Sodium Nitroprusside

Sodium nitroprusside is a fast acting intravenous vasodilator that releases nitric oxide. It lowers blood pressure within seconds and is used in hypertensive emergencies, acute severe heart failure with high afterload, and controlled hypotension in surgery. The effect disappears within minutes of stopping the infusion, which allows precise control. Its main risk is cyanide and thiocyanate toxicity, so it needs an arterial line, close nursing, and a short course. It is often unavailable in East African hospitals.

Classification. Nitric oxide donor; balanced arterial and venous vasodilator.

Mechanism. Breaks down in the circulation and in red cells to release nitric oxide, which raises cyclic GMP in smooth muscle and relaxes both arterioles and veins. Five cyanide ions are released for each molecule of nitroprusside.

Pharmacodynamics. Onset within 30 seconds, peak at 1 to 2 minutes, duration 1 to 10 minutes after stopping. Lowers preload and afterload; may raise intracranial pressure; reflex tachycardia is common; coronary steal can occur.

Pharmacokinetics. Plasma half life 2 minutes. Cyanide is converted in the liver by rhodanese to thiocyanate (half life 3 days, longer in kidney impairment), which is excreted in urine.

Hypertensive emergency, adult.

• Start 0.3 to 0.5 micrograms/kg/minute IV by infusion pump.

• Increase by 0.5 micrograms/kg/minute every 5 minutes to the target.

• Usual range 0.5 to 6 micrograms/kg/minute; maximum 10 micrograms/kg/minute, and only for up to 10 minutes.

• Keep the infusion at 2 micrograms/kg/minute or less when it continues beyond a few hours. Total dose over 1 hour should stay below 500 micrograms/kg.

• Aim to reduce mean arterial pressure by no more than 25% in the first hour.

Acute severe heart failure with high afterload, adult. Start 0.3 micrograms/kg/minute; titrate every 5 to 10 minutes to the lowest dose that improves the signs (usual 0.5 to 3 micrograms/kg/minute). Maximum 10 micrograms/kg/minute for 10 minutes.

Controlled hypotension in anaesthesia, adult. Specialist anaesthetic use only: 0.3 to 1.5 micrograms/kg/minute.

Children. Start 0.3 to 0.5 micrograms/kg/minute; maximum 4 micrograms/kg/minute (higher doses carry greater cyanide risk). Specialist units only.

Duration limit. Avoid beyond 48 hours where possible; if the infusion must continue, check thiocyanate levels, and stop earlier in kidney impairment.

Contraindications. Compensatory hypertension (arteriovenous shunt, coarctation of the aorta); Leber optic atrophy and tobacco amblyopia; vitamin B12 deficiency; severe hepatic impairment; hypothyroidism; congenital optic atrophy; concurrent phosphodiesterase type 5 inhibitor; hypersensitivity.

Warnings. Cyanide toxicity (unexplained metabolic acidosis with raised lactate, tachycardia, confusion, seizures, bright red venous blood); thiocyanate toxicity (nausea, tinnitus, blurred vision, confusion, psychosis); excess fall in blood pressure; raised intracranial pressure; hypothyroidism; rebound hypertension after stopping.

Adverse effects. Hypotension, nausea, vomiting, headache, palpitations, tachycardia, sweating, abdominal pain, methaemoglobinaemia, cyanide poisoning.

Interactions. Other antihypertensives and anaesthetic agents: additive hypotension. Phosphodiesterase type 5 inhibitors: profound hypotension. Beta blockers blunt reflex tachycardia (desirable). Drugs that cause methaemoglobinaemia add to risk.

Special groups.

• Pregnancy: avoid unless life saving; foetal cyanide accumulation can occur. Use labetalol or nifedipine first.

• Breastfeeding: no data; stop feeding during use.

• Patients of African ancestry: no change in dosing; control of malignant hypertension is the same.

• Older adults: lower start and slower titration.

• Kidney impairment: thiocyanate accumulates; limit to 48 hours and use the lowest possible dose.

• Liver impairment: cyanide detoxification is reduced; avoid in severe disease.

Cyanide toxicity treatment. Stop the infusion; give oxygen; hydroxocobalamin 5 g IV over 15 minutes (repeat once if needed) or sodium thiosulphate 12.5 g IV over 10 minutes; support ventilation. Take a blood gas and lactate.

Formulations. Powder for solution 50 mg vial, reconstituted with 2 to 3 mL of 5% glucose and diluted into 250 to 1000 mL of 5% glucose (final 50 to 200 micrograms/mL).

Administration. Infusion pump only; no other drug in the same line. Wrap the bag and tubing in opaque cover because light breaks it down. Discard the solution after 24 hours and when it turns brown. Use 5% glucose only.

Baseline. Arterial line, ECG, blood gas with lactate, creatinine, hepatic enzymes, intracranial pressure assessment where relevant, pregnancy test.

Monitoring. Continuous arterial pressure and ECG. Blood gas and lactate every 6 hours and with any unexplained deterioration. Thiocyanate level if the infusion runs beyond 72 hours or in kidney impairment (toxic above 100 micrograms/mL). Visual symptoms and mental state.

Stopping. Wean over 15 to 30 minutes while an oral agent takes over. Start the oral drug early (the half life of the infusion is minutes).

Common prescribing errors. Running at 10 micrograms/kg/minute for longer than 10 minutes; leaving the infusion for days without thiocyanate levels; exposing the infusion to light; flushing the line with a bolus, causing a sudden drop in blood pressure; using it in pregnancy when labetalol is available.