Introduction Heart failure is a complex syndrome resulting from a number of causes, most commonly coronary artery disease, and is associated with increased morbidity and mortality.1 In the United States, heart failure accounts for 65,000 deaths and 1 million hospitalizations annually.2 Heart failure is characterized by the heart’s inability to move blood throughout the circulatory system, due to dysfunction in heart contractility and filling.1,3 Adaptive responses by the body can compensate for cardiac dysfunction seen in heart failure, making it a chronic condition. However, even with adaptive responses, acute decompensation can occur. This acute phase of decompensation is known as acute heart failure syndrome (AHFS). Symptoms of AHFS, most commonly dyspnea, can develop rapidly and require immediate treatment, usually in the emergency department.3,4 One distinct subgroup of AHFS manifests with systolic hypertension and rapid onset (minutes to hours) pulmonary congestion and severe dyspnea, and is referred to by several names, including hypertensive acute heart failure (H-AHF), flash pulmonary edema, and sympathetic crashing acute pulmonary edema (SCAPE).5-8 Untreated, SCAPE can result in respiratory failure and death. The sudden onset of pulmonary congestion and dyspnea in SCAPE is primarily a result of vascular redistribution, caused by sympathetic stimulation of splanchnic veins.3,5 This stimulation causes venoconstriction and mobilization of up to 800 mL of blood into the systemic circulation. With existing cardiac dysfunction, both preload and afterload are increased, with eventual movement of that volume into the pulmonary circulation precipitating rapid pulmonary congestion and severe dyspnea. Hypertension is also present in SCAPE, with systolic blood pressures exceeding 140 mm Hg. Treatment of SCAPE The initial focus on the treatment of any AHFS is stabilization in the emergency department, followed by in-hospital management and discharge planning.9 For SCAPE, rapid stabilization can reduce the need for mechanical ventilation and intensive care unit admission and prevent morbidity and mortality.3 Treatment options for AHFS include diuretics, morphine, nitroglycerin, and assisted ventilation. Although diuretics and morphine are commonly used for the treatment of pulmonary edema resulting from fluid overload in decompensated heart failure, the underlying mechanism of pulmonary edema in SCAPE differs, making use of these agents less beneficial. 4,5 Nitroglycerin can be effective for treatment of SCAPE by reducing both preload and afterload when dosed appropriately. For AHFS, nitroglycerin is typically given as intravenous infusion doses of 10 to 20 mcg/min. While venodilatation can be achieved, this low dose does not provide arteriodilatation for afterload reduction; therefore, higher doses of nitroglycerin are needed for SCAPE. Efficacy of high-dose nitroglycerin in SCAPE Literature is available describing the use of high-dose nitroglycerin for the treatment of SCAPE. Overall, when given at doses of up to 800 mcg/min by infusion or by repeated 2 mg intravenous bolus, nitroglycerin has been associated with reduced need for intubation and intensive care unit admission, and symptom stabilization in patients with SCAPE or hypertensive acute heart failure with dyspnea. These reports are summarized in the Table.
Additionally, Agrawal et al have proposed an algorithm for nitroglycerin use for the treatment of SCAPE.4 The authors suggest a nitroglycerin bolus dose of 500 to 1000 mcg over 2 minutes, followed by a nitroglycerin infusion at 100 mcg/min, with rapid titration to 400 mcg/min, then a rapid reduction to 100 mcg/min and tapering with clinical improvement. This regimen includes concurrent use of non-invasive ventilation, close monitoring of blood pressure and oxygen saturation, and avoidance of diuretics. Paone et al propose an initial infusion rate of nitroglycerin of 400 mcg/min (the maximum infusion rate), with titration down by 50 mcg/min every 5 minutes, with BiPAP as needed; endotracheal intubation may be performed after 20 minutes if no symptom resolution is seen.7 Criteria for resolution include improvements in at least 2 of the following: tachypnea, dyspnea, hypoxia, and systolic blood pressure or mean arterial pressure. Summary Treatment of acute heart failure generally consists of diuretics for management of volume overload, with vasodilators used for patients resistant to this therapy.9 However, for patients with SCAPE, the underlying cause of decompensation is not volume overload but rather vascular redistribution of fluid, resulting in sudden onset of pulmonary edema and severe dyspnea in the presence of hypertension.4,5,7 For these patients, reduction in both preload and afterload is needed, requiring the use of vasodilators such as nitroglycerin. To achieve this effect, doses of nitroglycerin higher than those typically used in acute heart failure are needed. Although data are limited, nitroglycerin has been shown to be effective for the treatment of SCAPE when administered at initial infusion rates of 400 mcg/min, with rapid downward titration, or with intravenous bolus doses of 1 to 2 mg.4,7,10-12 This approach has resulted in symptom resolution and avoidance of mechanical ventilation in patients with SCAPE. However, more study is needed to determine the optimal dose of nitroglycerin in SCAPE. References
Prepared by: Joan Stachnik, PharmD Clinical Assistant Professor, Drug Information Specialist University of Illinois at Chicago College of Pharmacy March 2021 The information presented is current as March 6. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making. |