A retrospective evaluation of the efficacy of intravenous bumetanide and comparison of potency with furosemide
Background: The potency of intravenous bumetanide to furosemide using a ratio of 1:40 has been suggested; however, there are little data supporting this ratio. Recent drug shortages required the use of bumetanide in a large patient population, enabling further characterization of the efficacy of IV bumetanide.
Objective: The primary objective of this study was to estimate a dose-response effect of IV bumetanide on urine output (UOP) in all patients that received 48 hours of therapy as well as in a subgroup of patients with heart failure (HF). This subgroup was used to compare the potency of bumetanide with furosemide. A secondary safety objective described electrolyte replacement required during therapy.
Methods: This was a single-center retrospective study examining the dose-response effect of IV bumetanide in patients receiving at least 48 hours of intermittent (iIV) or continuous (cIV) dosing, measured by UOP per mg of drug received (mL/mg). The potency of IV bumetanide was compared with furosemide in a subset of patients with HF using pre-existing data. The safety of IV bumetanide was analyzed by quantifying electrolyte replacement received during the study period.
Results: The primary outcome was higher in the iIV group (n=93) at 1273 ± 844 mL/mg compared with the cIV group (n=16) at 749 ± 370 mL/mg (P=0.002). Among patients with HF who received furosemide (iIV n=30, cIV n=26) or bumetanide (iIV n=30, cIV n=3), a potency ratio of 41:1 was found for the iIV group and 34:1 for all patients with HF. There was no significant difference in electrolyte replacement between groups.
Conclusion: A greater response was seen with intermittent bumetanide compared with continuous infusion bumetanide. This study supports the 40:1 dose equivalence ratio (furosemide:bumetanide) in patients with HF receiving at least 48 hours of intravenous intermittent bumetanide.
2. Runyon BA. Management of adult patients with ascites due to cirrhosis: an update. American Association for the Study of Liver Disease Practice Guidelines. Hepatology. 2009;49(6):2087-107. doi: 10.1002/hep.22853.
3. Kidney Disease Outcomes Quality Initiative (K/DOQI). Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Am J Kidney Dis. 2004;43(5 Suppl 1):S1-290.
4. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J.. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009;53(17):1573-619. doi: 10.1016/j.jacc.2009.01.004.
5. Puschett JB. Pharmacological classification and renal actions of diuretics. Cardiology. 1994;84(Suppl 2):4-13.
6. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, Konstam MA, Mancini DM, Rahko PS, Silver MA, Stevenson LW, Yancy CW. 2009 Focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration with the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 2009;53(15):1343-1382. doi:10.1016/j.jacc.2008.11.009.
7. Konecke LL. Clinical trial of bumetanide versus furosemide in patients with congestive heart failure. J Clin Pharmacol. 1981;21(11-12 Pt 2):688-90.
8. Dixon DW, Barwolf-Gohlke C, Gunnar RM. Comparative efficacy and safety of bumetanide and furosemide in long-term treatment of edema due to congestive heart failure. J Clin Pharmacol. 1981;21(11-12 Pt 2):680-7.
9. Cleland JGF, Coletta A, Witte K. Practical applications of intravenous diuretic therapy in decompensated heart failure. Am J Med. 2006;119(12 Suppl 1):S26-36.
10. Ward A, Heel RC. Bumetanide: A review of its pharmacodynamic properties and therapeutic use. Drugs. 1984;28(5):426-64.
11. Product information. Bumex (Bumetanide). Bedford, OH: Bedford Laboratories; February 2010.
12. Eshaghian S, Horwich TB, Fonarow GC. Relation of loop diuretic dose to mortality in advanced heart failure. Am J Cardiol. 2006;97(12):1759-64.
13. Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswai A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velaquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O’Connor CM for the NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797-805. doi: 10.1056/NEJMoa1005419.
14. Whelton A. Long-term bumetanide treatment of renal edema. Comparison with furosemide. J Clin Pharmacol. 1981;21(11-12 Pt 2):591-8.
15. Hutcheon DE, Vincent ME, Sandhu RS. Renal electrolyte excretion pattern in response to bumetanide in healthy volunteers. J Clin Pharmacol. 1981;21(11-12 Pt 2):604-9.
16. Brater DC, Fox WR, Chennavasin P. Electrolyte excretion patterns. Intravenous and oral doses of bumetanide compared to furosemide. J Clin Pharmacol. 1981;21(11-12 Pt 2):599-603.
17. Peacock WF, Costanzo MR, De Marco T, Lopatin M, Wynne J, Mills RM, Emerman CL for the ADHERE Scientific Advisory Committee and Investigators. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: Insights from the ADHERE registry. Cardiology. 2009;113(1):12-9. doi: 10.1159/000164149.
18. Fonarow GC, Peacock WF, Horwich TB, et al.: ADHERE Scientific Advisory Committee and Investigators. Usefulness of B-type natriuretic peptide and cardiac troponin levels to predict in-hospital mortality from ADHERE. Am J Cardiol. 2008;101(2):231-7. doi: 10.1016/j.amjcard.2007.07.066.
19. Berg KJ, Tromsdal A, Wideroe TE. Diuretic action of bumetanide in advanced chronic renal insufficiency. Eur J Clin Pharmacol. 1976;9(4):265-75.
20. Voelker JR, Cartwright-Brown D, Anderson S, Leinfelder J, Sica DA, Kokko JP Brater DC. Comparison of loop diuretics in patients with chronic renal insufficiency. Kidney Int. 1987;32(4):572-8. doi: 10.1038/ki.1987.246.
21. Brater DC, Day B, Burdette A, Anderson S. Bumetanide and furosemide in heart failure. Kidney Int. 1984;26(2):183-9.
22. Brater DC. Diuretic therapy. N Engl J Med. 1998;339(6):387-95.
23. McCrindle JL, Li Kam Wa TC, Barron W, Prescott LF. Effect of food on the absorption of furosemide and bumetanide in man. Br J Clin Pharmacol. 1996;42(6):743-6.
24. Marcantonio LA, Auld WH, Murdoch WR, Purohit R, Skellern GG, Howes CA. The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease. Br J Clin Pharmacol. 1983;15(2):245-52.
25. Almeshari K, Ahlstrom NG, Caparo FE, Wilcox CS. A volume-independent component to postdiuretic sodium retention in humans. J Am Soc Nephrol. 1993;3(12):1878-83.
26. Thomson MR, Nappi JM, Dunn SP, Hollis IB, Rodgers JE, Van Bakel AB. Continuous versus intermittent infusion of furosemide in acute decompensated heart failure. J Card Fail. 2010;16(3):188-93. doi: 10.1016/j.cardfail.2009.11.005
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