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Development of an optimal furosemide infusion strategy in infants with modeling and simulation
Author(s) -
Schoemaker Rik C.,
Vorst Maria M. J.,
Heel Isabelle RuijsDudok,
Cohen Adam F.,
Burggraaf Jacobus
Publication year - 2002
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2002.127608
Subject(s) - furosemide , medicine , dosing , pharmacokinetics , regimen , renal function , anesthesia , creatinine , pharmacodynamics , bolus (digestion) , cardiac surgery , urinary system , urology , pharmacology , surgery
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 · 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 · 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 · h on the basis of clinical assessment should lead to adequate control over urinary output. Clinical Pharmacology & Therapeutics (2002) 72 , 383–390; doi: 10.1067/mcp.2002.127608