Population Pharmacokinetics of Gentamicin in Neonates with Hypoxemic-Ischemic Encephalopathy Receiving Controlled Hypothermia.

OBJECTIVE: Identify population pharmacokinetics and pharmacodynamic target attainment of gentamicin in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing controlled hypothermia (CH). DESIGN: Prospective open-label pharmacokinetic study. Gentamicin concentrations were modeled and dosing regimens simulated for a 5000-patient neonatal population with HIE receiving CH using PMetrics, a nonparametric, pharmacometric modeling, and simulation package for R. SETTING: A 189-bed children's tertiary care teaching hospital. RESULTS: Twelve patients, 5 (42%) females and 7 (58%) males, met inclusion criteria with a median gestation age of 39.9 weeks (interquartile range [IQR] 38.5-40.2 wks) and a median birthweight (BW) of 3.3 kg (IQR 3.1-3.7 kg). Gentamicin concentrations were best described by a two-compartment model with first-order elimination with BW as a covariate on volume of distribution (Vd). The mean total body population clearance (CL) was 2.2 ± 0.7 ml/minute/kg, and the volume of the central compartment was 0.44 ± 0.06 L/kg. The R2 , bias, and precision for the observed versus population predicted model were 0.917, 1.15, and 10.9 µg/ml; the R2 , bias, and precision for the observed versus individual predicted model were 0.982, -0.132, and 0.932 µg/ml, respectively. The calculated mean population estimate for the total Vd was 0.96 ± 0.4 L/kg. The dosing regimen that most consistently produced a maximum concentration (Cmax ) in the range of 10-12 mg/L with a minimum concentration (Cmin ) level less than 2 mg/L was 5 mg/kg/dose given every 36 hours. CONCLUSION: These data suggest the population pharmacokinetics of gentamicin in neonates with HIE receiving CH have an increase in gentamicin CL and are different from previous reports in neonates with HIE not receiving CH and/or neonates without HIE. This analysis suggests a dosing regimen of 5 mg/kg/dose every 36 hours results in a gentamicin Cmax within the range of 10-12 mg/L with a Cmin lower than 2 mg/L, which is appropriate for treating susceptible gram-negative organisms with minimum inhibitory concentrations of 1 mg/L or lower.

Transition to Routine Premedication for Nonemergent Intubations in a Level IV Neonatal Intensive Care Unit.

OBJECTIVE: This study aims to test whether implementing a guideline for nonemergent intubation improves the rate of premedication for nonemergent intubations in an academic level IV neonatal intensive care unit (NICU). We further sought to test the hypothesis that neonates who receive premedication for a nonemergent intubation have decreased pain scores at the time of intubation, fewer intubation attempts, and no associated adverse events. STUDY DESIGN: This was a prospective observational study with ongoing audit and feedback as well as statistical process control analysis. Data collection began on October 1, 2014. Clinical guideline implementation began in October 2015. A percent "P"-chart spanning seven-quarters was constructed with statistical process control analysis plotting premedication rates over time. Student's t-tests or Wilcoxon rank-sum tests were used for secondary outcomes. RESULTS: The mean number of nonemergent intubations given premedications increased from 34 to 82%. The mean pain score was lower when premedications were given: 0.34 (95% confidence interval [CI]: 0.10-0.58) versus 2.8 (95% CI: 1.9-3.6) (p < 0.001). The number of intubation attempts did not differ with premedications. CONCLUSION: Adopting a guideline with supporting educational initiatives to standardize premedication before nonemergent intubations increased this practice. This regimen lowered clinical pain scores with no difference in the number of intubation attempts.