Development of an optimal furosemide infusion strategy in infants with modeling and simulation

Abstract

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.

Evaluation of furosemide regimens in neonates treated with extracorporeal membrane oxygenation

“…Currently, a prospective study is being conducted in our unit to evaluate a continuous furosemide regimen, 0.2 mg/kg per hour, based on the PK/PD model developed for infants after CPB surgery for a predefined urine output of approximately 6 ml/kg per hour [19]. During the continuous furosemide infusion, serum furosemide levels are monitored at regular intervals to evaluate furosemide toxicity in newborns treated with ECMO.…”

“…Therefore, dosing regimens for continuous IV furosemide therapy in infants treated with ECMO should be developed. Because ECMO and CPB are 'comparable' procedures, the developed PK/PD model for infants after cardiac surgery might also be applicable for patients treated with ECMO [8,19]. …”

“…In the patients who received a 'loading' bolus, a positive effect was observed in urine output (Figure 2), but no statistically significant difference was reached in urine output in the first 24 hours or in the time to reach a urine output of 6 ml/kg per hour, which might be explained by the inter-individual variability and the difference in group size. In previous studies by our group on infants after CPB surgery, we suggested that continuous IV furosemide therapy would be more effective if initially started at a relatively high infusion rate and preferably preceded by a loading bolus [8,19]. With the developed PK/PD model for infants after cardiac surgery, we simulated various furosemide regimens and observed the effect of a furosemide loading bolus on urine production as well as on the time to reach the predefined urine output [8,19].…”

“…In previous studies by our group on infants after CPB surgery, we suggested that continuous IV furosemide therapy would be more effective if initially started at a relatively high infusion rate and preferably preceded by a loading bolus [8,19]. With the developed PK/PD model for infants after cardiac surgery, we simulated various furosemide regimens and observed the effect of a furosemide loading bolus on urine production as well as on the time to reach the predefined urine output [8,19]. …”

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement

“…As such, in patients with impaired renal function and decreased renal excretion of furosemide, higher dosing may be beneficial (85,86). In patients receiving repeated or chronic doses of furosemide, pharmacologic tolerance may develop related to a compensatory increase in sodium reabsorption in the distal tubule.…”