II. Indications
-
Hypertensive Emergency
- Nicardipine is now preferred instead for Hypertensive Emergency
- Reduces Blood Pressure rapidly
- However difficult to titrate due to a wide variation in bloold pressure variation
- Well tolerated
- Easily reversed by discontinuing infusion
-
Congestive Heart Failure with pulmonary congestion
- Refractory to Diuretics
- Often used in combination with Dopamine
- Similar net effect to Dobutamine
- Nitroglycerin is preferred in Coronary Artery Disease
III. Mechanism
- Converted to Nitrous Oxide which stimulates cGMP
- cGMP stimulates dephosphorylation of myosin, resulting in arteriole Smooth Muscle relaxation
- Potent peripheral vasodilation
- Effects arterial and venous Smooth Muscle
- Reduces arterial Blood Pressure
- Reduces peripheral arterial resistance
- Increases venous capacitance
- Decreases Preload
- Risk of reflex Tachycardia
IV. Metabolism
-
Red Blood Cells metabolize to Hydrocyanic acid and Liver converts to thiocyanate
- Onset within 2 minutes
- Thiocyanate effect wanes rapidly on stopping infusion
- Metabolites include Cyanide and Thiocyanate, risk accumulation
- Hepatic dysfunction
- High doses (esp. >3 to 10 mcg/kg/min)
- Prolonged infusions (>3 to 7 days)
- Renal Excretion
V. Pharmacokinetics
- Very short Half-Life
- Effects are seen almost immediately on infusion
- Effects cease as soon as infusion is stopped
VI. Dosing
- Preparation
- Reconstitute 50-100 mg powder in 2-3 ml D5W
- Dilute with 250 ml D5W or Normal Saline
- Final Concentration: 200-400 mcg/ml
- Additional Measures
- Wrap solution immediately in aluminum foil
- Prevents deterioration under light exposure
- Use solution immediately after making it
- Discard solution if becomes highly colored
- Solution with faint brown tint is still usable
- Wrap solution immediately in aluminum foil
-
Hypertensive Emergency
- Start 0.1 to 0.3 mcg/kg/min (e.g. 6 ml/hour in a 70 kg adult)
- Titrate 0.5 to 8.0 ug/kg/min
- Carefully monitor hemodynamic parameters
- Maximum: 10 mcg/kg/min
- Discontinue if inadequate response after 10 minutes
- Use lower doses in elderly
VII. Precautions
- Small changes in infusion rate result in large changes in Blood Pressure
- Significant Hypotension may precipitate secondary events
- Myocardial Ischemia or Myocardial Infarction
- Cerebral Vascular accident
- Avoid Nitroprusside in Coronary Artery Disease
- Use Nitroglycerin instead
- Thiocyanate Intoxication (cyanide Poisoning)
- Rarely seen unless:
- Nitroprusside doses over 3 mcg/kg/min (esp. >10 mcg/kg/min)
- Prolonged Nitroprusside infusion over 2-3 days
- Renal Failure
- Monitor blood thiocyanate level
- Levels below 10 mg/100 ml are safe
- Signs of thiocyanate Intoxication
- Rarely seen unless:
VIII. Resources
IX. References
- Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 66-7
- Hamilton (2020) Tarascon Pocket Pharmacopoeia