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Author: Brent N. Reed, PharmD, BCPS-AQ Cardiology, FAHA

In the first part of this two-part series, I highlighted some issues with the methodology of the Diuretic Optimization Strategies Evaluation (DOSE) trial, which I think limit the conclusions that can be made regarding continuous infusion loop diuretics in patients with acute decompensated heart failure (ADHF).1 Although I asserted that there may be some populations in which continuous infusions may have advantages over intermittent boluses, I stopped short of saying they were a superior strategy in all patients with ADHF. In this follow-up post, I wanted to share with you what I see as being the disadvantages of continuous infusions.

First, as is the case with other continuous infusions, the use of continuous infusion loop diuretics may promote a “set it and forget it” approach to diuresis, limiting what would otherwise be a more frequent assessment of a patient’s volume status. A common practice in the acute care setting is to assess a patient’s volume status in the evening and administer an extra bolus if diuretic goals are not being met (or holding diuretics if goals have been exceeded). In my experience, this occurs less often with continuous infusions patients, as they are thought of as being “on the drip” all night. Although there are undoubtedly examples where overnight providers may neglect to administer an extra bolus because the service becomes very busy, I contend that neglecting to perform an assessment and responding to it is far worse. A similar phenomenon may occur for those patients who remain on the infusion until they can be rounded upon by the team the next day, which may not occur until late morning or early afternoon.

Secondly, as with boluses being administered late at night, patients receiving loop diuretics as a continuous infusion feel the urge to urinate intermittently all night long. For patients without a Foley catheter, this means getting up throughout the night to urinate, which may increase the risk of falls, an important quality measure for hospitalized patients. Patients with a Foley catheter still feel the urge to urinate even if they do not actually have to get up to do it. Overnight disruptions can have a significant impact on sleep quality and may increase the risk of delirium, especially in older patients or in those admitted to the intensive care unit.

Thirdly, although continuous infusions permit higher doses of loop diuretic therapy to be administered, the potentially deleterious effects of this practice have not been adequately studied. In the DOSE trial, patients randomized to continuous infusion furosemide received a median of 406 mg (interquartile range 292-832 mg) in the first 48 hours, or approximately 8.5 mg/hour; after including the additional 24 hours of open-label therapy, the median dose was 480 mg (interquartile range 370-884 mg), or 6.7 mg/hour.1,2 It should be no surprise that an excess rate of renal dysfunction was absent in the continuous infusion arm, as these rates are far from the typically reported maximum infusion rates for furosemide (i.e., 20-40 mg/hour). We have evidence from the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS) trial that continuous fluid removal with ultrafiltration disrupts the kidney’s counterregulatory response to changes in intravascular volume, increasing the risk of renal impairment.3 Could a similar phenomenon occur with extended durations of high-dose continuous infusion diuretics? At this point we do not know.

A few other disadvantages of continuous infusion loop diuretics are that they may limit where a patient may be located (i.e., some units may not permit continuous infusions) and that they may not effectively combat diuretic resistance. In the latter case, there are a variety of mechanisms in which diuretic resistance may occur, and only one of these – compensatory sodium reabsorption in the intra-diuretic period – is specifically targeted by continuous infusion administration.

Finally, as is the case with continuous infusions of other drugs with longer half-lives (e.g., diltiazem), mismanagement is common. With half-lives of approximately 1-2 hours, loop diuretics cannot be effectively titrated to response (e.g., to a specific urine output), contrasting them with other continuous infusions, such as vasopressors or vasodilators. The full effect of each change to the rate of a continuous infusion loop diuretic will not be observed for 4-8 hours, and this is particularly true if boluses are not given with each dose increase. Additionally, because of the steep dose-response curve of loop diuretics in ADHF, if the drug is started at a low rate without a bolus, it may not exceed the threshold necessary to elicit a diuretic response.

For the aforementioned reasons, the following pearls are recommended to assist with the appropriate management of continuous infusion loop diuretics in ADHF:

  • Administer a bolus at the initiation of a continuous infusion loop diuretic, and with each dose increase. The dose of the bolus should be a dose the patient has responded to previously, or up to 2.5-times the oral dose prior to admission. At minimum, the dose should equal or exceed the total diuretic dose the patient will receive from the infusion over the next 4-8 hours (i.e., a 40-80 mg bolus for an infusion being initiated at 10 mg/hour).
  • Begin considering other options (e.g., adjunct use of thiazide-type diuretics) when doses of furosemide approach 20-30 mg/hr (or 2 mg/hr of bumetanide) rather than continuing to increase the infusion rate. A similar approach was shown to be efficacious and safe in patients randomized to the “stepped pharmacologic arm” of the CARRESS trial.3 Higher doses may place patients at greater risk of ototoxicity with furosemide (as cumulative doses exceed 1 gram in 24 hours) or myalgias with bumetanide.4
  • Convert to bolus dosing (or preferably oral loop diuretic therapy) for at least 24 hours prior to discharge to observe the patient’s response to intermittent diuretic administration, as this will help determine an appropriate discharge dose. Even so, recognize that the diuretic effects of an infusion may persist for another 6-12 hours after discontinuation, and longer if thiazides were concomitantly administered.

Have other pearls for continuous infusions, or other experiences to share? Contact us at atrium@rx.umaryland.edu!

 

 
Brent N. Reed, PharmD, BCPS-AQ Cardiology, FAHA

Dr. Reed is an assistant professor in the Department of Pharmacy Practice and Science at the University of Maryland School of Pharmacy, and practices as a clinical pharmacy specialist in advanced heart failure at the University of Maryland Medical Center in Baltimore, MD. Follow him on Twitter @brentnreed

 

References

  1. Felker GM, Lee KL, Bull DA, et al; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805.
  2. Supplementary Appendix for: Felker GM, Lee KL, Bull DA, et al; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. Available at http://www.nejm.org/action/showSupplements?doi=10.1056%2FNEJMoa1005419. Accessed 2016 Oct 1.
  3. Bart BA, Goldsmith SR, Lee KL, et al; Heart Failure Clinical Research Network. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012 Dec 13;367(24):2296-304. doi: 10.1056/NEJMoa1210357.
  4. Howard PA, Dunn MI. Severe musculoskeletal symptoms during continuous infusion of bumetanide. Chest. 1997 Feb;111(2):359-64.
Which Patients with Heart Failure Should Get Loop Diuretics as a Continuous Infusion? (Part 2)

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