Enteral nutrition and immune modulation of acute pancreatitis

Enteral nutrition has been strongly recommended by major scientific societies for the nutritional management of patients with acute pancreatitis.Providing severe acute pancreatitis patients with enteral nutrition within the first 24-48 h of hospital admission can help improve outcomes compared to parenteral nutrition and no feeding.New research is focusing in on when and what to feed to best improve outcomes for acute pancreatitis patients.Early enteral nutrition have the potential to modulate the immune responses.Despite this consistent evidence of early enteral nutrition in patients with acute pancreatitis,clinical practice continues to vary due to individual clinician preference.Achieving the immune modulating effects of enteral nutrition heavily depend on proper placement of the feeding tube and managing any tube feeding associated complications.The current article reviews the immune modulating effects of enteral nutrition and pro-and prebiotics and suggests some practical tools that help improve the patient adherence and tolerance to the tube feeding.Proper selection of the type of the tube,close monitoring of the tube for its placement,patency and securing its proper placement and routine checking the gastric residual volume could all help improve the outcome.Using peptide-based and high medium chaintriglycerides feeding formulas help improving feeding tolerance.     

Nutritional management of acute pancreatitis

Most patients with acute pancreatitis have mild to moderate disease and require no specialized nutritional support. Twenty percent to 30% have severe cases, resulting in a catabolic hypermetabolic state, and these patients may require early aggressive nutritional support. Traditionally, this support has been in the form of total parenteral nutrition. However, recent data suggest that enteral nutrition infused into the jejunum is feasible, well tolerated, associated with fewer complications, and significantly less expensive than parenteral nutrition. The pathophysiology of gut function in acute pancreatitis and the rationale and evidence for parenteral and enteral nutritional support are reviewed herein. An algorithm on the nutritional management of acute pancreatitis is suggested.     

急性胰腺炎的营养管理

急性胰腺炎尤其是重症急性胰腺炎病情凶险,死亡率高。胰腺炎时,消化系统受累严重而能量消耗增加,供需矛盾突出,禁食导致的继发性肠道细菌易位更加重了患者的死亡率。对急性胰腺炎患者进行营养管理不仅关系到营养本身的问题,更是对减少并发症、改善患者预后产生重要的影响。从传统的"胰腺休息"理论到目前主张的积极早期"胃肠激活"理论,营养问题在急性胰腺炎病理生理过程中所起的作用逐渐清晰。     

Nutritional support in acute pancreatitis

Acute pancreatitis is a catabolic condition requiring adequate nutritional support to avoid severe nitrogen loss. Providing nutrition to the patients with acute pancreatitis is, however, limited by the fact that oral feeding may stimulate the pancreas and aggravate the pancreatitis. Hence, total parenteral nutrition (TPN) is recommended for such patients but that too has limitations apart from its prohibitive cost. At the same time, therefore, enteral feeds have been developed, which provide adequate nutrition and are fairly well tolerated by these patients. Based on the available studies, a rational scheme of managing acute pancreatitis has been recommended. Patients with moderately severe acute pancreatitis who are malnourished or are likely to develop complications requiring surgery should be supported with total parenteral nutrition from an early stage. All patients with severe acute pancreatitis should, on the other hand, be supported with total parenteral nutrition from the beginning, but enteral nutrition via a jejunostomy should be commenced as early as possible since such patients often run a protracted course and giving them TPN might become exorbitantly expensive and impractical. Mixed or polymeric feeds are tolerated well from the sixth or seventh postoperative day but in an occasional patient elemental diet via the jejunostomy may become necessary.     

Early management of acute pancreatitis: A review of the best evidence

In the 20th century early management of acute pancreatitis often included surgical intervention, despite overwhelming mortality. The emergence of high-quality evidence (randomized controlled trials and meta-analyses) over the past two decades has notably shifted the treatment paradigm towards predominantly non-surgical management early in the course of acute pancreatitis. The present evidence-based review focuses on contemporary aspects of early management (which include analgesia, fluid resuscitation, antibiotics, nutrition, and endoscopic retrograde cholangiopancreatography) with a view to providing clear and succinct guidelines on early management of patients with acute pancreatitis in 2017 and beyond.     

Restoration of energy level in the early phase of acute pediatric pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatmentof acute pediatric pancreatitis. The preferred reporting items for systematic review(PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (Pub Med: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly(SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence.     

Nutritional support in acute pancreatitis

Acute pancreatitis can present as a mild or severe disease. Most patients have a mild disease and recover without requiring nutritional support. Patients with severe acute pancreatitis may develop systemic inflammatory response syndrome and progress to multi-organ failure. These ill patients have high metabolism and protein catabolism. Hence, the nutritional management of these patients can be challenging. The aim of nutritional support is to meet the elevated metabolic demands as far as possible without stimulating pancreatic secretion and yet maintaining the gut integrity. The concept of pancreatic rest has evolved over the years. To date, there is a substantial scientific proof that enteral nutrition (EN) in comparison to parenteral nutrition significantly reduces infectious complications, surgical interventions and mortality in predicted severe acute pancreatitis. EN may be able to improve outcome in these patients if given early. In this review, we summarized the current knowledge on nutrition in acute pancreatitis and shared our local experience.     

Nutrition in acute pancreatitis

Nutritional concepts in acute pancreatitis are undergoing a rapid change. An early start of nutrition via nasojejunal tubes is about to replace parenteral nutrition. Yesterday it was believed that the pancreas had to be put at rest. Thus, stimulation of pancreatic secretion by enteral nutrition was believed to be detrimental. However, on comparing the results of enteral with those of parenteral nutrition, the pancreatic infection rates, rate of surgical interventions, days of hospital stay, and costs are found to be significantly reduced. Whether or not enteral nutrition decreases mortality has not been clearly proven. Pancreatitis is associated with the risk of paralytic ileus. Thus, data suggesting that one does not have to feed via a nasojejunal tube but rather via an easier to place nasogastric tube, are provocative. Numerous questions still have to be answered such as composition of tube diet, nutrition in mild to moderate pancreatitis, ways to reduce pain and composition of diet when oral refeeding is started. The nutrition of tomorrow may implicate immunonutrition. There are only a few small studies suggesting beneficial effects by supplementation of tube feeding with MCT/LCT triglycerides, glutamine, arginin, omega-3-fatty acids, nucleotides. So far, these supplements have failed to show efficacy for clinically relevant endpoints. In an recently published study, prebiotics were associated with a high complication rate. In this review, we summarise the current knowledge on nutrition in acute pancreatitis and discuss future developments.     

Enteral nutrition in acute pancreatitis: A review of the current evidence

The use of enteral feeding as part of the management of acute pancreatitis dates back almost two decades.This review describes the indications for and limitations of enteral feeding for the treatment of acute pancreatitis using up-to-date evidence-based data.A systematic review was carried out to analyse current data on the use of enteral nutrition in the management of acute pancreatitis.Relevant literature was analysed from the viewpoints of enteral vs parenteral feeding,early vs delayed enteral nutrition,nasogastric vs nasojejunal feeding,and early oral diet and immunonutrition,particularly glutamine and probiotic supplementation.Finally,current applicable guidelines and the effects of these guidelines on clinical practice are discussed.The latest meta-analyses suggest that enteral nutrition significantly reduces the mortality rate of severe acute pancreatitis compared to parenteral feeding.To maintain gut barrier function and prevent early bacterial translocation,enteral feeding should be commenced within the first 24 h of hospital admission.Also,the safety of nasogastric feeding,which eases the administration of enteral nutrients in the clinical setting,is likely equal to nasojejunal feeding.Furthermore,an earlylow-fat oral diet is potentially beneficial in patients with mild pancreatitis.Despite the initial encouraging results,the current evidence does not support the use of immunoenhanced nutrients or probiotics in patients with acute pancreatitis.     

Enteral versus parenteral nutrition in acute pancreatitis.

Conventional wisdom has previously dictated that, in order to avoid stimulation of pancreatic secretion during acute pancreatitis, and thus avoid the perpetuation of the enzymatic activation from which the pancreatitis originated, enteral feeding should be avoided. With greater understanding of the potential role of the gastrointestinal tract in the development of a systemic inflammatory response within a number of scenarios, this dogma has recently been challenged. Moreover, there is some evidence to suggest that starving the gastrointestinal tract and providing nutritional support via the parenteral route may be associated with an increased incidence of septic complications. Experimental and clinical evidence suggests that feeding the gut may diminish intestinal permeability to endotoxin and diminish bacterial translocation, thus reducing the cytokine drive to the generalized inflammatory response and preventing organ dysfunction. Preliminary experience suggests that the institution of jejunal (but not gastric or duodenal) nutrition within 48 hours of the onset of severe acute pancreatitis diminishes endotoxic exposure, diminishes the cytokine and systemic inflammatory responses, avoids antioxidant consumption and does not cause the radiological appearances of the pancreas to deteriorate. These observations are paralleled by improvements in clinical outcome measures such as intensive care unit stay, septic complications and mortality. Whist parenteral nutrition continues to have a role in the management of acute pancreatitis particularly when complicated by fistulae or prolonged ileus, the early introduction of jejunal nutrition merits further investigation in acute pancreatitis.     

Nutritional support in acute pancreatitis: an update on management issues

About 20% of acute pancreatitis cases develop necrosis and have a high risk of inflammatory and infectious complications and a high mortality rate. Acute pancreatitis has a variety of causes and despite years of research its pathogenesis remains complex and obscure. Both local and systemic inflammatory responses play key roles in the pathophysiology of this disorder. Treatment plans continue to rely on supportive care without proven specific therapies. Pancreatic rest and use of total parenteral nutrition (TPN) were the gold standard for nutritional support of these challenging patients. Because numerous studies in other critically ill patients demonstrated benefits of enteral nutrition, recent investigations compared TPN to enteral nutrition in acute pancreatitis. These studies indicated that enteral nutrition delivered into the jejunum was tolerated well, even in patients with severe acute pancreatitis. "Mild' cases of pancreatitis should improve and tolerate oral nutrition within a few days. In contrast, "severe' cases of pancreatitis or those with a protracted clinical course require nutritional support to aid in preventing adverse effects of starvation and nutrient deficiencies. Current recommendations are to attempt enteral nutrition in patients with acute pancreatitis prior to instituting TPN. Further studies to determine optimal nutrient composition are warranted and should investigate the possibility of modulating the inflammatory response induced by pancreatitis to improve outcomes.     

Consensus of primary care in acute pancreatitis in Japan

The incidence of acute pancreatitis in Japan is increasing and ranges from 187 to 347 cases per million populations. Case fatality was 0.2% for mild to moderate, and 9.0% for severe acute pancreatitis in Japan in 2003. Experts in pancreatitis in Japan made this document focusing on the practical aspects in the early management of patients with acute pancreatitis. The correct diagnosis of acute pancreatitis and severity stratification should be made in all patients using the criteria for the diagnosis of acute pancreatitis and the multifactor scoring system proposed by the Research Committee of Intractable Diseases of the Pancreas as early as possible. All patients diagnosed with acute pancreatitis should be managed in the hospital, Monitoring of blood pressure, pulse and respiratory rate, body temperature, hourly urinary volume, and blood oxygen saturation level is essential in the management of such patients. Early vigorous intravenous hydration is of foremost importance to stabilize circulatory dynamics. Adequate pain relief with opiates is also important. In severe acute pancreatitis, prophylactic intravenous administration of antibiotics at an early stage is recommended. Administration of protease inhibitors should be initiated as soon as the diagnosis of acute pancreatitis is confirmed. A combination of enteral feeding with parenteral nutrition from early stage is recommended if there are no clear signs and symptoms of ileus and gastrointestinal bleeding. Patients with severe acute pancreatitis should be transferred to ICU as early as possible to perform special measures such as continuous regional arterial infusion of protease inhibitors and antibiotics, and continuous hemodiafiltratton. The Japanese Government covers medical care expense for severe acute pancreatitis as one of the projects of Research on Measures for Intractable Diseases.     

Nutrition support in acute pancreatitis

The benefit of early enteral nutrition (EN) for the disease process and for patient outcome in severe acute pancreatitis is dramatic. A narrow window of opportunity exists during which there is potential for EN to decrease disease severity and reduce overall complications. Most patients with severe pancreatitis tolerate enteral feeds. Any signs of symptom exacerbation or increasing inflammation in response to EN may be ameliorated by subtle adjustments in the feeding strategy. In this manner, provision of EN represents primary therapy in the management of the patient with acute pancreatitis and is emerging as the gold standard of therapy in nutrition support for this disease process.     

Current management of acute pancreatitis

The incidence of acute pancreatitis varies considerably between regions and is estimated at 5-80 per 100,000 population. The mortality rate of acute edematous-interstitial pancreatitis is below 1%, whereas 10-24% of patients with severe acute pancreatitis die. The early prognostic factors that can be used to determine whether the clinical course is likely to be severe are three or more signs of organ failure according to the Ranson or Imrie scores, the presence of nonpancreatic complications, and the detection of pancreatic necrosis by imaging techniques. Elevated C-reactive protein levels above 130 mg/l can also predict a severe course of acute pancreatitis with high sensitivity. Although no causal treatment exists, replacing the dramatic fluid loss that takes place in the early disease phase is critical and determines the patient's prognosis. Adequate pain relief with opiates is another therapeutic priority. In patients with pancreatic necrosis, the high mortality rate between the third and fourth week after the initial episode is determined largely by the development of pancreatic infection, and can therefore be reduced by early antibiotic treatment. Early enteral nutrition for the treatment of acute pancreatitis has been shown to be superior and much more cost-effective than parenteral nutrition. Infected pancreatic necrosis or pancreatic abscess are two of the few remaining indications for open surgery in acute pancreatitis. Even when indicated, surgery is frequently delayed or even replaced by minimally invasive surgical techniques.     

Antioxidative phytoceuticals to ameliorate pancreatitis in animal models: An answer from nature

Despite enthusiastic efforts directed at elucidating critical underlying mechanisms towards the identification of novel therapeutic targets for severe acute pancreatitis(SAP), the disease remains without a specific therapy to be executed within the first hours to days after onset of symptoms. Although earlier management for SAP should aim to either treat organ failure or reduce infectious complications, the current standard of care for the general management of AP in the first hours to days after onset of symptoms include intravenous fluid replacement, nutritional changes, and the use of analgesics with a close monitoring of vital signs. Furthermore, repeated evaluation of severity is very important, as the condition is particularly unstable in the early stages. In cases where biliary pancreatitis is accompanied by acute cholangitis or in cases where biliary stasis is suspected,an early endoscopic retrograde cholangiopancreatography is recommended.However,practice guidelines regarding the treatment of pancreatitis are suboptimal.In chronic pancreatitis,conservative management strategies include lifestyle modifications and dietary changes followed by analgesics and pancreatic enzyme supplementation.Recently,attention has been focused on phytoceuticals or antioxidants as agents that could surpass the limitations associated with currently available therapies.Because oxidative stress has been shown to play an important role in the pathogenesis of pancreatitis,antioxidants alone or combined with conventional therapy may improve oxidativestress-induced organ damage.Interest in phytoceuticals stems from their potential use as simple,accurate tools for pancreatitis prognostication that could replace older and more tedious methods.Therefore,the use of antioxidative nutrition or phytoceuticals may represent a new direction for clinical research in pancreatitis.In this review article,recent advances in the understanding of the pathogenesis of pancreatitis are discussed and the paradigm shift underway to develop phytoceuticals and antioxidants to treat it is introduced.Despite the promise of studies evaluating the effects of antioxidants/phytoceuticals in pancreatitis,translation to the clinic has thus far been disappointing.However,it is expected that continued research will provide solid evidence to justify the use of antioxidative phytoceuticals in the treatment of pancreatitis.     

Nutrition support in acute pancreatitis

In the majority (80%) of patients with acute pancreatitis, the disease is self limiting and, after a few days of withholding feeding and intravenous administration of fluids, patients can again be normally fed orally. In a small percentage of patients, the disease progresses to severe necrotic pancreatitis, with an intense systemic inflammatory response and often with multiple organ dysfunction syndrome. As mortality is high in patients with severe disease and as mortality and morbidity rates are directly related to the failure of establishing a positive nitrogen balance, it is assumed that feeding will improve survival in patients with severe disease. The aim of nutritional support is to cover the elevated metabolic demands as much as possible, without stimulating pancreatic secretion and maximizing self-digestion. The administration of either total parenteral nutrition or jejunal nutrition does not stimulate pancreatic secretion. Recently, a series of controlled clinical studies has been conducted in order to evaluate the effectiveness of enteral nutrition with jejunal administration of the nutritional solution. The results have shown that enteral nutrition, as compared to total parenteral nutrition, was cheaper, safer and more effective as regards the suppression of the immunoinflammatory response, the decrease of septic complications, the need for surgery for the management of the complications of acute pancreatitis and the reduction of the total hospitalization period. It did not seem to affect mortality or the rate of non-septic complications. In conclusion, enteral nutrition should be the preferred route of nutritional support in patients with acute pancreatitis.     

Fundamental and intensive care of acute pancreatitis

Patients who have been diagnosed as having acute pancreatitis should be, on principle, hospitalized. Crucial fundamental management is required soon after a diagnosis of acute pancreatitis has been made and includes monitoring of the conscious state, the respiratory and cardiovascular system, the urinary output, adequate fluid replacement and pain control. Along with such management, etiologic diagnosis and severity assessment should be conducted. Patients with a diagnosis of severe acute pancreatitis should be transferred to a medical facility where intensive respiratory and cardiovascular management as well as interventional treatment, blood purification therapy and nutritional support are available. The disease condition in acute pancreatitis changes every moment and even symptoms that are mild at the time of diagnosis may become severe later. Therefore, severity assessment should be conducted repeatedly at least within 48 h following diagnosis. An adequate dose of fluid replacement is essential to stabilize cardiovascular dynamics and the dose should be adjusted while assessing circulatory dynamics constantly. A large dose of fluid replacement is usually required in patients with severe acute pancreatitis. Prophylactic antibiotic administration is recommended to prevent infectious complications in patients with severe acute pancreatitis. Although the efficacy of intravenous administration of protease inhibitors is still a matter of controversy, there is a consensus in Japan that a large dose of a synthetic protease inhibitor should be given to patients with severe acute pancreatitis in order to prevent organ failure and other complications. Enteral feeding is superior to parenteral nutrition when it comes to the nutritional support of patients with severe acute pancreatitis. The JPN Guidelines recommend, as optional continuous regional arterial infusion and blood purification therapy.     

The role of the intestine in the pathophysiology and management of severe acute pancreatitis

BACKGROUND: The outcome of severe acute pancreatitis has scarcely improved in 10 years. Further impact will require new paradigms in pathophysiology and treatment. There is accumulating evidence to support the concept that the intestine has a key role in the pathophysiology of severe acute pancreatitis which goes beyond the notion of secondary pancreatic infection. Intestinal ischaemia and reperfusion and barrier failure are implicated in the development of multiple organ failure. DISCUSSION: Conventional management of severe acute pancreatitis has tended to ignore the intestine. More recent attempts to rectify this problem have included 1) resuscitation aimed at restoring intestinal blood flow through the use of appropriate fluids and splanchnic-sparing vasoconstrictors or inotropes; 2) enteral nutrition to help maintain the integrity of the intestinal barrier; 3) selective gut decontamination and prophylactic antibiotics to reduce bacterial translocation and secondary infection. Novel therapies are being developed to limit intestinal injury, and these include antioxidants and anti-cytokine agents. This paper focuses on the role of the intestine in the pathogenesis of severe acute pancreatitis and reviews the implications for management.     

Glutamine supplementation in acute pancreatitis: A meta-analysis of randomized controlled trials

BackgroundThere is emerging evidence that glutamine supplementation should be considered in patients with acute and critical illness associated with a catabolic response. There are reports of glutamine supplementation in acute pancreatitis but the results of these studies are conflicting. The aim of this study was to systematically review the randomised controlled trials (RCT) of glutamine in patients with acute pancreatitis.MethodsThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SCOPUS and 3 major Chinese databases were searched. The outcomes studied were mortality, total infectious complications, and length of hospital stay. A random effects model was used for meta-analysis of the outcomes in the included trials. A number of pre-specified subgroup analyses were also conducted. The summary estimates were reported as risk ratio (RR) for categorical variables and mean difference (MD) for continuous variables together with the corresponding 95% confidence interval.ResultsTwelve RCT that enrolled 505 patients with acute pancreatitis were included in the final analysis. Overall, glutamine supplementation resulted in a significantly reduced risk of mortality (RR 0.30; 95% CI, 0.15 to 0.60; P < 0.001) and total infectious complications (RR 0.58; 95% CI, 0.39 to 0.87; P = 0.009) but not length of hospital stay (MD ?1.35; 95% CI, ?3.25 to 0.56, P = 0.17). In the subgroup analyses, only patients who received parenteral nutrition and those who received glutamine in combination with other immunonutrients demonstrated a statistically significant benefit in terms of all the studied outcomes.ConclusionsThis meta-analysis demonstrates a clear advantage for glutamine supplementation in patients with acute pancreatitis who receive total parenteral nutrition. Patients with acute pancreatitis who receive enteral nutrition do not require glutamine supplementation. Further studies are warranted to determine whether patients who receive combined enteral and parenteral nutrition need glutamine supplementation.     

Biliary emergencies: pancreatitis,cholangitis, and more

The most common cause of acute pancreatitis is gallstones, although many other etiological factors have been identified. The management of the initial episode depends on the severity of the attack and the etiology. In most patients, acute pancreatitis has a benign, self-limited course. However, in the minority who develop infected pancreatic necrosis the mortality can reach 25%. The early assessment of severity and aggressive management of these patients is critical. The roles of endoscopic retrograde cholangiopancreatography, surgical intervention, enteral feeding and use of antibiotics in acute pancreatitis are discussed in this article. Finally, the origin of recurrent acute pancreatitis is discussed, with particular reference to conditions such as pancreas divisum and sphincter of Oddi dysfunction whose role in the development of acute pancreatitis is controversial, and to hereditary or familial pancreatitis.