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.     

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.     

Treatment strategy for acute pancreatitis

When a diagnosis of acute pancreatitis (AP) is made, fundamental medical treatment consisting of fasting, intravenous (IV) fluid replacement, and analgesics with a close monitoring of vital signs should be immediately started. In parallel with fundamental medical treatment, assessment of severity based on clinical signs, blood test, urinalysis and imaging tests should be performed to determine the way of treatment for each patient. A repeat evaluation of severity is important since the condition is unstable especially in the early stage of AP. At the time of initial diagnosis, the etiology should be investigated by means of blood test, urinalysis and diagnostic imaging. If a biliary pancreatitis accompanied with acute cholangitis or biliary stasis is diagnosed or suspected, an early endoscopic retrograde cholangiopancreatography with or without endoscopic sphincterotomy (ERCP/ES) is recommended in addition to the fundamental medical treatment. In mild cases, the fundamental medical treatment should be continued until clinical symptom is subsided with normal laboratory data. In cases with severe acute pancreatitis (SAP) referral should be considered to medical centers experienced in the treatment of SAP, and intensive care is recommended for preventing both organ failures and infectious complications. Hemodynamic stabilization with vigorous fluid resuscitation, respiratory support and antibiotics are the major parts of intensive care in the early period of SAP. Continuous hemodiafiltration (CHDF) and continuous regional arterial infusion (CRAI) of protease inhibitor and/or antibiotics may be effective to improve pathophysiology of AP especially in the early stage of the disease. In the late stage of AP, infectious complications are critical. If an infectious complication is suspected based on clinical signs, blood test and imaging, a fine needle aspiration (FNA) is recommended to establish a diagnosis. The accuracy of FNA is reported to be 89 ~ 100%. For patients with sterile pancreatitis, non-surgical treatment should be indicated. For patients with infected pancreatic necrosis, therapeutic intervention either by percutaneous, endoscopic, laparoscopic or surgical approach are indicated. The most preferred surgical intervention is necrosectomy, however, non-surgical treatment with antibiotics is still the treatment of choice if the general condition is stable. Necrosectomy should be performed as late as possible. For patients with pancreatic abscess, drainage is recommended.     

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.     

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.     

Invasive and non-invasive diagnostic methods for evaluation of hypovolemia in acute pancreatitis

Severe acute pancreatitis leads to a dramatic fluid loss in the intraperitoneal space which may result in circulatory decompensation. Sequestration of fluid can amount up to 40 percent of the circulating blood volume. The amount of fluid and electrolyte replacement is often misjudged leading to a higher rate of complications and a higher mortality rate of the disease. Furthermore, subsequent and adequate fluid resuscitation seems to influence the prognostic course of the disease by improving the perfusion and oxygenation of the pancreas. Otherwise volume overload may cause cardiopulmonary decompensation in the case of synchronous cardiopulmonary comorbidities. Therefore, an important part of treatment relies on careful haemodynamic monitoring, if necessary managed in an intensive care unit. Usually most patients with acute pancreatitis will be treated on a non-intensive medical ward which allows a differentiated and continuous haemodynamic monitoring only to a limited extent. Apart from monitoring circulatory parameters and measuring central venous pressure, there are other clinical methods, laboratory tests and radiological diagnostic procedures to determine the amount of intravascular fluid deficit and the individual volume demand of patients with acute pancreatitis. Prospective clinical trials for evaluation of pancreatitis-specific volume management do not exist so far. The aim of this review is to provide background information on invasive and non-invasive diagnostic methods for detection of circulatory hypovolemia in acute pancreatitis.     

Acute pancreatitis: treatment strategies

Acute pancreatitis is an acute painful abdominal disease of sudden onset that ranges from a mild and self-limited illness to a severe and severe life-threatening condition. In spite of decades of intensive research, there are no causal therapeutic options. Treatment relies on supportive treatment principles based on adequate volume replacement to compensate for fluid loss in the intraperitoneal space and analgesics for pain relief. In cases with acute pancreatitis predicted to have a severe course of the disease, antibiotic therapy is recommended to avoid infection of pancreatic necrosis. Despite a substantial set of clinical trials in favor of antibiotic treatment to reduce morbidity, there is no general consensus on the prophylactic antibiotic treatment. Adequate nutritional support is required for patients with severe acute pancreatitis and a protracted course of the disease. Enteral nutrition appears to be superior to enteral nutrition.     

Medical management of acute pancreatitis and complications]

Medical management of acute pancreatitis relies on supportive care such as fluid resuscitation and pain control. Prophylactic antibiotics can reduce the opportunity of infection in severe pancreatitis. The effect of somatostatin or protease inhibitors still needs to be evaluated through further study. Early endoscopic retrograde cholangiopancreatography (ERCP) can ameliorate the course of severe biliary pancreatitis. Although sterile pancreatic necrosis, acute fluid collection, and pseudocyst usually resolve spontaneously, endoscopic or percutaneous drainages are needed when these complications are infected.     

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.     

ICU management of severe acute pancreatitis

In intensive care medicine, severe acute pancreatitis (SAP) remains a very challenging disease with multiple complications and high mortality. The main pathophysiological mechanisms determining outcome are an uncontrolled systemic hyperinflammatory response early on and infection of pancreatic necrosis later on in the disease process. Despite a better understanding in recent years of the mechanisms and the mediators involved in the hyperinflammatory response, there is, as yet, no generally recognized specific treatment for this disease. Since early identification and aggressive treatment of associated organ dysfunction can have a major impact on outcome, early assessment of prognosis and severity is important. The evidence available indicates that patients with severe acute pancreatitis do not benefit from therapy with available antisecretory drugs or protease inhibitors. Supportive therapy, such as vigorous hydration, analgesia, correction of electrolyte and glycemia disorders, and pharmacological or mechanical support targeted at specific organs, is still the mainstay of therapy. In spite of meager evidence, prophylactic antibiotics with good penetration in pancreatic tissue are recommended in severe acute pancreatitis. Enteral nutrition via a nasojejunal tube has become the preferred route of feeding. Most patients with sterile necrosis do not benefit from surgical intervention. In patients with proven infection of pancreatic tissue, surgery is necessary. Percutaneous, radiological drainage techniques may eventually become an alternative form of drainage in selected patients.     

Fluid resuscitation in acute pancreatitis

Acute pancreatitis remains a clinical challenge, despite an exponential increase in our knowledge of its complex pathophysiological changes. Early fluid therapy is the cornerstone of treatment and is universally recommended; however, there is a lack of consensus regarding the type, rate, amount and end points of fluid replacement. Further confusion is added with the newer studies reporting better results with controlled fluid therapy. This review focuses on the pathophysiology of fluid depletion in acute pancreatitis, as well as the rationale for fluid replacement, the type, optimal amount, rate of infusion and monitoring of such patients. The basic goal of fluid epletion should be to prevent or minimize the systemic response to inflammatory markers. For this review, various studies and reviews were critically evaluated, along with authors’ recommendations, for predicted severe or severe pancreatitis based on the available evidence.     

Management strategy for acute pancreatitis in the JPN Guidelines

The diagnosis of acute pancreatitis is based on the following findings: (1) acute attacks of abdominal pain and tenderness in the epigastric region, (2) elevated blood levels of pancreatic enzymes, and (3) abnormal diagnostic imaging findings in the pancreas associated with acute pancreatitis. In Japan, in accordance with criteria established by the Japanese Ministry of Health, Labour, and Welfare, the severity of acute pancreatitis is assessed based on the clinical signs, hematological findings, and imaging findings, including abdominal contrast‐enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Severity must be re‐evaluated, especially in the period 24 to 48 h after the onset of acute pancreatitis, because even cases diagnosed as mild or moderate in the early stage may rapidly progress to severe. Management is selected according to the severity of acute pancreatitis, but it is imperative that an adequate infusion volume, vital‐sign monitoring, and pain relief be instituted immediately after diagnosis in every patient. Patients with severe cases are treated with broad‐spectrum antimicrobial agents, a continuous high‐dose protease inhibitor, and continuous intraarterial infusion of protease inhibitors and antimicrobial agents; continuous hemodiafiltration may also be used to manage patients with severe cases. Whenever possible, transjejunal enteral nutrition should be administered, even in patients with severe cases, because it seems to decrease morbidity. Necrosectomy is performed when necrotizing pancreatitis is complicated by infection. In this case, continuous closed lavage or open drainage (planned necrosectomy) should be the selected procedure. Pancreatic abscesses are treated by surgical or percutaneous drainage. Emergency endoscopic procedures are given priority over other methods of management in patients with acute gallstone‐associated pancreatitis, patients suspected of having bile duct obstruction, and patients with acute gallstone pancreatitis complicated by cholangitis. These strategies for the management of acute pancreatitis are shown in the algorithm in this article.     

Principles of conservative treatment of severe acute pancreatitis

The main principles of conservative treatment of severe acute pancreatitis include early diagnosis of the disease, diagnosis of its severe form and assessment of the etiology of pancreatitis, replacement of fluids, adjustment of the milieu intérieur, administration of antibiotics in patients with confirmed necroses, in particular if they exceed 25 - 30%, early endoscpic treatment of pancreatitis with a biliary etiology, adequate nutrition, prevention and treatment of complications. The diagnosis of pancreatitis is based on clinical examination, biochemical evidence of elevated amylase and lipase concentrations and on the imaging of the pancreas. In the severe form necroses of the pancreas are present or other local complications and/or organ dysfunction. As regards assessment of the etiology rapid diagnosis of biliary pancreatitis is fundamental as it leads to therapeutic consequences. Fluid replacement should not be discontinued even during transport and diagnostic procedures. Infection remains the main cause of mortality in patients who got over the hypovolaemic stage of pancreatitis. Antibiotics are therefore indicated in all patients with necroses or biliary infection. Systemic complications include renal failure, pulmonary failure, coagulopathy, cardiac and hepatic failure--frequently manifested as combined multiple organ dysfunction. Local complications such as pseudocysts, abscesses, compression conditioned stenoses of the bile ducts or haemorrhage from impaired visceral arteries are treated as a rule in an interdisciplinary manner with preference of less invasive procedures. Clinical deterioration of patients in particular the development of multiple organ failure in patients with extensive infiltrates and necroses is caused in the great majority of cases by infection of necroses and is an indication for early, usually surgical intervention.     

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.     

Hypertriglyceridemia and acute pancreatitis

Hypertriglyceridemia is the third most common cause of acute pancreatitis. It typically occurs in patients with an underlying disorder of lipoprotein metabolism and in the presence of a secondary condition such as uncontrolled diabetes, alcohol abuse, or medication use.The presentation of hypertriglyceridemia-induced pancreatitis is similar to that of acute pancreatitis due to other causes; however, patients with hypertriglyceridemia-induced pancreatitis are more likely to have severe disease courses and have a higher likelihood of persistent organ failure. The initial treatment of hypertriglyceridemia-induced pancreatitis is also similar to acute pancreatitis from other causes and consists of aggressive fluid resuscitation, pain control, and nutritional support. Hypertriglyceridemia is specifically treated with apheresis or insulin therapy when necessary.The prompt recognition of hypertriglyceridemia in the setting of acute pancreatitis is essential in both the initial and long-term management of this disease and are essential to prevent recurrent acute pancreatitis. The review seeks to highlight the etiology, pathogenesis, and clinical course of hypertriglyceridemia-induced acute pancreatitis.     

Modern management of acute pancreatitis

There is a rising incidence of acute pancreatitis in the United States. Numerous clinical prognostic scoring systems have been developed, including the BISAP score. Vigorous fluid resuscitation remains a cornerstone of early management of acute pancreatitis. Cross-sectional imaging in the early phase of evaluation has not been associated with improvement of outcomes. There is no role for prophylactic antibiotics in early management. However, there is growing emphasis on the identification and treatment of extrapancreatic infections. Enteral nutrition in severe acute pancreatitis has reduced mortality, systemic infection, and multiorgan dysfunction compared to parenteral nutrition. Conservative management consisting of percutaneous drainage and delayed surgical intervention is now favored for local complications, such as infected necrosis. These developments have contributed to improved outcomes for patients with acute pancreatitis.     

Nutrition in acute pancreatitis

Pancreatitis is a common disorder. Numerous factors have been implicated in the pathogenesis of acute and chronic pancreatitis, but the exact mechanisms of these conditions are still poorly understood. Depending on the cause of the disorder, patients who have pancreatitis are usually not malnourished and are able to eat within 5 to 7 days of disease onset. In these patients, nutritional support is unnecessary. However, severe disease induces a catabolic state similar to that seen in trauma and sepsis, resulting in rapid weight loss and increased morbidity and mortality. Thus, vigorous nutritional support may be useful in the treatment of severe pancreatitis. Studies have shown that parenteral and enteral nutritional support are well tolerated and can maintain or improve nutritional status in patients with pancreatitis. This article reviews nutritional assessment and therapy in pancreatitis.     

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.     

重症急性胰腺炎的早期处理

重症急性胰腺炎起病凶险,病死率较高。对重症急性胰腺炎的早期识别及早期治疗有助于减少器官衰竭、感染等并发症的发生,降低病死率。该文从早期病情评估、早期病情监测及早期治疗3个方面介绍重症急性胰腺炎的早期处理,以期提高临床医生对重症急性胰腺炎早期诊治的认识。     

Early management of acute pancreatitis

Acute pancreatitis is the most common gastro-intestinal indication for acute hospitalization and its incidence continues to rise. In severe pancreatitis, morbidity and mortality remains high and is mainly driven by organ failure and infectious complications. Early management strategies should aim to prevent or treat organ failure and to reduce infectious complications. This review addresses the management of acute pancreatitis in the first hours to days after onset of symptoms, including fluid therapy, nutrition and endoscopic retrograde cholangiography. This review also discusses the recently revised Atlanta classification which provides new uniform terminology, thereby facilitating communication regarding severity and complications of pancreatitis.