Sodium nitroprusside (SNP) is a potent vasodilator that first gained FDA approval for the treatment of severe hypertension in 1974. First discovered in 1849 by Playfair, its applications in human medicine can be traced back to the early 1920s, with the first safety and efficacy data published in 1955. After an initial delay in gaining FDA approval due to difficulty in development of a chemically stable formulation, SNP gained widespread use as a fast-acting antihypertensive agent and has been used clinically for hypertensive crises, heart failure, cardiac/vascular surgery, pediatric surgery, and a variety of other acute applications. While sodium nitroprusside potential adverse effects and toxicity have led to its replacement by newer agents in some practices, it remains a useful tool in certain difficult clinical situations that require a potent, fast-acting, titratable vasodilator.
Off-label uses for nitroprusside include:
A water-soluble sodium salt, sodium nitroprusside is comprised of ferrous iron complexed with nitric oxide (NO) and five cyanide ions. Acting as a prodrug, SNP reacts with sulfhydryl groups on erythrocytes (as well as albumin and other proteins) to produce nitric oxide (NO). Upon binding to vascular smooth muscle, NO triggers intracellular cGMP-mediated activation of protein kinase G and subsequent inactivation of myosin light chains, resulting in relaxation of vascular smooth muscle. The result of this signaling cascade is peripheral vasodilation of both arteries and veins (with slightly more selectivity for veins).
From a hemodynamic perspective, the net result is a decrease in systemic vascular resistance (afterload), ventricular filling pressures, and systemic blood pressure with an increase in cardiac output. Onset is rapid (within 2 minutes), and the duration of its hypotensive effect is roughly 10 minutes; these properties make nitroprusside useful in situations requiring an immediate reduction in preload or afterload. In contrast to nitroglycerin, nitroprusside causes a more balanced vasodilatory effect between arteries and veins.
Nitroprusside is administered only as an IV infusion diluted in D5W (it is not suitable for direct injection). It must be protected from light at all times.
Typical infusion rates range from 0.5 to 4 mcg/kg/minute which are then titrated to desired effect. Typical infusion concentrations for adults are 200 mcg/mL or 400 mcg/mL.
The maximum infusion rate is approximately 10 mcg/kg/minute, not to be sustained for more than 10 minutes at a time. If sufficient blood pressure control has not been achieved at that point, alternative agents should be considered (e.g., clevidipine).
The half-life elimination of sodium nitroprusside in circulation is roughly 2 minutes. Once metabolized into thiocyanate, half-life elimination occurs in approximately three days; renal dysfunction can easily double or triple this figure.
SNP is ultimately excreted from the body via urine as thiocyanate.
Adverse effects include the following:
Nitroprusside is Contraindicated in the Following Situations
*These patients are deficient in rhodanese. (rhodanese, also known as rhodanase, thiosulfate cyanide transsulfurase, thiosulfate sulfurtransferase, and thiosulfate thiotransferase, is a mitochondrial enzyme that detoxifies cyanide by converting it to thiocyanate).
Pregnancy Category C
Intensive hemodynamic monitoring is critical when administering nitroprusside. As a result, the use of SNP has classically been restricted to highly monitored settings such as the ICU or operating theater. Continuous blood pressure monitoring is required using an indwelling arterial line. With prolonged infusions or high infusion rates, close attention should also be paid to acid-base balance and mixed venous oxygen concentration, as unexplained acidemia and/or hypoxemia are often early signs of cyanide toxicity. However, It should be noted that these laboratory measures may not always provide reliable guidance. In most settings, serum cyanide concentrations are not of practical use due to long turnaround times. Thiocyanate levels can be monitored in high-risk patients (those with renal dysfunction and/or infusions >3 days).
The toxicity of nitroprusside is related to its potent antihypertensive effects and the accumulation of toxic metabolites (cyanide, thiocyanate, and methemoglobin).
1. Cyanide toxicity: Nitroprusside combines with hemoglobin and is subsequently metabolized to 5 cyanide ions and cyanmethemoglobin. Cyanide then converts to thiocyanate via rhodanese-mediated donation of a sulfur group (from thiosulfate or cysteine); this final step can quickly become overwhelmed with large quantities of the drug.
One strategy that has helped to combat cyanide toxicity in patients receiving high doses or prolonged infusions of nitroprusside involves the co-administration of sodium thiosulfate (a sulfur group donor) at a 10 to 1 ratio. It is important to note that thiocyanate toxicity may still occur with this approach.
2. Hypotension: Profound hypotension may occur with resultant compromised perfusion to vital organs
4. Methemoglobinemia: Methemoglobinemia most often occurs in patients receiving infusions >10 mcg/kg/minute and presents with signs of impaired oxygen delivery despite normal PaO2 and cardiac output.
5. Increased intracranial pressure: a result of cerebral vasodilation.
Nitroprusside is a fast-acting, easily titratable, highly effective antihypertensive agent that must be used with extreme care. While its use has declined in recent years as newer agents have become available, this drug still has a role in the treatment of hypertensive emergencies and other disease processes that require an urgent reduction in arterial blood pressure.
Interprofessional communication is critical to the safe use of nitroprusside as these patients require intensive monitoring of hemodynamic parameters. All members of the interprofessional healthcare team must be familiar with the potential adverse effects and toxicity syndromes. Careful patient selection based on comorbidities and risk factors is required, and clinicians (surgeons, anesthesiologists, intensivists) should engage in shared decision making with their pharmacists to assess each patient's risk factors and determine an appropriate dosing protocol. In utilizing this team-oriented approach, sodium nitroprusside can be a safe and effective therapeutic option for managing the acutely hypertensive patient. [Level 5]
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