Nitroprusside Sodium
**Nitroprusside sodium** is a highly potent, ultra-short-acting **mixed vasodilator** used exclusively in intensive care settings. Key clinical highlights: * **Primary Indications**: Management of hypertensive crises, acute heart failure secondary to severe mitral regurgitation, and refractory congestive heart failure (CHF). * **Hemodynamic Effects**: Rapidly reduces both preload and afterload by relaxing arterial and venous smooth muscle. * **Clinical Pearl**: Because of its profound hypotensive effects and ultra-short half-life, it must be administered as a Constant Rate Infusion (CRI) with **continuous direct arterial blood pressure monitoring**. * **Toxicity Risk**: Prolonged use (>48-72 hours) or high doses can lead to accumulation of toxic metabolites (cyanide and thiocyanate), especially in patients with renal or hepatic impairment.
Mecanismo: Nitroprusside acts as a **nitric oxide (NO) donor**. * Once in the bloodstream, it interacts with tissue sulfhydryl groups to release NO. * NO activates the enzyme **soluble guanylate cyclase** in vascular smooth muscle cells. * This leads to an increase in intracellular **cyclic guanosine monophosphate (cGMP)**. * Elevated cGMP activates protein kinase G, which reduces intracellular calcium concentrations → **vascular smooth muscle relaxation**. This mechanism causes direct peripheral vasodilation of both arterioles and venules (independent of autonomic innervation), resulting in: * Lowered blood pressure * Significant reduction in total peripheral resistance (afterload) * Reduced left ventricular end-diastolic pressure (preload) * Mild decrease in cardiac output (though in severe heart failure, CO may actually increase due to afterload reduction) * Reflex tachycardia (increase in heart rate)
Dosificación por especie
- Hypertensive crisis (systolic arterial BP >200 mm Hg) · Initiate dose at 0.5 micrograms/kg/minute; increase dosage incrementally every 3-5 minutes until a predetermined target BP is attained. Reduce BP 25% over 4-hour period to allow readaptation of cerebral blood vessels. · IV · CRI · Titrate to effect
- Adjunctive treatment of heart failure (cardiogenic shock; fulminant pulmonary edema) · Initiate dose at 0.5 micrograms/kg/minute; increase dosage incrementally every 3-5 minutes. Goal to decrease or maintain mean arterial pressure to support vital organ functions-approx. 70 mmHg. · IV · CRI · Titrate to effect · Concurrent use of dobutamine (1-5 micrograms/kg/min) often indicated.
- Adjunctive treatment of heart failure · Initiate dose at 0.5 micrograms/kg/minute constant rate infusion and increase by 0.5-1 microgram/minute every 5 minutes to desired systolic pressure (90-100 mmHg). · IV · CRI · Titrate to effect · Cats are more sensitive to oxidative damage; keep total dosages to a minimum. Use dedicated line; never flush.
- Catastrophic pulmonary edema · As a CRI initiated at 1 microgram/kg/min and carefully titrated to effect by increasing by 1 microgram/kg/min increments every 15 minutes as long as BP remains stable and until perfusion and pulmonary function improves (cats usually requires between 1-2 micrograms/kg/min with the upper limit being 2 micrograms/kg/min). · IV · CRI · Maintain most effective dose for 12-15 hours · Systolic BP must remain >90 mm Hg. Wean nitroprusside over 6 hours first, then dobutamine over 6 hours.
- Hypertensive crisis (systolic arterial BP >200 mm Hg) · Initiate dose at 1-2 micrograms/kg/minute; increase dosage incrementally every 3-5 minutes until a predetermined target BP is attained. Reduce BP 25% over 4-hour period to allow readaptation of cerebral blood vessels. · IV · CRI · Titrate to effect
Vías de administración
Contraindicaciones
- Compensatory hypertension (e.g., AV shunts, coarctation of the aorta, Cushing's reflex)
- Inadequate cerebral circulation
- Emergency surgery in patients near death
Efectos adversos
- Profound hypotension
- Nausea
- Retching
- Restlessness
- Apprehension
- Muscle twitching
- Dizziness
- Infusion site irritation (avoid extravasation)
- Thiocyanate and cyanide toxicity (with prolonged use)
Interacciones farmacológicas
- General Anesthetics (e.g., halothane, enflurane) · May enhance the hypotensive effects of nitroprusside.
- Dobutamine · Synergistic effects (increased cardiac output and reduced wedge pressure) may result; often used together beneficially in severe heart failure.
- Other Hypotensive Agents (e.g., beta-blockers, ACE inhibitors) · Patients may be more sensitive to the hypotensive effects of nitroprusside.
Monitoreo
- Blood pressure (constant, direct arterial monitoring preferred)
- Acid/base balance (to detect early metabolic acidosis/cyanide toxicity)
- Electrolytes (especially Na+)
- Respiratory effort and thoracic auscultation
- Serum thiocyanate levels (if on prolonged therapy or concurrent renal dysfunction)
Sobredosis
**Acute Overdosage**: Manifests as profound hypotension. * **Treatment**: Reduce or stop the infusion and administer IV fluids. Blood pressure will typically recover within 1-10 minutes. Monitor BP constantly. **Toxicity (Cyanide/Thiocyanate)**: Excessive doses, prolonged therapy (>3 days), depleted hepatic thiosulfate, or severe hepatic/renal insufficiency may lead to cyanogen or thiocyanate toxicity. * **Signs**: Metabolic acidosis (early sign of cyanogen toxicity), tolerance to therapy, delirium (thiocyanate toxicity in dogs). * **Monitoring**: Monitor acid/base status. Serum thiocyanate levels >100 mcg/mL are considered toxic. * **Treatment**: Hydroxocobalamin (Vitamin B12a) may prevent or treat cyanogen toxicity. Contact an animal poison control center for specific antidotal protocols if suspected.
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