Acute pancreatitis (AP) is a complex and variable disease, which brings great trauma to patients and challenges to clinical management. the classification and diagnostic criteria of AP established in Atlanta, USA in 1992 are regarded as a milestone in the history of AP, and the criteria have had a positive impact on the diagnosis and treatment of AP in the past decades.
However, with the advancement of imaging technology and the development of multidisciplinary treatment concepts, more and more clinical practices have found that the “Atlanta criteria” have had a positive impact on the classification, severity, and complications of AP.
However, with the advancement of imaging technology and multidisciplinary treatment concept, more and more clinical practices found that the “Atlanta criteria” are inadequate in the classification, severity, definition of complications, prognosis assessment and treatment of AP. In this context, the International Association of Pancreatology (IAP) released the Atlanta Classification Criteria (Revised) in 2012 after five years of investigation and discussion, and the Pancreatic Disease Group of the Chinese Medical Association’s Gastroenterology Branch also formulated the Guidelines for the Diagnosis and Treatment of Acute Pancreatitis in China in 2012. In 2012, the Pancreatic Disease Group of the Chinese Society of Gastroenterology also formulated the “Guidelines for the diagnosis and treatment of acute pancreatitis in China.
The American College of Gastroenterology (ACG), the IAP and the American Pancreatic Associa-tion (APA) published the Guidelines for the Management of Acute Pancreatitis (hereinafter referred to as the 2013 ACG) and the Guidelines for the Management of Acute Pancreatitis (hereinafter referred to as the 2013 ACG) in 2013 based on evidence-based medical evidence. 2013 ACG) and the Evidence-Based Guidelines for the Management of Acute Pancreatitis (hereafter referred to as 2013 IAP/APA). How to evaluate the similarities and differences of different guidelines is particularly important for the diagnosis and treatment of AP and international exchange in China. This article compares and interprets the relevant guidelines with the hot issues in the clinical treatment of AP.
Changes in the diagnostic system of acute pancreatitis
1. Diagnostic criteria
The diagnostic criteria of AP are basically the same in domestic and international guidelines, and it is considered that the diagnosis of AP must meet at least 2 of the following 3 criteria: (1) symptoms of abdominal pain consistent with AP; (2) serum amylase and/or lipase ≥ 3 times the upper limit of normal value; (3) imaging features consistent with AP.
Due to the high incidence of biliary pancreatitis (about 40%-70% of AP) and the importance of recurrence prevention, both the 2013 ACG and the IAP/APA recommend abdominal B-ultrasound for all patients with AP on admission. In contrast, the Chinese Guidelines for the Diagnosis and Treatment of Acute Pancreatitis considers that although ultrasonography can initially determine the morphological changes of the pancreas and help determine the presence of biliary tract disease, it is susceptible to the influence of gas accumulation in the gastrointestinal tract and cannot make accurate judgments on AP, so CT scan is recommended as the standard imaging method for the diagnosis of AP. 2.
2. complications and severity grading of AP
(1) Major local complications
Local complications of AP have been classified according to the fluid accumulation around the pancreas into four conditions: acute fluid accumulation, pancreatic necrosis, pseudocyst and pancreatic abscess, which can easily cause confusion.
The Atlanta Classification Criteria (Revised) distinguishes between acute peripancreatic fluid collection (acute peripancre-atic fluid collection, APFC) and acute necrotizing fluid collection (acute necrotizing fluid collection, ANC) depending on whether the acute fluid collection is accompanied by necrosis of the pancreatic parenchyma or peripancreatic tissue within 4 weeks of the disease course. After 4 weeks of disease, APFC becomes pancreatic pseudocyst once it forms a cystic wall, and ANC becomes walled-off necroses (WON) when it is encapsulated by the cystic wall, and is defined as pancreatic abscess if it is co-infected (enhanced CT suggests bubble sign and positive bacterial or fungal culture of fine needle aspiration).
The significance of differentiating between these local complications is that: most APFC will resolve on their own, APFC and pseudocysts are considered for puncture drainage only when infected or symptomatic; aseptic ANC or WON requires intervention based on a combination of clinical symptoms; unlike pseudocysts, ANC or WON contains necrotic pancreatic tissue or fat, and in case of infection usually requires percutaneous puncture drainage and, if necessary, a laparoscopic, endoscopic or surgical removal, whereas pseudocysts are fluid components and in most cases only require drainage even if they are infected.
(2) Systemic complications of AP and grading of severity
The systemic complications of AP mainly include organ failure (OF), systemic inflammatory response syndrome (SIRS), systemic infection, intra-abdominal hypertension or abdominal septal compartment syndrome, and pancreatic encephalopathy. Of these, OF is the most important systemic complication.
OF: According to the modified Marshall scoring system, OF is considered to exist when any one of the respiratory, circulatory and urinary scores is ≥2. OF is a major factor affecting the prognosis of AP. The latest domestic and international guidelines for grading the severity of AP have adopted the Atlanta Classification Criteria (Revised), which classifies AP into mild acute pancreatitis (MAP), moderately severe acute pancreati-tis (MAP) and severe acute pancreatitis (MAP) based on the presence and duration of OF. pancreati-tis (MSAP) and severe acute pancreatitis (SAP).
MAP is an AP without OF, without local or systemic complications, and is the most common type of clinical condition; MSAP is a transient OF (recoverable within 48 h), or an AP with local or systemic complications.
recovery within 48 h), or with local or systemic complications without persistent OF; SAP is AP with OF duration >48 h.
SIRS: AP activates a cascade of cytokines that clinically manifests as SIRS, and the persistence of SIRS increases the risk of OF. SIRS is diagnosed with 2 or more of the following clinical signs: (1) heart rate >90 beats/min; (2) body temperature <36< span="">°C or >38°C; (3) total white blood cell count <4×109>12×109/L; and (4) respiratory rate >20 breaths/min or PCO2 <32 mm Hg.
Abdominal septal compartment syndrome ( ACS): inflammatory exudation and increase in organ volume caused by AP can cause an acute increase in intra-abdominal pressure, leading to circulatory disorders and tissue necrosis. The Chinese Guidelines for the Management of Acute Pancreatitis states that ACS should be considered when the bladder pressure (UBP) is ≥20 mm Hg, accompanied by oliguria, anuria, dyspnea, increased inspiratory pressure, and decreased blood pressure.
ACS plays an important role in the development of multipleorgan dysfunction syndrome (MODS) in SAP, and is an important indicator for determining the prognosis of SAP. Reducing intra-abdominal pressure has a role in improving symptoms, reversing organ function, and improving patient survival. It is noteworthy that recent foreign guidelines do not describe ACS much, probably because of the low evidence of relevant clinical studies.
The concept of “fulminant acute pancreatitis (FAP)” is not recommended to be used in both domestic and international guidelines, because the time of onset “within 72 h” mentioned in this term does not accurately reflect the prognosis of AP. In addition, SIRS, one of the diagnostic criteria, is only a partial clinical manifestation of AP and does not reflect the severity of the disease.
(3) Clinical staging of AP
Based on the 2 peaks of death in AP, the Atlanta Classification Criteria (Revised) divides the course of AP into 2 overlapping intervals.
(The severity of early disease is mainly determined by the presence or absence of OF and the duration of OF.
(2) Late stage, 1 week after onset (>7 d), the disease can last for weeks or even months. Only MSAP or SAP has a late stage, which is characterized by the persistence of local and/or systemic complications, the nature of which and the duration of OF determine the severity of the disease.
The formation of an early treatment system based on non-surgical treatment
Domestic and international guidelines have different opinions on the early diagnosis and treatment of AP: 2013 ACG, 2013 IAP/APA emphasize the importance of initial assessment and risk stratification, timely referral, early resuscitation and intravenous fluid replacement, and propose the indications of transendoscopic retrograde cholangiopancreatography ( ERCP) in AP; the Chinese Guidelines for the Diagnosis and Treatment of Pancreatitis emphasize the organ function from the perspective of internal medicine (early The Chinese Guidelines for the Diagnosis and Treatment of Pancreatitis emphasize the maintenance of organ functions (early fluid resuscitation, pulmonary function, renal function, liver function, and intestinal and coagulation functions) from the perspective of internal medicine, and mention the application of pancreatic exocrine inhibition and pancreatic enzyme inhibitors.
The system of early diagnosis and treatment of AP, mainly non-surgical treatment, is being gradually formed: dynamic assessment of disease development, effective early fluid resuscitation, maintenance and replacement of organ function, and multidisciplinary collaboration when necessary.
1. Dynamic assessment of disease progression
Many patients with severe AP do not show OF and pancreatic necrosis at the time of initial diagnosis, leading to delays in some clinical treatment measures. It is important to accurately determine the severity of patients with AP within the first 48 h of admission. Pancreatic necrosis often appears 48 h after admission, so early abdominal CT and magnetic resonance imaging (MRI) do not accurately assess the severity of AP.
Similarly, C-reactive protein (CRP) also takes 72 h to be measured accurately and therefore cannot be used as an early evaluation indicator. 2013 IAP/APA considers persistent SIRS as the best predictor of SAP. The dynamic assessment of early fluid deficiency, hypovolemic shock, and organ dysfunction not only helps to reflect the development of OF at an early stage and distinguish MSAP from SAP, but also helps SAP patients to be referred in time for more effective fluid resuscitation and organ function protection.
2. Early fluid resuscitation
Early fluid resuscitation is the cornerstone of early treatment of AP, and effective fluid resuscitation can maintain patient hemodynamics and improve pancreatic microcirculation. 2013 ACG and 2013 IAP/APA recommended early fluid rehydration principles can be summarized as follows.
(1) early rehydration: massive rehydration within 12-24 h; (2) crystalloid rehydration: isotonic Ringer’s lactate is recommended; (3) rapid rehydration: 250-500 ml/h, and intravenous pressurized infusion if necessary in patients with severe volume deficiency; (4) assessment of rehydration: repeatedly assess the adequacy of rehydration during the first 6 h and 24-48 h of admission, and reduce the blood urea nitrogen (BUN) level at the same time. ) levels, while preventing complications caused by aggressive rehydration (such as volume overload, pulmonary edema, abdominal septal compartment syndrome, etc.).
Foreign guidelines recommend early rehydration with lactated Ringer’s solution because isotonic equilibrium fluid can reduce the incidence of SIRS, while a randomized controlled trial (RCT) study confirmed that in AP patients with severe sepsis, the use of hydroxyethyl starch increases the incidence of renal failure and morbidity and mortality.
3. Maintenance and replacement of organ function
Because of the combination of OF in patients with SAP, it is important to support the failing organs during the 48 h-7 d of admission. Pulmonary, cardiovascular and renal function are the most vulnerable organs in patients with SAP and are the focus of treatment.
The following patients are recommended to be transferred to the intensive care unit (ICU) for treatment: (1) those with persistent dyspnea or tachycardia; (2) those who do not respond to initial resuscitation within 6-8 h of admission; and (3) those who do not respond to initial resuscitation within 6-8 h of admission.
(2) patients with respiratory failure or hypotension who do not respond to initial resuscitation within 6-8 h of admission; (3) patients with respiratory failure requiring mechanical ventilation; (4) patients with renal insufficiency requiring dialysis.
4. Inhibition of pancreatic exocrine secretion and application of pancreatic enzyme inhibitors
There are differences between domestic and international guidelines on the use of growth inhibitors and pancreatic enzyme inhibitors: The Chinese Guidelines for the Diagnosis and Treatment of Acute Pancreatitis suggest that growth inhibitors and their analogues (octreotide) can inhibit pancreatic exocrine secretion directly and have a positive effect on the prevention of postoperative pancreatitis after ERCP. H2 receptor antagonists or proton pump inhibitors can indirectly suppress pancreatic secretion by inhibiting gastric acid secretion, and can also prevent the development of stress ulcers.
All of them are recommended for use in SAP. Protease inhibitors (ustekin, gabex) can broadly inhibit the release and activity of trypsin, elastase, phospholipase A, etc., which are related to the development of AP, and also stabilize the lysosomal membrane. It improves pancreatic microcirculation and reduces AP complications, and early and adequate application is recommended. Due to the lack of data from multicenter clinical studies with large samples, the 2013 ACG, 2013 IAP/APA does not give a clear recommendation in this regard.
Nutritional support
The 2013 ACG recommends nasogastric tube feeding for patients in the ICU because it is easy and economical to place, while the Chinese guidelines consider nasojejunal tube feeding to be preferable to nasogastric tube feeding. The nasogastric tube is preferred over the nasogastric tube because it reduces intestinal permeability and reduces the incidence of endotoxemia and infection.
In addition, the Chinese Guidelines for the Diagnosis and Treatment of Acute Pancreatitis give indications for stopping or reducing EN: (1) intestinal bleeding, mechanical intestinal obstruction, abdominal pain, and abdominal distension are significantly worse; (2) accompanied by deterioration of general condition; and (3) bladder pressure >20 mm Hg.
Application of antibiotics
The application of antibiotics during the course of AP can be divided into prophylactic and therapeutic. The indications for the application of therapeutic antibiotics are basically the same in domestic and international guidelines, but the application of prophylactic antibiotics is more controversial.
1. prophylactic application of antibiotics
The efficacy of prophylactic antibiotics for SAP and non-biliary pancreatitis has been controversial. The Japanese guidelines for the diagnosis and treatment of AP recommend the prophylactic application of antibiotics; our guidelines for the diagnosis and treatment of severe acute pancreatitis also suggest that the prophylactic application of antibiotics that can cross the hemopancreatic barrier can be considered for the translocation of enteric-derived Gram-negative bacilli.
However, several high-quality meta-analyses published recently showed that prophylactic antibiotics did not significantly reduce the incidence of patient death, pancreatic necrotizing infections and surgical procedures, but only the incidence of infections outside the pancreas. Further analysis revealed that studies before 2000 showed that prophylactic antibiotic use reduced patient mortality, but studies after 2000 showed that prophylactic antibiotic use did not reduce patient mortality, suggesting that studies before 2000 may have a large bias. Based on the above evidence-based basis, the Chinese Acute Pancreatitis Diagnostic and Treatment Guidelines, 2013 ACG, and 2013 IAP/APA do not recommend prophylactic use of antibiotics.
2. Therapeutic application of antibiotics
The 2013 ACG suggests indications for antibiotics in patients with AP: (1) evidence of pancreatic or extra-pancreatic infection; (2) for patients with AP suspected of infectious necrosis, CT-guided fine needle aspiration (CT – FNA) for bacterial staining plus culture, or antibiotics based on drug sensitivity results after obtaining the necessary cultures of infectious material; (3) while waiting for culture results In the meantime, antibiotics can be used cautiously and stopped promptly if the culture result is negative.
The Chinese Guidelines for the Diagnosis and Treatment of Acute Pancreatitis specifies a “step-down” treatment strategy for AP patients: that is, the antibiotics chosen for initial treatment should be broad-spectrum and potent, and then the antibiotics should be adjusted as soon as possible according to the drug sensitivity results.
The recommended initial treatment regimens include: (1) carbapenems: imipenem, meropenem, donipenem; (2) penicillin + B-lactamase inhibitors: paracetamol; and (3) penicillin + B-lactamase inhibitors.
lactamase inhibitors: piperacillin a tazobactam; (3) third-generation cephalosporins + anti-anaerobic bacteria: cefepime + metronidazole or ceftazidime + metronidazole; (4) quinolones + anti-anaerobic bacteria: ciprofloxacin + metronidazole or levofloxacin + metronidazole.
Endoscopic treatment of acute biliary pancreatitis ( acute biliary pancreatitis, ABP)
The persistence of bile duct stones can cause obstruction of the pancreatic duct and biliary tract in some patients with AP. ERCP can, on the one hand, relieve the obstruction caused by stones and reduce the incidence of related complications, but on the other hand, it may also lead to serious complications such as postoperative pancreatitis. Therefore, the timing of ERCP in patients with ABP has been the focus of discussion.
The Chinese guidelines for the diagnosis and treatment of acute pancreatitis suggest that for patients with suspected or confirmed ABP, nasobiliary drainage or endoscopic duodenal papillary sphincterotomy (EST) should be performed if they meet the index of severe disease and/or have cholangitis, jaundice, or dilated common bile duct. ERCP treatment is available during hospitalization.
The 2013 ACG and 2013 IAP/APA strictly limit the indications and timing of ERCP in AP patients: ERCP is only recommended within 24 h of hospitalization in AP patients with combined acute cholangitis. It is also suggested that NSAIDs and pancreatic duct stents can reduce the risk of severe pancreatitis after ERCP.
Therapeutic principles of surgical intervention in AP
The timing and modalities of surgical interventions have always been a hot topic in the clinical management of AP and an urgent issue for surgeons. Multidisciplinary combination and minimally invasive treatment are the new highlights of surgical treatment for AP patients.
Experts from different countries agree that patients with ABP should undergo cholecystectomy “as soon as possible” after recovery from pancreatitis, but the exact timing of surgery is controversial. Some scholars believe that surgery should be performed 1-3 months after the patient is discharged from the hospital to reduce the risk of surgery and complications caused by edema and adhesions in AP. Another group of scholars suggested that cholecystectomy should be performed during this hospitalization in addition to ERCP for mild ABP to reduce the risk of pancreatitis or acute cholangitis during recovery.
The Chinese Guidelines for the Management of Acute Pancreatitis did not reach a consensus on the timing of cholecystectomy in patients with ABP, while the 2013 ACG and 2013 IAP/APA recommend cholecystectomy during the current hospitalization for patients with mild ABP to reduce the possibility of recurrence of biliary pancreatitis; for patients with severe ABP, delayed cholecystectomy (≥6 weeks after onset) is recommended until the acute inflammation subsides, the peripancreatic fluid is absorbed, and the disease is resolved. For patients with severe ABP, delayed cholecystectomy (≥ 6 weeks after onset) is recommended, and cholecystectomy should be performed after the acute inflammation has subsided, the peripancreatic fluid has been absorbed, and the condition has stabilized to reduce the chance of infection.
For asymptomatic aseptic necrosis, domestic and international guidelines recommend conservative treatment. 2013 IAP/APA states that interventional or surgical intervention can be considered for specific aseptic necrosis: (1) encapsulated necrosis with progressive gastrointestinal and biliary obstruction due to occupying effects; (2) necrotic effusion without signs of infection but with persistent pain, consider pancreatic duct dissection syndrome.
For patients with necrotizing pancreatitis with high suspicion of infection or proven infection, it is beneficial to first treat them conservatively with antibiotics for a period of time, which may effectively clear the source of infection or provide a transition for surgery. The Chinese Acute Pancreatitis Guidelines and the 2013 ACG suggest that surgical drainage should be delayed until 4 weeks after onset to allow time for liquefaction of the necrotic foci and formation of the surrounding fibrous cyst wall, and that a minimally invasive approach is preferable to open surgery.
The 2013 IAP/APA gave a detailed treatment strategy: surgical intervention should follow the step-up principle, preferring percutaneous or retroperitoneal puncture for drainage or endoscopic transmural drainage, followed by endoscopic or surgical removal of necrotic tissue if necessary.
It is important to point out that the pancreatic necrosis is surrounded by complex and large blood vessels, so if it is not completely removed at once, it will increase the risk of postoperative pancreatic fistula, infection, bleeding, and even death. For patients with large areas and many necrotic lesions, minimally invasive treatment is often difficult to achieve the desired results, and open surgery under direct vision may be advantageous at this time. Therefore, minimally invasive treatment still requires full consideration of the extent and liquefaction status of the necrotic material.
Summary
The introduction of evidence-based guidelines for the clinical management of AP
The introduction of evidence-based guidelines has provided strong guidance for clinical diagnosis and treatment of AP, as well as assistance for clinical communication and scientific research. However, it is still necessary to objectively evaluate and correctly understand the foreign guidelines, because any guideline has certain limitations and is time-sensitive. Our scholars have participated in the development of international guidelines, which indicates that the level of pancreatitis diagnosis and treatment in China is at the forefront of the international level, and it is necessary to further improve the update of the Guidelines for the diagnosis and treatment of severe acute pancreatitis in China.