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Gentamicin pharmacokinetics in term newborn infants receiving high-frequency oscillatory ventilation or conventional
Varsha Bhatt-Mehta1, Steven M Donn
1Department of Clinical Sciences, College of Pharmacy, University of Michigan, 200 E. Hospital Drive, Ann Arbor, MI 48109-0225, USA.
Insights
Infants on high-frequency oscillatory ventilation (HFOV) show reduced gentamicin clearance. Adjust gentamicin dosing intervals to 18 hours for these infants to ensure effective treatment.
Area of Science:
- Neonatal pharmacokinetics
- Pediatric critical care medicine
- Respiratory support
Background:
- Gentamicin is a critical antibiotic for neonatal infections.
- Mechanical ventilation strategies impact drug pharmacokinetics in infants.
- High-frequency oscillatory ventilation (HFOV) is used for severe respiratory distress.
Purpose of the Study:
- To compare gentamicin pharmacokinetics between infants receiving HFOV and conventional mechanical ventilation (CMV).
- To inform optimal gentamicin dosing strategies in neonates requiring different ventilation modes.
Main Methods:
- A case-controlled study reviewed records of full-term infants (≥37 weeks gestational age) from 1991-2001.
- Gentamicin administration, plasma concentrations, and renal function data were collected.
- Pharmacokinetic parameters including elimination rate constant, half-life, volume of distribution, and clearance were calculated.
Main Results:
- Infants on HFOV exhibited significantly reduced gentamicin clearance compared to those on CMV (p<0.05).
- Elimination rate constant and half-life also differed significantly between the ventilation groups.
- Mean peak airway pressure was higher in the HFOV group, but not statistically significant.
Conclusions:
- Infants receiving HFOV demonstrate impaired gentamicin elimination.
- Initial gentamicin dosing intervals should be extended to 18 hours for full-term infants on HFOV, deviating from the standard 12-hour interval.
Objective:
To compare the pharmacokinetics of gentamicin in infants receiving high-frequency oscillatory ventilation (HFOV) with infants receiving conventional mechanical ventilation.
Design:
A case-controlled study design was used to compare the pharmacokinetics of gentamicin in critically ill infants receiving HFOV and conventional mechanical ventilation. Medical records of all full-term newborn infants (> or =37 weeks gestational age) who received either high-frequency mechanical ventilation or conventional mechanical ventilation between 1991 and 2001 were reviewed and relevant patient demographics, renal function tests and gentamicin administration and plasma concentration data collected. Elimination rate constant, half-life, volume of distribution and clearance for both groups were calculated using standard kinetics equations.
Setting:
A tertiary care children's hospital.
Patients:
Newborn infants, > or =37 weeks gestational age, receiving gentamicin and high-frequency mechanical ventilation or conventional mechanical ventilation.
Measurements And Main Results:
In total, 18 patients were included in the conventional mechanical ventilation group and 15 in the HFOV group. The mean gentamicin dose for conventional mechanical ventilation and HFOV groups infants were 2.52+/-0.07 and 2.5+/-0.07 mg/kg/dose, respectively. Initial dosing interval was 12 hours in all of the conventional mechanical ventilation infants and 13 of the 15 HFOV infants. The dosing interval for the remaining two HFOV infants was 18 hours. No patient in either group demonstrated oliguria. Statistical analysis using the Student t-test for unequal variances yielded significant differences between the two groups with regard to elimination rate constant, half-life, volume of distribution and clearance, with a p value of <0.05 for all the observations. The mean of the highest P(aw) received by each patient in the HFOV group (19.2+/-4.05) was considerably higher than in the conventional mechanical ventilation group (13.4+2.23) (p>0.05).
Conclusion:
Infants receiving HFOV had reduced gentamicin clearance. Full-term infants receiving HFOV should be initiated at gentamicin dosing intervals of 18 hours rather than the traditional 12 hours recommended for this age group.
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