The incidence of acute pancreatitis (AP) is increasing year by year, and the death rate is still high. The Chinese Society of Gastroenterology formulated the “Draft Guidelines for the Diagnosis and Treatment of Acute Pancreatitis in China” in 2003, which played an important role in improving the level of treatment of AP in China. In the past 10 years, with the update of the diagnosis and classification criteria of AP. In recent years, with the updating of the diagnostic and classification criteria of AP and the continuous research on the clinical management of this disease at home and abroad, it is necessary to revise the new AP guidelines to further standardize the clinical management of this disease in China.
AP is a disease caused by activation of pancreatic enzymes from various etiologies, followed by local inflammatory response of the pancreas, with or without functional changes in other organs. Clinically. The majority of patients have a self-limiting course. 20%- 30% of patients have an aggressive clinical course. The overall morbidity and mortality rate is 5-10%.
I. Terms and definitions
According to the latest revised AP grading and classification system of the International AP Symposium (2012′ Atlanta, USA), combined with the specific situation in our
According to the latest revision of the AP grading and classification system of the International AP Symposium (2012′ Atlanta, USA), the terminology and definitions of AP are stipulated with the specific situation in China, aiming at guiding clinical and scientific work. The purpose is to guide clinical and scientific work and to standardize the academic
The terminology used in this field.
(A) Clinical AP
1, mild AP (mild acute pancreatitis, MAP): with the clinical manifestations and biochemical changes of AP, not accompanied by organ failure and local or systemic complications, usually within 1-2 weeks recovery. The rate of death is very low.
2. Moderate AP (moderately severe acutepancreatltls, MSAP) has the clinical manifestations and biochemical changes of AP with transient organ failure (recoverable within 48 h), or with local or systemic complications without persistent organ failure (not recoverable within 48 h). For patients with severe tendency of AP, all vital signs should be monitored regularly and continuously evaluated.
3.Severe acute pancreatitis (SAP): with the clinical manifestations and biochemical changes of AP. Must be accompanied by persistent organ failure (lasting more than 48 h, not self-recovery of respiratory, cardiovascular or renal failure, may involve one or more organs), sAP morbidity and mortality is high, 36%-50% if the late co-infection is extremely high mortality rate.
4. Recommendation: MSAP is divided from the SAP defined in the 2003 edition of the “Chinese Guidelines for the Diagnosis and Treatment of Acute Pancreatitis (Draft)”. It meets the conditions of the original “SAP”. However, it is not associated with persistent organ failure. The term “Fulminam acute pancreatitis (FAP)” is not recommended. Because this term refers to the time of onset within 72 h” does not reflect the prognosis. And one of its diagnostic criteria is the systemic inflammatory response syndrome (systermic lnflammatory responessyndrome, SIRS). It is only a clinical manifestation of some APs. It cannot reflect the severity of the disease.
(B) imaging academic wu
1, interstitial edematous pancreatitis: most patients with AP have diffuse pancreatic enlargement due to inflammatory edema, occasionally there is limited enlargement, CT shows uniform enhancement of the pancreatic parenchyma, but the peripancreatic fat gap is blurred, also can be accompanied by peripancreatic fluid.
2. Necrotizing pancreatitis: 5%-10% of AP patients have pancreatic parenchymal necrosis or peripancreatic tissue necrosis, or both. Early enhancement CT has the potential to underestimate the extent of pancreatic and peripancreatic necrosis, and enhancement CT after 1 week of onset is more valuable, with parenchymal pancreatic necrosis appearing as an unenhanced area.
(C) Other terms
1, acute peripancreatic fluld co1lection (APFC): occurs early in the course of the disease, manifested as fluid accumulation in the pancreas, peripancreatic or distal interstitial space of the pancreas. It also lacks an intact envelope. It can be single or multiple.
2, acute necrotic collection (ANC): occurs early in the course of the disease, manifesting as liquid contents.
The acute necrotic collection (ANC): occurs early in the course of the disease, manifested as liquid contents, including mixed liquid and necrotic tissue. The necrotic material includes necrosis of the pancreatic parenchyma or peripancreatic tissue.
3, pancreatic pseudocyst (pancreatlc pseudocyst): a fluid accumulation with intact non-epithelial envelope, containing pancreatic secretions, granulation groups longitudinal, fibrous tissue, etc.. It mostly occurs 4 weeks after the onset of AP.
4.Walled-off necrosis (WON): a mature, cystic structure containing pancreatic and/or peripancreatic necrotic tissue with a well-defined inflammatory envelope, mostly occurring 4 weeks after the onset of AP.
5, pancreatic abscess (infected necrosis): pus accumulation in the pancreas or peri-pancreatic, peripheral fibrous cystic wall, enhanced CT suggests bubble sign, fine needle puncture material positive for bacterial or fungal culture.
II. Etiology of AP
On the basis of the diagnosis of AP, the cause of the disease should be clarified as much as possible. And efforts to remove the cause to prevent recurrence.
1, common causes: gallstone disease (including biliary microstones). Hypertriacylglycerolemia. Ethanol, biliary pancreatitis is still the main cause of AP in China_. The incidence of hypertriglyceridemic pancreatitis is on the rise. When the triacylglycerol ≥ 11.30 mmol/L. The clinical vulnerability to AP: When the triacylglycerol < 5.65 mmol/L., the risk of AP is reduced.
2, other etiology: sphincter of Oddi dysfunction (SOD). Drugs and poisons
Drugs and toxins. Traumatic. Hypercalcemia. Vasculitis. Congenital (pancreatic split, annular pancreas, paraduodenal papillary diverticulum, etc.). Tumorigenic (peripancreatic cancer, pancreatic cancer). Infectious (coxsackievirus, mumps virus, acquired immunodeficiency virus, ascariasis), autoimmune (systemic lupus erythematosus, desiccation syndrome), 1-antitrypsin deficiency, etc. In recent years, endoscopic retrograde cholangio pancreattography (ERCP), post-abdominal surgery, etc. The incidence of AP induced by medical factors is also on the rise.
3.After clinical, imaging and biochemical examinations, the cause of AP cannot be determined. Those who cannot determine the cause are called idiopathic.
III. Investigation of AP etiology
1, detailed medical history: including family history, past medical history, history of ethanol intake, history of drug intake, etc. Calculate BMI.
2, basic examination: including physical examination, serum amylase, serum lipase, liver function, lipids, blood glucose and calcium measurement, abdominal ultrasound examination.
Further examination: viral, autoimmune markers, tumor markers (cEA, CA19-9) measurement, enhanced CT scan, ERCP or magnetic resonance pancreatic bile duct imaging, ultrasound endoscopy, potbelly papillary sphincter manometry (if necessary), pancreatic exocrine function test, etc.
IV. Diagnostic process of AP
(I) Clinical manifestations of AP
Abdominal pain is the main symptom of AP. It is located in the upper abdomen. It often radiates to the back. Most of them are acute attacks and are persistent. A few do not have abdominal pain and can be accompanied by nausea and vomiting. Fever often originates from SIRS, necrotic pancreas group longitudinal secondary bacterial or fungal infection. Fever and jaundice are mostly seen in biliary pancreatitis. In terms of clinical signs, mild cases only show light pressure pain. In severe cases, signs of peritoneal irritation, ascites, GreyTurner’s sign and CUllen’s sign may appear. In a small number of patients, portal hypertension is present due to splenic vein embolism. The spleen is enlarged. Transverse colon necrosis is rare. A mass may be palpable in the abdomen due to fluid accumulation or pseudocyst formation. Other signs may be present with the corresponding complications.
Local complications include acute fluid accumulation, acute necrotic accumulation, pancreatic pseudocysts, encapsulated necrosis, and pancreatic abscesses. Other local complications include pleural effusion, gastric outflow tract obstruction, gastrointestinal fistula, abdominal hemorrhage, pseudocyst hemorrhage, splenic or portal vein thrombosis, and necrotizing colitis. Local complications are not the basis for judging the severity of AP.
Systemic complications mainly include organ failure, SIRS, systemic infection, intra-abdominal hypertension (IAH) or abdominal compartment syndrome (ACS), pancreatic encephalopathy (PE).
1, organ failure: the severity of AP depends on the appearance and duration of organ failure (whether it exceeds 48h).
The presence of more than 2 organs failure is called multipe organ failure (MOF). Respiratory failure mainly includes acute resplratorydistress syndrome (ARDS), circulatory failure mainly includes tachycardia, hypotension or shock, and renal failure mainly includes oliguria, anuria and elevated serum creatinine.
2.SIRS: SIRS can be diagnosed if 2 or more of the following clinical manifestations are met. heart rate >90 beats/min; body
Temperature <36℃ or >38℃; WBC count <4×109>12×10 9/L; respiratory rate >20 times/min or PCO2 <32 mm Hg (1 mm Hg= 0.133 kPa), the persistence of SIRS will increase the risk of organ failure.
3, systemic infection: If SAP patients are combined with sepsis, the morbidity and mortality rate increases. It is 50%-80%. Mainly gram-negative bacillary infections, but also fungal infections.
4, IAH and ACS: the incidence of IAH and ACS in SAP is about 40% and 10%, respectively, IAH has been used as one of the important indicators to determine SAP
IAH and ACS: The incidence of IAH and ACS in SAP is about 40% and 10%, respectively. It is easy to conduct convergence multiple organ dysfunction syndrome (M0DS). Bladder pressure (urinary bladdor pressure, UBP) measurement is an important indicator for the diagnosis of ACS, bladder pressure ≥ 20 mm Hg, accompanied by oliguria, anuria, dyspnea, increased inspiratory pressure, blood pressure reduction should be considered when the emergence of ACS.
5. Pancreatic encephalopathy: It is one of the serious complications of AP, which can manifest as tinnitus, diplopia, delirium, speech impairment and limb stiffness, coma, etc. It mostly occurs in the early stage of AP, but the specific mechanism is unknown.
(II) Ancillary tests
1, serum enzymatic examination: emphasize the clinical significance of serum amylase measurement. Urinary amylase changes are only for reference. Serum amylase activity is not correlated with the severity of the disease. Whether the patient is open to diet or the degree of disease can not rely solely on whether the serum amylase down to normal. A comprehensive judgment should be made. Persistent increase in serum amylase should be noted for recurrent disease, complications of pseudocysts or abscesses, suspected stones or tumors, renal insufficiency, hyperamylasemia, etc. Attention should be paid to identify other acute abdominal conditions causing increased serum amylase. The determination of serum lipase activity has important clinical significance, especially when the serum amylase activity has decreased to normal, or when the serum amylase activity is increased due to other reasons. The measurement of serum lipase activity has a complementary effect. Similarly. Serum lipase activity is not positively correlated with disease severity.
2, serum markers: CRP is recommended, and CRP > 150 mg/L after 72 h of onset suggests pancreatic tissue necrosis. Dynamic measurement of serum interleukin (IL)-6 level, if increased suggests poor prognosis. Elevated serum amyloid also has some value for AP diagnosis.
3. Diagnostic imaging: Ultrasound examination at 24 to 48 hours after the initial onset of the disease can initially determine the morphological changes of the pancreatic tissue. It also helps to determine the presence of biliary tract disease. However, due to the influence of gas accumulation in the gastrointestinal tract during AP, an accurate diagnosis of AP cannot be made. CT scan is recommended as a standard imaging method for the diagnosis of AP, and enhanced CT at about 1 week of onset has higher diagnostic value and can effectively differentiate the extent of fluid accumulation and necrosis. In the course of SAP, close follow-up CT examinations should be emphasized. It is recommended that CT examinations be performed as needed. On average, it should be performed once a week. According to the modified CT severity index (MCSI), the inflammatory response of the pancreas is graded as follows: normal pancreas (0 points). Pancreatic and/or peripancreatic inflammatory changes (2 points). Single or multiple areas of fluid accumulation or peripancreatic fat necrosis (4 points); pancreatic necrosis graded as: no pancreatic necrosis (0 points), necrosis ≤ 30% in extent (2 points), necrosis > 30% in extent (4 points): extra-pancreatic complications including pleural effusion, ascites, vascular or gastrointestinal tract (2 points). A score of ≥4 is diagnostic of MSAP or SAP. in addition, MRI can also aid in the diagnosis of AP.
(C) Diagnostic system of AP
1. Diagnostic criteria of AP: clinically, 2 of the following 3 features are met. AP can be diagnosed as ① abdominal pain consistent with AP (acute, sudden, continuous, severe upper abdominal pain, often radiating to the back); ② serum amylase and/or lipase activity at least >3 times the upper limit of normal; ③ enhanced CT/MRl or abdominal ultrasound showing AP imaging changes.
2, the graded diagnosis of AP: ①MAP for meeting the diagnostic criteria of AP, meeting one of the following conditions. No organ failure, no local or systemic complications, Ranson score <3, acute physiology and chronic health evaluatlon (APACHE) Ⅱ score <8, bedside index for severity in AP (BISAP) score <3, modified CT severity index (modifide) <3. CT severity index (MCTSI) score <4. ②MSAP was defined as meeting the diagnostic criteria for AP with one of the following conditions in the acute phase: Ranson score ≥ 3, APACHe II score ≥ 8, BISAP score ≥ 3, MCTSI score ≥ 4. There may be transient (<48 h) organ dysfunction. Pseudocysts, pancreatic fistulas or peri-pancreatic abscesses requiring intervention were present during the recovery period. (③SAP as meeting the diagnostic criteria for AP with persistent (>48 h) organ dysfunction (single or multiple organs) with a modified Marshall score ≥2 (Table 1).
3. Recommendations: ①The complete clinical diagnosis of AP should include disease diagnosis, etiological diagnosis, graded diagnosis, and diagnosis of complications, such as AP (biliary origin, severe, ARDS). ② Clinically, attention should be paid to the possibility that a portion of AP patients have been transformed into SAP since MAP, therefore, dynamic observation of the disease is necessary. In addition to Ranson score and APACHE II score, other valuable discriminatory indicators such as BMI>28 kg/m2, pleural exudate, especially bilateral pleural effusion, and CRP>150 mg/L after 72 h with persistent increase are all clinically valuable indicators for severity assessment.
Table 1 Modified marshall scoring system for determining SAP with organ failure
Note: PaO2 is the partial pressure of arterial blood oxygen; FiO2: is the concentration of inhaled oxygen, according to air (21%), pure oxygen 2L/min (25%), pure oxygen 4L/min (30%), pure oxygen 6-8L/min (40%), pure oxygen 9-10L/min (50%); conversion: 1mmHg=0.133Kpa
IV. AP diagnostic flow chart
MAP MSAP SAP
V. Principles of AP treatment
1.The main purpose of the treatment at the early stage of the disease is to correct water and electrolyte disorders, support treatment, and prevent local and systemic complications. The observation includes routine determination of blood, urine and coagulation, fecal occult blood, renal function, liver function determination, blood sedimentation, blood calcium determination, cardiac monitoring, blood pressure monitoring, blood gas analysis, serum electrolyte determination, chest X-ray, central venous pressure determination, dynamic observation of abdominal signs and intestinal The abdominal signs and bowel sounds were observed dynamically. The 24h urine output and volume changes were recorded. The above indexes can be selected according to the patient’s specific condition, and the severity and prognosis of AP can be judged according to APACHE score, Ranson score, BISAP score, etc. If the condition of SAP is critical, close monitoring of vital signs, adjustment of infusion rate and fluid composition, routine fasting, gastrointestinal decompression and other related measures should be taken for those with severe abdominal distension and paralytic intestinal obstruction. The open diet can be considered when the patient’s abdominal pain is reduced or disappears, abdominal distension is reduced or disappears, and intestinal dynamics is restored or partially restored, starting with sugar and gradually transitioning to a low-fat diet, without taking the high or low serum amylase activity as a necessary condition for the open diet.
2, maintenance of organ function: (1) early fluid resuscitation, controlled fluid resuscitation should be started immediately upon diagnosis, mainly divided into 2 stages of rapid volume expansion and adjustment of fluid distribution in the body, using vasoactive drugs if necessary. The volume of rehydration includes the amount of basic needs and the amount of fluid flowing into the tissue interstitial space, and the type of infusion includes colloidal substances, 0.9% NaCl solution and equilibrium fluid. Attention should be paid to the ratio of crystals to colloids and supplementation of trace elements and vitamins during volume expansion. (2) For the treatment of acute lung injury or respiratory failure, nasal catheter or mask oxygenation is given when acute lung injury occurs in SAP, maintaining oxygen saturation above 95%, the patient’s blood gas analysis results should be monitored dynamically, and when progressing to ARDS, treatment includes mechanical ventilation and high-dose glucocorticoid application, and bronchoscopic alveolar lavage when available. (3) Treatment for acute kidney injury or renal failure. The main treatment for acute renal failure is supportive therapy, stabilization of hemodynamic parameters, and dialysis if necessary. The indications for continuous renal replacement therapy are: with acute renal failure, or urine volume ≤ 0.5 ml/kg/h; early with 2 or more organ dysfunction; SIRS with tachycardia and shortness of breath, which is not obvious by general treatment; with severe water-electrolyte disorders; with pancreatic encephalopathy. It can be combined with 2 modes of continuous veno-venous hemofiltration and continuous plasma filtration and adsorption. (4) Support of other organ functions. Hepatoprotective drugs can be given in case of abnormal liver function, heparin in case of diffuse intravascular coagulation, and proton pump inhibitors in case of upper gastrointestinal bleeding. Patients with SAP should also pay special attention to the maintenance of intestinal function, because the stability of the intestinal mucosal barrier plays an important role in reducing systemic complications. It is necessary to closely observe abdominal signs and defecation, monitor changes in bowel sounds, give early pro-intestinal motility drugs, including raw rhubarb, mannitol, magnesium sulfate, fructose, etc., and apply glutamine preparations to protect the intestinal mucosal barrier. At the same time, Chinese herbal medicines, such as skin nitrate, can be applied externally. If the condition allows, early resumption of diet or implementation of enteral nutrition is important for the prevention of intestinal failure.
The use of H2 receptor antagonists or proton pump inhibitors can indirectly inhibit pancreatic secretion by inhibiting gastric acid secretion. It can also prevent the development of stress ulcers. Protease inhibitors (ustekin, gabex) can widely inhibit the release and activity of trypsin, elastase, phospholipase A, etc., which are related to the development of AP. They can also stabilize the lysosomal membrane, improve pancreatic microcirculation and reduce AP complications. Early and adequate application is advocated.
4, nutritional support: MAP patients only need short-term fasting, so they do not need enteral or parenteral nutrition. MSAP or SAP patients often implement parenteral nutrition first, and then implement enteral nutrition early (within 48 h of onset) when the patient can tolerate gastrointestinal motility. The most common route of enteral nutrition is endoscopically guided or X-ray guided placement of nasojejunal tube. Infusion of elemental nutrients with energy density of 4.187 J/ml can be supplemented with parenteral nutrition if the energy is insufficient, and the patient’s response can be observed, and if it is tolerated, the dose is gradually increased, and attention should be paid to supplementation of glutamine preparation. For patients with hyperlipidemia. The supplementation of fatty substances should be reduced. When enteral nutrition is carried out, attention should be paid to whether the patient’s abdominal pain, intestinal paralysis, abdominal pressure and other symptoms and signs of pancreatitis are aggravated, and electrolytes, blood lipids, blood glucose, TBil, serum A1h level, blood routine and renal function should be reviewed regularly to evaluate the metabolic status of the body and adjust the dose of enteral nutrition. Short peptide preparations can be used. Then gradually transition to whole protein preparations, according to the patient’s lipid and blood glucose situation for the selection of enteral nutrition dosage form.
5, antibiotic application: it has been confirmed that the prophylactic application of antibiotics can not significantly reduce the morbidity and mortality rate, therefore. For non-biliary AP, preventive antibiotics are not recommended, but for biliary MAP or MSAP and SAP with infection, antibiotics should be used routinely. The causative agents of pancreatic infection are mainly Gram-negative bacteria and anaerobic bacteria and other intestinal resident bacteria. The application of antibiotics should follow the strategy of “descending ladder”, choosing drugs with antibacterial spectrum targeting mainly gram-negative and anaerobic bacteria, with strong lipid solubility and effective passage through the blood-pancreatic barrier, with the recommended regimen: carbapenems; penicillin + lactamase inhibitors; third-generation cephalosporins + anti-anaerobic bacteria; quinolones + anti-anaerobic bacteria, with a treatment course of 7 -14 d. In special cases, the application can be extended. d. The duration of application can be extended in special cases, and attention should be paid to the diagnosis of fungal infections. The possibility of fungal infection should be considered when fever and other manifestations cannot be clinically explained by bacterial infection. Antifungal drugs can be applied empirically. At the same time, blood or body fluid fungal culture.
6. Endoscopic treatment of biliary pancreatitis: It is recommended that in conditional units, for patients with suspected or confirmed AP (biliary origin type). If indicators of severe disease are met. and/or have cholangitis, xanthogranuloma, dilated common bile duct, or those initially judged to be MAP but whose condition worsens during treatment, nasobiliary drainage or endoscopic duodenal papillary sphincterotomy (endoscopic sphincterotomy, EST) should be performed. The best time to perform ERCP is within 48-72 h of the onset of biliary SAP, while ERCP is feasible for biliary MAP during hospitalization.
7. Management of local complications: Most APFC and ANC can disappear on their own within a few weeks after the onset without intervention, and puncture and drainage is indicated only in case of co-infection. Most aseptic pseudocysts and WON can be self-absorbed, but a few have a diameter of >6 cm and have clinical manifestations such as compression, or can be treated with minimally invasive drainage when the diameter increases under continuous observation or when symptoms of infection appear. In case of peripancreatic abscess and/or infection, puncture and drainage is preferred, and if the drainage effect is poor, further surgical procedures are performed, and surgery is a relative indication. It is recommended that endoscopic puncture and drainage or endoscopic removal of necrotic tissue should be carried out in units that are in a position to do so.
8, the management of systemic complications: the occurrence of SIRS should be early application of ustekin or glucocorticoid kinase. CRRT can well remove the inflammatory mediators in the blood, while regulating fluid and electrolyte balance. Therefore, it is recommended for early use in SIRS complicated by AP; and there is a trend to gradually replace abdominal lavage treatment; antibiotics should be adjusted according to the results of drug sensitivity tests in those with bacteremia or sepsis, and the transition from broad-spectrum antibiotics to the use of narrow-spectrum antibiotics. SAP combined with ACS (abdominal septal compartment syndrome), should take active rescue measures, in addition to reasonable fluid therapy, the use of anti-inflammatory drugs. Hemofiltration, minimally invasive decompression and open decompression can also be used.
9, Chinese herbal medicine: single herbal medicine (such as raw rhubarb, mannitol), compound preparations (such as Qing pancreas soup, Chai Shao Cheng Qi Tang, etc.) have been proven effective in clinical practice. Chinese herbal preparations achieve therapeutic efficacy by reducing vascular permeability, inhibiting macrophage and neutrophil activation, and removing endotoxin.
10.Surgical treatment: In the early stage of AP, surgical treatment is not recommended except for severe ACS (abdominal septal compartment syndrome). In the late stage of AP, if combined with pancreatic abscess and (or) infection, surgical treatment should be considered.
11. Other measures: Analgesic treatment should be considered in case of severe pain. Pethidine hydrochloride (Duoduoleng) can be injected under close observation of the condition. Morphine or cholinergic receptor antagonists, such as atropine and scopolamine (654-2), are not recommended because the former will contract the sphincter of Oddi and the latter will induce or aggravate intestinal paralysis. Immune-enhancing agents and vasoactive substances, such as prostaglandin E1 agents and platelet-activating factor antagonists, can be considered for selective application in SAP. Probiotics can regulate intestinal immunity and correct dysbiosis in the intestine, thus re-establishing intestinal microecological balance, but it is still controversial whether patients with SAP should be treated with probiotics.