Nitropress: After reconstitution, nitroprusside is not suitable for direct injection. The reconstituted solution must be further diluted in dextrose 5% injection before infusion.
Nitroprusside can cause precipitous decreases in blood pressure. In patients not properly monitored, these decreases can lead to irreversible ischemic injuries or death. Use only when available equipment and personnel allow blood pressure to be continuously monitored.
Except when used briefly or at low (less than 2 mcg/kg/min) infusion rates, nitroprusside injection gives rise to important quantities of cyanide ion, which can reach toxic, potentially lethal levels. The usual dose rate is 0.5 to 10 mcg/kg/min, but infusion at the maximum dose rates should never last more than 10 minutes. If blood pressure has not been adequately controlled after 10 minutes of infusion at the maximum rate, terminate administration immediately. Although acid-base balance and venous oxygen concentration should be monitored and may indicate cyanide toxicity, these laboratory tests provide imperfect guidance.
Acute hypertension: Initial: 0.3 to 0.5 mcg/kg/minute; may be titrated by 0.5 mcg/kg/minute every few minutes to achieve desired hemodynamic effect (Rhoney 2009); maximum dose: 10 mcg/kg/minute (for a maximum of 10 minutes). To avoid toxicity, some recommend a maximum dose of 2 mcg/kg/minute (Marik 2007).
Acute ischemic stroke, BP management with reperfusion therapy (off-label use):
Note: During and 24 hours after reperfusion therapy, maintain a target BP of ≤180/105 mm Hg; reserve nitroprusside for hypertension that is refractory to first-line agents or diastolic BP >140 mm Hg (AHA/ASA [Powers 2019]).
Continuous IV infusion: Initial: 0.25 to 0.5 mcg/kg/minute; titrate by 0.5 mcg/kg/minute every 5 minutes. Maximum dose: 10 mcg/kg/minute (for a maximum of 10 minutes); consider a maximum dose of 2 mcg/kg/minute to avoid toxicity (Der-Nigoghossian 2019; Marik 2007; manufacturer’s labeling).
Acute decompensated heart failure: IV: Initial: 5 to 10 mcg/minute; may be titrated rapidly (eg, up to every 5 minutes) to achieve desired hemodynamic effect; usual dosage range: 5 to 300 mcg/minute. Doses >400 mcg/minute are not recommended due to minimal added benefit and increased risk for thiocyanate toxicity (HFSA 2010).
Use in patients with renal impairment may lead to the accumulation of thiocyanate and subsequent toxicity; limit use.
eGFR <30 mL/minute/1.73 m2: Limit mean infusion rate to <3 mcg/kg/minute.
Anuric patients: Limit mean infusion rate to 1 mcg/kg/minute.
No dosage adjustment provided in manufacturer's labeling; due to the risk of cyanide toxicity, use with caution.
(For additional information see "Nitroprusside: Pediatric drug information")
Hypertension, acute including hypertensive crisis: Infants, Children, and Adolescents: Continuous IV infusion: Initial: 0.3 to 0.5 mcg/kg/minute, titrate every 5 minutes to desired effect; usual dose: 3 to 4 mcg/kg/minute; maximum dose: 10 mcg/kg/minute (Chandar 2012; Hegenbarth 2008; NHBPEP 2004; Park 2014); increased infusion rates are correlated with increased cyanide concentrations (Hammer 2015); a study in pediatric postoperative cardiac surgery patients found patients with rates ≥1.8 mcg/kg/minute had increased cyanide concentrations (Moffett 2008); monitor cyanide levels with prolonged use (eg, >72 hours) (NHBPEP 2004)
Cardiac output maintenance/stabilization, postresuscitation (PALS [Kleinman 2010]): Infants, Children, and Adolescents: Continuous IV infusion: Initial: 0.5 to 1 mcg/kg/minute, titrate to desired effect; maximum dose: 8 mcg/kg/minute
Infants, Children, and Adolescents: Use in patients with renal impairment may lead to the accumulation of thiocyanate and subsequent toxicity; limit use and monitor thiocyanate blood concentrations
eGFR <30 mL/minute/1.73 m2: Limit mean infusion rate to <3 mcg/kg/minute
Anuric patients: Limit mean infusion rate to 1 mcg/kg/minute
There are no dosage adjustments provided in the manufacturer's labeling; due to the risk of cyanide toxicity, use with caution.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as sodium:
Nipride RTU: 20 mg/100 mL in NaCl 0.9% (100 mL)
Nitropress: 25 mg/mL (2 mL [DSC])
Generic: 25 mg/mL (2 mL)
Solution, Intravenous, as sodium [preservative free]:
Nipride RTU: 10 mg/50 mL in NaCl 0.9% (50 mL [DSC]); 50 mg/100 mL in NaCl 0.9% (100 mL)
Generic: 25 mg/mL (2 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as sodium:
Nipride: 25 mg/mL (2 mL)
Generic: 25 mg/mL (2 mL)
IV: IV infusion only; infusion pump required. Due to potential for excessive hypotension, continuously monitor patient’s blood pressure during therapy. Product should always be protected from light, even during administration.
Parenteral: Administer as continuous IV infusion via infusion pump. Solution should be protected from light, but not necessary to wrap administration set or IV tubing.
Concentrated solution (25 mg/mL): Not for direct injection; must dilute prior to administration.
Ready to use (0.5 mg/mL): No further dilution required
IV infusion: 50 mg in 250 mL (concentration: 200 mcg/mL) or 100 mg in 250 mL (concentration: 400 mcg/mL) of D5W
IV infusion: 100 mcg/mL or 200 mcg/mL
Acute decompensated heart failure (HF): Management of acute decompensated HF
Acute hypertension: Management of hypertensive crises; used for controlled hypotension to reduce bleeding during surgery
Acute ischemic stroke, BP management with reperfusion therapy
Nitroprusside may be confused with nitroglycerin
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Bradycardia, ECG changes, flushing, palpitations, severe hypotension, substernal pain, tachycardia
Central nervous system: Apprehension, dizziness, headache, increased intracranial pressure, restlessness
Dermatologic: Diaphoresis, localized erythematous streaking, skin rash
Endocrine & metabolic: Hypothyroidism
Gastrointestinal: Abdominal pain, intestinal obstruction, nausea, retching
Hematologic & oncologic: Decreased platelet aggregation, methemoglobinemia
Local: Irritation at injection site
Neuromuscular & skeletal: Muscle twitching
Treatment of compensatory hypertension (aortic coarctation, arteriovenous shunting); to produce controlled hypotension during surgery in patients with known inadequate cerebral circulation or in moribund patients (A.S.A. Class 5E) requiring emergency surgery; acute heart failure associated with reduced systemic vascular resistance (eg, septic shock); congenital (Leber's) optic atrophy or tobacco amblyopia; concomitant use with sildenafil, tadalafil, vardenafil, or riociguat
Canadian labeling: Additional contraindication (not in US labeling): Hypersensitivity to nitroprusside or any component of the formulation; uncorrected anemia or hypovolemia; hepatic disease; severe renal disease; disease states associated with vitamin B12 deficiency
Concerns related to adverse effects:
• Cyanide toxicity: [US Boxed Warning]: Except when used briefly or at low (<2 mcg/kg/minute) infusion rates, nitroprusside gives rise to large cyanide quantities. Do not use the maximum dose for more than 10 minutes; if blood pressure is not controlled by the maximum rate (ie, 10 mcg/kg/minute) after 10 minutes, discontinue infusion. Monitor for cyanide toxicity via acid-base balance and venous oxygen concentration; however, clinicians should note that these indicators may not always reliably indicate cyanide toxicity. Patients at risk of cyanide toxicity include those who are malnourished, have hepatic impairment, or those undergoing cardiopulmonary bypass, or therapeutic hypothermia (Rindone 1992). Discontinue use of nitroprusside if signs and/or symptoms of cyanide toxicity (eg, metabolic acidosis, decreased oxygen saturation, bradycardia, confusion, convulsions) occur. Although not routinely done, sodium thiosulfate has been co-administered with nitroprusside using a 10:1 ratio of sodium thiosulfate to nitroprusside when higher doses of nitroprusside are used (eg, 4 to 10 mcg/kg/minute) for extended periods of time in order to prevent cyanide toxicity (Shulz 2010; Varon 2008); thiocyanate toxicity may still occur with this approach (Rindone 1992). The use of other agents (eg, clevidipine, labetalol, nicardipine) should be considered if blood pressure is not controlled with nitroprusside.
• Hypotension: [US Boxed Warning]: Excessive hypotension resulting in compromised perfusion of vital organs may occur; continuous blood pressure monitoring by experienced personnel is required.
• Increased intracranial pressure: Use may elevate intracranial pressure; in patients whose intracranial pressure is already elevated, use only with extreme caution.
Methemoglobinemia: Nitroprusside can cause a dose-dependent conversion of hemoglobin to methemoglobin. Methemoglobinemia should be suspected in any patient receiving >10 mg/kg of nitroprusside and exhibiting signs of impaired oxygen delivery despite adequate cardiac output and arterial pO2. Symptomatic patients, regardless of methemoglobin level should be treated with methylene blue (first-line). Treatment is suggested if level is ≥30% even if asymptomatic unless patient has a preexisting condition (eg, coronary artery disease) and are incapable of tolerating reductions in oxygen carrying capacity then treatment is suggested if level reaches 10% (Cortazzo 2013).
• Thiocyanate toxicity: Can occur in patients with renal impairment or those on prolonged infusions (ie, >3 mcg/kg/minute for >72 hours).
Disease-related concerns:
• Anemia: When nitroprusside is used for controlled hypotension during surgery, correct pre-existing anemia prior to use when possible.
• Hepatic impairment: Use with extreme caution in patients with hepatic impairment.
• Hypovolemia: When nitroprusside is used for controlled hypotension during surgery, correct pre-existing hypovolemia prior to use when possible.
• Myocardial infarction: Use caution in patients with acute myocardial infarction because of hemodynamic effects and possible coronary steal.
• Renal impairment: Use with extreme caution in patients with renal impairment; use the lowest end of the dosage range; monitor thiocyanate concentrations closely.
Other warnings/precautions:
• Appropriate administration: Nitropress: [US Boxed Warning]: Solution must be further diluted with 5% dextrose in water. Do not administer by direct injection.
None known.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Nitroprusside. Risk X: Avoid combination
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Riociguat: May enhance the hypotensive effect of Nitroprusside. Risk X: Avoid combination
Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Animal studies have shown that nitroprusside may cross the placental barrier and result in fetal cyanide levels that are dose-related to maternal nitroprusside levels. However, information related to use in pregnancy is limited.
It is not known if nitroprusside is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
Blood pressure via arterial line and heart rate (cardiac monitor and blood pressure monitor required) (Friedrich 1995); monitor for cyanide and thiocyanate toxicity; monitor venous oxygen saturation; monitor acid-base status as acidosis can be the earliest sign of cyanide toxicity; monitor thiocyanate levels if requiring prolonged infusion (>3 days) or dose >3 mcg/kg/minute or patient has renal dysfunction; monitor cyanide blood levels (if available with appropriate turnaround time) in patients with decreased hepatic function
Consult individual institutional policies and procedures.
Serum thiocyanate levels are not helpful in detecting toxicity. A level may be confirmatory if a patient is exhibiting signs and symptoms of thiocyanate toxicity. Initial signs of toxicity (eg, tinnitus) may be observed at levels >35 mcg/mL (manufacturer suggests 60 mcg/mL), but serious toxicity typically may not occur with levels <100 mcg/mL.
Causes peripheral vasodilation by direct action on venous and arteriolar smooth muscle, thus reducing peripheral resistance; will increase cardiac output by decreasing afterload; reduces aortal and left ventricular impedance
Onset of action: Hypotensive effect: <2 minutes
Duration: Hypotensive effect: 1-10 minutes
Metabolism: Nitroprusside combines with hemoglobin to produce cyanide and cyanmethemoglobin. Cyanide detoxification occurs via rhodanase-mediated conversion of cyanide to thiocyanate; rhodanase couples cyanide molecules to sulfane sulfur groups from a sulfur donor (eg, thiosulfate, cystine, cysteine). This process has limited capacity and may become overwhelmed with large exposures once sulfur donor supplies are exhausted resulting in toxicity.
Half-life elimination: Nitroprusside, circulatory: ~2 minutes; Thiocyanate, elimination: ~3 days (may be doubled or tripled in renal failure)
Excretion: Urine (as thiocyanate)
Solution (Nipride RTU Intravenous)
20 mg/100 mL 0.9% (per mL): $0.54
50 mg/100 mL 0.9% (per mL): $0.66
Solution (Nitroprusside Sodium Intravenous)
25 mg/mL (per mL): $9.75 - $161.82
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