Parenteral nutrition | |
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Parenteral nutrition (PN), or intravenous feeding, is the feeding of nutritional products to a person intravenously, [1] bypassing the usual process of eating and digestion. The products are made by pharmaceutical compounding entities or standard pharmaceutical companies. [2] [3] The person receives a nutritional mix according to a formula including glucose, salts, amino acids, lipids and vitamins and dietary minerals. [4] It is called total parenteral nutrition (TPN) or total nutrient admixture (TNA) when no significant nutrition is obtained by other routes, and partial parenteral nutrition (PPN) when nutrition is also partially enteric. It is called peripheral parenteral nutrition (PPN) when administered through vein access in a limb rather than through a central vein as in central venous nutrition (CVN). [5]
Total parenteral nutrition (TPN) is provided when the gastrointestinal tract is nonfunctional because of an interruption in its continuity (it is blocked, or has a leak – a fistula) or because its absorptive capacity is impaired. [6] It has been used for comatose patients, although enteral feeding is usually preferable, and less prone to complications. Parenteral nutrition is used to prevent malnutrition in patients who are unable to obtain adequate nutrients by oral or enteral routes. [7] The Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition recommends waiting until the seventh day of hospital care. [8]
Diseases that would require the use of TPN include: [8]
TPN may be the only feasible option for providing nutrition to patients who do not have a functioning gastrointestinal tract or who have disorders requiring complete bowel rest, including bowel obstruction, [9] short bowel syndrome, [9] gastroschisis, [9] prolonged diarrhea regardless of its cause, [9] very severe Crohn's disease [9] or ulcerative colitis, [9] and certain pediatric GI disorders including congenital GI anomalies and necrotizing enterocolitis. [10]
There are physical, physiological, or mental differences in the geriatric population that could potentially lead to poor nutrient intake that would require them to have nutrition therapy. [11] Geriatric patients are more inclined to have delayed muscle restoration compared to the younger population. Additionally, older patients are observed to have greater cardiac and renal impairment, insulin resistance, and to have deficiencies in vitamins and crucial elements. Patients who require nutrition therapy but have contraindications for or cannot tolerate enteral nutrition are appropriate candidates for parenteral nutrition. In the geriatric population, it is indicated if oral or enteral nutrition is impossible for 3 days or when oral or enteral nutrition is likely insufficient for more than 7 to 10 days. While there are no complications of parenteral nutrition specific to the geriatric population, complications are more prevalent in this population due to increased comorbidities. [12]
Patients who are diagnosed with cancer, whether as outpatient undergoing treatment or hospitalized, are at a greater risk of malnutrition and cachexia. Cancer-related malnutrition can be attributed to the decrease in food intake, increase in the need for energy, and the alteration of metabolism. [13] Patients should be assessed early on in their cancer treatment for any nutritional risk, such as by taking routine weights and BMI. Parenteral nutrition is indicated in cancer patients when it is not possible to access the digestive tract or if the tract is ineffective. In advanced cancer patients, the use of PN should be discussed in context of the risks and benefits, such as if the approximate survival rate is longer than 3 months and if PN would be expected to greatly improve the patients' quality of life. [13]
It is uncertain whether home parenteral nutrition improves survival or quality of life in people with malignant bowel obstruction. [14]
Short-term PN may be used if a person's digestive system has shut down (for instance by peritonitis), and they are at a low enough weight to cause concerns about nutrition during an extended hospital stay. Long-term PN is occasionally used to treat people suffering the extended consequences of an accident, surgery, or digestive disorder. PN has extended the life of children born with nonexistent or severely deformed organs.
Approximately 40,000 people use TPN at home in the United States, and because TPN requires 10–16 hours to be administered, daily life can be affected. [15] Although daily lifestyle can be changed, most patients agree that these changes are better than staying at the hospital. [16] Many different types of pumps exist to limit the time the patient is "hooked up". Usually a backpack pump is used, allowing for mobility. The time required to be connected to the IV is dependent on the situation of each patient; some require once a day, or five days a week. [15]
It is important for patients to avoid as much TPN-related change as possible in their lifestyles. This allows for the best possible mental health situation; constantly being held down can lead to resentment and depression. Physical activity is also highly encouraged, but patients must avoid contact sports (equipment damage) and swimming (infection). Many teens find it difficult to live with TPN due to issues regarding body image and not being able to participate in activities and events. [15]
TPN fully bypasses the GI tract and normal methods of nutrient absorption. Possible complications, which may be significant, are listed below. Other than those listed below, common complications of TPN include hypophosphatemia, hypokalemia, hyperglycemia, hypercapnia, decreased copper and zinc levels, elevated prothrombin time (if associated with liver injury), hyperchloremic metabolic acidosis and decreased gastrointestinal motility. [8]
TPN requires a chronic IV access for the solution to run through, and the most common complication is infection of this catheter. Infection is a common cause of death in these patients, with a mortality rate of approximately 15% per infection, and death usually results from septic shock. [17] When using central venous access, the subclavian (or axillary) vein is preferred due to its ease of access and lowest infectious complications compared to the jugular and femoral vein insertions. [6]
Catheter complications include pneumothorax, accidental arterial puncture, and catheter-related sepsis. The complication rate at the time of insertion should be less than 5%. Catheter-related infections may be minimised by appropriate choice of catheter and insertion technique. [18]
Chronic IV access leaves a foreign body in the vascular system, and blood clots on this IV line are common. [19] Death can result from pulmonary embolism wherein a clot that starts on the IV line breaks off and travels to the lungs, blocking blood flow. [20]
Patients on TPN who have such clots occluding their catheter may receive a thrombolytic flush to dissolve the clots and prevent further complications.
Fatty liver is usually a more long-term complication of TPN, though over a long enough course it is fairly common. The pathogenesis is due to using linoleic acid (an omega-6 fatty acid component of soybean oil) as a major source of calories. [21] [22] TPN-associated liver disease strikes up to 50% of patients within 5–7 years, correlated with a mortality rate of 2–50%. The onset of this liver disease is the major complication that leads TPN patients to requiring an intestinal transplant. [23]
Intralipid (Fresenius-Kabi), the US standard lipid emulsion for TPN nutrition, contains a 7:1 ratio of n-6/n-3 ratio of polyunsaturated fatty acids (PUFA). By contrast, Omegaven has a 1:8 ratio and showed promise in multiple clinical studies. Therefore, n-3-rich fat may alter the course of parenteral nutrition associated liver disease (PNALD). [24]
Because patients are being fed intravenously, the subject does not physically eat, resulting in intense hunger pangs (pains). The brain uses signals from the mouth (taste and smell), the stomach and gastrointestinal tract (fullness) and blood (nutrient levels) to determine conscious feelings of hunger. [25] In cases of TPN, the taste, smell and physical fullness requirements are not met, and so the patient experiences hunger, although the body is being fully nourished.
Patients who eat food despite the inability can experience a wide range of complications, such as refeeding syndrome. [26]
Total parenteral nutrition increases the risk of acute cholecystitis [27] due to complete disuse of the gastrointestinal tract, which may result in bile stasis in the gallbladder. Other potential hepatobiliary dysfunctions include steatosis, [28] steatohepatitis, cholestasis, and cholelithiasis. [29] Six percent of patients on TPN longer than three weeks and 100% of patients on TPN longer than 13 weeks develop biliary sludge. The formation of sludge is the result of stasis due to lack of enteric stimulation and is not due to changes in bile composition. Gallbladder sludge disappears after four weeks of a normal oral diet. Administration of exogenous cholecystokinin (CCK) or stimulation of endogenous CCK by a periodic pulse of large amounts of amino acids has been shown to help prevent sludge formation. These therapies are not routinely recommended. [30] Such complications are suggested to be the main reason for mortality in people requiring long-term total parenteral nutrition, such as in short bowel syndrome. [31] In newborn infants with short bowel syndrome with less than 10% of expected intestinal length, thereby being dependent upon total parenteral nutrition, five-year survival is approximately 20%. [32]
Infants who are sustained on TPN without food by mouth for prolonged periods are at risk for developing gut atrophy. [33]
Hypersensitivity is a rarely described but significant complication of parenteral nutrition therapy. First reported in 1965, [34] the incidence of these reactions is speculated to be around one in 1.5 million patients who are provided parenteral nutrition. [35] There is a wide range in how and when these reactions manifest. Cutaneous manifestations are the most common presentation. Hypersensitivity is thought to occur to the individual components of TPN, with the intravenous lipid emulsion being the most frequently implicated component, followed by the multivitamin solution and the amino acid solution. [35]
Medications
Patients who are receiving intravenous parenteral nutrition may also need to receive intravenous medications as well using the same Y-site. It is important to assess the compatibility of the medications with the nutrition components. Incompatibilities can be observed physically through discoloration, phase separation, or precipitation. [36]
Metabolic complications include the refeeding syndrome characterised by hypokalemia, hypophosphatemia and hypomagnesemia. Hyperglycemia is common at the start of therapy, but can be treated with insulin added to the TPN solution. Hypoglycaemia is likely to occur with abrupt cessation of TPN. Liver dysfunction can be limited to a reversible cholestatic jaundice and to fatty infiltration (demonstrated by elevated transaminases). Severe hepatic dysfunction is a rare complication. [37] Overall, patients receiving TPN have a higher rate of infectious complications. This can be related to hyperglycemia. [38]
Pregnancy can cause major complications when trying to properly dose the nutrient mixture. Because all of the fetus' nourishment comes from the mother's blood stream, the doctor must properly calculate the dosage of nutrients to meet both recipients’ needs and have them in usable forms. Incorrect dosage can lead to many adverse, hard-to-guess effects, such as death, and varying degrees of deformation or other developmental problems. [39]
It is recommended that parenteral nutrition administration begins after a period of natural nutrition so doctors can properly calculate the nutritional needs of the fetus. Otherwise, it should only be administered by a team of highly skilled doctors who can accurately assess the fetus’ needs. [39]
Solutions for total parenteral nutrition may be customized to individual patient requirements, or standardized solutions may be used. The use of standardized parenteral nutrition solutions is cost-effective and may provide better control of serum electrolytes. [40] Ideally each patient is assessed individually before commencing on parenteral nutrition, and a team consisting of specialised doctors, nurses, clinical pharmacists, and registered dietitians evaluate the patient's individual data and decide what PN formula to use and at what infusion rate.
For energy only, intravenous sugar solutions with dextrose or glucose are generally used. This is not considered to be parenteral nutrition as it does not prevent malnutrition when used on its own. Standardized solutions may also differ between developers. Following are some examples of what compositions they may have. The solution for normal patients may be given both centrally and peripherally.
Substance | Normal patient | High stress | Fluid-restricted |
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Amino acids | 85 g | 128 g | 75 g |
Dextrose | 250 g | 350 g | 250 g |
Lipids | 100 g | 100 g | 50 g |
Na+ | 150 mEq | 155 mEq | 80 mEq |
K+ | 80 mEq | 80 mEq | 40 mEq |
Ca2+ | 360 mg | 360 mg | 180 mg |
Mg2+ | 240 mg | 240 mg | 120 mg |
Acetate | 72 mEq | 226 mEq | 134 mEq |
Cl− | 143 mEq | 145 mEq | 70 mEq |
P | 310 mg | 465 mg | 233 mg |
MVI-12 | 10 mL | 10 mL | 10 mL |
Trace elements | 5 mL | 5 mL | 5 mL |
Prepared solutions generally consist of water and electrolytes; glucose, amino acids, and lipids; essential vitamins, minerals and trace elements are added or given separately. Previously lipid emulsions were given separately but it is becoming more common for a "three-in-one" solution of glucose, proteins, and lipids to be administered. [41] [42]
Individual nutrient components may be added to more precisely adjust the body contents of it. That individual nutrient may, if possible, be infused individually, or it may be injected into a bag of nutrient solution or intravenous fluids (volume expander solution) that is given to the patient.
Administration of individual components may be more hazardous than administration of pre-mixed solutions such as those used in total parenteral nutrition, because the latter are generally already balanced in regard to e.g. osmolarity and ability to infuse peripherally. Incorrect IV administration of concentrated potassium can be lethal, but this is not a danger if the potassium is mixed in TPN solution and diluted. [43]
Vitamins may be added to a bulk premixed nutrient immediately before administration, since the additional vitamins can promote spoilage of stored product.[ citation needed ] Vitamins can be added in two doses, one fat-soluble, the other water-soluble. There are also single-dose preparations with both fat- and water-soluble vitamins such as Cernevit. [44] [45]
Minerals and trace elements for parenteral nutrition are available in prepared mixtures, such as Addaven. [46]
These additional components in parenteral nutritions, however were subject to stability checks, since they greatly affect the stability of lipid emulsions that serve as the base for these formulations. Studies have shown differences in physical and chemical stabilities of these total parenteral nutrition solutions, [47] [48] [49] which greatly influences pharmaceutical manufacturing of these admixtures.
Only a limited number of emulsifiers are commonly regarded as safe to use for parenteral administration, of which the most important is lecithin.[ medical citation needed ] Lecithin can be biodegraded and metabolized, since it is an integral part of biological membranes, making it virtually non-toxic. Other emulsifiers can only be excreted via the kidneys,[ citation needed ] creating a toxic load. The emulsifier of choice for most fat emulsions used for parenteral nutrition is a highly purified egg lecithin, [50] due to its low toxicity and complete integration with cell membranes.
Use of egg-derived emulsifiers is not recommended for people with an egg allergy due to the risk of reaction. In situations where there is no suitable emulsifying agent for a person at risk of developing essential fatty acid deficiency, cooking oils may be spread upon large portions of available skin for supplementation by transdermal absorption. [51]
Another type of fat emulsion Omegaven is being used experimentally within the US primarily in the pediatric population. It is made of fish oil instead of the soybean oil based formulas more widely in use. Research has shown use of Omegaven may reverse and prevent liver disease and cholestasis. [52]
Developed in the 1960s by Dr. Stanley Dudrick, who as a surgical resident in the University of Pennsylvania, working in the basic science laboratory of Dr. Jonathan Rhoads, was the first to successfully nourish initially Beagle puppies and subsequently newborn babies with catastrophic gastrointestinal malignancies. [53] Dudrick collaborated with Dr. Willmore and Dr. Vars to complete the work necessary to make this nutritional technique safe and successful. [54]
In 2019 the UK experienced a severe shortage of TPN bags due to safety restrictions at the sole manufacturing site, operated by Calea. The National Health Service described the situation as an emergency. [55]
Crohn's disease is a chronic inflammatory bowel disease characterized by recurrent episodes of intestinal inflammation, primarily manifesting as diarrhea and abdominal pain. Unlike ulcerative colitis, inflammation can occur anywhere in the gastrointestinal tract, though it most frequently affects the ileum and colon, involving all layers of the intestinal wall. Symptoms may be non-specific and progress gradually, often delaying diagnosis. About one-third of patients have colonic disease, another third have ileocolic disease, and the remaining third have isolated ileal disease. Systemic symptoms such as chronic fatigue, weight loss, and low-grade fevers are common, along with extraintestinal manifestations affecting organs like the skin and joints. Complications can include bowel obstructions, fistulas, and an increased risk of intestinal cancers.
Glutamine is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, polar amino acid. It is non-essential and conditionally essential in humans, meaning the body can usually synthesize sufficient amounts of it, but in some instances of stress, the body's demand for glutamine increases, and glutamine must be obtained from the diet. It is encoded by the codons CAA and CAG. It is named after glutamic acid, which in turn is named after its discovery in cereal proteins, gluten.
Dietary fiber or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition and can be grouped generally by their solubility, viscosity and fermentability which affect how fibers are processed in the body. Dietary fiber has two main subtypes: soluble fiber and insoluble fiber which are components of plant-based foods such as legumes, whole grains, cereals, vegetables, fruits, and nuts or seeds. A diet high in regular fiber consumption is generally associated with supporting health and lowering the risk of several diseases. Dietary fiber consists of non-starch polysaccharides and other plant components such as cellulose, resistant starch, resistant dextrins, inulin, lignins, chitins, pectins, beta-glucans, and oligosaccharides.
A central venous catheter (CVC), also known as a central line (c-line), central venous line, or central venous access catheter, is a catheter placed into a large vein. It is a form of venous access. Placement of larger catheters in more centrally located veins is often needed in critically ill patients, or in those requiring prolonged intravenous therapies, for more reliable vascular access. These catheters are commonly placed in veins in the neck, chest, groin, or through veins in the arms.
Intravenous therapy is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrients for those who cannot, or will not—due to reduced mental states or otherwise—consume food or water by mouth. It may also be used to administer medications or other medical therapy such as blood products or electrolytes to correct electrolyte imbalances. Attempts at providing intravenous therapy have been recorded as early as the 1400s, but the practice did not become widespread until the 1900s after the development of techniques for safe, effective use.
In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body.
A feeding tube is a medical device used to provide nutrition to people who cannot obtain nutrition by mouth, are unable to swallow safely, or need nutritional supplementation. The state of being fed by a feeding tube is called gavage, enteral feeding or tube feeding. Placement may be temporary for the treatment of acute conditions or lifelong in the case of chronic disabilities. A variety of feeding tubes are used in medical practice. They are usually made of polyurethane or silicone. The outer diameter of a feeding tube is measured in French units. They are classified by the site of insertion and intended use.
Short bowel syndrome is a rare malabsorption disorder caused by a lack of functional small intestine. The primary symptom is diarrhea, which can result in dehydration, malnutrition, and weight loss. Other symptoms may include bloating, heartburn, feeling tired, lactose intolerance, and foul-smelling stool. Complications can include anemia and kidney stones.
A peripherally inserted central catheter, also called a percutaneous indwelling central catheter or longline, is a form of intravenous access that can be used for a prolonged period of time or for administration of substances that should not be done peripherally. It is a catheter that enters the body through the skin (percutaneously) at a peripheral site, extends to the superior vena cava, and stays in place for days, weeks or even months.
A Hickman line is a central venous catheter most often used for the administration of chemotherapy or other medications, as well as for the withdrawal of blood for analysis. Some types are used mainly for the purpose of apheresis or dialysis. They have also been used in total parenteral nutrition (TPN). Hickman lines may remain in place for extended periods and are used when long-term intravenous access is required.
Lipid emulsion or fat emulsion refers to an emulsion of fat for human intravenous use, to administer nutrients to critically-ill patients that cannot consume food. It is often referred to by the brand name of the most commonly used version, Intralipid, which is an emulsion containing soybean oil, egg phospholipids and glycerin, and is available in 10%, 20% and 30% concentrations. The 30% concentration is not approved for direct intravenous infusion, but should be mixed with amino acids and dextrose as part of a total nutrient admixture.
Cholestasis is a condition where the flow of bile from the liver to the duodenum is impaired. The two basic distinctions are:
Intestinal pseudo-obstruction (IPO) is a clinical syndrome caused by severe impairment in the ability of the intestines to push food through. It is characterized by the signs and symptoms of intestinal obstruction without any lesion in the intestinal lumen. Clinical features mimic those seen with mechanical intestinal obstructions and can include abdominal pain, nausea, abdominal distension, vomiting, dysphagia and constipation depending upon the part of the gastrointestinal tract involved.
A medium-chain triglyceride (MCT) is a triglyceride with two or three fatty acids having an aliphatic tail of 6–12 carbon atoms, i.e. a medium-chain fatty acid (MCFA). Rich food sources for commercial extraction of MCTs include palm kernel oil and coconut oil.
An umbilical line is a catheter that is inserted into one of the two arteries or the vein of the umbilical cord. Generally the UAC/UVC is used in Neonatal Intensive Care Units (NICU) as it provides quick access to the central circulation of premature infants. UAC/UVC lines can be placed at the time of birth and allow medical staff to quickly infuse fluids, inotropic drugs, and blood if required. It is sometimes used in term or near-term newborns in whom the umbilical cord stump is still connected to the circulatory system. Medications, fluids, and blood can be given through this catheter and it allows monitoring of blood gasses and withdrawing of blood samples. Transumbilical catheter intervention is also a method of gaining access to the heart, for example to surgically correct a patent ductus arteriosus.
Fish oil, sold under the brand name Omegaven, is a fatty acid emulsion. It is used for total parenteral nutrition, e.g. in short bowel syndrome. It is rich in omega-3 fatty acids.
Taurolidine is an antimicrobial that is used to prevent infections in catheters. Side effects and the induction of bacterial resistance is uncommon. It is also being studied as a treatment for cancer.
Fibre supplements are considered to be a form of a subgroup of functional dietary fibre, and in the United States are defined by the Institute of Medicine (IOM). According to the IOM, functional fibre "consists of isolated, non-digestible carbohydrates that have beneficial physiological effects in humans".
Intestine transplantation is the surgical replacement of the small intestine for chronic and acute cases of intestinal failure. While intestinal failure can oftentimes be treated with alternative therapies such as parenteral nutrition (PN), complications such as PN-associated liver disease and short bowel syndrome may make transplantation the only viable option. One of the rarest type of organ transplantation performed, intestine transplantation is becoming increasingly prevalent as a therapeutic option due to improvements in immunosuppressive regimens, surgical technique, PN, and the clinical management of pre and post-transplant patients.
Stanley John Dudrick was a surgeon who pioneered the use of total parenteral nutrition (TPN).