Premixed Parenteral Nutrition Solution Use in Children.

OBJECTIVES: In response to national drug shortages, our institution established criteria for the use of commercial premixed parenteral nutrition (PN) solutions in select pediatric patients. Although these solutions have been marketed for use in children, there are no data in this patient population. The objective of this study was to review our use of commercial premixed PN solutions in children. METHODS: This was a retrospective review of patients ≤18 years of age who received a premixed PN solution from October 2010 to April 2012. All premixed PN courses were assessed for incidence of premixed PN discontinuation due to laboratory abnormalities. Estimated goal and actual protein and total caloric intake were evaluated for premixed PN courses that were continued for >48 hours. RESULTS: Sixty-nine patients received 74 courses of premixed PN solutions for a mean duration of 5.6 ± 6.2 (range, 1-31) days. Fifteen courses (20%) required discontinuation of premixed PN as a result of mild laboratory abnormalities. No changes in clinical status were observed in patients and all abnormalities were corrected after switching to individualized PN. In patients receiving PN for >48 hours, premixed PN solutions provided goal protein in 48/49 (98%) courses and goal calories in 33/49 (67%) courses. CONCLUSIONS: Premixed PN solutions were used in a wide range of pediatric patients and provide a potential option for PN support in pediatric patients when drug shortages limit PN product supply. Close monitoring for electrolyte abnormalities and protein and caloric intake is recommended when using premixed PN solutions in children.

Ethanol lock therapy: a pilot infusion study in infants.

BACKGROUND: Ethanol lock therapy (ELT) has emerged as an effective method for the prevention and treatment of central line-associated bloodstream infections (CLABSIs), but the safety of ELT in infants has not been established. OBJECTIVE: The objective of this study was to determine blood alcohol concentration (BAC) and evidence of hepatic injury in infants after infusing a small one-time dose of ethanol, equivalent to the volume that would be flushed through the central venous catheter (CVC) after ELT is completed. METHODS: This was a prospective pilot study in infants weighing ≤6 kg with and without liver dysfunction who had a CVC. The primary end points were 5-minute and 1-hour BACs after a 0.4-mL dose of 70% ethanol was flushed through the CVC. Acceptable BACs were defined as <0.025% at 5 minutes and <0.01% at 1 hour. The secondary end point was evidence of hepatic injury, defined as a change of greater than 2 times the upper limit of normal of any component in the hepatic panel in patients with a normal baseline panel or doubling of any component in the hepatic panel in patients with an abnormal baseline panel (aspartate aminotransferase, alanine transaminase, total or direct bilirubin, gamma-glutamyl transferase, or alkaline phosphatase). RESULTS: A total of 10 patients were included for analysis, with a mean age and weight of 3.5 ± 2.4 months and 4.5 ± 0.9 kg, respectively. All patients had acceptable BACs and no evidence of hepatic injury. In 8 patients, 5-minute BACs were undetectable; BACs of the other 2 patients were 0.011%. One-hour BACs in all patients were undetectable. CONCLUSIONS: Flushing ELT resulted in acceptable BACs and no evidence of hepatic injury in this patient cohort. Further studies are needed to investigate the long-term safety and efficacy of ethanol infusion after ELT in this patient population for the prevention and treatment of CLABSIs.

Significant publications for pharmacy nutrition support practice in 2013.

PURPOSE: To assist the pharmacy clinician engaged in nutrition support in staying current with the most pertinent literature. METHODS: Several experienced board-certified clinical pharmacists in nutrition support compiled a list of publications published in 2013 that they considered to be important to their practice. The citation list was compiled into a Web-based survey whereby pharmacist members of the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), GI-Liver-Nutrition Practice Research Network of the American College of Clinical Pharmacy, and the Pharmacy and Pharmacology Section of the Society of Critical Care Medicine were asked to rank each article according to level of importance in their practice. RESULTS: A total of 30 articles were identified by the author group. Thirty-six participants responded to the survey. The top-ranked papers by participants from the Web-based survey were reviewed by the authors. Due to its high level of importance, the parenteral nutrition safety consensus recommendations article, to be published in 2014 by A.S.P.E.N., was also reviewed. CONCLUSION: It is recommended that the informed pharmacist, who is engaged in nutrition support therapy, be familiar with the majority of these publications.

Glomerular filtration rate equations do not accurately predict vancomycin trough concentrations in pediatric patients.

BACKGROUND: The Bedside Chronic Kidney Disease in Children (CKiD) equation was developed using data from children with chronic kidney disease. Some institutions are using this equation in all pediatric patients, regardless of renal function, to adjust medications. No data have shown that the Bedside CKiD equation is equivalent or better than the Schwartz equation in estimating glomerular filtration rate (GFR) in pediatric patients with normal renal function. OBJECTIVE: To compare GFR estimates using the Bedside CKiD and Schwartz equations and determine if either offers sufficient vancomycin dosing guidance in hospitalized pediatric patients. METHODS: This retrospective review at a single-center, academic, pediatric hospital included patients 2 to 12 years old with a steady-state vancomycin trough collected between January 1, 2010 and December 31, 2011. Patients with acute kidney injury or lacking essential data (e.g., height and serum creatinine), were excluded. An estimated GFR (eGFR) was calculated using the Schwartz and Bedside CKiD equations. Pearson correlations and linear regressions compared the eGFR values and vancomycin troughs. RESULTS: A total of 50 vancomycin troughs were analyzed. There was a weak relationship between the eGFR and troughs for the Schwartz equation (r (2) = 0.028) and Bedside CKiD equation (r (2) = 0.028). A weak relationship between serum creatinine and troughs was observed (r (2) = 0.132). Limitations include small sample size and retrospective design. CONCLUSIONS: Neither equation correlates well with vancomycin troughs, suggesting that therapeutic monitoring remains important. Better GFR estimation methods are needed in pediatrics to aid appropriate dosing of renally eliminated medications.

Evaluation of parenteral nutrition-associated liver disease in infants with necrotizing enterocolitis before and after the implementation of feeding guidelines.

BACKGROUND: In 2009, an intestinal rehabilitation team implemented feeding guidelines for infants following gastrointestinal surgery at our institution. The purpose of this study was to determine the effect of enteral feeding guidelines on the incidence of parenteral nutrition (PN)-associated liver disease (PNALD) in infants with surgically managed necrotizing enterocolitis (NEC). METHODS: This retrospective study included infants treated during 18-month time periods before and after the implementation of feeding guidelines. PNALD diagnosis was based on serum direct bilirubin >2 mg/dL after ≥14 days of PN exposure. RESULTS: Of the 140 infants identified, 64 were surgically managed and included in the analysis. The duration of PN and the time nil per os (NPO) were significantly reduced after guideline implementation from a median of 106 days to 65 days (P = .03) and from 29 days to 16 days (P = .02), respectively. The incidence of PNALD decreased from 73% before guideline implementation to 42% after guideline implementation (P = .01). CONCLUSIONS: Implementation of feeding guidelines resulted in decreased time NPO and duration of PN support. Significantly fewer infants developed PNALD after guideline implementation. These data suggest that feeding guidelines may expedite the transition from PN to enteral nutrition and may improve outcomes.

Enteral fish oil for treatment of parenteral nutrition-associated liver disease in six infants with short-bowel syndrome.

STUDY OBJECTIVE: To evaluate the use of enteral fish oil for the treatment of parenteral nutrition-associated liver disease (PNALD). DESIGN: Retrospective case series. SETTING: Pediatric academic hospital and outpatient clinic. PATIENTS: Six parenteral nutrition-dependent infants with short-bowel syndrome and PNALD. MEASUREMENTS AND MAIN RESULTS: The six infants received supplementation with enteral fish oil, and treatment was evaluated over a 12-week period. The PNALD, as reflected by elevated total bilirubin levels, completely reversed in four of the six infants within a mean ± SD of 5 ± 2.6 weeks (range 2-8 wks) after initiation of the enteral fish oil supplementation. In addition, improvement in enteral feedings occurred after starting enteral fish oil therapy. CONCLUSION: Enteral fish oil may be an effective adjunctive treatment option for infants with PNALD, particularly for those infants with PNALD who are tolerating some amount of enteral nutrition as the result of an adequate amount of small bowel.

Optimizing the transition to home parenteral nutrition in pediatric patients.

Parenteral nutrition (PN) is commonly used in pediatric institutions in patients who either cannot be fed enterally or are unable to tolerate sufficient enteral calories to provide their nutrition requirements. Many pediatric patients, particularly those with short bowel syndrome or intestinal failure, will eventually require home PN (HPN) therapy. Although discharge to HPN is complex and can be associated with both immediate and long-term complications, it can be successfully achieved through collaboration between healthcare providers within the institution and the home care company and HPN education of the patient and caregivers. This review describes the processes that clinicians and institutions should consider when preparing for HPN discharge and serves as a guide for the effective transition to HPN in pediatric patients.

Evaluation of microbial contamination associated with different preparation methods for neonatal intravenous fat emulsion infusion.

PURPOSE: Microbial contamination associated with different methods of neonatal intravenous fat emulsion (IVFE) preparation and delivery was evaluated. METHODS: Sterility testing was performed on IVFE dispensed via three different methods: (1) in the original container (n = 60), (2) repackaged into a syringe (n = 90), and (3) drawdown of the original container (n = 60). At the end of each infusion (24 hours for methods 1 and 3, 12 hours for method 2), a sample of the IVFE was withdrawn from the container using a sterile syringe in an International Organization for Standardization class 5 hood and sent to the hospital microbiology laboratory, where the samples were introduced into blood culture bottles and incubated for five days. Each sample was then subcultured on a blood agar plate with olive oil and left for an additional two days in a carbon dioxide incubator to assess for Malassezia furfur. RESULTS: None of the samples from the original containers showed bacterial or fungal growth. Three of the samples from syringes had bacterial growth (two samples contained coagulase-negative staphylococcus and one contained both Klebsiella oxytoca and Citrobacter freundii), yielding a contamination rate of 3.3%. The number of contaminated samples did not significantly differ among the three preparation methods (p = 0.13). CONCLUSION: Repackaging IVFE into sterile syringes resulted in bacterial contamination and should be avoided in clinical practice. IVFE samples obtained using the drawdown procedure under sterile conditions for infusion over 24 hours revealed no microbial contamination.

Iodine in enteral and parenteral nutrition.

Iodine deficiency (ID) has multiple adverse effects on growth and development due to inadequate thyroid hormone production. Methods for assessment of iodine nutrition in individuals include the urinary iodine concentration (UI), thyroid size and thyroid function tests. The UI measured in several repeat 24-h urine samples can detect inadequate iodine intake in individuals receiving enteral or parenteral nutrition (PN) and allow for iodine supplementation before the onset of hypothyroidism. A daily dose of 1 microg iodine/kg body weight is currently recommended for children receiving PN, but this is far below their requirements. Daily iodine requirements in adults receiving enteral nutrition or PN are estimated to be 70-150 microg, but most PN formulations do not contain iodine. Despite this, ID has been unlikely because absorption from iodine-containing skin antiseptics and other adventitious sources can provide sufficient iodine. However, if chlorhexidine replaces iodine-containing antiseptics for catheter care, ID may occur during long-term PN, and periodic testing of UI and thyroid function may be prudent. Infants may be particularly vulnerable to ID because of their small thyroidal iodine store. In this review, we describe three recent patients (an infant, a child and an adult) who developed ID and thyroid hypofunction during PN.

Integration of first- and second-year introductory pharmacy practice experiences.

OBJECTIVES: To describe the integration of a first- and second-year introductory pharmacy practice experience (IPPE) involving direct patient contact in hospitals and clinics as a means of more efficiently using academic and preceptor resources. DESIGN: Two IPPE courses were integrated in fall 2004 to accommodate increasing enrollment in classes and limited clinical practice sites and preceptors, as well as to meet the increased need for students and clinicians to practice principles of self-education. P1 and P2 students interviewed patients and presented patient cases; preceptor expectations were structured by instructional objectives. Student and preceptor course evaluations were assessed from survey data. ASSESSMENT: During the assessment period, all students passed the courses. Following integration of the IPPEs, both courses received positive evaluations from students and preceptors. Initial advanced pharmacy practice experience (APPE) grades for students completing the courses further suggests that the integrated IPPEs were beneficial to students. CONCLUSION: The successful integration of first- and second- year IPPE courses resulted in more efficient use of academic and preceptor resources and created a model for other colleges of pharmacy to consider.

The use of carnitine in pediatric nutrition.

Carnitine is synthesized endogenously from methionine and lysine in the liver and kidney and is available exogenously from a meat and dairy diet and from human milk and most enteral formulas. Parenteral nutrition (PN) does not contain carnitine unless it is extemporaneously added. The primary role of carnitine is to transport long-chain fatty acids across the mitochondrial membrane, where they undergo beta-oxidation to produce energy. Although the majority of patients are capable of endogenous synthesis of carnitine, certain pediatric populations, specifically neonates and infants, have decreased biosynthetic capacity and are at risk of developing carnitine deficiency, particularly when receiving PN. Studies have evaluated for several decades the effects of carnitine supplementation in pediatric patients receiving nutrition support. Early studies focused primarily on the effects of supplementation on markers of fatty acid metabolism and nutrition markers, including weight gain and nitrogen balance, whereas more recent studies have evaluated neonatal morbidity. This review describes the role of carnitine in metabolic processes, its biosynthesis, and carnitine deficiency syndromes, as well as reviews the literature on carnitine supplementation in pediatric nutrition.

Antimicrobial impregnated catheters in the prevention of catheter-related bloodstream infection in hospitalized patients.

Catheter-related bloodstream infections have a significant impact on increasing health care costs and morbidity and mortality in hospitalized patients. Many technologies have been created in an attempt to decrease the incidence of catheter-related bloodstream infection. One of these is the impregnation of central venous catheters with antiseptics (e.g., chlorhexidine and silver sulfadiazine) or antibiotics (e.g., minocycline and rifampin). While studies evaluating the efficacy of impregnated catheters have been conducted, the data are limited and their use remains variable across institutions. This paper will discuss catheter-related factors that predispose patients to catheter-related bloodstream infection, the types of antimicrobial-impregnated catheters in use today, studies evaluating their efficacy, and common concerns associated with the use of these catheters. Issues related to the cost-effectiveness of impregnated catheters and future directions for the prevention of catheter-related bloodstream infection will also be presented.

Should adding albumin to parenteral nutrient solutions be considered an unsafe practice?

PURPOSE: The technical issues surrounding the use of albumin in parenteral nutrient (PN) solutions are reviewed. SUMMARY: Five criteria have been suggested to determine which compounds are optimal for addition to PN solutions: (1) stable dosage regimen over 24 hours, (2) pharmacokinetic profile supporting a 24-hour infusion, (3) stable PN solution infusion rate, (4) documented physical stability over at least 24 hours, and (5) documented chemical stability over at least 24 hours. Albumin is stable in solutions containing dextrose and electrolytes, but its stability in solutions containing dextrose and amino acids has not been evaluated. Signs of precipitation and flocculation have been reported when albumin and zinc chloride were added simultaneously to a two-in-one PN solution. Similar to hemoglobin, albumin is nonenzymatically glycosylated in vivo. One of the most common complications associated with the use of PN solutions is catheter-related bloodstream infection. Albumin 25 g/L in two-in-one PN solutions has been shown to clog 0.2-microm filters. Albumin products have historically contained a large amount of aluminum contamination; thus, the addition of albumin to PN solutions would further contribute to accumulated aluminum contaminants in patients receiving PN therapy, particularly neonates. CONCLUSION: Based on the available evidence, the addition of albumin to PN solutions cannot be recommended. The potential for complications due to infection and physical and chemical incompatibility and instability exists. Adding albumin to PN solutions can affect infusion flow rates and pump pressures, thereby compromising the appropriate delivery of PN solutions to patients. The theoretical risk of glycosylation and related complications outweigh potential benefits of albumin administration via PN solution.

Relative bioavailability of carnitine supplementation in premature neonates.

BACKGROUND: Carnitine is an important nutrient in the infant diet. We compared total plasma carnitine concentrations in premature neonates supplemented with carnitine via parenteral and enteral nutrition. METHODS: This is a post hoc analysis of plasma total carnitine concentrations and carnitine intake in neonates randomized in a previous study to receive 20 mg/kg/d carnitine supplementation over 8 weeks. Neonates received l-carnitine initially via parenteral nutrition (PN). When neonates were fed enterally, oral supplementation of l-carnitine was given in divided doses with each feeding. RESULTS: Sixteen neonates (27 +/- 2 weeks gestation; 2.9 +/- 1.0 days postnatal age at enrollment; 965.6 +/- 279.1 g birth weight) are included. Concentrations were below reference range (31.1-60.5 nmol/mL) at baseline and exceeded reference range from week 1 through the last study period. Concentrations were not different from week 1 (108 +/- 49) through weeks 4 (87 +/- 34) and 8 (83 +/- 31). Carnitine intakes and concentrations were compared in neonates receiving 100% parenteral carnitine at week 1 (n = 6) and 100% enteral carnitine at week 8 (n = 8). Concentrations at week 1 (100.1 +/- 27.9) were not different (p = .19) from week 8 (78.6 +/- 29.3); an estimate of relative bioavailability was 78.6%. Bioavailability with paired analysis of neonates (n = 5) receiving 100% parenteral carnitine at week 1 and 100% enteral carnitine at week 8 was 83.7% +/- 41.2% (30.1%-140.6%). CONCLUSIONS: Parenteral and enteral supplementation of 20 mg/kg/d carnitine results in plasma total carnitine concentrations that exceed the reference range. Concentrations are not different between parenteral to enteral supplementation, suggesting that enteral carnitine is well absorbed when given daily in divided doses with enteral feedings.

Carnitine supplementation in premature neonates: effect on plasma and red blood cell total carnitine concentrations, nutrition parameters and morbidity.

BACKGROUND & AIMS: Carnitine may be considered conditionally essential in the neonatal population. The purpose of this study was to evaluate the effects of long-term carnitine supplementation on total carnitine status and morbidity in premature neonates. METHODS: In this prospective, randomized, placebo-controlled, double-blinded study, premature neonates received carnitine supplementation (20mg/kg/day) or placebo. Plasma (nmol/ml) and red blood cell (RBC) (nmol/mg hemoglobin) total carnitine concentrations, 24-h nitrogen excretion, intake and weight, and respiratory, gastroesophageal, and infectious morbidity were assessed. RESULTS: Twenty-nine neonates (13 placebo, 16 carnitine; 27+/-2 weeks gestation; 976+/-259g birthweight) were studied for up to 8 weeks. Plasma total carnitine concentrations exceeded the reference range in the carnitine group (weeks 1-8); however, concentrations did not reach reference range until week 4 in the placebo group. RBC total carnitine concentrations increased, but remained below reference range in both the carnitine (weeks 1-6) and placebo (weeks 1-8) groups. Carnitine group neonates regained their birthweight more rapidly than placebo group neonates (day of life 11.8+/-6 vs. 16.9+/-6.3, P=0.034). In addition, percent periodic breathing calculated from cardiopulmonary trend monitor data (weeks 1-8) was lower in the carnitine group (0.4+/-0.9 vs. 1.4+/-1.9, P=0.014). There was no difference with respect to other markers of respiratory, gastroesophageal and infectious morbidity or nitrogen balance. CONCLUSIONS: Carnitine supplementation at 20mg/kg/day results in increased plasma and RBC total carnitine concentrations, has a positive effect on catch-up growth, and may improve periodic breathing in premature neonates.

Increased parathyroid hormone and decreased calcitriol during neonatal extracorporeal membrane oxygenation.

OBJECTIVE: We noted that age-related normal calcium doses in neonates on venoarterial extracorporeal membrane oxygenation result in hypercalcemia. To avoid hypercalcemia and its potential consequences these infants are given one-half the normal calcium dose. We studied the pathogenesis of hypercalcemia and hypomagnesemia by evaluating calcitriol, intact parathyroid hormone, and calcitonin status during extracorporeal membrane oxygenation. DESIGN AND SETTING: Prospective, observational study in the intensive care unit of a 225-bed tertiary care pediatric hospital. PATIENTS AND PARTICIPANTS: Twelve neonates under 7 days old with severe pulmonary disease requiring extracorporeal membrane oxygenation. MEASUREMENTS AND RESULTS: Blood was obtained for intact parathyroid hormone and calcitriol concentrations before cannulation, during (extracorporeal membrane oxygenation days 2, 4, and predecannulation in those on >6 days), and after decannulation on days 1 and 3. Calcitonin concentrations were measured before cannulation, during, and after decannulation in the last seven patients. Prior to cannulation parathyroid hormone was normal (1.4-5.7 pmol/l) and on day 2 increased to 7.8+/-8.4 pmol/l. Before cannulation calcitriol was 14.5+/-8.21 pmol/l (normal 41-143 pmol/l), and concentrations remained low until after decannulation. In three of the seven infants calcitonin concentrations (normal <73 ng/l) were above the upper limit of the assay (>1150 ng/l) prior to cannulation and during extracorporeal membrane oxygenation. CONCLUSIONS: Regulation of the vitamin D-endocrine system during neonatal venoarterial extracorporeal membrane oxygenation appears to be aberrant compared to normal vitamin D-endocrine system regulation. The pathogenesis of this abnormality remains unclear and requires further study.

Evaluation of gastric pH and guaiac measurements in neonates receiving acid suppression therapy during extracorporeal membrane oxygenation.

STUDY OBJECTIVES: To assess gastric pH measurements, evaluate the frequency of guaiac-positive gastric aspirates, and characterize the appearance of gastric aspirates in neonates receiving acid suppression therapy during extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective, observational study. SETTING: Intensive care unit in a 225-bed tertiary care pediatric referral hospital. SUBJECTS: Thirteen neonates receiving ECMO. MEASUREMENTS AND MAIN RESULTS: Gastric pH measurements, guaiac test results, appearance of gastric aspirates, and ranitidine and antacid dosing were recorded. On ECMO day 1, mean+/-SD gastric pH was 4.3+/-2.8 in the five neonates whose pH was documented. Intravenous ranitidine 2.9+/-0.4 mg/kg/day was started in all neonates by ECMO day 2. Gastric pH was less than 4.0 in seven neonates; these low pH values accounted for only 10% of gastric pH measurements. The frequency of positive guaiac results in neonates with pH measurements below 4.0 was 27% compared with 41% for neonates with a gastric pH of 4.0 or greater (p=0.125). Guaiac tests were positive in 69 (42%) aspirates in 11 neonates. Of the guaiac-positive aspirates that had a corresponding pH measurement, 94% had a pH of 4.0 or greater. Guaiac-positive aspirates had evidence of bile (49%), antacid (17%), and blood (7%) in gastric fluid. In six patients, ranitidine dosages were increased to 3.9+/-0.6 mg/kg/day due to low pH and/or positive guaiac results. In two of these neonates, gastric pH remained below 4.0 in nine of 35 pH measurements despite increased ranitidine dosing. Guaiac results remained positive in all subsequent aspirates in five out of six of these neonates. No neonates developed clinically significant upper gastrointestinal bleeding (UGIB). CONCLUSIONS: Gastric pH is variable in neonates receiving histamine2-receptor antagonist and antacid therapy during ECMO, and gastric pH of 4.0 or greater does not decrease the frequency of guaiac-positive aspirates. Higher gastric pH measurements are confounded by duodenogastric reflux and the presence of blood and/or antacid in gastric fluid. Motility agents in combination with acid suppression therapy for prevention of UGIB may be necessary in this setting based on gastric pH measurements, appearance of gastric aspirates, and guaiac testing.