the impact of oral feeding on the severity of acute pancreatitis

The Impact of Oral Feeding on the Severity ofAcute Pancreatitis

Mustafa Sahin, MD, Sukru Ozer, MD, Celalettin Vatansev, MD, Mehmet Akoz, MD, Husamettin Vatansev, PhD,Faruk Aksoy, MD, Alaattin Dilsiz, MD, Osman Yilmaz, MD, Mehmet Karademir, MD, Murat Aktan, MD,

Konya, Turkey

BACKGROUND: In the management of acute pan-creatitis, oral feeding is prohibited and either en-teral or parenteral feeding is commenced for thepatients in an effort to not increase the secretionof the pancreatic enzymes.

PURPOSE: This study was undertaken in an at-tempt to determine the impact of oral feeding onthe severity of acute pancreatitis and to comparethis impact with that of parenteral feeding.

MATERIALS AND METHODS: Twenty-four femaleSprague-Dawley rats were divided into twogroups. In both groups, acute pancreatitis wasinduced by ligation of the main biliopancreaticduct. The rats in group I were fed orally and therats in group II were fed parenterally. The ratswere sacrificed at 48 hours, and blood sampleswere obtained from the heart upon exposure ofthe abdominal and thoracic cavities. The pan-creas and the left lung were removed for his-topathological examination. The levels of lacticdehydrogenase (LDH), serum glutamic oxaloace-tic transaminase (SGOT), glucose, calcium andblood urea nitrogen, base deficit, partial oxygenpressure, leukocyte count, and hematocrit levelamong Ranson criteria and the level of amylasewere measured. The pancreas and the lung wereexamined under a light microscope.

RESULTS: The levels of LDH, SGOT, and calciumfor the rats in group I were significantly higherwhen compared with the rats in group II (P<0.05). Similarly, the levels of amylase for therats in group I were found to be higher whencompared with the rats in group II, but the differ-ence was not significant. Inflammatory changesobserved in the pancreas were less severewhereas inflammatory changes observed in thelung were more severe for the rats in group Iwhen compared with the rats in group II.

CONCLUSION: The blood levels of the enzymeswere adversely affected for the rats fed orally. Incontrast, inflammatory changes observed in thepancreas were more severe for the rats fed par-enterally. The study suggests that certain hor-mones released from the duodenum upon stimu-lation by oral nutrient intake lessens the severityof pancreatitis through protective effects on thepancreas, whereas the elevated levels of the en-zymes cause endothelial damage resulting in de-struction in distant organs such as the lung.Am J Surg. 1999;178:394–398. © 1999 by Ex-cerpta Medica, Inc.

Acute pancreatitis is a serious clinical entity that canbe caused by various etiological factors. Besides theassociated diagnostic difficulties, acute pancreatitis

can be life threatening through local and systemic compli-cations, and the impact of management protocols em-ployed is limited.1,2 The primary components of manage-ment of acute pancreatitis are the relief of pain and thereplacement of the fluid and electrolyte deficits. Further-more, respiratory support and hemodynamic monitoringare interventions of significant contribution.1,3 Proceduresother than these, namely, the prohibition of oral feedingand the administration of parenteral feeding, nasogastricsuction, prophylactic antibiotics, peritoneal lavage, andthe use of various blockers, antagonists, and other drugsremain to be discussed.1–4

Until recently, the prohibition of oral feeding and theadministration of nasogastric suction have been routinepractice for all cases of acute pancreatitis but those of mildseverity.1,4,5 This practice attempts to lessen the severity ofpancreatitis through inhibition of the secretion of enzymesfrom the gastrointestinal system, the pancreas in particular.For the last couple of years, it has been suggested that thispractice does not meet expectations and, on the contrary,various experimental studies have demonstrated bacteria togrow in numbers in the presence of stasis caused by thedecreased intestinal motility and to contribute to the de-velopment of local and systemic complications of pancre-atitis by the way of bacterial translocation.6–9

Based on these findings and pioneered by clinicians suchas Imrie,5 suggestions in support of a soft diet provided inthe early phases of acute pancreatitis of mild and moderateseverity as being beneficial have gained increasing accep-tance. This study was designed to determine the impact oforal feeding on the severity of acute pancreatitis. Acutepancreatitis was experimentally induced and biochemicaland histopathological parameters were compared in thegroup of rats fed orally and in the group of rats fed paren-terally.

From the Departments of General Surgery (MS, SO, CV, FA,MK), Biochemistry (MA, HV), Pediatric Surgery (AD), Pathology(OY), and Histology (MA), Selcuk University Faculty of Medicine,Konya, Turkey.

This study was performed in the Experimental Medical Re-search Center of Selcuk University, Konya, Turkey.

Requests for reprints should be addressed to Mustafa Sahin,Department of General Surgery, Selcuk University Faculty ofMedicine, Akyokus, TR-42080 Konya, Turkey.

Manuscript submitted May 10, 1999, and accepted in revisedform September 8, 1999.

394 © 1999 by Excerpta Medica, Inc. 0002-9610/99/$–see front matterAll rights reserved. PII S0002-9610(99)00204-4

MATERIALS AND METHODSTwenty-four female Sprague-Dawley rats were used in the

study. All rats were at equal age and of equal weight (mean280 6 25 g). The rats were divided into two equal groupsof 12. They were kept in cages in groups of 6 under roomconditions at 22 to 24°C. The rats were fed orally with astandard laboratory rat diet on the day of the operation.The operation was performed under ether anesthesia andunder sterile conditions. Following employment of antisep-tic povidone iodine solutions over the anterior abdominalwall, a long incision was made through the median plane.The stomach and the duodenum were mobilized, and thepancreatic duct was ligated at the entrance to the duode-num using 3/0 vicryl sutures.8,9 The abdomen was closedusing continuous 2/0 silk sutures. Analgesia was providedwith dichlofenac sodium at a dose of 2 mg/kg, diluted andadministered subcutaneously over the left groin area priorto recovery from anesthesia. The rats were placed in cagesfollowing the operation. Analgesic administration was re-peated at 24 hours. For the rats in group I, an equally mixedsolution of 5% dextrose and 0.9% normal saline was ad-ministered at a dose of 10 cc orally every 8 hours. Oralintake was prohibited for the rats in group II. The samesolution was administered at a dose of 10 cc subcutaneouslyover both groin areas every 8 hours.

The rats were reoperated at 48 hours under ether anes-thesia, and the abdominal and thoracic cavities were ex-posed under sterile conditions. Heparinized insulin injec-tors were used to draw 0.5 cc blood from the heart for themeasurement of blood gases. A further 3 cc blood wasdrawn, 1 cc to tubes containing sodium-EDTA for com-plete blood count and 2 cc to standard glass tubes for themeasurement of biochemical parameters. The pancreas andthe left lung were removed for histopathological examina-tion, and formalin was used for tissue fixation. The sacri-ficed rats were placed in medical waste bags and presentedto the medical waste elimination facility of the ResearchCenter.

Levels of (LDH), (SGOT), glucose, calcium, and bloodurea nitrogen, base deficit, partial oxygen pressure, leuko-cyte count, and hematocrit level among Ranson criteria,and level of amylase were measured in order to determinethe severity of acute pancreatitis.1,10,11

Paraffin sections of the pancreas tissue samples and thelung tissue samples were prepared and stained with hema-toxylin-eosin. These sections were examined under a light

microscope, and color photographs were taken. Four sec-tions from each of the pancreatic tissue samples wereprepared. The presence of infiltration of inflammatory cells,fat necrosis, parenchymal necrosis, and hemorrhagic fociwere examined in the sections prepared from the pancre-atic tissue samples; and scoring was undertaken based onthese findings for histopathological determination of theseverity of acute pancreatitis.12 The presence of a criterionon any of the four sections was decided to be sufficient. Thepresence of each of the four criteria was scored as one andthe severity of acute pancreatitis was scored from zero tofour by the summation of the individual scores. The pres-ence and extent of infiltration of inflammatory cells andthe presence of necrotic and hemorrhagic foci were exam-ined in the sections prepared from the lung tissue samples.

Statistical analysis was performed using Student’s t testand the Mann-Whitney U test. Statistical significance wasconsidered at P ,0.05.

RESULTSMean levels with standard errors of SGOT, LDH, glu-

cose, calcium, blood urea nitrogen, hematocrit, leukocyte,base deficit, and partial oxygen pressure are presented inTable I. Differences in levels of blood urea nitrogen, he-matocrit, leukocyte, base deficit and partial oxygen pressurewere not significant between the rats in group I and the ratsin group II. LDH and SGOT levels were significantlyhigher whereas glucose and calcium levels were signifi-cantly lower for the rats in group I when compared with therats in group II. Mean level of serum amylase was 3,655 61,521 IU/L for the rats in group I and 2,857 6 1,350 IU/Lfor the rats in group II. Mean level of serum amylase washigher for the rats in group I when compared with the ratsin group II, although the difference was not statisticallysignificant. Of Ranson criteria, three items were found tobe worse and one item was found to be better for the ratsin group I when compared with the rats in group II.

Histopathological examination of the pancreatic tissuesamples revealed infiltration of inflammatory cells in all, fatnecrosis in 7, parenchymal necrosis in 4, and hemorrhagicfoci in 1 of the rats in group I. Of the rats in group II,infiltration of inflammatory cells was observed in all, fatnecrosis in 10, parenchymal necrosis in 9, and hemorrhagicfoci in 4. Histopathological findings were more commonand more severe for the rats in group II when comparedwith the rats in group I (Figures 1 and 2). Scoring

TABLE IBiochemical, Hematological, and Blood Gas Measurements of the Groups

(Mean 6 Standard Deviation)

Parameters Group I Group II T P

SGOT (IU/L) 1,345 6 222 1,060 6 371 2.29 0.032Glucose (mg/dL) 76 6 5 81 6 6 22.08 0.049LDH (IU/L) 1,367 6 648 890 6 212 2.42 0.030Calcium (mg/dL) 11 6 0.7 12 6 0.7 22.15 0.042Blood urea nitrogen (mg/dL) 41 6 4 44 6 9 21.30 0.214Hematocrite % 39 6 2 41 6 2 22.07 0.050Leukocyte/mm3 9,381 6 4,246 10,383 6 3,812 20.61 0.549Base deficient (mmol/L) 23.50 6 1.7 23.85 6 2.7 0.36 0.705Partial oxygen pressure (mm Hg) 85 6 3 84 6 4 1.09 0.291Amylase (IU/L) 3,655 6 1,521 2,857 6 1,350 21.98 0.076

SGOT 5 serum glutamic oxaloacetic transaminase; LDH 5 lactic dehydrogenase.

IMPACT OF ORAL FEEDING ON ACUTE PANCREATITIS/SAHIN ET AL

THE AMERICAN JOURNAL OF SURGERY® VOLUME 178 NOVEMBER 1999 395

for histopathological findings revealed acute pancreatitiswas more severe for the rats in group II when comparedwith the rats in group I, the difference being statisticallysignificant (P ,0.05; Table II).

Histopathological examination of the lung tissue samplesrevealed significant thickening of the alveolar septa andinfiltration of inflammatory cells in the bronchial wall andthe alveolar septa for all of the rats in group I (Figure 3).For all of the rats in group II, segmental thickening of thealveolar septa and segmental infiltration of inflammatorycells in the bronchial wall and the alveolar septa wereobserved (Figure 4). In contrast to the changes observed inthe pancreatic tissue samples, the changes observed in thelung tissue samples were more severe for the rats in groupI when compared with the rats in group II.

COMMENTSFor patients with severe pancreatitis, energy consumption

at rest increases and the breakdown of the muscular tissueaccelerates due to the inflammation and necrosis observedin the pancreatic tissue and the retroperitoneal tissues.13,14

For these patients, impairment of nutrition and the succes-sive losses result in functional impairments and structural

alterations in organ systems. These alterations, in turn,result in increased mortality.14,15 In attempt to prevent thisnegative sequence, feeding is suggested to be commencedas early as possible and to be continued as long as need-ed.14,16,17

Total parenteral nutrition (TPN) has been accepted andpracticed as the standard method of feeding in attempt toprevent nitrogen loss in patients with acute pancreati-tis.16,18 The complications (catheter sepsis and metabolicdisturbances), the difficulties in administration, and thehigh costs associated with TPN have necessitated studieson alternative methods of feeding.19–21 Enteral feeding hasbeen accepted as the alternative method of feeding forTPN following several clinical and experimental stud-ies.10,19,21,22

In a clinical study, Kalfarentzos et al21 administered TPNto a group of patients and enteral feeding through a naso-duodenal tube to another group of patients. They observedthe total number of complications and the number of septiccomplications were less in the group of patients fed enter-ally, and enteral feeding were well tolerated. Similar resultshave been reported by other investigators.10,11,22

Oral feeding is prohibited in the early phases of acute

Figure 1. Modest parenchymal necrotic foci with infiltration ofinflammatory cells in the tissue space in a pancreatic tissuesample from a rat fed orally, as observed under a light micro-scope (hematoxylin and eosin 3 100).

Figure 2. Extensive parenchymal necrotic foci and hemorrhagicfoci with infiltration of inflammatory cells in the tissue space in apancreatic tissue sample from a rat fed parenterally, as observedunder a light microscope (hematoxylin and eosin 3 100).

Figure 3. Thickening of the alveolar septa and infiltration ofinflammatory cells in the bronchial wall and the alveolar septa ina lung tissue sample from a rat fed orally (hematoxylin andeosin 3 100).

TABLE II.Scores Based on the Histopathological Findings Indicating

the Severity of Acute Pancreatitis

Points*(p)

Group I Group II

nTotal Score

(pxn)† nTotal Score

(pxn)†

1 5 5 2 22 3 6 1 23 3 9 5 154 1 4 4 16Total 12 24 12 35Mean 1 SE 2.0 6 1.0 2.9 6 1.1

Z 5 1.98 P 5 0.047

* One point was given for the prescence of each parameter (inflammatory cellinfiltration, fat necrosis, hemorrhagic foci, and paranchymal necrosis).† Total score was obtained by multiplying points and rat number.


396 THE AMERICAN JOURNAL OF SURGERY® VOLUME 178 NOVEMBER 1999

pancreatitis based on the belief that oral feeding will in-duce the secretion of enteral hormones and directly en-hance the secretion and the activation of the pancreaticenzymes, thus aggravating the severity of the inflammationand worsening the pain.1–3,23,24 In this study, SGOT,LDH, and calcium levels were found to be significantlyhigher for the rats fed orally when compared with the ratsfed parenterally (Table I). These findings agree with theproposals that oral feeding stimulates the secretion of theenteral hormones and the pancreatic enzymes, thus aggra-vating the severity of the disease. However, there exist noclinical or experimental studies histopathologically dem-onstrating an aggravation of the pancreatic inflammationupon oral feeding. Upon histopathological examination ofthe pancreatic tissue samples in this study, the histopatho-logical changes caused by the process of pancreatitis werefound to be lower in the group of rats fed orally, in contrastto the serum levels of the enzymes and the common beliefthat high enzyme levels mean severe tissue damage (Figures1 and 2). Infiltration of inflammatory cells and fat necrosiswere the prominent findings for the rats in group I, whereasfor the rats in group II, the prominent findings were pa-renchymal necrosis and hemorrhagic foci. The numericalevaluation of the histopathological findings revealed thatthe changes observed in rats fed parenterally were statisti-cally significant as well (Table II). In contrast to thefindings in the pancreatic tissue samples, the histopatho-logical findings in the lung tissue samples were more severein the group of rats fed orally (Figures 3, 4). This findingagreed with the serum levels of the enzymes.

Similar to the literature, the serum levels of the enzymeswere found to be higher for the rats fed orally, but incontrast to these high levels, the less-pronounced his-topathological findings in pancreas appeared to be contra-dictory. However, the authors believe some of the enteralhormones to have a protective effect, thus limiting theinflammation process in the pancreas. CCK/PZ is a hor-mone with trophic effect on the pancreatic tissue.23,24 Inaddition, serotonin and motilin exert a protective effect onthe pancreas through increasing the gastrointestinal motil-ity, and vasoactive intestinal peptide through increasing

the blood flow by way of vasodilatation and other immu-nological changes.25,26

Stasis, both as a result of the cessation of oral feeding andas a result of the inflammation, has been shown to promotebacterial translocation in experimental studies; and thegastrointestinal flora has been blamed as the source of thelocal and systemic complications associated with acutepancreatitis.8,9,20 Based on these results, oral feeding mightbe proposed to reverse this negative sequence.

Death from acute pancreatitis is a result of the functionaland structural impairments observed in the organ sys-tems.3,14 Oral nutrient intake will induce the secretion ofsome gastrointestinal hormones, and these hormones pro-tect the pancreas tissue from the inflammatory changes bydirect or indirect effects.1,23 Meanwhile, the same hor-mones induce pancreatic enzyme secretion and activation.These phospholipases and proteolitic enzymes enter intothe blood flow and cause end-organ damage.23 Activationof proteases and increased concentrations of phospho-lipases due to the stimulus of oral feeding may play aprimary role in the pathogenesis of the lung injury in acutepancreatitis.26–28 This might be an explanation for theinflammatory changes observed in the lung tissue samplesin this study being more severe in the group of rats fedorally. Milani et al29 described a model of severe pancre-atitis-associated pulmonary injury in rats. They reportedthe mechanical and morphological alterations were similarto those alterations observed in human adult respiratorydistress syndrome.29

Criteria developed by Ranson and Imrie might be usefulin terms of clinical follow-up. The authors believe thatthese criteria would not indicate the severity of inflamma-tory and histopathological changes in the pancreas withperfection. Based on these findings, it could be suggestedthat the commencement of oral feeding in the early phasesof acute pancreatitis of mild and moderate severity wouldnot negatively affect the course of the disease but ratherpositively affect the pancreatic tissue and the gastrointes-tinal system.5,9,20 In addition, the complications resultingfrom enteral feeding or parenteral feeding would be elim-inated. Other advantages for oral feeding include the lackof need for special instrumentation and personnel and thelow cost. An elemental oral diet deficient in fat and pro-teins would be of help in preventing the induction of thesecretion and activation of the pancreatic enzymes.30 Be-ing the natural method of feeding, oral feeding is associatedwith benefits such as increasing the gastrointestinal bloodflow, inducing the secretion of IgA, having a trophic effecton the intestinal mucosa, preventing bacterial growth byeliminating stasis, and regulating hormonal and enzymaticsecretions in healthy individuals.

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Figure 4. Segmental thickening of the alveolar septa and seg-mental infiltration of inflammatory cells in the bronchial wall andthe alveolar septa in a lung tissue sample from a rat fed paren-terally (hematoxylin and eosin 3 100).


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Istanbul, Turkey, 30 September–4 October 1997. Abstract book, p.33.6. Wang XD, Wang Q, Andersson R, Ihse I. Alterations in intes-tinal function in acute pancreatitis in an experimental model. Br JSurg. 1996;83:1537–1543.7. Medich DS, Lee TK, Melhem MF, et al. Pathogenesis of pan-creatic sepsis. Am J Surg. 1993;165:46–52.8. Runkel NS, Moody FG, Smith GS, et al. The role of the gut inthe development of sepsis in acute pancreatitis. J Surg Res. 1991;51:18–23.9. Sahin M, Yol S, Ciftci E, et al. Does large bowel enema reduceseptic complications in acute pancreatitis? Am J Surg. 1998;176:331–334.10. Mc Clave SA, Snider H, Owens N, Sexton LK. Clinicalnutrition in pancreatitis. Dig Dis Sci. 1997;42:2035–2044.11. Simpson WG, Marsano L, Gates L. Enteral nutritional supportin acute alcoholic pancreatitis. J Am Coll Nutr. 1995;14:662–665.12. Crawford JM, Cotran RS. The pancreas. In: Schoen FJ, ed.Robbins Pathologic Basis of Disease. Philadelphia: WB Saunders;1994:897–927.13. Havala T, Shrants E, Cerra F. Nutritional support in acutepancreatitis. Gastroenterol Clin North Am. 1989;18:525–542.14. Latifi R, McIntosh JK, Dudrick SJ. Nutritional management ofacute and chronic pancreatitis. Surg Clin North Am. 1991;71:579–595.15. Kalfarentzos FE, Karavias DD, Karatzas TM, et al. Total par-enteral nutrition in severe acute pancreatitis. J Am Coll Nutr.1991;10:156–162.16. Goldbach BA, Nickleach J. Nutritional care in disease of theliver, biliary system and exocrine pancreas. In: Krause’s Food,Nutrition and Diet Therapy. Philadelphia: WB Saunders; 1996:641–661.17. Pisters PW, Ranson JH. Nutritional support for acute pancre-atitis. Surg Gynecol Obstet. 1992;175:275–284.18. Alhan E, Kucuktulu U, Ercin C, et al. Effects of total parenteral

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