In order to facilitate the estimation of prognosis and guide treatment, acute pancreatitis (AP) is often divided into mild AP and severe AP (SAP). The mild type accounts for 80% of the cases, causing only very mild organ dysfunction and smooth clinical recovery. In severe cases, shock, ARDS, renal insufficiency and other multi-organ and systemic insufficiency, and even death, require active monitoring and treatment.
I. Diagnosis and severity of AP
The diagnosis of AP mainly relies on clinical manifestations, blood and urine amylase and CT and other auxiliary examinations. In clinical practice, it is important not only to make the diagnosis of AP, but also to distinguish between SAP and mild AP. AP has a variety of different clinical classifications because of its complex etiology, different degrees of severity, and inconsistent clinical course. The “Clinically Based Classification of AP” developed at the 1992 Atlanta International Symposium on Pancreatitis represents the current level of understanding of pancreatitis and was revised again at the 1999 Santorini Conference in Greece. SAP is defined as AP with organ dysfunction, or those with local complications such as necrosis, abscess or pseudocyst, or both.SAP can be with (grade II) or without organ dysfunction (grade I), and local complications include acute pancreatic pseudocyst, acute fluid accumulation, pancreatic and peripancreatic tissue necrosis and pancreatic abscess, which are relatively simple, objective and accurate criteria.
In addition, about 25% of SAP cases develop uncontrollable multi-organ failure early in the course of the disease, with a lack of effective clinical treatment and a mortality rate of 30-60%, which most scholars call fulminant acute pancreatitis (FAP). Although there were differences in the concept and diagnostic criteria of FAP, FAP has received much attention in recent years because of its aggressive onset, many complications and high mortality. With the in-depth study of SAP, scholars at home and abroad have gradually realized that the occurrence of early organ dysfunction is closely related to the waterfall-like cascade reaction caused by cytokines and other inflammatory mediators, and the role of cytokines in the early stage of SAP cannot be ignored. Isenmann and Beger reported a group of patients with SAP who were hospitalized within 72 hours and developed organ dysfunction, which was called early severe AP ( Early severe acute pancreatitis (ESAP), with a mortality rate of 42%. A retrospective study of 209 cases of SAP admitted within 72 hours of onset at Xuanwu Hospital, Capital Medical University, showed that 56 cases of organ dysfunction (i.e., FAP) occurred within 72 hours of onset, with a mortality rate of 26.7% (8/30) within three days and 53.3% (16/30) within one week.
FAP has the following clinical characteristics: (1) rapid progression of the disease with progressive multi-organ dysfunction of the lungs, cardiovascular and kidneys; (2) early onset of uncorrectable hypoxemia; (3) high incidence of abdominal compartment syndrome (ACS); (4) high incidence of late complications such as pancreatic infection; (5) high CT score of pancreatic damage; (6) poor prognosis and high early mortality. High. high risk factors associated with mortality in FAP are early hypoperfusion of tissues and organs, hypoxemia and number of organ dysfunctions.
The severity of AP depends on the extent of pancreatic necrosis and the presence or absence of local complications such as infection and systemic complications such as ARDS and other organ dysfunction. It is necessary to determine the severity and extent of pancreatic lesions and other organ involvement based on appropriate clinical, biochemical and imaging studies, which can help in the selection of treatment options and prognosis. Since the introduction of Ranson’s criteria in 1974, new methods have been introduced, which reflects the increasing level of understanding of AP. For example, Imrie, Bank criteria, Agarwal and Pitchumoni simplified prognostic criteria, Japanese and Hong Kong criteria, APACHE II score and Balthazar CT grading system. Inflammatory markers such as C-reactive protein, IL-1β, IL-6, IL-8, trypsinogen-activated peptide (TAP) and tumor necrosis factor (TNF) are of limited use in determining the severity of AP, and it still seems that C-reactive protein (CRP) is relatively more specific, longer lasting, and easy to perform. The ideal index for determining the severity of AP should meet the following conditions: (i) high positive predictive value and sensitivity; (ii) appearing early in the course of the disease (<48 hours); (iii) easy to perform; and (iv) objectivity. Although many studies have been devoted to the exploration of this aspect in recent years, unfortunately, no single indicator has yet met all of the above conditions. At present, the more accurate criteria for judging the severity of SAP are often clinically based, combined with the combined application of multiple indicators, such as the combination of APACHE II score and Balthazar CT grading system.
Second, the treatment of SAP
In 2002, the International Society of Pancreatic Diseases adopted an evidence-based medicine approach and formulated the Guidelines for the Surgical Management of AP, whose 11 recommendations have important guiding significance for the treatment of SAP. However, clinical medicine is a practical and highly variable science, so some problems cannot be completely solved by the evidence-based medicine approach. Many empirical measures for the treatment of pancreatitis are not based on the evidence-based approach, but are still applied clinically. the general principles of SAP treatment are to try to stop further progression of the disease, systemic support, prevention and treatment of various complications. FAP has a very high risk of developing into MODS with a very high mortality rate, so in addition to maximum ICU monitoring and treatment of organ dysfunction, treatment should also be tailored to the characteristics of FAP.
(I) Basic treatment
1, supportive treatment: (1) replenishment of blood volume, hemodynamic monitoring, correction of water-electrolyte disorders: although non-invasive hemodynamic monitoring and central venous pressure monitoring can be applied, Swan-Ganz catheter is still the best way to evaluate the appropriateness of the amount of rehydration and the ability of the heart to withstand fluids, while the hourly urine volume, urine specific gravity and red blood cell pressure (generally around 32%) should be monitored. In the early course of SAP, patients with “internal burns” mostly have a large amount of blood volume loss into the third interval in a short period of time, so special attention should be paid to preventing shock, stabilizing hemodynamics and preventing the occurrence of multi-organ tissue hypoperfusion damage in the early course of the disease. Pancreatic necrosis, damage to the gastrointestinal mucosa and bacterial translocation, and the occurrence of cardiopulmonary and renal insufficiency are all related to hypoperfusion and hypoxia. Rapid and appropriate volume expansion is essential, and the daily volume of rehydration should often exceed 5-6L, especially the supplemental colloid fluid including plasma substitutes should account for about 1/3 of the total intake, while ensuring blood pressure and urine volume, and should try to keep “dry”. Mannitol helps to protect renal function and has the effect of antioxidant free radicals, so it should be given appropriately. (2) Correction of hypoxemia: For respiratory insufficiency, continuous positive pressure assisted ventilation should be given early to correct hypoxemia. If the respiratory rate is still fast after treatment and hypoxia does not improve, tracheal intubation ventilator support should be performed as early as possible. Initially, the main changes in the respiratory system are mainly manifested by ARDS, and with the continuation of the disease, respiratory lung injury and lung infection can occur on the basis of ARDS, and even the presence of lung infection foci can become the main cause of further deterioration of SAP. Therefore, the monitoring and treatment of the respiratory system is mainly aimed at the development of ARDS during the inflammatory response period, and at the continued deterioration of ARDS and the combined lung infection during the infection period. (3) Nutritional support: Patients in the early stage of SAP show disorders of sugar and fat metabolism and large amounts of muscle protein loss, while patients are in high catabolism, and exogenous high caloric nutrients further promote metabolic disorders, so nutritional support must be carried out in a stable systemic condition, which can support patients through the long and dangerous course of the disease and play an important role in maintaining cellular metabolism and organ function. Parenteral nutrition (TPN) is used first in the early stage, and enteral nutrition (EN) is given after the intestinal function is restored to replenish sufficient calories, reduce the body’s consumption, enhance the body’s ability to resist infection and promote tissue repair. Especially, transjejunal EN can maintain the intestinal mucosal barrier and prevent or reverse the damage of the intestinal mucosal barrier; and it can avoid the exocrine stimulation of the pancreas in the head, stomach and duodenal phase, so that the pancreas can remain relatively quiescent. Generally, 20kcal/kg.d of calories should be given in the early stage (especially in the first 4-5 days of the disease), and then gradually increase the calories to 30~35kcal/kg.d. (4) Prevention and control of infection: pancreatic necrosis is prone to secondary infection. Once SAP is diagnosed, preventive antibiotics should be given early, and broad-spectrum antibiotics that can pass the blood-pancreatic barrier and are effective against common intestinal bacteria should be used. The drug should be administered through the arterial cannula as much as possible to increase the concentration of the drug received by the pancreas and reduce the incidence of pancreatic infection. In case of secondary infection, sensitive antibiotics should be selected according to culture and drug sensitivity results. If you have been using the drug for too long or have a fungal infection, you can use antifungal drugs such as Dafukang, but it is not a broad-spectrum antifungal drug, so you must further identify the type of fungus, and if necessary, use the broad-spectrum antifungal drug amphotericin B. Systemic fungal infection is also one of the main causes of death in the late stages of SAP, and should be taken seriously.
2.Analgesia: pain relief with dulcolax, etc.
3, inhibition of exocrine pancreatic secretion: fasting, gastrointestinal decompression, the use of drugs that inhibit pancreatic secretion such as H2 receptor antagonists, acid suppressants and growth inhibitors.
4, pancreatic enzyme inhibitors: Although they are applied, there is not enough evidence to prove that peptidase, gabester and fresh frozen plasma have a definite therapeutic effect. Fresh frozen plasma can increase pancreatic enzyme inhibitors and can increase blood volume, so it is recommended to apply.
5, early to promote the recovery of gastrointestinal function: early application of magnesium sulfate, Da Cheng Qi Tang and Du Mi Ke can promote gastrointestinal peristalsis, reduce intra-abdominal pressure, and can reduce bacterial overgrowth, protect the function of the gastrointestinal barrier, reduce the displacement of bacteria and endotoxin; can also promote the absorption of abdominal exudate. Magnesium sulfate can also reduce the chance of bacterial infection by promoting bile excretion and reducing bacterial infection. Abdominal physical therapy, etc. can also promote the recovery of gastrointestinal function.
6, early hemofiltration: has the role of stabilizing hemodynamics and the internal environment, early removal of excessive cytokines and other inflammatory mediators, may be conducive to reducing the systemic inflammatory response, improve the function of the heart, lungs and kidneys and other organs, so that the severity of the disease can be reduced.
7, CT examination: CT can show the extent and scope of pancreatitis lesions, repeated CT examination can understand the changes in pancreatic lesions and also predict the possibility of secondary infection, if necessary, CT-guided fine-needle aspiration (FNA) bacteriological examination is feasible to determine the presence of pancreatic infection.
8, the application of glucocorticoids: most FAP patients have systemic inflammatory response syndrome (SIRS), which is caused by the interaction between multiple inflammatory cytokines, and there is no specific treatment method because the mechanism is unclear. In recent years, for those with unstable circulation, we have used small doses of continuous administration until the circulation is stable. If hydrocortisone is available, 200mg is given first, then 0.16mg/kg/h is administered continuously, generally applied for no more than 7 days, and the drug is discontinued once the blood pressure is stable.
9. Relief of abdominal hypertension: The diagnosis of ACS can be clarified if the intra-abdominal pressure is greater than 15 mmHg, accompanied by reduced cardiac output or progressive oliguria, and hypoxia in the presence of normal or increased peak airway pressure. Intra-abdominal pressure can be indirectly reflected by simple cystometry, and FAP intra-abdominal hypertension is predominant. Intra-abdominal hypertension can affect the function of the lungs, heart, kidneys and liver, inducing or aggravating organ dysfunction, so the function of the heart, lungs, kidneys and other important organs should be closely monitored. ACS is divided into two types, one type is dominated by fluid accumulation in the abdominal cavity, accompanied by edema of the mesentery, omentum, intestinal canal and retroperitoneum, early laparoscopic administration of abdominal flushing and drainage can reduce intra-abdominal high pressure, and at the same time dilute and drain the abdominal exudate containing pancreatic fluid and inflammatory mediators out of the abdominal cavity, reducing The systemic inflammatory response can be reduced, and the inhibitory effect of peristalsis on intestinal motility by abdominal exudate can also be reduced. The other type is caused by intestinal paralysis and pneumatization of the gastrointestinal tract, and the treatment of this type of ACS should pay attention to the restoration of gastrointestinal function. Generally speaking, those with early remission of ACS will recover faster and have a good prognosis.
(B) Early identification of secondary pancreatic infections
Secondary pancreatic infection includes infected pancreatic necrosis and pancreatic abscess, especially infected pancreatic necrosis is often accompanied by systemic physiological disorders, high mortality, diagnosis can first dynamic CT examination, if there are bubbles can be diagnosed infection, such as no bubbles and clinical suspicion of secondary pancreatic infection, CT-guided fine needle aspiration can be early diagnosis of pancreatic infection, this method is simple, safe and reliable, is the early diagnosis of pancreatic infection. It is the most reliable method for early diagnosis of pancreatic infection. The puncture site can be chosen via the anterior abdominal wall, lateral abdominal wall or paraspinal, and the color and properties of the puncture fluid can be observed, along with bacteriological examination including smear and culture (common, anaerobic and mycobacterial culture). In case of multiple foci care should be taken to puncture at multiple sites to avoid false negatives; and avoid the gastrointestinal tract to avoid false positives. Postoperative hyperthermia or rehyperthermia requires additional CT or puncture to look for foci of infection.