Nutrition in Clinical Care

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1 Nutrition in Clinical Care July 2007: The Importance of Nutrition Status Assessment: The Case of Severe Acute Pancreatitis Andrea Kopp Lugli, MD, MSc, Franco Carli, MD, MPhil, and Linda Wykes, PhD Severe acute pancreatitis is associated with high mortality. Adequate nutrition support improves clinical outcome. Nevertheless, several recent trials have focused primarily on the route of nutrition support and neglected the role of nutrition status assessment in tailoring nutrition support to individual needs. Key words: acute pancreatitis, biochemical indicator, body mass index, nutrition support, nutrition status assessment 2007 International Life Sciences Institute doi: /nr.2007.jul INTRODUCTION Acute pancreatitis is a potentially life-threatening condition and a common gastroenterological disease. The incidence is increasing and ranges between 5 and 80 cases per 100,000 people per year. 1 The highest rates are observed in the United States and Finland. 1 Although a considerable geographic variation exists, 80% of acute pancreatitis cases are caused either by a biliary disease or by alcohol consumption. 1 From a pathophysiological point of view, acute pancreatitis is a complex disease with several important issues affecting the clinical outcome and the rate of complications. The clinical symptoms of acute pancreatitis, which include belt-like abdominal pain, nausea, and vomiting, force patients to avoid food intake for days at a time. Therefore, acute pancreatitis patients often Drs. Kopp Lugli and Carli are with the Department of Anaesthesia, McGill University Health Centre, Montreal, Canada; Drs. Kopp Lugli and Wykes are with the School of Dietetics and Human Nutrition, McGill University; Dr. Kopp Lugli is also with the Department of Anesthesia and Perioperative Intensive Care Medicine, Kantonsspital, Aarau, Switzerland. Please address all correspondence to: Dr. Andrea Kopp Lugli, Department of Anaesthesia, McGill University Health Centre, 1650 Avenue Cedar, D10-144, Montreal, Quebec, H3G 1A4, Canada; Phone: , ext ; Fax: ; andrea.kopplugli@mail.mcgill.ca. present in a state of malnutrition upon admission to the hospital. Additionally, the ongoing acute inflammatory response causes increased protein breakdown, thirdspace fluid loss, and higher oxygen extraction from the blood, thus altering the supply to vital organs. Finally, decreased gut integrity or infected pancreatic necrosis due to enzymes leaking from the organ itself may lead to sepsis. 2 The mild form represents 75% to 85% of acute pancreatitis cases and corresponds to a low mortality rate (1%). 1 These patients usually recover within 5 to 7 days without nutrition support. 3 Despite the existence of numerous scoring systems (Ranson score, Imrie/Glasgow criteria, APACHE score, or the most recent Atlanta criteria), it remains difficult to predict the course and outcome of acute pancreatitis. Therefore, the main challenge is to identify within the first 48 hours those patients who will go on to develop the severe form of acute pancreatitis, which is typically characterized by multiple organ system failure, as well as necrosis, abscesses, or pseudocysts in the pancreas. These patients benefit from an early aggressive intensive care treatment, which includes fluid resuscitation, rehydration, accurate pain relief, and in some cases, antibiotics or even an interventional approach such as endoscopic retrograde cholangiopancreatography (ERCP) or surgery. 1,4,5 The importance of nutrition support in severe acute pancreatitis has been emphasized in several treatment guidelines. 2,4 CONTROVERSY ABOUT THE OPTIMAL ROUTE OF NUTRITION The management of nutrition support has changed considerably over the last three decades. The traditional strategy of fasting was based on avoiding pancreatic stimulation with an increased production of digestive enzymes because this negatively affects the course of the disease. 6 Parenteral nutrition was adapted as a standard prescription after studies reported a reduction in mortality and complication rate. 6 Additionally, parenteral nutrition meets the targeted energy levels and therefore maintains the lean body mass of the patient. Because Nutrition Reviews, Vol. 65, No

2 catheter-related sepsis, gut atrophy with consequent bacterial translocation, and hyperglycemia are well known parenteral nutrition-related complications, several recent studies have introduced enteral nutrition as an alternative. 6 Enteral nutrition positively influences immune modulation, gut integrity, and the incidence of sepsis. It is as effective as parenteral nutrition with regard to disease resolution and mortality rate but is less expensive. 3 Although an adynamic ileus seems to be less frequent than anticipated, the use of enteral nutrition is still disputed because of possible pancreatic stimulation, the invasive placement of the feeding tube, and diarrhea. 3,6 Recent randomized clinical trials investigated the controversial topic of the optimal route of nutrition support. One of these studies assessed 28 patients with severe acute pancreatitis (Ranson s score 3) and inability to tolerate oral fluids within 96 hours of admission to the hospital. 3,6 Patients were randomly assigned to receive either parenteral nutrition (n 18) or enteral nutrition (n 10), both getting a daily nutrition support of 105 kj/kg (25 kcal/kg) and 1.5 g/kg of protein, based on their ideal body weight. Three variables (serum albumin, prealbumin, and urinary nitrogen balance) were measured to determine the adequacy of the nutrition support. The study population included patients with broad demographic indicators such as being elderly or obese, as well as several alcohol-induced cases. As the measurements of nutritional effectiveness were comparable in both groups, the authors concluded that enteral nutrition is a safe and cheaper support that offers adequate nutrition in severe acute pancreatitis and shows a trend toward faster attenuation of inflammation. No major complications related to nutritional modality were reported. 6 APPROACH TO MANAGING NUTRITION SUPPORT IN ACUTE PANCREATITIS Considering the pathophysiological complexity of acute pancreatitis, the study design of many of these recent trials 1-5,7 lacks adequate measurements of the nutritional effectiveness of the treatments studied. Many of the standardized tools to assess the nutrition status of a patient are influenced by the ongoing disease and can lead to confusing and erroneous results. Additionally, adaptation of nutrition support to the specific requirements of acute pancreatitis as well as to particular risk groups should be performed when planning nutrition support in daily clinical routine. The advantage of such an individualized approach contributes to a more accurate prescription for nutrition support. In 30% of acute pancreatitis patients, a preexisting state of malnutrition has to be expected at the time of the initial attack. 2 This proportion may be reflected by subpopulations such as alcoholics or the elderly. On the other hand, obesity itself is an adverse prognostic factor in acute pancreatitis. 4 According to published guidelines, nutrition support in mild pancreatitis has shown no beneficial effect, whereas it is essential in patients with severe disease and may have to be reconsidered for patients with complications if refeeding is delayed. 2 The principal aim in the management of nutrition support in acute pancreatitis should thus be: 1) to assess the patient s nutrition status, 2) to adapt nutrition support according to the severity of the disease, and 3) to identify risk groups with special nutritional needs. NUTRITION STATUS ASSESSMENT IN ACUTE PANCREATITIS When performing a nutrition status assessment it is mandatory to establish the standard concepts for the evaluation in context of an ongoing disease. Many commonly used tools have to be abandoned or reevaluated in terms of their accuracy and relevance to the specific disease. The following considerations examine the potential drawbacks of several established nutrition assessment techniques in acute pancreatitis patients. Anthropometric Measurements Anthropometric measurements are difficult to obtain. First, it may be impossible to weigh the patient due to his or her condition. Second, this measurement cannot be regarded as accurate since the weight is severely affected by the third-space fluid loss associated with acute pancreatitis. The same concern has to be stated regarding the measurement of triceps skin-fold and arm circumference. Furthermore, elderly patients show a reduced turgor of the skin that may also alter the evaluation. In a recent study, we have shown a statistically significant correlation between the thickness of the abdominal fat tissue and the body mass index (BMI) in men. 8 As an abdominal CT scan is recommended by many guidelines to diagnose acute pancreatitis, 1,4 the thickness of the abdominal fat tissue can be easily obtained. This may be an opportunity to estimate a patient s BMI when an accurate weight is not determinable. Dietary Measurement This is an important approach to identify high-risk patients such as elderly or alcoholic individuals, but it may not be feasible to obtain in severely ill and intubated patients. In this case, family members might provide 330 Nutrition Reviews, Vol. 65, No. 7

3 important information about the patient s typical nutrient intake and course of weight. Additionally, medical files should be screened. Physical Examination The major physical signs of specific nutrient deficiencies are well established, although their sensitivity and specificity vary considerably. According to the most common deficiencies seen in elderly patients, physical examination may reveal signs of lack of protein, iron, zinc, selenium, and vitamins B 12, B 1, B 6, and D. In alcoholic patients, physical signs may indicate affected stores of the vitamins C, thiamine, riboflavin, and pyridoxine, as well as folic acid or even clinical signs of hepatic cirrhosis. Laboratory Measurements The presence of an inflammatory response perturbs many laboratory parameters used in evaluating nutrition status. Changes in levels of acute-phase proteins are associated with both increased and decreased plasma levels of protein status and micronutrients. Acute-phase proteins are subject to change due to hemodilution as well as sequestration and alterations in rates of synthesis and breakdown. 9 Protein Status Plasma protein levels are not a good indicator for nutrition status during inflammation, due to many factors such as the acute-phase response, concomitant diseases, and the long half-life of certain proteins (albumin and transferrin). The relevant factors influencing protein serum levels are summarized in Table 1. Changes in the Albumin d Hydration status; liver disease; acute-phase response; sepsis; edema; dietary protein; zinc status Retinolbinding protein 12 h Liver diseases; vitamin A and zinc status; dietary protein Transferrin 8 9 d End-state hepatic disease; high-dose antibiotic therapy; iron status: dietary protein Transthyretin (pre-albumin) 2 d Stress; active chronic inflammatory disease; acute-phase response; dietary protein profile of plasma proteins are related to acute inflammation and include increases in positive acute-phase proteins such as C-reactive protein and fibrinogen. Alternatively, decreases in some negative acute-phase proteins such as albumin may not be connected to decreased synthesis related to malnutrition, but to increased extravascular loss due to the increased capillary permeability during inflammation. In this case, some serum proteins may be indicators of morbidity and mark patients who are most at risk of developing malnutrition. 10 Urinary nitrogen balance reflects the net status of protein metabolism, but does not yield any data on the size of muscle mass or on protein nutrition status. The most useful indication for these is to monitor changes during nutritional therapy. 10 Micronutrient Status Evidence exists for the impact of inflammation on biomarkers of micronutrient status. Although many effects of inflammatory response upon micronutrients have been documented, there remains a need to further elucidate the exact alterations in micronutrient levels during inflammation. There are four main categories that affect micronutrient biomarkers: 1) the inflammatory response, 2) pancreas-specific alterations, 3) influences due to other, concomitant diseases, and 4) primary micronutrient deficiency. Table 2 provides information about relevant influencing factors on micronutrient status in acute pancreatitis patients. Vitamin A. The levels of plasma retinol and retinol binding protein (RBP) are decreased during inflammation. Despite different approaches to relate levels of acute-phase proteins to the impact of inflammation on plasma retinol and RBP, there is no evidence for a direct interaction. Additionally, the production of RBP can be affected by liver diseases, which must be considered in alcoholic patients. 9 Iron. Ferritin and serum iron levels are considerably influenced by the inflammatory response. Ferritin as a positive acute-phase protein can be elevated over 20 g/l even in the presence of an iron deficiency. Recently, the use of the transferrin receptor assay has been proposed because inflammation has less of an effect on it than on ferritin. 9 Plasma ferritin levels are also increased by alcohol consumption and obesity. 10 Zinc. Plasma zinc is reduced during inflammation, and considerable urinary losses of zinc are seen in pronounced metabolic stress situations that cause a breakdown of muscle mass. During acute pancreatitis, plasma alkaline phosphatase can be elevated due to gallstoneinduced cholestasis. Therefore, the accuracy of plasma Nutrition Reviews, Vol. 65, No

4 Vitamin A Plasma retinol Decrease Retinol-binding protein Decrease Liver disease: RBP decrease Iron Serum iron Decrease TfR: less affected by inflammation Plasma ferritin Increase (APP) Alcohol consumption, obesity: increase Zinc Plasma zinc Decrease Alkaline phosphatase Pancreatitis: increase Folate Serum folate Decrease Red cell folate: less affected by inflammation Selenium Serum, whole blood selenium Decrease Copper Ceruloplasmin Increase (APP) but no comparison to levels of APP Thiamin Erythrocyte transketolase No comparison to levels of APP Riboflavin Erythrocyte glutathione reductase activation coefficient No comparison to levels of APP Niacin Nicotinamide adenine dinucleotide No link described to inflammation Vitamin C Ascorbic acid in plasma Affected, but no comparison to levels of APP Vitamin D Plasma 25-cholecalciferol No information on the effect Pancreatitis: hypocalcemia of inflammation Vitamin E Tocopherol Decrease, but no comparison to levels of APP APP, acute-phase proteins; RBP, retinol-binding proteins; TfR, transferrin receptors. alkaline phosphatase as an indirect approach to the measurement of zinc may be influenced. 9 Folate. The accuracy of the assessment of folate is improved by measuring red cell folate instead of serum folate levels, which are more affected by inflammation. 9 For many markers, such as thiamine, riboflavin, or niacin, no studies have been performed to elucidate a possible link between the micronutrient biochemical determination and the acute-phase proteins. 9 Resting Energy Expenditure The increased energy requirement of acute pancreatitis patients arising from their hypermetabolic and catabolic state emphasizes the need for an accurate measurement of resting energy expenditure. Unfortunately, indirect calorimetry, which is often used in research settings and increasingly recommended by guidelines, is not always available or feasible in clinical practice. 2 SPECIAL REQUIREMENTS OF NUTRITION SUPPORT IN ACUTE PANCREATITIS The inflammatory process is not limited to the pancreas itself during acute pancreatitis. The destruction of pancreatic tissue provokes profound systemic and metabolic derangements due to the release of hydrolytic enzymes, toxins, and cytokines. The latter affect several organ systems and generate a state of hypermetabolism and catabolism. 3 The resting energy expenditure measured by indirect calorimetry might increase up to 77% to 39% of the predicted value based on the Harris-Benedict equation. 2 An increased proteolysis of skeletal muscle (up to 80%) triggers nitrogen losses of up to 20 to 40 g/d. 2 Additionally, protein-energy malnutrition may be aggravated by a prolonged period of inadequate oral intake. Gluconeogenesis increases, while glucose clearance and oxidation decrease, generating glucose intolerance in 40% to 90% of patients and even requiring insulin treatment in 81%. 3 In 12% to 15% of patients, diminished lipid clearance has been detected. 3 Hypocalcemia also correlates with disease severity and occurs in 40% to 60% of acute pancreatitis patients. 3 According to the ESPEN guidelines, an optimal protein intake for most patients is 1.2 to 1.5 g/kg/d. Protein loads should be lowered to 1.2 g/kg/d in cases of renal or hepatic failure. For patients with a severe negative nitrogen balance, high-protein diets ( 1.5 g/kg/d) might ensure a positive protein balance Nutrition Reviews, Vol. 65, No. 7

5 Figure 1. Decision algorithm for nutrition status assessment in acute pancreatitis. SPECIAL RISK GROUPS WITHIN THE POPULATION OF ACUTE PANCREATITIS PATIENTS There are three groups of acute pancreatitis patients who deserve a special approach when planning a nutrition support strategy: elderly patients, alcoholic patients, and obese patients. Elderly Patients The aging process influences and modifies the clinical picture and treatment modalities of acute pancreatitis. The presence of concomitant diseases affecting renal, hepatic, and cardiopulmonary function make the early clinical assessment of the severity of acute pancreatitis inaccurate at the time of admission to the hospital. 11 In addition, 4% to 31% of elderly people living autonomously at home and up to 60% of geriatric patients in nursing homes are known to be malnourished upon admission. 12 The most common deficiencies reported are for protein, iron, zinc, selenium, and vitamins B 12,B 1, B 6, and D. 12 Furthermore, aging is associated with weaker cell-mediated and humoral immune responses, and this can be aggravated by protein-energy malnutrition and micronutrient deficiencies. 13 The association between nutrition status, age-related changes in the inflammatory response capacity, and clinical outcome of acute pancreatitis underlines the need for an accurate nutrition status assessment. Alcoholic Patients This group is heterogeneous in terms of nutrition status. Nutritional concerns differ with age, sex, and lifestyle (obesity and a broad spectrum of nutritional deficiencies). Chronic alcohol intake frequently leads to nutritional deficiency due to decreased intake, reduced absorption, and impaired utilization of nutrients. In addition, the nutritional requirements are increased by greater metabolic demands and constant tissue repair. Biochemical data show deficiency of several micronutrients including thiamine, riboflavin, pyridoxine, vitamin C, folic acid, and vitamin A in patients with liver cirrhosis. 14 Chronic alcoholic-related brain damage may be a direct result of nutrient depletion, particularly of the vitamins thiamine, B 12, nicotinamide, and pyridoxine. Obese Patients Epidemiological studies indicate a positive correlation between the incidence of acute pancreatitis and obesity. 4,15 Furthermore, there is evidence that increased fat deposits in the peripancreatic and retroperitoneal spaces in obese patients may elevate the risk of peripancreatic fat necrosis, abscess, and death. CONCLUSIONS Nutrition status assessment is an important component of the clinical management of acute pancreatitis Nutrition Reviews, Vol. 65, No

6 patients. Although the application of standard tools of nutritional evaluation are influenced by several factors due to acute pancreatitis, a three-part scheme for nutrition status assessment can be proposed: 1) dietary assessment, 2) physical examination, and 3) screening of the medical history. These tools have to consider the severity of acute pancreatitis and to pay attention to special risk groups. Additionally, an abdominal CT scan may help to estimate the patient s BMI as other anthropometric measurements are impaired by acute pancreatitis. The assessment of many biochemical markers is not indicated during an acute inflammatory response; however, some indicators offer opportunities for improved accuracy. A decision algorithm for nutrition status assessment in acute pancreatitis is proposed in Figure 1. This modified technique of nutrition status assessment contributes to a more adequate, individualized prescription of nutrition support that adapts to the severity of the disease and to special subpopulations while recognizing the impact of inflammatory response. Furthermore, the nutrition status assessment may complete a management approach based on guidelines that concentrate primarily on the composition of the supply, on the route of nutrient delivery, the avoidance of feedingrelated complications, and finally on the attenuation of the systemic inflammatory response. ACKNOWLEDGEMENTS Andrea Kopp Lugli was supported by a grant from the Swiss National Science Foundation, by a study grant from the Kantonsspital Aarau, and by Fresenius Switzerland. REFERENCES 1. Mayerle J, Hlouschek V, Lerch MM. Current management of acute pancreatitis. Nat Clin Pract Gastroenterol Hepatol. 2005;2: Meier R, Beglinger C, Layer P, et al. ESPEN guidelines on nutrition in acute pancreatitis. European Society of Parenteral and Enteral Nutrition. Clin Nutr. 2002;21: Abou-Assi S, O Keefe SJ. Nutrition support during acute pancreatitis. Nutrition. 2002;18: Gurusamy KS, Farouk M, Tweedie JH. UK guidelines for the management of acute pancreatitis: Is it time to change? Gut. 2005;54(9): Yousaf M, McCallion K, Diamond T. Management of severe acute pancreatitis. Br J Surg. 2003;90: Louie BE, Noseworthy T, Hailey D, Gramlich LM, Jacobs P, Warnock GL MacLean-Mueller prize enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment. Can J Surg. 2005; 48: Tenner S. Initial management of acute pancreatitis: critical issues during the first 72 hours. Am J Gastroenterol. 2004;99: Lugli A, Lugli AK, Horcic M. Napoleon s autopsy: new perspectives. Hum Pathol. 2005;36: Tomkins A. Assessing micronutrient status in the presence of inflammation. J Nutr. 2003;133:1649S 1655S. 10. Gibson RS. Principles of Nutritional Assessment. Oxford University Press; Uomo G. Inflammatory pancreatic diseases in older patients: recognition and management. Drugs Aging. 2003;20: Seiler WO. Clinical pictures of malnutrition in ill elderly subjects. Nutrition. 2001;17: Lesourd BM. Nutrition and immunity in the elderly: modification of immune responses with nutritional treatments. Am J Clin Nutr. 1997;66:478S 484S. 14. Lieber CS. Relationships between nutrition, alcohol use, and liver disease. Alcohol Res Health. 2003;27: Pitchumoni CS, Patel NM, Shah P. Factors influencing mortality in acute pancreatitis: can we alter them? J Clin Gastroenterol. 2005;39: Nutrition Reviews, Vol. 65, No. 7

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