Normally, fluid stays in the vascular space because of a balance between hydrostatic pressure (pumping pressure) and osmotic pull generated by plasma proteins and other dissolved particles in the blood. When hydrostatic pressure increases so that the balance is overcome, plasma is forced outward across the alveolar-capillary membrane into the interstitial space, resulting in increased alveolar-capillary distance and impaired diffusion of respiratory gases. Hypoxemia and hypercapnea soon follow.
Clinical presentation of acute pulmonary edema almost always manifests itself as severe respiratory distress, often accompanied by a constellation of associated signs and symptoms, including:
- Profound hypertension (hallmark sign)
- Paroxysmal nocturnal dyspnea
- Exaggerated air hunger
- Chest pain or tightness
- An S3 heart sound
- Adventitious lung sounds, such as crackles or wheezes
- Cyanosis or pallor.
Prehospital Treatment of APE
Treatment of acute pulmonary edema in past years has focused on dilatation of peripheral vasculature to improve venous capacitance and decrease peripheral arterial vascular resistance, and removal of the excess fluid through diuresis. The three pharmacologic agents traditionally used to accomplish this are nitroglycerin, morphine sulfate and a loop diuretic, such as furosemide (Lasix).
Ultimately, the goal of vasodilation is to reduce left ventricular preload. Nitroglycerin in low doses effectively dilates the venous system, resulting in increased venous capacitance and reduced blood return to the right ventricle. This reduction in right ventricular preload, in turn, results in less blood flow through the pulmonary vascular bed, and ultimately, less outflow to the left ventricle. This reduction in left ventricular preload allows for the damaged left ventricle to more closely match stroke volume to ventricular filling. The end result is decreased hydrostatic pressure in the pulmonary vasculature and less congestion.
However, it also became apparent that higher doses of nitroglycerin resulted in significant dilation of the arterial system as well, reducing peripheral vascular resistance, increasing forward flow and, ultimately, decreasing workload for the weak and damaged left ventricle. This global vasodilatory effect of nitroglycerin has been shown to significantly reduce mortality in APE patients treated in the prehospital setting, and even hypotensive patients (systolic BP < 100) were shown to benefit from intravenous nitroglycerin.2
Morphine sulfate, the second pharmacologic arm of traditional CHF treatment, was long thought to aid in vasodilation while simultaneously decreasing the anxiety common in APE patients, but recent studies indicate that the vasodilatory effects of morphine are transient and frequently overstated.3 Moreover, the vasodilation from morphine is histamine-mediated, and the increased capillary permeability—particularly in the pulmonary vasculature—common with histamine release may be detrimental to the patient in acute CHF. Many clinicians are also concerned with morphine’s potential for CNS and respiratory depression in the acute CHF patient. One retrospective study of APE patients treated in the ED found a significant increase in the number of intubations and ICU admissions in patients who received morphine versus those who were administered sublingual captopril.4
Furosemide is a loop diuretic that inhibits sodium reabsorption in the ascending loop of Henle and the distal convoluted tubules of the renal medulla. Following the principle that “water follows salt,” this increased sodium content in the collecting tubules results in increased water excretion from the kidneys.
Once pulmonary vascular pressure was decreased through vasodilation with nitroglycerin and morphine, it was considered necessary to remove the excess fluid via diuresis with furosemide. Many texts still emphasize this.
However, the assumption that pulmonary edema resulted from excess total body fluid may not be universally true. Most chronic CHF patients who are well-managed are euvolemic or even slightly dehydrated, and most incidences of acute pulmonary edema occur in the early morning hours or during sleep, when oral fluid intake is lowest. Many factors figure into the syndrome of pulmonary edema, principally the changes that take place in the heart as a result of chronic hypertension (cardiac remodeling—changes in the size, shape and function of a chamber of the heart) leading to either systolic or diastolic heart failure. Inadequate cardiac output leads to activation of the renin/angiotensin/aldosterone system (RAAS), which results in sodium and water retention, but this does not necessarily mean the patient is overhydrated.5