Whiteboard Animation

Transcript

So once you’ve diagnosed cardiorenal syndrome, what is our initial diuretic approach? Let’s turn to our toolbox.

The typical approach is to start with our intravenous loop diuretics, our trusty hammers that form the backbone of our toolbox. These include IV furosemide and IV bumetanide. The famous DOSE trial established safety for starting with IV furosemide at a dose that is 2.5 times the patient’s usual home oral diuretic dose. You can give that dose either with intermittent boluses or a continuous drip. If they do not take diuretics at home, IV Lasix 40 mg up to 80 mg is a reasonable starting point.

Bumetanide is just a much more potent loop diuretic, so may be considered instead in cases where patients need very high doses to have a response.

How can we tell if our diuretic strategy is working? We can use traditional markers like changes in exam and symptoms as well as tracking weights and urine output… but these can take time and sometimes can leave you scratching your head, especially if things are inaccurately documented. Another marker to add to the mix is a spot urine sodium level, which comes back quickly. Ideally, a urine sodium greater than 70 mEq/L 1-2 hours after giving diuretics indicates a good response.

But interpret that urine sodium in context! There are many confounders, like the amount of urine output that can affect the measurement which we discuss in more detail in the full episode.

If the response isn’t adequate, escalating is often the next step — consider doubling your daily loop diuretic dose and see what happens.

So what if you’re hitting a wall? There’s not enough urine despite some pretty high and increasing doses of loop diuretics. This could indicate diuretic resistance. First, make sure you actually have a “diuretic problem” and not a blood flow problem. This means thinking back to our water supply. For example, does the patient have a sicker heart than we thought and not enough output from there? Or maybe they have a sick liver and/or their blood pressure is a bit softer than we remember? Sometimes, it can also be helpful to examine the urine again in case a different intrinsic kidney problem has emerged.

Once you have evaluated for these other issues and are confident there is adequate flow and “water supply”, then we can go back to our toolbox.

The next strategy is sequential nephron blockade, basically hitting other parts of the nephron besides the loop of Henle. The first of these additional tools are our thiazides, the drills that work in the distal tubule. These include metolazone or chlorothiazide. They also include chlorthalidone and HCTZ, which are more often used as blood pressure medications at least in the US. Between metolazone and chlorothiazide, there aren’t clear differences in efficacy but some useful differences in their kinetics. Metolazone notably lasts quite a bit longer while chlorothiazide is IV so is faster-acting.

Our next set of additional tools are our pliers of the proximal tubule of the nephron. The first of these is acetazolamide. The ADVOR trial showed that acetazolamide improved length of stay of heart failure patients when added to our loop diuretic hammers. Acetazolamide is helpful also if your patient has metabolic alkalosis that can come with using typical loop-diuretics.

Our other proximal plier is the famed SGLT2 inhibitor, which starts a little bit of our discussion about what our toolbox for home might look like. This has the added benefit of being important for GDMT and helps with diuresis. They are probably safe to add in cardiorenal AKI as well, though this is an area of ongoing study.

Our last set of tools we will talk about for now* are the mineralocorticoid receptor antagonists or MRAs. These can help with low potassium issues that come with all the other tools. Spironolactone is probably the most common/familiar (and cheapest) of them but has the most anti-androgen effects, for example with gynecomastia. Some others in this family are eplerenone and most newly finerenone, which is a more specific non-steroidal MRA. *There are ongoing studies in its use in heart failure specifically.

So , we’re getting close to discharge and the patient is all better. What should we send them on? Remember to get them back on their RAAS inhibitor or SGLT2 inhibitor if appropriate – these are the best medications to protect hearts and kidneys in the long-term, but are often stopped because of fear of kidney dysfunction.

So to wrap up, the full diuretic toolkit which is especially helpful in challenging cardiorenal cases. So to recap our toolkit, we have the different loop diuretics that we can give in the hospital, the intravenous hammers that form the backbone of our active diuresis. Then, we can tap into sequential nephron blockade with thiazides or the two pliers of the nephron: acetazolamide or SGLT2i working on the proximal tubules. Last but not least, we have your mineralocorticoid receptor antagonists. We should note that this toolkit is not exhaustive, but these tend to be the main staples, with lots of overlap between in-hospital and home.

Thank you for listening and please look at our full episodes on Cardiorenal Considerations and Diuretic Resistance cases for more.