IV Dilution &
Medication Reference

Nitroprusside (Nipride ®)

Usual Diluents

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

Stability / Miscellaneous

Onset: immediate.
Duration: 1 to 10 minutes.

Treat hypertensive emergency.
IV infusion rate: 0.5 to 10 mcg/ kg/ min--titrate to BP.

Dosing: Initial: 0.3 to 0.5 mcg/kg/min--increase by 0.5 mcg/kg/min increments. (usual dose: 3 mcg/kg/min-rarely need > 4 mcg/kg/min).

Note: when > 500 mcg/kg is administered by continuous infusion at > 2 mcg/kg/min--cyanide is produced faster than can be handled by endogenous mechanisms.

Maximum infusion rate: 10 mcg /kg /min.
Dosage rates well within product labeling have resulted in toxicity. Early signs of toxicity appear to be related to formation of cyanide.

Calculation of drip rate 50 mg/250 ml (ml/hr) = wt (kg) x mcg/min x 0.3.

Cyanide toxicity more likely if hepatic dysfunction is present; thiocyanate toxicity more likely if there is renal dysfunction or prolonged infusion. Cyanide toxicity symptoms: acidosis (decreased affinity of oxygen to hemoglobin resulting in anaerobic metabolism-increased lactic acid etc., tachycardia, coma, convulsions, almond smell on breath.
Patients with decreased hepatic or renal function are at the highest risk of developing toxicity. Cyanide toxicity may cause death or irreversible ischemic injury as a result of profound hypotension and metabolic acidosis.

To prevent cyanide toxicity, initial infusion rates should not exceed 0.3 mcg/kg/min, and maximum rates of 10 mcg/kg/min should not be maintained for more than 10 minutes.
Monitoring: Monitor for cyanide and thiocyanate toxicity; monitor acid-base status (acidosis may be earliest sign of cyanide toxicity; monitor thiocyanate levels if prolonged infusion (>3-4 days) or dose > 4 mcg/kg/min or renal dysfunction; monitor cyanide levels in patients with decreased hepatic function.

Cyanide toxicity: Patients exhibiting dyspnea and impaired mental status should be treated with the commercial cyanide antidote kit [ (1) amyl nitrate: inhale vapor for 15-30 seconds every 2 to 3 minutes. (2) Sodium nitrate: 300mg over 2-4 min (3) Sodium thiosulfate: 12.5g (25 ml of 50% solution) IV; may repeat with 6.25 grams in 30 minutes), without waiting for chemical confirmation of toxicity. Some studies have used hydroxocobalamin which chelates cyanide (large doses required). Thiosulfate infusions have been co-administered with nitroprusside to prevent toxicity.

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DOSAGE AND ADMINISTRATION

Dilution to proper strength for infusion: Depending on the desired concentration, the solution containing 50 mg of NITROPRESS must be further diluted in 250-1000 of sterile 5% dextrose injection. The diluted solution should be protected from light, using the supplied opaque sleeve, aluminum foil, or other opaque material. It is not necessary to cover the infusion drip chamber or the tubing.

Verification of the chemical integrity of the product: Sodium nitroprusside solution can be inactivated by reactions with trace contaminants. The products of these reactions are often blue, green, or red, much brighter than the faint brownish color of unreacted NITROPRESS. Discolored solutions, or solutions in which particulate matter is visible, should not be used. If properly protected from light, the freshly diluted solution is stable for 24 hours.

No other drugs should be administered in the same solution with sodium nitroprusside.

Avoidance of excessive hypotension: While the average effective rate in adults and children is about 3 mcg/kg/min, some patients will become dangerously hypotensive when they receive NITROPRESS at this rate. Infusion of sodium nitroprusside should therefore be started at a very low rate (0.3 mcg/kg/min), with upward titration every few minutes until the desired effect is achieved or the maximum recommended infusion rate (10 mcg/kg/min) has been reached.

Because sodium nitroprusside's hypotensive effect is very rapid in onset and in dissipation, small variations in infusion rate can lead to wide, undesirable variations in blood pressure. Sodium nitroprusside should not be infused through ordinary I.V. apparatus, regulated only by gravity and mechanical clamps. Only an infusion pump, preferably a volumetric pump, should be used.

Because sodium nitroprusside can induce essentially unlimited blood-pressure reduction, the blood pressure of a patient receiving this drug must be continuously monitored, using either a continually reinflated sphygmomanometer or (preferably) an intra-arterial pressure sensor. Special caution should be used in elderly patients, since they may be more sensitive to the hypotensive effects of the drug.

When sodium nitroprusside is used in the treatment of acute congestive heart failure, titration of the infusion rate must be guided by the results of invasive hemodynamic monitoring with simultaneous monitoring of urine output. Sodium nitroprusside can be titrated by increasing the infusion rate until:

*measured cardiac output is no longer increasing,
*systemic blood pressure cannot be further reduced without compromising the perfusion of vital organs, or
*the maximum recommended infusion rate has been reached, whichever comes earliest. Specific hemodynamic goals must be tailored to the clinical situation, but improvements in cardiac output and left ventricular filling pressure must not be purchased at the price of undue hypotension and consequent hypoperfusion.

The table below shows the infusion rates corresponding to the recommended initial and maximal doses (0.3 mcg/kg/min and 10 mcg/kg/min, respectively) for both adults and children of various weights. Some of the listed infusion rates are so slow or so rapid as to be impractical, and these practicalities must be considered when the concentration to be used is selected. Note that when the concentration used in a given patient is changed, the tubing is still filled with a solution at the previous concentration.

Avoidance of cyanide toxicity: As described in the package insert - CLINICAL PHARMACOLOGY section, when more than 500 mcg/kg of sodium nitroprusside is administered faster than 2 mcg/kg/min, cyanide is generated faster than the unaided patient can eliminate it. Administration of sodium thiosulfate has been shown to increase the rate of cyanide processing, reducing the hazard of cyanide toxicity. Although toxic reactions to sodium thiosulfate have not been reported, the co-infusion regimen has not been extensively studied, and it cannot be recommended without reservation. In one study, sodium thiosulfate appeared to potentiate the hypotensive effects of sodium nitroprusside.

CoCo-infusions of sodium thiosulfate have been administered at rates of 5-10 times that of sodium nitroprusside. Care must be taken to avoid the indiscriminate use of prolonged or high doses of sodium nitroprusside with sodium thiosulfate as this may result in thiocyanate toxicity and hypovolemia. Incautious administration of sodium nitroprusside must still be avoided, and all of the precautions concerning sodium nitroprusside administration must still be observed.

Consideration of methemoglobinemia and thiocyanate toxicity: Rare patients receiving more than 10 mg/kg of sodium nitroprusside will develop methemoglobinemia; other patients, especially those with impaired renal function, will predictably develop thiocyanate toxicity after prolonged, rapid infusions. In accordance with the descriptions in the package insert ADVERSE REACTIONS section, patients with suggestive findings should be tested for these toxicities.

WARNING: Do not use flexible container in series connections.

HOW SUPPLIED
NITROPRESS (sodium nitroprusside injection) is supplied in amber-colored, single-dose 50 mg/2 mL Fliptop Vials (List No. 3024).

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

To protect NITROPRESS from light, it should be stored in its carton until it is used.

Revised: March, 2006
©Hospira 2006 EN-1157
HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Source: [package insert]