Optimal Furosemide Therapy in Critically Ill infants

Furosemide as continuous infusion is used in infants after cardiopulmonary bypass (CPB) surgery and during extracorporeal membrane oxygenation (ECMO). The currently used regimens which start with low dose (0.05 - 0.1 mg/kg.hr) may not be optimal in this group of patients with varying renal function. In an observational study the pharmacokinetics/pharmacodynamics (PK/ PD) of continuous furosemide therapy were evaluated in infants after CPB surgery. The study confirmed that the effects of furosemide are dependent on renal function. Therefore it was hypothesized that furosemide therapy may be more effective when the infusion is started at a higher dose. With the data from the observational study a PK/PD model was developed. The proposed furosemide regimen (loading bolus: 1-2 mg/kg; infusion rate 0.2 mg/kg.hr) by the PK/PD model was evaluated in infants after CPB surgery. Since adaptation of the furosemide doses was hardly needed, the proposed regimen seems rational. In a retrospective study furosemide regimens used in neonates during ECMO were evaluated. The regimens varied widely in continuous and intermittent doses. Given the wide variety of doses used, the regimens might not be optimal. Therefore more standardized and efficacious dosing regimens should be developed. As CPB and ECMO are comparable procedures the PK/PD model developed for infants after CPB surgery might also be applicable for infants on ECMO. In a prospective study the proposed furosemide regimen (loading bolus: 1-2 mg/kg; infusion rate 0.2 mg/kg.hr) by the PK/PD model was evaluated in infants during ECMO. The results suggest that the proposed furosemide dose was too high, since the dose had to be decreased in the majority of the patients. Therefore a novel PK/PD model should be developed for infants on ECMO. In conclusion the evaluated continuous furosemide regimens are safe and effective to augment urine production in critically ill infants. The PK/PD model developed for infants after CPB surgery should be used with caution in infants treated with ECMO.

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