ACTIONS AND PHARMACOLOGY This rapidly acting arteriolar dilator and venodilator is the drug of choice for hypertensive emergencies and is the standard against which all other agents are compared. It acts by reacting with cysteine to form nitrosocysteine, a potent activator of guanylate cyclase, which in turn stimulates the formation of cyclic gMp to relax smooth muscle in both arteries and veins. This decreases preload and afterload, resulting in decreased myocardial oxygen demand. The heart rate may increase slightly secondary to a baroreceptor-mediated reflex, but there is no change in cardiac output or myocardial blood flow unless there is preexisting coronary artery disease which can result in a significant reduction in regional blood flow ("coronary steal") (see below). Cerebral blood flow may be affected, decreasing in a dose-dependent manner. Renal blood flow remains unchanged, but plasma renin activity is increased. Pulmonary shunting may occur with nitroprusside use.
The rate of onset is extremely rapid, with a duration of action of 1 to 2 min and a plasma half-life of 3 to 4 min. Nitroprusside is metabolized to thiocyanate in the liver and is excreted slowly by the kidneys. Cyanide is an intermediate metabolite, but cyanide toxicity is rare. 15
INDICATIONS Sodium nitroprusside is an excellent agent for all hypertensive emergencies except eclampsia prior to delivery (because it crosses the placenta). It is only indicated for postpartum eclampsia or in eclampsia resistant to other interventions.
USE The MAP should not be reduced by more than 20 to 25 percent within 30 to 60 min.15 The solution is made by mixing 50 mg of sodium nitroprusside in 500 mL of 5% dextrose in water (D5W) (10 mg/mL). The infusion is usually started at 0.5 (pg/kg)/min, titrating up to a maximum of 10 (pg/kg)/min until the desired blood pressure has been achieved. The blood pressure needs to be closely monitored; therefore, an arterial line should be placed once the infusion is initiated. Because of rapid degradation and sensitivity to light, sodium nitroprusside solution should be used within 24 h of mixing and be protected from the light by wrapping the solution and tubing in aluminum foil.
SIDE EFFECTS AND CONTRAINDICATIONS The most common complication is hypotension. Prolonged infusions may lead to the rare complications of cyanide toxicity, which may occur in patients with hepatic dysfunction, and thiocyanate toxicity, which is associated with renal failure. 15 This rarely occurs in the ED. Because nitroprusside inhibits hypoxia-induced vasoconstriction in the pulmonary vasculature, there may be increased perfusion to nonventilated areas of the lung. Myocardial ischemia may be worsened by a coronary steal syndrome because of dilation of coronary arteries or by the combination of nitroprusside and clonidine. Another consequence of the vasodilatory effect of nitroprusside is increased intracranial pressure.
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