The organism can undergo a series of pathophysiological changes, including changes in substance metabolism and energy metabolism, in the presence of starvation or trauma, which are regulated by neuro-endocrine regulation. Nutritional support treatment needs to adapt to these changes.
I. Metabolic changes during starvation
The metabolic response of the organism to starvation is to regulate the energy needs of the organism. Reduce activity and lower basal metabolic rate. Reduction of energy expenditure and thus of the breakdown of the body composition. Although the metabolic changes induced by starvation alone are different from those induced by severe trauma or disease, the sole purpose of their responses is to maintain survival.
1, endocrine and metabolic changes In order to make the body better adapt to the starvation state, many endocrine substances are involved in this response. The main ones are insulin, glucagon, growth hormone, catecholamines, thyroxine, adrenocorticotropic hormone and antidiuretic hormone. Changes in these hormones directly affect the body’s metabolism of carbohydrates, proteins and fats. During starvation, blood sugar drops. In order to maintain constant glucose metabolism, insulin secretion immediately decreases and glucagon, growth hormone and catecholamines secretion increases to accelerate glycogenolysis and increase gluconeogenesis. With the prolongation of starvation, the changes of the above hormones can prompt the mobilization of amino acids from muscles and the increase of hepatic gluconeogenesis, thus increasing the gluconeogenesis, but already consuming the body proteins at the same time. When starvation, governed by endocrine, the body fat hydrolysis increased, and gradually become the most important energy source of the body. Making full use of fat energy and minimizing gluconeogenesis, i.e., reducing protein decomposition, is the body’s own protective measure for survival in the late stage of starvation. Reflected in the changes in urinary nitrogen excretion, about 8.5g a few at the beginning, the late stage of starvation is reduced to 2-4g / d.
2, the body composition changes starvation can lead to significant changes in the composition of the body, including water loss, a large number of fat decomposition. Protein is inevitably broken down, so that the weight of tissues and organs to reduce the function. Such changes involve all organs, such as loss of renal concentration capacity, loss of hepatic protein, delayed gastrointestinal emptying movements, reduced secretion of digestive enzymes, and atrophy of intestinal epithelial cells. Prolonged starvation can reduce the ventilation and ventilatory capacity of the lungs, and the heart atrophies and decreases its function. Eventually, it can lead to death.
Second, the metabolic changes after trauma and infection
1.Neural and endocrine reactions Peripheral stimuli such as trauma are transmitted to the hypothalamus, and the latter then undergoes a series of reactions through neuro-endocrine. At this time, the sympathetic nervous system is excited, insulin secretion is reduced, adrenaline, norepinephrine, glucagon, adrenocorticotropic hormone, adrenocorticotropic hormone and anti-diuretic hormone secretion are increased.
2. Changes in body metabolism Under the effect of antidiuretic hormone and aldosterone, water and sodium are retained to preserve blood volume. Trauma and infection can cause imbalance of water, electrolytes and acid-base balance. Sympathetically induced hypermetabolic state increases the resting energy expenditure (XingE) of the body. The REE of a normal adult is about 104.6ld(25kcal)/(kg, d), but in case of trauma and infection, the REE can increase by 20% to 40% depending on the severity, and only in case of large burns the REE increases by 50% to 100%. The increase in REE is not large, about 10%, for the usual elective surgery. The right amount of energy provision is necessary for anabolism during trauma and infection. The body’s utilization of sugar decreases during trauma, and it is prone to hyperglycemia, and glycosuria. Protein decomposition increases, urinary nitrogen excretion increases, and negative nitrogen balance occurs. The process of gluconeogenesis is active, and lipolysis increases significantly.
3, enteral nutrition, where the function of the gastrointestinal tract is normal, or the presence of partial function, nutritional support should be preferred enteral nutrition (enteral nutrition, EN). The enteral nutrition preparation is absorbed into the liver through the intestine, and the various components required by the organism are synthesized in the liver, and the whole process is in accordance with physiology. The liver can play a detoxifying role. The direct stimulation of food helps to prevent intestinal mucosa atrophy and protects intestinal barrier function. Some nutrients in food (glutamine) can be directly used by mucosal cells, which is conducive to their metabolism and proliferation. The absence of serious complications of enteral nutrition is also an obvious advantage.
(I) Enteral nutrition preparation
In order to fit the metabolic needs of the organism, EN preparations are complete in composition, including carbohydrates, proteins, fats or their breakdown products, and also contain physiologically required amount of electrolytes, vitamins and trace elements, etc. The preparations are divided into two types: powder and solution, the former to be used after adding water. The final concentration of the two solutions is 24%, which can provide energy 4.18bJ (1kcal) / mi. According to the needs of the disease, EN preparations can be broadly divided into two categories.
1, the whole protein-based preparations The protein source is casein or soy protein, the carbohydrate source is maltose, dextrin, and the fat source is corn oil or soybean oil. Does not contain lactose. The osmotic volume (pressure) of the solution is low (about 320mmol/L). Suitable for people with normal gastrointestinal function.
2.Protein hydrolysis product (or amino acid)-based preparation The protein source is whey protein hydrolysis product, peptides or crystalline amino acids, the carbohydrate source is oligosaccharides, dextrin, and the fat source is soybean oil and medium-chain triglycerides. It also does not contain lactose. The osmolality (pressure) is high (470-850mmol/L). It is suitable for people with gastrointestinal digestion and malabsorption.
Some preparations also contain glutamine, dietary fiber, etc. The latter refers to soluble pectin, etc.
It has the effect of adjusting intestinal dynamics and stimulating the proliferation of intestinal mucosa. Fiber is broken down by bacteria in the colon into short-chain fatty acids (SCFA), which can be absorbed for energy. New products also include preparations for severe stress, diabetes, and cancer, as well as preparations for immune enhancement.
(II) Implementation of enteral nutrition
Since enteral nutrition preparations have special odor, patients are often reluctant to take them orally, or the amount taken orally cannot reach the therapeutic dose, so the implementation of EN basically requires input via catheter. The most commonly used is the nasogastric tube, but there are also nasoduodenal and nasojejunal tubes, which allow the nutrient solution to enter the intestine directly. A jejunostomy tube is also a common route of infusion.
The infusion of nutrient solution should be slow and uniform, and the infusion rate is often controlled by an infusion pump. In order to adapt to the intestinal tract, it can be diluted to 12% concentration at the beginning and input at the rate of 50ml/h. After every 8-12 hours, the concentration and speed will be increased one by one to reach the full amount after about 3-4 days, i.e. 24% 100ml/h, and the total amount of liquid is about 2,000ml a day. When the room temperature is low, the nutrient solution should be warmed up appropriately.
The complications of enteral nutrition are not many and not serious, mainly include.
1. Misaspiration Because of the patient’s old age and weakness, coma or presence of gastric retention, when nutrition solution is input through nasogastric tube, it can lead to aspiration pneumonia due to misaspiration after eruption. This is a more serious complication. The preventive measure is to take the patient in 30~half-lying position and stop the infusion for 30 minutes after infusion of nutrition fluid. If the amount of retracted fluid >150ml, the presence of gastric retention should be considered and the infusion through nasogastric tube should be suspended and can be replaced by nasojejunal tube.
2.Distension and diarrhea Occurrence 3%~5%. It is related to the speed of infusion and concentration of the solution, and also related to the osmolarity of the solution. Infusion too fast is the main cause of symptoms, so slow input should be emphasized. For symptoms caused by high osmotic pressure, drugs such as tincture of opium can be given as appropriate to slow down intestinal peristalsis.
IV. Indications for enteral nutrition
1.Normal gastrointestinal function, but the nutrient intake is insufficient or cannot be ingested. Such as coma patients (traumatic brain injury, etc.), large area burns, after complex surgery and critical illness (non-gastrointestinal diseases), etc. These patients have basically normal gastrointestinal tract function and should try to use enteral nutrition support.
2.Patients with poor gastrointestinal tract function. For example, gastrointestinal fistula, short bowel syndrome, etc. The EN preparation used for GI fistula is mainly peptides, which can reduce the stimulating effect on the secretion of digestive juices. Nutritional solutions should preferably be infused to the distal intestine of the fistula or measures should be taken to temporarily seal the fistula opening of an extraintestinal fistula. If the EN solution input causes a large increase in the drainage of the enterocutaneous fistula, the loss will be more than compensated, and the measures should be adjusted, or the parenteral nutrition should be used instead.
Acute severe pancreatitis has a long course, and after stabilization (about 3 to 4 weeks after onset), EN preparations can be entered via jejunostomy tube or nasojejunal tube. The application of EN can avoid complications caused by parenteral nutrition and can prevent the occurrence of damage to intestinal barrier function and bacterial translocation.
3.The gastrointestinal function is basically normal but with other organ malfunction, such as diabetes mellitus or liver and kidney failure. In principle, as long as the gastrointestinal function is basically normal, these patients still belong to the indications of enteral nutrition. The degree of glucose metabolism disorder caused by enteral nutrition in diabetic patients is less than that of parenteral nutrition, and it is easy to control. Although enteral nutrition for liver and kidney failure has less effect on liver and kidney function, such patients often have different degrees of gastrointestinal dysfunction, and the tolerance of enteral nutrition is poor, so it is appropriate to reduce the amount of use.
Parenteral nutrition
All patients who cannot or should not take food by mouth for more than 5-7 days are indications for parenteralnutrition (PN). From the surgical point of view, preoperative application for malnourished patients, gastrointestinal fistula, acute severe pancreatitis, short bowel syndrome, severe infection and sepsis, large burns, and liver and kidney failure are all indications for the application of PN. The application of PN after complex surgery is beneficial for patient recovery, especially after major abdominal surgery. Application of PN to inflammatory intestinal diseases, such as ulcerative colitis and Crohn’s disease, rests the intestine and facilitates remission. Patients with malignant tumors will proliferate and develop tumor cells after nutritional support, so chemotherapy drugs need to be added along with nutritional support. The application of PN during chemotherapy or radiotherapy can supplement the deficiency of ingestion.
(I) Parenteral nutrition preparation
Glucose is the main energy substance of parenteral nutrition. All organs and tissues of the body can use glucose for energy, and supplementing with 100g/24h of glucose has a significant effect of saving protein. The abundance of sources and low price are also its advantages. The monitoring of blood glucose and urine glucose makes it possible to understand its utilization, which is quite convenient. However, the application of glucose also has a number of disadvantages. The first is that the glucose solution used for PN is often highly concentrated, the osmolality (pressure) of 25% and 50% glucose solution is as high as 1,262 and 2,525 mmolA. respectively, which is very irritating to the venous wall and impossible to infuse via peripheral veins. Secondly, the body’s ability to use glucose is limited, 5mg/(kg?min), excessive or too fast input may lead to hyperglycemia, diabetes, and even hypertonic non-ketotic coma. Many surgical patients with combined diabetes mellitus are more prone to glucose metabolism disorders. In addition, the body’s ability to utilize glucose decreases during stress, and excess glucose is converted to fat and deposited in organs, such as liver fat infiltration, which impairs its function. Therefore, a single source of glucose energy is no longer used during PN.
Fat emulsions are another important energy source for PN. With soybean oil or safflower oil as raw material and phospholipids as emulsifier, the emulsion made has good physicochemical stability and particle diameter similar to that of natural celiac particles. The energy density of the emulsion is large, 10% solution contains heat 4.18k)(1kcal)/mi. 10% solution is isotonic, can be input via peripheral veins. Its oxidation rate is unchanged and even accelerated during stress. Fat emulsions are safe and non-toxic, but attention needs to be paid to the method of use. When infusing alone, the speed should be slow, starting with lml/min. 500ml of infusion needs 5-6ho infusion too fast may cause chest tightness, palpitations or fever and other reactions. The maximum dosage of fat emulsion is 2g/(ks?d). Fat emulsions can be divided into long-chain triglycerides (LCT) and medium-chain triglycerides (MCI) according to the length of their fatty acid carbon chains, LCT contains essential fatty acids (EFAs) – linoleic acid, linolenic acid and arachidonic acid, which are commonly used in clinical practice. MCT is metabolized faster than LCT in the body, and the metabolic process does not depend on carnosine, and is rarely deposited in organs and tissues. However, MCT does not contain EFAs and can cause toxic reactions when large amounts are administered. Clinically, fat emulsions containing both LCT and MCT (1:1 weight ratio) are often used for special patients (e.g., hepatic dysfunction). New formulations of fat emulsions include: emulsions made from olive oil, which have less polyunsaturated fatty acids (PUFA) than LCT emulsions and can reduce immunosuppression caused by lipid peroxidation. In addition, the addition of vitamin E in the emulsion also has the effect of reducing lipid peroxidation.
3.Compound amino acid solution It is a crystalline, LCT amino acid solution prepared in a reasonable pattern (human milk or egg white). Its formula meets the needs of human anabolism and is the only nitrogen source for parenteral nutrition. There are two types of compounded amino acids: balanced and special. The balanced amino acid solution contains 8 types of EAA and 8-12 types of NEAA, whose composition meets the needs of normal body metabolism and is suitable for most patients. Special amino acid solutions are dedicated to different diseases, with necessary adjustments in the formula composition. For example, the preparation for liver disease contains more BCAA and less aromatic amino acids. Preparations for renal diseases contain mainly 8 essential amino acids and only a few non-essential amino acids (arginine, histidine, etc.). Preparations for severe trauma or critically ill patients contain more BCAAs or contain glutamine dipeptide, etc. With regard to glutamine, due to its poor water solubility and its instability in solution, it is easily denatured. For this reason, glutamine preparations for parenteral nutrition are currently made with glutamine dipeptides (e.g., glycyl-glutamine, alanyl-glutamine). The water solubility of this dipeptide is good and stable, and it can be quickly decomposed into glutamine and used by tissues after entering the body.
4.Electrolytes Potassium, sodium, chloride, calcium, magnesium and phosphorus need to be supplemented during parenteral nutrition. The relevant preparations, many of which are commonly used in clinical preparations, such as 10% potassium chloride, 10% sodium chloride, 10% calcium gluconate and 25% magnesium sulfate. Phosphorus plays an important role in anabolic and energy metabolism, parenteral nutrition of phosphorus preparations are inorganic phosphorus and organic phosphorus preparations, the former because of easy precipitation reaction with calcium and basically not used, organic phosphorus preparations for sodium glycerophosphate, containing phosphorus 10mmol / 10ml.
5, vitamins for parenteral nutrition of vitamin preparations are water-soluble and fat-soluble two, are compound preparations. Each injection contains the basic daily requirement of various vitamins for normal people.
6.Trace elements are also compound injections, each containing zinc, copper, manganese, iron, chromium, iodine and other trace elements, each containing the daily requirement of normal people.
7.Growth hormone The genetically recombinant human growth hormone has obvious anabolic effect. For special patients (burns, short bowel syndrome, intestinal fistula, etc.), the simultaneous application of growth hormone can enhance the effect of parenteral nutrition, facilitate wound healing and promote recovery. Pay attention to the indications and avoid the critical period after severe stress. The usual dosage is 8-12U?d, and it is generally not suitable for long-term use.
(B) Total nutrition mixture
There are more kinds of nutrients supplied by parenteral nutrition. From the physiological point of view, the method of mixing various nutrients outside the body in 3L plastic bags (called total nutrient mixture) and then inputting them is the most reasonable. The various nutrients that enter the body at the same time, each in its own way, are beneficial to anabolism. In addition, the high concentration of glucose can be diluted after mixing, and the osmotic pressure is reduced, making it possible to infuse via peripheral veins. Infusion after mixing makes the fat emulsion input per unit time much lower than the single bottle infusion of fat emulsion, which can avoid the side effects due to too fast infusion of fat emulsion. The total nutrition mixture is prepared in a sterile environment, and there is no need to exhaust and change the infusion bottle during use. The fully closed infusion system greatly reduces the chance of contamination. The preparation process of the total nutrition mixture should conform to the prescribed procedures and be under the responsibility of a dedicated person to ensure that the physicochemical properties of the fat emulsion in the mixture remain in a normal state.
In the basic solution, various electrolyte solutions are added as appropriate according to the condition and blood biochemical examination. Since the organism has no water-soluble vitamin storage, all parenteral nutrition solutions should be supplemented with compounded water-soluble vitamin injection. Short-term fasters do not have fat-soluble vitamin or trace element deficiencies, so they should only be supplemented if they have been fasting for more than 2-3 weeks. The solution needs to be supplemented with the appropriate amount of regular insulin (insulin: glucose 1U: 8 to 10g).
The composition of the nutrition solution should be changed for various special patients. Diabetes mellitus should be limited in the amount of glucose and adequately supplemented with exogenous insulin to control blood sugar. The dosage of fat emulsion can be increased to make up for the lack of energy supply. For patients with liver function abnormalities (elevated bilirubin and liver enzyme profile) in cirrhosis, the composition and dosage of parenteral nutrition solution should be adjusted. At this time, the liver’s ability to synthesize and metabolize various nutrients is greatly reduced, so the amount of parenteral nutrition solution should be reduced (about 1/2 of the full amount). Adjustments should also be made in nutritional preparations, including the use of amino acid solutions with high BCAA content and fat emulsions containing both LCT and MCT. In patients with significant hypoproteinemia, the ability of the liver to synthesize albumin is limited, so supplementation with human albumin is needed to correct hypoalbuminemia more quickly. In the nutritional solution for patients with renal failure, the amount of glucose and fat emulsion is generally not limited, while the amino acid solution is often chosen as EAA-based nephrotic amino acids. Unless dialysis conditions are available, water intake should be strictly limited.
(C) Input route of parenteral nutrition
Since the osmolarity of total nutrition mixture is not high, it is not difficult to infuse via peripheral vein, and it is suitable for those with small dosage and PN support for no more than 2 weeks. For long-term PN supporters, infusion via central venous catheter is appropriate. The catheter is often placed into the superior vena cava through the internal jugular vein or subclavian vein puncture. The total nutrition mixture often needs 12-16h infusion, or 24h continuous infusion.
(D) Complications of parenteral nutrition
To fully understand the complications of parenteral nutrition and take measures to prevent and actively treat them is an important part of the implementation of parenteral nutrition. Complications can be divided into three categories: technical, metabolic and infectious.
1.Technical complications This kind of complications is related to the placement or retention of central venous catheter. They include pneumothorax from puncture, vascular injury, nerve or chest tube injury, etc. Air embolism is the most serious complication, and once it occurs, the consequences are serious and even lead to death.
Metabolic complications Metabolic complications can be summarized into three aspects: inadequate supplementation, abnormal glucose metabolism, and parenteral nutrition itself.
The complications caused by insufficient supplementation are mainly
①Serum electrolyte disorders: In the absence of additional losses, parenteral nutrition requires about 50 mmol of potassium, 40 mmol of sodium, 20-30 mmol of calcium and magnesium, and 10 mmol of phosphorus per day. if electrolytes are lost due to the condition (e.g., gastrointestinal decompression, intestinal fistula), the amount of electrolyte supplementation should be increased. Hypokalemia and hypophosphatemia are very common in clinical practice.
② Micronutrient deficiency: more common is zinc deficiency, with clinical manifestations such as perioral and limb rashes, skin wrinkles and neuritis. Long-term parenteral nutrition may also produce small cell anemia due to copper deficiency; chromium deficiency may lead to uncontrollable hyperglycemia. For patients with long duration of disease, the routine addition of trace element injection to parenteral nutrition solution can prevent the occurrence of deficiency.
③Essential fatty acid deficiency (EFAD): if long-term parenteral nutrition is not supplemented with fat emulsion, essential fatty acid deficiency may occur. The clinical manifestations of EFAD include dry skin, scaly flaking, hair loss and delayed wound healing. The deficiency can be prevented by supplementing with fat emulsions only once a week.
Complications due to disorders of glucose metabolism are.
① Hypoglycemia and hyperglycemia: Hypoglycemia is caused by excessive use of exogenous insulin or sudden cessation of infusion of high concentration glucose solution (containing insulin). Since high concentration glucose solution is rarely infused alone, this complication is rare. Hyperglycemia is still common, mainly due to the rapid infusion of glucose solution or a decrease in the body’s sugar utilization rate. The latter includes diabetic patients and those with severe trauma and infection. Severe hyperglycemia (blood glucose concentration over 40 mmol/L) division leads to hypertonic non-ketotic coma, which is life-threatening. For those with hyperglycemia, insulin supplementation (ranging from 1U: 1 to 4g) should be added to the parenteral nutrition solution and blood glucose levels should be monitored at all times. In severe cases, sugar-containing solutions should be stopped immediately and hypotonic saline (0.45%) should be infused at a rate of 250 ml/h to reduce blood osmotic pressure. At the same time, insulin (10-20U/h) should be injected to promote the entry of sugar into the cells and lower the blood glucose level. It should be noted that hypokalemia, which often exists at the same time, should also be corrected.
②Liver function damage: There are many factors that cause liver function changes due to parenteral nutrition, the main reason is liver steatosis caused by glucose overload. The clinical manifestations are elevated blood bilirubin concentration and elevated transaminases. To reduce this complication, dual energy sources should be used, replacing some of the energy sources with fat emulsions and reducing the amount of glucose.
Complications arising from parenteral nutrition itself are.
(1) Bile sludge and stone formation in the gallbladder: long-term total parenteral nutrition (TPN) treatment, due to lack of food stimulation in the digestive tract and reduced secretion of intestinal hormones such as cholecystokinin, is prone to the formation of bile sludge in the gallbladder and then stone formation. The incidence of gallstones can be as high as 23% in those who have been on TPN for 3 months. Switching to enteral nutrition as early as possible is the most effective measure to prevent gallstones.
②Cholestasis and elevated liver enzyme profile: Some patients will have elevated serum bilirubin, ALT, AKP and r-GT values after PN. The causes of such biliary stasis and elevated enzyme values are multiple: glucose overload, lack of food stimulation in the intestine during TPN, massive depletion of glutamine in the body, and impaired intestinal barrier function that displaces bacteria and endotoxins can all affect liver function. The breakdown products of some components of the compounded amino acid solution (e.g. tryptophan) and the possible presence of antioxidants (sodium bisulfate) also have toxic effects on the liver. Usually these abnormalities caused by TPN are reversible, and TPN reduction or discontinuation (switching to enteral nutrition) can restore liver function.
③Decreased intestinal barrier function: Lack of food stimulation in the intestine and lack of glutamine in the body are the main causes of decreased intestinal barrier function. The serious consequence is the displacement of intestinal bacteria and endotoxin, which damages the function of liver and other organs and causes intestinal-derived infection, eventually leading to multi-organ failure. For this reason, early switch to enteral nutrition and supplementation of glutamine is an effective measure to protect the intestinal barrier function.
3.Infectious complications , the infectious complication of parenteral nutrition is mainly catheter-based sepsis. Its development is closely related to the technique of tube placement, catheter use and catheter care. The clinical manifestation is sudden chills and high fever, which can lead to infectious shock in severe cases. When no other foci of infection can be found to explain the chills and hyperthermia, catheter sepsis should be considered to have existed. After the occurrence of the above symptoms, first make bacterial culture and blood culture of the fluid in the infusion bag, discard the infusion bag and the infusion tube, and replace the infusion with a new one. Observe for 8 hours, and if the fever still does not subside, the central venous catheter should be removed and the culture of the catheter tip should be done. Usually no medication is needed after the catheter is removed, and the fever will subside on its own. If the fever does not subside after 24 hours, antibiotics should be used. Preventive measures for catheter sepsis include: placement of catheter should strictly comply with aseptic technique; avoid multi-purpose use of central venous catheter and should not be used for infusion of blood products, blood sampling and pressure measurement; application of fully closed infusion system with full nutrition mixture; regular catheter care after catheter placement, etc.
(E) Monitoring of parenteral nutrition
1. Systemic condition Any dehydration, edema, fever, jaundice, etc.
2.Serum electrolytes, blood glucose and blood gas analysis Measure daily, and after 3 days, once or twice a week depending on the stability.
3.Liver and kidney function measurement, once every 1~2 weeks.
4.Nutritional indicators including body weight, lymphocyte count, serum albumin, transferrin, prealbumin measurement, once every 1~2 weeks. Measure nitrogen balance when available.