Filippo Mariano1, Marta Leporati2, Paola Carignano3, Maurizio Stella4, Marco Vincenti2,5, Luigi Biancone6. 1. Nephrology, Dialysis and Transplantation Unit, Department of Medical Sciences, City of Health and Science, CTO Hospital, University of Turin, Via G. Zuretti 29, 10126, Turin, Italy. fmariano@unito.it. 2. Regional Antidoping and Toxicology Center "Alessandro Bertinaria", Orbassano, Turin, Italy. 3. Anesthesia and Intensive Care 3, Department of Anesthesia and Intensive Care, City of Health and Science, CTO Hospital, Turin, Italy. 4. Plastic Surgery and Major Burns, Department of General and Specialized Surgery, City of Health and Science, CTO Hospital, Turin, Italy. 5. Department of Chemistry, University of Turin, Turin, Italy. 6. Nephrology, Dialysis and Transplantation Unit, Department of Medical Sciences, City of Health and Science, CTO Hospital, University of Turin, Via G. Zuretti 29, 10126, Turin, Italy.
Abstract
BACKGROUND: This study assessed the contribution of intracorporeal (IC) and extracorporeal clearance (EC) of furosemide in patients with septic acute kidney injury (AKI), and the relationship between plasma concentrations and urine volume. METHODS: Prospective cohort observational study of 15 patients with septic AKI undergoing continuous veno-venous hemodiafiltration (CVVHDF) divided according to urine volume (< 500 ml/12 h, Oliguria group, n = 5; > 500 ml/12 h, Diuresis group, n = 10) during continuous infusion of furosemide (120 mg/12 h) at steady-state condition. Plasma and effluent furosemide concentrations were determined by high-performance liquid chromatography (HPLC)-mass spectrometry every 12 h for 48 h. RESULTS: Furosemide plasma concentrations and total body clearance (TBC) were 6.14 mg/l and 22.1 ml/min for the Oliguria group, and 2.63 mg/l and 54.4 ml/min for the Diuresis group, respectively (p < 0.05). When urine volume was < 500 ml/24 h, the furosemide plasma concentrations peaked at the potentially toxic value of 13.0 mg/l. Furosemide EC was not relevant for the Diuresis group, but it represented 18% of TBC for the Oliguria group. Furosemide plasma concentrations correlated positively with dose infusion for both groups (r = 0.728 and 0.685, p < 0.05), and negatively with urine volume only for the Diuresis (r = - 0.578, p < 0.01) but not for the Oliguria group (r = - 0.089, p = 0.715). CONCLUSIONS: For patients with urine volume > 500 ml/12 h continuous infusion of furosemide up to 480 mg/24 h leads to increasing urine volume, which can predict furosemide plasma levels within its safety range. When the urine volume is lower, the furosemide plasma levels are increased beyond any further diuretic efficacy.
BACKGROUND: This study assessed the contribution of intracorporeal (IC) and extracorporeal clearance (EC) of furosemide in patients with septic acute kidney injury (AKI), and the relationship between plasma concentrations and urine volume. METHODS: Prospective cohort observational study of 15 patients with septic AKI undergoing continuous veno-venous hemodiafiltration (CVVHDF) divided according to urine volume (< 500 ml/12 h, Oliguria group, n = 5; > 500 ml/12 h, Diuresis group, n = 10) during continuous infusion of furosemide (120 mg/12 h) at steady-state condition. Plasma and effluent furosemide concentrations were determined by high-performance liquid chromatography (HPLC)-mass spectrometry every 12 h for 48 h. RESULTS:Furosemide plasma concentrations and total body clearance (TBC) were 6.14 mg/l and 22.1 ml/min for the Oliguria group, and 2.63 mg/l and 54.4 ml/min for the Diuresis group, respectively (p < 0.05). When urine volume was < 500 ml/24 h, the furosemide plasma concentrations peaked at the potentially toxic value of 13.0 mg/l. Furosemide EC was not relevant for the Diuresis group, but it represented 18% of TBC for the Oliguria group. Furosemide plasma concentrations correlated positively with dose infusion for both groups (r = 0.728 and 0.685, p < 0.05), and negatively with urine volume only for the Diuresis (r = - 0.578, p < 0.01) but not for the Oliguria group (r = - 0.089, p = 0.715). CONCLUSIONS: For patients with urine volume > 500 ml/12 h continuous infusion of furosemide up to 480 mg/24 h leads to increasing urine volume, which can predict furosemide plasma levels within its safety range. When the urine volume is lower, the furosemide plasma levels are increased beyond any further diuretic efficacy.