Amino Acids
Indications: Nutritional support
DESCRIPTION:
The amino-acids are the main building blocks of the body. Some of the amino-acids are nutritionally essential amino acids, ie, they must be obtained in the diet, whereas others can be synthesised in vivo at rates sufficient to meet metabolic needs. The essential amino-acids are ARGININE, HISTIDINE, ISOLEUCINE, LEUCINE, LYSINE, METHIONINE, PHENYLALANINE, THREONINE, VALINE.
Various other important amino acids such as ornithine, 5-hydroxytryptophan, l-dopa, taurine and thyroxine( T-4 ) occur in the body but are not found in the proteins. In higher animals, the L isomers of the amino acids are the only naturally occurring forms. The l-isomers of hormones such as thyroxine are much more active than the d-isomers.
* Histidine is considered an essential amino acid in uremic patients.
CLINICAL PHARMACOLOGY:
Essential amino acid injection provides an intravenously compatible mixture of essential amino acids which, when infused with hypertonic dextrose as a source of calories, plus electrolytes, minerals, and vitamins, provides in a small volume of fluid all ingredients (with the exception of essential fatty acids) needed for total parenteral nutrition in patients with renal disease.
Infusion of essential amino acid injection and hypertonic dextrose provides essential amino acids and calories for protein synthesis to promote improved cellular metabolic balance. Infusion of these components can decrease the rate of rise of blood urea nitrogen and minimize deterioration of serum potassium, magnesium and phosphorus balance in patients with impaired renal function. The extent to which essential amino acids and calories promote incorporation of waste urea nitrogen into newly synthesized amino acids in man, as it does in experimental animals, is, so far, not established.
The accelerated decrease in serum creatinine levels seen in patients with limited extra-renal complications suggests that treatment with essential amino acid injection and hypertonic dextrose leads to earlier return of renal function in patients with potentially reversible acute renal failure. By providing nutritional support and promoting biochemical improvement as well as earlier return of renal function, essential amino acid injection and hypertonic dextrose decrease morbidity associated with acute renal failure.
It is thought that acetate from lysine acetate, under the condition of parenteral nutrition, does not impact net acid-base balance when renal and respiratory functions are normal. Clinical evidence seems to support this thinking; however, confirmatory experimental evidence is not available.
The amounts of sodium and chloride present are not of clinical significance.
INDICATIONS AND USAGE:
essential amino acid injection is indicated for adult and pediatric use, in conjunction with other measures, to provide nutritional support for uremic patients, particularly when oral nutrition is infeasible or impractical. See PRECAUTIONS, Special Precautions in Pediatric Patients for additional information.
CONTRAINDICATIONS:
Essential amino acid injection is contraindicated in patients with severe, uncorrected electrolyte and acid-base imbalance, hyperammonemia, decreased (subcritical) circulating blood volume, inborn errors of amino acid metabolism, or hypersensitivity to one or more amino acids present in the solution.
WARNINGS:
This product contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Safe and effective use of central venous nutrition requires a knowledge of nutrition as well as clinical expertise in recognition and treatment of the complications which can occur. Frequent clinical evaluation and laboratory determinations are necessary for proper monitoring of central venous nutrition. Studies should include blood sugar, serum proteins, kidney and liver function tests, electrolytes, hemogram, carbon dioxide combining power, serum osmolarity, blood cultures, blood ammonia levels, and circulating blood volume.
Essential amino acid injection does not replace dialysis and conventional supportive therapy in patients with renal failure.
Administration of essential amino acid injection to children or low birth-weight infants, especially in high doses, may result in hyperammonemia.
Clinically significant hypokalemia, hypophosphatemia, or hypomagnesemia may occur as a result of therapy with essential amino acid injection and hypertonic dextrose and replacement therapy may become necessary.
Administration of nitrogen in any form to patients with marked hepatic insufficiency or hepatic coma may result in plasma amino acid imbalances, hyperammonemia, or central nervous system deterioration. Essential amino acid injection should, therefore, be used with caution in such patients.
The intravenous administration of these solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the solute concentration of the solution infused. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the concentration of the solution.
Conservative doses of amino acids should be given, dictated by the nutritional status of the patient.
PRECAUTIONS:
General
Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Significant deviations from normal concentrations may require the use of additional electrolyte supplements.
In order to promote urea nitrogen reutilization in patients with renal failure, it is essential to provide adequate calories with minimal amounts of the essential amino acids, and to severely restrict the intake of nonessential nitrogen. Hypertonic dextrose solutions are a convenient and metabolically effective source of concentrated calories.
Fluid balance must be carefully monitored in patients with renal failure and care should be taken to avoid circulatory overload, particularly in association with cardiac insufficiency.
In patients with myocardial infarct, infusion of amino acids should always be accompanied by dextrose, since in anoxia, free fatty acids cannot be utilized by the myocardium, and energy must be produced anaerobically from glycogen or glucose.
Strongly hypertonic nutrient solutions should be administered through an indwelling intravenous catheter with the tip located in the superior vena cava.
Special care must be taken when giving hypertonic dextrose to glucose-intolerant patients such as diabetic or prediabetic and uremic patients, especially when the latter are receiving peritoneal dialysis. To prevent severe hyperglycemia in such patients, insulin may be required.
Administration of glucose at a rate exceeding the patient's utilization may lead to hyperglycemia, coma, and death.
Administration of amino acids without carbohydrates may result in the accumulation of ketone bodies in the blood. Correction of this ketonemia may be achieved by the administration of carbohydrates.
Abrupt cessation of hypertonic dextrose infusion may result in rebound hypoglycemia.
When 5.4% essential amino acid injection is subjected to changes in temperature, there is a chance that some transient crystallization of amino acids may occur. Thorough shaking of the bottle for about one minute should redissolve the amino acids. If the amino acids do not completely redissolve, the bottle must be rejected.
To minimize the risk of possible incompatibilities arising from mixing this solution with other additives that may be prescribed, the final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration.
Use only if solution is clear and vacuum is present.
Pregnancy Category C
Animal reproduction studies have not been conducted with 5.4% essential amino acid injection. It is also not known whether essential amino acid injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Essential amino acid injection should be given to a pregnant woman only if clearly needed.
Special Precautions for Central Venous Nutrition
Administration by central venous catheter should be used only by those familiar with this technique and its complications.
Central venous nutrition may be associated with complications which can be prevented or minimized by careful attention to all aspects of the procedure including solution preparation, administration, and patient monitoring. It is essential that a carefully prepared protocol, based on current medical practices, be followed, preferably by an experienced team.
Although a detailed discussion of the complications of central venous nutrition is beyond the scope of this insert, the following summary lists those based on current literature:
Technical: The placement of a central venous catheter should be regarded as a surgical procedure. One should be fully acquainted with various techniques of catheter insertion as well as recognition and treatment of complications. For details of techniques and placement sites, consult the medical literature. X-ray is the best means of verifying catheter placement. Complications known to occur from the placement of central venous catheters are pneumothorax, hemothorax, hydrothorax, artery puncture and transection, injury to the brachial plexus, malposition of the catheter, formation of arteriovenous fistula, phlebitis, thrombosis, and air and catheter embolus.
Septic: The constant risk of sepsis is present during central venous nutrition. Since contaminated solutions and infusion catheters are potential sources of infection, it is imperative that the preparation of parenteral nutrition solutions and the placement and care of catheters be accomplished under controlled aseptic conditions.
Parenteral nutrition solutions should ideally be prepared in the hospital pharmacy under a laminar flow hood. The key factor in their preparation is careful aseptic technique to avoid inadvertent touch contamination during mixing of solutions and subsequent admixtures.
Parenteral nutrition solutions should be used promptly after mixing. Any storage should be under refrigeration for as brief a time as possible. Administration time for a single bottle and set should never exceed 24 hours.
Consult the medical literature for a discussion of the management of sepsis during central venous nutrition. In brief, typical management includes replacing the solution being administered with a fresh container and set, and the remaining contents are cultured for bacterial or fungal contamination. If sepsis persists and another source of infection is not identified, the catheter is removed, the proximal tip cultured, and a new catheter reinserted when the fever has subsided. Nonspecific, prophylactic antibiotic treatment is not recommended. Clinical experience indicates that the catheter is likely to be the prime source of infection as opposed to aseptically prepared and properly stored solutions.
Metabolic: The following metabolic complications have been reported: metabolic acidosis, hypophosphatemia, alkalosis, hyperglycemia and glycosuria, osmotic diuresis and dehydration, rebound hypoglycemia, elevated liver enzymes, hypo- and hypervitaminosis, electrolyte imbalances, and hyperammonemia in children. Frequent clinical evaluation and laboratory determinations are necessary, especially during the first few days of central venous nutrition, to prevent or minimize these complications.
Special Precautions in Patients with Renal Insufficiency
Frequent laboratory studies are necessary in patients with renal insufficiency due to underlying metabolic abnormalities. Hyperglycemia, a frequent complication, may not be reflected by glycosuria in renal failure. Blood glucose, therefore, must be determined frequently, often every six hours to guide dosage of dextrose and insulin if required.
Serum concentrations of potassium, phosphorus, and magnesium may dramatically decline with successful treatment, individually or together; these substances should be supplemented as required. Special care must be taken to avoid hypokalemia in digitalized patients, or those with cardiac arrhythmias.
Special Precautions in Pediatric Patients
5.4% Essential Amino Acid Injection should be used with special caution in pediatric patients, especially low birth-weight infants, due to limited clinical experience.
Laboratory and clinical monitoring of pediatric patients, especially when nutritionally depleted, must be extensive and frequent. Initial total daily dose should be low, and increased slowly. Dosage of essential amino acid injection above one gram of essential amino acids per kilogram body weight per day is not recommended.
Frequent monitoring of blood glucose is required in low birth-weight or septic infants as infusion of hypertonic dextrose carries a greater risk of hyperglycemia in such patients.
The absence of arginine in essential amino acid injection may accentuate the risk of hyperammonemia in infants.
ADVERSE REACTIONS:
See WARNINGS and PRECAUTIONS, Special Precautions for Central Venous Nutrition.
Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis, and hypervolemia.
Symptoms may result from an excess or deficit of one or more of the ions present in the solution infused, therefore, frequent monitoring of electrolyte levels is essential.
Infrequent instances of hyperammonemia have been reported following administration of essential amino acid solutions to patients with massive gastrointestinal infection.