Oral Diuretic Intensification, which may represent worsening congestion, has been proposed as a marker of worsening heart failure in clinical trials.

ODI is typically defined as an increase in the loop diuretic dose (doubling of furosemide equivalent) or addition of another oral diuretic (thiazide or mineralocorticoid receptor antagonist).

The addition of another oral diuretic is based upon the concept of sequential nephron blockade, where, another site of action within the nephron is targeted when a loop diuretic alone is not functional.

Switching of Bumetanide to furosemide, an example of a lateral substitution, does not meet the criteria for ODI.

In late stages, ODI might be a marker of a transition from “episodic decompensation” to “persistent symptom burden”, and represent breathlessness that is less likely to be reversible, while also signalling refractoriness to further diuretic escalation (or decongestion).

The goal shifts from decongestion at all costs to proportionate symptom control, at which stage, mild biochemical worsening in serum creatinine might be acceptable (permissive renal dysfunction) if is accompanied by symptomatic improvement.

Non-pharmacological measures at this stage may be used in addition to diuretics, and the onset of palliative measures need not necessarily imply an indication to stop diuretics.

When diuretics stop acting in heart failure, it may indicate decongestion that is potentially non-contributory to comfort provision.

Causes of breathlessness at this stage include low cardiac output, respiratory muscle fatigue and central perception (and affective components).

Diuretics at this stage might worsen hypotension, increase renal hypoperfusion and intensify thirst.

References

Van Spall, H. G. C., Trullàs, J. C., McGuire, D. K., Zannad, F., & McMurray, J. (2025). Oral Diuretic Intensification as a Worsening Heart Failure Event in the Primary Outcome of Clinical Trials. NEJM evidence, EVIDctw2500258. Advance online publication. https://doi.org/10.1056/EVIDctw2500258.

Marques, P., Blydt-Hansen, M., Takano, T., Ferreira, J. P., Tsoukas, M. A., Sharma, A., & Mavrakanas, T. A. (2025). Systematic Review on the Management of Diuretic Resistance in Acute Heart Failure across the Spectrum of Kidney Disease. Cardiorenal medicine, 15(1), 462–483. https://doi.org/10.1159/000546520

Beattie, J.M., Higginson, I.J. & McDonagh, T.A. Palliative Care in Acute Heart Failure. Curr Heart Fail Rep 17, 424–437 (2020). https://doi.org/10.1007/s11897-020-00494-8

Suha F, Modi P, Sharma S. Dyspnea. [Updated 2025 Dec 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499965/?utm_source=chatgpt.com