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

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

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

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

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

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

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

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

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

Grade A: normal pancreas with clinical pancreatitis

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

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

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

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

Grade E pancreatitis with normal enhancement - 0% necrosis

Grade E pancreatitis with <30% necrosis

Grade E pancreatitis with 40% necrosis

Grade E pancreatitis with 50% necrosis

Grade E pancreatitis with >90% necrosis and abscess formation

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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%

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

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

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%)

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

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

Pancreatitis: Effect of TPN Kalfarentzos et al. J. Am. Coll. Nutr., 10:156, 1991 < 72 hours>72 hours # Pts3829 Ranson’s Criteria 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%)

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

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)

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

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

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 g protein/kg/d and kcal/kg/d

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

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

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

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

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

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%)

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%)

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

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

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

Caloric Expenditure in Pancreatitis Author# PtsRQMEE Van Gossum Bluffard Dickerson Kcal/kg Velasco Duke Average ratio MEE/predicted = 1.24

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

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

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

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

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