Symposium 1 Feeding in Pancreatitis -Ruth Newton …...acute pancreatitis: results of a randomized...

Symposium 1

“F di i P titi ”“Feeding in Pancreatitis”

BAPEN Annual Conference

Feeding in Acute PancreatitisFeeding in Acute Pancreatitis

Clinical presentationClinical presentation

A 45 year old man with a history of binge drinking of alcohol is admitted with acute upper abdominal pain. There are no signs of chronic hepatocellular disease but he has upper abdominal tenderness and has an elevated serum amylase concentration of 1250 (normal <100).

His Imrie score is 4 and a CT scan confirms pancreatic inflammation. There is no evidence of gall-stones on CT or on ultrasound scanning.


He is transferred to HDU for further care.By day 2 there has been some nausea andBy day 2, there has been some nausea and

a little vomiting, for which metoclopramide is prescribedis prescribed.

Artificial nutritional support is considered.

Question 1Question 1

Would you provide artificial nutrition at this stage?g

1) Y R d1) Yes Red 2) No Yellow) o e o

MUSTMUST

MUST score at this stage is 2 ( BMI 26; no prior weight loss; acute illness and no p g ;expectation of oral intake for >5 days).


How would you provide artificial nutrition?

1) Naso-gastric feeding Red2) Naso-jejunal feeding Yellow3) Intravenous feeding Green3) Intravenous feeding Green

DiscussionDiscussion

What is the best route for providing artificialnutrition in acute pancreatitis?nutrition in acute pancreatitis?

Mr Ross CarterMr Ross Carter

What is the best route forWhat is the best route for providing artificial nutrition in acute pancreatitis?

BAPEN Annual Conference Harrogate Lister

Imrie

27th November, 2007

Pringle McEwen

Open debate?

Session programme

What is the best route for providing artificial nutrition in acutepancreatitis?

What evidence guides the prescription of naso-jejunalfeeds?

The effect of different routes of nutrient administration on human pancreatic exocrine function?human pancreatic exocrine function?

Changes in AP managementChanges in AP managementproblem traditional current

Prediction of severity Imrie/Ranson/CTSI Organ support

Nutrition TPN ?ERCP <48hrs in severes none (exc.cholangitis)( g )

Drug modulation Optimism none

Early Tx for sterile necrosis Open surgery noneEarly Tx for sterile necrosis Open surgery none

Prevention of infection Prophylactic Ab’s noneSurveillance for infection CT guided FNA none

1y surgery for sepsis Open surgery Perc necrosectomy

2y Tx for sepsis More open surgery Re-do necrosectomyy p p g y y

Treatment of OPN Open cyst gastro Lap cyst gastrostomy

Treatment of late pseudocyst Open cyst gastro EUS cyst gastrostomyTreatment of late pseudocyst Open cyst gastro EUS cyst gastrostomy

Nutritional issues in acute pancreatitis

Who needs fed? l th th t d it!…..only those that need it!

Wh t bidit i i t d ith h d lit ?What morbidity is associated with each modality?

Can feeding / the feed composition affect the clinical course of pancreatitis?

Spectrum of disease in acute pancreatitis

Mild acute Severe acuteMild acutepancreatitis

Severe acute pancreatitis

NO organ failure MOFNo necrosisRapid resolutionSecondary prevention

Extensive necrosisProlonged catebolic illnessTreatment of complicationsy p p

Spectrum of disease in acute pancreatitis

Mild acute Severe acuteMild acutepancreatitis

Severe acute pancreatitis

NO organ failure MOF80+%

No necrosisRapid resolutionSecondary prevention

Extensive necrosisProlonged catebolic illnessTreatment of complicationsy p p

“Rule of engagement”

Do no further harm:

- through neglect

- through establishing the delivery system

? through exacerbation of the disease process

Wh t i t d d t f tWhat is standard management of acute pancreatitis?

“Aggressive conservative therapy”

“drip and suck(?)” – concept of gut restoxygen(PsO2) and urinary catheterCVP Organ supportpethidine analgesiapethidine analgesiaInterval cholecystectomy Nutritional support as required

- how did it become standard

Hi t i l t f tHistorical management of acute pancreatitis

1878 Friedrich first described the association of alcohol with abdominal pain, vomiting and pancreatic inflammationp

1887 Socin was the first to describe an operation for acute pancreatitisp

1894 Werner Korte advised a conservative approach limiting surgery for “ suppuration in the ylesser sac (Arch Klin Chir 1894;48,720 )

1902 Kempe performed the first debridement

Diagnosis was generally at laparotomy / post mortem Mortality following surgery was 40-60%)Nutrition by diet as tolerated


1921 L i d i d h i l l NG b1921 Levin designed the single lumen NG tubefor feeding (JAMA 1921; 76(15), 1007)

1933 Wangensteen and Paine used the Levin tube for intestinal decompression (obstruction)JAMA 1933;101(20), 1532-1539.

1938 development of rapid amylase estimation(Somogyi M J Biol Chem 1938;125,399-414)

1940 promotion of initial conservative management including routine decompression of ileus using the “Wangensteen tube” (Morton JJ, Ann Surg. 1940 May;111(5):851-63)

GNutrition by diet or NG


1960 J h H d h h i i i l ill1960 John Howard – nurse through initial illnesssurgery for infectious complications(JAMA. 1960 Nov 26;174:1687-9 )

Overall mortaiity down to ~10%

1968 TPN a realistic option for nutritional support(Dudrick SJ Surgery 1968 64(1) 134-142)

1970 Feeding by a combination of diet, enteral (NG)gastrostomy / jejunostomy of TPN as required(Stephens RV – Use of concentrated, balanced, ( p , ,liquid elemental diet for nutritional management of catabolic states Ann Surg 1969, 170(4), 642-668)

Nutrition by diet or NG or occ. TPN

Historical management of acute pancreatitis

1970’s concern enteral feeding may exacerbate APKonturek SJ Am J Physiol 1972;222 16-20Konturek SJ Am J Physiol 1972;222,16 20Ragins H Am J Surg 1973, 126, 606-614Cassim MM Ann Surg 1974, 180,228-231Vidon N Gut 1978;19,194-8Mitchell CJ Scand J Gastro 1983;18,5-8Evander A Digestion 1982;24,159-167

1973 E li TPN f di t t d th b tt1973 Earlier TPN feeding started the betterFeller JH Am J Surg 1973;127,196-201Blackburn GL Am J Surg 1976;131(1),114-124

1977 Concern enteric feeding may increase septic complicationsR J S 1977 82(1) 99 106Ranson J Surgery 1977;82(1), 99-106

Feeding by (early TPN)


1980‘s Decade of Dogma

Gastric decompressionGastric decompressionGut restEarly TPNEarly TPN

Debridement for sepsisopen laparostomy /packingBradley EL Ann Surg 1987;206(4),542-550

closed lavageclosed lavageBeger HG Br J Surg 1988;75(3),207-212

“striking back”

Nasogastric suctionNavarro S Ros E Aused R et alNavarro S, Ros E,Aused R, et al Comparison of fasting, nasogastric suction and cimetidine in the treatment of acute pancreatitisDigestion 1984;30 224 230Digestion 1984;30,224-230

The use of nasogastric suction was associated with a delay the resumption of bowel activity, prolong the duration of pain, analgesic requirements and hospital stayrequirements and hospital stay

“striking back”

Nasogastric suctionNavarro S, Ros E,Aused R, et al , , ,Comparison of fasting, nasogastric suction and cimetidine in the treatment of acute pancreatitisDigestion 1984;30,224-230

The use of nasogastric suction was associated with a delay the resumption of bowel activity,

l th d ti f i l iprolong the duration of pain, analgesic requirements and hospital stay

NO role for the routine prolonged use of NG suction / decompression

Berlin wall 1989

Climate of change

Early parenteral support is beneficialEarly parenteral support is beneficialSax HC,Warner BW,Talamini MA et al Early total parenteral nutrition in acute pancreatitis: lack of beneficial effectsAm J Surg 1987;153,117-124

TPN associated with a significantly higher rate of catheter-related sepsis no difference in the number of days to oral intake total hospital stay or number of complicationsto oral intake, total hospital stay, or number of complications

Berlin wall 1989

Climate of change

Early parenteral support is beneficialEarly parenteral support is beneficialSax HC,Warner BW,Talamini MA et al Early total parenteral nutrition in acute pancreatitis: lack of beneficial effectsAm J Surg 1987;153,117-124

TPN associated with a significantly higher rate of catheter-related sepsis no difference in the number of days to oral intake total hospital stay or number of complicationsto oral intake, total hospital stay, or number of complications

Early (<7days) TPN is worse than no feedingno feeding

Is gut rest essential?McClave SA,et alComparison of the safety of early enteral vs parenteral nutrition in mild acute pancreatitis. pJPEN 1997;21(1):14-20.Nakad A, et alIs early enteral nutrition in acute pancreatitis dangerous? About 20 patients fed by an endoscopically placed nasogastrojejunal tube. Pancreas 1998;17(2):187-93.

Kalfarentzos F, et alEnteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: Results of a randomized prospective trial.B J S 1997 84(12) 1665 9Br J Surg 1997;84(12):1665-9.Abou-Assi S, et alHypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative studyacute pancreatitis: results of a randomized comparative study.Am J Gastroenterol 2002;97(9):2255-62.

Is gut rest essential?McClave SA,et alComparison of the safety of early enteral vs parenteral nutrition in mild acute pancreatitis. pJPEN 1997;21(1):14-20.Nakad A, et alIs early enteral nutrition in acute pancreatitis dangerous? About 20 patients fed by an endoscopically placed nasogastrojejunal tube. Pancreas 1998;17(2):187-93.

Kalfarentzos F, et alEnteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: Results of a randomized prospective trial.B J S 1997 84(12) 1665 9Br J Surg 1997;84(12):1665-9.Abou-Assi S, et alHypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative studyacute pancreatitis: results of a randomized comparative study.Am J Gastroenterol 2002;97(9):2255-62.

E l t l f d i t l t d d idEarly enteral feed is tolerated and avoids the TPN associated morbidity

? Other benefits of enteral nutrition

Mucosal barrier defence mechanism Ammori B et al J Gastrointest Surg 1999;3,252-262Kotani J et al Arch Surg1999;134,287-292

Improvements in metabolic controlpPetrov MS et al, Clin Nutr 2007;26,514-523

ImmunomodulationWindsor ACJ et al. Gut 1998; 42: 431-5Gupta R et al Pancreatology 2003,3,406-413

Enhanced feedingBengmark S Curr opin Clin Nutr Metab Care 2005;8,557-561

Feeding must be distal to the Ligament g gof Treitz

Eatock FC et al.Nasogastric feeding in severe acute pancreatitis may be practical and safe. Int J Pancreatol 2000; 28: 25-31

E t k FC t lEatock FC et al.A randomized study of early nasogastric versus nasojejunal feeding in severe APAm J Gastroenterol 2005; 100: 432-9.

Eckerwall GE et al Early nasogastric feeding in predicted severe AP - a randomised controlled studyAnn Surg 2006;244,959-967

Kumar A et alEarly enteral nutrition in severe acute pancreatitis – a prospective randomisedControlled trial comparing nasojejunal and nasogastric routesControlled trial comparing nasojejunal and nasogastric routesJ Clin Gastroenterol 2006;40,431-434

Feeding must be distal to the Ligament g gof Treitz

Eatock FC et al.Nasogastric feeding in severe acute pancreatitis may be practical and safe. Int J Pancreatol 2000; 28: 25-31

E t k FC t lEatock FC et al.A randomized study of early nasogastric versus nasojejunal feeding in severe APAm J Gastroenterol 2005; 100: 432-9.

Eckerwall GE et al Early nasogastric feeding in predicted severe AP - a randomised controlled studyAnn Surg 2006;244,959-967

Kumar A et alEarly enteral nutrition in severe acute pancreatitis – a prospective randomisedControlled trial comparing nasojejunal and nasogastric routes

Proximal feeding is possible without apparent exacerbation of disease

Controlled trial comparing nasojejunal and nasogastric routesJ Clin Gastroenterol 2006;40,431-434

apparent exacerbation of disease

Potential problems with enteral feeding

Theoretical prolongation of disease

Tolerance ( ? Peptide / fibre feeds / aspiration)

Ri k f t b i ti ( d i / di l i l)Risks of tube insertion ( endoscopic / radiological)

Adequate absorption of delivered feed?q p

Pain on refeeding? (25%)Petrov MSPetrov MSOral refeeding after onset of acute pancreatitis – a review of the literature ( Levy, Pandey and Chebli studies)Am J Gastroenterol 2007;102,2079-2084

Theoretical advantages Theoretical advantages Measurable clinically relevant Measurable clinically relevant relating to feed deliveryrelating to feed delivery morbidity of nutritional delivery morbidity of nutritional delivery

Theoretical advantages Theoretical advantages Measurable clinically relevant Measurable clinically relevant relating to feed deliveryrelating to feed delivery morbidity of delivery systemmorbidity of delivery system

Pragmatic approach to maintenance Pragmatic approach to maintenance of nutritional integrityof nutritional integrity

Oral dietOral diet NGNG NJNJ TPNTPNOral diet Oral diet NGNG NJNJ TPNTPN


A dual-lumen naso-jejunal tube is passed to enable naso-gastric aspiration and naso-g pjejunal feeding.


What type of feed would you use via a naso-jejunal tube?j j

1) P l i R d1) Polymeric Red2) Peptide-based Yellow) ept de based e o3) Elemental Green


What evidence guides the prescription of naso-jejunal feeds?j j

Miss Olivia Boydss O a oyd

What evidence guides the i ti f j j lprescription of naso-jejunal

feeds?feeds?

Olivia BoydManchester Royal Infirmaryy y

What we will coverWhat we will cover• Background• Background

• Literature search

• Results from the trials

• Nutritional assessment

C t li i l ti• Current clinical practice

• Future developments• Future developments

BackgroundBackground• Conventional treatment resting the pancreas• Conventional treatment - resting the pancreas

• Pancreatic rest enables pain relief

• Associated with increased catabolic state

• Leads to increased energy expenditure

D d t iti l t t• Decreased nutritional status

• Nutritional support prevents malnutritionpp p

• Debate: when using the enteral route, what feed should we use?we use?

Literature searchLiterature searchAim to look for RCT on enteral feeding in pancreatitis• Aim to look for RCT on enteral feeding in pancreatitis comparing feeds

• Databases searched included medline1950-onwards, EMBASE from 1974, CINAHL from 1982, Allied & Complementary medicine from 1985Complementary medicine from 1985

• Pancreatitis, enteral nutrition, nutritional support, words d i MESHtruncated using MESH terms

• Limited to English & human studies• Limited to English & human studies

• 340 hits, 48 related, 3 met criteria340 hits, 48 related, 3 met criteria

The studiesThe studies Author Sample Route Feeds Regimen Outcome p g

measures 1 Lasztity et

al, 2004 14 treatment (T)14 control (C)

NJ T = n-3 PUFAC = polymeric

Started with half strength feed increased

Time receiving NJ feed LOSfeed, increased

over 3 days LOSComplications

2 Tiengou et l 2006

15 treatment (T)15 t l (C)

NJ T = semi l t l

35kcal/kg over 18h

Weight loss & LOSal, 2006 15 control (C) elemental

C = polymeric18hrsIncreaed by 500ml/d until goal achieved

LOS

g

3 Pearce et al, 2006

15 treatment (T)16 control (C)

NJ T = immune enhancing C = polymeric

As per dietetic protocol Fed for a

CRP by 40mg/L

C po y e c ed o aminimum of 3 days

Polymeric Vs. n-3 PUFA’sLasztity et al, 2004

• Moderate - severe pancreatitis

• Enteral nutrition - commenced within 24hrsEnteral nutrition commenced within 24hrs

• Total of 3.3g n-3 PUFA plus additional Vit E given/day

• Feed tolerance was similar between the 2 groups

• LOS & duration of jejunal feed was reduced in the n-3• LOS & duration of jejunal feed was reduced in the n-3

PUFA group (p<0.05)

• Tendency for fewer complications in the n-3 PUFA group

Polymeric Vs. Peptide(Tiengou et al, 2006)

M d t t titi i i NJ• Moderate - severe acute pancreatitis requiring NJ feeding

• Patients were NBM for 7-8 days prior to NJ feeding

• 50% of patients in each group received PN for approximately 8 days

• Tolerance of the feed was similar between both groups

• Semi-elemental feed resulted in less weight loss (p=0 01) and shorter length of stay (P=0 006)(p=0.01) and shorter length of stay (P=0.006)– ITT LOS: remained significant (p< 0.03)

Polymeric Vs. Immune(Pearce et al, 2006)

P ti t di t d t d l t titi• Patients predicted to develop severe acute pancreatitis

• Enteral nutrition commenced within 72hrs of onset of• Enteral nutrition commenced within 72hrs of onset of symptoms

• CRP reduced in 2/15 treatment vs. 6/16 control– By day 3 CRP significantly less in control vs. treatment (p=0.028)

• Tolerance of feeds was similar – Vomiting – 7 treatment / 1 control (p=0.029)

Nutritional assessmentNutritional assessmentI iti l i MUST• Initial screening MUST – Body mass index– Percentage weight loss in previous 3-6 months– Percentage weight loss in previous 3-6 months

• History of oral intakeHistory of oral intake

• Weight historyWeight history

• Subjective global assessmentSubjective global assessment – Estimated dry weight– Physical assessmenty

Assessing requirementsAssessing requirements

• 30% will be malnourished presenting with acute pancreatitis (Meler et al., 2002)

• Basal metabolic rate increases due to:Basal metabolic rate increases due to:– Inflammatory stress– PainPain – 80% of patients are catabolic (Shaw et al., 1986)

Calculating requirementsCalculating requirementsSt d d ti t l l t BMR• Standard equation to calculate BMR e.g. Schofield

• Stress factors vary:Stress factors vary: – 3% chronic pancreatitis

10% acute pancreatitis– 10% acute pancreatitis – 20% sepsis & abscess

(PENG Clinical Handbook, 2004)( )

Current clinical practiceCurrent clinical practiceM t t i l h d tid b d f d• Most trials have used peptide-based feeds

Demonstrated to be safe• Demonstrated to be safe

Pragmatic view due to lack of robust clinical• Pragmatic view due to lack of robust clinical trials

• It is common to start with a polymeric feed

• If this is not tolerated change to a peptide formula (ESPEN Guidelines 2006)formula (ESPEN Guidelines 2006)

Future developmentsFuture developments

• Role of probiotics

• Novel substrates use

• n-3 fatty acids• n-3 fatty acids

• Specific micronutrient supplementation


One of the factors in treating acute pancreatitis is the concept of resting the p p gpancreas to reduce its exocrine secretion and limit autodigestionand limit autodigestion.


Which of the following methods of feeding stimulate pancreatic exocrine secretion?p

1) N t i R d1) Naso-gastric Red2) Naso-jejunal Yellow) aso jeju a e o3) Intravenous Green4) None of these Blue


What is the evidence that pancreatic secretion is influenced by different types of y ypartificial nutrition?

Is the concept of pancreatic rest important inIs the concept of pancreatic rest important in treating acute pancreatitis?

Professor Peter LayerProfessor Peter Layer

The effect of different routesThe effect of different routesThe effect of different routesThe effect of different routesThe effect of different routes The effect of different routes of nutrient administration onof nutrient administration onThe effect of different routes The effect of different routes of nutrient administration onof nutrient administration onof nutrient administration on of nutrient administration on human pancreatic exocrinehuman pancreatic exocrine

of nutrient administration on of nutrient administration on human pancreatic exocrinehuman pancreatic exocrinehuman pancreatic exocrine human pancreatic exocrine

functionfunctionhuman pancreatic exocrine human pancreatic exocrine

functionfunctionPeter LayerPeter Layer

Interdigestive And Postprandial Interdigestive And Postprandial g pg pPancreatic Secretion*Pancreatic Secretion*

MealMeal MealMeal

FedFastingFastingCephalic PhaseGastric PhaseIntestinal PhaseIntestinal Phase

*Coordinated with gastric and bile output, and GI motility

Oral NutrientsOral NutrientsOral NutrientsOral Nutrients

Pancreatic Enzyme Response To A Mixed Pancreatic Enzyme Response To A Mixed Meal In HumansMeal In HumansMeal In HumansMeal In Humans

Layer et al, Gastroenterology 1997;112:1624-34

7

8LipasekU/min

5

6

3

4Cephalic Phase + Gastric Phase+ Intestinal Phase

2

3

0

1

0 1 2 3 40 1 2 3 4Postprandial Hours

Pancreatic Enzyme Response To A Mixed Meal Pancreatic Enzyme Response To A Mixed Meal In HumansIn HumansIn HumansIn Humans

Layer et al, Gastroenterology 1997;112:1624-34*Beglinger et al, J Clin Invest 1985;75:1471-76

7

8LipasekU/min 100

% Maximum*

5

680

3

4 60Cephalic Phase + Gastric Phase+ Intestinal Phase

2

3

20

40

0

1

0 1 2 3 40

20

0 1 2 3 4Postprandial Hours

Pancreatic Secretion In Response To A Pancreatic Secretion In Response To A Carbohydrate Meal In HumansCarbohydrate Meal In HumansCarbohydrate Meal In HumansCarbohydrate Meal In Humans

Layer P et al, Gastroenterology 1986;91:41-48

600

700Trypsin

U/min 100% Total Response

500 80

100

Intestinal Phase

300

40060

200

20

40

0

100

0 1 2 3 4

Cephalic + Gastric Phase

0

20

0 1 2 3 4Postprandial Hours

Role ofRole ofo e oDuodenal

o e oDuodenalDuodenal N t i tDuodenal N t i tNutrientsNutrients

Human Pancreatic Enzyme Output During Human Pancreatic Enzyme Output During I t d d lI t d d l E ti l A i A idE ti l A i A idIntraduodenalIntraduodenal Essential Amino AcidsEssential Amino Acids

Go VLW et al, Gastroenterology 1970;68:321-328

Duodenal EAA Perfusion

100

„Wash Out“100

kU/20min

Stimulated Secretion50

Li

0

LipaseTrypsin

0 1 2 3 4 5 6 10 min Periods

Human Trypsin Response to Graded Human Trypsin Response to Graded D d l A i A id P f iD d l A i A id P f iDuodenal Amino Acid PerfusionDuodenal Amino Acid Perfusion

Keller J et al, Pancreas 1996;13:442

150

100in

Human Subjectsn = 23Mean ± SE

100

n, U

/m

p = 0.00350

Tryp

sin

0 56 112 225 4500

Essential Amino Acids, µmol/min i.d.

Pancreatic Response to Oral vs Pancreatic Response to Oral vs Duodenal NutrientsDuodenal NutrientsDuodenal NutrientsDuodenal Nutrients

O‘Keefe SJ et al, Am J Physiol 2003;284:G27-36

250Amylase

200

y aseOutput,U/kg.h

150

100

0

50

0Placebo Oral Duodenal Duod

Elemental

Duodenal Triglyceride Perfusion Duodenal Triglyceride Perfusion ±± Lipase Inhibitor Orlistat (THL)Lipase Inhibitor Orlistat (THL)±± Lipase Inhibitor Orlistat (THL)Lipase Inhibitor Orlistat (THL)

Hildebrand P et al, Gastroenterology 1998;114:123-129

TrypsinResponse

LipaseActivity

CCK Release

Free Fatty AcidGeneration

8

p

120

140 NaCl THL

140

160

h

60

6

80

100

U/h 100

120

pmol

/L.h

40A

4*

∆kU

/h

40

60∆kU

60

80

AU

C, p

20

% F

FA

2

20

40

* 20

40 *20

*00

*p<0.01

00

Digestion and Gastric Emptying of a Mixed Meal Digestion and Gastric Emptying of a Mixed Meal in Severe Pancreatic Insufficiency (PI)in Severe Pancreatic Insufficiency (PI)in Severe Pancreatic Insufficiency (PI)in Severe Pancreatic Insufficiency (PI)


80

IntraduodenalNutrient Digestion

500

CCK Release180

Gastric EmptyingTime

400

500

0 m

in

160

180

*p < 0.01g

60 *p < 0.001

kJ 300

*p < 0.01m

ol/l.

18140

mpt

yin

40% k

200

CK

, ∆pm

100

120

90%

Em

20 100H lth PI t t d

CC

80

100

HealthyControl

PI untreated HealthyControl

PI untreated HealthyControl

PI untreated

Digestion and Gastric Emptying of a Mixed Meal Digestion and Gastric Emptying of a Mixed Meal in Severe Pancreatic Insufficiency (PI)in Severe Pancreatic Insufficiency (PI)in Severe Pancreatic Insufficiency (PI)in Severe Pancreatic Insufficiency (PI) Layer et al,

Gastroenterology 1997;112:1624-34

80


500

CCK Release180

Gastric EmptyingTime

4000 m

in

160

180

*p < 0.01g

60 *p < 0.001

kJ 300

*p < 0.01m

ol/l.

18140

mpt

yin

40% k

200

CK

, ∆pm

100

120

90%

Em

20 100H lth PI t t dPI t t d

CC

80

100

HealthyControl

PI untreatedPI treated HealthyControl

PI untreatedPI treated HealthyControl

PI untreatedPI treated

Regulation of Postprandial Pancreatic Regulation of Postprandial Pancreatic g pg pSecretion: Role of Duodenal NutrientsSecretion: Role of Duodenal Nutrients

Duodenum: sufficient to elicit the full pancreatic stimulatory response to oral nutrientstimulatory response to oral nutrient administration

cephalic gastric contributions adjuvant– cephalic, gastric contributions adjuvant– Marginal stimulatory contribution of jejunum

Mill LJ t l Di Di S i 1979 24 150 54Miller LJ et al, Dig Dis Sci 1979;24:150-54

Stimulation stronger in response to complex vs elemental nutrients

Stimulatory response to lipid requiresStimulatory response to lipid requires predigestion (i.e., presence of FFA)

Regulation of Pancreatic Functional States:Regulation of Pancreatic Functional States:Regulation of Pancreatic Functional States:Regulation of Pancreatic Functional States:Induction of Fed ResponsesInduction of Fed Responses

CephalicGastric

DuodenalMediation

Interdigestive Fed*

State State

*Vagal cholinergic*Peptide hormones*Peptide hormones

Stimulation of Pancreatic Enzyme Secretion Stimulation of Pancreatic Enzyme Secretion yyBy Duodenal NutrientsBy Duodenal Nutrients

CNSDuodenalLumen

AfferentNeurons Efferent

Neurons

Neural ReflexesCNS

Neurons

PancreaticAcinus

NutrientsOsmolarity DistensionDistensionetc

GI RegulatoryPeptides:

± ReleasingPeptides ? CCKCCK

Peptides:Hormones, Neuromodulators

CCK Links Postprandial Motor and CCK Links Postprandial Motor and Secretory ResponsesSecretory Responses

Intraduodenal Nutrient Delivery Gastric

E t idetermines

Bile

Emptying

i hibit-

-

Nutrientincreases

increases

Bile Output

inhibits

++

++

Nutrient Digestion

increases

increasesPancreatic

Enzyme Outputti l t

++

++CCK

Releasestimulates

stimulates

ReleaseFed Motility

Patternstimulates

ParenteralParenteralParenteral Parenteral NutrientsNutrients

Parenteral Nutrients Do Not Stimulate Parenteral Nutrients Do Not Stimulate Exocrine Pancreatic SecretionExocrine Pancreatic Secretion

Animal experiments (dogs)Animal experiments (dogs) Traverso LW et al, 1981; Fried GM et al, 1982

H t diHuman studies Stabile BE 1984; Niederau C 1984; Variyam EP 1985

Pancreatic secretion in response to Pancreatic secretion in response to d d l IV f did d l IV f diduodenal vs IV feedingduodenal vs IV feeding

O‘Keefe SJ et al, Am J Physiol 2003;284:G27-36

250Amylase

200

y aseOutput,U/kg.h

150

100

50

0Placebo Duodenal Intravenous

Jejunal NutrientsJejunal NutrientsJejunal NutrientsJejunal Nutrients

Effects of Effects of JejunalJejunal Nutrients on Human Nutrients on Human Pancreatic Secretion Depend on Perfusion SitePancreatic Secretion Depend on Perfusion SitePancreatic Secretion Depend on Perfusion Site Pancreatic Secretion Depend on Perfusion Site

DiMagno EP et al, J Lab Clin Med 1973; Miller LR et al, Gastroenterology 1979Vu MK et al, Eur J Clin Invest 1999

100

% Maximum

5060 cm

0Basal Jejunal

Pancreatic enzyme response to jejunal Pancreatic enzyme response to jejunal d d l f did d l f divs duodenal feedingvs duodenal feeding

Kaushik N et al, Pancreas 2005;31:353-59

400Trypsin

300

ypsOutput,

U/h

200

100

0

Basal Intravenous Duodenal Mid-Jejunal

Ileal NutrientsIleal NutrientsIleal NutrientsIleal Nutrients

Ileal Pancreatic BrakeIleal Pancreatic BrakeIleal Pancreatic BrakeIleal Pancreatic BrakeLayer P et al, Am J Physiol 1990;G196-G201

N Cl CHO Li id

+ Ileal ExposureDuodenal Amino Acids

250

300NaCl CHO Lipid

AmylaseU/min

200

250

100

150N = 9

p<0.001

50

100 p

0-15 0 15 30 45 60 75 90 105 120 min

Effect of Ileal Nutrients on Effect of Ileal Nutrients on Plasma GlucagonPlasma Glucagon Like PeptideLike Peptide 11Plasma GlucagonPlasma Glucagon--Like PeptideLike Peptide--11

Layer P, Holst JJ et al, Dig Dis Sci 1995;40:1074-82

70Ileal NaCl / CHO / Lipid

Duodenal Amino Acids

60

70

40

50GLP-1

pmol/ml

20

30pmol/ml

N = 9p<0.001

10

20

0-15 0 15 30 45 60 75 90 105 120 min

Lipase Output In Response To A Mixed Lipase Output In Response To A Mixed Meal In HumansMeal In HumansMeal In HumansMeal In Humans

Keller J et al, Am J Physiol 1997;272:G632-G637

Meal5

“Switch-Off”:

4

min

Induced by ileal nutrients

2

3

e, k

U/m

1

2

Lipa

se

0

1

0 1 2 3 4Hours postprandially

Regulation of Gastrointestinal Fed and Regulation of Gastrointestinal Fed and ggFasting States: Contribution of IleumFasting States: Contribution of Ileum

CephalicGastric

DuodenalStimulation

Interdigestive FedState State

Ileal Inhibition(“Brake”)

SummarySummarySummarySummary

Regulation Of Human Pancreatic Regulation Of Human Pancreatic S ti B I t ti l N t i tS ti B I t ti l N t i tSecretion By Intestinal NutrientsSecretion By Intestinal Nutrients

Keller J & Layer P, Gut 2005; 54(S): 1-28

Oral vs Intraduodenal:no difference

O‘Keefe 2003

Oral/Gastric,Duodenal:

(Sub-)maximal100

∆ Output

O Keefe 2003(Sub )maximalstimulationBeglinger 1985

Layer 1997O‘Keefe 2003

50

Jejunum: 100 ∆ Output

O Keefe 20030

jModerate (proximal)or no (distal)stimulation

100 ∆ Output

Ileum:0

stimulationDiMagno 1973Miller 1979Vu 1999

50Ileum:

SubmaximalinhibitionL 1990

-50

Kaushik 2005 0Layer 1990Keller 1997

-100 ∆ Output

NutrientNutrient--Induced Integration of Postprandial Induced Integration of Postprandial Motor and Pancreatic ResponsesMotor and Pancreatic ResponsesMotor and Pancreatic ResponsesMotor and Pancreatic Responses

Keller J & Layer P, Gut 2005;54(S):1-28Camilleri M, Gastroenterology 2006;131:640-58

Duodenal Nutrients:StimulatePancreatic SecretionPancreatic SecretionIntestinal Fed Motor Pattern

InhibitGastric Emptying



Duodenal Nutrients:StimulatePancreatic SecretionPancreatic SecretionIntestinal Fed Motor Pattern

Inhibit

Induce, Regulate & IntegrateP t di l R

Gastric Emptying

Postprandial Response



Gastric Emptying

Duodenal Nutrients:StimulatePancreatic Secretion

Gastric &

EmptyingPancreatic SecretionIntestinal Fed Motor Pattern

Inhibit Gastric &PancreaticSecretionInduce, Regulate & Integrate

P t di l R

Gastric Emptying

Small Ileal Nutrients (“Brake”):


Intestinal Transit

Ileal Nutrients ( Brake ):Inhibit Fed Motility and Secretion



Gastric Emptying

Duodenal Nutrients:StimulatePancreatic Secretion

Gastric &

EmptyingPancreatic SecretionIntestinal Fed Motor Pattern

Inhibit Gastric &PancreaticSecretionInduce, Regulate & Integrate

P t di l R

Gastric Emptying

Small Ileal Nutrients (“Brake”):


Intestinal Transit

Switch Off Fed Response

Ileal Nutrients ( Brake ):Inhibit Fed Motility and Secretion

pInduce Subsequent Interdigestive Pattern

Digestion and Gastric Emptying of a Mixed Meal in Digestion and Gastric Emptying of a Mixed Meal in Pancreatic InsufficiencyPancreatic InsufficiencyPancreatic InsufficiencyPancreatic Insufficiency


80


500

CCK Release Gastric EmptyingTime

60

80

400

500

0 m

in

150 *p < 0.01g

40

60*p < 0.001

kJ

300 *p < 0.01m

ol/l.

18100m

ptyi

n

20

% k

100

200

CK

, ∆pm

90%

Em

0Healthy CP

0

100

Healthy CP

CC 50

HealthyControl

CPuntreated

HealthyControl

CPuntreated 0

Healthy Control CP untreated

Digestion and Gastric Emptying of a Mixed Meal in Digestion and Gastric Emptying of a Mixed Meal in Pancreatic InsufficiencyPancreatic InsufficiencyPancreatic InsufficiencyPancreatic Insufficiency


80


500

CCK Release Gastric EmptyingTime

60

80

400

500

0 m

in

150 *p < 0.01g

40

*p < 0.001

kJ

300*p < 0.01

mol

/l.18

100

mpt

yin

20

% k

100

200

CK

, ∆pm

5090%

Em

0

Healthy CP CP treated

0

100

Healthy CP CP

CC

0

Healthy CP CPHealthy

Control

CP

untreated

CP treated Healthy

Control

CP

untreated

CP

treatedHealthy

Control

CP

untreated

CP

treated

CCK Links Postprandial GI Motor and Secretory CCK Links Postprandial GI Motor and Secretory ResponsesResponses

Intraduodenal Nutrient Delivery GNutrient Delivery Gastric

Emptying determines

-Bile

Output inhibits-

Lipid Digestion

increasesincreases

p

Pancreatic ++

++

Digestionincreases Enzyme Output

stimulates

++

CCKRelease

stimulates


The patient makes a gradual recovery and resumes ad libitum food intake but is advised to avoid alcohol

Symposium 1 Feeding in Pancreatitis -Ruth Newton …...acute pancreatitis: results of a randomized...

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