Published in the January 2015 issue of Today’s Hospitalist
WHEN IT COMES TO treating heart failure, doctors have some sexy developments they can discuss: how stem cell therapy might revolutionize the field, for instance, or the benefits of extracorporeal membrane oxygenation (ECMO) and the latest advance in left ventricular assist devices (LVADs).
Or they might get excited about percutaneous mechanical supports or even a bona fide future blockbuster: neprilysin inhibitors. (See “The next big thing” on page 21.)
“But the most important topic in heart failure treatment is the one none of us ever wants to talk about: our old friend diuretics,” said Ronald Witteles, MD, a heart failure specialist and the program director for the internal medicine residency training program at Stanford University in Stanford, Calif. Dr. Witteles presented an update on heart failure at last fall’s management of the hospitalized patient conference at the University of California, San Francisco. “Diuretics are so simple, but so important to master.”
All the time, Dr. Witteles added, he hears statements like, “Diuretics are overrated!” and “No trial has ever demonstrated that they save lives or reduce hospitalizations!” But the fact remains: “If you manage heart failure, you need to learn to love diuretics or at least how to use them properly. And diuretic management should really be more sophisticated than it sometimes is.”
The most common mistake
Dr. Witteles emphasized that it is important not to overthink the problem: The point of diuresis is to remove excess extracellular fluid. “Its never a good idea to simply accept that a patient will remain with massive extracellular fluid volume overload.”
The most common mistake he sees in heart failure management is patients in the hospital not being diuresed enough. A patient comes in with, say, a 20-pound weight gain. After two days of IV diuretics, five pounds have come off, and the patient’s creatinine starts to rise slightly.
“Often, that creatinine going up has nothing to do with over-diuresis,” said Dr. Witteles. “Too many physicians at that point switch patients to oral diuretics and send them home, leaving them massively volume overloaded.”
What doctors should do instead is take an early hint from the blood urea nitrogen (BUN) levels. “The BUN should rise before the creatinine does if kidney dysfunction is being caused by over-diuresis,” he noted.
“As long as the BUN is not significantly rising, keep pushing ahead with diuretics if there is still excess fluid to go.” Once the BUN jumps significantly before the creatinine has started to go up, “that’s when you know you’ve probably hit your limit.”
Which loop diuretic should you use? Physicians have three options: furosemide (Lasix), bumetanide (Bumex) or torsemide (Demadex). According to Dr. Witteles, any of those is fine.
He noted that some physicians and patients prefer bumetanide. “People feel better about taking large doses of loop diuretics when you’re giving something that reads lower milligrams,” he said. Because Bumex is between 20 and 40 times as potent as Lasix, “there’s something viscerally more comfortable about getting 4 mg of Bumex instead of 120 mg of Lasix. There’s nothing wrong with Bumex, but there’s nothing special about it either.”
And while it usually doesn’t make a large clinical difference, torsemide may have better oral absorption. “What I would do is pick one and get comfortable with it,”
Dr. Witteles said. “Switching among them doesn’t tend to do much.”
Bolus vs. continuous drip
But consider a patient with volume overload who also has significant kidney dysfunction and presents with a baseline creatinine of 2.5. Because you’re worried about diuresis being hard on her kidneys, should you use loop diuretics in twice-daily bolus dosing or as a continuous drip? Or does it matter?
It doesn’t matter, Dr. Witteles answered, as per a randomized trial published in the March 3, 2011, issue of the New England Journal of Medicine. That study not only compared bolus to continuous drip in terms of patient symptoms and creatinine changes, but it also tested a high-dose against a low-dose diuretic strategy.
“No surprise, but the higher dose got patients out of the hospital faster,” he pointed out. In terms of a drip being gentler on the kidneys, “there was absolutely no difference between the bolus and drip groups in terms of symptom assessment or kidney function.”
Practically speaking, “there is no reason not to use twice daily “or more frequent, if needed “bolus doses,” Dr. Witteles said. “They’re easier to give and less resource-intensive.”
As for adding thiazide diuretics to loop diuretics for greater diuresis, doctors again have three main choices: IV chlorothiazide (Diuril), oral hydrochlorothiazide and metolazone. Chlorothiazide was commonly used for many years “until Ovation Pharmaceuticals bought the drug from Merck “and raised the price by more than 800%,” he said. “There should be very few occasions to ever use it because we have alternatives.”
But metolazone shouldn’t be one of them. “It causes hypotension and a massive shift of fluid and electrolytes,” Dr. Witteles explained, characterizing the drug as “evil. I honestly believe there is no prescription drug, short of opiates and other schedule II medications, that has led to more hospitalizations and deaths than metolazone.”
That leaves hydrochlorothiazide, which doctors know is not an effective antihypertensive in patients with reduced kidney function. “But it’s very effective combined with loop diuretics to diurese patients with kidney dysfunction,” Dr. Witteles noted. With an oral loop diuretic, give hydrochlorothiazide at the same time.
“If you’re giving it with an IV loop diuretic,” he advised, “give hydrochlorothiazide 30 minutes earlier.”
When using hydrochlorothiazide, however, it’s important to watch patients’ electrolytes. “Combining a thiazide and a loop diuretic does cause significant potassium wasting,” Dr. Witteles said. “And as with any thiazide, hyponatremia can be an issue.”
How about adding spironolactone? There is some evidence, he noted, that aldosterone antagonists can improve outcomes in patients with systolic heart failure “if patients’ potassium is closely monitored.
“As long as you’re replacing patients’ potassium anyway, I think it’s better to use an aldosterone antagonist from a neurohormonal standpoint,” he said. Aldactazide, a combination of hydrochlorothiazide and spironolactone, is inexpensive. “It gives you the advantage of the dual nephron blockage when combined with a loop diuretic, and it still has some potassium benefits.”
Skip the I and O goals
As for I and O (intake and output) goals in diuresis, Dr. Witteles maintained that they make no sense.
“Why do we even have an upper limit on this goal?” he asked. “Why isn’t the goal as much as we can possibly get off while keeping up with electrolytes?” Having output goals, he noted, leads nurses to ask if they should withhold an evening dose of diuretics if that goal has already been reached. “There’s no reason to have that upper limit.”
Another pointless trend in heart failure management: fluid restriction. Dr. Witteles quoted from several online sources ranging from WebMD to the Cleveland Clinic, all advocating for some form of fluid restriction.
“That is simply wrong,” he said. “Other than in extreme cases where there is significant hyponatremia, you’re going to pee out extra fluid you take in as long as you’re not taking extra salt with it.
Instead, the problem is salt. “Don’t waste your own or your patient’s time focusing on fluid restriction,” said Dr. Witteles. “The problem is too much sodium. That’s the dietary restriction that should trump everything else.”
Patients often want to know what their sodium threshold should be. “There isn’t one,” he pointed out. “The less, the better.” The problem with giving patients a certain number of milligrams to shoot for is that they end up relying on packaged food, with labels that spell out milligrams of sodium and allow patients to keep count.
“You don’t want patients eating prepackaged foods,” Dr. Witteles said. “My advice to them is to not count milligrams but to simply not eat anything out of a package.”
Phyllis Maguire is Executive Editor of Today’s Hospitalist.
The next big thing
THE HISTORY of heart failure treatment over the last several decades has been a golden age of advances followed by years of failure.
Everything tried in the 1980s and 1990s “beta-blockers, ACE inhibitors and angiotensin receptor blockers (ARBs), spironolactone “seemed to work, explained Ronald Witteles, MD, a cardiologist at Stanford University Medical Center who presented an update on heart failure last fall at the University of California, San Francisco.
“But starting in the early 2000s, nothing worked,” he said. Statins, vasopressin antagonists, sildenafil: All were flops. “It got depressing to be in the field because everything we tried was a failure. Even things like ultrafiltration that people got excited about turned out not to be helpful.”
But that long dry spell, Dr. Witteles said, is about to end. Results from the PARADIGM-HF trial were published in the Sept. 11, 2014, issue of the New England Journal of Medicine. Researchers tested a drug called LCZ696 “”I promise you, it’s going to get a better name” “that combined a neprilysin inhibitor and an ARB and compared it to Enalapril, a standard ACE inhibitor.
The trial was stopped early. “LCZ696 produced a 2.8% absolute risk reduction in death from any cause,” said Dr. Witteles. “The number needed to treat over two years to save a life was about 35.”
He expects the drug to be approved within months. “It’s hard to imagine what systolic heart failure patients with any symptoms who are on standard ACE inhibitor or ARB therapy shouldn’t be switched,” he noted. While it remains to be seen how the drug will be priced, “you’ll definitely see patients coming into the hospital on this.”
JVP: the right technique
SHORT OF PERFORMING a neurological exam, “there is probably no physical exam with more practical importance than assessing jugular venous pressure (JVP),” said Ronald Witteles, MD, a cardiologist at Stanford University Medical Center who presented an update on heart failure last fall at the University of California, San Francisco. The exam is key not only for managing heart failure patients and detecting volume overload, but for managing those who are hypovolemic or septic.
As for his recommended technique, “Forget the pen light and don’t use the light on your iPhone,” said Dr. Witteles. “Just get a nice, well-lit room.” Remove the pillow, have patients lean their head back against the bed, and have them propped at an angle of between 30 and 60 degrees.
“Ask the patient to turn his or her head to one side or the other, then stand back and look for pulsation in the neck,” said Dr. Witteles. “The most common error is to think you might be looking at the carotid. The venous pulsation will go up and down with respiration.”
Push on the right upper quadrant, and “if you see something puffing up, that’s the vein.” In terms of reporting, identify the vertical height of the pulsation in comparison to the sternal angle.
“Extend a card or ruler horizontally from the highest point of pulsation and cross it with a ruler placed on the sternal angle, then add five centimeters,” Dr. Witteles said. “That’s your JVP.”