Sodium Nitroprusside (Nipride)

Emergency & Prehospital

• Hypertensive crisis: Lowers the pressure now, in adults and children. You want it when a titratable, short-acting agent is the right tool (label indication). Many protocols reserve it for when nicardipine, clevidipine, labetalol or esmolol are unavailable or inadequate.
• Acute heart failure with high afterload: It cuts preload and afterload. In hospital, it is titrated to invasive hemodynamics (label indication).

ED / ICU / Transport

• Controlled hypotension during surgery: Less bleeding is the point. You need intra-arterial pressure monitoring (label indication).
• Aortic dissection (off-label): It is an add-on. Use it only after IV beta-blockade, and only when BP stays above target. The 2022 ACC/AHA aortic guideline names nicardipine, clevidipine and nitroprusside as vasodilator options.
• Refractory hypertension with cardiac decompensation (ICU, off-label): Reach for it when other agents fail, and only under invasive monitoring.

Other Uses

• Pheochromocytoma and other catecholamine-driven crises (off-label): Specialists only. The label does not cover this use.

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

• Concentrate: 50 mg/2 mL (25 mg/mL) single-dose vial; must be diluted in 5% dextrose before infusion (never direct injection)
• Premixed ready-to-use (Nipride RTU): 50 mg/100 mL (0.5 mg/mL), 20 mg/100 mL (0.2 mg/mL) and 10 mg/50 mL (0.2 mg/mL) in 0.9% sodium chloride; single-dose vials

Adult Dosing

Pediatric Dosing

Continuous Infusion

Pump rate (mL/hr) = dose (mcg/kg/min) × weight (kg) × 60 ÷ concentration (mcg/mL). Say the patient weighs 70 kg and the bag is 200 mcg/mL. At 0.3 mcg/kg/min, that runs 6.3 mL/hr. At 10 mcg/kg/min, it runs 210 mL/hr. Recheck the math against the bag label every time.

Preparation & Administration

• Dilution: Dilute the 50 mg vial in 250 to 1,000 mL of 5% dextrose. No other drug may be added to that solution.
• Push rate: Not applicable. It is infusion only, never a direct IV injection.
• Inspection: Discard it if the solution is blue, green or bright red, or has particulate matter. It should be clear to reddish brown.
• Light: Protect the bag and tubing from light with an opaque sleeve, foil or the carton. The supplied sleeve is for the bag.
• Stability: Protected from light, the diluted solution holds for 24 hours. Discard it after 24 hours.
• Pump: Use a volumetric infusion pump only. Never gravity or a mechanical clamp. After a change, the tubing still holds the previous concentration, so plan for that when you change the bag.
• Line: Use a dedicated line. The label says no other drugs go through it. Secure the line and check the site per protocol. The label does not specify central access.
• Flexible containers: Do not use them in series connections. That is a label warning.

Contraindications

• Compensatory hypertension: Coarctation of the aorta or arteriovenous shunting. The hypertension is what keeps perfusion going.
• Inadequate cerebral circulation, or moribund patients (ASA Class 5E) coming to emergency surgery
• Congenital (Leber) optic atrophy or tobacco amblyopia: These patients make unusually high cyanide-to-thiocyanate ratios. Avoid.
• Acute heart failure with reduced peripheral vascular resistance, such as high-output failure from endotoxic sepsis
• Concomitant sildenafil, tadalafil, vardenafil or riociguat: The Nipride RTU label lists this as a contraindication. Avoid it with every nitroprusside product. The effects add up and drop the pressure.

Precautions

• Intracranial pressure: Vasodilators can raise ICP. Use extreme caution when ICP is already raised.
• Acute ischemic stroke or intracranial hemorrhage: The label says nitroprusside raises ICP. Use it only with ICP monitoring. Let the neurocritical care protocol choose the agent.
• Acute coronary syndrome or MI: The label notes reflex tachycardia and coronary dilation. Reflex tachycardia can worsen ischemia. Use it only with monitoring and a clear benefit. This is clinical caution, not a label contraindication.
• Hepatic dysfunction: The patient is more susceptible to cyanide toxicity (Nipride RTU label). Use caution.
• Renal impairment: Thiocyanate builds up. Mean-rate limits are in Hold / Reassess If.
• Elderly and hypertensive patients: They are more sensitive to hypotension. Patients on other antihypertensives are at higher risk.
• Anemia or hypovolemia under anesthesia: The patient has less ability to compensate. Correct it first where possible.

Hold / Reassess If

• MAP or SBP below the ordered target, or signs of hypoperfusion (new confusion, falling urine output, rising lactate): Reduce or stop. The hypotension fades 1–10 min after you stop.
• Infusion above 10 mcg/kg/min, or above 10 minutes at the maximum rate: Stop and reassess. The label directs termination if BP is not controlled.
• eGFR <30 mL/min/1.73 m²: limit the mean infusion rate to less than 3 mcg/kg/min; anuric: limit to 1 mcg/kg/min (Nipride RTU label)
• Cumulative dose above 7 mg/kg/day (normal renal function, Nipride RTU label): Check plasma thiocyanate. The Mylan label instead sets a prolonged-infusion limit of 3 mcg/kg/min (1 mcg/kg/min if anuric). Above it, check thiocyanate daily.
• Suspected cyanide toxicity (rising dose requirement, lactic acidosis, bright red venous blood): stop infusion and start the antidote

Common

• Dose-related hypotension (the principal effect, not an adverse event when titrated)
• Abdominal pain, apprehension, diaphoresis, dizziness, headache, nausea, palpitations and retrosternal discomfort when BP is lowered too quickly (resolve when the infusion slows)
• Flushing, venous streaking and infusion-site irritation
• Tachycardia (reflex) or bradycardia

Other Label-Listed Effects

• Endocrine: Hypothyroidism. Thiocyanate blocks iodine uptake by the thyroid with prolonged use.
• Hematologic: decreased platelet aggregation
• Gastrointestinal: ileus
• Dermatologic: rash
• Neuromuscular: muscle twitching, restlessness and retching when BP is lowered too quickly (ease when the infusion slows)
• Cardiovascular: bradycardia and ECG changes

Serious / Life-Threatening

Overdose & Toxicity Management

• Signs: severe hypotension or cyanide toxicity (venous hyperoxemia, acidosis, air hunger, confusion, seizures, death); thiocyanate toxicity with prolonged infusion
• Immediate management: Stop the infusion. Support BP and ventilation. A reasonable suspicion of cyanide toxicity is enough reason to treat.
• Hydroxocobalamin (Cyanokit), first choice when hypotension, anemia or smoke inhalation limits reserve: 5 g IV over 15 minutes for adults. A second 5 g may follow (infusion 15 minutes to 2 hours), for a total of 10 g. Pediatric: the US label does not establish safety or dosing. 70 mg/kg has been used in non-US practice, so confirm the dose and cap per local protocol. Run it on a separate IV line, and give no other cyanide antidote through that line. Expect red skin and urine. It interferes with colorimetric lab tests and can set off false "blood leak" alarms on hemodialysis machines. Adult and pediatric dosing details are on the hydroxocobalamin page
• Sodium nitrite and thiosulfate (labeled kit): adults: sodium nitrite 3% 4–6 mg/kg (about 0.2 mL/kg) IV over 2–4 minutes, then sodium thiosulfate 150–200 mg/kg IV immediately after (typical adult dose 50 mL of 25%). Children (Nithiodote label): nitrite 0.2 mL/kg (6 mg/kg, max 10 mL), then thiosulfate 1 mL/kg (250 mg/kg, max 50 mL). Repeat at half the original doses after 2 hours if signs return. In known anemia, cut the nitrite dose in proportion to hemoglobin. Nitrite drops the BP and forms methemoglobin, so watch the pressure. Pulse oximetry is unreliable with methemoglobinemia. Do not give it through the same line as hydroxocobalamin.
• Nitrite caution: It causes methemoglobinemia, vasodilation and hypotension. Those must be managed. The label says to convert as much hemoglobin to methemoglobin as the patient can safely tolerate.
• Dialysis: Hemodialysis does not remove cyanide. It does clear most of the thiocyanate.
• Methylene blue: For methemoglobinemia, give 1 mg/kg IV over 5–30 minutes (ProvayBlue label). The older nitroprusside label says 1–2 mg/kg. Use extreme caution if cyanide may be bound to methemoglobin (label warning).

Clinically Significant Interactions

IV Compatibility

• Diluent: 5% dextrose for the concentrate; 0.9% sodium chloride is the Nipride RTU diluent
• Co-administration: The label prohibits other drugs in the same solution. Use a dedicated line.
• Light: protect the infusion from light throughout use
• Flexible containers: not in series connections

Check it against your institution's compatibility resource.

• Pediatrics: Efficacy is established for hypertensive crises in children. See the Pediatric Dosing table. Infants under 10 kg may need lower pump rates than the label table.
• Neonates: The data are thin, with 4 neonates in label trials. Specialist use only. With a prolonged infusion, cyanide toxicity is a particular concern.
• Pregnancy: The drug crosses the placenta. In pregnant sheep, fetal cyanide levels were dose-related, and high doses were fatal. Human reports of severe pregnancy-induced hypertension describe stillbirths, but those cannot be reliably blamed on the drug. The label says give it only if clearly needed. If no alternative is suitable, use it for the shortest possible time, after discussing the risk with the patient. Obstetric protocols govern agent choice in preeclampsia. ACOG Committee Opinion No. 767 (2019) lists IV labetalol and IV hydralazine as first-line for acute severe hypertension in pregnancy. It names immediate-release oral nifedipine when IV access is not available.
• Lactation: It is not known whether the drug enters human milk. Thiocyanate is present in human milk. Decide between stopping the drug and stopping breastfeeding, based on maternal need.
• Older Adults: They are more sensitive to hypotension (label). Start at the low end of the range and titrate in small steps.
• Renal Impairment: eGFR <30 mL/min/1.73 m² (Nipride RTU label): limit the mean infusion rate to less than 3 mcg/kg/min; anuric patients: 1 mcg/kg/min. Thiocyanate builds up in renal failure, and hemodialysis clears it.
• Hepatic Impairment: The patient is more susceptible to cyanide toxicity. Use caution and monitor closely.
• Obesity / Dosing Weight: The label gives per-kilogram rates but does not define the weight. Follow institutional policy for lean or adjusted weight. Do not use total body weight without a documented rule.
• Anemia or Hypovolemia: The patient has less capacity to compensate under anesthesia (label). Correct it before starting, where possible.

• Scope: Infusion management sits at the critical-care transport team level. Scope varies by state and agency protocol.
• Storage & Stability: Store at 20–25°C (68–77°F) in the carton until use. A diluted bag holds for 24 hours when protected from light. Discard it after that. Keep the vial in its carton during transport.
• Carried Concentration: The concentrate (25 mg/mL vial, diluted in D5W) and the premixed Nipride RTU (0.2 or 0.5 mg/mL in saline) look alike. They have different diluents. Label the bag with its mg/mL and mcg/mL values.
• Infusions in Transport: Use a volumetric pump only, on a dedicated line, with light protection (sleeve or foil). Calculate the mL/hr for the patient's weight and recheck it at each handoff. Plan the bag volume for the trip. Example: at 0.3 mcg/kg/min in a 70 kg patient, the 200 mcg/mL bag runs about 6.3 mL/hr.
• Handoff Essentials: time started, current rate in mcg/kg/min and mL/hr, bag concentration and time mixed, cumulative dose and duration at maximum rate, last BP and target, any cyanide or thiocyanate concern, and whether the cyanide antidote has been given.

Mechanism of Action

• Target: Smooth muscle in arteries and veins relaxes. It is a direct-acting vasodilator.
• Effect: Venodilation reduces preload, the filling pressure (LV end-diastolic and wedge pressures). Arteriolar relaxation reduces afterload, the resistance the heart pumps against (systemic vascular resistance).
• Clinical consequence: With an adequate infusion, BP falls within 1–2 min. Expect a reflex rise in heart rate and coronary dilation. At moderate doses, renal blood flow does not change appreciably.
• Metabolic consequence: It reacts with hemoglobin and releases cyanide. Thiosulfate helps clear that cyanide to thiocyanate.

Pharmacokinetics

• Half-life: The circulatory half-life is about 2 minutes. The drug is cleared by reacting with erythrocyte hemoglobin.
• Metabolism: One molecule releases one cyanmethemoglobin and four cyanide ions. The mitochondrial enzyme rhodanase converts cyanide to thiocyanate. Sulfur donors such as thiosulfate limit that step.
• Active metabolites: Cyanide, the most toxic, and thiocyanate. Cyanide clearance matches about 2 mcg/kg/min of steady infusion.
• Elimination: The kidney clears thiocyanate. Its half-time of accumulation is about 3 to 4 days (Mylan label). Hemodialysis removes thiocyanate but not cyanide.

Generic name

Sodium nitroprusside (dihydrate)

Brand names (US)

Nipride RTU (premixed; Exela Pharma Sciences); sodium nitroprusside injection concentrate (multiple generic manufacturers)

Pharmacologic class

Direct-acting vasodilator

Therapeutic class

Antihypertensive (hypertensive crisis); acute heart failure agent

Controlled substance

Not controlled

ISMP High-Alert

Treated as high-alert: FDA boxed warning for precipitous hypotension and cyanide toxicity

Look-Alike / Sound-Alike

None commonly reported; write the full name to avoid confusion with nitroglycerin

Error-Prone Abbreviations

None identified; write "sodium nitroprusside" in full