Development of Tolerance to Chronic Intermittent Furosemide Therapy in Pediatric Patients

Objectives: The purpose of this study is to describe whether tolerance develops in pediatric patients receiving chronic intermittent furosemide therapy, to characterize when it occurs and whether age-related variations exist. The effects of increasing total daily dose of furosemide and concurrent diuretics and vasopressors were assessed as secondary aims.

Methods: Charts from patients receiving intravenous or oral furosemide for at least 3 consecutive days of therapy between June 1, 2013, and December 31, 2013, were reviewed retrospectively. Daily net fluid balance was used as the objective marker for development of tolerance. Net fluid balance (mL/kg/mg) was defined as the difference in a patient's daily intake and urine output (mL), normalized by weight (kg) and total daily dose of furosemide (mg).

Results: Sixty-one patients, aged 2 days to 20 years (median 3 years), were included in this study. Median daily dose of furosemide was 1.96 mg/kg/day (range, 0-13.7 mg/kg/day). Average net fluid balance for all patients on the first day and last day of therapy was 6.83 and 26.66 mL/kg/mg, respectively (p = 0.011). Linear regression and Spearman's correlation found no significant relationship between age and difference in net fluid balance between the first and last day. Linear mixed-effects model for net fluid balance with day as covariate found that net fluid balance increases over time (p = 0.002).

Conclusions: Pediatric patients appear to develop tolerance to chronic intermittent furosemide therapy.