cholecystectomy
will prevent further attacks of gallstone
pancreatitis, dietary modifications can
prevent hypertriglyceridemia-induced
pancreatitis, and avoiding certain medi-
cations (Table 1) can prevent recurrent
episodes of drug-induced pancreatitis.
CONCLUSIONS
Pancreatitis in children has been di-
agnosed more frequently over the past
20 years; however, there are still mul-
tiple facets of management of pediatric
pancreatitis that are modeled after adult
studies. Further research is being con-
ducted to fully understand its course,
define optimal management, and create
better outcomes in children.
Salient points to remember about
pancreatitis in children are listed in
Table 2.
REFERENCES
1. Lopez MJ. The changing incidence of acute
pancreatitis in children: a single-institution
PEDIATRIC ANNALS • Vol. 46, No. 5, 2017
FEATURE ARTICLE
perspective. J Pediatr. 2002;140:622-624.
doi: 10.1067/mpd.2002.123880.
2. Morinville VD, Barmada MM, Lowe ME.
Increasing incidence of acute pancreatitis at
an American pediatric tertiary care center: is
greater awareness among physicians respon-
sible? Pancreas. 2010;39:5-8. doi: 10.1097/
MPA.0b013e3181baac47.
3. Werlin SL, Wilschanski M. Acute pancre-
atitis. In: Kliegman RM, ed. Nelsons Essen-
tials of Pediatrics. 20th ed. Philadelphia, PA:
Saunders/Elsevier; 2016:1913-1914.
4. Morinville CD, Lowe ME, Ahuja M, et al.
Design and Implementation of INSPPIRE. J
Pediatr Gastroenterol Nutr. 2014;59(3): 360-
364. doi: 10.1097/MPG.0000000000000417.
5. Kandula L, Lowe ME. Etiology and outcome
of acute pancreatitis in infants and toddlers.
J Pediatr. 2008;152:106-110. doi: 10.1016/j.
jpeds.2007.05.050.
6. Pant C, Deshpande A, Olyaee M, et al. Epi-
demiology of acute pancreatitis in hospi-
talized children in the United States from
2000–2009. PLoS One. 2014; 9:e95552. doi:
10.1371/journal.pone.0095552.
7. Cofini M, Quadrozzi F, Favoriti P, Favoriti M,
Cofini G. Valproic acid-induced acute pancre-
atitis in pediatric age: case series and review
of literature. G Chir. 2015;36(4):158-160.
8. DeBanto JR, Goday PS, Pedroso MR, et
al. Acute pancreatitis in children. Am J
Gastroenterol. 2002;97:1726-1731. doi:
10.1111/j.1572-0241.2002.05833.x.
9. Iqbal CW, Baron TH, Moir CR, Ishitani
MB. Post-ERCP pancreatitis in pediat-
ric patients. J Pediatr Gastroenterol Nutr.
2009;49(4):430-434. doi: 10.1097/01.
mpg.0000361657.54810.19.
10. Bai HX, Lowe ME, Husain S. What have we
learned about acute pancreatitis in children?
J Pediatr Gastroenterol Nutr. 2011;52:262-
270. doi: 10.1097/MPG.0b013e3182061d75.
11. Chen YT, Su JS, Tseng CW, Chen CC, Lin
CL, Kao CH. Inflammatory bowel disease on
the risk of acute pancreatitis: a population-
based cohort study. J Gastroenterol Hepatol.
2016;31(4):782-787. doi: 10.1111/jgh.13171.
12. Hamano H, Kawa S, Horiuchi A, et al.
High serum IgG4 concentrations in pa-
tients with sclerosing pancreatitis. N Engl J
Med. 2001;344(10):732-738. doi: 10.1056/
NEJM200103083441005.
13. Maccioni F, Martinelli M, Al Ansari N, et al.
Magnetic resonance cholangiography: past,
present and future: a review. Eur Rev Med
Pharmacol Sci. 2010;14:721-725.
14. Whitcomb DC. Value of genetic testing
in the management of pancreatitis. Gut.
2004;53(11):1710-1717. doi: http://dx.doi.
org/10.1136/gut.2003.015511.
15. DeBanto JR, Goday PS, Pedroso MR, et
al.; Midwest Multicenter Pancreatic Study
Group. Acute pancreatitis in children. Am J
Gastroenterol. 2002;97(7):1726-1731. doi:
10.1111/j.1572-0241.2002.05833.x.
16. Coffey MJ, Nightingale S, Ooi CY. Serum
lipase as an early predictor of severity in pe-
diatric acute pancreatitis. J Pediatr Gastroen-
terol Nutr. 2013;56:602-608. doi: 10.1097/
MPG.0b013e31828b36d8.
17. Sánchez-Ramírez CA, Larrosa-Haro A,
Flores-Martínez S, Sánchez-Corona J, Villa-
Gómez A, Macías-Rosales R. Acute and re-
current pancreatitis in children: etiological
factors. Acta Paediatr. 2007;96(4):534-537.
doi: 10.1111/j.1651-2227.2007.00225.x.
18. Werlin SL, Kugathasan S, Frautschy BC. Pan-
creatitis in children. J Pediatr Gastroenterol
Nutr. 2003;37(5):591-595.
19. Robin AP, Campbell R, Palani CK, Liu K,
Donahue PE, Nyhus LM. Total parenteral
nutrition during acute pancreatitis: clinical
experience with 156 patients. World J Surg.
1990;14(5):572-579.
20. Mirtallo JM, Forbes A, McClave SA, et al.
International consensus guidelines for nu-
trition therapy in pancreatitis. JPEN J Par-
enter Enteral Nutr. 2012;36(3):284-291. doi:
10.1177/0148607112440823.
21. Warndorf MG, Kurtzman JT, Bartel MJ, et al.
Early fluid resuscitation reduces morbidity
among patients with acute pancreatitis. Clin
Gastroenterol Hepatol. 2011;9:705-709. doi:
10.1016/j.cgh.2011.03.032.
22. Wu BU, Hwang JQ, Gardner TH, et al. Lactat-
ed Ringer’s solution reduces systemic inflam-
mation compared with saline in patients with
acute pancreatitis. Clin Gastroenterol Hepa-
tol. 2011;9(8):710-717.e1. doi: 10.1016/j.
cgh.2011.04.026..
23. Thompson DR. Narcotic analgesic ef-
fects on the sphincter of Oddi: a review
of the data and therapeutic implications in
treating pancreatitis. Am J Gastroenterol.
2001;96(4):1266–1272. doi:10.1111/j.1572-
0241.2001.03536.x.
24. Wilder-Smith CH, Hill L, Osler W, O’Keefe
S. Effect of tramadol and morphine on
pain and gastrointestinal motor func-
tion in patients with chronic pancreati-
tis. Dig Dis Sci. 1999;44:1107-1116. doi:
10.1023/A:1026607703352.
25. Bhardwaj P, Garg PK, Maulik SK, Saraya A,
Tandon RK, Acharya SK. A randomized con-
trol trial of antioxidant supplementation for
pain relief in patients with chronic pancreati-
tis. Gastroenterology. 2009;136(1):149-159.
doi: 10.1053/j.gastro.2008.09.028.
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