Usage
- Nitroprusside is prescribed for the immediate reduction of blood pressure in hypertensive crises and for controlled hypotension during surgery to reduce bleeding. It is also used in acute decompensated heart failure.
- Pharmacological Classification: Vasodilator (direct-acting, both arterial and venous).
- Mechanism of Action: Nitroprusside acts directly on vascular smooth muscle, causing vasodilation and reducing peripheral vascular resistance. This leads to a decrease in blood pressure.
Alternate Names
- Sodium Nitroprusside
- Brand Names: Nitropress, Nipride RTU
How It Works
- Pharmacodynamics: Nitroprusside causes rapid and balanced vasodilation of both arteries and veins, leading to decreased preload and afterload. This reduces cardiac work and blood pressure.
- Pharmacokinetics:
- Administered intravenously.
- Rapid onset of action (1-2 minutes).
- Short half-life (approximately 2 minutes).
- Metabolized in the blood to release nitric oxide (NO) and cyanide ions. Cyanide is subsequently converted to thiocyanate in the liver by the enzyme rhodanese and excreted renally.
- Mode of Action: Nitroprusside non-enzymatically releases NO in the bloodstream. NO activates guanylate cyclase within smooth muscle cells, leading to increased cyclic guanosine monophosphate (cGMP). This, in turn, activates protein kinase G, which ultimately causes vascular smooth muscle relaxation.
- Elimination Pathways: Primarily renal excretion of thiocyanate.
Dosage
Standard Dosage
Adults:
- Initial infusion rate: 0.3 mcg/kg/min.
- Titrate every 5 minutes to achieve the desired blood pressure.
- Usual dose range: 0.5-4 mcg/kg/min.
- Maximum dose: 10 mcg/kg/min (not to be sustained for more than 10 minutes).
Children:
- Initial infusion rate: 0.3 mcg/kg/min.
- Titrate every 5 minutes to effect.
- Maximum dose: 10 mcg/kg/min (not to be sustained for more than 10 minutes).
- Pediatric safety considerations: Close monitoring for cyanide toxicity is crucial in children, especially with prolonged or high-dose infusions.
Special Cases:
- Elderly Patients: Initiate with lower doses due to increased sensitivity to hypotensive effects.
- Patients with Renal Impairment: Use lowest effective dose and monitor thiocyanate levels. For eGFR < 30 mL/minute/1.73 m², limit infusion rate to less than 3 mcg/kg/minute. In anuria, limit to 1 mcg/kg/minute.
- Patients with Hepatic Dysfunction: Use with extreme caution and monitor for cyanide toxicity due to reduced thiocyanate conversion.
- Patients with Comorbid Conditions: Careful monitoring is essential for patients with conditions like myocardial infarction, increased intracranial pressure, and hypothyroidism.
Clinical Use Cases
- Intubation: Dosage titrated to achieve desired blood pressure control.
- Surgical Procedures: Dosage titrated to maintain controlled hypotension.
- Mechanical Ventilation: Dosage adjusted based on blood pressure response.
- Intensive Care Unit (ICU) Use: Continuous blood pressure monitoring and dosage titration are crucial.
- Emergency Situations (e.g., hypertensive crisis): Initial dose of 0.3 mcg/kg/min titrated rapidly to effect, not to exceed 10 mcg/kg/min.
Dosage Adjustments
- Adjust dose based on patient response and renal/hepatic function.
- Monitor thiocyanate levels with prolonged use, especially in renal impairment.
Side Effects
Common Side Effects
- Flushing
- Headache
- Dizziness
- Nausea
- Vomiting
Rare but Serious Side Effects
- Cyanide toxicity (manifested as metabolic acidosis, arrhythmias, and altered mental status)
- Methemoglobinemia
- Excessive hypotension
- Thiocyanate toxicity (with prolonged use)
Long-Term Effects
- Thiocyanate toxicity (hypothyroidism, tinnitus, disorientation)
Adverse Drug Reactions (ADR)
- Severe hypotension requiring fluid resuscitation and vasopressor support.
- Cyanide toxicity requiring immediate treatment with sodium nitrite and sodium thiosulfate.
Contraindications
- Compensatory hypertension (e.g., aortic coarctation, arteriovenous malformation).
- Inadequate cerebral perfusion.
- Leber’s hereditary optic atrophy.
- Tobacco amblyopia.
- Vitamin B12 deficiency.
- Concomitant use of phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil).
Drug Interactions
- Other antihypertensive medications: Additive hypotensive effects.
- Inhaled anesthetics: Enhanced hypotensive effects.
- Heparin: Reduced anticoagulant effect of heparin.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C
- Fetal risks: Cyanide toxicity, fetal death.
- Breastfeeding: Not recommended due to potential cyanide and thiocyanate exposure to the infant.
Drug Profile Summary
- Mechanism of Action: Direct vasodilation of arteries and veins via NO release.
- Side Effects: Hypotension, cyanide toxicity, methemoglobinemia, thiocyanate toxicity.
- Contraindications: Compensatory hypertension, inadequate cerebral perfusion, Leber’s optic atrophy, tobacco amblyopia, B12 deficiency.
- Drug Interactions: Other antihypertensives, inhaled anesthetics.
- Pregnancy & Breastfeeding: Category C; not recommended during breastfeeding.
- Dosage: 0.3-10 mcg/kg/min IV infusion, titrated to effect.
- Monitoring Parameters: Blood pressure, cyanide levels (with prolonged or high-dose infusions), thiocyanate levels (with prolonged use), acid-base status.
Popular Combinations
- Often used as a single agent for hypertensive emergencies.
- In controlled hypotension during surgery, it may be used with inhaled anesthetics.
Precautions
- General Precautions: Continuous blood pressure monitoring is mandatory. Close monitoring for cyanide toxicity, especially with high doses or prolonged infusions. Renal and hepatic function should be assessed prior to administration.
- Specific Populations: As described above.
- Lifestyle Considerations: Caution patients about potential dizziness and orthostatic hypotension.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nitroprusside?
A: Initial infusion rate: 0.3 mcg/kg/min IV, titrated to desired effect. Usual range: 0.5-4 mcg/kg/min. Maximum: 10 mcg/kg/min (not to exceed 10 minutes).
Q2: How does Nitroprusside work?
A: It releases NO, causing vasodilation and reducing blood pressure.
Q3: What are the serious side effects of Nitroprusside?
A: Cyanide toxicity, methemoglobinemia, excessive hypotension, thiocyanate toxicity.
Q4: What are the contraindications to using Nitroprusside?
A: Compensatory hypertension, inadequate cerebral perfusion, Leber’s optic atrophy, tobacco amblyopia, vitamin B12 deficiency, concurrent use of phosphodiesterase-5 inhibitors.
Q5: Can Nitroprusside be used in pregnancy?
A: Only if clearly needed. It is a Pregnancy Category C drug, posing a risk of cyanide toxicity to the fetus.
Q6: Can Nitroprusside be used during breastfeeding?
A: Not recommended due to the potential for cyanide and thiocyanate exposure to the infant.
Q7: How should I monitor patients receiving Nitroprusside?
A: Continuous blood pressure monitoring is essential. Monitor for signs of cyanide toxicity (acidosis, arrhythmias, altered mental status). With prolonged use, monitor thiocyanate levels.
Q8: What are the signs of cyanide toxicity?
A: Metabolic acidosis, arrhythmias, altered mental status, headache, weakness, nausea, vomiting, hyperventilation.
Q9: How is cyanide toxicity treated?
A: Discontinue Nitroprusside immediately. Administer sodium nitrite and sodium thiosulfate as antidotes. Supportive care including oxygen and ventilation may be necessary.
Q10: How should Nitroprusside be administered?
A: IV infusion only, diluted in D5W. Never administer as a bolus injection.
