Development of an optimal furosemide infusion strategy in infants with modeling and simulation.
BACKGROUND
The optimal dosing strategy for continuous intravenous furosemide infusion is unknown in pediatric patients. Eighteen patients less than 1 year old were studied after cardiac surgery during routine clinical care. The current strategy starts with a continuous infusion of 0.1 mg/kg x h, which may be adapted.


METHODS
A pharmacokinetic-pharmacodynamic model was developed that linked furosemide dose to furosemide serum concentrations, renal function (creatinine clearance), and urine output. Various regimens were simulated that adapt according to urine production. The modified dosing schedule was prospectively tested in a subsequent population of 18 pediatric patients after cardiac surgery.


RESULTS
Data from the follow-up study suggest that urine production is more controlled for the proposed regimen.


CONCLUSIONS
Both the modeling and simulation results and the follow-up study indicated that a bolus dose of 1 mg/kg followed 6 hours later with a 1- or 2-mg/kg loading dose and a 0.2-mg/kg x. h intravenous infusion provides a rational starting point for furosemide therapy after cardiac surgery in pediatric patients less than 1 year old. Adjustment of this regimen every 12 hours in steps of 0.1 mg/kg x h on the basis of clinical assessment should lead to adequate control over urinary output.
Schoemaker
Rik C
RC
Centre for Human Drug Research and the Pediatric Intensive Care Unit, Leiden University Medical Center, The Netherlands. rs@chdr.nl
van dDer Vorst
Maria M j
MM
van Heel
Isabelle Ruijs-Dudok
IR
Cohen
Adam F
AF
Burggraaf
Jacobus
J
D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005665:Furosemide / Q000008:administration & dosage* / Q000097:blood / Q000652:urine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D008956:Models, Chemical
D005665:Furosemide