Deonne Dersch-Mills

Extended interval dosing of gentamicin in premature neonates ≤ 28-week gestation

Aim:  To evaluate an extended interval dosing (EID) regimen of gentamicin in neonates ≤28‐week gestation.

Validation of a Dosage Individualization Table for Extended-Interval Gentamicin in Neonates

BACKGROUND: Extended-interval aminoglycoside dosing is increasingly used in neonates; however, guidance on how to monitor concentrations and adjust dosages accordingly is limited. OBJECTIVE: To prospectively validate the use of a 22-hour gentamicin concentration dosing table for the individualization of extended-interval dosing in the neonatal population by examining the peak and trough concentrations achieved through its use. METHODS: A prospective observational study was carried out on gentamicin concentrations achieved using a 22-hour post–first-dose gentamicin concentration dosing table for determining dosing intervals in neonates. Neonates (N = 104) in the first week of life, gestational age 23 weeks to full term, in level II and III neonatal intensive care units were included. Neonates were given gentamicin 5 mg/kg intravenously; a table using 22-hour post-first-dose gentamicin concentrations was then used to individualize dosing intervals. Pre- and post-serum gentamicin concentrations on the dosing interval indicated were measured with the second or third doses and used to calculate the peak and trough concentrations achieved. RESULTS: Use of the 22-hour post-first-dose gentamicin concentration dosing table resulted in dosing intervals that provided appropriate peak (mean 10.55 mg/L) and trough (mean 0.75 mg/L) concentrations (with second or third doses) in all neonates. All patients had trough concentrations less than 2 mg/L, and 73% had a trough concentration less than 1 mg/L. No peak concentrations were less than 5 mg/L, 82% of patients had a peak concentration from 5 to 12 mg/L, and the remaining 18% had concentrations from 12.1 to 16 mg/L. Peak and trough concentrations were similar across all gestational ages. CONCLUSIONS: Use of a 22-hour post-first-dose gentamicin concentration dosing table to individualize extended-interval gentamicin dosages in neonates resulted in appropriate peak and trough concentrations in all neonates studied. Use of this table will result in appropriate extended-interval aminoglycoside dosages in neonates early in treatment, using a single serum concentration.

Performance of a dosage individualization table for extended interval gentamicin in neonates beyond the first week of life

Abstract Objective: To assess the performance of a gentamicin dosing table for the individualization of extended-interval dosing (EID) in a neonatal population >7 days old. Methods: A prospective observational study was carried out on gentamicin concentrations achieved using a dosing table in neonates >7 days old. Neonates were given 5 mg/kg IV gentamicin; then a table using 22 h post-first dose gentamicin concentrations was used to individualize dosing intervals. Pre- and post-serum gentamicin concentrations were measured and used to calculate the true peak and trough concentrations achieved. Results: Use of the table resulted in dosing intervals that provided appropriate peak (mean 9.8 ± 1.8 mg/L) and trough (mean 0.6 ± 0.3 mg/L) concentrations in all neonates (n = 38). All trough concentrations were <2 mg/L, 83% were <1 mg/L. The majority of peak concentrations were in the usual target range (87%, 5–12 mg/L), with a few being in a higher, although likely safe range (13%, 12.1–15.7 mg/L). Conclusions: Use of this dosing table to individualize extended-interval gentamicin dosages in neonates >7 days old resulted in appropriate peak and trough concentrations in all neonates studied. This allows appropriate extended-interval aminoglycoside dosages in neonates early in treatment.

Dexmedetomidine Use in a Pediatric Intensive Care Unit: A Retrospective Cohort Study:

Background: Use of dexmedetomidine in critically ill pediatric patients is increasing despite limited data on effects on mechanical ventilation times, use of other sedatives, adverse effects, and withdrawal. Objectives: To describe the use and tolerability of dexmedetomidine in a large cohort of critically ill children. Methods: This was a retrospective cohort study of patients receiving dexmedetomidine in a pediatric intensive care unit. Ethical approval was granted by the local review board. Data on dexmedetomidine administration, ventilatory support, other sedatives, adverse effects, and withdrawal were collected. Results: There were 219 patients included. Dexmedetomidine was a first-line sedative in 47.9% of patients; the median infusion duration was 27 hours. Of patients on other sedatives at dexmedetomidine initiation, 39.5% had a dose reduction in those sedatives by 24 hours. Use of dexmedetomidine in noninvasively ventilated patients was common (19.6%), as was use in patients on no ventilatory support (35.6%). Patients receiving no ventilatory support used dexmedetomidine for shorter durations (P = 0.001) and were less likely to have received prior sedatives (P < 0.001). Adverse effects occurred in 42% of patients and were associated with younger age (P = 0.001) and longer dexmedetomidine duration (P < 0.001). The majority of patients (65%) were weaned off dexmedetomidine, and 80% of patients had at least one sign of withdrawal. Conclusions: Our data suggest substantial use in noninvasively ventilated patients. Adverse effects appeared more common in younger patients and those with prolonged infusions. A high rate of withdrawal effects was seen; no associations with age, dose, or duration were found.

Extended-interval gentamicin administration in neonates: an over-simplified approach

We read with interest the paper by El-Chaar et al on a simplified approach to extended interval dosing (EID) of gentamicin in neonates. We are pleased to see others recognize the benefits of using EID in neonates and approaching it in such a practical way. Our present practice is to adjust dosing intervals in neonates on EID using a single level drawn at 22 h post dose; we have validated this method in neonates less than and greater than 7 days of age and have found it a very effective and practical method. Our first concern with the authors’ approach is the very broad gestational age groupings. Maturation of nephrons occurs between 34 to 36 weeks, and the rate at which neonatal renal function increases ex utero is inversely related to the gestational age at birth. Because of this, the broad gestational age categories used in this study may not accurately account for these differences in renal function. For the authors’ dosing recommendation to be extended to infants of all gestational ages (GA), a much more detailed examination using smaller GA subgroups is required. The authors’ own data showing a higher rate of Cmin values 42 mg l − 1 in Group 1 supports this. In addition, the authors do not consider postnatal age in their suggested dosing scheme. Renal function changes rapidly over the first few weeks of life, and a lack of consideration of this in dosing aminoglycosides most certainly will render any dosing scheme inaccurate. There is a wide range of postnatal ages in the study groups (particularly in Group 1) and this most certainly will have created variability in the pharmacokinetic parameters of the study subjects. While the low rate of elevated Cmin values42 mg l 1 is reassuring, the authors may be missing a group of individuals in whom trough levels are undetectable for a prolonged period of time and may benefit from q24h dosing. For these reasons, we feel that the study results do not clarify the question of dosing for a 24-week GA infant in the first week of life compared with an ex 28-week infant with a corrected gestational age of 32 weeks or compared with a term infant on day 1 of life. The elevated mean AUC values and low percentage of target AUC values suggests that the values achieved in these groups may require closer examination for trends related to corrected gestational age and/or postnatal age. Dosage modifications in 24% of Group 1 study arm patients and 40% of Group 2 study arm patients raised further concern for adopting this proposed ‘simplified approach’ to EID gentamicin. It was good to see the positive safety outcomes reported by the authors, and we share the frustration when trying to determine clinical efficacy in this population.

Evolution of empiric vancomycin dosing in a neonatal population

BackgroundIn 2014, we assessed the effectiveness of our neonatal vancomycin empirical dosing regimen (15–45 mg/kg/day) which led to development of a revised regimen (20–60 mg/kg/day).ObjectiveTo validate the revised empirical vancomycin dosage regimen in achieving target troughs.MethodsThe primary outcome of this multicenter retrospective before-and-after cohort study was the proportion of neonates in the present cohort achieving trough levels below, at or above target (<10, 10–20 and >20 mg/L). Secondary outcomes included difference between cohorts (historical and present) in mean troughs and proportion of patients achieving target levels.ResultsOut of 118 participants, 63 (53.39%) achieved target troughs, 44 (37.29%) had below target troughs and 11 (9.32%) reached above target levels. Mean trough levels and proportion of patients achieving target levels were higher in the present versus historical cohort (p < 0.01 for all comparisons).ConclusionsThe revised empiric dosing regimen was more effective in achieving target serum trough concentrations.

Implementation of additional prescribing authorization among oncology pharmacists in Alberta

Purpose To describe the practice settings and prescribing practices of oncology pharmacists with additional prescribing authorization. Methods A descriptive, cross-sectional survey of all oncology pharmacists in Alberta was conducted using a web-based questionnaire over four weeks between March and April 2016. Pharmacists were identified from the Cancer Services Pharmacy Directory and leadership staff in Alberta Health Services. Descriptive statistics were used to describe the practice setting, prescribing practices, motivators to apply for additional prescribing authorization, and the facilitators and barriers of prescribing. Logistic regression was used to explore factors associated with having additional prescribing authorization. Results The overall response rate was 41% (71 of 175 pharmacists). Oncology pharmacists with additional prescribing authorization made up 38% of respondents. They primarily worked in urban, tertiary cancer centers, and practiced in ambulatory care. The top 3 clinical activities they participated in were medication reconciliation, medication counseling/education, and ambulatory patient assessment. Respondents thought additional prescribing authorization was most useful for ambulatory patient assessment and follow-up. Antiemetics were prescribed the most often. The median number of prescriptions written in an average week of clinical work was 5. Competence, self-confidence, and the potential impact on patient care/perceived impact on work environment were the strongest facilitators of prescribing. The strongest motivators to apply for additional prescribing authorization were relevancy to practice, the potential for increased efficiency, and advancing the profession. Conclusion The current majority of oncology pharmacist prescribing in Alberta occurs in ambulatory care with a large focus on antiemetic prescribing. Pharmacists found additional prescribing authorization most useful for ambulatory patient assessment and follow-up.