Perioperative Hemodynamic Control - Vasodilators (Table 20.4)
Sodium nitroprusside is a direct-acting vasodilator that acts on arterial and venous smooth muscle.
- The mechanism of action of sodium nitroprusside is common to all nitrates. The nitroso moiety decomposes to release nitric oxide. Nitric oxide is an unstable, short-lived free radical that activates guanylate cyclase. This activation leads to an increase in the concentration of cyclic guanosine monophosphate, which causes smooth muscle relaxation.
- Sodium nitroprusside reduces afterload through arteriolar dilation and reduces preload through venous dilation. These effects typically cause a reflex increase in heart rate and myocardial contractility, an increase in cardiac output, and marked decreases in SVR and PVR. Sodium nitroprusside dilates cerebral blood vessels and should be used with caution in patients with decreased intracranial compliance.
- Sodium nitroprusside dilates all vascular beds equally, increasing overall blood flow. A vascular steal phenomenon may be created when perfusion to an ischemic region that is already maximally vasodilated may be shunted to a nonischemic region that is able to vasodilate further. This is especially important in the coronary vasculature where regional ischemia may be exacerbated despite the decrease in overall myocardial oxygen consumption created by afterload reduction.
- Sodium nitroprusside is useful perioperatively because it has a fast onset time (1 to 2 minutes), and its effects dissipate within 2 minutes of discontinuation.
- Cyanide toxicity. In vivo, sodium nitroprusside reacts nonenzymatically with the sulfhydryl groups in hemoglobin to release five cyanide radicals per molecule. Some of these radicals can be converted to thiocyanate by tissue and liver rhodanese and excreted in the urine. Thiocyanate has a half-life of 4 days and will accumulate in the presence of renal failure. Cyanide radicals may also bind to intracellular cytochrome oxidase and disrupt the electron transport chain. This disruption can lead to cell hypoxia and death even in the face of adequate oxygen tensions.
- Clinical features. Cyanide toxicity typically occurs when more than 1 mg/kg has been administered within 2.5 hours or when the blood concentration of cyanide ion is greater than 100 μg/dL. Tachyphylaxis, metabolic acidosis, and elevated mixed venous oxygen tensions are early signs of cyanide toxicity. Symptoms of cyanide toxicity include fatigue, nausea, muscle spasms, angina, and mental confusion.
- Treatment. Cyanide toxicity is treated by discontinuing the sodium nitroprusside infusion and administering 100% oxygen and sodium thiosulfate. Sodium thiosulfate is a sulfur donor in the rhodanese reaction that converts cyanide to thiocyanate. It is administered as an infusion over 15 minutes at a dose of 150 mg/kg dissolved in 50 mL of water. Severe cyanide toxicity (base deficit >10 mEq, hemodynamic instability) may require the additional administration of amyl nitrate (0.3 mL by inhalation) or sodium nitrate (5 mg/kg IV over 5 minutes). These two compounds create methemoglobin, which will bind to the cyanide ion and form inactive cyanmethemoglobin.
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