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Determinants of Urinary Output Response to IV Furosemide in Acute Kidney Injury: A Pharmacokinetic/Pharmacodynamic
Benjamin I Silbert1, Kwok M Ho, Jeffrey Lipman
11Department of Intensive Care Medicine, Fiona Stanley Hospital, Murdoch, WA, Australia.2School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, WA, Australia.3Department of Intensive Care Medicine, Royal Perth Hospital, Perth, WA, Australia.4School of Population Health, University of Western Australia, Crawley, WA, Australia.5School of Veterinary and Life Sciences, Murdoch University, Murdoch, WA, Australia.6Burns, Trauma and Critical Care Research Centre, School of Medicine, University of Queensland, Brisbane, QLD, Australia.7Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.8Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.9Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, WA, Australia.10Department of Anaesthesia and Pain Medicine, Fiona Stanley Hospital, Murdoch, WA, Australia.
Objectives:
This study assessed the determinants of urinary output response to furosemide in acute kidney injury; specifically, whether the response is related to altered pharmacokinetics or pharmacodynamics.
Design:
Prospective cohort.
Setting:
Tertiary ICU.
Patients:
Thirty critically ill patients with acute kidney injury without preexisting renal impairment or recent diuretic exposure.
Intervention:
A single dose of IV furosemide.
Measurements And Main Results:
Baseline markers of intravascular volume status were obtained prior to administering furosemide. Six-hour creatinine clearance, hourly plasma/urinary furosemide concentrations, and hourly urinary output were used to assess furosemide pharmacokinetics/pharmacodynamics parameters. Of 30 patients enrolled, 11 had stage-1 (37%), nine had stage-2 (30%), and 10 had stage-3 (33%) Acute Kidney Injury Network acute kidney injury. Seventy-three percent were septic, 47% required norepinephrine, and 53% were mechanically ventilated. Urinary output doubled in 20 patients (67%) following IV furosemide. Measured creatinine clearance was strongly associated with the amount of urinary furosemide excreted and was the only reliable predictor of the urinary output after furosemide (area under the receiver-operating-characteristic curve, 0.75; 95% CI, 0.57-0.93). In addition to an altered pharmacokinetics (p < 0.01), a reduced pharmacodynamics response to furosemide also became important when creatinine clearance was reduced to less than 40 mL/min/1.73 m (p = 0.01). Acute kidney injury staging and markers of intravascular volume, including central venous pressure, brain-natriuretic-peptide concentration, and fractional urinary sodium excretion were not predictive of urinary output response to furosemide.
Conclusions:
The severity of acute kidney injury, as reflected by the measured creatinine clearance, alters both pharmacokinetics and pharmacodynamics of furosemide in acute kidney injury, and was the only reliable predictor of the urinary output response to furosemide in acute kidney injury.
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