Dose and Administration

1. 0.4-2.0 micrograms/kg/minute by continuous IV infusion.
2. Usual starting dose: 1 micrograms/kg/min; adjust rate as necessary to control BP.
3. Maximum dose: 10 micrograms/kg/min for 10 minutes.
4. Maximum infusion rate for prolonged therapy 2 micrograms/kg/min.

Sodium nitroprusside 5mg added to D5W to make 50ml = 100 micrograms/ml

Indications

1. Persistent pulmonary hypertension of the newborn.
2. Hypertensive crisis.
3. Severe congestive heart failure.

Contraindications and Precautions

1. Known hypersensitivity to sodium nitroprusside.
2. Coarctation of the aorta.
3. Arteriovenous fistula.
4. Compensatory hypertension.
5. Caution in preterm infants, especially extreme immaturity.
6. Caution in infants with hepatic or renal impairment.
7. Caution in infants with raised intracranial pressure.

Clinical Pharmacology

Sodium nitroprusside is a potent, direct acting vasodilator. Affects arteriolar and venous smooth muscle equally. Has little effect on gastrointestinal or uterine smooth muscle, autonomic nervous system or central nervous system.

Rapid distribution to the target tissues (smooth muscle of the arteriolar and venous vessels). Rapid and complete metabolism within erythrocytes to cyanide and cyanomethaemoglobin. Metabolism of cyanide to thiocyanate by hepatic enzyme rhodanase. Repeated enterohepatic circulation. Very slow elimination of thiocyanate by the kidney (elimination half life 4-7 days).

Very rapid onset of action (1-2 minutes). Toxicity due to accumulation of cyanide and thiocyanate. Associated with marked vasodilation and hypotension.

Possible Adverse Effects

1. Hypotension
2. Cyanide toxicity
3. Metabolic acidosis
4. Restlessness, agitation, muscle twitching
5. Vomiting
6. Skin rash
7. Drug intolerance (metabolic acidosis, increased serum lactate and thiocyanate levels).
8. Methaemoglobinaemia.
9. Raised intracranial pressure.

Special Considerations

1. The efficacy and safety of nitroprusside in neonates has not been established. Clinical experience is limited.
2. Titrate infusion rate against clinical response, especially blood pressure.
3. When discontinuing a nitroprusside infusion reduce the infusion rate steadily over a period of 10-30 minutes to avoid rebound hypertension.
4. Monitor haemoglobin (nitroprusside binds the haemoglobin), arterial blood gases for metabolic acidosis.
5. Serum thiocyanate levels should be measured. Toxic levels >2 mmol/L.
6. Management of thiocyanate or cyanide toxicity: stop nitroprusside infusion, infuse vitamin B12 0.1 mg/kg IV.