Be Ready With Strategies to Manage “Diuretic Resistance”

You’ll 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 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 meds 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...but costs about $3/dose vs $80.

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, Acute Heart Failure, for more on inotropes, routine HF meds (beta-blockers, etc) during decompensation, etc.

Key References

  • Circulation. 2022 May 3;145(18):e895-e1032
  • J Am Coll Cardiol. 2020 Mar 17;75(10):1178-1195
  • J Am Coll Cardiol. 2021 Feb 16;77(6):695-708
  • JACC Heart Fail. 2020 Mar;8(3):157-168
  • N Engl J Med. 2022 Sep 29;387(13):1185-1195
Hospital Pharmacist's Letter. April 2023, No. 390420

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