Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Severe acute pancreatitis

Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: Pancreatitis aguda grave

L. Bordejé Laguna^a, C. Lorencio Cárdenas^b and J. Acosta Escribano^c

^aHospital Universitario Germans Trias i Pujol. Badalona. Spain.
^bHospital Universitario Dr. Josep Trueta. Girona. Spain.
^cHospital General Universitario. Alicante. Spain.

ABSTRACT

Severe acute pancreatitis (SAP) causes local and systemic complications leading to high catabolic, hypermetabolic and hyperdynamic stress states with marked morbidity and mortality.
In the last decade, nutritional support has become a key element in the treatment of SAP. Thus, specialized nutrition is indicated from admission, with enteral nutrition being preferred to parenteral nutrition. Enteral nutrition should be initiated early using infusion through the jejunum beyond the ligament of Treitz to minimize pancreatic stress.
There are no specific studies that establish the type of diet to be used but experts recommend the use of polymeric diets.
Parenteral nutrition, without a specific formula, is indicated in patients with SAP who are intolerant to enteral nutrition or when the clinical signs of pancreatitis are exacerbated or aggravated by enteral nutrition. Even so, a minimal level of enteral infusion should be maintained to preserve the trophic effect of the intestinal mucosa.
In the last few years, several studies of the administration of immunomodulatory diets in patients with SAP have been carried out to demonstrate their effects on the course of the disease. However, there are few clear recommendations on the prognostic benefits of pharmaconutrient enriched diets in these patients. There is substantial scientific evidence suggesting that the only clear indication for pharmaconutrition in patients with SAP is parenteral glutamine administration, which is recommended by all clinical guidelines with distinct grades of evidence.

Key words: Pancreatitis. Lipids. Enteral nutrition.

La pancreatitis aguda grave es una patología que cursa con complicaciones locales y sistémicas que condicionan una situación de estrés altamente catabólica, hipermetabólica e hiperdinámica con marcada morbimortalidad.
En la última década, el soporte nutricional se ha convertido en uno de los puntos clave en el tratamiento de la pancreatitis aguda grave. Así, hay indicación de nutrición especializada desde el ingreso, siendo de elección la nutrición enteral sobre la nutrición parenteral administrada de forma precoz más allá del ligamento de treitz, para provocar el mínimo estímulo pancreático. No hay estudios específicos que nos aclaren cuál es el tipo de dieta a administrar, pero los expertos recomiendan la utilización de dietas poliméricas.
La nutrición parenteral, sin una fórmula concreta, quedaría indicada en los pacientes con pancreatitis aguda grave que presentan intolerancia a la nutrición enteral o cuando se agravan los signos clínicos de pancreatitis al administrar la dieta enteral. Aun así, se recomienda mantener una mínima perfusión de nutrición enteral para preservar el efecto trófico de la mucosa intestinal. En los últimos años se han realizado numerosos trabajos referentes a la administración de dietas inmunomoduladoras en pacientes con pancreatitis aguda grave, con la finalidad de objetivar cambios en su evolución. Sin embargo, hay pocas recomendaciones claras en cuanto a los beneficios pronósticos de la administración de dietas enriquecidas en farmaconutrientes, específicamente en pacientes con pancreatitis aguda grave. Sustentada por una evidencia científica relevante, el aporte de glutamina por vía parenteral en pacientes con pancreatitis aguda grave parece ser la única indicación clara de farmaconutrición en pancreatitis aguda grave recomendando su uso todas las guías de referencia para la práctica clínica con diferentes grados de evidencia.

Palabras clave: Pancreatitis. Lípidos. Nutrición enteral.

Introduction

Acute pancreatitis (AP) is one of the most common diseases of the pancreas, with an incidence of 5- 80/1,000 inhabitants/year. Patients admitted to the ICU show the severe forms, which account for 15-20% and are associated both with local complications (pancreatic necrosis, infection of necrosis, pancreatic abscess or pseudocyst) and systemic complications (multiple organ failure), with a high morbidity-mortality (over 50% in some series).

It is essential to establish the diagnosis and to stratify severity in the first 48 h, to establish its prognosis and start treatment early, where nutritional support (NS) is essential. In the consensus conference of the Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC), following the steps of the Conference of Atlanta, Severe Acute Pancreatitis (SAP) is defined by the presence of a number of signs and symptoms, including severity scales based on biological or tomographic signs. However, this classification does not include the presence or absence of organ failure, associated with general or local complications, that will be critical in the evolution of patients with SAP^1,2.

SAP causes a systemic inflammatory response leading to a highly catabolic, hypermetabolic and hyperdynamic stress condition^3,4. The previous nutritional status of the patient will be critical in the evolution; therefore, chronic alcohol intake and obesity are severity-independent factors.

A recent study of several intestinal function markers concluded that dysfunction of the intestinal barrier is an early fact during SAP, that is related to infection of pancreatic necrosis, occurrence of multiple organ failure and severity of pancreatitis with mortality increase⁹.

Therefore, the concept of classical NS, limited to reversing the catabolic state, is changing. The emerging data suggest that the route, time, amount and composition of artificial nutrition are aimed at reducing pancreatic secretion, treating and/or preventing associated malnutrition in a severe metabolic-catabolic stress state, modulating inflammatory response and preventing the development of local and systemic infections^10-14. Nutritional support can be a very important intervention in the management of patients with SAP.

What are the indications of nutritional support in patients with severe acute pancreatitis?

In SAP there is an indication of specialized nutrition since admission, as these patient will not restart intake in the next 5-7 days and degree of hypercatabolism is maximum^3,4 (IV).

The need for surgery or the development of local complications related to pancreatitis does not change the indication of NS, that should continue to be based on the severity and efficacy of intake to reach the calculated nutritional requirements.

Is enteral nutrition advisable in patients with severe acute pancreatitis?

Absence of enteral feeding induces gastrointestinal mucosa atrophy, bacterial overgrowth, increased intestinal permeability, and bacterial translocation. In an experimental study of AP, enteral nutrition, as compared to PN, reduced endotoxemia levels, bacterial translocation in portal and systemic blood, and the number of bacterial colonies in mesenteric nodes and in the pancreas¹⁵.

The latest revision by Cochrane 2010, with an analysis of subgroups with SAP, concluded that EN shows significant benefits over PN by reducing mortality, multiple organ failure, systemic infection and surgical procedures. In addition, it is associated with a trend in reducing hospital length of stay, local septic complications, and other local complications, and all this at a lower cost¹³ (Ib).

When should be enteral nutrition started?

Studies evaluating the effect of EN on systemic inflammatory response in patients with SAp show a faster reduction of APACHE II and inflammatory markers^9,10,14,16. It has been shown that bacterial colonization and infection occur a few hours following the onset of pancreatitis. A mortality reduction has been seen in several series, excluding studies starting NS after 48 h^16,17. The existence of previous malnutrition (as in the case of SAP of alcoholic origin) is another reason for starting early EN. Considering that EN started as soon as possible improves the disease process, we should recommend early EN in SAP, in the first 24-48 hours following admission, after the initial resuscitation phase^{5,12-14,16,17} (Ib).

How should enteral nutrition be administered?

Some studies in SAP have shown that exocrine secretion in response to cholecystokinin and other secretagogues is markedly reduced¹⁸. On the other hand, EN flow distal to the ligament of Treitz stimulates minimally pancreatic secretion, respecting "pancreatic rest". Randomized studies on EN vs PN have been publi shed, where EN was administered in the jejunum, with no complications secondary to the site^5,6. It is therefore concluded that the use of jejunal nutrition^12,14,16 (Ib) is safe for SAP. The use of a dual lumen catheter, which allows for jejunal infusion together with gastric decompression, monitoring the quantity and appearance of gastric output, enhances tolerability and management of EN in these patients.

However, randomized studies comparing EN by gastric versus jejunal route in SAP have demonstrated similar outcomes^19,20 (Ib), though the comparison of severity is difficult to establish, so the gastric route can be also used in some cases.

There is a single study in pancreatitis where the objective is to assess the type of diet administered. This study includes a small number of seriously ill patients with pancreatitis, and concludes that both oligomeric and polymeric diets are well tolerated in patients with pancreatitis²¹ (IIb).

There is theoretical tolerance advantage favorable to the semielemental diet, as it contains small peptides and middle-chain lipids, hat do not require pancreatic enzymes to be digested, but, in the opinion of the experts, polymeric diets may be used safely²² (IV).

When should parenteral nutrition be used?

The indication of PN would be subject to the unfeasibility of obtaining an adequate enteral approach, in case of intolerance to EN or when on starting EN the clinical and laboratory signs of the severe acute pancreatitis worsen^2,23,24.

Xian-Li confirmed that the start of PN 24-48 hours after obtaining hemodynamic control reduced complications, hospital stay and mortality²⁵ (Ib). Some authors recommend delaying the start of PN for at least 5 days, until the inflammatory response syndrome has subsided, in patients with SAP where EN cannot be started, but they are based on studies not performed on SAP¹². Thus, following the criterion of indication of PN in critically-ill patients, we consider that PN should be started in patients who require specialized NS, if this could not be started by enteral route or if a total nutritional supply is not achieved, within the first 48 hours following admission. With regard to the composition of PN, there are no data to recommend patterns of specific amino acids or certain lipid formulations in the SAP. No formulation has shown to be superior to another. It must be considered that lipid emulsions are not contraindicated in patients with SAP and, therefore, the energy supply must be mixed (carbohydrates/ fats)24. Hypertriglyceridemia and hyperglycemia values must be closely monitored.

In patients receiving PN it may be advisable to simultaneously supply a very low amount of enteral diet. The purpose of EN, though from a theoretical point of view, would be to maintain the trophic effect of intraluminal nutrient supply on the intestinal mucosa^23,26-28 (IV).

What specific nutrients are indicated in severe acute pancreatitis?

With regard to enteral pharmaconutrition in SAP, there is scant scientific evidence and the recommendations on the topic are ambiguous. In the literature publi shed, the benefits with scientific significance make refe rence to improvements in biochemical inflammation markers²⁹ and suggest outcome benefits in patients with SAP when nutrition enriched with pharmaconu trients is administered^29,30, though from the design of these studies it is not considered that there is sufficient evidence for recommending them^{12,16,24,31,32}(Ib).

Studies with administration of parenteral glutamine supplements, in patients with SAP receiving PN, have reported prognostic benefits with a shorter hospital stay and a reduction of infectious complications and the need for surgery, as well as a better control of blood sugar levels and faster improvement in biochemical markers of inflammation^12,14,33,34 (Ib).

With regard to the administration of probiotics and prebiotics in patients with SAP, currently, and analyzing the data obtained from the studies completed^8,9,35,36 (Ib), no recommendations can be made for their use, as the literature evidence is rather disparate, not always using the same organisms, and the doses used have been also different.

Few studies about the administration of trace elements and micronutrients with an antioxidant action by parenteral or enteral routes have been performed in patients with SAP^37,38.

Recommendations

- Enteral nutrition by jejunal route is of choice over parenteral nutrition (A).

- Specialized nutritional support in severe acute pancreatitis should be started early, within 48 h of initial resuscitation (A).

- Polymeric and oligomeric diets are equally recommended (C).

- It is suggested to assess the possibility for maintaining a minimum enteral nutrient supply, even in patients with intolerance to enteral nutrition and who are on treatment with parenteral nutrition (C).

- The use of glutamine is recommended in patients with severe acute pancreatitis receiving parenteral nutrition (B).

- There are no current recommendations for the use of prebiotics or probiotics in patients with severe acute pancreatitis (C).

Conflict of interests

The authors declare that they have participated in activities funded by the pharmaceutical industry for marketing of nutritional products (clinical studies, educational programmes and attendance to scientific events). No pharmaceutical industry has participated in the preparation, discussion, writing, and establishing of evidences in any phase of this article.

References

1. Vege SS, Gardner TB, Chari ST, Munukuti P, Pearson RK, Clain JE et al. Low mortality and high morbidity in severe acute pancreatitis without organ failure: a case for revising the Atlanta classification to include "moderately severe acute pancreatitis". Am J Gastroenterol 2009; 104: 710-5.         [ Links ]

2. Maraví E, Jiménez Urra I, Gener J, Zubia F, Pérez M, Casas JD et al. Recomendaciones de la 7.^a conferencia de consenso de la SEMICYUC. Pancreatitis aguda grave en medicina intensiva. Med Intensiva 2005; 29: 279-304.         [ Links ]

3. Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet 2008; 371: 143-52.         [ Links ]

4. Haney JC, Pappas TN. Necrotizing pancreatitis: diagnosis and management. Surg Clin North Am 2007; 87: 1431-46.         [ Links ]

5. Petrov MS, Kukosh MV, Emelyanov NV. A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition. Dig Surg 2006; 23: 336-44.         [ Links ]

6. Gupta R, Patel K, Calder PC, Yaqoob P, Primrose JN, Johnson CD. A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II > or = 6). Pancreatology 2003; 3: 406-13.         [ Links ]

7. Windsor AC, Kanwar S, Li AG, Barnes E, Guthrie JA, Spark JI et al. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut 1998; 42: 431-5.         [ Links ]

8. Oláh A, Belágyi T, Pótó L, Romics L Jr, Bengmark S. Synbiotic control of inflammation and infection in severe acute pancreatitis: a prospective, randomized, double-bind study. Hepatogastroenterology 2007; 54: 590-4.         [ Links ]

9. Besselink MG, Van Santvoort HC, Renooij W, De Smet MB, Boermeester MA, Fischer K et al. Intestinal barrier dysfunction in a randomized trial of a specific probiotic composition in acute pancreatitis. Ann Surg 2009; 250: 712-9.         [ Links ]

10. Casas M, Mora J, Fort E, Aracil C, Busquets D, Galter S et al. Total enteral nutrition vs total parenteral nutrition in patients with severe acute pancreatitis. Rev Esp Enferm Dig 2007; 99: 264-9.         [ Links ]

11. Petrov MS, Van Santvoort HC, Basselink MG, Van der Heijden GJ, Windsor JA, Gooszen HG. Enteral nutrition and the risk of mortality and infections complications in patients with severe acute pancreatitis: a meta-analysis of randomized trials. Arch Surg 2008; 143: 1111-7.         [ Links ]

12. McClave SA, Chang WK, Dhaliwal R, Heyland DK. Nutrition support in acute pancreatitis: a systematic review of the literature. JPEN J Parenter Enteral Nutr 2006; 30: 143-56.         [ Links ]

13. Al-omran M, AlBalawi ZH, Tashkandi MF, Al-Ansary LA. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev 2010; 20:CD002837.         [ Links ]

14. Gianotti L, Meier R, Lobo DN, Bassi C, Dejong CH, Ockenga J et al. ESPEN Guidelines on parenteral nutrition: pancreas. Clin Nutr 2009; 28: 428-35.         [ Links ]

15. Qin HL, Su ZD, Hu LG, Ding ZX, Lin QT. Effect of early intrajejunal nutrition on pancreatic pathological features and gut barrier function in dogs with acute pancreatitis. Clin Nutr 2002; 21: 469-73.         [ Links ]

16. Marik PE. What is the best way to feed patients with pancreatitis? Curr Opin Crit Care 2009; 15: 131-8.         [ Links ]

17. Petrov MS, Pylypchuk RD, Uchugina AF. A systematic review on the timing of artificial nutrition in acute pancreatitis. Br J Nutr 2009; 101: 787-93.         [ Links ]

18. Fan BG. Effects of parenteral nutrition on the exocrine pancreas in response to cholecystokinin. JPEN J Parenter Enteral Nutr 2008; 32: 57-62.         [ Links ]

19. Eatock FC, Chong P, Menezes N, Murray L, McKay CJ, Carter CR et al. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol2005; 100: 432-9.         [ Links ]

20. Kumar A, Singh N, Prakash S, Saraya A, Joshi YK. Early enteral nutrition in severe acute pancreatitis: a prospective randomized controlled trial comparing nasojejunal and nasogastric routes. J Clin Gastroenterol 2006; 40: 431-4.         [ Links ]

21. Tiengou LE, Gloro R, Pouzoulet J, Bouhier K, Read MH, Arnaud-Battandier F et al. Semi-elemental formula or polymeric formula: is there a better choice for enteral nutrition in acute pancreatitis?. Randomized comparative study. JPEN J Parenter Enteral Nutr 2006; 30: 1-5.         [ Links ]

22. Ziegler F, Ollivier JM, Cynober L, Masini JP, Coudray-Lucas C, Levy E et al. Efficiency of enteral nitrogen support in surgical patients: small peptides v nondegraded proteins. Gut 1990; 31: 1277-83.         [ Links ]

23. Garnacho J, García de Lorenzo A, Ordóñez FJ. Soporte nutricional en la pancreatitis aguda. Nutr Hosp 2005; 20 (Suppl. 2): 25-7.         [ Links ]

24. Gento Peña E, Martín de la Torre E, Miján de la Torre A. Nutrición artificial y pancreatitis aguda: revisión y actualización. Nutr Hosp 2007; 22: 25-37.         [ Links ]

25. Xian-Li H, Qing-Jiu M, Jian-Guo L, Yan-Kui C, Xi-Lin D. Effect of total parenteral nutrition (tpN) with and without glutamine dipeptide supplementation on outcome in severe acute pancreatitis (SAP). Clinical Nutrition Supplements 2004; 1: 43-7.         [ Links ]

26. Petrov MS, Pylypchuk R, Emelyanov N. Systematic review: nutritional support in acute pancreatitis. Aliment Pharmacol Ther 2008; 15: 704-12.         [ Links ]

27. Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A et al. ESPEN Guidelines on Parenteral Nutrition:intensive care. Clin Nutr 2009; 28: 387-400.         [ Links ]

28. Sun B, Gao Y, Xu J, Zhou ZQ, Zhou ZQ, Liu C et al. Role of individually staged nutritional support in the management of severe acute pancreatitis. Hepatobiliary Pancreat Dis Int 2004; 3: 458-63.         [ Links ]

29. Pearce CB, Sadek SA, Walters Am, Goggin PM, Somers SS, Toh SK et al. A double-blind, randomized controlled trial to study the effects of an enteral feed supplemented with glutamine, arginine, and omega-3 fatty acid in predicted acute severe pancreatitis. JOP 2006; 7: 361-71.         [ Links ]

30. Lasztity N. Effect of enterally administered n-3 polyunsaturated fatty acids in acute pancreatitis: a prospective randomized clinical trial. Clin Nutr 2005; 24: 198-205.         [ Links ]

31. Ioannidis O, Lavrentieva A, Botsios D. Nutrition support in acute pancreatitis. JOP 2008; 9: 375-90.         [ Links ]

32. Skipworth JR, Pereira SP. Acute pancreatitis. Curr Opin Crit Care 2008; 14: 172-8.         [ Links ]

33. Sahin H, Mercanligil SM, Inanç N, Ok E. Effects of glutamineenriched total parenteral nutrition on acute pancreatitis. Eur J Clin Nutr 2007; 61: 1429-34.         [ Links ]

34. Xue p, Deng LH, Xia Q, Zhang ZD, Hu WM, Yang XN et al. Impact of alanyl-glutamine dipeptide on severe acute pancreatitis in early stage. World J Gastroenterol 2008; 14: 474-8.         [ Links ]

35. Karakan T, Ergun M, Dogan I, Cindoruk M, Unal S. Comparison of early enteral nutrition in severe acute pancreatitis with prebiotic fiber supplementation versus standard enteral solution: a prospective randomized double-bind study. World J Gastroenterol 2007; 13: 2733-7.         [ Links ]

36. Muftuoglu MA, Isikgor S, Tosun S, Saglam A. Effects of probio tics on the severity of experimenttal acute pancreatitis. Eur J Clin Nutr 2006; 60: 464-8.         [ Links ]

37. Virlos IT, Mason J, Schofield D, McCloy RF, Eddleston JM, Siriwardena AK. Intravenous n-acetylcysteine, ascorbic acid and selenium-based anti-oxidant therapy in severe acute pancreatitis. Scand J Gastroenterol 2003; 38: 1262-7.         [ Links ]

38. Du WD, Yuan ZR, Sun J, Tang JX, Cheng AQ, Shen DM et al. therapeutic efficacy of high-dose vitamin C on a acute pancrea -titis and its potential mechanisms. World J Gastroenterol 2003;9: 2565-9.         [ Links ]

Correspondence:
L. Bordejé Laguna. ]]> Hospital Universitario Germans Trias i Pujol.
Badalona. Spain.
E-mail: luisabl@yahoo.com