Clinical Nutrition (2002) 21(2): 173–183 r 2002 Elsevier Science Ltd. All rights reserved. doi:10.1054/clnu.2002.0543, available online at http://www.idealibrary.com on CONSENSUS STATEMENT ESPEN guidelines on nutrition in acute pancreatitis R. MEIER,* C. BEGLINGER,w P. L AYER, z L. GULLO,} V. KEIM, z R. LAUGIER,8 H. FRIESSww,M.SCHWEITZER,zz J. MACFIE }} ESPEN CONSENSUS GROUP1 *University Hospital, Liestal, Switzerland, wUniversity Hospital, Basel, Switzerland, zIsraelitisches Krankenhaus, Akademisches Lehrkrankenhaus der UniversitÌt Hamburg, Hamburg, Germany, }Ospedale S. Orsola, Bologna, Italy, zUniversitÌt Leipzig, Leipzig, Germany, 8Ho“ pital d’Adultes de laT|mone, Marseille, France, wwRuprecht-Karls-UniversitÌt, Heidelberg, Germany, zzKlinikum Stadt Hanau, Hanau, Germany, }}Scarborough Hospital, Scarborough, UK, (Correspondence to: RM, GIUnit, University Hospital, Kantonsspital Liestal, CH-4410Liestal, Switzerland) Introduction physiology, to develop common terminology, to obtain consensus criteria to be adopted in clinical trials, and The two major forms of inflammatory pancreatic finally to stimulate cooperative European research. diseases – acute and chronic pancreatitis – are different entities which require different nutritional approaches. Despite increasing knowledge in the fields of metabo- Physiology and pathophysiology of pancreatic secretion lism, clinical nutrition, and intervention, there is still a and consequences for nutrient digestion lot of controversy with respect to the optimal approach Digestion of food and absorption of nutrients are a concerning treatment regimens. It is generally accepted complex and finely coordinated process which require that nutritional management depends on the underlying multiple and integrated gastrointestinal secretory pancreatic disease. For many years, textbooks have absorptive motor and circulatory systems (2, 3). The suggested that oral or enteral feeding may be harmful pancreas plays a central and crucial role: its intact in acute pancreatitis; feeding was thought to stimulate function is one of the prerequisites for adequate the exocrine pancreatic secretion and consequently processing and mucosal uptake of nutrient components. autodigestive processes. On the other hand, it is known that nutritional deficiencies can occur in patients with a prolonged and complicated course of Physiology of pancreatic secretion and luminal nutrient an acute necrotizing pancreatitis. Furthermore B30% digestion of patients with acute pancreatitis are already malnour- The normal human pancreas secretes more than 10 ished at the time of the initial attack (1). It has also different enzymes together with water, bicarbonate, and been questioned whether early feeding changes the other proteins (such as secretory enzyme inhibitors). outcome in uncomplicated acute pancreatitis. Thus These enzymes are secreted in abundance and hydrolyze far, there is no generally accepted or standardized within the intestinal lumen macronutrients of which approach for handling nutrition in patients with acute lipids, protein, and carbohydrates are of particular pancreatitis. importance. For an undisturbed digestion, not only the With this background, ESPEN invited a group of quantity of the secretory response is necessary, but even gastroenterologists, pancreatologists, intensive care spe- the timed, controlled, and coordinated release of these cialists, and nutritionists to prepare guidelines and a enzymes into the duodenal lumen in response to a meal consensus report on nutritional strategies in patients is required. Postprandially, regulation of human pan- with acute pancreatitis. The aim of this consensus was to creatic secretion must be seen as part of an overall share current knowledge from physiology and patho- integrated motor and secretory response (4). Whilst a meal is the most important physiologic stimulus, 1ESPEN Consensus Group pancreatic secretion also occurs in the fasting (inter- P. E. Ballmer, Kantonsspital, Winterthur, Switzerland C. Bassi, Dipartimenti di Scienze Chirurgiche, Servizio di Chirurgia digestive) state in a precisely regulated and coordinated Endocrina e Pancreatica, Verona, Italy fashion (5). Gassull A. Miquel, Hospital Universitari Germans Trias i Pujol, Badalona, Spain L. Harsa´ nyi, Semmelweis University, Budapest, Hungary Pancreatic response and luminal nutrient digestion M. Hiesmayr, AKH Universita¨ tskliniken, Vienna, Austria C.W. Imrie, Royal Infirmary, Glasgow, Scotland following meal ingestion J.P. Neoptolemos, Royal Liverpool University Hospital, Liverpool, UK Human pancreatic enzyme output reaches maximal M. Plauth, Sta¨ dtisches Klinikum, Dessau, Germany rates following a mixed meal of 20 kcal/kg body weight, 173 174 ESPEN GUIDELINES but the duration of the response increases with greater Regulation of postprandial pancreatic response caloric loads (6). The pancreatic response is also While a vagally mediated cephalic phase contributes up influenced by the physical properties of the meal: mixed to 40% of the overall pancreatic response, the most solid–liquid meals induce a longer response than important mechanism is the presence of nutrients within homogenized or liquid meals with a similar energy the duodenal lumen (intestinal phase). Maximal enzyme content (7–9). In both instances, the rate of gastric outputs are observed both with and without experi- retention and thus duodenal delivery of stimulatory mental diversion of postprandial chyme at the ligament nutrients are the key factors which determine the of Treitz (19). On the other hand, intrajejunal nutrients duration of pancreatic secretion underscoring the also elicit a marked stimulation of human pancreatic regulatory importance of the interaction of gastrointest- secretion. This normally redundant mechanism may inal motor and pancreatic function. Proportions of fat, become important in patients with gastrojejunostomies, carbohydrate, and protein contents within a meal also those with resected or bypassed antroduodenal segments influence the duration and enzyme composition of the (e.g. Billroth II, Roux-en-Y) and those with jejunos- pancreatic response in humans (10). The overall tomies (4). quantity of enzyme secreted exceeds by far the minimal Mediation of postprandial stimulation of human amount required to avoid manifest nutrient malabsorp- pancreatic secretion by duodenal nutrients involves the tion (4, 11). activation of neural pathways, in particular, vagal- Digestion of nutrients commences prior to the cholinergic reflexes, and release of regulatory peptides, exposure of chyme to pancreatico-biliary secretions, in particular, cholecystokinin (CCK), with a tight although it is not precisely clear and is partly interaction of neural and humoral systems. The current controversial to what extent salivary amylase, pepsin, concept assumes that CCK may act both as a and gastric lipase contribute to the degradation of stimulatory neuromodulator of the cholinergic pathway, carbohydrate, protein, and fat (2, 3, 12–14). It is con- and as a hormone (4, 20–22). The regulation of human ceivable and supported by experimental evidence that postprandial pancreatic exocrine secretion also involves pepsin and gastric lipase are more important for inhibitory mechanisms that eventually terminate the digestion during pathological conditions such as acute response. These are induced by nutrient exposure both or chronic pancreatitis. Yet, in humans, the finely tuned in the proximal and the distal (via physiologic gastric emptying of portions of preprocessed, liquid malabsorption) small intestine (7, 23, 24). Candidate chyme into the duodenum starts the pivotal period of mediators include somatostatin, pancreatic polypeptide intraluminal digestion. Under physiologic conditions, (PP), peptide YY (PYY), and glucagon-like peptide-1 the duodenal entry of nutrients is accompanied by (24–26). bursts of pancreatico-biliary digestive secretions with which nutrients are instantly mixed and exposed to a large mucosal area, and digestion; subsequent absorp- Coordination of motility with intestinal transit of chyme tion occurs rapidly. As a result, up to 70–80% of the cumulative prandial nutrient load may have been In parallel with the induction of the postprandial absorbed from the lumen as proximal as at the pancreatic response to nutrient ingestion, gastrointest- duodeno–jejunal junction (7, 12, 15–17). inal motility is converted from a basal interdigestive It is important to note that the generation of products state into postprandial activity (fed pattern). Evidently, that occurs as a result of the intraduodenal digestive motor activity determines the rates of gastric emptying process is the key event for the regulation and and small intestinal transit of chyme; conversely, loads integration of the postprandial gastrointestinal re- and sites of mucosal exposure to nutrients determine sponse. It activates multiple postprandial neuro-humor- both motor and secretory responses. Thus, the coupling al mechanisms controlling motor (e.g. feedback control of motor with secretory events is an important of gastric emptying rate) and secretory (e.g. pancreatic postprandial function which serves to maintain intra- and bile output) as well as metabolic (e.g. release of luminal homeostasis. This process ensures maximal insulin and other hormones) responses. Indeed, de- nutrient assimilation within the proximal small intestine, creased intraduodenal nutrient digestion is associated and economizes the effects of digestive secretions. This with disturbed postprandial