Nutritional Support in Acute Pancreatitis What are the Key Issues ?

Nutritional Support in Acute PancreatitisNutritional Support in Acute Pancreatitis What are the Key IssuesWhat are the Key Issues??

Stephen A. McClave, MDStephen A. McClave, MD Professor of MedicineProfessor of MedicineUniversity of Louisville School of MedicineUniversity of Louisville School of Medicine

Louisville, KentuckyLouisville, Kentucky

ObjectivesObjectives

To know how our perspective toward nutritional support in To know how our perspective toward nutritional support in acute pancreatitis in the past differs from that of today.acute pancreatitis in the past differs from that of today.

To learn which factors are important in promoting tolerance To learn which factors are important in promoting tolerance to artificial nutritional support.to artificial nutritional support.

To understand how to utilize route, timing, dose, and To understand how to utilize route, timing, dose, and content to optimize outcome from nutritional therapy.content to optimize outcome from nutritional therapy.

To know how our perspective toward nutritional support in To know how our perspective toward nutritional support in acute pancreatitis in the past differs from that of today.acute pancreatitis in the past differs from that of today.

To learn which factors are important in promoting tolerance To learn which factors are important in promoting tolerance to artificial nutritional support.to artificial nutritional support.

To understand how to utilize route, timing, dose, and To understand how to utilize route, timing, dose, and content to optimize outcome from nutritional therapy.content to optimize outcome from nutritional therapy.

ObjectivesObjectives

• To understand the benefits of enteral nutrition (EN) in acute To understand the benefits of enteral nutrition (EN) in acute pancreatitis and the timing of the “window of opportunity” pancreatitis and the timing of the “window of opportunity” during which feeds should be started.during which feeds should be started.

• To learn the risks and consequences of inadvertently To learn the risks and consequences of inadvertently stimulating the pancreas with EN in acute pancreatitis.stimulating the pancreas with EN in acute pancreatitis.

• To evaluate the benefits and compare actual experience of To evaluate the benefits and compare actual experience of gastric feeding with jejunal feeds in acute pancreatitis.gastric feeding with jejunal feeds in acute pancreatitis.

IntroductionIntroduction

Benefit of early EN on disease process and on patient Benefit of early EN on disease process and on patient outcomeoutcome

is dramaticis dramatic

Consequences of inadvertent pancreatic stimulation minimalConsequences of inadvertent pancreatic stimulation minimalWith vigilence, little chance of doing net harmWith vigilence, little chance of doing net harm

Any signs of symptom exaccerbation or inflamation in Any signs of symptom exaccerbation or inflamation in response to EN ameliorated by subtle adjustments in response to EN ameliorated by subtle adjustments in feeding strategyfeeding strategy

Benefit of early EN on disease process and on patient Benefit of early EN on disease process and on patient outcomeoutcome

is dramaticis dramatic

Consequences of inadvertent pancreatic stimulation minimalConsequences of inadvertent pancreatic stimulation minimalWith vigilence, little chance of doing net harmWith vigilence, little chance of doing net harm

Any signs of symptom exaccerbation or inflamation in Any signs of symptom exaccerbation or inflamation in response to EN ameliorated by subtle adjustments in response to EN ameliorated by subtle adjustments in feeding strategyfeeding strategy

IntroductionIntroduction

Narrow window of opportunity possibly 48-72 hrsNarrow window of opportunity possibly 48-72 hrsPotential for EN to Potential for EN to ↓↓disease severity, disease severity, ↓complications↓complicationsDelays may result in loss of chance for EN to improve outcomeDelays may result in loss of chance for EN to improve outcome

Vast majority of severe pancreatitis patients may tolerate feedsVast majority of severe pancreatitis patients may tolerate feedsMinimizing duration of ileus may improve toleranceMinimizing duration of ileus may improve tolerance

Dropping a Dobhoff NG tube simplest most expedient strategyDropping a Dobhoff NG tube simplest most expedient strategyAttains rapid accessAttains rapid accessQuickens time to initiation of feedsQuickens time to initiation of feedsInvolves minimal expertiseInvolves minimal expertiseFascilitates delivery of ENFascilitates delivery of EN

Narrow window of opportunity possibly 48-72 hrsNarrow window of opportunity possibly 48-72 hrsPotential for EN to Potential for EN to ↓↓disease severity, disease severity, ↓complications↓complicationsDelays may result in loss of chance for EN to improve outcomeDelays may result in loss of chance for EN to improve outcome

Vast majority of severe pancreatitis patients may tolerate feedsVast majority of severe pancreatitis patients may tolerate feedsMinimizing duration of ileus may improve toleranceMinimizing duration of ileus may improve tolerance

Dropping a Dobhoff NG tube simplest most expedient strategyDropping a Dobhoff NG tube simplest most expedient strategyAttains rapid accessAttains rapid accessQuickens time to initiation of feedsQuickens time to initiation of feedsInvolves minimal expertiseInvolves minimal expertiseFascilitates delivery of ENFascilitates delivery of EN

Controversial Study Controversial Study Gastric Feeds in SevereGastric Feeds in Severe

Acute PancreatitisAcute Pancreatitis

Eatock PRCT nasogastric vs nasojejunalEatock PRCT nasogastric vs nasojejunal

Severe pancreatitis (AP II >6, 25% mort) Severe pancreatitis (AP II >6, 25% mort) EN initiated within 72 hrs onset painEN initiated within 72 hrs onset painReached goal feeds in mean 36 hrsReached goal feeds in mean 36 hrs

No significant differences:No significant differences: CRP levels CRP levels Pain scores Pain scores

AP II scores Mortality AP II scores Mortality Hosp LOSHosp LOS Days to PO Days to PO

Conclusion: NG feeds can be considered as therapeutic optionConclusion: NG feeds can be considered as therapeutic option

Eatock PRCT nasogastric vs nasojejunalEatock PRCT nasogastric vs nasojejunal

Severe pancreatitis (AP II >6, 25% mort) Severe pancreatitis (AP II >6, 25% mort) EN initiated within 72 hrs onset painEN initiated within 72 hrs onset painReached goal feeds in mean 36 hrsReached goal feeds in mean 36 hrs

No significant differences:No significant differences: CRP levels CRP levels Pain scores Pain scores

AP II scores Mortality AP II scores Mortality Hosp LOSHosp LOS Days to PO Days to PO

Conclusion: NG feeds can be considered as therapeutic optionConclusion: NG feeds can be considered as therapeutic option

Amer J Gastro 2005 FebAmer J Gastro 2005 Feb

GlasgowGlasgow

NGNG

NJNJ

Double-Edged SwordDouble-Edged Sword

• Why are we asking for trouble?Why are we asking for trouble?• What is the risk of stimulating the pancreas ?What is the risk of stimulating the pancreas ?• What is the benefit from providing EN ?What is the benefit from providing EN ?• How strong is the evidence for benefit from How strong is the evidence for benefit from EN ?EN ?

Increase Stress with EN (Pancreatic Stimulation)

Reduce Stress with EN (Gut Integrity)

Pancreatic Rest: What Does it Mean?Pancreatic Rest: What Does it Mean?

Basal versus subclinical outputBasal versus subclinical output Clinical guidance by symptoms Clinical guidance by symptomsPoor management strategy alone Feedback monitor for tolerance Poor management strategy alone Feedback monitor for tolerance

Reduced level of stimulation that allows resolution of inflamationReduced level of stimulation that allows resolution of inflamation

Benefit of Providing ENBenefit of Providing EN

Maintain gut integrity (Less bacterial challenge, endotoxemia)Maintain gut integrity (Less bacterial challenge, endotoxemia) Set tone for systemic immunity (Oppose Th1 thru Th2 stimulation)Set tone for systemic immunity (Oppose Th1 thru Th2 stimulation) Attenuate stress response, disease severity (CRP, glucose, TAC)Attenuate stress response, disease severity (CRP, glucose, TAC) Faster resolution of disease process (Duration SIRS, Nutrit Rx, LOS)Faster resolution of disease process (Duration SIRS, Nutrit Rx, LOS) Fewer complications (Infection, surgical intervention, possibly MOF)Fewer complications (Infection, surgical intervention, possibly MOF)

Maintain gut integrity (Less bacterial challenge, endotoxemia)Maintain gut integrity (Less bacterial challenge, endotoxemia) Set tone for systemic immunity (Oppose Th1 thru Th2 stimulation)Set tone for systemic immunity (Oppose Th1 thru Th2 stimulation) Attenuate stress response, disease severity (CRP, glucose, TAC)Attenuate stress response, disease severity (CRP, glucose, TAC) Faster resolution of disease process (Duration SIRS, Nutrit Rx, LOS)Faster resolution of disease process (Duration SIRS, Nutrit Rx, LOS) Fewer complications (Infection, surgical intervention, possibly MOF)Fewer complications (Infection, surgical intervention, possibly MOF)

Impact on OutcomeImpact on Outcome

ParametersParameters

Impact on OutcomeImpact on Outcome

ParametersParameters

PN

McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)

Infection by 52%Infection by 52%

ENEN

Impact on Outcome Impact on Outcome ParametersParameters

Hospital LOS by 3.94 Days Hospital LOS by 3.94 Days

McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)

Impact on Outcome ParametersImpact on Outcome ParametersOrgan Failure (MOFS) by 41%Organ Failure (MOFS) by 41%

MOFS MOFS EN EN PN PN SignifSignif12.9%12.9% 26.7%26.7% p=0.18p=0.18

(13/101) (32/120)(13/101) (32/120) RR=0.59 RR=0.59

McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)

Impact on Outcome Impact on Outcome ParametersParameters

Need for Surgical Need for Surgical Intervention by 52% Intervention by 52%

PE Marik, GP Zaloga (BMJ 2004;328:1407)PE Marik, GP Zaloga (BMJ 2004;328:1407)

EN vs No Nutrition RxEN vs No Nutrition Rx

• Powell (Brit J Surg 2000;87:1375)• Powell (Brit J Surg 2000;87:1375)

TNFTNF

IL- 6IL- 6

CRPCRP

( ) = EN (n=13) ( ) = Stand (n=14)

Initial Initial AdmissionsAdmissions

EN vs No Nutrition RxEN vs No Nutrition RxPost-op for Complications of Post-op for Complications of Acute PancreatitisAcute Pancreatitis

p = 0.06p = 0.06

Mortality

EN STD

McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)

Mortality by 74%Mortality by 74%

Consequences of Consequences of Providing ENProviding EN

Three potentially adverse scenarios result from EN provision Three potentially adverse scenarios result from EN provision to patients with acute severe pancreatitisto patients with acute severe pancreatitis

Three potentially adverse scenarios result from EN provision Three potentially adverse scenarios result from EN provision to patients with acute severe pancreatitisto patients with acute severe pancreatitis

Warning: Early advanceWarning: Early advance to oral diet will increaseto oral diet will increase late complicationslate complications (abdominal abscess)(abdominal abscess)

Ranson (Surg 1997;82:99)Ranson (Surg 1997;82:99)

First Scenario: First Scenario: Silent Stimulation Silent Stimulation

of Secretionof Secretion

(iu/h)(iu/h) TrypsinTrypsin AmylaseAmylase Lipase Lipase

Healthy vol ENHealthy vol EN 439(27)439(27) 11,791(1106)11,791(1106) 610(61) 610(61)Healthy vol PNHealthy vol PN 266(49)*266(49)* 1,064(272)* 1,064(272)* 76(14)* 76(14)*

Patients ENPatients EN 209(33)209(33) 9,165(3787) 9,165(3787) 235(73) 235(73)Patients PNPatients PN 34(5) 34(5)‡‡ 674(137) 674(137) ‡‡ 13(2) 13(2)‡‡

( ‡ p<0.05, * p<0.005 ) ( ‡ p<0.05, * p<0.005 ) 1 1 O’Keefe (Gastro 2003;122:A34)O’Keefe (Gastro 2003;122:A34)

• Example: Patients from O’Keefe studyExample: Patients from O’Keefe study• Occurs in 100% of patientsOccurs in 100% of patients

Shhhhh!!Shhhhh!!

Second Scenario: Exacerbation of SymptomsSecond Scenario: Exacerbation of SymptomsExample: Jejunal Formula versus PO Clear Liquids Example: Jejunal Formula versus PO Clear Liquids 11

11 McClave (JPEN 1997;21:14) McClave (JPEN 1997;21:14) 22 Levy (Gut 1997;40:262) Levy (Gut 1997;40:262)

Uncomplicated exacerbation of sx in 21.0% Uncomplicated exacerbation of sx in 21.0% 22

Third Scenario: Exacerbation of Disease Process Third Scenario: Exacerbation of Disease Process Example: Jejunal versus Gastric Infusion Example: Jejunal versus Gastric Infusion 11

1 1 McClave (JPEN 1997;21:14) McClave (JPEN 1997;21:14) 22 Levy (Gut 1997;40:262) Levy (Gut 1997;40:262)

AmylaseAmylase

LipaseLipase

WBC CountWBC Count

Exacerbation of disease process in 4.3% Exacerbation of disease process in 4.3% 22

Who Needs Nutritional Rx?Who Needs Nutritional Rx?Correlation to Disease SeverityCorrelation to Disease Severity

Intestinal PermeabilityIntestinal Permeability(% Urinary Excretion PEG 3350)(% Urinary Excretion PEG 3350)

Controls 0.009Controls 0.009

Mild 0.008Mild 0.008

SevereSevere

No MOFS 0.040 *No MOFS 0.040 *

MOFS 0.160 *MOFS 0.160 *

Intestinal PermeabilityIntestinal Permeability(% Urinary Excretion PEG 3350)(% Urinary Excretion PEG 3350)

Controls 0.009Controls 0.009

Mild 0.008Mild 0.008

SevereSevere

No MOFS 0.040 *No MOFS 0.040 *

MOFS 0.160 *MOFS 0.160 *

Ammori ( J Gastrointest Surg 1999;3:252 ) * p<0.001Ammori ( J Gastrointest Surg 1999;3:252 ) * p<0.001

Who Needs Nutritional Rx ?Who Needs Nutritional Rx ?

APACHE II APACHE II < < 99 APACHE II APACHE II >> 10 10Rans Crit Rans Crit << 2 2 Rans Crit Rans Crit

>> 3 3

Degree of pancDegree of panc mild/mod mild/mod severe severeCT scanCT scan no necrosisno necrosis necrosis necrosisMortalityMortality 0% 0% 19% 19%ComplicationsComplications 6% 6% 38% 38%PO diet in 7dPO diet in 7d 81% 81% 0% 0%ManagementManagement supportive EN/PNsupportive EN/PN

Not exclusions: Necrosis, pseudocyst, ascites, surgeryNot exclusions: Necrosis, pseudocyst, ascites, surgeryExclusions: IntoleranceExclusions: Intolerance

Sax Sax (Amer J Surg 1987;153:117) (Amer J Surg 1987;153:117) WilsonWilson (Brit J Surg 1990;77:1260) (Brit J Surg 1990;77:1260) AgarwalAgarwal (Amer J Gastro 1991;86:1385) (Amer J Gastro 1991;86:1385)

APACHE II APACHE II < < 99 APACHE II APACHE II >> 10 10Rans Crit Rans Crit << 2 2 Rans Crit Rans Crit

>> 3 3

Degree of pancDegree of panc mild/mod mild/mod severe severeCT scanCT scan no necrosisno necrosis necrosis necrosisMortalityMortality 0% 0% 19% 19%ComplicationsComplications 6% 6% 38% 38%PO diet in 7dPO diet in 7d 81% 81% 0% 0%ManagementManagement supportive EN/PNsupportive EN/PN

Not exclusions: Necrosis, pseudocyst, ascites, surgeryNot exclusions: Necrosis, pseudocyst, ascites, surgeryExclusions: IntoleranceExclusions: Intolerance

Sax Sax (Amer J Surg 1987;153:117) (Amer J Surg 1987;153:117) WilsonWilson (Brit J Surg 1990;77:1260) (Brit J Surg 1990;77:1260) AgarwalAgarwal (Amer J Gastro 1991;86:1385) (Amer J Gastro 1991;86:1385)

Identifying Patients Identifying Patients with Severe Pancreatitiswith Severe Pancreatitis

AdmissionAdmission 48-72 48-72 HoursHours

Sensitivity Sensitivity SensitivitySensitivity

Clinical Assessment 34-44% Clinical Assessment 34-44% 44-66%44-66%

APACHE II Score >9 63% APACHE II Score >9 63% 75-82%75-82%

Ranson Criteria >2 N/A Ranson Criteria >2 N/A 75% 75%

Sensitivity higher for biliary >> ethanol etiologiesSensitivity higher for biliary >> ethanol etiologies

AdmissionAdmission 48-72 48-72 HoursHours

Sensitivity Sensitivity SensitivitySensitivity

Clinical Assessment 34-44% Clinical Assessment 34-44% 44-66%44-66%

APACHE II Score >9 63% APACHE II Score >9 63% 75-82%75-82%

Ranson Criteria >2 N/A Ranson Criteria >2 N/A 75% 75%

Sensitivity higher for biliary >> ethanol etiologiesSensitivity higher for biliary >> ethanol etiologiesWilson Wilson (Brit J Surg 1990;77:1260)(Brit J Surg 1990;77:1260) Larvin Larvin (Lancet 1989;2:201)(Lancet 1989;2:201)

He looks good to me…

Who Needs Nutritional Rx?Who Needs Nutritional Rx?Correlation to Disease SeverityCorrelation to Disease Severity

McClaveMcClave1 1 WindsorWindsor2 2 Abou-AssiAbou-Assi 3 3 KalferentosKalferentos4 4

* p<0.05* p<0.05 (n=32) (n=34) (n=33)(n=32) (n=34) (n=33) (n=38) (n=38)

% Severe% Severe 19% 38% 35% 19% 38% 35% 100% 100%Attenuate stressAttenuate stress RCRC CRP* CRP*

Glucose AII*Glucose AII* SIRS * SIRS *

Time to ResolutionTime to Resolution 11.8 6.2* 11.8 6.2*% Complications % Complications 75% 44% *75% 44% *% Septic Complications% Septic Complications 50% 28% *50% 28% *

11JPEN 1997;21:14JPEN 1997;21:14 2 2 Gut 1998;42:431 Gut 1998;42:431 3 3 Gastro 2001;120:A469 Gastro 2001;120:A469 4 4 Brit J Surg 1997;84:1665Brit J Surg 1997;84:1665

McClaveMcClave1 1 WindsorWindsor2 2 Abou-AssiAbou-Assi 3 3 KalferentosKalferentos4 4

* p<0.05* p<0.05 (n=32) (n=34) (n=33)(n=32) (n=34) (n=33) (n=38) (n=38)

% Severe% Severe 19% 38% 35% 19% 38% 35% 100% 100%Attenuate stressAttenuate stress RCRC CRP* CRP*

Glucose AII*Glucose AII* SIRS * SIRS *

Time to ResolutionTime to Resolution 11.8 6.2* 11.8 6.2*% Complications % Complications 75% 44% *75% 44% *% Septic Complications% Septic Complications 50% 28% *50% 28% *

11JPEN 1997;21:14JPEN 1997;21:14 2 2 Gut 1998;42:431 Gut 1998;42:431 3 3 Gastro 2001;120:A469 Gastro 2001;120:A469 4 4 Brit J Surg 1997;84:1665Brit J Surg 1997;84:1665

FormulaFormula Selection Selection

Study Pts ControlsStudy Pts Controls

• Small peptide/MCT formula (n=30) Small peptide/MCT formula (n=30) 11

Hosp LOS 23.0d* 27.0dHosp LOS 23.0d* 27.0d

• Fish oil formula (n=28) Fish oil formula (n=28) 22

Hosp LOS 13.1d* 19.3dHosp LOS 13.1d* 19.3d Durat EN 10.6d* 17.6dDurat EN 10.6d* 17.6d Complics 42% 64%Complics 42% 64%

• Arginine/fish oil formula (n=15) Arginine/fish oil formula (n=15) 33

ICU LOSICU LOS 8.6d 34.8d 8.6d 34.8d Hosp LOS 27.2d 38.4dHosp LOS 27.2d 38.4d

• Clinical SignificanceClinical Significance Below Lig Treitz – Tolerate STDBelow Lig Treitz – Tolerate STD Gastric – Content is tolerance factorGastric – Content is tolerance factor Pharmaconutrit – Fears of SIRSPharmaconutrit – Fears of SIRS

1 1 Tiengou (JPEN 2006;30:1) Tiengou (JPEN 2006;30:1) 2 2 Lasztity (Clin Nutrit 2005;24:198)Lasztity (Clin Nutrit 2005;24:198) 3 3 Hallay (Hepatogastroent 2001;48:1488) *pHallay (Hepatogastroent 2001;48:1488) *p<<0.050.05

Gastric vs Jejunal FeedingGastric vs Jejunal Feeding

Time to initiation of EN signif less for gastric feeds Time to initiation of EN signif less for gastric feeds 11

Gastric initiated mean 16 hrs (range 12-20 hrs) earlier Gastric initiated mean 16 hrs (range 12-20 hrs) earlier Eventually post-pyloric feeds “catch up” (time to goal, % Eventually post-pyloric feeds “catch up” (time to goal, %

goal)goal)

Track record of intragastric feeding in acute pancreatitis is good!Track record of intragastric feeding in acute pancreatitis is good!

McClave Louisville Study McClave Louisville Study 22

One patient jejunal-gastric displacement - SIRSOne patient jejunal-gastric displacement - SIRS Responded immediately to replacement back to jejunumResponded immediately to replacement back to jejunumEatock Glasgow Study Eatock Glasgow Study 33

70.4% Tolerated >75% goal kcal within 48 hrs (vs 77.2% 70.4% Tolerated >75% goal kcal within 48 hrs (vs 77.2% NJ)NJ)

Pain in 2/27 - No ▲infus rate, CRP, APain in 2/27 - No ▲infus rate, CRP, AII II scores, analgesia scores, analgesia Kumar Indian Study Kumar Indian Study 44

One patient each group experienced pain (no One patient each group experienced pain (no ▲amylase)▲amylase)

Partial PN required first week only in 6 NG (4NJ)Partial PN required first week only in 6 NG (4NJ)

Time to initiation of EN signif less for gastric feeds Time to initiation of EN signif less for gastric feeds 11

Gastric initiated mean 16 hrs (range 12-20 hrs) earlier Gastric initiated mean 16 hrs (range 12-20 hrs) earlier Eventually post-pyloric feeds “catch up” (time to goal, % Eventually post-pyloric feeds “catch up” (time to goal, %

goal)goal)

Track record of intragastric feeding in acute pancreatitis is good!Track record of intragastric feeding in acute pancreatitis is good!

McClave Louisville Study McClave Louisville Study 22

One patient jejunal-gastric displacement - SIRSOne patient jejunal-gastric displacement - SIRS Responded immediately to replacement back to jejunumResponded immediately to replacement back to jejunumEatock Glasgow Study Eatock Glasgow Study 33

70.4% Tolerated >75% goal kcal within 48 hrs (vs 77.2% 70.4% Tolerated >75% goal kcal within 48 hrs (vs 77.2% NJ)NJ)

Pain in 2/27 - No ▲infus rate, CRP, APain in 2/27 - No ▲infus rate, CRP, AII II scores, analgesia scores, analgesia Kumar Indian Study Kumar Indian Study 44

One patient each group experienced pain (no One patient each group experienced pain (no ▲amylase)▲amylase)

Partial PN required first week only in 6 NG (4NJ)Partial PN required first week only in 6 NG (4NJ)11Crit Care 2003;7:R46 Crit Care 2003;7:R46 22 JPEN 1997;21:14 JPEN 1997;21:14 3 3 AJG 2005;100:432 AJG 2005;100:432 44 J Clin Gastr 2006;40:431 J Clin Gastr 2006;40:431

Potential Changes in StrategyPotential Changes in StrategyIn Response to IntoleranceIn Response to Intolerance

Divert level of EN infusion lower in GI tractDivert level of EN infusion lower in GI tract

Infusion >40cm below Ligament Treitz no stimulation Infusion >40cm below Ligament Treitz no stimulation 44

Change content of formula to Change content of formula to ↓stimulation↓stimulation

Louisville study – Peptamin (33% fat) Louisville study – Peptamin (33% fat) 11

Glasgow study – Pepti-2000 LF (9% fat) Glasgow study – Pepti-2000 LF (9% fat) 22

Indian study – Peptamin (33% fat) Indian study – Peptamin (33% fat) 33

Divert level of EN infusion lower in GI tractDivert level of EN infusion lower in GI tract

Infusion >40cm below Ligament Treitz no stimulation Infusion >40cm below Ligament Treitz no stimulation 44

Change content of formula to Change content of formula to ↓stimulation↓stimulation

Louisville study – Peptamin (33% fat) Louisville study – Peptamin (33% fat) 11

Glasgow study – Pepti-2000 LF (9% fat) Glasgow study – Pepti-2000 LF (9% fat) 22

Indian study – Peptamin (33% fat) Indian study – Peptamin (33% fat) 33

NGNG

NJNJ

1 1 JPEN 1997;21:14 JPEN 1997;21:14 22 AJG 2005;100:432 AJG 2005;100:432 33 J Clin Gastro 2006;40:431 J Clin Gastro 2006;40:43144 O’Keefe (Gastro 2003;122:A34) O’Keefe (Gastro 2003;122:A34)

Change in ContentChange in Content

Volume Bicarb Amylase LipaseVolume Bicarb Amylase Lipase

VivonexVivonex +27% -24% -62% +4461%+27% -24% -62% +4461%

CriticareCriticare 0% -21% -25% +1317% 0% -21% -25% +1317%

OsmoliteOsmolite -7% -65% -7% -65% -84% +21,283% * -84% +21,283% *

Volume Bicarb Amylase LipaseVolume Bicarb Amylase Lipase

VivonexVivonex +27% -24% -62% +4461%+27% -24% -62% +4461%

CriticareCriticare 0% -21% -25% +1317% 0% -21% -25% +1317%

OsmoliteOsmolite -7% -65% -7% -65% -84% +21,283% * -84% +21,283% *

( * p<0.05)( * p<0.05) 11Parekh (S African J Surg 1993;31:57) Parekh (S African J Surg 1993;31:57) 22Grant Grant (JPEN 1987;11:302)(JPEN 1987;11:302)

FeedAspirate

Isolated duodenal fistulaIsolated duodenal fistula22Acute PancreatitisAcute Pancreatitis11

What Factors What Factors Affect Tolerance?Affect Tolerance?

Level of infusion Level of infusion

Content Content

Duration of ileus Duration of ileus

Institutional experience and expertiseInstitutional experience and expertise

Individual variation Individual variation

Level of infusion Level of infusion

Content Content

Duration of ileus Duration of ileus

Institutional experience and expertiseInstitutional experience and expertise

Individual variation Individual variation

ToleranceToleranceEffect of Duration of Ileus Effect of Duration of Ileus

• Prospective non-randomized series of 102 acute pancreatitis pts Prospective non-randomized series of 102 acute pancreatitis pts 11

SubsetSubset Duration of Ileus Duration of Ileus Achieve Tolerance ENAchieve Tolerance EN

Group 1 (n=11)Group 1 (n=11) >> 6 days 6 days 0% (PN)0% (PN)

Group 2 (n=8)Group 2 (n=8) << 5 days 5 days 50%50%

Group 3 (n=83)Group 3 (n=83) << 2 days 2 days 92%92%

• Early onset feeding EN within 48 hours thru 2 studies: Early onset feeding EN within 48 hours thru 2 studies: 22

Maintains gut function, improves toleranceMaintains gut function, improves tolerance

Fewer problems with ileus, gastric stasisFewer problems with ileus, gastric stasis

11 Cravo (Clin Nutrit Suppl 1989;8:14) Cravo (Clin Nutrit Suppl 1989;8:14) 2 2 Eatock (AJG 2005;100:432)Eatock (AJG 2005;100:432)

• Prospective non-randomized series of 102 acute pancreatitis pts Prospective non-randomized series of 102 acute pancreatitis pts 11

SubsetSubset Duration of Ileus Duration of Ileus Achieve Tolerance ENAchieve Tolerance EN

Group 1 (n=11)Group 1 (n=11) >> 6 days 6 days 0% (PN)0% (PN)

Group 2 (n=8)Group 2 (n=8) << 5 days 5 days 50%50%

Group 3 (n=83)Group 3 (n=83) << 2 days 2 days 92%92%

• Early onset feeding EN within 48 hours thru 2 studies: Early onset feeding EN within 48 hours thru 2 studies: 22

Maintains gut function, improves toleranceMaintains gut function, improves tolerance

Fewer problems with ileus, gastric stasisFewer problems with ileus, gastric stasis

11 Cravo (Clin Nutrit Suppl 1989;8:14) Cravo (Clin Nutrit Suppl 1989;8:14) 2 2 Eatock (AJG 2005;100:432)Eatock (AJG 2005;100:432)

Tolerance: InstitutionalTolerance: InstitutionalExperience and Expertise Experience and Expertise

Windsor Study in 34 patients PN vs EN Windsor Study in 34 patients PN vs EN 11

Some degree of ileus in 5/16 on ENSome degree of ileus in 5/16 on ENRequired decreased rate for 2 to 4 daysRequired decreased rate for 2 to 4 days

Schneider Study in 69 ICU pts on EN protocol (prospective) Schneider Study in 69 ICU pts on EN protocol (prospective) 22

Mean APACHE II = 18 (range 4-40)Mean APACHE II = 18 (range 4-40)

ResultsResults % Total Patients% Total Patients MortalityMortality

EN aloneEN alone 25% (17/69)25% (17/69) 24%24%EN/PN EN/PN 28% (19/69)28% (19/69) --PN AlonePN Alone 14% (10/69)14% (10/69) 60%60%NoneNone 33% (23/69)33% (23/69) --

11Gut 1998;42:431Gut 1998;42:431 22BritJSurg 2000;87:362BritJSurg 2000;87:362

Windsor Study in 34 patients PN vs EN Windsor Study in 34 patients PN vs EN 11

Some degree of ileus in 5/16 on ENSome degree of ileus in 5/16 on ENRequired decreased rate for 2 to 4 daysRequired decreased rate for 2 to 4 days

Schneider Study in 69 ICU pts on EN protocol (prospective) Schneider Study in 69 ICU pts on EN protocol (prospective) 22

Mean APACHE II = 18 (range 4-40)Mean APACHE II = 18 (range 4-40)

ResultsResults % Total Patients% Total Patients MortalityMortality

EN aloneEN alone 25% (17/69)25% (17/69) 24%24%EN/PN EN/PN 28% (19/69)28% (19/69) --PN AlonePN Alone 14% (10/69)14% (10/69) 60%60%NoneNone 33% (23/69)33% (23/69) --

11Gut 1998;42:431Gut 1998;42:431 22BritJSurg 2000;87:362BritJSurg 2000;87:362

Tolerance: IndividualTolerance: IndividualVariationVariation

Intolerance of gastric feeds involvingIntolerance of gastric feeds involving

a single patient in McClave Study a single patient in McClave Study 11

Nasogastric feeds tolerated in 27 pts as wellNasogastric feeds tolerated in 27 pts as well

as nasojejunal feeds in Eatock Study as nasojejunal feeds in Eatock Study 22

Intolerance of nasojejunal feedsIntolerance of nasojejunal feeds

Louisville case - 10cm below Lig of TreitzLouisville case - 10cm below Lig of TreitzRichmond case - Exaccerbation on NJ feeds Richmond case - Exaccerbation on NJ feeds 33

Intolerance of gastric feeds involvingIntolerance of gastric feeds involving

a single patient in McClave Study a single patient in McClave Study 11

Nasogastric feeds tolerated in 27 pts as wellNasogastric feeds tolerated in 27 pts as well

as nasojejunal feeds in Eatock Study as nasojejunal feeds in Eatock Study 22

Intolerance of nasojejunal feedsIntolerance of nasojejunal feeds

Louisville case - 10cm below Lig of TreitzLouisville case - 10cm below Lig of TreitzRichmond case - Exaccerbation on NJ feeds Richmond case - Exaccerbation on NJ feeds 33

11 McClave (JPEN 1997;) McClave (JPEN 1997;) 22 Eatock, Imrie (Gastro 2001;120:A469) Eatock, Imrie (Gastro 2001;120:A469)33 O’Keefe (Clin Gastro Hepat 2003;1:315) O’Keefe (Clin Gastro Hepat 2003;1:315)

Window of OpportunityWindow of Opportunity Early vs Delayed Enteral Nutrition Early vs Delayed Enteral Nutrition

Two meta-analyses: Early (<36 hrs) vs delayed (>36 hrs) ENTwo meta-analyses: Early (<36 hrs) vs delayed (>36 hrs) ENInfection reduced 55% (p=0.0006) Infection reduced 55% (p=0.0006) 11

Hospital LOS shortened 2.2 days (p=0.0004) Hospital LOS shortened 2.2 days (p=0.0004) 11

Mortality decreased 48% (p=0.08) Mortality decreased 48% (p=0.08) 22

1 Marik (CCM 2001;29:2264) 2 Heyland (JPEN 2003;27:355)

Window of OpportunityWindow of Opportunity Early vs Delayed EN in PancreatitisEarly vs Delayed EN in Pancreatitis

Six PRCTs EN vs PN randomized/feeding Six PRCTs EN vs PN randomized/feeding within 48hrswithin 48hrs

Five showed impact on outcome:Five showed impact on outcome: IInfectious morbidity nfectious morbidity ↓↓ (Abou-Assi, Kalfarentzos, (Abou-Assi, Kalfarentzos,

Olah)Olah) Shorter hosp LOS (Gupta)Shorter hosp LOS (Gupta) Less overall complications (Kalfarentzos)Less overall complications (Kalfarentzos) Duration dz process Duration dz process ↓ ↓ , nutrit Rx , nutrit Rx ↓ ↓ (Abou-Assi, (Abou-Assi,

Gupta)Gupta) Faster resolution SIRS (Windsor)Faster resolution SIRS (Windsor)One showed no effect on outcomeOne showed no effect on outcome McClave (mean Ranson Criteria 1.1)McClave (mean Ranson Criteria 1.1)

One PRCT EN vs PN randomized/feeding One PRCT EN vs PN randomized/feeding after 4 daysafter 4 days (Louie) (Louie)

Mean Ranson Criteria 4.7-5.0Mean Ranson Criteria 4.7-5.0No effect on any clinical outcome parametersNo effect on any clinical outcome parameters

Six PRCTs EN vs PN randomized/feeding Six PRCTs EN vs PN randomized/feeding within 48hrswithin 48hrs

Five showed impact on outcome:Five showed impact on outcome: IInfectious morbidity nfectious morbidity ↓↓ (Abou-Assi, Kalfarentzos, (Abou-Assi, Kalfarentzos,

Olah)Olah) Shorter hosp LOS (Gupta)Shorter hosp LOS (Gupta) Less overall complications (Kalfarentzos)Less overall complications (Kalfarentzos) Duration dz process Duration dz process ↓ ↓ , nutrit Rx , nutrit Rx ↓ ↓ (Abou-Assi, (Abou-Assi,

Gupta)Gupta) Faster resolution SIRS (Windsor)Faster resolution SIRS (Windsor)One showed no effect on outcomeOne showed no effect on outcome McClave (mean Ranson Criteria 1.1)McClave (mean Ranson Criteria 1.1)

One PRCT EN vs PN randomized/feeding One PRCT EN vs PN randomized/feeding after 4 daysafter 4 days (Louie) (Louie)

Mean Ranson Criteria 4.7-5.0Mean Ranson Criteria 4.7-5.0No effect on any clinical outcome parametersNo effect on any clinical outcome parametersMcClave (JPEN 2006;30:143)McClave (JPEN 2006;30:143)

Is PN a Dead Issue?Is PN a Dead Issue?

Early TPN may be a liabilityEarly TPN may be a liability

PRCT in 54 pancreatitis patients PRCT in 54 pancreatitis patients 11

ControlsControls Early TPNEarly TPN

LOHLOH 10 days 10 days 16 days * 16 days *

Cath sepsisCath sepsis 1.5% 1.5% 10.5% * 10.5% *

ComplicationsComplications no differenceno difference

• Up to 47% pts may still need TPN Up to 47% pts may still need TPN 22

11Sax (Amer J Surg 1987;153:117) Sax (Amer J Surg 1987;153:117) 22Schneider (Gut 1998;42:431)Schneider (Gut 1998;42:431) *p<0.05*p<0.05

Early TPN may be a liabilityEarly TPN may be a liability

PRCT in 54 pancreatitis patients PRCT in 54 pancreatitis patients 11

ControlsControls Early TPNEarly TPN

LOHLOH 10 days 10 days 16 days * 16 days *

Cath sepsisCath sepsis 1.5% 1.5% 10.5% * 10.5% *

ComplicationsComplications no differenceno difference

• Up to 47% pts may still need TPN Up to 47% pts may still need TPN 22

11Sax (Amer J Surg 1987;153:117) Sax (Amer J Surg 1987;153:117) 22Schneider (Gut 1998;42:431)Schneider (Gut 1998;42:431) *p<0.05*p<0.05

Options for Nutrition SupportOptions for Nutrition Support in the Individual Patientin the Individual Patient

ENENStandard RxStandard Rx (Do nothing)(Do nothing)

PNPN

Options in acuteOptions in acutepancreatitis based on:pancreatitis based on:

Disease severityDisease severity TimingTiming ToleranceTolerance

Priorities of “Nutritional Management”Priorities of “Nutritional Management”

Time (days)

Benefit (%)

100

50

0

1 2 3 54 6 7

( ) = Immune Modulation

( ) = Protein/calorie Provision

Is PN a DeadIs PN a Dead Issue? Issue?

Xian-Li PRCT of PN in “severe” acute pancreatitis (after resuscitation)Xian-Li PRCT of PN in “severe” acute pancreatitis (after resuscitation)

Group IGroup I Group IIGroup II Group IIIGroup III STD (n=23) PN (n=21) PN/Glut (n=20)STD (n=23) PN (n=21) PN/Glut (n=20)

MortalityMortality 43.5% 43.5% 14.3% * 14.3% * 0.0% * 0.0% *ComplicationsComplications 21 21 11 * 11 * 4 4 ##

Panc infectionPanc infection 8 8 5 5 0 * 0 *##

Hosp LOS (d)Hosp LOS (d) 39.139.1++10.610.6 28.628.6++6.9*6.9* 25.3 25.3++7.6*7.6*

(*p<0.05 Groups II or III vs Group I) ((*p<0.05 Groups II or III vs Group I) (##p<0.05 Group III vs Group II)p<0.05 Group III vs Group II)

Clin Nutrit Suppl 2004;1:43Clin Nutrit Suppl 2004;1:43

Management AlgorhythmManagement AlgorhythmPlace NG in ERPlace NG in ER

Start Peptide/MCT FeedsStart Peptide/MCT Feeds

At 48 Hrs – RC/APACHE At 48 Hrs – RC/APACHE IIII

Mild to Moderate DzMild to Moderate Dz Severe Dz Severe Dz <<2RC, 2RC, <<9A9AIIII >>3RC, 3RC, >>10A10AIIII

Tolerates NG EN NG EN IntoleranceTolerates NG EN NG EN Intolerance

Switch to NJ feedsSwitch to NJ feeds

Start PN if intolerantStart PN if intolerant > 5 days> 5 days

Advance to Oral Clear LiquidsAdvance to Oral Clear Liquids

Place NG in ERPlace NG in ER Start Peptide/MCT FeedsStart Peptide/MCT Feeds

At 48 Hrs – RC/APACHE At 48 Hrs – RC/APACHE IIII

Mild to Moderate DzMild to Moderate Dz Severe Dz Severe Dz <<2RC, 2RC, <<9A9AIIII >>3RC, 3RC, >>10A10AIIII

Tolerates NG EN NG EN IntoleranceTolerates NG EN NG EN Intolerance

Switch to NJ feedsSwitch to NJ feeds

Start PN if intolerantStart PN if intolerant > 5 days> 5 days

Advance to Oral Clear LiquidsAdvance to Oral Clear Liquids

ConclusionsConclusions

Gold Standard