INTRODUCTION — Parenteral nutrition (PN) support refers to the provision of calories, amino acids, electrolytes, vitamins, minerals, trace elements, and fluids via a parenteral route. Access, prescribing, monitoring, and complications of parenteral nutrition are reviewed here.
The goals, outcomes, indications, contraindications, and nutritional requirements for parenteral nutrition are discussed separately. (See "Nutrition support in critically ill patients: An overview".)
Shortages of individual components of PN are frequent, and may significantly impact on the care of patients receiving it. The American Society of Parenteral and Enteral Nutrition recommendations for managing shortages relevant to components of parenteral nutrition can be accessed at the following site: http://www.nutritioncare.org/Professional_Resources/Drug_Shortages_Update/.
INDICATIONS AND CONTRAINDICATIONS — The indications and contraindications for parenteral nutrition are described elsewhere. (See "Nutrition support in critically ill patients: An overview".)
INITIATION — In order to initiate parenteral nutrition, appropriate access must be obtained and the prescription (ie, composition and infusion rate) must be determined. Guidelines suggest that when tolerance to enteral nutrition is evident, parenteral nutrition should be weaned and discontinued when >60 percent of the patients' needs are met enterally, although there are no data to support this practice [1]. Our practice is to wean parenteral nutrition proportionate to the amount of enteral nutrition being delivered, thus meeting but not exceeding the daily goals. For ease of calculation, most standard PN solutions contain approximately 1 kcal/mL.
Access — Parenteral nutrition given for more than a few days must be delivered via a central venous catheter, so called central parenteral nutrition (CPN) because its high osmotic load is not tolerated by peripheral veins [2,3]. Parenteral nutrition may be given via a peripheral vein if it is significantly more dilute (<900 mOsm), so called peripheral parenteral nutrition (PPN). Because of the ease of obtaining central access in the hospital, the large volume usually required to administer PPN, and the lack of benefit from short-term parenteral nutrition, PPN is rarely indicated. (See 'Peripheral parenteral nutrition' below.)
Choosing among a peripherally inserted central catheter (PICC) or a tunneled central venous catheter ([TCVC]; also referred to as TICC, eg, Hickman catheter, Groshong catheter, or implanted infusion port) should be individualized and depend upon duration of need for PN, local expertise, ability of the facility or individual to take care of the device, and presence of other risk factors for catheter-related blood stream infections (CRBSI; eg previous sepsis with CVC in place). The American Society for Parenteral and Enteral Nutrition (ASPEN) has issued clinical guidelines to describe best practices in the selection and care of central venous access devices (CVADs) for the infusion of home parenteral nutrition in adult patients [4]. In the absence of guidelines specific to the critically ill, similar principles can be used when selecting CVADs for hospitalized critically ill patients in whom PN is indicated. ASPEN guidelines use an arbitrary cutoff of 30 days to distinguish short-term from long-term PN use.
●In general, we agree that patients in whom short-term administration of PN is desirable or intended that PN be delivered through a PICC. Alternatively, while not preferable, PN may be administered through a subclavian, internal jugular, or femoral central venous catheter if PN is only needed for very short periods (eg, a few days) or if a PICC is not feasible or reasonable. Tradition teaches that the femoral site is least desirable due to an increased risk of CRBSIs [5], and is consequently not preferred. (See 'Bloodstream infection' below.)
●For long term administration of PN, A.S.P.E.N. guidelines indicated a preference for a TCVC. However, the rationale for this choice is based upon expert opinion and observational studies that suggest infection rates may be lower with TCVC rather than randomized trials that validate this finding [6-9]. In fact, one systematic review suggested that rates were no different between PN delivered through a PICC compared with a TCVC (relative risk 0.40; 95% CI 0/19-0.83) [6]. It is our practice to use PICCs preferentially, because of the relative ease of removal and insertion compared to TCVC.
●When possible, a single lumen central venous catheter should be used for the infusion of parenteral nutrition. If a multiple lumen central venous catheter is used it should have one port dedicated solely for the infusion of parenteral nutrition. In addition, catheter manipulations should be minimized. These precautions may decrease the infectious complications associated with parenteral nutrition [10,11]. For patients who have an existing CVC, a new CVC is not typically required unless there has been septicemia during the life of the existing line.
Indications, insertion, and complications of central venous catheters are discussed separately. (See "Overview of complications of central venous catheters and their prevention in adults" and "Central venous access: General principles" and "Catheter-related upper extremity venous thrombosis in adults".)
Prescription — The Institute for Safe Medication Practices (ISMP) has listed PN as a “high alert medication,” in the same category of complexity and potential for error or harm as chemotherapy. Guidelines that describe safe practices for parenteral nutrition have been published by professional organizations [11-15]. These recommend that parenteral nutrition be prescribed by a multidisciplinary team of physicians, nutritionists, pharmacists, and nurses [11]. Parenteral nutrition should not be prescribed by clinicians nor compounded by pharmacists without specific training because it is complicated and requires advanced knowledge about issues such as nutrient metabolism and solute compatibility [14,15].
Parenteral nutrition is an admixture of solutions containing dextrose, amino acids, electrolytes, vitamins, minerals, and trace elements. Lipid emulsion may be infused separately or added to the mixture. However, mixing all three, a so-called total nutrient admixture, or 3-in-1 parenteral nutrition, is favored by most experts [16]. The exact composition and infusion rate are tailored to the nutritional and fluid needs of each patient. (See "Nutrition support in critically ill patients: An overview", section on 'Nutritional requirements'.)
Dextrose — Dextrose-containing stock solutions are available in a variety of concentrations, most commonly 40, 50, and 70 percent. The percentage of calories that is contributed by dextrose is titrated according to individual factors, such as severity of illness, the caloric needs of the patient, and the patient's ability to tolerate fluid volume.
The caloric contribution of dextrose in medical solutions is 3.4 kcal/gm, which differs from dietary carbohydrate (4 kcal/gm). The reason for the difference is that water contributes to the weight of the dextrose-hydrate that is used to prepare parenteral nutrition.
Amino acids and electrolytes — Amino acid solutions contain most essential and nonessential amino acids. The exceptions are arginine and glutamine. While these are thought to be conditionally essential in critical illness, due to blockade of their metabolic pathways in catabolism, research does not support their supplementation. The caloric contribution of amino acids is approximately 4 kcal/gm. The buffer used in amino acid solution contains electrolytes, usually in small quantities. Amino acid solutions with large amounts of electrolytes have been used infrequently because they limit the degree to which parenteral nutrition can be customized. However, with the increasing use of premixed parenteral nutrition with a variety of available electrolyte content, customization may not be as necessary. It is occasionally necessary to use amino acid solutions with further electrolyte restriction (usually these are 15 percent amino acid solutions), particularly in patients with renal failure when electrolytes, particularly phosphate levels, are difficult to control.
The amino acid stock solutions come in concentrations ranging from 5.5 to 15 percent. Higher concentrations are useful for minimizing volume and electrolytes delivered to patients. Enteral protein, peptide, and arginine supplementation is discussed separately. (See "Nutrition support in critically ill patients: Enteral nutrition", section on 'Composition'.)
Enrichment of parenteral nutrition with branched chain amino acids has been studied, but there is insufficient evidence of benefit to recommend this approach. A meta-analysis of four randomized trials (202 patients) that compared branched chain amino acid-enriched parenteral nutrition to standard parenteral nutrition found a trend toward decreased mortality among patients who received branched chain amino acids (24 versus 36 percent, relative risk 0.58, 95% CI 0.26-1.28) [17]. However, the meta-analysis was limited by methodological differences among the trials and an imprecise estimate of the magnitude of effect. Other meta-analyses have found no difference in infection rate, ICU length of stay, or hospital length of stay.
Lipids — Lipids are provided as an emulsion that may be infused separately or added to the mixture (total nutrient admixture [TNA] or three-in-one). In the United States, most lipid emulsion consists of long-chain omega-6 triglycerides derived from soybean and safflower oils and then emulsified using egg phospholipids and glycerin. Mixtures of several types of lipids (eg, refined olive, soybean, and fish oil emulsions), have been approved and are also available for use in the US. We observe improvement in liver enzymes in many patients with parenteral nutrition-related hepatic dysfunction when switching from soy-base to mixed lipid emulsions. But we also note this when the percent of fat is decreased and when total calories are decreased. To date, randomized trials have not conclusively demonstrated any clinical meaningful benefits among patients receiving parenteral nutrition, nor justify the added expense of using mixed fat emulsions for all patients [18-22]. (See "Intestinal failure-associated liver disease in infants", section on 'Fish oil-based lipid emulsions'.)
Unlike omega-6 fatty acids, omega-3 fatty acids are metabolized to mediators that are noninflammatory and anti-inflammatory. Manipulation of the inflammatory process has been of strong interest in the nutrition support, as it is the cause of disease-related wasting. One meta-analysis of 49 randomized trials reported that omega-3 fatty acid-enriched parenteral nutrition was associated with a 40 percent lower risk of infection (relative risk [RR] 0.60, 95% CI 0.49-0.72) and 56 percent lower risk of sepsis (RR 0.44, 95% CI 0.28-0.70;) compared with patients receiving standard parenteral nutrition without omega-3 fatty acid enrichment [23]. Hospital and ICU length of stay was also lower in the fatty-acid enriched group. These are appealing results, but large randomized trials are needed before we can recommend supplementation of parenteral nutrition with omega-3 fatty acids.
The caloric contribution of a typical lipid emulsion is 10 kcal/g or 2 kcal/mL in 20 percent emulsion and 11 kcal/g or 1.1 kcal/mL in 10 percent emulsion. Dietary fat provides 9 kcal/g, but there is a contribution of calories from the emulsifiers used to create the lipid suspension for intravenous administration. Because propofol is provided in a 10 percent fat emulsion, and fat dosing in PN should be adjusted accordingly. Intravenous fat emulsions should be given with care to patients with prior allergy to eggs. Egg phospholipid is used to emulsify the triglycerides in intravenous fat emulsions and allergic cross-reactions have been reported. But these are very rare.
Cautious initiation of ILE has been recommended when serum triglycerides exceed 200 mg/dL (eg, infuse lipid emulsion three times weekly) [24]. Severe hypertriglyceridemia and other severe disorders of lipid metabolism are a contraindication to lipid emulsion infusion (eg, serum triglycerides >1000 mg/dL due to pathologic hypertriglyceridemia, lipoid necrosis, acute pancreatitis accompanied by hypertriglyceridemia, disorders of fat metabolism). Monitoring for hypertriglyceridemia is discussed below. (See 'Metabolic effects' below.)
Vitamins and trace elements — Patients receiving parenteral nutrition must receive adequate vitamins and minerals to prevent deficiencies. For most patients, a unit dose of a standard multivitamin and multi-trace element solution will suffice to provide minimum daily requirements. It is advisable that patients with cholestasis not receive copper or manganese, as these are excreted in bile. A total bilirubin of 2 is often used as a cut off to restrict these, and it is often necessary to order the remaining trace elements individually and then follow levels. There are also concerns about clearance of some vitamins in anephric patients. It is not our practice to restrict either vitamins or minerals in these patients, and to monitor levels if patients are on parenteral nutrition for extended periods.
Therapeutic vitamin and mineral supplementation — It is not our practice to supplement vitamins and minerals above the recommended daily amounts, unless a deficiency is documented or strongly suspected. It should be noted that a deficiency is not the same as a low level. Rather, a deficiency occurs only when a lack of a substance causes an undesired health outcome that is reversed or prevented by supplementation. For example, levels of vitamin D, which is protein bound, drop in critical illness. But even though there is a correlation between vitamin D levels and ICU mortality, supplementation of vitamin D has no effect. [25,26]. The decrease in vitamin D levels is due to the decrease in carrier protein levels, much in the same way a decrease in albumin lowers calcium levels. Despite the incorrect use of the term "deficiency" in a vast literature, low vitamin D levels in this context do not constitute a deficiency.
Numerous clinical trials have examined the effect of antioxidants on critically ill patients when given as single nutrients (eg, selenium) or as a combination of nutrients (selenium, copper, zinc, vitamin A, vitamin C, vitamin E, and N-acetylcysteine). The trials administered the antioxidants in various ways, including as a separate intravenous infusion, as a component of parenteral nutrition, as a component of enteral nutrition, and orally.
A meta-analysis of 15 randomized trials (1647 patients) found that critically ill patients who received vitamins and trace elements, either alone or in combination, had a lower mortality rate than patients who did not receive vitamins or trace elements (20 versus 27 percent, relative risk 0.76, 95% CI 0.65-0.88) [27]. Similar meta-analyses showed improvement in the duration of mechanical ventilation, but no differences in infectious complications, hospital length of stay, or ICU length of stay.
Few of the trials looked specifically at patients receiving parenteral nutrition. Rather, most enrolled a heterogeneous sample of patients receiving either parenteral or enteral nutrition and did not look for differences in the effects of the vitamins and trace elements in these subgroups. Given their safety, it seems reasonable to provide standard doses of vitamins and trace elements to most critically ill patients, regardless of the type of nutrition support that they are receiving. The optimal mixture of vitamins and trace elements is yet to be determined. Enteral vitamin and trace element supplementation is discussed separately. (See "Nutrition support in critically ill patients: Enteral nutrition", section on 'Vitamins and trace elements'.)
Glutamine — Glutamine is a precursor for nucleotide synthesis and an important fuel source for rapidly dividing cells, such as gastrointestinal epithelia. Despite evidence that indicates that parenteral glutamine may be beneficial to patients who are receiving parenteral nutrition [28-30], in one large multicenter randomized study of glutamine supplementation in critically ill patients a trend toward increased 28-day mortality in those receiving glutamine-enriched enteral nutrition was reported [31]. Glutamine is not available in the United States in a form that can be added to parenteral nutrition. Enteral glutamine supplementation is discussed separately. (See "Nutrition support in critically ill patients: Enteral nutrition", section on 'Glutamine'.)
MONITORING — Routine monitoring of parenteral nutrition includes measurement of fluid intake and output, as well as selected laboratory studies. It is reasonable to measure serum electrolytes, glucose, calcium, magnesium, and phosphate daily until they are stable, or more frequently when the patient is at high risk for or exhibiting refeeding syndrome. It is similarly reasonable to measure aminotransferases, bilirubin, and triglyceride at least once each week during treatment. More frequent measurements should be performed in the period immediately after parenteral nutrition is initiated, or after changes in the composition. Triglyceride levels should be measured at baseline and once PN has been initiated, then monthly or more frequently if elevated. We measure trace elements, including iron, approximately every three months, or if deficiency is suspected. Frequency of monitoring should be adjusted to the individual patient’s acuity, stability, and risks for deficiencies. General guidelines have been published [13]. (See "Anorexia nervosa in adults and adolescents: The refeeding syndrome".)
COMPLICATIONS — Patients who receive parenteral nutrition support are at risk for infection, adverse metabolic effects, and complications related to venous access. Clinical practice guidelines, protocols, and oversight by multidisciplinary teams have been shown to reduce the complications and total cost of parenteral nutrition [11,27,32].
Bloodstream infection — Access to the central venous system is necessary when PN is indicated such that PN is typically administered through a peripherally inserted central venous catheter (PICC) or a tunneled central venous catheter (TCVC) (see 'Access' above). Patients receiving parenteral nutrition are at slightly increased risk of acquiring a bloodstream infection (bacterial and fungal; approximately one episode per 100 inpatient PN days) [33].
Among patients receiving parenteral nutrition, factors that are independently associated with bloodstream infection include poor patient hygiene, insertion of the central venous catheter under emergent circumstances, and, to a lesser extent, the severity of illness and duration of central venous catheterization [34]. Conversely, proper hand hygiene and maximal barrier precautions during insertion of the central venous catheter are associated with fewer bloodstream infections [34]. Diagnosis and treatment of catheter-related bloodstream infection is discussed separately. (See "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis" and "Intravascular non-hemodialysis catheter-related infection: Treatment".)
Metabolic effects — Parenteral nutrition is associated with metabolic complications, including hyperglycemia, serum electrolyte alterations, macro- or micro-nutrient excess or deficiency, refeeding syndrome [35], Wernicke's encephalopathy [36], and hepatic dysfunction. Routine monitoring of serum glucose, electrolytes, and volume status may minimize the impact of such complications.
Hyperglycemia is particularly common among patients who receive parenteral nutrition. In a meta-analysis of six randomized trials (264 critically ill patients with acute pancreatitis), the incidence of hyperglycemia was approximately two times greater for patients who received parenteral nutrition than patients who received enteral nutrition [37]. Both groups had similar nutrient intake. The relationship between hyperglycemia and clinical outcomes in critically ill patients is discussed in detail elsewhere. (See "Glycemic control in critically ill adult and pediatric patients", section on 'Rationale for blood sugar control'.)
Refeeding syndrome is a potentially fatal condition resulting from rapid changes in fluids and electrolytes when malnourished patients (eg, anorectics, alcoholics) are given oral, enteral, or parenteral feedings [38]. Patients with ongoing electrolyte losses (eg, from diarrhea, vomiting, fistulas) are at increased risk of refeeding syndrome. It is defined primarily by manifestations of severe hypophosphatemia (including respiratory failure, cardiovascular collapse, rhabdomyolysis, seizures, and delirium), but hypokalemia, hypomagnesemia, and Wernicke’s encephalopathy also occur. Refeeding syndrome is described in greater detail elsewhere. (See "Eating disorders: Overview of prevention and treatment", section on 'Refeeding syndrome'.)
Treatment-emergent hypertriglyceridemia or worsening of existing hypertriglyceridemia may result from the infusion of lipid emulsion. Concentrations up to 400 mg/dL are acceptable during therapy without altering the rate of lipids during therapy [24]. Doses of lipid emulsion should be reduced when triglyceride concentrations rise above 400 mg/dL (eg, once or twice per week). It is also reasonable to attempt decreasing the proportion of calories provided by dextrose. Levels >1000 mg/dL are a contraindication to infusion [11,24].
Venous access — Parenteral nutrition requires venous access, which is associated with potential complications. Examples include bleeding, vascular injury, pneumothorax, venous thrombosis, arrhythmia, and air embolism. The complications of venous access for parenteral nutrition are not different from access for other purposes, and are described separately. (See "Overview of complications of central venous catheters and their prevention in adults" and "Catheter-related upper extremity venous thrombosis in adults" and "Air embolism".)
PERIPHERAL PARENTERAL NUTRITION — Peripheral parenteral nutrition (PPN) is rarely prescribed because of the uncertain clinical benefit of short-term parenteral nutrition. It is a type of parenteral nutrition that can be delivered for short periods through a peripheral intravenous catheter because it has an osmolarity lower than that of conventional parenteral nutrition (<900 mOsm). To deliver adequate nutrients, either a large volume and/or a high fat formulation must be used. Frequent replacement of intravenous access is usually necessary. Despite an osmolarity lower than conventional parenteral nutrition, PPN is still quite hyperosmolar and irritating to the peripheral veins. We recommend against infusing PPN via midline catheters as we have seen late stenosis at the midline catheter tip location.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Nutrition support (parenteral and enteral nutrition) in adults".)
SUMMARY AND RECOMMENDATIONS
●Parenteral nutrition is a mixture of solutions that contain dextrose, amino acids, electrolytes, vitamins, minerals, and trace elements. Lipid emulsion may be infused separately or added to the mixture (ie, a total nutrient or three-in-one admixture). (See 'Prescription' above.)
●Parenteral nutrition should be prescribed by a multidisciplinary team with advanced knowledge about how to tailor the composition and infusion rate to the needs of each patient, rather than by untrained individual clinicians. Guidelines exist that describe safe practices for parenteral nutrition. (See 'Prescription' above.)
●For critically ill patients receiving parenteral nutrition, we suggest the inclusion of multivitamins and trace elements (Grade 2B). They are typically already included as a component of the parenteral nutrition, in the multivitamin, and multi-trace element solutions that are usually given in unit doses. The optimal mixture of nutrients has not been determined. (See 'Vitamins and trace elements' above.)
●Routine monitoring of parenteral nutrition includes measurement of fluid intake and output, as well as selected laboratory studies. (See 'Monitoring' above.)
●Patients who receive parenteral nutrition support are at risk for infection, adverse metabolic effects, and complications related to venous access. (See 'Complications' above.)
