Heart failure and hypertensive crises are treated with nitroprusside (Nitropress), a powerful, fast-acting vasodilator.

Nitroprusside (Nitropress) Uses:

• Acute decompensated heart failure (HF):

  • It is used in acute decompensated HF management.

• Acute hypertension:

  • Management of hypertension crisis. 
  • Used to treat hypotension during surgery to lessen bleeding.

• Off Label Use of Nitroprusside in Adults:

  • Acute ischemic stroke during hypertension 

Nitroprusside (Nitropress) Dose in Adults

Nitroprusside (Nitropress) Dose in the treatment of Acute hypertension:

• Initial:
  • 0.3-0.5 mcg/kg/min.
  • To obtain the optimal hemodynamic impact, the dose may be adjusted by 0.5 mcg/kg/min every few minutes.
• Max dose:
  • 10 mcg/kg/min (for a max of 10 mins).
  • Some recommend a max dose of 2 mcg/kg/min to avoid toxicity.

Nitroprusside (Nitropress) treatment for acute decompensated heart failure:

• IV:
• Initial:
  • 5-10 mcg/min.
  • Rapid dosage adjustments (up to every 5 minutes) are possible to produce the desired hemodynamic impact 
  • The typical dosage range is 5-300 mcg/min.
  • Due to the negligible extra benefit & elevated risk for thiocyanate poisoning, doses beyond 400 mcg/min are not advised.

Nitroprusside (Nitropress) Dose in Childrens

Nitroprusside (Nitropress) Dose in the treatment of Acute Hypertension including hypertensive crisis:

• Continuous IV infusion:

  • Initial:
    • 0.3-0.5 mcg/kg/min, titrate every 5 mins to desired effect.
  • Usual dose:
    • 3-4 mcg/kg/min.
  • Max dose:
    • 10 mcg/kg/min (Chandar 2012; Hegenbarth 2008; NHBPEP 2004; Park 2014).
    • Increased cyanide concentrations are associated with increased infusion rates.
    • Children with postoperative cardiac surgery rates below 1.8 mcg/kg/min had higher cyanide amounts, according to a study.
    • Analyze cyanide levels after prolonged use (e.g., more than 72 hours).

Nitroprusside (Nitropress) Dose in the treatment of Cardiac output maintenance/ stabilization, post-resuscitation:

• Infants, Children, and Adolescents:

  • Continuous IV infusion:
  •  Initial:
    • 0.5-1 mcg/kg/min, titrate to desired effect.
  • Max dose:
    • 8 mcg/kg/min.

Pregnancy Risk Factor C

• Nitroprusside can pass the placental barrier and result in foetal cyanide levels that are dose related to maternal nitroprusside,  according to animal studies.
• However, the available data on pregnant use is scant.

Nitroprusside use during breastfeeding:

• It is unknown if breast milk contains nitroprusside.
• Choosing whether to quit breastfeeding or stop taking the medication is crucial.
• Due to the likelihood of the baby experiencing major adverse responses, this decision must take the mother's treatment into account.

Dose in Kidney Disease:

• Thiocyanate can accumulate in persons with impaired kidney function, which can then cause toxicity.
• limit use.
• eGFR <30 mL/min/1.73 m :
  • Limit mean infusion rate to <3 mcg/kg/min.
• Anuric patients:
  • Limit mean infusion rate to 1 mcg/kg/min.

Dose in Liver disease:

• In manufacturer's labeling, no dosage adjustment provided.
• Due to the risk of cyanide toxicity, use cautiously.

Side effects of Nitroprusside (Nitropress):

• Cardiovascular:

  • Bradycardia
  • Tachycardia
  • Severe Hypotension
  • ECG Changes
  • Palpitations
  • Substernal Pain
  • Flushing

• Central Nervous System:

  • Apprehension
  • Restlessness
  • Headache
  • Increased Intracranial Pressure
  • Dizziness

• Dermatologic:

  • Diaphoresis
  • Skin Rash
  • Localized Erythematous Streaking

• Endocrine & Metabolic:

  • Hypothyroidism

• Gastrointestinal:

  • Abdominal Pain
  • Retching
  • Nausea
  • Intestinal Obstruction

• Hematologic & Oncologic:

  • Decreased Platelet Aggregation
  • Methemoglobinemia

• Local:

  • Irritation At Injection Site

• Neuromuscular & Skeletal:

  • Muscle Twitching

Contraindications to Nitroprusside (Nitropress):

• Compensatory hypertension treatment (aortic comarctation, arteriovenous Shunting)
• (A.S.A. Class 5E is essential for emergency surgery) To induce controlled
• Hypotension during surgery in individuals with insufficient cerebral circulation.
• Acute heart failure brought on by a decrease in systemic blood pressure 
• Amblyopia brought on by smoke or congenital optic atrophy (Leber's).
• Concurrently taking sildenafil with vardenafil or tadalafil

Canadian labeling:

• Additional contraindications (not in US labeling).
  • Hypersensitivity to any ingredient in the mix, including nitroprusside
  • Anemia and hypovolemia that are not being addressed.
  • Hepatic disease.
  • Grave renal disease.
  • Vitamin B deficiency can lead to certain diseases

Warnings and precautions

• Cyanide toxicity:

  • [US Boxed Warning]

  • Nitroprusside can produce large amounts of cyanide, even if it is used sparingly or at very low rates (2 mg/kg/min).
  • Don't take the maximum dose for longer than 10 minutes.
  • Discontinue infusion if blood pressure does not stabilise at the maximum rate (10 mcg/kg/min).
  • Analyze the acid-base balance, venous oxygen concentration and to determine if cyanide toxicity is present.
  • Clinicians need to be aware that cyanide poisoning may not always be indicated by these symptoms.
  • Malnourished people and people with liver problems are among the patients who are most at risk for cyanide poisoning.
  • If you have any cyanide poisoning symptoms or indications, such as metabolic acidosis, low oxygen saturation, or bradycardia, stop using nitroprusside.
  • Even though it is not a common practice, sodium thiosulfate can be administered with nitroprusside in a 10 to 1 ratio.
  • This is used when longer periods of time requiring larger nitroprusside dosages (4 10 mcg/kg/minute) are necessary to  prevent cyanide poisoning.
  • Thiocyanate toxicities may still be possible with this approach.
  • If nitroprusside is unable to control your blood pressure, you should think about additional medications like clevidipine or labetalol.

• Hypotension

  • [US Boxed Warning]

  • Vital organ perfusion may be compromised as a result of hypotension.
  • Continuous blood pressure checks must be done by trained staff.

• Increased intracranial pressure

  • Use may cause an increase in intracranial pressure.
  • Patients who have increased intracranial pressure need to be handled carefully.

• Methemoglobinemia:

  • The dose-dependent conversion of hemoglobin into methemoglobin can be caused by nitroprusside
  • Patients receiving more than 10 mg/kg of nitroprusside should be investigated for methemoglobinemia if they exhibit indications of  decreased oxygen supply despite having a sufficient cardiac output.
  • Patients should receive methylene blue treatment regardless of the level of methemoglobin present (first line).
  • Treatment is advised if the level is more than 30%, even if there are no symptoms.
  • However, treatment is indicated if the patient cannot tolerate reductions in oxygen carrying capacity of 10% or more  due to a previous condition such coronary artery disease.

• Toxicity to Thiocyanate

  • This can happen in patients with kidney impairment and those who receive extended infusions (ie >3 mg/kg/min for >72hrs).

• Anemia:

  • Pre-existing anemia should be corrected before using nitroprusside. This is to prevent hypotension from occurring during surgery.

• Hepatic impairment

  • Patients with severe hepatic impairment should be cautious.

• Hypovolemia:

  • • Pre-existing hypovolemia should be corrected before nitroprusside can be used to control hypotension.

• Myocardial Infarction

  • Acute myocardial damage patients should exercise caution because to probable coronary theft and hemodynamic complications.

• Renal impairment

  • In individuals with compromised renal function, exercise extreme caution.
  • Choose the lowest possible dosage.
  • Pay attention to the concentrations of thiocyanate.

Nitroprusside: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Arterial blood pressure and heart rate (a cardiac monitor and blood pressure monitor are necessary) 
• Check for toxicity from cyanide and thiocyanate.
• Check the oxygen saturation in the veins.
• Analyze your acid-base balance because acidosis may be the first indication of cyanide exposure.
• If the patient has renal impairment or needs a long-term infusion (more than three days), the levels of thiocyanate should be checked.
• In patients with impaired hepatic function, check the blood levels of cyanide (if available with a sufficient turnaround time). 
• Consult the specific institutional regulations & procedures.

How to administer Nitroprusside (Nitropress)?

IV:

• IV infusion only.
• An infusion pump needed.
• Due to the risk of severe hypotension, keep an eye on the patient's blood pressure throughout treatment.
• Even during administration, products should always be protected from light.

Mechanism of action of Nitroprusside (Nitropress):

• By directly affecting the venous and arteriolar smooth muscles
• It causes peripheral vasodilation to lower peripheral resistance.
• By doing so, afterload will drop and cardiac output will rise.
• Reduces left ventricular and aortal impedance

Onset of action:

• Hypotensive effect:
• <2 mins

Duration:

• Hypotensive effect:
• 1-10 mins

Metabolism:

• To produce cyanide and cyanmethemoglobin, combine Nitroprusside with hemoglobin.
• Through the conversion of cyanide to thiocyanate, which is mediated by rhodanase, cyanide is detoxified.
• Rhodanase joins sulphur groups from a sulphur donor to cyanide molecules (eg, thiosulfate, cystine, cysteine).
• Once the supply of sulphur donors is depleted, this mechanism may be overwhelmed by large exposures and become hazardous due to its  limited capacity.

Half-life elimination:

• Nitroprusside, circulatory:
• ~2 mins.
• Thiocyanate, elimination:
• ~3 days (may be doubled or tripled in renal failure)

Excretion:

• Urine (as thiocyanate)

International Brands of Nitroprusside (Nitropress):

• Nipride RTU
• Nitropress
• Doketrol
• Naniprus
• Nipride
• Niprusodio
• Nipruss
• Nitan
• Nitriate
• Nitrocef
• Nitroprus
• Nitroprusiato de sodio
• Nitroprusiato de sodio-ecar
• Nitroprussiat Fides
• Sodio Nitroprussiato
• Sodium Nitroprusside
• Sodium Nitroprusside BP
• Sonide

Nitroprusside Brand Names in Pakistan:

No Brands Available in Pakistan.