Pharmacodynamic Determinants of Furosemide Diuretic Effect in Children

Abstract

The pharmacodynamics of 1 or 2 mg/kg of furosemide administered as a single dose orally or intravenously were studied in 34 hospitalized children (ranging in age from 9 days to 16.5 years) with normal renal function. These patients were divided into 3 groups: infants (furosemide 1 mg/kg, intravenously); children with steroid-responsive nephrotic syndrome (furosemide 2 mg/kg, orally and intravenously); patients with urinary tract infections and mild hypertension (furosemide 2 mg/kg, orally). A statistically significant positive linear relationship was found in these groups between the furosemide urinary excretion rate and urine flow rate, but log dose-response curves to furosemide were found to vary between the groups of patients studied. This variability reflects differences in the relationship between the amounts of furosemide reaching active sites and the pharmacodynamic effect of the drug. No sigmoid-shaped log dose-response curve (i.e., one approaching a zero response at very low furosemide urinary excretion rates, and a maximum response at very high excretion rates) was attained in this study. This suggests that the capacity of the kidney tubules to respond diuretically to the administered doses of furosemide was not exceeded in the studied patients. However, in the infants, a very steep log dose-response curve to a 1 mg/kg intravenous dose of furosemide suggests that higher doses may not result in a significant increase in diuretic response in infants with reasonably normal renal function. The lowest mean furosemide urinary excretion rate associated with significant diuresis was 0.58 ± 0.33 gg/kg/min. Also, a significant correlation was found between the amount (in milligrams), of furosemide excreted in the urine during the first 6 h after administration and the urine volume collected during that time (r = 0.71; p < 0.001; number of measurements = 43).

Renal Response to Furosemide in Very Low Birth Weight Infants during Chronic Administration

“…Urinary furosemide excretion increased dramatically, from Table 3. Furosemide dose size (mg/kg) and route of administration adults and in newborn animals have demon strated that tubular response to furosemide can be evaluated by studying the dose-re sponse relationship between the logarithm of urinary furosemide excretion rate and di uretic/natriuretic response [6,7,10]. In the current study, we have used this technique to investigate changes in renal response to furo semide in premature infants with BPD.…”

“…Furosemide's site of action is within the lumen of the ascending limb of the loop of Henle [6], In both adults and infants a doseresponse relationship has been demon strated between the urinary excretion rate of drug and diuretic and natriuretic response [6,7], In adults, sustained furosemide ad ministration results in decreased response to luminal furosemide, as renal compensatory mechanisms limit drug response [8]. This prospective, longitudinal study was designed to use urinary excretion data to examine the effects of chronic administration and matu ration on renal responsiveness to furosemide in premature infants.…”

An exploratory study with an adaptive continuous intravenous furosemide regimen in neonates treated with extracorporeal membrane oxygenation

“…The renal function (median creatinine 30 μmol/l) was normal for age in the ECMO patients, whereas (transient) renal failure (median creatinine 95 μmol/l) was observed in the majority of the patients after CPB surgery [ 12 , 16 ]. Therefore it can be hypothesized that the acute renal failure observed in the patients after CPB surgery had a major impact on renal clearance, which is most closely related with drug response, since furosemide is excreted renally and only acts after reaching the tubular lumen [ 24 - 27 ]. This hypothesis might explain why higher doses were needed in the patients after CPB surgery.…”

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

“…For this reason, urinary excretion rates of furosemide are better predictors than serum concentrations with regard to the diuretic effect of the drug. 6 Furosemide is predominantly excreted by the kidneys, and because it only exerts its action after excretion, this means that both the serum concentration profile and the effect profile are influenced by renal function. After cardiac surgery, renal insufficiency may occur, leading to volume overload.…”