Fight diuretic resistance with the right dose

Treating decompensated heart failure is more complicated than simply prescribing a diuretic.

Doing the same thing and expecting different results is a common scenario in treatment of acute decompensated heart failure, according to Viviana Navas, MD.

“A lot of the times [at] admission, as soon as we see edema or volume overload, the patient gets one or two doses of IV diuretics. They diurese around a liter, feel better the next morning, and get discharged, most of the time on the same dose of diuretic, and they come back in three to five days,” she said. “We need to know how to manage these patients when they're in the hospital and what to discharge them on so they don't come back within 30 days, or at all.”

Viviana Navas MDslashPhoto by Kevin Berne
Viviana Navas, MD/Photo by Kevin Berne.

In a session titled “Approach to the Swollen Patient” at Internal Medicine Meeting 2017, Dr. Navas, who is medical director of heart failure, cardiac transplantation, and mechanical circulatory support in the department of cardiology at the Cleveland Clinic in Weston, Fla., said that while diuretic therapy is first-line treatment for cardiac congestion, it can decrease renal function.

“Worsening renal function is very common in decompensated heart failure patients, and it's usually associated with a greater hospital resource utilization and mortality,” she said. “We know that the patients that are already getting worsening kidney function are not going to do as well. Patients who respond and their kidneys stay the same, we know they have a better prognosis.”

Dr. Navas noted that diuretic resistance is the main obstacle to overcome in patients with heart failure and that it can be related to many factors, the most common of which is inadequate diuretic dose. If a diuretic dose wasn't working at hospital admission, it's not going to work afterward, she stressed.

Delayed intestinal absorption of oral drugs, decreased diuretic excretion into the urine, and increased sodium reabsorption at sites in the nephron that aren't sensitive to diuretics are other potential factors related to diuretic resistance, Dr. Navas said.

Sodium intake is also a crucial part of the puzzle, since a high intake can prevent net fluid loss even if adequate diuresis is being achieved, she noted. However, she acknowledged that limiting sodium intake is difficult in inpatients and even more so in outpatients. “It's very hard for someone to have 2 grams of sodium in their diet a day, which is what I usually recommend,” she said.

Treatment of diuretic resistance should start by determining the single effective diuretic dose, Dr. Navas recommended. “It's not the same, for example, to have a patient who's taking 20 mg of furosemide and say ‘OK, let's just increase it to 20 twice a day.’ Because it's the same dose, just twice a day,” she said “You have to determine what the single effective dose is. If the 20's not working, don't try 20 twice a day or three times a day. Just go with a higher dose once and see what happens.”

Dr. Navas stressed that only approximately 50% of oral furosemide is absorbed in edematous states and recommended considering a switch to bumetanide or torsemide, both of which have better bioavailability. “That's usually my order of doing things,” she said. “If the patient is already on furosemide, then my next drug would be bumetanide and the next medication would be torsemide. When the patient is really advanced and is not responding to anything, I go straight to torsemide.”

Physicians should also change oral drugs to IV drugs whenever possible. “Usually that's the whole point of having the patient in the hospital, because you know that the intestinal perfusion is decreased,” Dr. Navas said. In addition, there is reduced intestinal motility, and mucosal edema can cause decreased drug absorption, she noted.

There is no significant difference in efficacy or safety between bolus injections or infusion of IV diuretics, but Dr. Navas said that she usually gives advanced heart failure patients a bolus when they first come in and then switches to a drip because it is easier to manage. “Usually I use furosemide, 5 to 10 mg per hour, and see how they respond. I do it that way just because I feel like I have more control over the diuretic,” she said. “Some of them just will overdiurese and all of the sudden they put out five liters in six hours. [If that happens,] stop the drip. It's easier than if you just gave a huge bolus.”

She also recommended that physicians avoid discharging patients immediately after the last dose of IV diuretics. Instead, she said, test their response to the dose of oral medication that is scheduled to be prescribed at home. Without this step, Dr. Navas predicted, “the patient is going to come back to the hospital within a week or two.”

A short-term trial of inotropic agents may be considered in a monitored setting if a patient's worsening renal function might be related mainly to low cardiac output and decreased renal perfusion, Dr. Navas noted. “This happens in the hospital when we don't want to go to ultrafiltration and they're not really responding to diuresis,” she said. While Dr. Navas usually doesn't give inotropes without a Swan-Ganz catheter, she said that physicians who know their patients very well can try a fixed dose of milrinone or dobutamine in the hospital for a day or two. “They will start diuresing most of the time,” she said.

Dopamine has traditionally been thought to help improve or preserve renal function by increasing renal flow and cardiac output, Dr. Navas noted. “There was a whole thing I remember when I was a resident and when I was a cardiology fellow about the effect of dopamine on the kidney and how you can increase the diuresis just by giving it,” she said. However, she pointed out that a small trial of 60 patients failed to establish its clinical efficacy and safety.

“I don't love to give dopamine unless the patient is severely hypotensive and they won't tolerate either dobutamine or milrinone, just because it makes them really tachycardic and increases their arrhythmia risk,” she said. She is more likely to use milrinone or dobutamine in patients who have very low output in cardiogenic shock. “Just be very careful with milrinone in chronic kidney disease patients,” she stressed. “It can get toxic.”

Ultrafiltration can be considered in heart failure for patients with acute decompensation, diuretic resistance, and renal dysfunction, Dr. Navas said. Ultrafiltration was associated with a significantly greater rate of fluid loss but no difference in creatinine in both the UNLOAD trial and the RAPID-CHF trials. In the CARESS-HF trial, which compared ultrafiltration with stepped pharmacologic therapy, both groups had similar weight loss but ultrafiltration was associated with increased creatinine and more adverse events.

Dr. Navas noted that the available evidence does not establish ultrafiltration as first-line therapy for acute decompensated heart failure but added that the 2009 American Heart Association/American College of Cardiology guidelines consider it reasonable for patients with refractory congestion that is not responding to medical therapy. Although it can be very useful when indicated and in the right patients, it is a treatment of last resort, she said: “I try everything first before asking my nephrology colleagues to come and ultrafiltrate the patient.”