Nutrition in Acute Pancreatitis“An Evidence Based Approach” Which patients benefits from nutritional support in acute pancreatitis? All patients with acute pancreatitis? (Mild pancreatitis is different from severe(Mild pancreatitis is different from severe pancreatitis) pancreatitis) Enteral or parenteral?Where is the evidence?Severity (Clinical, laboratory and radiological signs)(Clinical, laboratory and radiological signs)Nutritional status Outcome predictors- Mild form (- Mild form ( 80%)80%)- Severe form (- Severe form ( 20%)20%)1068 patients, mean age 52.8 yrs, 1068 patients, mean age 52.8 yrs, 589 edematous AP, 479 severe AP589 edematous AP, 479 severe APMORTALITY: total 7.8%,MORTALITY: total 7.8%, mildmild a aP 1%,P 1%, severe severe a aP 16.1%P 16.1%Severity and outcomeMortality can increase to up to 40% if sepsis and MOF occurMortality can increase to up to 40% if sepsis and MOF occurESPEN GuidelinesEnteral Nutrition:Clinical Nutrition Vol 25 (2), April 2006Parenteral Nutrition: Clinical Nutrition Vol 28, July 2009 guidelines.htm Severity of acute pancreatitisSeverity of acute pancreatitis can be can be assessed adequatelyassessed adequatelyFor artificial nutritional interventionsFor artificial nutritional interventions mild pancreatitis has to be separated from mild pancreatitis has to be separated from severe pancreatitis severe pancreatitisNutritional status has to be assessedNutritional status has to be assessed on on admission and during the course of the admission and during the course of the diseasediseaseRecommentation IMain goals for nutrition in acute pancreatitisTo provide calories with EN or PN to To provide calories with EN or PN to reverse protein catabolism without reverse protein catabolism without stimulation of the exocrine pancreatic stimulation of the exocrine pancreatic secretionsecretionTo improve or to avoid nutritional To improve or to avoid nutritional depletiondepletionTo reduce morbidity and mortality To reduce morbidity and mortality How should nutritional support be done?Parenteral or enteral? Gastral or jejunal?EN vs PN and acute pancreatitisMild to moderate pancreatitisMild to moderate pancreatitisEarlyEarly ENEN (ED, NJ) vs(ED, NJ) vs PNPNPRCT PRCT N=32N=32 ENEN PNPN n = 16n = 16 n = 16n = 16Caloric goal (day 4)Caloric goal (day 4) 72%72% 86%86%Days to normal amylase 4.8 Days to normal amylase 4.8 0.6 0.6 6.8 6.8 1.5 1.5Days to diet by mouthDays to diet by mouth 5.6 5.6 0. 7.1 0. 7.1 1.1 1.1LOH (days)LOH (days) 9.7 9.7 1.3 11.9 1.3 11.9 2.6 2.6Lengh of ICU stay (days) 1.3 Lengh of ICU stay (days) 1.3 0.9 2.8 0.9 2.8 1.3 1.3% Nosocomial infection 12.5 % Nosocomial infection 12.5 8.5 12.5 8.5 12.5 8.5 8.5Mortality (%)Mortality (%) 0.0 0.0 0.0 0.0Cost (US$)Cost (US$) 761 761 50.3 50.3 3294 3294 551.9* 551.9*McClave et al, JPEN, 1997McClave et al, JPEN, 1997 * p 0.05 * p 0.05 Is the situation differentin mild to moderate or severe pancreatitis?EN vs PN and acute pancreatitis Severe pancreatitisSevere pancreatitisENEN (SED, NJ) vs(SED, NJ) vs PNPNPRCTPRCTN=38N=38 ENEN PNPN n = 18n = 18 n = 20n = 20LOH (d)LOH (d) 40 (25-83) 40 (25-83) 39(22-73) 39(22-73)LOICU (d)LOICU (d) 10 (5-21) 10 (5-21) 12 (5-24) 12 (5-24)Complication Complication -septic (Tot.nb)-septic (Tot.nb) 5 (6)5 (6) 10 (15)*10 (15)*- Hyperglycaemia- Hyperglycaemia 4 4 9 9- Pancr. necrosis- Pancr. necrosis 1 1 4 4- -PneumoniaPneumonia 2 2 4 4- -CostsCosts 3 times higher3 times higherKalfarentzos et al, B J Surg, 1997EN vs PN and acute pancreatitisSevere pancreatitisSevere pancreatitis ENEN (NJ Hypocaloric) vs(NJ Hypocaloric) vs PNPNPRCTPRCTN=156N=156Enroled patientsEnroled patients 87% mild87% mild 10% moderate10% moderate 3% severe 3% severe 75% improved on 48h bowel rest and iv. fluids 75% improved on 48h bowel rest and iv. fluids discharged within 4 daysdischarged within 4 days Rest randomized to jejunal EN or PN Rest randomized to jejunal EN or PNAbou-Assi, et al, Am J Gastroenterology, 2002Abou-Assi, et al, Am J Gastroenterology, 2002Results of the randomized patients n = 27 n = 27 n = 26n = 26Ransons Criteria 2.5 (0.5) 3.1 (0.6)Ransons Criteria 2.5 (0.5) 3.1 (0.6)Nutr. Goal 88%* Nutr. Goal 88%* 54%54%Hyperglycemia (MOF) 14 pt.* (8) Hyperglycemia (MOF) 14 pt.* (8) 4 pt.(7)4 pt.(7)Catheter Sepsis 9 pt.* Catheter Sepsis 9 pt.* 1 pt.1 pt.Death 6 pt. 8 pt.Death 6 pt. 8 pt.Duration of feeding (d) 10.8* Duration of feeding (d) 10.8* 6.76.7Hosp. Days 18.4 (2.9)* Hosp. Days 18.4 (2.9)* 15.2 (2.6)15.2 (2.6)Hosp. Costs (US dollarHosp. Costs (US dollar) ) lower in EN (saving 2360.-)lower in EN (saving 2360.-)*p0.03*p 195 mg/L107 Patients 54 TPN54 TPN 115 kJ/KG/d 1,2 g N 250 ml 20% Intralipid 53 TEN53 TEN 115 kJ/KG/d 1,5 g N Survimed jejunalAPACHE II 16 4CRP 218 8 APACHE II 14 2CRP 211 9 Wu et al, Pancreas 2010EN vs PN and severe acute pancreatitisWu et al, Pancreas 2010EN vs PN and severe acute pancreatitis Enteral nutrition Enteral nutrition (N= 25)(N= 25)TPNTPN(N=25)(N=25)P valueP valueInfectionInfection 16 (64.0%)16 (64.0%) 15 (60.0%)15 (60.0%)1.0001.000ICU stay (days; ICU stay (days; median and range)median and range) 10 (0-44)10 (0-44) 15 (0-60)15 (0-60)0.6250.625Hospital stay Hospital stay (days; median and (days; median and range)range) 42 (15-108)42 (15-108) 36 (20-77)36 (20-77)0.7550.755MortalityMortality 5 (20.0%)5 (20.0%) 4 (16.0%)4 (16.0%)1.0001.000Doley et al, J Pancreas 2009EN vs PN in acute pancreatitisOlah et al, Langenbecks Arch Surg 2010847 patients847 patients16 RCT16 RCTRecommendation II There is no evidenceThere is no evidence that neither EN orthat neither EN or PN PN has a clinical beneficial effecthas a clinical beneficial effect onon clinical outcome in patients with clinical outcome in patients with mild mild pancreatitis, pancreatitis, if you can predict that the patient can if you can predict that the patient can consume normal food in between 5 daysconsume normal food in between 5 days (A)(A) If oral nutrition is not possible in 5 daysIf oral nutrition is not possible in 5 days enteral nutrition should be started immetiately enteral nutrition should be started immetiately (C)(C) If this is true in patients with malnutritionIf this is true in patients with malnutrition is not known is not known ESPEN, Guidelines 2006/2009ESPEN, Guidelines 2006/2009Treatment mild Treatment mild pancreatitispancreatitisAssessment of severity of acute pancreatitisAssessment of severity of acute pancreatitismild to moderatemild to moderatefasting (2-5 days)fasting (2-5 days) analgesics analgesics i.v. fluid/electrolytes i.v. fluid/electrolytesno pain, enzymesno pain, enzymesrefeeding (3-7 days)refeeding (3-7 days) diet rich in CH diet rich in CH diet moderate in protein/fat diet moderate in protein/fatnormal dietnormal dietRecommendation III Nutritional support in essential in patients with severe Nutritional support in essential in patients with severe diseasedisease and nutritional risk factors and nutritional risk factors (A)(A) The route of nutrient delivery (parenteral/enteral) The route of nutrient delivery (parenteral/enteral) should be determined by the patient toleranceshould be determined by the patient tolerance EN should be attempted in all patients first (C)EN should be attempted in all patients first (C) Intakes should be monitored carefully to ensure Intakes should be monitored carefully to ensure adequate nutritional supportadequate nutritional support When enteral nutrition is not sufficient combine it with When enteral nutrition is not sufficient combine it with PNPN (C)(C)ESPEN, Guidelines 2006/2009ESPEN, Guidelines 2006/2009Treatment severe Treatment severe pancreatitispancreatitisAssessment of severity Assessment of severity of acute pancreatitisof acute pancreatitisseveresevereearly continuous enteral nutrition (naso-jejunal tube) elemental diet or polymeric diet or immune-enhancing diet?enteral nutrition enteral nutrition is not possibleis not possibleadd parenteral nutritionadd parenteral nutrition- all in one - all in one - or single component solutions- or single component solutions (CH, protein (AS), fat) (CH, protein (AS), fat) TPNTPN and and continuous small continuous small amount of an amount of an enteral diet enteral diet (10-30 ml/h) (10-30 ml/h) perfused to perfused to the jejunum the jejunumnutritional goal not reachednutritional goal not reached Recommendation IVPatients with severe disease, complications or thePatients with severe disease, complications or theneed for surgery require early nutritional support toneed for surgery require early nutritional support toprevent the adverse effects of nutrient deprivationprevent the adverse effects of nutrient deprivationC Continous early enteral jejunal feeding over ontinous early enteral jejunal feeding over 24h is recommended 24h is recommended (A)(A)When side effects occur or the caloric goal When side effects occur or the caloric goal can not be achieved, PN should be combined can not be achieved, PN should be combined with EN with EN (C)(C)How nutrients should be applied? 4 trials showed that jejunal tubes are well 4 trials showed that jejunal tubes are well toleratedtolerated there was no exacerbation of pancreatitis-related there was no exacerbation of pancreatitis-related symptomssymptomsMcClave, JPEN, 1997McClave, JPEN, 1997Cravo, Clin Nutr, 1989Cravo, Clin Nutr, 1989Kudsk, Nutr Clin Pract, 1990Kudsk, Nutr Clin Pract, 1990Nakad, Pancreas, 1998Nakad, Pancreas, 1998Nasogastric or nasojejunal feeding in patients with severe pancreatitis?Nasogastric vs nasojejunal feeding in patients with acute pancreatitisPetrow et al, JOP 2008Nutritional intolerancePain exazerbationNasogastric vs nasojejunal feeding in patients with acute pancreatitisPetrow et al, JOP 2008DiarrheaMortalityNasogastric vs nasojejunal feeding in patients with acute pancreatitisPetrow et al, JOP 2008; 9(4):440-448.Recommendation VJejunal tube placement is safe and well Jejunal tube placement is safe and well tolerated tolerated (C)(C)If nasogastric tube feeding is a useful and If nasogastric tube feeding is a useful and practical approach can not be answered practical approach can not be answered up to now!up to now!Which formula should be used? Elemental, semielemental, polymeric, or Elemental, semielemental, polymeric, or immunenhancing (Arg, RNA, n-3-FA, Glu)immunenhancing (Arg, RNA, n-3-FA, Glu) Enteral diet with pre- or probioticsEnteral diet with pre- or probiotics TPN and glutamine and or n-3-FA TPN and glutamine and or n-3-FAThere is no clear consensus about the There is no clear consensus about the preferred formula but most trials were preferred formula but most trials were performed withperformed with semielemental dietssemielemental dietsTiengou et al, JPEN, 2006 Semielemental vs polymeric diet in acute pancreatitisEN (immunmodulating) vs EN (standard) HospitalHospitalICUICUMortalityMortalityN NStayStayStayStayEN EN (Arg/Glu)(Arg/Glu)27.2 d* 27.2 d* 8.6 d*8.6 d* 22.2%22.2%vs vs 1)1)1616EN (STD)EN (STD)38.4 d38.4 d34.8 d 28.6%34.8 d 28.6%EN EN (n-3-FA)(n-3-FA)13.1 d *13.1 d * 7.1%7.1%vsvs 2)2)2828EN (STD)EN (STD)19.3 d19.3 d 14.2% 14.2%* p 0.05* p 0.051) Hallay et al, Hepatogastroenterol, 20012) Lasztity et al, Clin Nutr, 2005Algorythm for using enteral formulaSevere acute pancreatitisSevere acute pancreatitisGI-function GI-function NormalNormalGI-function GI-function ImpairedImpairedPolymeric dietPolymeric dietElemental- or semielemental dietElemental- or semielemental dietGI-function GI-function ImpairedImpairedElemental- or semielemental diatElemental- or semielemental diatGI-function GI-function NormalNormalPolymeric dietPolymeric dietSynbiotics* in severe pancreatitis - - Incidence of infected Incidence of infected necrosis and abscess 4.5 30.4% (p 0.02) necrosis and abscess 4.5 30.4% (p 0.02)- - LOHS LOHS 13.7 21.4 d (ns) 13.7 21.4 d (ns)- - Need for re-surgery 1 7 (p 0.02) Need for re-surgery 1 7 (p 0.02)Olah et al, Br J Surg 2002Enteral nutrition with 10g oat fibreEnteral nutrition with 10g oat fibre ( ( -glucan)-glucan) andand Lactobacillus plantarum 299, 10Lactobacillus plantarum 299, 109 9Rand, db, controlled trial (N = 45), 1 weekRand, db, controlled trial (N = 45), 1 week*Probio*ProbioProbiotics Control pProbiotics Control pSynbiotics* in severe pancreatitis Probiotics Control pProbiotics Control p MOF 15% 31% sig MOF 15% 31% sig Septic complicatios 27% 52% ns Septic complicatios 27% 52% ns LOHS (d) LOHS (d) 15 20 ns 15 20 ns Need for surgery 12% 24% ns Need for surgery 12% 24% ns Mortality 6% 21% ns Mortality 6% 21% nsOlah et al, Hepatogastroenterol 2007Enteral nutrition withEnteral nutrition with 10g 10g -glucan, inulin, pectin, resistant -glucan, inulin, pectin, resistant starchstarch andand Lb plantarum 299, pediacoccus, leuconostoc, Lb plantarum 299, pediacoccus, leuconostoc, paracasei, 10paracasei, 101010 Rand, db, controlled trial (N = 62), 1 weekRand, db, controlled trial (N = 62), 1 week* *Synbiotic 2000Synbiotic 2000Synbiotics* in severe acute pancreatitis Probiotics Placebo Probiotics Placebo N=152 N=144N=152 N=144 Infectious compl. 30% 28% Infectious compl. 30% 28% Bowel ischaemia (N) 9* 0Bowel ischaemia (N) 9* 0 Mortality 24 (16%)* 9 (6%) Mortality 24 (16%)* 9 (6%)Multifibre diet plus and cornstarch, maltodextrinMultifibre diet plus and cornstarch, maltodextrin Besselink et al, Lancet 2008 and 4 Lactobacilli, 2 Bifidobacteria 10and 4 Lactobacilli, 2 Bifidobacteria 101010, , twice dailytwice dailyRand, db, placebo-controled trial, N= 298, 4 weeksRand, db, placebo-controled trial, N= 298, 4 weeks*Ecolocgic 641*Ecolocgic 641(*/* sig)(*/* sig)Comparison of the 3 studies using probiotics in acute pancreatitis Olah 2002Olah 2002Olah 2007Olah 2007Besselink 2008Besselink 2008ProbioProbioControlControlSynbioticSynbioticControlControlEcologicEcologicControlControl(n = 22)(n = 22)(n = 23)(n = 23)(n = 33)(n = 33)(n = 29)(n = 29)(n = 152)(n = 152)(n = 144)(n = 144) BaselineBaselineAPACHE IIAPACHE II8.98.99.49.411.711.710.410.48.68.68.48.4Imrie ScoresImrie Scores2.52.52.82.82.92.93.13.13.33.33.43.4Mean CRP Mean CRP 206206188188216216191191268268270270% Alcohol% Alcohol59%59%70%70%60%60%62%62%18%18%19%19% Necrosis% Necrosis41%41%48%48%60%60%62%62%30%30%24%24%AgeAge44.144.146.546.547.547.546.046.060.460.459.959.9What went wrong?Aggressive enteral Nutrition (30kcal/Tag)Aggressive enteral Nutrition (30kcal/Tag)Patients with vasoactive treatmentPatients with vasoactive treatmentMultifibre diet plus prebiotics Multifibre diet plus prebiotics (30g fibre/day)(30g fibre/day)6 probiotic strains (2x/day 106 probiotic strains (2x/day 101010) )- For the first time Bifidobacteria)- For the first time Bifidobacteria)Fermentation distension ischaemiaFermentation distension ischaemia? ?PN (immunmodulating) vs PN (standard)GlutamineN- 3 fatty acidsMcClave et al, JPEN, 2006Acute pancreatitisGlutamine vs standard PNComplicationsRR 0.68RR 0.68p= 0.11p= 0.11Acute pancreatitisGlutamine vs standard PN3 further randomized controlled trials3 further randomized controlled trials Significant reduction of complications (N=40) Significant reduction of complications (N=40) Significant reduction of mortality Significant reduction of mortality Sahin et al, Eur J Cin Nutr 2007 Significant reduction of complications (N= 44Significant reduction of complications (N= 44) ) Fuentes-Orozco et al, JEPN 2008 Significant reduction in the length of Significant reduction in the length of organ failure N=76) organ failure N=76) Reduction of infection (early vs late) 8 vs 23% Reduction of infection (early vs late) 8 vs 23% Reduction of surgery (early vs late) 13 vs 43% Reduction of surgery (early vs late) 13 vs 43% Reduction of mortality (early vs late) 5 vs 21% Reduction of mortality (early vs late) 5 vs 21% Xue et al, W J Gastroenterol 2008 N-3-FA in TPN in patients with severe acute pancreatitisN=40N=40ControlControlN-3-FA N-3-FA SIRS ratioSIRS ratio9/209/204/204/20ARDS ratioARDS ratio5/205/204/204/20Infectious complication, nInfectious complication, n5/205/203/203/20Renal dysfunction, nRenal dysfunction, n2/202/201/201/20CRRT, daysCRRT, days263.4 263.4 182.3182.3ICU, daysICU, days27.55.627.55.621.44.221.44.2Length of hospital stay, daysLength of hospital stay, days70.59.170.59.165.27.365.27.3Wang et al, JPEN 2008Prospective, randomized, double-blind study, PN over 5 daysProspective, randomized, double-blind study, PN over 5 daysN-3-FA in TPN in patients with severe acute pancreatitisPatients supplemented with fish oilPatients supplemented with fish oilhad significantly lower CRP levels had significantly lower CRP levels after 5 days of parenteral nutritionafter 5 days of parenteral nutritionWang et al, JPEN 2008N-3-FA in TPN in patients with severe acute pancreatitisN=60N=60ControlControlN-3-FA N-3-FA Apache II, 7th dayApache II, 7th day132.3132.381.9*81.9*Fluid equilibrium, daysFluid equilibrium, days8.42.38.42.35.12.25.12.2SIRS score, 7th daySIRS score, 7th day2.50.72.50.71.70.5*1.70.5*Xiong et al, JPEN 2008Prospective, randomized, double-blind studyProspective, randomized, double-blind study*P 0.05During the initial stage of acute pancreatitis n-3 FA efficiently reduceDuring the initial stage of acute pancreatitis n-3 FA efficiently reducethe magnitude and persistence time of SIRS and retrieve the the magnitude and persistence time of SIRS and retrieve the unbalance of the pro/anti-inflammatory cytokinesunbalance of the pro/anti-inflammatory cytokinesRecommendation VIElemental and semielemental formulas can Elemental and semielemental formulas can be used safely in acute pancreatitis be used safely in acute pancreatitis (A)(A)Standard polymeric formulas can be tried if Standard polymeric formulas can be tried if they are tolerated they are tolerated (C)(C)There is no evidence for using There is no evidence for using immunomodulating formulas or probioticsimmunomodulating formulas or probioticsIf TPN has to be used, glutamineIf TPN has to be used, glutaminecould have a beneficial effect could have a beneficial effect (B), (B), for n-3 FA for n-3 FA we need further trialswe need further trialsConclusion Nutritional support is essential in Nutritional support is essential in severe severe acute pancreatitisacute pancreatitisStarting with early enteral nutrition is Starting with early enteral nutrition is recommendedrecommendedThe combination of EN and PE make The combination of EN and PE make sense if enteral nutrition is inadaequatesense if enteral nutrition is inadaequateProbiotics can not be recommended yetProbiotics can not be recommended yetMore studies in this field are necessaryMore studies in this field are necessaryIn PE glutamine ca be helpfulIn PE glutamine ca be helpful