Loop Diuretics in Clinical PracticeCharleston, SC United States. The potency of intravenous bumetanide to furosemide using a ratio of 1: Recent drug shortages required the use of bumetanide in a large patient population, enabling further characterization of the efficacy of IV bumetanide. 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 oral to iv furosemide conversion as in oral to iv furosemide conversion 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.
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Charleston, SC United States. The potency of intravenous bumetanide to furosemide using a ratio of 1: Recent drug shortages required the use of bumetanide in a large patient population, enabling further characterization of the efficacy of IV bumetanide. 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. 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. There was no significant difference in electrolyte replacement between groups. A greater response was seen with intermittent bumetanide compared with continuous infusion bumetanide. This study supports the Intravenous IV loop diuretics serve an important role in the management of patients with volume overload in order to improve symptoms and optimize hemodynamic status.
The role diuretics play is illustrated by their inclusion in guidelines for the management of acute and chronic heart failure, cirrhosis with ascites, renal insufficiency, and pulmonary hypertension.
While diuresis is necessary in the management of a number of disease states, studies have repeatedly demonstrated the deleterious outcomes associated with these agents and a precise optimal dosing strategy has yet to be found. High diuretic doses have also been associated with increased hospital length of stay and a dose-related increase in mortality in patients with heart failure.
Loop diuretic-induced decrease in renal blood flow is evident by an average increase in serum creatinine of 0. Bumetanide, however, may have a less potent kaliuretic effect compared with furosemide. Reported equipotent doses of furosemide and bumetanide range from Given the dose-related adverse effects of these agents, thoughtful consideration must be taken when choosing a diuretic dose in order to achieve the maximum therapeutic benefit while minimizing adverse effects.
Recently, due to a national shortage of IV furosemide, practitioners at the Medical University of South Carolina were forced to use IV bumetanide as the formulary loop diuretic for six months. With the increased utilization of IV bumetanide, we sought to retrospectively quantify the dose-response effect of continuous and intermittent dosing of IV bumetanide, compare the dose-response of IV bumetanide with IV furosemide in a subset of patients with HF, and to describe adverse effects seen with the use of bumetanide.
The primary objective of this study was to identify the dose-response effect of intermittent and continuous infusion bumetanide in all patients at our institution. We also sought to compare the potency of IV bumetanide to IV furosemide in a subset of patients with HF, using data previously collected at our institution and described by Thomson and colleagues. This was a retrospective, observational study that examined patients who received intravenous bumetanide for at least 48 hours from June through October At this time, the Medical University of South Carolina Medical Center implemented an automatic substitution for orders of IV furosemide to be converted to IV bumetanide at a ratio of All patients in the hospital were eligible for this substitution.
Patients were excluded from the study if they were less than 18 years old, received less than 48 hours of bumetanide, or did not have urine output recorded. Data collection included patient demographic information, past medical history, admission diagnosis, length of hospital stay, and pertinent home and hospital medications.
Data collected daily included total dose of bumetanide, intermittent iIV or continuous infusion cIV administration, total fluid intake and urine output UOP , serum sodium, blood urea nitrogen, serum creatinine, albumin, and any doses of potassium or magnesium given for electrolyte replacement.
Patient weight and B-type natriuretic peptide BNP were collected on admission and discharge when available. This was done by using the sum of the total urine output during the study period for each patient and dividing by total drug received. The mean standard deviation; SD of this number was reported as our primary outcome.
In order to compare the potency of IV bumetanide to IV furosemide, a more homogenous patient population was chosen by selecting only those patients with systolic HF and comparing daily UOP per mg of drug administered to preexisting data describing this outcome with furosemide. Data were analyzed for significant differences using the Mann-Whitney-U test.
Sample size was based on number of patients available for analysis and feasibility of data analysis within a required time frame. Correlation analysis was performed using Spearman rank correlation with pairwise exclusion to identify independent variables associated with the primary outcome.
Data was analyzed using SPSS version A total of patients received intravenous bumetanide for at least 48 hours from June 1, October 30, Of these, patients were used in analysis of the primary outcome of bumetanide efficacy, after excluding patients who did not have urine output recorded or those who had doses held resulting in less than 48 hours of bumetanide therapy.
Of the patients, 33 patients Baseline characteristics were similar between groups, as shown in Table 1. All non-Caucasian patients were Black with the exception of one patient of Asian descent. The average age was Serum sodium concentration was significantly higher in the iIV group at baseline. Pertinent medications administered concomitantly with bumetanide are listed in Table 2 , with beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and dihydropyridine calcium channel blockers being the most frequently administered cardiac medications.
In order to determine if the use of thiazide diuretics impacted the results, the primary endpoint was also analyzed while excluding those patients that received a thiazide diuretic. The average duration of therapy was five days for both the iIV and cIV groups.
Many of the baseline characteristics age, race, serum creatinine of patients in this study resemble those in the study by Thomson et al. However the populations differed in a major respect. The current study included patients with indications for diuresis beyond heart failure exacerbation.
Baseline demographic information and laboratory values for all patients who received intravenous bumetanide. Shown below is the primary outcome of urine output per mg of bumetanide per patient per day. Based on previously published data, we were able to compare the dose-response effect of IV bumetanide to IV furosemide in patients with HF.
Table 4 shows the primary outcome result for the subgroup of patients with HF who received iIV or cIV bumetanide or furosemide. When comparing only the intermittent dosing strategies, there was a dose-equivalence ratio of In the entire subgroup of patients with HF, the overall dose-equivalence ratio was Comparison of potency between bumetanide and furosemide in patients with heart failure, analyzed as intermittent dosing or continuous dosing and total population.
Electrolyte disturbances with iIV and cIV bumetanide were measured as average potassium and magnesium electrolyte replacement per patient per day during the study period. There was no significant difference in mean electrolyte replacement between dosing strategies. The average potassium replacement was The average magnesium replacement was 0. Our retrospective analysis was able to quantify the dose-response effect of IV bumetanide and found the intermittent dosing group to have a higher dose-response effect.
Variability in response was seen when comparing patients with HF, RI, or otherwise healthy individuals, however significance was not able to be determined. Lastly, these results uphold the In recent literature there have been many studies evaluating clinical outcomes that assume a diuretic equivalence ratio other than the well-accepted For example, Eshagian and colleagues evaluated independent predictors of mortality in patients with advanced heart failure.
In this study oral furosemide 80 mg was considered equal to bumetanide 3 mg. More recently, the authors of the Diuretic Optimization Strategies Evaluation DOSE trial evaluated four different dosing strategies for patients hospitalized with acute decompensate heart failure.
This hypothesis is limited due to the highly variable oral bioavailability of furosemide. There are a number of limitations to our study. As a retrospective study it was not possible to control for baseline characteristics, acuity of illness and concomitant medications administered.
Little can be concluded from this subgroup analysis except that those patients receiving a thiazide diuretic were poor responders to any form of diuretic therapy. Additionally, because randomization was not possible, we do not know how many patients in the cIV group may have previously failed intermittent dosing.
If more patients in the cIV group failed intermittent therapy, it may offer a reason for the cIV group having a poorer response than the iIV group, as seen in this study. One would expect to see equal or improved efficacy in the continuous infusion bumetanide group when compared to intermittent dosing because of the higher doses used and the avoidance of potential rebound sodium reabsorption between intermittent doses. Further, because the baseline serum sodium was lower in the cIV group, it may be hypothesized that this group had a more severe degree of volume overload, necessitating, but not manifesting in a greater need for diuresis.
Further, we used electrolyte replacement as a surrogate marker to measure the potential for adverse effects such as arrhythmias. Because of the retrospective nature of the study we were not able to appropriately assess other potential adverse reactions of loop diuretics including increases serum creatinine, hyponatremia, hypotension, ototoxicity, and myalgias.
The reason for this was multifactorial including both limitations in retrospective data collection and the technology used to identify potential patients.
Retrospective data collection did not allow for regulation of urine output monitoring and poor records led to the exclusion of many patients. Because of medication barcode administration we were able to determine the actual number of doses administered, which at times was less than the number of doses dispensed and, thus resulted in less than 48 hours of therapy.
The limitations of this study are reflected in the wide variability of our results, represented by large standard deviations. It also must be considered that these data may not be applicable to patients receiving less than 48 hours of therapy. Clear limitations also apply when comparing new data to the previously collected data by Thomson and colleagues. The different study designs and time frames used in each study limit the ability to accurately compare and scientifically analyze the potency of bumetanide and furosemide.
With our retrospective data we have quantified the dose-response effect of IV bumetanide and compared the potency with IV furosemide in patients with heart failure. While our study supports the We should consider this ratio when interpreting literature that may have used alternative ratios in data analysis.
We propose that clinicians should continue to utilize the intravenous dose equivalence ratio of Future studies may be beneficial to evaluate the efficacy of bumetanide in furosemide-resistant patients and determine appropriate dosing strategies in edematous patients. The author would like to recognize the contribution of Mary Bradbury, PharmD to this project. The author has no conflicts of interest to disclose.
This project was not funded. National Center for Biotechnology Information , U. Journal List Pharm Pract Granada v. Find articles by Jean M. Received Sep 6; Accepted Feb 9. This article has been cited by other articles in PMC. Abstract Background The potency of intravenous bumetanide to furosemide using a ratio of 1: