Nephrotoxic Medications and Associated Acute Kidney Injury in Very Low Birth Weight Infants.

Preterm infants are at risk for acute kidney injury (AKI) for multiple reasons. Reports on the frequency and timeline of iatrogenic renal insults and potential consequences are limited. Our objectives are to estimate the prevalence and timing of exposure to nephrotoxic medications, and assess the association of these nephrotoxic medications with AKI in preterm infants. We performed a retrospective chart review of infants <30 weeks postmenstrual age and/or <1500 g birth weight admitted to the neonatal intensive care units at Cincinnati Children's Hospital Medical Center and University of Cincinnati Medical Center from 2011 to 2014. We queried the electronic health record for exposures to nephrotoxic medications and/or radiologic contrast media and correlated to serum creatinine concentration proximate to the exposure. Using the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria, we assessed the AKI rate associated with the exposures. The cohort included 276 preterm infants. 233 (84%) received nephrotoxicity-associated medications. Antibiotics were the most common type (80%). AKI occurred in 9% of infants and was associated with exposure to a nephrotoxic medication. In a forward stepwise logistical regression, birth weight (OR: 0.995 (95% CI: 0.991-0.998), p=0.004) and number of exposures (OR: 1.83 (95% CI: 1.33-2.53), p=0.0002) were predictive of AKI. Nephrotoxic medication exposure increased the odds of AKI in preterm and low birth weight infants. Future prospective surveillance through the electronic health record in addition to routine serum creatinine monitoring may reduce the rate of exposure and subsequent AKI.

Effect of heparin and other factors associated with complications of peripherally inserted central venous catheters in neonates.

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.

Maternal and neonatal factors impacting response to methadone therapy in infants treated for neonatal abstinence syndrome.

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=0.009). There was an inverse correlation between the amount of mother's breast milk ingested and length of stay (ß=-0.03, P=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.

Optimal gentamicin therapy in preterm neonates includes loading doses and early monitoring.

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.