Jay M. Mirtallo

State of the Art Review: Intravenous Fat Emulsions: Current Applications, Safety Profile, and Clinical Implications

Objective To review the current state of the science regarding intravenous fat emulsions (IVFEs), with an emphasis on their safety profile. Data sources Articles were identified via a search of the MEDLINE database, including publications from 1979 to December 2009, using a search string that included the terms parenteral nutrition, lipid emulsion, fat emulsion, IVFE, safety, adverse effect, neonate intralipid, and terms describing a range of specific adverse events (AEs) such as pancreatitis. Study selection and data extraction We selected articles that allowed us to compare the results of clinical trials involving delivery of medications via IVFEs with the historical use and effects of IVFEs in parenteral nutrition, with an emphasis on AEs. We focused on 2 drugs in current use that are administered intravenously in lipid emulsions: propofol and clevidipine. Data synthesis Clearance of the fat particles in IVFEs is mediated by the enzyme lipoprotein lipase. AEs are more likely if the rate or duration of IVFE administration exceeds the enzymes clearance capacity. AEs are also more likely after administration of a 10% IVFE formulation than a 20% formulation, because the higher concentration of free phospholipid in the 10% formulation interferes with lipoprotein lipase activity. AEs can be reduced by administering IVFEs at a dosage ≤2.5 g/kg/day and at a rate ≤0.11 g/kg/h. The anesthetic agent propofol, which is formulated in a 10% IVFE, has been used clinically for 25 years. Typical AEs associated with propofol use include infection, high plasma triglyceride concentrations, and pancreatitis. Recent clinical trials involving clevidipine, which is formulated in a 20% IVFE, have demonstrated a low rate of lipid-related AEs. Conclusions The results of this review demonstrate that IVFEs are well tolerated when administered in accordance with guideline recommendations.

A.S.P.E.N. Statement on Parenteral Nutrition Standardization

In response to questions regarding use of stan- dardized parenteral nutrition (PN) formulations, the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) devel- oped a Task Force to address some of these issues. A.S.P.E.N. envisions standardized PN as a broader issue rather than simply using a standardized, commercially available PN product. A stan- dardized process for PN must be explored in order to improve patient safety and clinical appropriateness, and to maximize resource efficiency. A standardized process may include use of standardized PN formulations (including standardized, commer- cial PN products) but also includes aspects of ordering, labeling, screening, compounding, and administration of PN. A safe PN system must exist which minimizes procedural incidents and maximizes the ability to meet individual patient requirements. Using clinicians with nutrition support therapy expertise will contribute to that safe PN system. The purpose of this statement is to present the published literature associated with standardized PN formulations, to provide recommendations, and to identify areas in need of future research. ( Journal of Parenteral and Enteral Nutrition 31:441-448, 2007)

A Comparison of Essential and General Amino Acid Infusions in the Nutritional Support of Patients with Compromised Renal Function

A comparative study of an essential amino acid (EAA) solution versus a general amino acid (GAA) solution in combination with a high density caloric solution (350 gram dextrose per 750 milliliter total volume) in patients with impaired renal function and receiving total parenteral nutrition was conducted. Forty-five patients were randomly assigned to receive either EAA [17 grams per liter (24)] or GAA [20 grams per liter (21)]. BUN values for days 1 to 10 of the study for each group declined at the same rate, 3.7 milligrams per deciliter per day for the GAA group and 2.8 milligrams per deciliter per day for the EAA group (p > 0.05, analysis of variance). BUN values at the start of the study were 78 ± 6.5, mean ± standard error of mean milligram per deciliter for the GAA group and 75 ± 7.5, mean ± standard error of mean, mg/dl for the EAA` group which were not different (p > 0.05, analysis of variance). Serum creatinine values of 5.9 ± 0.9, mean ± standard error of mean, milligram per deciliter for the GAA ...

International consensus guidelines for nutrition therapy in pancreatitis.

Guidelines for nutrition support in pancreatitis have been inconsistently adapted to clinical practice. The International Consensus Guideline Committee (ICGC) established a pancreatitis task force to review published guidelines for pancreatitis in nutrition support. A PubMed search using the terms pancreatitis, acute pancreatitis, chronic pancreatitis, nutrition support, parenteral nutrition, enteral nutrition, and guidelines was conducted for the period from January 1999 to May 2011. Eleven guidelines were identified for review. The ICGC used the following process to develop unified guideline statements: summarize the strength of evidence (grading) of the guidelines; establish level of evidence for ICGC statements as high, intermediate, and low; assign published guideline levels of evidence; and define an ICGC grading system. International Pancreatitis Guideline Grades were established as follows: platinum-high level of evidence and consistent agreement among the guidelines; gold-acceptable level of evidence and no conflicting statements in guidelines; and silver-single existing guideline statement with no conflict in other guidelines. Eighteen ICGC statements were derived from the 11 published pancreatitis guidelines. Uniform agreement from widely disparate groups (United States, Europe, Japan, and China) resulted in 4 platinum-level guideline statements for nutrition in pancreatitis: nutrition support therapy (NST) is generally not needed for mild to moderate disease, NST is needed for severe disease, enteral nutrition (EN) is preferred over parenteral nutrition (PN), and use PN when EN is contraindicated or not feasible. This methodology provides a template for future ICGC nutrition guideline development.

Compatibility of Medications With 3-in-1 Parenteral Nutrition Admixtures

BACKGROUND The absence of drug compatibility information with 3-in-1 parenteral nutrition admixtures has been problematic. The purpose of this project was to evaluate the physical compatibility of 106 selected drugs during simulated Y-site injection into nine different 3-in-1 parenteral nutrition admixture formulations. METHODS Four-milliliter samples of each of the representative 3-in-1 parenteral nutrition admixture formulations were combined in a 1:1 ratio with 4-mL samples of each of 106 drugs, including supportive care drugs, anti-infectives, and antineoplastic drugs. Six replicate samples of each combination were prepared. Two samples were evaluated initially after mixing, two more after 1 hour, and the last two after 4 hours at 23 degrees C. At each test interval, the samples were subjected to centrifugation, causing the fat to rise to the top. The top fat layer and most of the aqueous phase were removed, and the remaining liquid was diluted with about 7 mL of particle-free, high-performance liquid chromatography-grade water to facilitate observation of any particulates that might have formed. Visual examinations were performed in normal diffuse fluorescent laboratory light and under high-intensity, monodirectional light. RESULTS Most of the drugs tested were physically compatible with the 3-in-1 parenteral nutrition admixtures for 4 hours at 23 degrees C. However, 23 drugs exhibited various incompatibilities with one or more of the parenteral nutrition admixtures. Six drugs resulted in the formation of precipitate with some or all of the admixtures. Seventeen drugs caused disruption of the emulsion, usually with oiling out. CONCLUSIONS Most of the test drugs were physically compatible with the nine representative 3-in-1 parenteral nutrition admixtures. However, the 23 drugs that resulted in incompatibilities should not be administered simultaneously with the incompatible parenteral nutrition admixtures via a Y injection site.

The Effect of Catheter Type and Site on Infection Rates in Total Parenteral Nutrition Patients

Infections pose a major problem in patients receiving total parenteral nutrition. Controversy continues concerning the effect of catheter type (triple-, double-, single-lumen, or pulmonary artery), insertion site (subclavian, internal jugular, or femoral vein), and the incidence of catheter-related infections. We retrospectively studied multi-lumen catheter use for total parenteral nutrition over a 6-month period in 192 patients, a total of 3334 catheter days. Nonintensive care unit catheters were inserted by the Nutrition Support Service, and intensive care unit catheters were inserted by the intensive care unit staff. All catheters were cared for using Nutrition Support Service protocols, with multi-lumen catheters changed every 7 to 10 days and pulmonary artery catheters changed every 4 days. Infections were determined by semiquantitative cultures (> 15 colonies/plate). The incidence of infections for triple-lumen catheters was 5 (subclavian), 17 (internal jugular), and 36% (femoral) respectively; total infection rate for triple-lumen catheters was 10%. Infection rates for pulmonary artery catheters were 4 (subclavian), and 6% internal (jugular site), respectively, the overall infection rate was 5%. There were no differences in infection rates at any site based on catheter type; however, when triple-lumen catheter sites were compared, the differences were significant (p < .001 vs subclavian, chi 2). Catheter duration was 7.8 days (subclavian),, 7.3 days (internal jugular), and 4.6 (femoral) days. These data suggest that the use of multi-lumen catheters for total parenteral nutrition is safe, that there is a benefit associated with the subclavian route, and that the femoral site should be avoided.

A Parenteral Nutrition Use Survey With Gap Analysis

BACKGROUND Parenteral nutrition (PN) is a high-alert medication for which safe practice guidelines are available. Recent adverse events associated with PN have been widely reported. A survey of current practices was indicated as new guidelines are being considered. METHODS A web-based survey consisting of 70 items was made available for the month of August 2011. Respondents provided answers to questions that addressed all aspects of the PN use process. RESULTS There were a total of 895 respondents to the survey, including dietitians, nurses, pharmacists, and physicians. They predominantly represented hospital settings (89%), with 44% from academic institutions. Most organizations use a once-daily PN admixture with 21% outsourcing preparation. Electronic PN order entry is available in one-third of organizations, and the use of standardized order sets prevails. Unfortunately, electronic interfaces between computer systems remain infrequent, meaning that at least one transcription step is required by most in the PN use process. There are a wide variety of methods for ordering PN components, many of which are inconsistent with safe practices. Most organizations dedicate a pharmacist to review the PN orders, many of which require clarifications. Documentation at each step of the PN use process with oversight to identify deviations from best practice recommendations is infrequent. A significant proportion (44%) does not track PN-related medication errors. CONCLUSIONS The survey data are a valuable snapshot of current practices with PN. Poor compliance with some of the safe practice guidelines continues. This will help guide new safety initiatives for the PN use process.

Femoral catheters increase risk of infection in total parenteral nutrition patients.

Central venous access for the administration of total parenteral nutrition is usually achieved via the subclavian or internal jugular veins. Although a high incidence of complications has been reported with the use of femoral catheters for central venous access, this route has been used when traditional central venous access is contraindicated. We retrospectively reviewed 171 patients who received total parenteral nutrition via a central venous triple-lumen catheter and compared the rates of infections in femoral vs nonfemoral access. A literature review was performed to identify associated complications of and appropriate indications for femoral catheter use. In the 171 patients studied, 355 triple-lumen catheters were placed; these included 331 nonfemoral catheters and 24 femoral catheters. Femoral catheters were placed in nine patients. Femoral catheters had a greater incidence of positive tips (42% vs 6.9%, p < .001) and related bacteremia (16.7% vs 1.8%, p = .002) than did nonfemoral catheters. The organisms most commonly isolated from the blood and catheter tips of both catheter access sites were methicillin-resistant Staphylococcus epidermidis and Candida. The use of femoral catheters for central venous access for total parenteral nutrition administration results in an increased risk of infectious complications.

Parenteral Nutrition for Marrow Transplant Recipients: Evaluation of an Increased Nitrogen Dose

The use of total parenteral nutrition in bone marrow transplant (BMT) recipients is well recognized. These patients as a result of treatment with chemotherapy and immunosuppressive agents undergo catabolic stress. The metabolic effect of an increased nitrogen dose during total parenteral nutrition (TPN) was studied in 28 BMT patients. Patients were given TPN formulas providing a nitrogen intake of either 267 +/- 44 mg of N/kg/d or 330 +/- 60 mg of N/kg/d. Total calories, nonprotein and protein, were held constant at 40 kcal/kg/d for all patients. Data was collected for three periods posttransplant beginning at 3 days posttransplant through day 16. Both study TPN formulas improved patient weight and TIBC values over baseline. Nitrogen balance (NB) values were not significantly different at any study period. However, an overall group effect favored the H-N formula (p less than 0.01). BMT patients undergo catabolic stress which was reflected by average values of 24-hour urine urea nitrogen increasing from 8.1 +/- 4 g/d at baseline to 19.8 +/- 7.2 g/d at period 3 (p less than 0.01). The H-N formula did not differentially increase blood urea nitrogen or serum creatinine levels. Metabolic cart measures also showed no increase in metabolic rate, oxygen consumption, carbon dioxide production, or percent contribution of protein to total metabolic expenditure. Providing a caloric intake of 40 kcal/kg/d was excessive, where 30 to 35 kcal/kg/d would meet metabolic demands. Pertinent clinical outcomes including length of stay, relapse rate, and survival were monitored, but no conclusions could be drawn in this study. The H-N formula was more effective in reducing loss of lean body mass without causing detrimental metabolic effects in BMT patients.

Nutrition Care Given New Importance in JCAHO Standards

The 1995 standards developed by the Joint Commission on Accreditation of Healthcare Organizations are now in effect. In an unprecedented shift, the manual focuses on performance rather than structure and process. It emphasizes the interdisciplinary delivery of care, including nutrition care. This article describes the new standards as they relate to nutrition support professionals.