Objective: To identify maternal and neonatal factors that impact response to methadone therapy for neonatal abstinence syndrome.Study Design: This is a retrospective review of 128 infants that received pharmacotherapy for opiate withdrawal to identify factors associated with favorable response to methadone therapy. Maternal and neonatal data were analyzed with univariate statistics and multivariate logistic regression.Result: Maternal methadone maintenance dose during pregnancy correlated with length of stay (P ¼ 0.009). There was an inverse correlation between the amount of mother's breast milk ingested and length of stay (b ¼ À0.03, P ¼ 0.02). Methadone was initiated later, tapered more rapidly and was more successful as monotherapy in preterm infants. Five percent of infants were admitted to hospital again for rebound withdrawal following reduction of breast milk intake. Conclusion:Severity of neonatal abstinence syndrome may be mitigated by titrating methadone to the lowest effective dose during pregnancy and by encouraging breast milk feeds, which should be weaned gradually.

Objective To characterize the population pharmacokinetic (PK) of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome (NAS) and to develop a PK model towards an evidence-based treatment protocol. Study design Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed via high performance liquid chromatography-tandem mass spectrometry from dried blood spots. Population PK analysis was performed to determine the volume of distribution and clearance of oral methadone. Methadone plasma concentration-time profiles were simulated from the deduced PK model to optimize the dosing regimen. Results There was substantial inter-individual variability in methadone concentrations. Blood concentrations of methadone were best described by a one-compartment model with first-order absorption. The population mean estimates (coefficient of variation percentage) for oral clearance and volume of distribution were 8.94 (103%) L/h/70 kg and 177 (133%) L/70 kg, respectively. Optimized dosing strategies were developed based on the simulated PK profiles. We suggest a starting dose of 0.1 mg/kg per dose every 6 hours for most patients requiring pharmacologic treatment of NAS followed by an expedited weaning phase. Conclusions The proposed dosing regimen may reduce the cumulative dose of opioid and shorten the length of hospitalization. Future studies should aim to validate the simulated dosing schemes with clinical data and expand our understanding of the between-patient PK variability. Trial registration ClinicalTrials.gov: NCT01754324

Sodium supplementation of enteral feedings in very premature infants averts hyponatremia and enhances weight gain.

The choice of pharmacotherapeutic agent is an important determinant of hospital outcomes in infants with NAS. Sublingual buprenorphine may be superior to methadone for management of NAS in infants with select intrauterine opioid exposures.

No abstract

An NAS prediction tool combining three clinical signs with and without category of opioid exposure had high positive predictive values for requiring and for not requiring pharmacotherapy. This tool may expedite pharmacotherapy decisions and optimize management for infants at risk for NAS.

Objective: To identify factors associated with complications necessitating unplanned removal of peripherally inserted central venous catheters (PICCs) in neonates.Study Design: A before-and-after comparison following the exclusion of heparin from continuous infusions through PICCs placed by a designated team. Duration of use was assessed during epochs immediately preceding and following the practice change. Multivariable logistic regression was performed to identify independent risk factors associated with unplanned catheter removal.Result: We analyzed 189 PICC placements with heparin (epoch 1) and 188 with no heparin (epoch 2) added to infusions. Rates of complication (23.7 vs 17.2 per 1000 catheter days) and median durations of use (7 vs 8 days) did not differ significantly between the epochs. Non-central position of the catheter tip, use of dual lumen catheters and placement through the cephalic vein were independently associated with complications (each P<0.05). Conclusion:In neonates requiring short-term intravenous access, heparin may be safely omitted from continuous infusions without compromising catheter usability.

Recent studies have suggested the inadequacy of an initial gentamicin 2.5 mg/kg standard dose in neonates and the need for a loading dose. The purpose of this prospective, randomized study was to compare initial peak and initial trough serum gentamicin concentrations (SGC) in neonates after a standard dose (2.5 mg/kg) or a loading dose (4 mg/kg) on the first day of life. A secondary objective of the study was to evaluate the use of two SGC drawn after the first dose in designing individualized dosage regimens, despite the many changes in gentamicin disposition that occur over the first week of life. Forty infants admitted to the NICU were randomized to receive either 2.5 or 4 mg/kg gentamicin. Individual gentamicin pharmacokinetic parameters were determined after the first dose. Initial peak SGC were > 5 mcg/ml in only 6% of neonates receiving 2.5 mg/kg, versus 94% of neonates receiving 4 mg/kg. The initial trough after the first dose was < 2 mcg/ml in 100% of patients receiving 2.5 mg/kg and only 39% of patients receiving 4 mg/kg. Using two SGC after the first dose successfully predicted steady state peaks in 13/16 infants and steady state troughs in 14/16 infants. Thus, standard treatment of 2.5 mg/kg gentamicin yields initial peak serum gentamicin concentrations < 5 mcg/ml in neonates while a 4 mg/kg gentamicin loading dose, combined with pharmacokinetic monitoring after the first dose, optimizes gentamicin therapy in neonates.