You're working the overnight shift, it's 6:15 a.m., and you're starting to dream of a breakfast sandwich and bed. But, no, it's your lucky morning, and in rolls a 55-year-old man in acute respiratory distress. He is hypertensive, tachycardic, and tachypneic. A quick bedside ultrasound reveals bilateral B lines that convince you that the patient is in acute pulmonary edema (APE) or acute decompensated heart failure (ADHF). The 12-lead ECG reveals only sinus tachycardia, and your nurse asks you how much furosemide you want to give.
Congestive heart failure is a common problem in the United States with more than five million patients carrying the diagnosis and 500,000 new diagnoses each year. (Mt. Sinai J Med 2006;73:506.) APE occurs when blood backs up into the pulmonary vasculature, leading to increased oncotic pressure and leakage of fluid into the alveolar spaces. Put more simply: These patients are drowning.
APE patients suffer from increased afterload — making it more difficult for the left ventricle to function — and increased preload. As such, the goals of treatment must be directed at decreasing cardiac filling pressures (preload) and decreasing afterload. Neurohormonal activation also worsens cardiac performance and increases intravascular volume and vascular tone. The mainstay of APE treatment for decades has been loop diuretics, mainly furosemide. The central role these drugs continue to play highlights a lack of understanding of the underlying pathophysiology of the disease.
Pathophysiology of APE
The cardiorenal model was first put forward in the 1940s as the predominant explanation for APE. It was believed that decreased blood flow to the kidneys led to decreased renal function and fluid retention leading to volume overload. This was the basis for loop diuretics being recommended. It was clear, however, that this model was insufficient because it did not explain why the disease progressed or the finding of increased peripheral vasoconstriction from invasive monitoring studies.
The cardiocirculatory model was first put forth in the 1970s. This model argued that peripheral vasoconstriction led to decreased cardiac function, and that increased preload and afterload were at the center of the problem. This model explained much of what we see occurring in APE.
Finally, researchers in the 1990s established the neurohormonal model, in which neurohormones (norepinephrine, renin, angiotensin, aldosterone) are upregulated in APE. These compounds have vasoactive properties leading to vasoconstriction and increase intravascular volume. Current recommendations for APE treatment are based on the integration of the cardiovascular and the neurohormonal models.
The Myth of Volume Overload
Regardless of the pathophysiology, patients are still volume overloaded, right? The best evidence suggests it is not that simple. Zile, et al. demonstrated that most patients with APE have increased cardiac filling pressures, but most did not have a significant increase from their dry weight on presentation. (Circulation 2008;118:1433.)
More than 50 percent of patients, in fact, gain less than two pounds. (Circulation 2007;116:1549.) If this is not fluid gain, where did the increased filling pressure originate? It turns out it is largely a result of changes in compliance in the splanchnic system that leads to fluid shifting from here to the cardiopulmonary circulation. (Circ Heart Fail 2011;4:669.)
Even in the face of this evidence, the loop diuretic supporters argue that some patients are overloaded, so why not give all of these patients the drug? This approach does not account for the potential downsides. Administration of furosemide activates the neurohormonal system, which leads to increased plasma renin and norepinephrine levels. This results in decreased LV function, increased LV filling pressure, increased MAP and SVR, and decreased GFR. (Ann Intern Med 1985;103:1.) An ICU study from 1990 found that furosemide increased pulmonary capillary wedge pressure in the first 20 minutes of treatment. (Chest 1990;98:124.) This is particularly worrisome because APE is a deadly disease, and what we do in the first 10 to 15 minutes of the patient's presentation makes a huge difference.
So how should we treat patients with APE?
• Non-Invasive Positive Pressure Ventilation (NIPPV): NIPPV has multifactorial action in APE. It decreases work of breathing, stents-open alveoli during the entire respiratory cycle, leading to improved gas exchange, and, in the case of bilevel NIPPV, decreases afterload.
A number of papers have shown decreased intubation rates and decreased ICU utilization with the use of NIPPV. The most recent study showed a decreased ICU admission from 92 to 38 percent. (J Emerg Med 2014;46:130.) A 2008 Cochrane review also found that NIPPV reduced hospital mortality (RR 0.6) and endotracheal intubation (RR 0.53). (Cochrane Database Syst Rev 2008 Jul 18;:CD005351.)
The key for NIPPV is to start it immediately on presentation to the ED. It will likely help with preoxygenation even if it does not stave off intubation.
• Nitroglycerin: Many studies have looked at the use of nitroglycerin, comparing it with furosemide and evaluating at high-dose therapy. (Am J Cardiol 1978;41:931; Lancet 1998;351:389; Ann Emerg Med 2007;50:144.) Nitroglycerin is recommended for all patients with APE. It reduces preload and at higher doses (> 100 mcg/min), and it decreases afterload, leading to increased cardiac output and decreased SVR. (Am J Cardiol 1978;41:931.) Despite widespread use, robust randomized studies enrolling the sickest APE patients are lacking.
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