Journal of Nephrology & Renal Therapy Category: Clinical Type: Review Article

Continuous Intravenous Infusion of Bumetanide to Achieve Diuresis in Patients with Congestive Heart Failure and Chronic Kidney Disease: A Rapid Review

Deepak Goyal1, 2*, Michael Talalaev2, Prerana Upadhyaya3, George Yatzkan2, Javier Perez-Fernandez2 and Marcos Sanchez-Gonzalez1, 2
1 College of Biomedical Science, Larkin University, Miami, Florida, USA
2 Larkin Community Hospital, Miami, Florida, USA
3 International American University, Vieux Fort, Saint Lucia
*Corresponding Author:

Deepak Goyal, M.D,
College of Biomedical Science,
Larkin University,
Miami, Florida, USA,
E-mail: dgoyal@myularkin.org

Received Date: Jan 08, 2021
Accepted Date: Jan 25, 2021
Published Date: Feb 08, 2021

Abstract

Bumetanide falls in the class of loop diuretics like furosemide. The effects of both have been extensively researched and are well documented. In medical practice furosemide is more widely used in patients both orally and through intravenous administration. Limited information is available regarding the use of bumetanide through continuous intravenous infusion therapy in patients suffering from congestive heart failure and chronic kidney disease with an endpoint of maximal or average diuresis. A summary of what is available and key findings are presented here for rapid review. We do not make any recommendations apart from further research that needs to be conducted using bumetanide continuous infusion therapy to achieve diuresis in patients suffering from congestive heart failure and chronic kidney disease. Even more specifically, one that could estimate the amount of diuresis that can be achieved with a given rate of infusion within a set of parameters to match patient population.

Keywords

Bumetanide; Chronic kidney disease; Congestive heart failure; Diuresis; Furosemide; Intravenous infusion

Abbreviations

CHF: Congestive Heart Failure

CKD: Chronic Kidney Disease

IV: Intravenous

IM: Intramuscular

cFI: Continuous Furosemide Infusion

cBI: Continuous Bumetanide Infusion

BUN/Cr: Blood Urea Nitrogen/Creatinine

eGFR: Estimated Glomerular Filtration Rate

BNP: Brain Natriuretic Peptide

Introduction

Bumetanide is a medication used in the treatment of patients for Edema (Pulmonary, peripheral, or generalized) as it is a potent loop diuretic [1]. The potency of 1mg bumetanide is close to the equivalent of 40mg of Furosemide or 20mg Torsemide respectively [1-4]. The profound diuretic effects of the medication are well known. Many of the studies conducted show its use either as a bolus or continuous intravenous infusion but with some conflicts [5]. The authors wish to show the superior efficacy of bumetanide as a continuous infusion in patients with Congestive Heart Failure (CHF) and Chronic Kidney Disease (CKD). Current practices indicate the use of furosemide to achieve diuresis however we think bumetanide will achieve a greater response in these patients warranting further investigation into its potential use over other medications. The article will summarize key findings from various studies and present them here for analysis as a rapid review.

Understanding the Mechanism of Action of Bumetanide

Bumetanide is part of the same drug family as other loop diuretics such as furosemide, torsemide and ethacrynic acid [3]. This entire class has an effect in the thick ascending limb of the loop of Henle in the medullary segment [2-4]. More specifically they compete for the sodium-potassium-chloride cotransporter located along the membrane [2,3]. Ultimately leading to an excretion of water and solutes such as magnesium phosphate, calcium, and sodium chloride [3]. These solutes being excreted in certain patient populations can become extremely concerning as they play an important role in numerous different physiologic mechanisms that are not discussed here. 

Holazo A et al. [6], evaluated the pharmacokinetics of bumetanide by administering 1mg of the drug in different forms to 12 different subjects in a random crossover design study. They recorded the mean maximum plasma concentration, time to reach maximum plasma concentration, half-life and the amount of drug excreted in the urine. From their findings, pharmacokinetics based on the routes of administration were described as having first-order absorption and elimination for the oral and IM routes of administration. For the IV route, the authors concluded the two phases were: An initial rapid disposition with half-life of 5.1 minutes and a slower elimination phase with half-life of 44 minutes. Bioavailability, as expected, was higher in the IM/IV routes versus the oral route. Their summary findings are presented in table 1. 

Route

Mean ± SD Maximum Plasma Concentration (ng/mL)

Amount of Time after Dosing to Reach Mean Max Plasma Concentration

Half Life Range

(minutes)

Amount of Intact Drug Excreted in Urine between 0 and 24 hours

IV

*

*

24-86

(62) min

70%

IM

38.2 ± 9.8

0.34 ± 0.23 hr

47-139 (92) min

Oral solution

34.0 ±10.6

0.76 ± 0.27 hr

27-71

(44) min

60%

Oral tablet

0.9 ±14.6

1.8 ±1.2 hr

26-99

(73) min

Table 1: Bumetanide bioavailability summary. 

Felker G et al. [7], has summarized pharmacokinetic properties of bumetanide while comparing it to furosemide and torsemide. Properties such as bioavailability, half-life, metabolism, onset time, and average cost are all found within table 2.  

Property

Furosemide

Bumetanide

Torsemide

Relative IV potency, mg

40

1

20

Bioavailability, %

10-100 (average, 50)

80-100

80-100

Oral to intravenous conversion

2:1

1:1

1:1

Initial outpatient total daily oral dose, mg

20-40

0.5-1

5-10

Maintenance outpatient total daily oral dose, mg

40-240

1-5

10-200

Maximum daily intravenous dose, mg

400-600

10

200

Onset, min

     

Oral

30-60

30-60

30-60

Intravenous

5

2-3

10

Peak serum concentration after oral administration, h

1

1-2

1

Affected by food

Yes

Yes

No

Metabolism

50% renal conjugation

50% hepatic

80% hepatic

Half-life, h

     

Normal

1.5-2

1

3-4

Renal dysfunction

2.8

1.6

4–5

Hepatic dysfunction

2.5

2.3

8

Heart failure

2.7

1.3

6

Average duration of effect, h

6-8

4-6

6-8

Approximate cost for oral 30-day supply (community pharmacy), $

4

4

19-23

Table 2: Pharmacokinetic properties of loop diuretics.

Bumetanide VS. Rosemide in Congestive Heart Failure

In a study done by Tein Ng et al. [8], dealing with Acute Heart Failure, they found that between continuous furosemide infusion at the median dose of 7mg/hr (cFI) and continuous bumetanide infusion at the median dose of 1mg/hr (cBI), there was a significant increase in the mean hourly urine output for both the regimens when compared to baseline. 

However, there was an even larger amount of urine produced when looking at cFI vs. cBI. They did conclude that greater urine output may have occurred with cBI however at the cost of greater electrolyte disturbances. They did not specifically mention the degree of the disturbance, but this author would recommend the provider be cognizant of these changes. 

Wargo and Banta [5], conducted a comprehensive review of loop diuretics specifically asking the question if furosemide should be first line. They did look at torsemide, furosemide and bumetanide and how they compared. In summation of their findings, symptoms of dyspnea were significantly more improved with bumetanide over furosemide. Furthermore, they found two trials that did compare the agents however, there were conflicting results. One of the trials analyzed showed that bumetanide was more effective but a direct comparison to furosemide could not be made due to a small sample size. The second trial also had a small sample size, and the comparison groups were not similar. Finally, the authors concluded that the oral bioavailability of bumetanide is considerably higher, and the time of onset is similar regardless of the route of administration (oral versus intravenous).

Adverse Reactions of Bumetanide

Many adverse events are due to the direct effect of solutes lost in the urine and concentration of several electrolytes within the blood. All these changes are related to pharmacologic action of the medication [1,3]. These disturbances can lead to the patient having symptoms of weakness, lethargy, confusion, muscle cramps, headache, and nausea [1,4]. Like other diuretics, we recommend the provider be cautious when choosing this powerful drug and closely monitor electrolytes by ordering a complete metabolic panel and monitor urine output. When treating these symptoms, simply replace the electrolytes and fluids [1,3].

Role of Bumetanide with Severe Congestive Heart Failure and Chronic Kidney Disease

In clinical medicine, bumetanide, like furosemide and torsemide, is used to treat fluid overload in conditions such as congestive heart failure, cirrhosis with ascites, and other highly edematous states to provide symptomatic relief [1,9-14]. Parameters like shortness of breath, generalized swelling are usually described together with an improvement of renal function and the overall hemodynamic status of the patient [9,10,12]. It can be administered orally in an outpatient setting, or IV bolus or continuous intravenous infusion over a set time frame [3,4,9]. 

Mandal AK [9], illustrated a female patient with severe CHF and stage 5 CKD where an infusion of bumetanide was started. Strict input and output were measured, along with several other parameters such as symptoms, BUN/Cr, eGFR and the serum Potassium. Prior to infusion, this patient had a BUN/Cr of 50/3.28 and eGFR of 14. The infusion was given over a period of 5 days at an undefined rate but believed to be titrated up to approximately 1mg/hr. In that duration the patient’s urine output increased between 100ml-200ml/hr which improved her BUN/Cr to 23/1.25, eGFR to 44, and improved her CHF symptoms to the point where she was no longer having shortness of breath. This patient had a BNP of 1514 prior to infusion and at the end it decreased substantially to 352. The author did mention that while her renal function was poor to start, her urine output did not increase as much as expected given her eGFR improvement. With this information on a single patient, a causal relationship could not be fully established as this requires further review as to why the urine output did not increase as expected when compared to an improving eGFR.

Conclusion

Very few studies exist that can credibly show the effect of bumetanide in patients with CHF and CKD during a continuous intravenous infusion. It may partially be because finding similar baselines proves to be too difficult in this delicate patient population. For example, while some of them have stage 3 CKD they may all have different degrees of heart failure. It may also be associated with a cost factor of the medication as furosemide is much more readily available than bumetanide. After a comprehensive literature review, this author would suggest further studies be done into bumetanide. Especially one that could explore the average expected urine output in mL/hr directly correlated to the mg/hr infusion of bumetanide.

Acknowledgement

The author would like to thank Larkin Health System and Larkin University for the opportunity to conduct this rapid review and to all the contributing authors for their hard work on this article.

References

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Citation: Goyal D, Talalaev M, Upadhyaya P, Yatzkan G, Perez-Fernandez J, et al. (2021) Continuous Intravenous Infusion of Bumetanide to Achieve Diuresis in Patients with Congestive Heart Failure and Chronic Kidney Disease: A Rapid Review. J Nephrol Renal Ther 7: 045.

Copyright:© 2021 Goyal D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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