General: Like other vasodilators, sodium nitroprusside can cause increases in intracranial pressure. In patients whose intracranial pressure is already elevated, sodium nitroprusside should be used only with extreme caution.

Hepatic: Use caution when administering nitroprusside to patients with hepatic insufficiency.

Use in Anesthesia: When sodium nitroprusside (or any other vasodilator) is used for controlled hypotension during anesthesia, the patient's capacity to compensate for anemia and hypovolemia may be diminished. If possible, pre-existing anemia and hypovolemia should be corrected prior to administration of sodium nitroprusside injection.

Hypotensive anesthetic techniques may also cause abnormalities of the pulmonary ventilation/perfusion ratio. Patients intolerant of these abnormalities may require a higher fraction of inspired oxygen.

Extreme caution should be exercised in patients who are especially poor surgical risks (A.S.A. Class 4 and 4E).

Laboratory Tests: The cyanide-level assay is technically difficult, and cyanide levels in body fluids other than packed red blood cells are difficult to interpret. Cyanide toxicity will lead to lactic acidosis and venous hyperoxemia, but these findings may not be present until an hour or more after the cyanide capacity of the body's red-cell mass has been exhausted.

Drug Interactions: The hypotensive effect of sodium nitroprusside is augmented by that of most other hypotensive drugs, including ganglionic blocking agents, negative inotropic agents, and inhaled anesthetics.

Carcinogenesis, Mutagenesis, and Impairment of Fertility: Animal studies assessing sodium nitroprusside's carcinogenicity and mutagenicity have not been conducted. Similarly, sodium nitroprusside has not been tested for effects on fertility.

Pregnancy: Teratogenic effects: Pregnancy Category C.

There are no adequate, well-controlled studies of sodium nitroprusside injection in either laboratory animals or pregnant women. It is not known whether sodium nitroprusside can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Sodium nitroprusside injection should be given to a pregnant woman only if clearly needed.

Nonteratogenic effects: In three studies in pregnant ewes, nitroprusside was shown to cross the placental barrier. Fetal cyanide levels were shown to be dose-related to maternal levels of nitroprusside. The metabolic transformation of sodium nitroprusside given to pregnant ewes led to fatal levels of cyanide in the fetuses. The infusion of 25 mcg/kg/min of sodium nitroprusside for one hour in pregnant ewes resulted in the death of all fetuses. Pregnant ewes infused with 1 mcg/kg/min of sodium nitroprusside for one hour delivered normal lambs.

According to one investigator, a pregnant woman at 24 weeks gestation was given sodium nitroprusside to control gestational hypertension secondary to mitral valve disease. Sodium nitroprusside was infused at 3.9 mcg/kg/min for a total of 3.5 mg/kg over 15 hours prior to delivery of a 478 gram stillborn infant without any obvious anomalies. Cyanide levels in the fetal liver were less than 10 mcg/mL. Toxic levels have been reported to be more than 30-40 mcg/mL. The mother demonstrated no cyanide toxicity.

The effects of administering sodium thiosulfate in pregnancy, either by itself or as a co-infusion with sodium nitroprusside, are completely unknown.

Nursing Mothers: It is not known whether sodium nitroprusside and its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from sodium nitroprusside, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: Efficacy in the pediatric population was established based on adult trials and supported by the dose-ranging trial (Study 1) and an open label trial of at least 12 hour infusion at a rate that achieved adequate MAP control (Study 2) with pediatric patients on sodium nitroprusside. No novel safety issues were seen in these studies in pediatric patients. See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.