Robert L. Poole

Treatment of catheter occlusion in pediatric patients.

A proper initial assessment of catheter occlusion is the key to successful management. The assessment screens are for both thrombotic and nonthrombotic causes (including mechanical occlusion). If mechanical occlusion is excluded, thrombotic occlusion is treated with alteplase. Nonthrombotic occlusions are treated according to their primary etiologies: lipid occlusion is treated with 70% ethanol, mineral precipitates are treated with 0.1-N hydrochloric acid (HCl), drug precipitates are treated according to their pH-acidic drugs can be cleared with 0.1-N HCl, basic medications can be cleared with sodium bicarbonate or 0.1-N sodium hydroxide (NaOH). Prevention of occlusion of central venous access devices is also critical. To date, no data conclusively show heparin flushes to be superior to saline flushes. No prophylactic regimen, including low-dose warfarin, low-molecular-weight heparin, or 1 unit heparin/mL of parenteral nutrition has been endorsed by any major medical, nursing, or pharmacy group due to lack of scientific evidence. The most encouraging information on decreasing occlusion rate comes from experience with positive-pressure devices that attach to the hub of most catheter lumens and prevent retrograde blood flow and, consequently, decrease the risk of thrombus formation in the catheter lumen.

Copper Deficiency During Parenteral Nutrition: A Report of Four Pediatric Cases:

The standard of care for patients with cholestasis (direct bilirubin >or=2 mg/dL) while receiving parenteral nutrition (PN) solutions is to reduce or discontinue the copper and manganese. The repercussions of this action have not been studied. Two adult case reports document low serum copper levels associated with clinical symptoms of copper deficiency after the removal of copper from their PN solutions. We now describe the first known series of pediatric patients to develop copper deficiency after copper was removed from their PN solutions.

Calcium and Phosphorus in Neonatal Parenteral Nutrition Solutions

Due to calcium and phosphorus solubility problems in parenteral nutrition solutions, it is difficult to provide the premature infant with enough of these two minerals for adequate bone mineralization. In order to determine the maximum amounts of both Ca and P soluble in neonatal parenteral nutrition solutions, we employed the following procedure: (1) using concentrations of dextrose 10 to 25% and amino acid 0.5 to 4.0% with standard electrolyte and vitamin concentrations, Ca and P additions were sequentially made to determine the critical concentrations at which precipitates formed; (2) the pH of each test solution was determined; (3) all test solutions were incubated for 30 hr at room temperature; (4) following incubation, all tests were visually observed for calcium-phosphate crystals; (5) the solutions not obviously precipitated were filtered using black Millipore filters to determine the presence of any microprecipitates. Multiple graphs of Ca and P solubility in various dextrose/amino acid solutions were prepared from data generated by the study. The Ca and P interaction is primarily pH sensitive. Factors affecting the solution pH include both dextrose and amino acid concentrations. Our study showed that increases in amino acid concentrations enabled us to increase both Ca and P in the solutions.

The Use of IV Fat in Neonates

IV fat emulsion (IVFE) is an integral part of the parenteral nutrition (PN) regimen in neonates. It provides a concentrated isotonic source of calories and prevents or reverses essential fatty acid deficiency. Continuous administration of IV fat with PN regimens prolongs the viability of peripheral IV lines in infants who might have limited venous access. IVFE must be administered separately from the PN solution in neonates. The acidic pH of a PN solution is necessary for maximum solubility of calcium and phosphorus. If fat emulsion is added to the PN solution, as is done in 3-in-1 (total nutrient admixture) solutions, the high amount of calcium and phosphorus needed by these infants may result in an unseen precipitate with serious consequences. Continuous fat infusion over 24 hours is the preferred method in neonates. The administration rate of 0.15 g/kg/hour for IVFE in the neonate should not be exceeded. Essential fatty acid deficiency can be prevented in neonates by providing IVFE in a dose of 0.5-1.0 g/kg/day. Carnitine is not routinely required to metabolize IVFE in the neonate. Infants should receive 20% lipid emulsion to improve clearance of triglycerides and cholesterol. Serum triglyceride levels should be maintained at <150-200 mg/dL in neonates. There are concerns about potential adverse effects of early administration of IV fat in very-low-birth-weight infants weighing <800 g. We hold the IV fat dose at 1.0-1.5 g/kg/day until the second week of life in infants <30 weeks gestation.

Clinical pathway for pediatric parenteral nutrition.

The nutrition support team at Lucile Salter Packard Childrens Hospital at Stanford developed a clinical pathway for infants and children receiving parenteral nutrition (PN). Use of clinical pathways for health care delivery is one way in which clinicians and institutions are responding to pressure from managed care organizations to reduce costs and maintain or improve quality. This pathway was developed to standardize the process for ordering, implementing, and monitoring PN. Specific goals for the pathway are as follows: to decrease the number of patients receiving PN inappropriately, to decrease the duration of PN for those patients who require it, to determine complication rates, and to monitor outcomes of therapy. Such comprehensive monitoring will help identify areas for improvement. By developing and implementing action plans to address these issues, we expect to improve continuously the processes and outcomes associated with PN therapy.

The use of alteplase for restoring patency to occluded central venous access devices in infants and children.

A 21-month retrospective review was completed at the Lucile Packard Children’s Hospital to assess the experience of 22 infants and children who received alteplase for the clearance of occluded central venous access devices. After the first dose, 86% (n = 19) of the catheters cleared. Two additional catheters cleared with a second dose. With alteplase treatment, 95% (n = 21) of the catheters cleared. No adverse events were noted within 24 hours after the alteplase was received. Infusion of alteplase appeared to be safe and effective in restoring patency to occluded central venous access devices in infants and children.

Aluminum exposure in neonatal patients using the least contaminated parenteral nutrition solution products.

Aluminum (Al) is a contaminant in all parenteral nutrition (PN) solution component products. Manufacturers currently label these products with the maximum Al content at the time of expiry. We recently published data to establish the actual measured concentration of Al in PN solution products prior to being compounded in the clinical setting [1]. The investigation assessed quantitative Al content of all available products used in the formulation of PN solutions. The objective of this study was to assess the Al exposure in neonatal patients using the least contaminated PN solutions and determine if it is possible to meet the FDA “safe limit” of less than 5 μg/kg/day of Al. The measured concentrations from our previous study were analyzed and the least contaminated products were identified. These concentrations were entered into our PN software and the least possible Al exposure was determined. A significant decrease (41%–44%) in the Al exposure in neonatal patients can be achieved using the least contaminated products, but the FDA “safe limit” of less than 5 μg/kg/day of Al was not met. However, minimizing the Al exposure may decrease the likelihood of developing Al toxicity from PN.

Propylene Glycol Toxicity in Children

Propylene glycol (PG) is a commonly used solvent for oral, intravenous, and topical pharmaceutical agents. Although PG is generally considered safe, when used in high doses or for prolonged periods, PG toxicity can occur. Reported adverse effects from PG include central nervous system (CNS) toxicity, hyperosmolarity, hemolysis, cardiac arrhythmia, seizures, agitation, and lactic acidosis. Patients at risk for toxicity include infants, those with renal or hepatic insuficiency, epilepsy, and burn patients receiving extensive dermal applications of PG containing products. Laboratory monitoring of PG levels, osmolarity, lactate, pyruvate, bicarbonate, creatinine, and anion gap can assist practitioners in making the diagnosis of PG toxicity. Numerous studies and case reports have been published on PG toxicity in adults. However, very few have been reported in pediatric patient populations. A review of the literature is presented.

Echinocandin and ethanol lock therapy treatment of fungal catheter infections.

Ethanol lock therapy has been implemented to prevent infections of central venous catheters as well as to treat infections. Fungal catheter-associated blood stream infections are historically more difficult to treat and have required removal of central venous catheters. We report the largest case series to date, successfully treating 5 of 7 fungal catheter-associated blood stream infections with ethanol lock therapy and systemic echinocandin administration.

Medication Errors in Children

To the Editor: Dr Kaushal and colleagues 1 reported that more than 93% of the medication errors they identified in children might have been prevented by computerized physician order entry (CPOE) and ward-based clinical pharmacists. The problem of medication errors in pediatric inpatients has been known for some time. We reported the value of clinical pharmacist involvement in preventing medication errors in children’s hospitals in 1987. 2 Clinical pharmacists in children’s hospitals deal daily with the special medication needs of pediatric and neonatal patients, whose weights can vary from 400 g to 120 kg. Because the dosing of most drugs is based on weight, there is the potential for a 300-fold dosing error. In adult patients, a 2-fold dosing error is usually the maximum encountered, as pharmaceutical manufacturers provide medications in adult unit dose packaging. Few drugs are available from manufacturers in ready-to-administer pediatric or neonatal unit doses or dosage forms. Pediatric pharmacists are routinely required to prepare dilutions, repackage, or compound dosage forms. In addition, most of the more than 10000 drugs on the market in the United States are not labeled with a pediatric indication nor have they been studied in pediatric or neonatal populations. These problems put pediatric and neonatal patients at increased risk for an adverse drug event. Also, hospital computer systems and software applications are usually developed for adult patient populations. Currently, CPOE is estimated to be installed in less than 5% of the 6600 hospitals in the United States with the nation’s 75 children’s hospitals representing a very small proportion (unpublished data). This safety system is therefore least available to the most vulnerable patient population. Additional resources should be allocated for studies to prevent and reduce medication errors. Hospitals, health systems, insurance companies, and state and federal governments must invest in making the health care system safer for all patients, but especially for children. More than media attention is needed to address this serious and complex problem.