1. Nutritional Management of Acute and Chronic Pancreatitis John P. Grant, MD Duke University Medical Center

2. Clinical Spectrum of Pancreatitis u Acute edematous - mild, self limiting u Acute necrotizing or hemorrhagic - severe u Chronic

3. Etiology of Acute Pancreatitis u Biliary u Alcoholic u Traumatic u Hyperlipidemia u Surgery u Viral u Others

4. Diagnosis and Monitoring of Severity of Acute Pancreatitis u Amylase and lipase u Temperature and WBC u Abdominal pain

5. Determination of Severity u Ranson’s Criteria u Imire ’s Criteria u Balthazar’ Severity Index

6. Ranson’s Criteria Surg Gynecol Obstet 138:69, 1974 u Age > 55 years u Blood glucose > 200 mg% u WBC > 16,000 mm 3 u LDH > 700 IU/L u SGOT > 250 U/L If > 3 are present at time of admission, 60% die

7. Ranson’s Criteria Surg Gynecol Obstet 138:69, 1974 u Hct decreases > 10% u Calcium falls to < 8.0 mg% u Base deficit > 4 mEq/L u BUN increases > 5 mg% u P a O 2 is < 60 mmHg If > 3 are present within 48 hours of admission, 60% die

8. Imrie’s Criteria Gut 25:1340, 1984 u Age > 55 u WBC 15,000 mm 3 u Glucose > 190 mg% u BUN > 23 mg% u PaO2 < 60 mmHg u Calcium <8.0 mg% u Albumin < 3.2 g% u LDH> 600 U/L If > 3 or more present, 40% will be severe If < 3 present, only 6% will be severe Predicts 79% of episodes In first 48 hours of admission

9. Balthazar’s Criteria u Appearance on unenhanced CT: Grade A to E –Edema within gland –Edema surrounding gland –Peripancreatic fluid collections u Appearance on enhanced CT: 0 to 100% necrosis of gland –Degree of pancreatic necrosis

10. Grade A: normal pancreas with clinical pancreatitis

11. Grade B: Diffuse enlargement of the pancreas without peripancreatic inflammatory changes

12. Grade C: Enlarged pancreas with haziness and increased density of peripancreatic fat

13. Grade D: Enlarged body and tail of pancreas with fluid collection in left anterior pararenal space

14. Grade E: Fluid collections in lesser sac and anterior pararenal space

15. Grade E pancreatitis with normal enhancement - 0% necrosis

16. Grade E pancreatitis with <30% necrosis

17. Grade E pancreatitis with 40% necrosis

18. Grade E pancreatitis with 50% necrosis

19. Grade E pancreatitis with >90% necrosis and abscess formation

20. Pancreatic Necrosis M&M Balthazar, Radiology 174:331, 1990

21. CT Severity Index u Grade –Grade A = 0 –Grade B = 1 –Grade C = 2 –Grade D = 3 –Grade E = 4 u Degree of necrosis –None = 0 –33% = 2 –50% = 4 –>50% = 6

22. Balthazar, Radiology 174:331, 1990 CT Severity Index and M&M

23. Standard Management u Restore and maintain blood volume u Restore and maintain electrolyte balance u Respiratory support u ± Antibiotics u Treatment of pain

24. Indications for Surgery u Need for pressors after adequate volume replacement u Persistent or increasing organ dysfunction despite maximum intensive care for at least 5 days u Proven or suspected infected necrosis u Uncertain diagnosis, progressive peritonitis or development of an acute abdomen

25. Standard Management u High M&M felt to be due to several factors: –High incidence of MOF –Need for surgery - often multiple –Development or worsening of malnutrition

26. Mechanisms Leading to Progression of Acute Pancreatitis u Stimulation of pancreatic secretion by oral intake (<24 hours) u Release of cytokines, poor perfusion of gland (24-72 hours)

28. Optimal Medical Management u Minimize exocrine pancreatic secretion u Avoid or suppress cytokine response u Avoid nutritional depletion

29. Optimal Medical Management u Minimize exocrine pancreatic secretion –NPO –Ng tube decompression of stomach –Cimetidine –Provision of a hypertonic solution in proximal jejunum

30. Optimal Medical Management u Minimize exocrine pancreatic secretion u Avoid or suppress cytokine response

33. Suppression of Cytokines u Antagonizing or blocking IL-1 and/or TNF activity – antibody and receptor antagonists u Preventing IL-1 and/or TNF production –Generic macrophage pacification –IL-10 regulation of IL-1 and TNF –Inhibiting posttranscriptional modification of pro-IL-1 u Gene therapy to inhibit systemic hyperinflammatory response of pancreatitis

35. Postburn Hypermetabolism and Early Enteral Feeding u 30% BSA burn in guinea pigs u Enteral feeding via g-tube at 2 or 72 hours following burn u Mucosal weight and thickness were similar Postburn day 175 Kcal - 72 h 200 Kcal - 72 h 175 Kcal - 2 h Alexander, Ann Surg 200:297, 1984

36. Optimal Medical Management u Minimize exocrine pancreatic secretion u Avoid or suppress cytokine response u Avoid nutritional depletion –If gut not functioning – TPN –If gut functioning - Enteral

37. Pancreatic Exocrine Secretion u Water and Bicarbonate: –Acid in duodenum –Meat extracts in duodenum –Antral distention u Enzymes: –Fat and protein in duodenum –Ca, Mg, meat extracts in duodenum –Eating, antral distention Stimulants

38. Pancreatic Exocrine Secretion u IV amino acids u Somatostatin u Glucagon u Any hypertonic solution in jejunum Depressants

39. Summary of Ideal Feeding Solutions in Acute Pancreatitis u Parenteral: Crystalline amino acids, hypertonic glucose solutions (IV fat emulsions tolerated) u Enteral: Low fat, elemental, hypertonic solutions given into jejunum

42. Pancreatitis: Effect of TPN Sitzmann et al, Surg Gynecol Obstet, 168:311, 1989 u 73 patients with acute pancreatitis (ave. Ranson’s 2.5) were given TPN. –81% had improved nutrition status –Mortality was increased 10-fold in patients with negative nitrogen balance –60% required insulin (ave. 35 U/d) –Lipid well tolerated

43. Pancreatitis: Effect of TPN Robin et al, World J Surg, 14:572, 1990 u 156 patients with acute MILD to MODERATE pancreatitis received TPN (70 simple – Ranson’s 1.6; 86 complex pancreatitis – Ranson’s 2.2) Male/Female112/44 Average age39.3 ± 1.0 Etiology124 EtOH (79%), 19 Biliary (12%) MortalitySimple 4%, Complex 5%

44. Pancreatitis: Effect of TPN Robin et al, World J Surg, 14:572, 1990 u Complications –20 catheters were removed suspected sepsis (11%), 3 proven –55% of patients required insulin (ave. 69 U/d) –15% developed respiratory failure, 3% hepatic failure, 1% renal failure, and 1% GI bleeding

45. Pancreatitis: Effect of TPN Robin et al, World J Surg, 14:572, 1990 u Nutritional status improved during TPN u TPN solution was well tolerated u TPN had no impact on course of disease

46. Pancreatitis: Effect of TPN Kalfarentzos et al. J. Am. Coll. Nutr., 10:156, 1991 u 67 patients with SEVERE pancreatitis (Ranson’s criteria > 3) were given TPN –Age: 57.8 ± 2 –Male/Female 25/42 –Average Ranson’s 3.8 ±.21 –Etiology Alcohol2 (3%) Cholelithiasis57 (85%) Hypertriglyceridemia2 (3%) Trauma/Idiopathic6 (9%)

47. Pancreatitis: Effect of TPN Kalfarentzos et al. J. Am. Coll. Nutr., 10:156, 1991 u Fat emulsion did not cause clinical or laboratory worsening of pancreatitis u 8.9% catheter-related sepsis vs 2.9% in other patients u Hyperglycemia occurred in 59 patients (88%) and required an average of 46 U/d insulin

48. Pancreatitis: Effect of TPN Kalfarentzos et al. J. Am. Coll. Nutr., 10:156, 1991 u If TPN started within 72 hours: 23.6% complication rate and 13% mortality u If TPN started after 72 hours: 95.6% complication rate and 38% mortality

49. Pancreatitis: Effect of TPN Kalfarentzos et al. J. Am. Coll. Nutr., 10:156, 1991 < 72 hours>72 hours # Pts3829 Ranson’s Criteria3.23.9 Complications Respiratory Failure3 (7.8%)5 (17.2%) Renal Failure1 (2.6%)2 (6.8%) Pancreatic Necrosis2 (5.3%)7 (34.1%) Abscesses05 (17.2%) Pseudocysts1 (2.6%)5 (17.2%) Pancreatic Fistulae2 (5.3%)4 (13.8%) Total9 (23.6%)28 (96.5%) Death5 (13%)11 (38%)

50. Pancreatitis: Effect of TF Kudsk et al, Nutr Clin Pract, 5:14, 1990 u 9 patients with acute pancreatitis were given jejunostomy feedings following laparotomy –Although diarrhea was a frequent problem, TF was not stopped or decreased, TPN was not required –No fluid or electrolyte problems occurred –Serum amylase decreased progressively –Hyperglycemia was common but responded to insulin

51. Pancreatitis: TPN vs TF McClave et al, JPEN, 21:14, 1997 u 32 middle aged male alcoholics with mild pancreatitis (Ranson’s ave. 1.3) u Randomized to receive either nasojejunal (Peptamen) or TPN within 48 hours of admission (25 kcal, 1.2 g protein/kg/d)

52. Pancreatitis: TPN vs TF McClave et al, JPEN, 84:1665, 1997 u There was no difference in serial pain scores, days to normal amylase, days to PO diet, or percent infections between groups u The mean cost of TPN was 4 times greater than TF

53. Pancreatitis: TPN vs TF Kalfarentzos et al, Br J Surg, 84:1665, 1997 u 38 patients with severe necrotizing pancreatitis were given either jejunostomy feedings or TPN within 48 hours of diagnosis –3 or more Ranson’s criteria –APACHE II score > 8 –Grade D or E Balthazar criteria

54. Pancreatitis: TPN vs TF Kalfarentzos et al, Br J Surg, 84:1665, 1997 u Jejunal feedings with Reabilan HN containing 52 g/L fat (61% long-chain and 39% medium-chain triglycerides) u TPN with Vamin as all-in-1 using Lipofudin long-chain/medium-chain triglycerides u Target support 1.5-2 g protein/kg/d and 30-35 kcal/kg/d

55. Pancreatitis: TPN vs TF Kalfarentzos et al, Br J Surg, 84:1665, 1997 u Outcome: –Both enteral and parenteral nutrition were well tolerated with no adverse effects on the course of pancreatitis –No difference in total days on nutrition support (33 d); total days in ICU (11 d); time on ventilator (13 d); use of and time on antibiotics (22 d); mean length of hospital stay (40 d); or mortality

56. Pancreatitis: TPN vs TF Kalfarentzos et al, Br J Surg, 84:1665, 1997 u Outcome: –TF patients had significantly less morbidity than TPN patients »Septic complications 5 vs 10 p <.01 »Hyperglycemia 4 vs 9 »All complications 8 vs 15 p <.05 –Risk of developing complications with TPN was 3.47 times greater than with TF

57. Pancreatitis: TPN vs TF Kalfarentzos et al, Br J Surg, 84:1665, 1997 u Outcome: –Cost of TPN was 3 times higher than TF u Conclusion: –Early enteral nutrition should be used preferentially in patients with severe acute pancreatitis

58. Duke Experience u 455 patients with moderate to severe pancreatitis were referred to NSS from 1990 – 1999 –Ave. age: 48 (range 5-94) –Male/Female: 247/208

59. Duke Experience Weight gain1.6 Albumin (pre/post)2.6/3.5* Transferrin (pre/post)128/176* PNI (pre/post)59.4/49.8 * p <.05

60. Duke Experience: TPN # Pts Ranson’s Criteria > 3305 Ave. Days of TPN16 Range1-127 Outcome Surgical Intervention223 Recovered diet PO/TF211/54 Home TPN8 Died32 (10.5%) TPN-related sepsis18 (5.9%)

61. Duke Experience: Enteral # Pts Ranson’s Criteria > 3150 Ave. Days of TF11 Range1-60 Outcome Surgical Intervention24 Recovered oral diet115 Home Enteral Nutrition33 Died2 (1.3%)

62. TPN vs TF and Acute Phase Response Windsor et al, Gut 42:431, 1998 u 34 patients with acute pancreatitis were randomized to TPN or TF for 7 days u Evaluated initially and at 7 days for systemic inflammatory response syndrome, organ failure, ICU stay

63. TPN vs TF and Acute Phase Response Windsor et al, Gut 42:431, 1998 u CT scan remained unchanged u Acute phase response significantly improved with TF vs TPN –CRP 156 to 84 –APACHE II scores 8 to 6 –Reduced endotoxin production and oxidant stress u Enteral feeding modulates the inflammatory response in acute pancreatitis and is clinically beneficial

64. Summary Recommendations u Initiate standard medical care immediately u Determine severity of pancreatitis u If severe, initiate early nutrition support (within 72 hours)

65. Caloric Expenditure in Pancreatitis Author# PtsRQMEE Van Gossum40.812080 Bluffard60.872525 Dickerson50.7826 Kcal/kg Velasco230.861687 Duke60.861817 Average ratio MEE/predicted = 1.24

66. Nitrogen and Fat Needs in Pancreatitis u Nitrogen: 1.0 – 2.0 gm/kg/d –Nitrogen balance study is helpful –Value of BCAA not determined u Fat: Fat well tolerated IV and to limited degree in jejunum, no oral fat should be given –Value of lipids ? as stress increases

67. Other Nutritional Needs in Pancreatitis u Calcium, Magnesium, Phosphorus u Vitamin supplements – especially B-complex u Supplement insulin as needed

68. Summary Recommendations u If ileus is present, precluding enteral feeding, begin TPN within 72 hours: –Standard amino acid product –IV fat emulsions are safe –Supplement insulin and vitamins –Beware of catheter sepsis

69. Summary Recommendations u If intestinal motility is adequate, initiate enteral nutrition with jejunal access within 72 hours: –Low fat, elemental, hypertonic –Give fat intravenously as needed –Add extra vitamins –Decompress stomach as needed

70. Summary Recommendations u As disease resolves: –Begin TF if on TPN –Begin oral diet if on TF »low fat, small feedings »Then, high protein, high calorie, low fat »Supplement with pancreatic enzymes and insulin as needed