Severe acute pancreatitis (SAP) patients have severe disease and high mortality, and the body is in high metabolism, high catabolism and obvious negative nitrogen balance, so nutritional support is imperative; and the treatment of SAP patients often requires fasting, impaired gastrointestinal function, endotoxin and bacterial translocation, nutritional support can provide the body with essential nutrients, maintain the intestinal mucosa barrier, reduce the occurrence of complications, and support patients to pass the long course of the disease. barrier, reduce the occurrence of complications, and support patients to pass the long course of the disease; at the same time, the application of nutritional support makes the treatment mode of pancreatitis has also changed greatly, and the treatment effect has improved significantly, which is also a major progress in the treatment of pancreatitis.
The significance of nutritional support treatment for patients with severe acute pancreatitis
1.Pathophysiological changes
The main pathological basis of acute pancreatitis is the self-digestion of the pancreas and peripancreatic tissues by pancreatic enzymes, leading to pancreatic parenchyma or peripancreatic tissue necrosis and concurrent local (pseudocysts, pancreatic abscesses, etc.) and systemic complications (SIRS and MODS). Glucagon released from duodenal mucosa is the main hormone that stimulates pancreatic enzyme secretion, while cholecystokinin stimulates gallbladder contraction to secrete bile, which has the effect of activating pancreatic lipase. The amount of exocrine pancreatic secretion normally exists in the basal, cephalic, gastric and duodenal phases, and the amount of glucagon released from the intestinal mucosa stimulated by food breakdown products is less the farther away from the pylorus. Intra-jejunal infusion of neutral elemental diet has no significant effect on pancreatic secretion, while intragastric infusion of elemental diet also significantly promotes pancreatic secretion, which is caused by increased secretion of gastric acid and gastrin leading to increased secretion of pancreatin and glucagon, which stimulates massive pancreatic secretion.
The release of cytokines, the activation of complement and the production of arachidonic acid metabolites in SAP patients have a high metabolic response similar to sepsis, and the energy consumption can reach 3-4 times normal. In recent years, we applied the indirect energy meter to actually measure the energy consumption of SAP patients without infection increased by 1.2-1.5 times, and patients with other complications could be up to 2 times. The high catabolism of the organism leads to a large amount of skeletal muscle decomposition, and nitrogen loss is as high as 40-50g, which is equivalent to protein loss of 1200g.
50g, equivalent to a protein loss of 1200-1500g. Therefore, SAP patients are at high risk of malnutrition, while the incidence of hyperglycemia in SAP patients is high due to impaired pancreatic secretion and stress factors, which is closely related to the presence of insulin resistance, increased gluconeogenesis, increased reverse-regulatory hormones and other metabolic disorders in the body. In addition, about 10% of SAP patients themselves have hyperlipidemia, which is also one of the triggers for the development of SAP.
On the one hand, the organism is heavily depleted and the nutrient metabolism is disturbed, disturbing the internal homeostasis; on the other hand, SAP patients need to rest and consume significantly less nutrients due to the pancreas; this affects the energy metabolism and function of the organs and becomes one of the important causes of organ functional damage. Inflammatory necrosis of the pancreas often affects gastrointestinal function, so SAP patients often have severe gastrointestinal impairment, which is clinically manifested by varying degrees of nausea, vomiting, abdominal distension, abdominal pain, and diminished or even absent bowel sounds. It has been shown that damage to the intestinal barrier occurs earlier in SAP patients, and elevated abdominal pressure and fasting cause significant changes in intestinal mucosal morphology, shortened villi, weakened interepithelial junctions, and bacterial or endotoxin translocation is thought to be the cause of peripancreatic infection and MODS. Some patients also develop complications such as gastrointestinal bleeding, gastrointestinal fistula, enterocutaneous fistula, biliary fistula or pancreatic fistula and other intestinal tube injuries. Therefore, nutritional support is often used throughout the course of SAP, and it is important how to use a functional intestine for nutritional support and to use nutritional support to protect the intestinal mucosal barrier function and reduce infectious complications.
2. The significance of nutritional support therapy
Although nutritional support cannot change the pathological process of pancreatitis, it can enable the patient to pass the long course of the disease more smoothly, return to a transoral diet, and significantly improve the prognosis. Compared with conventional treatment without nutritional support, the mortality rate of SAP patients decreased significantly after the application of TPN. A retrospective analysis of 200 cases of acute pancreatitis by Feller showed that TPN reduced the mortality rate of SAP patients from 22% to 14%. In contrast, intra-jejunal EN in SAP has good nutritional tolerance, maintenance of immune response and intestinal integrity, and reduces bacterial and endotoxin translocation compared with TPN. In addition early EN reduces the degree of inflammation in the pancreas, decreases the incidence of infectious complications and reduces mortality in SAP [1].
Nutritional support has an important significance in patients with SAP in two ways:
(1) maintaining complete nutrition of the organism in gastrointestinal failure and severe disease conditions: (1) SAP patients are in a state of high metabolism and high catabolism, with a significant increase in energy consumption, providing reasonable nutritional substrates through appropriate pathways to minimize the decomposition of body tissues and prevent and reduce malnutrition; (2) correcting abnormal nutrient metabolism in SAP patients through appropriate pathways and the administration of special substrates, such as Hyperglycemia, hypoproteinemia, low calcium and low magnesium, etc.; ③ almost all SAP have different degrees of intestinal dynamics and barrier dysfunction (intestinal paralysis, delayed gastric motility and duodenal stasis), some patients have intestinal tube damage, gastrointestinal function can only gradually recover after a long time, nutritional support throughout the whole process of SAP treatment;
(2) positive blocking effect on the pathological process of disease deterioration: ④ fasting gastrointestinal decompression, nutritional support application, leaving the pancreas at rest, reducing pancreatic secretion, reducing pancreatic enzyme activation and corrosion of the pancreas and surrounding tissues, preventing the continued development of peripancreatic inflammation; ⑤ early enteral nutrition helps to improve the intestinal mucosal barrier, reduce endotoxin and bacterial translocation, reduce the inflammatory response, and reduce the occurrence of late SAP patients (5) Early enteral nutrition helps improve the intestinal mucosal barrier, reduce endotoxin and bacterial translocation, reduce the inflammatory response, and reduce the occurrence of infection and MODS in the later stages of SAP. (6) Meanwhile, the administration of many special nutrients (glutamine, ω-3 fatty acids, etc.) can regulate the inflammatory immune response and enhance the intestinal mucosal barrier.
Implementation of nutritional support for patients with severe acute pancreatitis
1. Indications for nutritional support in severe acute pancreatitis
Acute pancreatitis patients with different severity, the 1992 Atlanta diagnostic criteria are divided into mild acute pancreatitis and heavy acute pancreatitis, the former usually improves quickly after non-surgical treatment, most of which do not need or short-term nutritional support transition. Although most patients with severe acute pancreatitis have good nutritional status before the onset of the disease, they are at high risk of malnutrition and need nutritional support after the onset of the disease. 2002 American society of parenteral and enteral nutrition (American Society of Parenteral and Enteral Nutrition)
society of parenteral and enteral nutrition (ASPEN) incorporated nutritional support into the guidelines in 2002, stating that patients with SAP who need or may need nutritional support need to be identified through nutritional evaluation, and that nutritional support must be provided if patients with SAP have insufficient oral intake of nutrients for 5 to 7 consecutive days based on evidence-based principles [2]. The European society of parenteral and enteral
The European society of parenteral and enteral nutrition (ESPEN) also pointed out that nutritional support is an important treatment for SAP patients [3]. 2004, the Nutrition Support Group of the Chinese Society of Medical Surgery proposed the indications of nutritional support for SAP patients, which is based on the evaluation of the nutritional status of SAP patients, the number of days of fasting and the comprehensive judgment of the condition, course and prognosis to determine whether the patient has malnutrition or malnutrition risk, and if so, nutritional support should be provided [4].
2. The timing of starting nutritional support in severe acute pancreatitis
As early as the 1980s, the time to start nutritional support for SAP patients was about 1 month after the onset of SAP, and in the mid and late 1990s it was gradually advanced to 2 weeks after the patient was admitted to the hospital; recently, it was proposed to start 5-7 d after the patient was admitted to the hospital, or even as early as 2-3 d after admission. especially whether PN exacerbates metabolic disturbances of SAP nutritional substrates, endostasis imbalances and whether EN potentially exacerbates SAP or prolongs the course of the disease. A review of studies suggests that starting parenteral nutrition (PN) within 24 h of admission in SAP patients would be prognostically unfavorable, whereas applying PN after full fluid resuscitation would improve the prognosis. Other studies also suggest that PN should be chosen and started after 5 d. And our study also showed that SAP patients should start nutritional support early with hemodynamic and cardiopulmonary stability, and SAP patients who started PN 72 h after admission had significantly lower complications and mortality residence than those who started after 72 h. SAP patients have excessive systemic inflammatory response in the acute phase, and often have major complications such as shock, acute respiratory distress syndrome, pancreatic encephalopathy, and even MODS. SAP patients are often in good nutritional status, and the contradiction of insufficient nutrient intake is not prominent; at the same time, due to metabolic hormone disorders and inflammatory mediators, the body has varying degrees of organ dysfunction and poor tolerance to exogenous nutrients. Therefore, fluid resuscitation is performed at the beginning of treatment to suppress pancreatic secretion, maintain organ function, and prevent serious complications such as shock, acute renal dysfunction, and abdominal septal syndrome.SAP patients need nutritional support, which should be performed under the premise of stable vital signs, hemodynamic and endostasis stability.
However, PN has a high incidence of catheter infections and other metabolic complications, so the application of enteral nutrition (EN) in SAP patients is becoming more and more urgent, and it is now believed that intrajejunal infusion of nutrition does not increase pancreatic fluid It is now believed that enteral nutrition infusion does not increase pancreatic fluid secretion, that a nasojejunal nutrition tube can be placed under the Treitz ligament under endoscopic or X-ray guidance, and that establishing a suitable EN route to give a certain nutritional formula is the key to implementing EN. The early view was that premature administration of gastrointestinal diet would cause recurrence of pancreatitis symptoms because gastric and duodenal delivery of nutrition could significantly increase pancreatic fluid secretion. However, in recent years, with the advancement of technology in establishing EN access, the placement of nutrition tubes to the upper jejunum and infusion of EN has been effective in overcoming the gastroduodenal dysfunction due to pancreatic inflammatory necrosis, and significant efficacy has been achieved.
The acute treatment of SAP course is anti-shock, maintenance of endostasis and organ function, with the main focus on replenishing water electrolytes. EN support can be started in about a week as gastrointestinal function is gradually restored and abdominal distension is reduced. Recent studies have also shown that enteral nutrition infused via nasojejunal tube at 48h-72h after the onset of the disease is also well tolerated by patients, with no adverse clinical reactions observed. It has also been shown that starting EN early in the disease is beneficial for the body to regulate the stress response, promote recovery and produce a better prognosis, and it is suggested that replacing PN with EN is the new “gold standard” of nutritional therapy. We believe that for most SAP patients, early nutritional support is necessary to improve the patient’s defense, reduce malnutrition-related complications and promote recovery, but only if the internal environment is stable, especially for SAP patients should not be rushed, and stabilization of vital signs is still the first priority, otherwise it will increase the metabolic burden of the body and is not conducive to the correction of internal environmental disorders. Once the gastrointestinal function is restored, it should be switched from PN to EN as soon as possible.
3. The way of nutritional support for severe acute pancreatitis
SAP patients start PN before the endostasis is stabilized and gastrointestinal function is restored, focusing on metabolic disorders such as hyperglycemia, hyperlipidemia, hypoproteinemia and hypocalcemia and hypomagnesemia. Since Feller proposed in 1974 that TPN could improve the prognosis of SAP patients, TPN was considered for quite a long time as the only nutritional modality in the treatment of SAP, but later studies also concluded that the rate of catheter infection was significantly higher in TPN patients without significant improvement in hospital days and complications, so the view in recent years has been that SAP patients are at high risk of malnutrition in TPN is considered before recovery of gastrointestinal function in the acute phase and when complications such as combined gastrointestinal fistulas in the infected phase preclude the implementation of EN, and that TPN containing sugar and fat is more conducive to improving negative nitrogen balance in patients with SAP.
Once gastrointestinal function starts to recover, SAP patients should be given EN in time and find ways to establish EN access, and EN is the most important mode of late nutritional support for SAP patients. Foreign studies of the effects of PN and EN in SAP patients have shown that although there was no difference in the effects of the two on mortality and pain scores, patients in the EN group had reduced Ranson scores and significantly lower treatment costs and infection-related complications. National studies have also shown that EN can significantly reduce a range of inflammatory indicators such as SIRS, CRP levels and cytokines, and improve APACHEII scores and severity of disease in SAP patients relative to PN. This is related to the ability of TPN to affect metabolic adaptations by amplifying the anti-hormonal regulatory response and enhancing systemic and visceral formation of pro-inflammatory cytokines. In contrast, EN improves the shortening of intestinal villi and disruption of intestinal barrier integrity in patients with fasting and TPN, increases intestinal SIgA production, and regulates the immune function of the body [5].
The main manifestations of SAP patients around 2 weeks to 2 months into the disease course are widespread peripancreatic and retroperitoneal bacterial or fungal infections, sepsis and its mediated MODS. EN is preferred for nutritional support in patients at this stage, and parenteral nutrition is considered only when enteral fistulae exist and enteral nutrition cannot be implemented. Saline is infused before the infusion of EN to promote intestinal peristalsis, and then the infusion rate is regulated by an enteral nutrition infusion pump and gradually increased to the required level. The nutritional formula is gradually transitioned from elemental camp to whole protein nutrition, and gastrointestinal motility drugs can be added to increase the tolerance of the gastrointestinal tract to enteral nutrition. At the same time, pancreatic enzyme preparations are given, and the collection of bile or pancreatic fluid is drained back to increase the digestion and absorption of nutrients, and the improvement of nutritional support is obvious. After 2-3 months, some patients have posterior peritoneal or intra-abdominal residual pus cavity, often with poor drainage and long-lasting sinus tracts, and individual patients with gastrointestinal fistulas, at this time, EN provides patients with sufficient nutrients to promote the body to restore positive nitrogen balance and promote wound and sinus tract healing. In this case, EN can provide sufficient nutrients to promote the restoration of positive nitrogen balance, promote the healing of wounds and sinus tracts, or support definitive surgery.
4. The need for nutritional support in severe acute pancreatitis
In the acute phase of SAP, the presence of high metabolism and high catabolism in the patient is almost inevitable, so the principle of nutritional support at this stage is to correct the metabolic disorder and reduce the loss of protein to a reasonable level as much as possible, neither to cause additional catabolism in the organism due to insufficient nutrients, nor to add an inappropriate load to the respiratory and circulatory system and liver due to unreasonable nutritional support is the goal of nutritional therapy. Nutritional route is based on parenteral nutrition, caloric intake at 1.0-1.1 times REE or about 20kcal・kg・d, nitrogen amount 0.2-0.24g・kg・d, under the condition of strict detection of blood lipids, fat emulsion can be applied to patients without hyperlipidemia, and if the fat profile is good, the sugar-lipid ratio can reach 5:5.
Once the gastrointestinal function of SAP patients is restored, enteral nutrition pathway will be established in time and EN will be given. at this time, there is malnutrition in the body, and the recovery of the function of each organ system is closely related to the recovery of nutritional status. at the same time, due to the recovery of organ function, each system can gradually tolerate the increased load of improving nutrition. At this time, the nutrients provided must exceed the nutrients consumed by the organism in order to obtain a positive balance of energy and nitrogen. Therefore, the focus of nutritional support at this stage is to increase the nutritional intake and obtain positive nitrogen balance, the total caloric intake should be 1.2-1.5 times REE or about 30-35kcal・kg・d, and the nitrogen quantity is 0.2-0.24g・kg・d. The nutritional route should be mainly enteral nutrition as far as possible, and find ways to establish the jejunal nutritional route, and the caloric and nitrogen quantity of nutritional support can be further increased after 2 months. The energy supply can be increased to 1.5-2.0 times REE or about 35-40kcal/kg・d and 0.25-0.3g/kg・d of nitrogen, and eventually transition to transoral diet.
In recent years, research on the application of immune nutrition in SAP patients is of interest. TPN with glutamine can significantly maintain the intestinal barrier in SAP patients, reduce endotoxin and bacterial translocation; and improve leukocyte function and reduce the release of pro-inflammatory mediators. Nutritional support enriched with fish oil reduces the inflammatory response and improves the prognosis of ARDS patients, making the application of fish oil in SAP promising.
Although nutritional support cannot change the prognosis of SAP patients, its role in disease treatment cannot be ignored. Nutritional support, especially EN, can prevent or treat malnutrition, reduce the incidence of infection, reduce immune suppression, and support patients through the long course of the disease in SAP patients without aggravating the stimulation of pancreatic secretion. In the future, we still need more studies to further clarify the significance of nutritional support in the treatment of patients with SAP and to standardize its implementation.