Efficacy of Low-Dose Epinephrine Continuous Infusion in Neonatal Intensive Care Unit Patients.

OBJECTIVES: Although epinephrine is used in the neonatal intensive care unit, few data exist on efficacy of doses <0.05 mcg/kg/min. This study evaluates the efficacy and safety of low-dose epinephrine continuous infusion at doses <0.05 mcg/kg/min in infants. METHODS: Single-center, retrospective review of hypotensive infants from 2011-2018. Charts were reviewed for initial and maximum epinephrine doses, additional vasoactive agents, short-term efficacy, and adverse effects. The primary outcome was percentage of patients initiated on low-dose epinephrine whose dose did not require titration to ≥0.05 mcg/kg/min. RESULTS: A total of 115 patients met study criteria with 131 distinct occurrences of low-dose epinephrine initiation. Most patients were unresponsive to other vasopressors at the time of epinephrine initiation. The median (IQR) starting dose of low-dose epinephrine was 0.01 (0.01-0.04) mcg/kg/min and median (IQR) maximum dose was 0.04 (0.02-0.08) mcg/kg/min. Fifty-five percent were responders. Patients in this cohort demonstrated significant improvement of blood pressure and urine output (p < 0.001) without adverse effects. CONCLUSIONS: Low-dose epinephrine infusion may be considered as an alternative treatment to standard starting doses in hypotensive neonatal intensive care unit patients.

Rhizopus Infection in a Preterm Infant: A Novel Use of Posaconazole.

Posaconazole is a triazole antifungal with activity against Rhizopus, but data on its use and pharmacokinetics in preterm infants are scarce. In this case, a 24 4/7-week neonate's Rhizopus infection is successfully treated with debridement and combination antifungal therapy with amphotericin B, micafungin and enteral posaconazole. This is the first reported posaconazole use in a preterm neonate with Rhizopus.

Effect of Exogenous Antithrombin Administration on Anti-Xa Levels in Infants Treated With Enoxaparin.

OBJECTIVES: Determine the effect of exogenous antithrombin III administration on low molecular weight heparin anti-Xa levels in the context of enoxaparin dosing in infants. METHODS: A retrospective chart review of infants receiving concomitant antithrombin III and enoxaparin. The primary objective of this study was to determine the median change in anti-Xa level with antithrombin III supplementation. Secondary objectives were to analyze the median change in antithrombin III levels after administration of exogenous antithrombin III, the dosing of antithrombin III, and the dose of enoxaparin throughout therapy. For a safety analysis, any bleeding events were recorded. RESULTS: The study included 17 patients who received a total of 33 doses of antithrombin III. The median change in anti-Xa levels in infants receiving exogenous antithrombin III was 0.2 units/mL (p < 0.001). The median dose of antithrombin III was 50 units/kg and was administered when patients were receiving a median enoxaparin dose of 1.71 mg/kg. The median increase in antithrombin III levels was 16.5% (p < 0.001). CONCLUSIONS: These results demonstrated that administration of exogenous antithrombin III to infants who were being treated with enoxaparin results in a significant increase in anti-Xa levels. At this time, there is insufficient evidence to recommend routine administration of antithrombin III to infants on enoxaparin. However, antithrombin III supplementation could be considered a potential option for patients who are unable to adequately achieve therapeutic anti-Xa levels with enoxaparin alone.

Pharmaceutical considerations with conjoined twins.

Sharing of the vascular system in conjoined twins creates pharmaceutical dilemmas that require individualization of protocols. One of the major goals for the medical team is to determine how medications should be administered, dosed, and monitored in each set of conjoined twins. In order to achieve these goals, the team must determine the extent of shared circulation, volume of distribution, effectiveness of enteral absorption, renal clearance, and develop processes to ensure medication safety. In this article, we discuss unique challenges in medication practices in conjoined twins and present general principles that can be applied to determine optimal pharmaceutical strategies.

Phenobarbital population pharmacokinetics across the pediatric age spectrum.

OBJECTIVE: Phenobarbital is frequently used in pediatric patients for treatment and prophylaxis of seizures. Pharmacokinetic data for this patient population is lacking and would assist in dosing decisions. METHODS: A retrospective population pharmacokinetic analysis was designed for all pediatric patients <19 years of age initiated on phenobarbital at our institution from January 2011 to June 2017. Patients were included if they were initiated on intravenous or enteral phenobarbital for treatment or prophylaxis of seizures and had a serum phenobarbital concentration monitored while an inpatient. Data collection included the following: age, weight, height, gestational age, core body temperature, serum creatinine, blood urea nitrogen, aspartase aminotransferase, alanine aminotransferase, urine output over the prior 12 hours, phenobarbital doses and serum concentrations, and potential drug-drug interactions. Descriptive statistical methods were used to summarize the data. Pharmacokinetic analysis was performed with NONMEM and simulation was performed for doses of 10, 20, 30, and 40 mg kg-1  dose-1 , iv, followed by enteral doses of 3, 4, 5, and 6 mg kg-1  d-1 . RESULTS: A total of 355 patients (50.3% male, median gestational age 39 weeks (interquartile range [IQR] 35, 40), median age 0.28 years (IQR 0.06, 0.82). Median phenobarbital dose was enteral = 2.6 (IQR 1.9, 3.9) mg kg-1  dose-1 ; intravenous = 2.6 (IQR 2.2, 4.9) mg kg-1  dose-1 ) and mean serum concentration was 41.1 ± 23.9 mg/L at median 6.5 (IQR 2.9, 11.1) hours after a dose. A one-compartment proportional error model best fit the data where clearance and volume of distribution were allometrically scaled using fat-free mass. Significant covariates included serum creatinine, postmenstrual age, and drug-drug interactions on clearance, and age in years on volume of distribution. SIGNIFICANCE: Phenobarbital dosing of 30 mg kg-1  dose-1 ,iv, followed by 4 mg kg-1  d-1 had the highest probability of attaining a therapeutic concentration at 7 days. Postmenstrual age and drug-drug interactions should be incorporated into dosing decisions.

A survey of mothers' comfort discussing contraception with infant providers at well-child visits.

OBJECTIVE: To determine whether mothers feel comfortable with their infants' providers discussing contraception with them at their infants' well-child checks. METHODS: A cross-sectional survey was conducted using a convenience sample of 114 mothers presenting at a community family medicine residency program for well-child visits among infants up to 17 months old. RESULTS: Almost all mothers (87%) felt comfortable talking with their infants' providers about contraception and were likely to accept the advice of their infants' providers to see their own doctors regarding contraception (83%) or to use a prescription from their infants' providers for contraception (75%). CONCLUSION: Many mothers miss or delay their postpartum visits but see their infants' doctor multiple times within the first year. Mothers are comfortable talking with infant providers about contraception. By discussing contraception with mothers at well-child visits, physicians may encourage mothers to use contraception and prevent unintended pregnancies.