Related Experiment Videos
Gentamicin pharmacokinetics in neonates undergoing extracorporal membrane oxygenation
P Cohen1, L Collart, C G Prober
1Department of Pediatrics, Stanford University School of Medicine, CA 94305.
Insights
Extracorporeal membrane oxygenation (ECMO) significantly alters gentamicin pharmacokinetics in neonates. Dosing adjustments, including lower rates and longer intervals, are recommended during ECMO therapy.
Area of Science:
- Neonatal pharmacokinetics
- Critical care medicine
- Pharmacology
Background:
- Sepsis is a common complication in neonates requiring extracorporeal membrane oxygenation (ECMO).
- Gentamicin is frequently used to treat suspected sepsis in this vulnerable population.
- Understanding drug pharmacokinetics during ECMO is crucial for effective treatment.
Purpose of the Study:
- To evaluate the impact of ECMO on gentamicin pharmacokinetics in neonates.
- To determine appropriate gentamicin dosing strategies for infants undergoing ECMO.
Main Methods:
- Prospective pharmacokinetic study involving 18 neonates receiving ECMO.
- Gentamicin levels were measured during ECMO and after its discontinuation.
- Key pharmacokinetic parameters including volume of distribution, clearance, and half-life were analyzed.
Main Results:
- Neonates on ECMO exhibited a significantly higher volume of distribution (0.58 L/kg) compared to post-ECMO (0.45 L/kg).
- Gentamicin clearance was lower during ECMO (42 mL/kg/hr) versus post-ECMO (57 mL/kg/hr).
- The elimination half-life of gentamicin was prolonged during ECMO (10.0 hrs) compared to post-ECMO (5.7 hrs).
Conclusions:
- ECMO therapy significantly alters gentamicin pharmacokinetics in neonates, leading to increased distribution and reduced clearance.
- Current gentamicin dosing may result in subtherapeutic levels during ECMO.
- A dose reduction of approximately 25% and extended dosing intervals are recommended for gentamicin in neonates receiving ECMO.
Abstract:
We evaluated the effects of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics of gentamicin in 18 infants who underwent ECMO therapy for severe respiratory failure and received gentamicin for possible sepsis. Twelve of these infants continued to receive gentamicin after ECMO had been discontinued. The volume of distribution (Vd) of gentamicin in the newborns receiving ECMO was 0.58 +/- 0.04 liter/kg, compared with a Vd of 0.45 +/- 0.02 liter/kg after ECMO had been discontinued (P = 0.02). The clearance of gentamicin in the patients undergoing ECMO was 42 +/- 3 ml/kg/hour compared with 57 +/- 4 ml/kg/hour in those patients off ECMO (P = 0.003). The elimination half-life in patients receiving ECMO was 10.0 +/- 0.7 hours compared with 5.7 +/- 0.4 hours after ECMO had been discontinued (P less than 0.0001). Neonates undergoing ECMO demonstrate a higher volume of distribution of gentamicin, a lower clearance, and consequently a longer half life for this drug. We conclude that gentamicin and probably other aminoglycosides should be given at dose rates about 25% lower than usual and at longer dosing intervals in patients undergoing ECMO therapy.