MONTREAL — The most common emergency department treatments for cardiogenic pulmonary edema actually make the condition worse and should be abandoned in favor of aggressive, high-dose nitroglycerin combined with angiotensin-converting enzyme inhibitors, Amal Mattu, M.D., said at the International Interdisciplinary Conference on Emergencies.
Most emergency physicians combine low doses of nitroglycerin (NTG) with either morphine or a diuretic, or a combination of both—to the detriment of the patient, according to Dr. Mattu of the University of Maryland, Baltimore.
“For most physicians, nitroglycerin is first-line therapy, but it is still very underdosed. Most physicians are still not comfortable reaching doses like 50 mcg to 100 mcg to 200 mcg per minute—they are using very low doses, which don't really help that much,” he said in an interview with this newspaper.
Dr. Mattu recommends aggressive use of NTG sublingually as first-line therapy for rapid and effective treatment initiation, followed by topical NTG in those with moderate symptoms and intravenous NTG in those with the severe symptoms.
Caution should be exercised in hypotensive patients as well as those patients with acute mitral regurgitation, aortic stenosis, pulmonary hypertension, and those taking sildenafil, he said.
The goals in treating cardiogenic pulmonary edema (CPE) patients should be to decrease preload and afterload—both of which can be done with aggressive NTG therapy, Dr. Mattu said.
Although morphine is a common addition to the NTG regimen for preload reduction, there is very little evidence that it is effective in this regard, he said.
In fact, there is significant evidence that it can cause respiratory and myocardial depression at high doses, Dr. Mattu said, and its histamine-related side effects such as rash, urticaria, nausea, and vomiting can actually increase catecholamine release, which worsens the problem.
The basis for morphine's reputation for decreasing preload largely comes from studies in the 1970s in which morphine produced venodilation in the hands and forearms of pulmonary edema patients (Circulation 1976;54:335–7), but a handful of more recent studies actually show deterioration in patients receiving morphine, he said.
Furthermore, an abstract presented at this year's Society for Academic Emergency Medicine meeting demonstrated an almost fivefold increase in mortality among acute decompensated heart failure patients receiving morphine, compared with those who were not.
“Once this study is published, it may almost be malpractice to administer morphine to these patients,” Dr. Mattu said.
The other common addition to NTG therapy is a diuretic such as furosemide to aid in preload reduction and act as a vasodilator.
But because many CPE patients have significantly impaired renal blood flow, this therapy takes between 30 minutes and 2 hours to reach the kidneys and initiate diuretic action, said Dr. Mattu.
It is important to remember that up to 50% of pulmonary edema patients may have general body euvolemia and are not actually fluid overloaded; they just have the wrong distribution of fluid in their lungs. “Diuretics drain the body, but not the lungs, so they will not necessarily produce the desired effect,” he said.
Again, although studies showing hand and forearm venodilation with furosemide have formed the basis for this treatment approach (Circulation 1997;96:1847–52), many more studies demonstrate initial adverse hemodynamic effects, with only a delayed reduction in preload, Dr. Mattu said.
“This should be a third-line medication,” he added.
For afterload and preload reduction, Dr. Mattu recommended angiotensin converting enzyme (ACE) inhibitors (enalapril or captopril), either intravenously or sublingually, as second-line therapy after NTG. This therapy produces an abrupt increase in diuresis even prior to the use of a diuretic, by improving renal blood flow, and significant hemodynamic and subjective improvements in as little as 6–12 minutes, he said.
“This is something I hope more people will catch on to. Almost everybody who I know who has tried this is a big fan of it,” he said. “They are seeing a lot of patients who look like they are going to need intubation who will often turn around within 15 minutes and not need intubation, and often not even need to go to the intensive care unit.”
The combination of ACE inhibitors with NTG therapy exceeds the benefit of either drug alone; however, ACE inhibitors are also an acceptable single agent for patients who cannot tolerate NTG therapy, he said.
The use of the recombinant natriuretic peptide nesiritide has come under fire recently, Dr. Mattu said, after publication of two metaanalyses associating it with increases in mortality and worsening of renal function in acute decompensated heart failure patients (Circulation 2005;111:1487–91; JAMA 2005;293:1900–5).
“This therapy is unproven as an additional therapy in patients who are already receiving optimal treatment,” he said.