General (including evidence of efficacy)
For the purpose of practical clinical application, this chapter is divided into Acute Vasodilator Intervention and Chronic Vasodilator Therapy.
Differences between drugs within the class
Acute vasodilator intervention
Acute vasodilator therapy is directed at more urgent clinical conditions; most commonly characterized by cardiogenic dyspnea from high left ventricular end-diastolic pressure, resulting in elevated pulmonary capillary wedge pressure and varying degrees of pulmonary edema and congestion.
The major contraindication for acute vasodilator therapy is systemic hypotension (typically <90 mmHg). Patients with marginally low blood pressure, especially when accompanied by intense peripheral vasoconstriction (e.g., cool moist hands), may also respond favorably to intravenously administered vasodilator therapy with careful follow-up.
The three most common drugs employed for acute vasodilator intervention are nitroprusside, nitroglycerin, and nesiritide.
Nitroprusside is a sodium or potassium salt of a molecule that includes Fe++, cyanide and nitric acid. The vasodilator properties are mediated through the production of local nitrosothiol and subsequent generation of cyclic guanosine monophosphate in vasculature.
Nitroprusside is a powerful vasodilator. Because it is a powerful vasodilator, physicians are reluctant to prescribe nitroprusside routinely. The drug also needs to be administered agent under carefully monitored conditions to avoid hypotension.
Furthermore, continued administration of nitroprusside (after the initial relief of dyspnea) generally requires the placement of an arterial line and oftentimes, a pulmonary flow-directed catheter (Swan-Ganz) for optimal safe dosing. Prolonged (>3 days), high dose (≥3 mcg/kg/min) administration can lead to cyanide and thiocyanate toxicity, particularly in the setting of renal dysfunction, causing some to avoid this agent.
The onset of pharmacologic effect is rapid, within 60 to 90 seconds. The initial dose is 0.10 to 0.30 mcg/kg/min with dose advancement as needed to achieve the optimal response, generally at 0.50 to 2.00 mcg/kg/min. Upon stopping nitroprusside, its effects are reversed within 10 to 30 minutes. Nitroprusside is cleared by spontaneous breakdown, by vascular clearance, and by release of cyanide. It is somewhat light sensitive, requiring shielded protection during administration.
After initial dosing to offer relief for severe dyspnea, continued nitroprusside administration is most effective and safest with hemodynamic monitoring with an indwelling arterial line and oftentimes a pulmonary artery flow-directed catheter.
Nitroprusside is currently the ultimate pharmacologic preload- and afterload-reducing agent. Nitroprusside reduces left ventricular diastolic pressure, left atrial pressure, pulmonary wedge pressure (pulmonary artery occlusive pressure), right atrial pressure, and pulmonary and systemic vascular resistance.
The resultant afterload-reduction (fall in vascular resistance) invariably results in a rise in cardiac output. In addition to the fall in systemic vascular resistance, some of the drop in left atrial pressure and pulmonary capillary wedge pressure may also be secondary to a reduction in mitral regurgitation and aortic valvular insufficiency. Similarly, a fall in pulmonary vascular resistance and subsequent decrease in tricuspid valvular regurgitation lowers right atrial and right ventricular diastolic pressure.
Individual patients may experience an improvement in renal function as the intense systemic vasoconstriction is relieved, assuming hypotension is avoided.
Indications and contraindications
Nitroprusside is indicated in clinical settings where moderate to severe dyspnea is caused by cardiogenic conditions. These conditions generally revolve around acute heart failure or decompensated chronic heart failure.
Clinical situations causing acute heart failure include, but are not limited to, acute myocardial infarction and the complications of acute infarction (e.g., ruptured myocardium or papillary muscle), acute myocarditis, and acute valvular disruptions (e.g., acute severe mitral regurgitation, acute aortic valvular insufficiency). In these conditions, nitroprusside lowers systemic and pulmonary vascular resistance, left and right ventricular diastolic pressure, and pulmonary capillary wedge pressure; dyspnea is generally improved in a matter of minutes.
Nitroprusside is then continued until a patient’s condition is improved or stabilized, allowing placement of intraaortic balloon counterpulsation, definitive catheter or surgical intervention (e.g., angioplasty-stent deployment, coronary artery bypass surgery, mitral valve replacement), or the insertion of a ventricular assist device. In the author’s experience, failure to achieve the expected pharmacologic responses despite advancing the nitroprusside dose to high levels (>3.0 mcg/kg/min) is a bad prognostic sign.
In decompensated chronic heart failure, nitroprusside can also improve severe dyspnea with pharmacologic mechanisms similar to those described above for acute heart failure. In addition, nitroprusside has been used to select the optimal oral vasodilators and doses (“tailored therapy”) for chronic administration.
Chronic, advanced stages of aortic stenosis can respond favorably to the cautious administration of nitroprusside and thus better prepare these patients for surgical aortic valve replacement. The vasodilating properties of nitroprusside are commonly used by transplant cardiologists to determine the reversibility of elevated pulmonary artery pressure and resistance; bringing the transpulmonic gradient to <15 mmHg and pulmonary arteriolar-vascular resistance to <3 Wood units with nitroprusside portends a better prognosis after cardiac transplant than the failure to achieve these objectives.
Interestingly, nitroprusside has never undergone a blinded, placebo-controlled trial. In the setting of acute heart failure, placebo-control may pose a problem. In decompensated chronic heart failure, comparisons have been made with nitroglycerin (active control) and nitroprusside is uniformly a more powerful vasodilator than IV nitroglycerin.
A prior history of an adverse reaction to nitroprusside, an inadequate left ventricular diastolic filling pressure (<18 mmHg), and prolonged administration in renal dysfunction-failure are the major contraindications to nitroprusside. Because of potential coronary artery steal, caution is recommended when nitroprusside is administered to a patient whose dyspnea is accompanied by unstable angina and high grade occlusive coronary artery disease.
Systemic hypotension is the most common adverse effect. Hypotension can be avoided with frequent blood pressure recordings and monitoring during administration; an indwelling arterial line provides the optimal means of avoiding systemic hypotension.
Flushing is not uncommon. Abrupt discontinuation of the infusion can lead to a detrimental rebound effect, whereby hemodynamics return to a level worse than baseline. Renal failure can occur in the patient in whom nitroprusside caused prolonged hypotension.
A rare patient may experience some systemic desaturation from ventilation-perfusion mismatch secondary to dilatation of arterioles in hypoventilated or nonventilated regions of the lung. In the setting of critical coronary artery stenosis, nitroprusside is capable of causing coronary steal by dilating the arterioles of less involved coronary arteries considerably more than those of the artery with the fixed coronary lesion and the maximally dilated artery-arterioles distal to the lesion. Chronic nitroprusside can lower platelet number and evoke hypothyroidism.
Cyanide-prussic acid and thiocyanate toxicity can occur when high dose nitroprusside (>3.0 mcg/kg/min) is administered for > 72 hours, particularly in the setting of renal dysfunction. Cyanide-prussic acid toxicity can result in a fall in oxygen-carrying capacity and lactic acidosis; thiocyanate can cause nausea, vomiting, weakness, confusion, psychosis, convulsions, and skeletal muscle findings (e.g., spasm, hyperreflexia). Cyanide toxicity has been treated with thiosulfate, sodium nitrate, and hydroxycobalamin. Thiocyanate can be removed with hemodialysis.
IV nitroglycerin and nesiritide also evoke vasodilatation, but to a lesser degree than nitroprusside. In decompensated chronic heart failure, oral vasodilators, diuretics, ACE inhibitors, or angiotensin receptor blockers may also gradually reduce dyspnea and improve hemodynamics.
What's the Evidence?
Leier, CV, Bambach, D, Thompson, MJ, Cattaneo, SM, Goldberg, RJ, Unverferth, DV. ” Central and regional hemodynamic effects of intravenous isosorbide dinitrate, nitroglycerin and nitroprusside in patients with congestive heart failure”. Am J Cardiol. vol. 48. 1981. pp. 1115-23. (The hemodynamic profile of nitroprusside in severe heart failure compared to intravenous nitrates.)
Mann, T, Cohn, PF, Holman, LB. ” Effect of nitroprusside on regional myocardial blood flow in coronary artery disease”. Circulation. vol. 57. 1978. pp. 732-8. (A study showing that nitroprusside may have adverse effects on myocardial perfusion in patients with occlusive coronary disease.)
Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.
No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.
- General (including evidence of efficacy)
- Differences between drugs within the class
- Pharmacologic action
- Indications and contraindications
- Undesirable effects
- Alternative approaches
- What's the Evidence?