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Nutritional Support in Acute Pancreatitis What are the Key Issues ?

Nutritional Support in Acute Pancreatitis What are the Key Issues ? . Stephen A. McClave, MD Professor of Medicine University of Louisville School of Medicine Louisville, Kentucky. Objectives.

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Nutritional Support in Acute Pancreatitis What are the Key Issues ?

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  1. Nutritional Support in Acute Pancreatitis What are the Key Issues? Stephen A. McClave, MD Professor of Medicine University of Louisville School of Medicine Louisville, Kentucky

  2. Objectives • To know how our perspective toward nutritional support in acute pancreatitis in the past differs from that of today. • To learn which factors are important in promoting tolerance to artificial nutritional support. • To understand how to utilize route, timing, dose, and content to optimize outcome from nutritional therapy.

  3. Objectives • To understand the benefits of enteral nutrition (EN) in acute pancreatitis and the timing of the “window of opportunity” during which feeds should be started. • To learn the risks and consequences of inadvertently stimulating the pancreas with EN in acute pancreatitis. • To evaluate the benefits and compare actual experience of gastric feeding with jejunal feeds in acute pancreatitis.

  4. Introduction • Benefit of early EN on disease process and on patient outcome is dramatic • Consequences of inadvertent pancreatic stimulation minimal With vigilence, little chance of doing net harm • Any signs of symptom exaccerbation or inflamation in response to EN ameliorated by subtle adjustments in feeding strategy

  5. Introduction • Narrow window of opportunity possibly 48-72 hrs Potential for EN to ↓disease severity, ↓complications Delays may result in loss of chance for EN to improve outcome • Vast majority of severe pancreatitis patients may tolerate feeds Minimizing duration of ileus may improve tolerance • Dropping a Dobhoff NG tube simplest most expedient strategy Attains rapid access Quickens time to initiation of feeds Involves minimal expertise Fascilitates delivery of EN

  6. Controversial Study Gastric Feeds in SevereAcute Pancreatitis • Eatock PRCT nasogastric vs nasojejunal Severe pancreatitis (AP II >6, 25% mort) EN initiated within 72 hrs onset pain Reached goal feeds in mean 36 hrs No significant differences: CRP levels Pain scores AP II scores Mortality Hosp LOS Days to PO • Conclusion: NG feeds can be considered as therapeutic option Glasgow NG NJ Amer J Gastro 2005 Feb

  7. Double-Edged Sword Reduce Stress with EN (Gut Integrity) Increase Stress with EN (Pancreatic Stimulation) • Why are we asking for trouble? • What is the risk of stimulating the pancreas ? • What is the benefit from providing EN ? • How strong is the evidence for benefit from EN ?

  8. Pancreatic Rest: What Does it Mean? Reduced level of stimulation that allows resolution of inflamation Basal versus subclinical output Clinical guidance by symptoms Poor management strategy alone Feedback monitor for tolerance

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

  10. EN PN Infection by 52% Impact on Outcome Parameters McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)

  11. Impact on Outcome Parameters Hospital LOS by 3.94 Days McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)

  12. Impact on Outcome Parameters Organ Failure (MOFS) by 41% MOFS EN PN Signif 12.9% 26.7% p=0.18 (13/101) (32/120) RR=0.59 McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)

  13. Impact on Outcome Parameters Need for Surgical Intervention by 52% PE Marik, GP Zaloga (BMJ 2004;328:1407)

  14. EN vs No Nutrition Rx Initial Admissions ( ) = EN (n=13) ( ) = Stand (n=14) • Powell (Brit J Surg 2000;87:1375) IL- 6 CRP TNF

  15. EN vs No Nutrition Rx Post-op for Complications of Acute Pancreatitis Mortality by 74% Mortality EN STD p = 0.06 McClave SA, Chang WK, Heyland DK, Dhaliwal R (JPEN In Press)

  16. Consequences of Providing EN Three potentially adverse scenarios result from EN provision to patients with acute severe pancreatitis Warning: Early advance to oral diet will increase late complications (abdominal abscess) Ranson (Surg 1997;82:99)

  17. Shhhhh!! First Scenario: Silent Stimulation of Secretion • Example: Patients from O’Keefe study • Occurs in 100% of patients (iu/h) Trypsin Amylase Lipase Healthy vol EN 439(27) 11,791(1106) 610(61) Healthy vol PN 266(49)* 1,064(272)* 76(14)* Patients EN 209(33) 9,165(3787) 235(73) Patients PN 34(5)‡ 674(137) ‡ 13(2)‡ ( ‡ p<0.05, * p<0.005 ) 1 O’Keefe (Gastro 2003;122:A34)

  18. Second Scenario: Exacerbation of SymptomsExample: Jejunal Formula versus PO Clear Liquids 1 Uncomplicated exacerbation of sx in 21.0% 2 1 McClave (JPEN 1997;21:14) 2 Levy (Gut 1997;40:262)

  19. Third Scenario: Exacerbation of Disease Process Example: Jejunal versus Gastric Infusion 1 WBC Count Lipase Amylase Exacerbation of disease process in 4.3% 2 1 McClave (JPEN 1997;21:14) 2 Levy (Gut 1997;40:262)

  20. Who Needs Nutritional Rx?Correlation to Disease Severity Intestinal Permeability (% Urinary Excretion PEG 3350) Controls 0.009 Mild 0.008 Severe No MOFS 0.040 * MOFS 0.160 * Ammori ( J Gastrointest Surg 1999;3:252 ) * p<0.001

  21. Who Needs Nutritional Rx ? • APACHE II < 9 APACHE II > 10 Rans Crit < 2 Rans Crit > 3 • Degree of panc mild/mod severe • CT scan no necrosis necrosis • Mortality 0% 19% • Complications 6% 38% • PO diet in 7d 81% 0% • Management supportive EN/PN • Not exclusions: Necrosis, pseudocyst, ascites, surgery • Exclusions: Intolerance • Sax (Amer J Surg 1987;153:117) Wilson (Brit J Surg 1990;77:1260) • Agarwal (Amer J Gastro 1991;86:1385)

  22. Identifying Patients with Severe Pancreatitis He looks good to me… • Admission 48-72 Hours • Sensitivity Sensitivity • Clinical Assessment 34-44% 44-66% • APACHE II Score >9 63% 75-82% • Ranson Criteria >2 N/A 75% • Sensitivity higher for biliary >> ethanol etiologies Wilson (Brit J Surg 1990;77:1260) Larvin (Lancet 1989;2:201)

  23. Who Needs Nutritional Rx?Correlation to Disease Severity McClave1 Windsor2 Abou-Assi 3 Kalferentos4 * p<0.05 (n=32) (n=34) (n=33) (n=38) % Severe 19% 38% 35% 100% Attenuate stress RC CRP* Glucose AII* SIRS * Time to Resolution 11.8 6.2* % Complications 75% 44% * % Septic Complications 50% 28% * 1JPEN 1997;21:14 2 Gut 1998;42:431 3 Gastro 2001;120:A469 4 Brit J Surg 1997;84:1665

  24. Study Pts Controls • Small peptide/MCT formula (n=30) 1 • Hosp LOS 23.0d* 27.0d • Fish oil formula (n=28) 2 • Hosp LOS 13.1d* 19.3d • Durat EN 10.6d* 17.6d • Complics 42% 64% • Arginine/fish oil formula (n=15) 3 • ICU LOS 8.6d 34.8d • Hosp LOS 27.2d 38.4d • Clinical Significance • Below Lig Treitz – Tolerate STD • Gastric – Content is tolerance factor • Pharmaconutrit – Fears of SIRS Formula Selection 1 Tiengou (JPEN 2006;30:1) 2 Lasztity (Clin Nutrit 2005;24:198) 3 Hallay (Hepatogastroent 2001;48:1488) *p<0.05

  25. Gastric vs Jejunal Feeding • Time to initiation of EN signif less for gastric feeds 1 Gastric initiated mean 16 hrs (range 12-20 hrs) earlier Eventually post-pyloric feeds “catch up” (time to goal, % goal) • Track record of intragastric feeding in acute pancreatitis is good! McClave Louisville Study 2 One patient jejunal-gastric displacement - SIRS Responded immediately to replacement back to jejunum Eatock Glasgow Study 3 70.4% Tolerated >75% goal kcal within 48 hrs (vs 77.2% NJ) Pain in 2/27 - No ▲infus rate, CRP, AII scores, analgesia Kumar Indian Study 4 One patient each group experienced pain (no ▲amylase) Partial PN required first week only in 6 NG (4NJ) 1Crit Care 2003;7:R46 2 JPEN 1997;21:14 3 AJG 2005;100:432 4 J Clin Gastr 2006;40:431

  26. Potential Changes in StrategyIn Response to Intolerance NG • Divert level of EN infusion lower in GI tract Infusion >40cm below Ligament Treitz no stimulation 4 • Change content of formula to ↓stimulation Louisville study – Peptamin (33% fat) 1 Glasgow study – Pepti-2000 LF (9% fat) 2 Indian study – Peptamin (33% fat) 3 NJ 1 JPEN 1997;21:14 2 AJG 2005;100:432 3 J Clin Gastro 2006;40:431 4 O’Keefe (Gastro 2003;122:A34)

  27. Change in Content Volume Bicarb Amylase Lipase Vivonex +27% -24% -62% +4461% Criticare 0% -21% -25% +1317% Osmolite -7% -65% -84% +21,283% * Aspirate Feed Acute Pancreatitis1 Isolated duodenal fistula2 ( * p<0.05)1Parekh (S African J Surg 1993;31:57) 2Grant (JPEN 1987;11:302)

  28. What Factors Affect Tolerance? • Level of infusion • Content • Duration of ileus • Institutional experience and expertise • Individual variation

  29. ToleranceEffect of Duration of Ileus • Prospective non-randomized series of 102 acute pancreatitis pts 1 Subset Duration of Ileus Achieve Tolerance EN Group 1 (n=11) > 6 days 0% (PN) Group 2 (n=8) < 5 days 50% Group 3 (n=83) < 2 days 92% • Early onset feeding EN within 48 hours thru 2 studies: 2 Maintains gut function, improves tolerance Fewer problems with ileus, gastric stasis 1 Cravo (Clin Nutrit Suppl 1989;8:14) 2 Eatock (AJG 2005;100:432)

  30. Tolerance: InstitutionalExperience and Expertise • Windsor Study in 34 patients PN vs EN 1 Some degree of ileus in 5/16 on EN Required decreased rate for 2 to 4 days • Schneider Study in 69 ICU pts on EN protocol (prospective) 2 Mean APACHE II = 18 (range 4-40) Results % Total Patients Mortality EN alone 25% (17/69) 24% EN/PN 28% (19/69) - PN Alone 14% (10/69) 60% None 33% (23/69) - 1Gut 1998;42:431 2BritJSurg 2000;87:362

  31. Tolerance: IndividualVariation • Intolerance of gastric feeds involving a single patient in McClave Study 1 • Nasogastric feeds tolerated in 27 pts as well as nasojejunal feeds in Eatock Study 2 • Intolerance of nasojejunal feeds Louisville case - 10cm below Lig of Treitz Richmond case - Exaccerbation on NJ feeds 3 1 McClave (JPEN 1997;) 2 Eatock, Imrie (Gastro 2001;120:A469) 3 O’Keefe (Clin Gastro Hepat 2003;1:315)

  32. Window of Opportunity Early vs Delayed Enteral Nutrition Two meta-analyses: Early (<36 hrs) vs delayed (>36 hrs) EN Infection reduced 55% (p=0.0006) 1 Hospital LOS shortened 2.2 days (p=0.0004) 1 Mortality decreased 48% (p=0.08) 2 1 Marik (CCM 2001;29:2264) 2 Heyland (JPEN 2003;27:355)

  33. Window of OpportunityEarly vs Delayed EN in Pancreatitis • Six PRCTs EN vs PN randomized/feeding within 48hrs Five showed impact on outcome: Infectious morbidity ↓ (Abou-Assi, Kalfarentzos, Olah) Shorter hosp LOS (Gupta) Less overall complications (Kalfarentzos) Duration dz process ↓ , nutrit Rx ↓ (Abou-Assi, Gupta) Faster resolution SIRS (Windsor) One showed no effect on outcome McClave (mean Ranson Criteria 1.1) • One PRCT EN vs PN randomized/feeding after 4 days (Louie) Mean Ranson Criteria 4.7-5.0 No effect on any clinical outcome parameters McClave (JPEN 2006;30:143)

  34. Is PN a Dead Issue? • Early TPN may be a liability • PRCT in 54 pancreatitis patients 1 Controls Early TPN LOH 10 days 16 days * Cath sepsis 1.5% 10.5% * Complications no difference • Up to 47% pts may still need TPN 2 1Sax (Amer J Surg 1987;153:117) 2Schneider (Gut 1998;42:431)*p<0.05

  35. Options for Nutrition Support in the Individual Patient Options in acute pancreatitis based on: • Disease severity • Timing • Tolerance Standard Rx (Do nothing) PN EN

  36. Priorities of “Nutritional Management” 100 ( ) = Immune Modulation Benefit (%) 50 ( ) = Protein/calorie Provision 0 1 2 3 4 5 6 7 Time (days)

  37. Is PN a Dead Issue? Xian-Li PRCT of PN in “severe” acute pancreatitis (after resuscitation) Group I Group II Group III STD (n=23) PN (n=21) PN/Glut (n=20) Mortality 43.5% 14.3% * 0.0% * Complications 21 11 * 4 # Panc infection 8 5 0 *# Hosp LOS (d) 39.1+10.6 28.6+6.9* 25.3+7.6* (*p<0.05 Groups II or III vs Group I) (#p<0.05 Group III vs Group II) Clin Nutrit Suppl 2004;1:43

  38. Management Algorhythm Place NG in ER Start Peptide/MCT Feeds At 48 Hrs – RC/APACHE II Mild to Moderate Dz Severe Dz <2RC, <9AII>3RC, >10AII Tolerates NG EN NG EN Intolerance Switch to NJ feeds Start PN if intolerant > 5 days Advance to Oral Clear Liquids

  39. Conclusions Gold Standard

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