Sodium Nitroprusside (Nitropress, Nipride)

Anesthesia Implications

Classification: direct-acting vasodilator
Therapeutic Effects: Treatment of acute hypertension, venous and arterial dilation
Time to Onset: 1-2 min

Duration: 10 minutes

Contraindications

Contraindicated in patients with:
Patients taking phosphodiesterase inhibitors (eg. vardenafil, sildenafil, tadalafil)
Vitamin B12 deficiency
compromised/inadequate cerebral perfusion
Acute heart failure with low SVR
Leber’s hereditary optic atrophy – deficient rhodanese (which detoxifies cyanide)
Tobacco amblyopia – deficient rhodanese (which detoxifies cyanide)
Compensatory hypertension (eg arteriovenous malformations or aortic coarctation)
Caution with patients on bypass – prolonged exposure to bypass increases a patient’s risk for cyanide toxicity
Caution with patients who have or are at risk of increased ICP
Caution with renal dysfunction – keep the dose as low as possible and monitor for thiocyanate toxicity

Primary Considerations

Hemodynamics – decreases afterload, preload, and SVR. Cardiac output is improved. Vessel dilation is both arterial and venous (slightly more).

Cerebral vasodilator – Nitroprusside will INCREASE intracranial pressure due to increased cerebral blood flow and resultant increased blood volume.

Anemia/Hypovolemia – Natural mechanisms to compensate for anemia or hypovolemia can be impaired by Nitropress. If possible, correct these issues prior to using this drug.

Protect from light – this is to prevent degradation and the subsequent rapid cyanide anion release upon administration.

Cyanide toxicity – this is the big concern when using nitroprusside. Monitor closely for this – especially in patients with hepatic impairment. This manifests as restlessness, agitation, and sinus tachycardia, which are difficult to evaluate intraoperatively and can easily lead to a misdiagnosis. Elevated lactate concentrations are an excellent queue and serve as a marker of cyanide toxicity.

Methemoglobinemia – can occur if infusions are prolonged at the higher doses. Symptoms appear as impaired oxygen in spite of adequate hemodynamics. Methylene blue (1-2 mg of 1% solution) should be given in those exhibiting methemoglobin levels of > 30% or exhibiting symptoms.

Side effects – increased ICP, erythema, diaphoresis, decreased platelet aggregation, nausea, vomiting

IV push dose

Contraindicated

IV infusion dose

Adult: 0.3 – 10.0 mcg/kg/min. MAX 10 mcg/kg/min. 10 mcg/kg/min is not to be maintained for more than 10 minutes. Titrate q5 min.

In patients with eGFR <30 mL/min/1.73 m2, limit the mean infusion rate to less than 3 mcg/kg/min. In anuric patients, limit the mean infusion rate to 1 mcg/kg/min.

Pediatric: Maintain below 0.2 mcg/kg/min. Doses above this should be for short periods to establish blood pressure control.

Typically diluted in D5W. Diluted to 200 or 400 mcg/mL

Method of Action

Nitric oxide donor. Nitroprusside is a prodrug – it reacts with hemoglobin, erythrocytes, albumin, and other proteins to produce nitric oxide (as well as cyanide and cyanmethemoglobin), which results in vascular smooth muscle relaxation. Vasodilation subsequently happens in both venous (slightly more) and arterial blood vessels.

Metabolism

Reacts with hemoglobin erythrocytes, albumin, and other serum proteins to produce nitric oxide, cyanide and cyanmethemoglobin. Cyanide is converted to thiocyanate by rhodanese (otherwise known as rhodanase, thiosulfate cyanide transsulfurase, thiosulfate sulfurtransferase, and thiosulfate thiotransferase) and excreted renally.

Elimination

Excreted in the urine as thiocyanate. The elimination half life of this metabolite is approximately 3 days. Renal dysfunction can extend it to 6-9 days.

Additional Notes
Thiocyanate toxicity – use cautiously (lowest possible dose) in renal failure/compromise. Thiocyanate is a metabolite of Nitropress and is renally cleared. Toxicity is rare but can happen in patients with compromised renal failure and/or long infusions (greater than 72 hours). Early signs are tinnitus, abdominal pain, weakness, and altered mental status. Late symptoms include lethargy, seizures, and coma if not treated. Serum thiocyanate levels can be assessed if toxicity is suspected. Early symptoms can be observed at 35 mcg/mL and late signs are typically observed at greater than 100 mcg/mL