Strategies to manage DIURETIC resistance
As a critical care pharmacist, you will hear debate about the best approach for managing "diuretic resistance" in acute decompensated heart failure.
Continue to start IV furosemide at 1 to 2.5 times the TOTAL DAILY oral home dose. For example, if the home oral furosemide dose is 40 mg daily, multiply this by 1 to 2.5 for an initial dose of 40 to 100 mg of IV furosemide. Plan to give this dose BID to TID. Monitor response, beginning with the first dose, and titrate. Be aware, "diuretic resistance" is often due to underdosing. Generally double the IV dose if urine output is less than 150 mL/hour, or if spot urine sodium is less than 50 mmol/L, 2 hours post dose. Urine sodium seems to be a good predictor of diuretic response, and avoids the challenges of measuring urine output.
Don’t think of max loop diuretic doses as cut-and-dried. Guidelines note a usual IV max of furosemide 600 mg/day. But some experts push much higher based on response, and limited data in acute HF suggest this can be safely done to optimize diuresis. Ensure that your protocol includes close monitoring, such as blood pressure (BP), electrolytes, and kidney function, and electrolyte replacement. But don’t automatically back down diuretics due to a bump in serum creatinine, such as 0.5 mg/dL or less. Data suggest that this is often transient, and NOT linked to worse CV or kidney outcomes.
If higher boluses (furosemide 200 mg IV, etc) aren’t enough, consider repeating the bolus and starting a continuous infusion or adding medications to augment response. There’s no clear BEST choice between these options, and practice varies. Combine these strategies if needed. When adding another diuretic to a loop, generally choose a thiazide first, these have the most data in diuretic resistance. For example, add oral metolazone for patients with inadequate response to a high-dose loop. Metolazone leads to comparable weight loss as adding IV chlorothiazide.
Be ready for questions about IV acetazolamide, a recent study suggests adding it to a loop improves diuresis in acute HF. Explain that this is based on adding acetazolamide early to loops, and it’s too soon to say what its role is in diuretic resistance. See our resource, "Use Inotropes for select cases of acute or end-stage heart failure", AND "Loop diuretic use in heart failure" & "Steps to manage loop diuretics" for more on inotropes, routine HF medications during decompensation, etc.
References
- Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032.
- Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Mar 17;75(10):1178-1195.
- Writing Committee; Maddox TM, et al. 2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021 Feb 16;77(6):772-810.
- Cox ZL, Hung R, Lenihan DJ, Testani JM. Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure: The 3T Trial. JACC Heart Fail. 2020 Mar;8(3):157-168.
- Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, et al. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Sep 29;387(13):1185-1195.
