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Development of an optimal furosemide infusion strategy in infants with modeling and simulation
Rik C Schoemaker1, Maria M j van dDer Vorst, Isabelle Ruijs-Dudok van Heel
1Centre for Human Drug Research and the Pediatric Intensive Care Unit, Leiden University Medical Center, The Netherlands. rs@chdr.nl
Insights
Optimal intravenous furosemide dosing for infants after heart surgery remains unclear. A new regimen, including a bolus and adjusted infusion, showed improved urine output control in pediatric patients.
Area of Science:
- Pediatric pharmacology
- Cardiovascular surgery
- Nephrology
Background:
- Optimal dosing for continuous intravenous furosemide infusion in pediatric patients is not well-established.
- Current strategies may require adaptation for effective use.
- Infants under one year undergoing cardiac surgery are a specific focus group.
Purpose of the Study:
- To determine an optimal dosing strategy for intravenous furosemide in pediatric patients.
- To develop and test a pharmacokinetic-pharmacodynamic model for furosemide therapy.
- To improve urine output management in infants post-cardiac surgery.
Main Methods:
- Developed a pharmacokinetic-pharmacodynamic model linking furosemide dose, serum concentrations, renal function, and urine output.
- Simulated various dosing regimens adapted to urine production.
- Prospectively tested a modified dosing schedule in a cohort of pediatric patients.
Main Results:
- The proposed furosemide dosing regimen demonstrated more controlled urine production in follow-up studies.
- Modeling and simulation supported the efficacy of the adjusted regimen.
Conclusions:
- A starting regimen of a 1 mg/kg bolus, followed by a 1- or 2-mg/kg loading dose and a 0.2 mg/kg/h infusion, is recommended for infants post-cardiac surgery.
- Adjustments every 12 hours based on clinical assessment can optimize urinary output.
- This provides a rational approach to furosemide therapy in this vulnerable population.
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.