Treat Acute Heart Failure With High-Dose Nitrates

Boluses equivalent to a drip of 600 mcg/min or more have been shown to be effective.

July 2008

By Greg Muirhead
Elsevier Global Medical News

WAIKOLOA, HAWAII - High-dose rather than low-dose nitrates should be given as first-line therapy to patients with acute heart failure.

"I think most of us would agree that nitrates are the mainstay of our therapy," said Dr. Matthew Strehlow of the division of emergency medicine, Stanford (Calif.) University. "Instead of asking, 'Should we be giving nitrates?' we should be asking, 'How should we be giving nitrates?' "

Plenty of U.S. studies have supported the use of nitrates; studies from outside the United States have shown benefits from the use of high-dose nitrates, Dr. Strehlow said at a symposium on emergency medicine sponsored by Stanford University.

In one such study, a group of 56 patients using a combination of high-dose nitrates and low-dose furosemide were compared with a group of 54 patients using high-dose furosemide and low-dose nitrates, he said (Lancet 1998;351:389-93). Six patients were withdrawn from the study because chest radiography results were not compatible with pulmonary congestion. The high-dose group received a 3-mg bolus of isosorbide dinitrate every 5 minutes, which is equivalent to a drip of 600 mcg/min, he said.

The researchers found that the group receiving the high-dose nitrates did better in the combined end point of death, mechanical ventilation, and heart attacks. There were no episodes of hypotension requiring treatment, and there were no recorded blood pressure values less than 85 mm Hg during this treatment protocol, Dr. Strehlow said.

In a more recent Chicago-based safety study of 29 patients who had severe or acute heart failure (AHF) and hypertension (Ann. Emerg. Med. 2007;50:144-52), patients received a nitroglycerin infusion and a high-dose bolus at the equivalent of a drip at 700 mcg/min, he observed. "Those are high doses, right?"

Just one patient developed symptomatic hypotension, Dr. Strehlow noted. "The boluses were stopped. [The patient] was given a 500-cc fluid bolus and did fine."

The researchers concluded that high-dose nitroglycerin therapy was safe, he said. What made the findings more impressive was that 38% of the patients receiving the high-dose nitroglycerin therapy were also taking morphine. Morphine has been shown to portend worse outcomes in acute heart failure when it's used, because it's an indirect venodilator, Dr. Strehlow pointed out.

Also significant: Good results were found even in the 10% of high-nitrate patients who were using β-blockers. "β-Blockers are contraindicated in heart-failure patients," he noted. "I don't know why this group got β-blockers, but it was higher than I expected when I looked at it, because that's also a cardiac depressant. It's going to decrease stroke volume; it's going to decrease cardiac output."

In addition, just 7% of the high-nitrate patients used bilevel positive airway pressure (BiPAP), he said. "BiPAP decreases mortality, decreases the intubation rate, and you can see ... how low the BiPAP is."

Given the support for high-dose nitrate use, the next issue is choosing the best initial dosing option. Dr. Strehlow commented on the following two options:

arrow redNitro paste. "I see that slapped on a lot," he observed. "What's the problem with nitro paste? Basically, it doesn't absorb well," he said. "These patients are often peripherally clamped down, and it's not going to start for 20 minutes. These patients are either going to get better or get worse - probably very rapidly."

arrow redSublingual nitroglycerin. "I actually use this pretty frequently--either the spray or the tablets - and both work pretty well," Dr. Strehlow said. "I use this as a bridge to setting up an infusion. So, when I first see the patient, I can start giving this while everybody's getting set up to run an infusion. And it works pretty well."

Keep in mind, however, that sublingual tablets every 5 minutes are equivalent to a dose of 60-80 mcg/min by drip, he cautioned. "So, when you start your drip at 20, what are you doing? You're backing way off on the nitro," he cautioned. "That's why a high-dose drip generally works better. If you're at 80, then you bump up to 100, and you rapidly titrate to symptom improvement."

Dr. Strehlow said he had no financial conflicts.

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