Unintentional Manganese Delivery in Neonatal Parenteral Nutrition.

Iatrogenic manganese (Mn) neurotoxicity is a safety concern in neonates receiving parenteral nutrition (PN). Prior studies suggest Mn contamination of PN ingredients represents an unintended source of Mn delivery. In order to determine the relative contribution of unsourced Mn to total Mn exposure in neonatal PN, this study measured Mn concentrations in neonatal PN solutions using inductively coupled plasma mass spectrometry. Solutions prepared using a standard fixed dose neonatal multiple trace element product were compared with test solutions prepared using individual trace element ingredients not including Mn. The standard solutions (n = 6) contained a mean (SD) Mn concentration of 56.63 µg/L (0.94), compared with 6.04 µg/L (0.39) in the test solutions without added Mn (n = 6). This study suggests that neonatal PN contains significant quantities of Mn not intentionally added during PN preparation. Further studies are needed to identify individual ingredient sources of unintentional Mn, and the feasibility of Mn omission strategies.

Quality and Clinical Outcomes Associated with a Gentamicin Use System Change for Managing Chorioamnionitis.

Chorioamnionitis is an intra-amniotic infection with serious maternal and neonatal complications. Clinical studies suggest antibiotic administration before delivery reduces the risk of complications compared to after delivery. Our center implemented a standardized intrapartum gentamicin computerized provider order entry and dosage form dispensing system intended to improve treatment initiation efficiency in hospitalized obstetric patients. The primary objective of this retrospective study was to determine if these system changes were associated with decreased time from gentamicin ordering to administration in patients with chorioamnionitis. A secondary objective was to compare clinical outcomes before and after system changes. Classification and regression tree (CART) analyses was applied to identify key predictors. Results demonstrated a trend towards reduced time to administration in the post-implementation group. Clinical outcomes were not altered. CART analysis revealed that post-implementation assignment and length of membrane rupture predicted shorter time to gentamicin initiation. This study suggests that the specific system changes we implemented were safe and improved efficiency, but additional changes are needed to have a clinically significant impact.

A Pilot Randomized Controlled Trial of Early versus Routine Caffeine in Extremely Premature Infants.

OBJECTIVE: This study aims to compare the effects of early and late (routine) initiation of caffeine in nonintubated preterm neonates. STUDY DESIGN: A total of 21 neonates < 29 weeks gestational age were randomized to receive intravenous caffeine citrate (20 mg/kg) or placebo either before 2 hours of age (early) or at 12 hours of age (routine). This was an observational trial to determine the power needed to reduce the need for endotracheal intubation by 12 hours of age. Other outcomes included comparisons of cerebral oxygenation, systemic and pulmonary blood flow, hemodynamics, hypotension treatment, oxygen requirement, and head ultrasound findings. RESULTS: There was no difference in the need for intubation (p = 0.08), or vasopressors (p = 0.21) by 12 hours of age. Early caffeine was associated with improved blood pressure (p = 0.03) and systemic blood flow (superior vena cava flow, p = 0.04 and right ventricular output, p = 0.03). Heart rate, left ventricular output, and stroke volume were not significantly affected. Cerebral oxygenation transiently decreased 1 hour after caffeine administration. There were no differences in other outcomes. CONCLUSION: This pilot study demonstrated the feasibility of conducting such a trial in extremely preterm neonates. We found that early caffeine administration was associated with improved hemodynamics. Larger studies are needed to determine whether early caffeine reduces intubation, intraventricular hemorrhage, and related long-term outcomes.

Transmission of meropenem in breast milk.

A case is presented of a breast-feeding mother receiving meropenem treatment for a postpartum urinary tract infection caused by extended-spectrum beta-lactamase producing Escherichia coli. Five milk samples were collected in a 48-hour period during meropenem therapy. The average and maximum meropenem concentrations in milk were 0.48 and 0.64 µg/mL, respectively. Based on the maximum concentration, the calculated infant daily exposure from breast milk was 97 µg/kg/d, and the infant weight-adjusted percentage of maternal dosage was 0.18%. There were no dermatologic or gastrointestinal side effects noted in the breastfed infant. Meropenem appears to be acceptable to use during breast-feeding.

Breast milk hydrocodone and hydromorphone levels in mothers using hydrocodone for postpartum pain.

OBJECTIVE: To estimate the extent of passage of hydrocodone and its active metabolite, hydromorphone, into breast milk. METHODS: This is a pharmacokinetic study of 30 postpartum women receiving hydrocodone bitartrate for postpartum pain in the inpatient setting. Mothers donated timed breast milk samples for the analysis of hydrocodone and hydromorphone. RESULTS: Fully breastfed neonates received 1.6% (range 0.2%-9%) of the maternal weight-adjusted hydrocodone bitartrate dosage. When combined with hydromorphone, the total median opiate dosage from breast milk is 0.7% of a therapeutic dosage for older infants. Most mothers excreted little to no hydromorphone into breast milk. CONCLUSION: Standard postpartum dosages of hydrocodone bitartrate appear to be acceptable to use in women nursing newborns. Prolonged use of high dosages is not advisable.

Origins of and solutions for neonatal medication-dispensing errors.

PURPOSE: Five cases of sound-alike, look-alike, neonatal medication-dispensing errors and their resolution are reviewed. SUMMARY: In 2008, there were five cases in which look-alike or sound-alike neonatal medication-dispensing errors occurred at our institution. A mix-up between neonatal and adult or pediatric products occurred in four of the five cases. Three of the five errors resulted in near misses with the potential to cause harm. The other two errors reached the patients but did not cause harm. The medication mix-ups involved adult and neonatal phytonadione injectable emulsion, sodium citrate injection and vancomycin-heparin combination injection, adult tetanus-diphtheria-acellular pertussis and infant diphtheria-tetanus-acellular pertussis (DTaP) vaccines, Haemophilus B and DTaP vaccines, and cisatracurium and vecuronium. Each error exposed weaknesses in the system of neonatal medication storage, labeling, delivery, knowledge, and administration documentation at our institution. Resolution of system problems was made possible by a collaborative approach and involved reorganizing shelving used to store neonatal medications; using a differently colored labeling scheme for products whose syringes were nearly identical; implementing changes to the infant vaccine ordering, storage, dispensing, and documentation systems; and instituting centralized and decentralized pharmacist review of pharmacy technician automated dispensing cabinet-filling activities. CONCLUSION: An institution providing services to both neonatal and adult patients experienced five cases of medication-dispensing errors with look-alike or sound-alike medications. Multidisciplinary collaboration within the system helped the pharmacy identify, resolve, and prevent errors related to medication storage, labeling, delivery, knowledge, and administration documentation.

Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the neonate.

BACKGROUND: Hospitalized neonates are exposed to antibiotic-resistant bacterial pathogens and develop nosocomial infections. Limited data are available regarding the neonatal pharmacokinetics of meropenem, a broad spectrum carbapenem antibiotic. METHODS: Neonates <2 months of age received a single dose of meropenem at 10 or 20 mg/kg. Meropenem serum concentrations were measured at specified times during the 24 hours postinfusion. Population pharmacokinetics (PPK) were evaluated using NONMEM. Using Monte Carlo simulation (MCS), the probability of pharmacokinetic-pharmacodynamic target attainment was evaluated by computer modeling from predictions extrapolated from PPK data, using "virtual" dosing regimens of 10, 20, and 40 mg/kg administered every 8 or 12 hours against community- and hospital-acquired pathogens. RESULTS: Thirty-seven neonates were enrolled, 22 were born at <36 weeks (range, 23-41 weeks) gestational age. Meropenem clearance was greater in neonates with older chronologic ages and in those born at later gestational ages. Serum creatinine and postconceptional age (PCA) were the best overall predictors of meropenem elimination: CL (L/h/kg) = 0.041 + 0.040/SCr + 0.003 x (PCA-35). MCS demonstrated that in infants during the first 2 weeks of life, a dosage of 20 mg/kg/dose every 8 hours achieved the desired PD target in 95% of preterm neonates and 91% of term neonates against Pseudomonas aeruginosa isolated from patients managed in adult and pediatric intensive care units in the United States. CONCLUSIONS: MCS based on PPK determinations demonstrated that a meropenem dose of 20 mg/kg every 8 hours should provide adequate therapy for most nosocomial Gram-negative pathogens.

Hydrocodone excretion into breast milk: the first two reported cases.

Hydrocodone is a narcotic that is widely used, often in nursing mothers. Although case reports suggest that hydrocodone in breast milk sometimes may be problematic for the breastfed infant, no reports exist on the amount of its excretion into breast milk. Two mothers who were taking an acetaminophen and hydrocodone combination product donated pumped milk for analysis of hydrocodone. Their infants received an estimated 3.1% and 3.7% of the maternal weight-adjusted dosage, but the absolute hydrocodone dosages were 8.58 microg/kg per day and 3.07 microg/kg per day because of the differences in the dosages ingested by their mothers. Moderate dosages of hydrocodone appear acceptable during breastfeeding, but more data are needed to determine the maximum safe dosage for nursing mothers. Neonates and preterm infants may be more susceptible than older infants to adverse effects of hydrocodone and its metabolites in breast milk.