NITROPRUSSIDE

Nitroprusside is a vasodilator agent that shares many features with nitroglycerin. One of these is the participation of nitric oxide in the vasodilator actions of the drug. It contains one nitrosyl group (NO), and this is released in the bloodstream as nitric oxide, which then can move into the vessel wall and move along the pathway. As a result of their shared mechanisms of action, nitroprusside and nitroglycerin are classified as nitrovasodilators.

There is one feature that distinguishes nitroprusside from nitroglycerin: Nitroprusside is a dangerous drug and may be responsible for over 1000 deaths yearly. Because the major actions of nitroprusside may be its toxic effects, the adverse effects will be presented first.

TOXICOLOGY

The toxic nature of nitroprusside is due to its molecular composition. The nitroprusside molecule contains five cyanide ions, and almost half of the molecular weight of the parent molecule is cyanide. When nitroprusside disrupts to release nitric oxide and exert its actions, the cyanide is released into the bloodstream. Sulfur from a donor source combines with the free cyanide and forms thiocyanate (SCN), which is cleared by the kidneys. The sulfur donor for this reaction is thiosulfate.

Cyanide

The capacity of the human body to clear cyanide was grossly overestimated when nitroprusside was first introduced . The limiting factor is thiosulfate, which is stored in limited quantities and is easily depleted. The result is early and frequent accumulation of cyanide during nitroprusside infusions.

Thiocyanate

The clearance of thiocyanate by the kidneys is impaired when renal function or renal blood flow is compromised. The accumulation of thiocyanate produces a toxic syndrome that is distinct from cyanide intoxication. Thus, nitroprusside toxicity can be expressed as either cyanide or thiocyanate intoxication.

ACTIONS

Nitroprusside has been favored because the vascular responses are prompt and short lived and this allows for rapid dose titration. Vasodilator effects are often evident at low dose rates (0.5 ug/kg/min), and the sequence of hemodynamic responses is the same as described for nitroglycerin. Blood pressure does not usually decline at dose rates below 1 ug/kg/min. An immediate drop in blood pressure at low dose rates can be a sign of hypovolemia.

Indications

Because of the toxic potential of the drug, nitroprusside should be used only when there is no alternative available. The drug seems best suited for the management of severe hypertension combined with a low cardiac output.

DRUG ADMINISTRATION

Note the recommendation to add thiosulfate to the nitroprusside infusate. This provides the sulfur needed to detoxify cyanide and should be a mandatory practice. A proportional dose of 500 mg thiosulfate per 50 mg nitroprusside should be used. Thiosulfate is provided as sodium thiosulfate (290 mg sodium per gram thiosulfate) and is commercially available as a 10% solution (5 mL = 500 mg thiosulfate).

The FDA recommends starting nitroprusside at a low dose rate (0.2 ug/kg/min) and titrating the dose upward in 5-minute increments. The maximum allowable dose rate is 10 ug/kg/min for no longer than 10 minutes.

ADVERSE EFFECTS

In addition to cyanide and thiocyanate intoxication, nitroprusside has adverse hemodynamic effects that are identical to those described for nitroglycerin. Nitroprusside increases intracranial pressure, and thus it is not advised for patients with intracranial hypertension. Because hypertensive encephalopathy is associated with a raised intracranial pressure, nitroprusside seems ill-advised for managing hypertensive encephalopathy.

Related Post :

Hemodynamic Drug