Furosemide as a functional marker of acute kidney injury in ICU patients: a new role for an old drug

Abstract

New pharmacokinetics insight suggests that the furosemide pharmacology occurring in ICU patients with AKI is similar, but not equal to that described in chronic stable renal patients. Even if the diuretic response to furosemide is expressed by a steep dose-response curve positively correlated with renal function, pharmacodynamic limitations occur when creatinine clearance is < 20 ml/min or urine output is < 500 ml/12 h. In such cases, other factors specifically due to acute tubular injury can interfere with the furosemide-induced diuretic output. As modality of administration recent reports and metanalysis, even if not conclusive, suggest that for the same given dose a continuous infusion of furosemide was superior in diuretic response. For septic shock patients on CVVHDF where treatment adds an additional clearance of furosemide the maximum diuretic response is achieved by a continuous infusion of 20 mg/h of furosemide. At this infusion rate the reached plasma level was < 20 mg/L, a range considered safe and not ototoxic. Therefore, the severity of AKI establishes whether a patient will respond to furosemide. In this review we summarized all these recent updates, also suggesting that the diuretic response under continuous infusion may allow assessing glomerular and tubular functions with increased reliability than a bolus dose. However, validation studies are still needed to support continuous infusion as a stress test.

Keywords: Acute kidney injury; Critically ill patients; Furosemide; Ototoxicity; Pharmacokinetics/pharmacodynamics; Urine output.