Determinants of urinary output response to IV furosemide in acute kidney injury: a pharmacokinetic/pharmacodynamic study

Silbert, Benjamin I., Ho, Kwok M., Lipman, Jeffrey, Roberts, Jason A., Corcoran, Tomas B., Morgan, David J., Pavey, Warren, Mas, Emilie, Barden, Anne E. and Mori, Trevor A. (2016) Determinants of urinary output response to IV furosemide in acute kidney injury: a pharmacokinetic/pharmacodynamic study. Critical Care Medicine, 44 10: e923-e929. doi:10.1097/CCM.0000000000001823


Author Silbert, Benjamin I.
Ho, Kwok M.
Lipman, Jeffrey
Roberts, Jason A.
Corcoran, Tomas B.
Morgan, David J.
Pavey, Warren
Mas, Emilie
Barden, Anne E.
Mori, Trevor A.
Title Determinants of urinary output response to IV furosemide in acute kidney injury: a pharmacokinetic/pharmacodynamic study
Journal name Critical Care Medicine   Check publisher's open access policy
ISSN 1530-0293
0090-3493
Publication date 2016-10-01
Sub-type Article (original research)
DOI 10.1097/CCM.0000000000001823
Open Access Status Not yet assessed
Volume 44
Issue 10
Start page e923
End page e929
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Collection year 2017
Language eng
Formatted abstract
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 m2 (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.
Keyword Diuretics
Pharmacology
Prediction
Renal failure
Response
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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