(See also the boxed warning at the beginning of this insert.)

The principal hazards of sodium nitroprusside injection administration are excessive hypotension and excessive accumulation of cyanide (see also OVERDOSAGE and DOSAGE AND ADMINISTRATION).

Excessive Hypotension: Small transient excesses in the infusion rate of sodium nitroprusside can result in excessive hypotension, sometimes to levels so low as to compromise the perfusion of vital organs. These hemodynamic changes may lead to a variety of associated symptoms; see ADVERSE REACTIONS. Nitroprusside-induced hypotension will be self-limited within 1-10 minutes after discontinuation of the nitroprusside infusion; during these few minutes, it may be helpful to put the patient into a head-down (Trendelenburg) position to maximize venous return. If hypotension persists more than a few minutes after discontinuation of the infusion of sodium nitroprusside injection, sodium nitroprusside is not the cause, and the true cause must be sought.

Cyanide Toxicity: As described in CLINICAL PHARMACOLOGY above, sodium nitroprusside infusions at rates above 2 mcg/kg/min generate cyanide ion (CN–) faster than the body can normally dispose of it. (When sodium thiosulfate is given, as described under DOSAGE AND ADMINISTRATION, the body's capacity for CN– elimination is greatly increased.) Methemoglobin normally present in the body can buffer a certain amount of CN–, but the capacity of this system is exhausted by the CN– produced from about 500 mcg/kg of sodium nitroprusside. This amount of sodium nitroprusside is administered in less than an hour when the drug is administered at 10 mcg/kg/min (the maximum recommended rate). Thereafter, the toxic effects of CN– may be rapid, serious, and even lethal.

The true rates of clinically important cyanide toxicity cannot be assessed from spontaneous reports or published data. Most patients reported to have experienced such toxicity have received relatively prolonged infusions, and the only patients whose deaths have been unequivocally attributed to nitroprusside-induced cyanide toxicity have been patients who had received nitroprusside infusions at rates (30-120 mcg/kg/min) much greater than those now recommended. Elevated cyanide levels, metabolic acidosis, and marked clinical deterioration, however, have occasionally been reported in patients who received infusions at recommended rates for only a few hours and even, in one case, for only 35 minutes. In some of these cases, infusion of sodium thiosulfate caused dramatic clinical improvement, supporting the diagnosis of cyanide toxicity.

Cyanide toxicity may manifest itself as venous hyperoxemia with bright red venous blood, as cells become unable to extract the oxygen delivered to them; metabolic (lactic) acidosis; air hunger; confusion; and death. Cyanide toxicity due to causes other than nitroprusside has been associated with angina pectoris and myocardial infarction; ataxia, seizures, and stroke; and other diffuse ischemic damage.

Hypertensive patients, and patients concomitantly receiving other antihypertensive medications, may be more sensitive to the effects of sodium nitroprusside than normal subjects.