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- 03:17 Clinical Assessment of HF exacerbation
- 10:09 Labs in HF
- 17:14 Home medications
- 22:12 Adjusting diuretics
- 28:43 Additional Volume Removal
- 38:09 Expert Recap
Heart Failure (HF) exacerbation is a clinical syndrome (collection of signs and symptoms) due to elevated intracardiac filling pressures leading to vasoconstriction and/or volume retention.
Pearl 1: Initial clinical assessment
- Blood pressure:
- Hypotension is more common among HFrEF patients, and can be a sign of poor perfusion and even shock
- Hypertension can cause someone to go into a heart failure exacerbation
- Improve BP control with vasodilation/afterload reduction
- Pulse pressure is the difference between systolic and diastolic blood pressure
- Heart Rate:
- Tachycardia could be a sign of shock, but if beta-blockers are on board, they can prevent this physiologic response. A normal heart rate does not rule out shock in a heart failure patient.
- Jugular venous distention/pulsation
- Used to determine the intracardiac filling pressure, which is a marker for LV preload
- 2 ways to check:
- One way is to sit them upright at 90 degrees and check if you can see their JVD above the clavicle
- If you see it, they have elevated intracardiac pressures
- Sit the side of the bed at 45 degrees and assess how high the JVD is (Don’t forget to look at the ear and bilaterally!)
- One way is to sit them upright at 90 degrees and check if you can see their JVD above the clavicle
- Tricuspid regurgitation can cause JVD elevation in the absence of elevated cardiac filling pressures
- Need to differentiate between atrial and venous when assessing JVD
- Check the radial pulse. Venous pulsation should result in two upstrokes for every pulsation in the wrist. If it correlates 1:1, it may be arterial.
- JVP should have increased fullness of the pulsation when applying abdominal pressure
Pearl 2: Initial lab workup
- Elevated BNP (>1000) supports HF diagnosis, and <100 makes CHF less likely
- BNP of 350 has a likelihood ratio of 1 in one study
- Assess the trend. Some factors increase or decrease the BNP
- BNP levels are usually lower in obese patients with heart failure
- Patients with chronic kidney disease tend to have elevated BNP levels
- Neprilysin inhibitors (e.g. sacubitil-valsartan) can cause elevated BNPs, so we generally check a pro-BNP instead of BNP in patients on neprilysin inhibitors
- Particularly for patients with impending shock or shock or if any clinical symptoms concerning of acute coronary syndrome as a culprit of decompensated heart failure
- In patients with an acute MI who developed cardiogenic shock, early revascularization lowers 6 month mortality
- Low Na on admission is a predictor of both all-cause mortality and cardiovascular mortality for patients admitted with a heart failure exacerbation
- A drop in sodium levels of >3 mEq/L was associated with increased mortality
- Risk of death was particularly worse for Na <125 in heart failure exacerbations
- Assess cause of elevated creatinine, since you may not always need to hold or decrease diuresis
- Elevation compared to baseline on admission is usually a sign of cardiorenal syndrome from elevated renal venous congestion
- Management of cardiorenal syndrome is with diuresis
- If the elevation occurs during diuresis, it may not be due to renal injury so much as elevation in creatinine without true kidney injury
- Small elevations secondary to diuresis in a patient who is clinically improving, the best course of management may be continuing diuresis if no other cause of the elevated creatinine is found
Pearl 3: Home meds
- In heart failure exacerbations, beta-blockers should be continued unless the patient is in cardiogenic shock (i.e. in a low output state)
- Consider altered mental status or somnolence, cool and/or clammy extremities, livedo reticularis, low blood pressure or pulse pressure, tachycardic, or thready radial pulse can all suggest cardiogenic shock
- Decreasing or discontinuing beta blockers is associated with increased mortality
- If a patient’s beta-blocker is discontinued during a heart failure exacerbation, they are less likely to be on it, even MONTHS after follow up
- Observational data suggests improved outcomes in HF patients discharged on beta-blockers compared to those who are not
- In heart failure exacerbations, beta-blockers should be continued unless the patient is in cardiogenic shock (i.e. in a low output state)
- Angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), Mineralocorticoid receptor antagonists (MRA), and angiotensin receptor–neprilysin inhibitors (ARNI) are often held due to elevated creatinine on admission or during diuresis, then patients are discharged without them.
- Continuation of these medications as able or certainly resumption prior to discharge. These medications are important for improving lifetime morbidity and mortality
- It may be reasonable to consider continuing the ACE/ARB or decreasing dose in patients who have only a mild AKI
Pearl 4: Loop diuretics
- Various clinician’s practices range from starting with 2-2.5 times the patient’s home diuretic dose to using 1mg/kg IV
- Thresholds and ceiling
- Loop diuretics have a threshold dose below which they don’t have much effect
- Loop diuretics also are considered to have a “ceiling” dose, and doses above that will not cause a significant increase in diuresis
- Dose adjustment
- A “good” dose of a loop diuretic will result in excretion of 250 mEq (~6g) of Na in about 2-3L of urine
- Increase the dose if the patient does not have adequate response to the dose
- Increase the frequency of administration if the patient has an adequate response to dose but 24h UOP is not sufficient
- A spot urine sodium can be checked if unsure about the effectiveness of diuresis based on questionable Is/Os and inability to do accurate weights
- If spot urine Na >100, the dose was effective
- If significantly lower, you may need to increase dose
- Furosemide drip
- Per DOSE trial, it has not been proven to improve symptoms or length of stay in a typical heart failure patient
- Reasonable to consider for diuretic resistant patients
Pearl 5: Additional Volume Removal
- Thiazide and Thiazide like Diuretics: Addition of a thiazide diuretic to a loop diuretic can lead to improved diuresis in a diuretic resistant patient.
- They act on the distal convoluted tubule, working downstream of furosemide, which can help augment diuresis
- Hydrochlorothiazide and chlorthalidone are reasonable options. Metolazone, a thiazide like diuretic, is also commonly used because it is cheap and effective.
- Be cautious, as thiazides can cause significant lab abnormalities, particularly potassium and magnesium
- Check electrolytes twice daily, especially is metolazone is used
- Metolazone can be effective for a few days, so does not need to be dosed daily
- Typical dose ranges from 5mg to 20mg. Typically start with 5mg and add extra dose if needed.
- Be cautious, as thiazides can cause significant lab abnormalities, particularly potassium and magnesium
- Diuresis in COPD:
- Need to monitor bicarbonate levels
- Can start retaining CO2 to compensate (respiratory acidosis) for the metabolic alkalosis that diuresis causes
- Can lead to dangerously elevated PCO2s
- Aggressive chloride repletion can be used to help prevent this
- Chloride depletion metabolic alkalosis:
- Often referred to as “contraction alkalosis” though that is a misnomer since administration of albumin does not improve the alkalosis, but chloride repletion does
- Pendrin is a sodium bicarbonate exchanger that will remove bicarb and reabsorb chloride
- Pendrin activity decreases with hypokalemia, elevated aldosterone, and chloride depletion
- Aggressive diuresis will lead to more chloride depletion and hypokalema, which decrease pendrin’s ability to remove bicarbonate.
- Therefore, decreased activity of pendrin in aggressive diuresis will worsen the chloride depletion metabolic alkalosis and result in elevated bicarbonate.
- If patient can tolerate, consider adding spironolactone to help with hypokalemia
- Give KCl for help the cloride depletion state
- Ultrafiltration: another option for volume removal
- Usually will only do after diuresis fails, however there are exceptions:
- If a patient is on a very large dose of home diuretics and are very volume up, can consider going straight to ultrafiltration
- A decision to do ultrafiltration in this situation is often stylistic, and determined in conjunction with the heart failure specialist and nephrologist
- Usually will only do after diuresis fails, however there are exceptions:
Additional Nuggets from Dr. Kittleson in the expert recap:
- Presence of an S3 is a specific sign of overload in heart failure
- Crackles and rales are neither sensitive nor specific for pulmonary edema in chronic heart failure
- High creatinine does signify it will be a more complex diuresis
- Spironolactone helps with long term remodeling and potassium sparing properties
Pearls 4 and 5:
- In the warm and wet patient, rapid diuresis is ok in a patient who can hemodynamically tolerate. Don’t fear the ins and outs. Lets the patient guide you!
MF: This is Dr. Marty Fried, a primary care physician from THE Ohio State Wexner Medical Center, Dr. Shreya Trivedi, an Internist at Beth Israel Deaconess Medical Center and Dr. Michael Dunleavy, a Clinician Educator Fellow at Ohio State. This is the CORE IM 5 pearls podcast, bringing you high-yield evidence-based pearls. Today we are kicking off a two-part series on advanced heart failure.
S: Our first episode pearls will address care of the heart failure patient on gen med floors. Next episode, we’ll tackle ICU-level care with a discussion about advanced therapies.
MF: We are suuuuuper excited to introduce a new friend of the pod – Dr. Michael Patrick Dunleavy.
MD: Great to be here!
MF: Let’s get started with the pearls we’ll be covering in this episode. Test yourself by pausing after each of the 5 questions:
S: Remember, the more you test yourself the deeper your learning gains.
- Initial clinical assessment
- What are the key clinical variables to evaluate when you first meet an a patient in acute decompensated heart failure?
- Initial lab workup
- What are the most important lab findings for patients in decompensated heart failure?
- Home meds
- Which home meds can be continued during a heart failure admission, and in what circumstances?
- Loop diuretics
- What are some dosing strategies and monitoring tips to help guide initial volume removal?
- Diuresis 2.0 – Advanced topics in volume removal
- What role do thiazides and ultrafiltration play in diuresis, why does diuretic-induced metabolic alkalosis happen and what should you do about it?
MF: Ok, before we dive deep, lets make sure we are on the same page.
Greg: Heart failure is a clinical syndrome, meaning it’s a constellation of signs and symptoms that lead to a diagnosis and decompensated heart failure and refers to somebody who has the clinical syndrome of heart failure with elevated intracardiac filling pressures.
MF: That’s Dr . Greg Katz, our Core IM in-house cardiology consultant and cardiologist and cardiovascular intensivist at Vassar Brothers hospital in Poughkeepsie, NY.
Greg: So I think about a heart failure exacerbation as being the result of elevated intracardiac filling pressures and that leading to a cascade of a neurohormonal response that causes vasoconstriction and fluid retention and all of the subsequent symptoms that people who have those things will develop.
MF: Alright that’s a perfect place to start the initial clinical assessment of a patient who we suspect is having a heart failure exacerbation.
Pearl 1: Initial Clinical Assessment
S: So Mike you just got the call from the ED that your next admission is a middle-aged guy with a history of coronary artery disease s/p a couple stents, ejection fraction in the 20’s who is reporting worsening progressive lower extremity edema and shortness of breath after binging on Netflix and ramen noodles for the last 2 weeks. What is the first thing you are looking out for?
MD: When I’m getting an admission and I’m suspecting it’s a heart failure exacerbation, my spidey senses are way up when I’m looking at the vitals. After all, vitals are vital!
Dr. Hasan: Blood pressure is going to be a sign of a patient’s perfusion status and I think will help determine what your next steps of therapy are. I mean the hypotensive patient who’s maybe poorly perfused and could need an ionotrope. Also, for hypertensive patients… it is more blood pressure control that they need – vasodilatation, some afterload reduction.
MD: That’s Dr. Ayesha Hasan from Ohio State. Dr. Hasan is the medical director of the heart failure program and section chief for heart failure and transplant. Her point here is easily overlooked but obviously crucial to triage – what is their pressure and what does that tell me about perfusion status? And when I’m listening for the blood pressure, I’m also tuning in to what’s the pulse pressure, which is the difference between the systolic and diastolic blood pressure.
Greg: Narrow pulse pressure can be a sign that somebody is in a low output state and if you’re not taking that seriously, occasionally you will miss a vulnerable patient because their blood pressure is 130 over 110 when they’re normally 180 over 140. And you will take someone who is relatively hypotensive but has a pulse pressure of 20 and just create damage.
S: Eek, listening to those number your spidey senses must be tingling, walk us through the pulse pressure Peter Parker.
MD: So pulse pressure is usually determined in large part by aortic elasticity. But, if someone with a reduced ejection fraction comes in with a low pulse pressure — its more likely a sign that their sick heart has a poor systolic function and can’t generate enough force to even get a normal pulse pressure rather than being related to their aortic elasticity.
MF: The other variable not to lose track of is heart rate. Remember that Cardiac Output = Stroke Volume x Heart Rate. Sometimes resting sinus tachycardia may mean that the heart might be on struggle street and making up for the low cardiac output by working overtime.
S: Ya, exactly… but to me the rookie mistake is interpreting that heart rate without looking to see, hey is the patient is on a AV nodal blocker. Think we’ve all been fooled by the normal heart rate with metoprolol on board…
MF: One strategy I’ve seen is people including this in documentation or hand-offs “HR in the 90s on home metoprolol succinate 100mg”.
S: Yes! I appreciate qualifiers to take objective data in context! So that’s vitals, moving to the rest of the physical exam, obviously there are MANY classic overload signs, but if we are going to focus on ONE aspect about the physical exam in heart failure, what would that be?
Greg: You are committing malpractice if you are not looking at someone’s neck veins when they’re admitted with heart failure.
MF: Ooookkaayyy. Note to self, might think twice about asking Greg for expert witness testimony in the future…
Greg: So the reason I focus so much on my physical exam on jugular venous distention is because that is your window into what the intracardiac filling pressures are. The absence of pulmonary edema or lower extremity swelling, or all of these sort of traditional physical exam findings doesn’t tell me that a patient doesn’t have heart failure. You can have heart failure without swelling and swelling without heart failure. And you’re juggler venous pressure is your bedside Swan that tells you what your right atrial pressure is.
S: Ok, sold JVP is our window to how backed up things are in the heart.
Greg: All you need to do is spend one week rounding with a heart failure attending who is able to figure out a patient who the medical team stopped diuresing, but still 20 pounds up just by looking at their neck veins, you will be persuaded too. You can’t just do it once or twice. And watch a couple of YouTube videos. You need to look at a thousand necks.
MD: Alright, well I don’t know about you all but I’m pretty convinced about JVP now. But that’s a pretty tough exam, and I have heard of at least 8 different ways to do it. The real question is, how can we accurately find JVP?
Greg: The simplest like quick and dirty way to do it is you sit somebody up at 90 degrees and you see, do they have any palpable jugular venous pressure above their, uh, above their clavicle. And if you see anything venus above the clavicle in the absence of severe TR, that’s elevated, right Atrial pressure, assuming that it’s not like SVC syndrome or tamponade. Then, the second thing that I’ll do is I’ll put someone at 45 or 60 degrees, just sort of like, not super flat, but also not completely upright. And I’ll look to see, do they have a pulsation at their ear? And you need to look at both sides because sometimes only one side will show it for whatever reason.
MF: Ok, yep, I’ve definitely been guilty of looking only at the right side. I always feel like I’m trying to figure out if the pulsation I’m seeing is venous or arterial?
Greg: When you’re finding someone’s jugular venous pressure, put your finger on their wrist, find the pulse, your juggler venous pressure should have two pulsations for every one pulse beat that you feel at someone’s wrist. And if the upstroke of what you’re feeling on the wrist corresponds to the upstroke of a pulsation in the neck, that’s the carotid pulse… and it’s not the one that you want to be using.
S: Great! So to recap, my big takeaways from the initial clinical assessment is that blood pressure, specifically low pulse pressure that can clue us in if that heart squeeze isn’t that great and they are in a low perfusion state. And I’m all for changing our culture of how we present and document vitals, particularly in HF patient say “HR in the 80s on diltiazem 100mg daily” so we don’t feel reassured by a normal heart rate for a patient on an AV nodal blocker. And will forever be terrified not looking at JVD because thats our window into their right atrial pressure.
Greg: The whole point of the exam is to inform our decision about how we take care of a patient. And so when you’re looking for JVD and figuring out someone’s volume status, you also need to pay attention to anything that might indicate hypoperfusion. And those findings are often subtle. A leg that’s cool, but isn’t frankly cold, a little bit of somnolence, which can be really tricky to find first thing in the morning. If they have a foley in place, you look at the bag to see how much urine there is, cause a drop in urine output can be a sign of something dangerous. You look at the pulse pressure on the monitor. If you’re not looking at the neck veins, you’re wasting your time. But if you’re not looking at all of that other stuff, you’re wasting your time too.
Pearl 2: Additional workup in a heart failure admission (what will labs and imaging tell you about severity/trajectory of the patient?)
S: Alright, guys can we talk about all those times when you’re there at the bedside, with your interns and med students shining your iphone light on the patient’s neck and the JVD exam is umm, quote unquote limited by habitus… sometimes we just need a little bit more objective measures. Lets talk about labs in HF.
MF: Yeah, so a lot of attention gets paid to the BNP – brain natriuretic peptide – and for good reason. BNPs >1,000 supports the diagnosis, BNP <100 makes CHF less likely. BNPs in the hundreds are usually just not as helpful – For example one paper noted that a BNP of 350 has a LHR of 1 – which so doesn’t change your pretest probability at all.
MD: For me, the “TREND” is important as well as the actual numbers. I love when patients coming in with a heart failure exacerbation have had an outpatient BNP when they were feeling well. That way I can compare what the BNP is when they are sick on admission to the hospital to what it was when they were feeling well outpatient.
S: And another reason why that trend is important, I’d argue even more important than the actual numbers is that there are factors that make the BNP higher or lower so it’s important to compare the current BNP to where that patient particularly lives. So say for example, patients with chronic kidney disease usually tend to have a higher BNP. And there are a few other conditions to be aware of…
Dr. Hasan: And then BMI is important when it comes to assessing the BNP because of morbidly obese patients tend to run a lower BNP. So it’s just looking more at the trend. If patients are on the new drug, sacubitil, the neprilysin inhibitor, then BNP will be elevated. So you have to do a pro-BNP.
MD: Yeah, that neprilysin inhibitor BNP bump can be significant, even tripling from the baseline levels. And the reason is neprilysin breaks down BNP. So BNP levels will rise if you are on a neprilysin inhibitor. Instead, you actually want to order a pro-BNP in patients on neprilysin inhibitors since its not a substrate for neprilysin.
MF: So listen BNP gets a lot of attention, but when I’m talking about the heart failure workup with my interns and residents, I always to try to impart a healthy respect for the troponin in decompensated heart failure as well, especially if they their pressures are low and you are concerned about shock.
Greg: You don’t want to miss an opportunity to revascularize somebody when you had that opportunity because that’s the intervention… that that’s the only intervention that we know seems to make a difference in cardiogenic shock.
S: Exactly, if there is any consideration for acute coronary syndrome being a culprit for their decompensated heart failure, especially if their pressures are low — getting them to the cath lab to see if ACS is precipitating their heart failure is one of the few things that can improve their mortality.
M: Love it. Alright, let’s move on to the next important lab. Dunleavy – what else is on your list of never-misses?
MD: Lets talk about sodium. Fun fact, hyponatremia is actually associated with a worse prognosis.
Greg: Sodium corresponds really closely with somebody’s mortality and their degree of chronicity of illness. When I see somebody come in with decompensated heart failure and a sodium of 129 I think about them in a completely different prognostic place than I do in someone who comes in with a sodium of 138.
MD: And there’s data to back that up. Admission hyponatremia is a predictor of all-cause mortality. The risk of death was especially worse for Na <125 in heart failure exacerbations. Even a sodium drop of just 3 mEq/L during the admission was associated with increased mortality.
MF: Wow. OK, respect the sodium. Respect the trop – I feel like we do a fairly good job of that. But yeah, for real, respect that sodium!
S: Alright, any other labs to respect?
MD: There are definitely others, but we might be respecting some lab values a bit too much, like the creatinine …
MF: Yeah – so Mike I don’t think you’re talking about the critically ill patient who arrives in extremis and you are rushing to the CCU – I mean true kidney injury like ATN or acute tubular necrosis – can occur in really sick folks and we definitely care about that – I think we do respect the Cr too much when it comes to small bumps that occur during diuresis.
S: Ughh yes. Happens all the time – and we know the answer is to keep diuresing right through that acute kidney injury
Swapnil: This is not really acute kidney injury. It’s “hyper-creatininemia.”
S: Yes! That is Dr. Swapnil Heremeth to the rescue!! Nephrologist at Ottawa Hospital and from twitter’s NephJC. Wait, but what is he saying?
MF: That hyper-creatinemia that Swapnili mentions referring to the work of Dr. Steve Coca who wrote a great paper on this idea of permissive AKI in treatment of HF.
Swapnil: He’s playing with words yet it’s a question of semantics. Uh, but this kind of framing changes it from thinking of it as a kidney injury to just a rise in creatinine and… and you should be following a principle of “permissive hypercreatininemia”. So letting the creatinine go up… look at the patient. If they are in volume overload, let them be diuresed. Instead of the creatine being 1.5, it is 1.8. That’s okay. Take a deep breath. Clinically the patient is getting better. That’s what matters.
MF: Alright, yes, take a deep breath. Be brave. Channel your inner Swanpil.
MD: So If you see a creatinine bump, reassess what else might be going on. Are they obstructed and need a foley? Or was it just a small bump in a patient who is otherwise clinically improving but still overloaded and needs more diuresis? The knee jerk reaction is often to just hold the diuretics. But if it’s a small creatinine bump in a patient who is otherwise improving, continuing the course may actually be the best thing for them.
S: Haha – yes, I think we all could do better by channeling our inner Swapnil. Alright, so to summarize this pearl on labs to respect in the management of patients with heart failure exacerbation.
(1) Its great to compare BNPs to those from the outpatient setting or the last time they were in decompensated heart failure, especially in patients with CKD, patients on neprilysin inhibitors or obesity.
(2) remember hyponatremia is an independent marker of mortality for patients with CHF, especially if it’s worsening during the admission. (3) Remember to check a trop if there concern acute coronary syndrome as a cause of the decompensated heart failure, especially if they are in that “cold” category that we discussed in pearl 1, because the benefits of early revascularization. (4) And finally, cardiorenal syndrome is important and complicated, but if your patient is still edematous the answer to a small creatinine bump might be continue diuresis.
Pearl 3: GDMT in a HF exacerbation (+/- cardiorenal syndrome and ACEi in AKI)
MF: So, guys, can I tell you what really grinds my gears?
MD: The fact that it costs more to replace an ink cartridges than it does to buy a whole new printer? When you call someone back within seconds of missing their phone call and the person doesn’t answer? Chris Harrison’s merciless pre-commercial teasers during Bachelor Season Finales?
MF: What? Well, yes, obviously, but.. Even worse than that.
MD: Ohh. The fact that some people STILL believe flat earth conspiracies?
M: Oh – no not that bad. That’s bad. No – I reallllllly can’t stand it when my primary care patients have their guideline-directed medical therapy – like beta blockers and ace inhibitors – held during admission and then never restarted on discharge!
S: Yeah, I had worked on changing this habit that I had picked up over time – most of the time, we take precautionary measures just in case, because we don’t know what direction the patient is going to go.
Dr. Hasan: In most cases, we wouldn’t hold the beta blocker. And I think that’s the biggest thing we see. Um, when patients are admitted at night holding a beta blocker on every decompensated patient. So we try not to. If they’re in shock, if they’re tachycardic, very low blood pressure, you think in shock, that would be the time that I would hold it. Otherwise, I would continue the beta block or give a lower dose.
S: And interestingly our “just in case” holding of home meds and not wanting do harm can actually do more harm.
Dr. Hasan: There’s data that shows, um, when we hold beta blockers with patients coming into the hospital, it’s hard to get them restarted on it back to their target dose especially if they came in on 25 milligrams twice a day of Carvedilol. Um, and when the patients were seen months post hospital discharge, oftentimes they weren’t back on their beta blocker. So that’s why we need to continue it unless it’s truly a shock situation.
MF: Thank you Dr. Hasan – that is what I’m talking about… stop stopping my beta blockers!
Greg: Just like big picture, what do I look at? Are they altered or somnolent, what are their extremities feel like? Cool, clammy. Do they have any livedo reticularis? What is their pulse pressure, how thready is their radial pulse? And the combination of all of those things is going to give you a sense of should you stop their beta blocker or should you continue their beta blocker.
S: Ok, so that’s the beta blocker story. I’m guessing things get a bit more dicey with what to do about holding or continuing ACE inhibitors when patients are admitted with heart failure exacerbation.
MF: Well yeah, it’s the kidneys, it’s obviously going to get more complicated here. Tell me we have a Swapnil sound bite for the win?
Swapnil: I don’t blame anyone for stopping the ace inhibitor. Stopping the ace inhibitor is the easy way out. No one is going to blame you for doing that. It’s the, you know, it’s the path of least resistance.
MD: So I just met Swapnil, but I feel like this isn’t the whole story…
Swapnil: So I would encourage people to become courageous and brave and, and not stop the ace inhibitor.
MD: Yep, knew it. But what if someone’s creatinine is rising?
Swapnil: There are, there is little data about what should be done. The knee jerk reflex remains to stop ACE/ARB. The best data we have is there was a um, observation study from Alberta a couple of years ago. And they actually showed that patients whose ACE/ARB stopped had higher mortality subsequently.
MF: Now Swapnil did acknowledge the paper he is referencing is not a trial and despite propensity score matching and other stats wizardry there is a high probability that sicker patients had ACE/ARBs held and you just can’t eliminate all the confounding there.
S: I think it’s a similar logic to the beta blockers argument. If I may try to summarize this pearl, there is a knee jerk reaction to stopping ACE inhibitors when someone is decompensated. There are certainly situations where this is the correct answer, buuut it sounds like there are a lot of situations where ACEs and beta blockers can comfortably be left on, or at least dose reduced, to ensure that we don’t lose all the mortality benefit of those medications if they aren’t restarted on discharge.
Greg: And what you commonly see is a patient comes in on an ACE or an ARB or an Arni or an MRA. And then we’ll have their neuro hormonal blockade held when they’re de-compensated and their Lasix dose or their diuretic dose increased. And then they’re discharged without the neuro hormonal blockade, but with a higher dose of a diuretic. And if you’re thinking about the long-term survival of the patient, that’s the exact opposite thing that you want to do.
Pearl 4: Volume removal
MF: Alright, so at this point we have diagnosed our patient with heart failure, completed a thorough evaluation of their perfusion and congestion status and considered which, if any, of their home meds we need to hold during the admission. Let’s bust out the diuretics and get this person peeing!
Dr. Hasan: For a while we were seeing everybody getting 40 milligrams of IV Lasix when they got admitted, regardless of the home dose. But now I think people are better at looking at the home dose of Lasix, torsemide, whatever. And trying to, our rule of thumb is double it. So if it’s 40 milligrams of torsemide that they’re on at home twice a day, then give them 80 IV twice a day coming in or something like that to figure it out.
S: Ya, I mean everyone has their own practice like some cardiologist really advocate for that initial diuretic dose to be 1mg/kg in the hospital. But lets back and ask what is a good dose of a loop diuetic?
Zaven: For a dose of furosemide to result in an effective diuretic episode for a single dose, it’s considered effective if you excrete from that single dose about two to three liters of water with proportional amount of, uh, sodium chloride in it.
S: That’s Dr. Zaven Sargsyan, hospitalist and APD at Baylor. Obviously every patient has different goals of how much you want them to pee in a day based on what they can tolerate hemodynamically. But what peeves me is we rarely go back after 6 hours and see if that was an effective dose or not – did we hit the threshold for that patient to get effective duresisis?
MD: Dr. Sargsyan broke this down beautifully in a recent tweetorrial, where he astutely asks, what’s a better dose for your patient. 40mg daily or 20mg BID? And it depends on what that person’s individual dose threshold and dose ceiling is.
MF: Yeah, so basically this idea is that the dose threshold is the dose where you will start seeing a meaningful diuresis – around 2-3L of urine per dose. And the dose ceiling is the point where you start getting diminishing returns on your diuretics – further increases no longer lead to more urine output.
Zaven: If that threshold dose for a given patient is 15 milligrams, then giving them 20 BID will result in two episodes of effective diuresis each causing the patient to pee two and a half liters say for a total daily diuresis of five liters. Whereas, if you give that patient a single 40 milligram dose, sure, they might pee a little bit more than the 20. Say they pee three liters, but they only have one of those episodes. And their total daily diuresis is three liters.
MF: Alright, lets put this togethers with a couple cases– it’s going to be a few numbers I think it will be worth going through this exercise so if you can you try to pause or slow down, so patient A got lasix 40mg IV twice a day and his daily urine output is 1.5L. Considering that output- Dunleavy – how are you adjusting his diuretics?
MD: So 40mg clearly isn’t reaching this patient’s threshold. If total urine output is 1.5L after two doses, that means with each 40mg IV dose, the patient only puts out 750 cc. That’s nowhere near our target of 2-3L per dose, so we need to up the dose to 80mg.
MF: Alright so lets say patient B is on 40mg IV twice a day and has UOP of 4L per day, tolerating it well but still quite overloaded. What are you doing?
MD: So each dose of 40mg IV is leading patient B to put out almost 2L per dose. That means increasing the amount given per dose will likely hit the ceiling for that patient. So it will only have a marginal effect. Instead of going up on the dose, I’d increase the frequency of the medication to TID. And maybe for the sake of the patient, consider giving it at 6am, noon and 6pm, so they aren’t up all night peeing.
MF: Quite thoughtful of you there Dunleavy. Alright. But then sometimes you run into those situations where tracking urine output is, like, inconceivably difficult…
Greg: Yeah, so if you’re not sure whether somebody responded to a dose of diuretic either because they can’t tell you qualitatively if they peed a lot or because you have poor tracking of I’s and O’s you can send a spot, urine sodium, if that is over a hundred, they probably responded to the dose of diuretic. If it’s under a hundred, they probably didn’t. It’s 95. You can like take some poetic license and say it’s probably fine. But uh, in general, a hundred is a decent cutoff.
MD: Yeah so the point here is that if someone did not have a significant urine output, or they have a low urine sodium after their diuretic dose, you probably need to increase the dose of the diuretic.
MF: And at what point do you reach for the furosemide infusion – the old lasix drip?
S: We asked all of our experts about this – and it really came back to style.
Greg: I have a very low threshold to start a lasix drip… if they’re not responding to a bolus of 80, that’s usually when I’ll start them on a drip.
MF: And it’s also OK to not have a strong opinion here.
Swapnil: So, I’m a little bit agnostic about whether you want to use a bolus versus infusion. Uh, but if you cannot do an infusion, it’s completely fine to use, you know, multiple bolus doses.
S: Haha thank you Swapnil. Alright, so to summarize if we can loop in our patients and nurses to help out with accurate urine outputs, its great because we can then adjust the dose if they haven’t his their threshold dose or, if they have hit the threshold, increase frequency of the diuretic to get even more volume off. A good effective out per dose is 2-3L urine. And if its hard to get accurate urine output, we can try spot urine sodium to see if our patient reached their threshold dose. Intermittent vs continuous dosing is a style question.
Pearl 5: Additional Volume Removal options/tips
MF: So with most patients all you need is a splash of furosemide and they are going to be juuuuust fine.
S: Hopefully! But sometimes things always don’t go so smoothly. What if that furosemide just isn’t cutting it?
Dr. Hasan: If you’re up to 80 or 100 milligrams three times a day on Lasix, adding a thiazide is very appropriate. And so we usually turn to metolazone just because it’s relatively inexpensive.
MD: Yeah, the idea here is that thiazides such as chlorthalidone, and thiazide like diuretics, such as metolazone, work in the distal convoluted tubule, which is downstream of the loop of henle where furosemide does its dirty work. And, thiazides are especially useful in situations where long term presence of loop diuretics are causing diuretic resistance.
MF: Anything specific about the addition of thiazides we should know about?
Dr. Hasan: We would turn to metolazone five milligrams, sometimes 10 milligrams, and use it on an, on a PRN basis. The thing about metolazone is it lasts up to 72 hours, the effect from it. So it’s not something that we need to dose daily when we use it to augment diuresis.
MF: Ok – so the point here is that we shouldn’t be writing metolazone q-day and just set-it-and-forget-it.
Greg: The risk of adding thiazides is that you get way more electrolyte disturbances, particularly hypokalemia.
MD: Yeah – we see this commonly. So I’m definitely checking lytes twice daily if I’m reaching for a thiazide or thiazide-like diuretic.
S: And while double-diuresing with loops and thiazides, other electrolytes to keep an eye on is that chloride and that bicarb – gotta watch out for pesky diuretic-induced metabolic alkalosis that we sometimes mistakenly call contraction alkalosis.
Swapnil: The assumption or the crude way of putting it is that everything else contracts, but the bicarb remains the same. So the bicarb concentration goes up, right? So that’s the and it makes intuitively, Right? Sodium goes down, fluid goes down, the potassium goes down. But the bicarbonate concentration for some reason stays the same. But as we know, that’s not the entire story.
MF: (a) I don’t think I ever realized exactly why it was called contraction alkalosis and (b) I feel like I’ve been lied to my entire life. But, as usual, credit to Swapnil for completely opening my eyes to something I hadn’t appreciated before.
Swapnil: The terminology has evolved from volume contraction alkalosis to a chloride depletion or chloride depleted alkalosis, CDA. So the reason contraction alkalosis is not right is because if you give these patients albumin for example, you will correct the volume state, but it doesn’t correct the alkalosis. It’s only when you give them chloride that the alkalosis seems to get corrected.
S: And without chloride and being in metabolic alkalosis state for a bit can have some significant implications for some of our patient with obstructive lung disease.
Greg: And when you’re retaining bicarb that will, that metabolic alkalosis can cause a respiratory compensation. And when you have patients who have COPD and have baseline PCO2s in the fifties or sixties all of a sudden for them to be retaining more CO2 is a really bad thing. When that bicarb starts to creep up to 36 and then 38 and then 41 and every once in awhile there will be a really catastrophic outcome because somebody has a metabolic alkalosis that’s induced by diuretics and then they have respiratory compensation and there are a PCO2 shoots up to 90 and then they get CO2 narcosis and so you need to be cautious about that.
MD: Ya, I actually saw this very recently on the wards. We had a patient whose bicarb was slowly increasing over several days of diuresis. But thanks to our conversation with Greg, we got on top of it. We treated the diuretic-induced metabolic alkalosis by repleting their chloride using potassium chloride. The bicarb improved and fortunately the patient didn’t develop any respiratory issues.
MF: Nice – I guess we could just memorize metabolic alkalosis give KCl, but I kind of want to channel my inner Tony Breu ask WHY?!?
Swapnil: The understanding has really changed. And one of the key channels I should say is this thing called Pendrin. Pendrin is a chloride bicarbonate exchanger. So it will throw out the bicarb and reabsorb chloride.
MD: Yeah this chloride-bicarb exchanger allows our kidneys to “remove” excess bicarbonate in the urine by “reabsorbing” a chloride ion. Basically, if there is chloride available, pendrin can pick one up and toss out a bicarb into the urine
S: Right, BUT when we diurese people with loops plus thiazides they end up losing all of their chloride, so pendrin doesn’t have its mojo, doesn’t have that chloride and they can’t correct the metabolic alkalosis.
MD: And pendrin’s activity also shuts down more with hypokalemia and when there is elevated aldosterone. When you think about problems with patients in heart failure – elevated RAAS system, diuretic-induced hypokalemia, and chloride depletion – it’s almost like we are doing everything we can to shut down pendrin!
MF: Oh dear. So uhhhh, can we do anything to prevent that?
Swapnil: In situations where you know you’re going to need to use either high doses of furosemide or you’re adding on metolazone, or a potent distal diuretic, I would, I almost proactively add on spironalactone.
MF: Oh wow that makes so much sense – hypokalemia is bad for pendrin so preventing that with a potassium-sparing diuretic helps keep pendrin going.
S: So just to recap: when we add on thiazide-like diuretics to loops we cause lots of electrolyte issues including hypokalemia, chloride depletion and a resulting metabolic alkalosis. The metabolic alkalosis is largely due to the decreased activity of pendrin, a chloride-bicarb exchanger that spits out bicarb if it can absorb chloride. But, in heart failure patients being aggressively diuresing, when there’s no much chloride around, not much spitting out bicarb. AND pendrin activity is further decreased with hypokalemia and hyperaldosteronism – so one work around is preemptively giving spironolactone – something thats good for these patients anyway.
MF: Well put Shrey. Alright. Let’s finish out this pearl with a quick discussion of what to do when we have started with a loop, added a thiazide, and maybe even a potassium-sparing diuretic – the old total nephron blockade – and STILL aren’t getting the diuresis we want…
Swapnil: If you have given enough of that and you’re still not having enough response, then we go to the, you know, removing fluid by mechanical means – Barbarian manners like dialysis and ultrafiltration!
S: Haha yes, ultrafiltration is definitely an option once you have run out of the more sophisticated ways to get volume off using medication. But ya, there are definitely situations where we might reach for ultrafiltration earlier.
Dr. Hasan: Sometimes we start with ultrafiltration right away on some of the patients who come in on massive doses of torsemide at home, a hundred BID and they’re up 30 pounds or so. That might be a patient you go straight to ultrafiltration because you know they’re going to be very diuretic resistant. Um, but otherwise as you’re escalated in the hospital, you’re on big boluses of a loop or a drip and then the thiazide and try ultrafiltration and you get a higher sodium removal with ultrafiltration. And also you don’t have some of the electrolyte issues because it doesn’t pull off potassium and magnesium so you can usually use it in that situation. We put somebody on ultrafiltration because they had terrible gout with their loop diuretics. So we did ultrafiltration and everything… Everything went pretty well.
MF: Oh wow, pretty cool – so ultrafiltration allows us to remove fluid manually without mucking with those electrolytes.
MD: So to summarize this section on trouble-shooting diuresis. Once you are on a fairly high dose of loop diuretic and not achieving significant diuresis consider adding a thiazide diuretic like chlorthalidone or a thiazide-like diuretic such as metolazone. Remember these can cause substantial electrolyte abnormalities and contribute to chloride-depletion metabolic alkalosis, which as we saw can be a major issue when diuresing patients, especially those who have COPD. In those patients reach for the KCl to replete their chloride and prevent worsening of their chronic respiratory acidosis – or even consider adding spironolactone to prevent the cascade from the start.
S: Finally, ultrafiltration definitely is an option if all else fails, but there are cases where you can reach for it earlier such as if someone has already demonstrated significant diuretic resistance and you know you are going to have a tough time using just medications.
M: Alright well that’s all for us – we are now going to have Dr. Michelle Kittleson for an expert recap of our pearls as well as a few nuggets of her own! Dr. Kittleson is a professor of medicine at UCLA and the director of the advanced heart failure and transplantation fellowship at Cedars Sinai Medical Center. She also tweets from @MKittlesonMD so check her out there.
Expert Recap with Michelle Kittleson:
Lets start with Pearl 1:Initial clinical assessment: the key clinical variables and lab findings
Signs of volume overload are relatively well-known:
Elevated JVP + S3 gallop are the more specific signs of congestion. Rales are neither sensitive nor specific for pulmonary edema in chronic HF- there may be no rales due to upregulation of pulmonary lymphatics or lots of rales due to atelectasis- the best way to irritate your heart failure attending is to base your assessment of volume status on the lung exam alone! But I digress.
Signs of poor perfusion are just as important- there is low pulse pressure, as noted, but tachycardia is important too—because it’s a symptom, not a disease. Don’t move to knee-jerk lower the heart rate in a patient with ADHF. Instead, respect that the high HR is an attempt to compensate for low SV in a tenuous patient.
What labs can tell you about the severity/trajectory of a patient? If I were stranded on a desert island with a HF patient and could only choose 3 labs (OK, maybe the analogy stretches credulity, but let’s run with it), I would want sodium, potassium, and Cr. Na and Cr would tell me how sick the patient is—low Na and high Cr means it will not be a straightforward set-it-and-forget-it ride, and high/low K would help me decide on how much RAAS inhibition and loop diuretic therapy the patient can tolerate.
What about home meds? If the K and BP can take it, continue all the wonderful GDMT that they came in on. The acute hemodynamic benefit of afterload reduction of the ARNI/ACEI/ARB and the natriuretic effect of the ARNI can only be a good thing. The MRA is also essential, not just for long-term remodeling, but K-sparing properties. Have you ever swallowed a K horse pill? You don’t want to! Keep up the K in the least offensive way by continuing the MRA. Finally, as noted, observational studies indicate that discontinuation of beta-blockers during hospitalization results in reduced beta-blocker usage at follow-up, which is likely to contribute to poorer long-term outcomes. So unless you think the patient is sick enough to need a PA catheter and inotropic support (so advanced that there is little benefit from GDMT and imminent discharge is unlikely anyway) there is no reason to stop the ARNI/BB/MRA.
And best for last, my favorite topic: IV diuresis. I have 3 rules for inpatient diuresis: The right answer is what works: I love loop diuretic drips because I find, in my experience, that I just get more bang for my buck. Yes, there was no difference in the DOSE trial, but what did they test? Global improvement in symptoms at 72 hours? What does that even mean?
My rule of thumb: if lasix 80 IV BID doesn’t give me what I want (which is usually minimum of 2L diuresis) within the first 24 hours, a drip it is. What about metolazone? It’s a big gun to be used sparingly given the hyponatremia and hypokalemia that results. If a patient isn’t responding to lasix drip at 80 mg/h, I reach for metolazone, but I also start talking advanced HF therapies with the patient—needing metolazone to achieve decongestion is a bad sign.
Rule 2 the longer you stay, the longer you stay.
The longer you stay. . . I think every + of edema is 5-10 lbs, so someone with 3+ bilateral LE edema could have 30-40 lbs to lose, let’s say 15 L. If you make them 4L negative daily, they’ll be there 4 days. If you make them 2L negative daily, they’ll be there twice as long, giving them more time to fall out of bed or get C diff. In the warm + wet patient with stable BP, K, and Cr, don’t be afraid of rapid diuresis- let the patient guide you, not fear of I/Os.
It’s mean to disrupt sleep. I turn off loop diuretic drips 11 PM to 5 AM and unless a patient is in significant respiratory distress, never spot diuretic doses after 6 PM! Yet more reason to be more aggressive in the AM.
S: And with that’s a wrap for todays episode. If you found this episode helpful, please share with your colleagues or your team and give it a rating on Apple podcasts or whatever podcast app you use! It really does help people find us!
If you want to add any of your own tips or share challenges, tweet us and leave a comment on our website page, on instagram or facebook page. Thank you to Dr. Cathy Cichon from UCSD for the accompanying graphic, to Solon Kellaher for audio editing especially all the ones the day before publications, to peer reviewers Dr. Stephan Pan and Dr. Eugene Yurditsky, as well as the many hospitalists and residents for reviewing this episode and thanks to you!
As always we love hearing feedback, email us at email@example.com. Opinions expressed are our own and do not represent the opinions of any affiliated institutions.
- Regnault, V., Lagrange, J., Pizard, A., Safar, M. E., Fay, R., Pitt, B., … & Lacolley, P. (2014). Opposite predictive value of pulse pressure and aortic pulse wave velocity on heart failure with reduced left ventricular ejection fraction: insights from an eplerenone post–acute myocardial infarction heart failure efficacy and survival study (EPHESUS) substudy. Hypertension, 63(1), 105-111.
- Jackson, C. E., Castagno, D., Maggioni, A. P., Køber, L., Squire, I. B., Swedberg, K., … & Dobson, J. (2015). Differing prognostic value of pulse pressure in patients with heart failure with reduced or preserved ejection fraction: results from the MAGGIC individual patient meta-analysis. European heart journal, 36(18), 1106-1114.
- Rocklin, D. M. (2018). The Role of the Clinical Examination in Patients With Heart Failure: EZ CVP. JACC: Heart Failure, 6(11), 972-973.
- Sinisalo, J., Rapola, J., Rossinen, J., & Kupari, M. (2007). Simplifying the estimation of jugular venous pressure. The American journal of cardiology, 100(12), 1779-1781.
- Chiaco, J. M. S. C., Parikh, N. I., & Fergusson, D. J. (2013). The jugular venous pressure revisited. Cleveland Clinic journal of medicine, 80(10), 638.
- Thibodeau, J. T., & Drazner, M. H. (2018). The role of the clinical examination in patients with heart failure. JACC: Heart Failure, 6(7), 543-551.
- Mangini, S., Pires, P. V., Braga, F. G. M., & Bacal, F. (2013). Decompensated heart failure. Einstein, 11(3), 383.
- Nohria, A., Tsang, S. W., Fang, J. C., Lewis, E. F., Jarcho, J. A., Mudge, G. H., & Stevenson, L. W. (2003). Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure. Journal of the American College of Cardiology, 41(10), 1797-1804.
- Myhre, P. L., Vaduganathan, M., Claggett, B., Packer, M., Desai, A. S., Rouleau, J. L., … & McMurray, J. J. (2019). B-type natriuretic peptide during treatment with sacubitril/valsartan: the PARADIGM-HF trial. Journal of the American College of Cardiology, 73(11), 1264-1272.
- Horwich, T. B., Hamilton, M. A., & Fonarow, G. C. (2006). B-type natriuretic peptide levels in obese patients with advanced heart failure. Journal of the American College of Cardiology, 47(1), 85-90.
- Hochman, J. S., Sleeper, L. A., Webb, J. G., Sanborn, T. A., White, H. D., Talley, J. D., … & McKinlay, S. M. (1999). Early revascularization in acute myocardial infarction complicated by cardiogenic shock. New England Journal of Medicine, 341(9), 625-634.
- Lu, D. Y., Cheng, H. M., Cheng, Y. L., Hsu, P. F., Huang, W. M., Guo, C. Y., … & Sung, S. H. (2016). Hyponatremia and worsening sodium levels are associated with long‐term outcome in patients hospitalized for acute heart failure. Journal of the American Heart Association, 5(3), e002668.
- Zannad, F., & Rossignol, P. (2018). Cardiorenal syndrome revisited. Circulation, 138(9), 929-944.
- Parikh, C. R., & Coca, S. G. (2019). “Permissive AKI” with treatment of heart failure. Kidney international, 96(5), 1066-1068.
- Metra, M., Torp‐Pedersen, C., Cleland, J. G., Di Lenarda, A., Komajda, M., Remme, W. J., … & COMET investigators. (2007). Should beta‐blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET. European journal of heart failure, 9(9), 901-909.
- Jondeau, G., Neuder, Y., Eicher, J. C., Jourdain, P., Fauveau, E., Galinier, M., … & Tanguy, M. L. (2009). B-CONVINCED: Beta-blocker CONtinuation Vs. INterruption in patients with Congestive heart failure hospitalizED for a decompensation episode. European heart journal, 30(18), 2186-2192.
- O’Connor, C. M., Abraham, W. T., Albert, N. M., Clare, R., Stough, W. G., Gheorghiade, M., … & Fonarow, G. C. (2008). Predictors of mortality after discharge in patients hospitalized with heart failure: an analysis from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF). American heart journal, 156(4), 662-673.
- R Teerlink, J., Alburikan, K., Metra, M., & E Rodgers, J. (2015). Acute decompensated heart failure update. Current cardiology reviews, 11(1), 53-62.
- Ellison, D. H. (2019). Clinical pharmacology in diuretic use. Clinical Journal of the American Society of Nephrology, 14(8), 1248-1257.
- Ellison, D. H., & Felker, G. M. (2017). Diuretic treatment in heart failure. New England Journal of Medicine, 377(20), 1964-1975.
- Brater, D. C. (1998). Diuretic therapy. New England Journal of Medicine, 339(6), 387-395.
- Felker, G. M., Lee, K. L., Bull, D. A., Redfield, M. M., Stevenson, L. W., Goldsmith, S. R., … & Anstrom, K. J. (2011). Diuretic strategies in patients with acute decompensated heart failure. New England Journal of Medicine, 364(9), 797-805.
- Ellison, D. H. (1991). The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Annals of internal medicine, 114(10), 886-894.
- Jentzer, J. C., DeWald, T. A., & Hernandez, A. F. (2010). Combination of loop diuretics with thiazide-type diuretics in heart failure. Journal of the American College of Cardiology, 56(19), 1527-1534.
- Hill, N. S. (1986). Fluid and electrolyte considerations in diuretic therapy for hypertensive patients with chronic obstructive pulmonary disease. Archives of internal medicine, 146(1), 129-133.
- Luke, R. G., & Galla, J. H. (2012). It is chloride depletion alkalosis, not contraction alkalosis. Journal of the American Society of Nephrology, 23(2), 204-207.
- Costanzo, M. R., & Jessup, M. (2012). Treatment of congestion in heart failure with diuretics and extracorporeal therapies: effects on symptoms, renal function, and prognosis. Heart failure reviews, 17(2), 313-324.
- Singh, D., Shrestha, K., & Tang, W. W. (2010). Spot Measurement of Urine Sodium as an Index of Natriuretic and Diuretic Response to Intravenous Furosemide Infusion in Acute Decompensated Heart Failure. Journal of Cardiac Failure, 16(8), S18.
- Soleimani, M. (2015). The multiple roles of pendrin in the kidney. Nephrology Dialysis Transplantation, 30(8), 1257-1266.
Tags: 5 Pearls, cardiology, Clinical Practice, CME