Nitroprusside hemodynamic effects

Aim for a 10-15% reduction in mean arterial pressure (MAP) ° Nitroprusside—0.25-0.5 mcg/kg/min continuous IV infusion increase in increments of 0.25-0.5 mcg/kg/min until desired hemodynamic effect. Usual doses up to 2-3 mcg/kg/min. High-alert medication—read package insert before use... 

Sodium nitroprusside is a mixed arterial-venous vasodilator that acts directly on vascular smooth muscle to increase cardiac index and decrease venous pressure. Despite its lack of direct inotropic activity, nitroprusside exerts hemodynamic effects that are qualitatively similar to those of dobutamine and milrinone. However, nitroprusside generally decreases PAOP, SVR, and blood pressure more than those agents do. 

Tolerance to nitrates is defined as the reduction in hemodynamic effect or the requirement for higher doses to achieve a persistent effect with continuous use in the face of constant plasma concentrations [15]. Nitrate tolerance was first described for nitroglycerin in 1888 [36] it occurs with all organic nitrates, albeit to different extents. For reasons that are not understood, PETN appears to be the least susceptible to the development of tolerance. No, or much less, tolerance is observed with nitrite esters, such as amyl nitrite [37], molsidomine, and sodium nitroprusside. Earlier investigations suggested that a depletion of intracellular thiols is involved in tolerance development [17], but this has not been substantiated in later studies [38, 39]. As with organic nitrate bioactivation, the precise mechanism(s) involved in nitrate tolerance remain(s) unknown, but it is likely to be complex and multifactorial. Two principal... 

Koller-Strametz J, Wolzt M, Fuchs C, Putz D, Wisser W, MensikC, Eichler H, Laufer G, Schmetterer L. Renal hemodynamic effects of L-arginine and sodium nitroprusside in heart transplant recipients. Kidney Int 1999 55 1871-1877. 

Nitroglycerin should be initiated at a dose of 5 to 10 mcg/min (0.1 mcg/kg per minute) and increased every 5 to 10 minutes as necessary and tolerated. Hypotension and an excessive decrease in PAOP are important dose-limiting side effects. Maintenance doses usually vary from 35 to 200 mcg/min (0.5 to 3 mcg/kg per minute), although doses over 1000 mcg/min (15 mcg/kg per minute) have been used in rare cases. Tolerance to the hemodynamic effects of nitroglycerin may develop over 12 to 72 hours of continuous administration, but some patients have a sustained response. Neither nitroglycerin nor nitroprusside should be used in the presence of elevated intracranial pressure because either may worsen cerebral edema in this setting. 

SODIUM NITROPRUSSIDE Sodium nitroprusside (NITROPRESS) is a prodrug and potent vasodilator that reduces both ventricular filling pressures and systemic vascular resistance. It has a rapid onset (2-5 minutes) and offset (quickly metabolized to cyanide and NO, the active vasodilator) of action and its dose can be titrated expeditiously to achieve the desired hemodynamic effect. For these reasons, nitroprusside is commonly used in intensive-care settings for rapid control of severe hypertension and for the management of decompensated heart failure. The basic pharmacologic properties of this drug are described in Chapter 32. 

Leier, C. V., Bambach, D., Thompson, M. J., Cattaneo, S. M., Goldberg, R. J., and Unverferth, D. V. (1981a). Central and regional hemodynamic effects of intravenous isosorbide dinitrate, nitroglycerin, and nitroprusside in patients with congestive heart failure. Am. J. Cardiol. 48, 1115-1123. 

Hypotension is an important dose-limiting adverse effect of nitroprusside and other vasodilators. Therefore, nitroprusside is primarily used in patients who have a significantly elevated SVR and often requires invasive hemodynamic monitoring. 

Nitroprusside has a rapid onset of action and a duration of action of less than 10 minutes, necessitating its administration by continuous intravenous infusion. This allows for precise dose titration based on measured clinical and hemodynamic parameters. It, like other vasodilators used in heart failure, should be initiated at a low dose (0.1 to 0.2 mcg/kg per minute) to avoid excessive hypotension and then increased by small increments (0.1 to 0.2 mcg/kg per minute) every 5 to 10 minutes as needed and tolerated. Usually effective doses range from 0.5 to 3 mcg/kg per minute. A rebound phenomenon has been reported after abrupt withdrawal of nitroprusside in patients with heart failure and is apparently due to reflex neurohormonal... 

In patients with elevated systemic vascular resistance and normal-to-elevated systemic blood pressure, afterload reduction with nitroprusside is logical it should be emphasized that nitroprus-side also increases venous capacitance, thereby also decreasing preload. In the context of myocardial dysfunction, afterload reduction will typically lead to improved forward cardiac output. Nitroprusside may also be effective when the systemic vascular resistance is elevated and systemic blood pressure is reduced the caveat in this more complex hemodynamic setting is that the load reduction produced by nitroprusside must be counterbalanced by an increase in stroke volume. This derivative increase in stroke volume may not occur in the patient with advanced heart failure rather, the result will be a further reduction in mean arterial pressure and the potential risk of peripheral organ hypoperfusion. An alternative approach would be the use of an inotropic-dilator drug such as milrinone, which will provide both preload and afterload reduction its concurrent positive inotropic effect may offset the reduction in mean arterial pressure that can occur from vasodilation alone. 

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