Index
Medication is indicated for immediate blood pressure reduction in adult and pediatric patients in hypertensive crisis.
A concomitant long-acting antihypertensive medication should be administered so that the duration of treatment with nitroprusside can be minimized.
Nitroprusside is also indicated to produce controlled hypotension to reduce bleeding during surgery and is also used to treat acute congestive heart failure.
Dosage and administration
Proper dilution: Depending on the desired concentration, the solution containing 50 mg of nitroprusside should be further diluted in 250-1000 ml of 5% sterile dextrose injection.
The diluted solution should be protected from light using the supplied opaque sleeve, aluminum foil, or other opaque material. It is not necessary to cover the drip chamber of the infusion or the tubing.
Verification of the chemical integrity of the product: The nitroprusside solution can be inactivated by reactions with contaminants. The effects of these reactions are often blue, green, or red, much brighter than the light brown color of unreacted nitroprusside.
Discolored solutions, or solutions in which particulate matter is visible, should not be used. If adequately protected from light, the freshly diluted solution is stable for 24 hours.
Other medicines should not be administered in the same solution as nitroprusside.
Avoid excessive hypotension: Although the average effective rate in adult and pediatric patients is approximately three mcg/kg/min, some patients become dangerously hypotensive when they receive nitroprusside at this rate.
Therefore, nitroprusside infusion should be initiated at a meager rate (0.3 mcg/kg/min), with titration ascending every few minutes to reach the desired effect or the maximum recommended infusion rate (10 mcg/kg/min) reached.
Because the hypotensive effect of nitroprusside is very rapid at onset and dissipation, slight variations in the infusion rate can lead to broad and undesirable variations in blood pressure.
Since there is an inherent variation in blood pressure measurement, confirm the drug’s effect at any infusion rate after an additional 5 minutes before adjusting the dose to a higher amount to achieve the desired blood pressure.
The nitroprusside should not be infused through an ordinary intravenous device, regulated only by gravimetry and mechanical clamps. Only one infusion pump, preferably a volumetric pump, should be used.
Because nitroprusside can induce an essentially unlimited reduction in blood pressure, the blood pressure of a patient receiving this drug must be continuously monitored.
They are using a continuously inflated sphygmomanometer or (preferably) an intraarterial pressure sensor. Particular caution should be exercised in elderly patients, as they may be more sensitive to the hypotensive effects of the drug.
When nitroprusside is used to treat acute congestive heart failure, the titration of infusion rate should be guided by invasive hemodynamic monitoring with simultaneous monitoring of urine output.
The nitroprusside can be assessed by increasing the rate of infusion until:
- The measured cardiac output no longer increases.
- Systemic blood pressure can not be reduced further without compromising the perfusion of vital organs.
- The recommended maximum infusion rate has been reached, whichever comes first.
Specific hemodynamic targets should be adapted to the clinical situation. Still, improvements in cardiac output and left ventricular filling pressure should not be purchased at the price of excessive hypotension and consequent hypoperfusion.
How to supply it
The nitroprusside is supplied in Fliptop flasks of 50 mg / 2 ml of a single dose of amber.
Store between 20 and 25 ° C (68 to 77 ° F).
To protect the nitroprusside from light, it must be stored in its cardboard box until it is used.
Side effects
The most significant adverse reactions to nitroprusside are excessive hypotension and cyanide toxicity. The adverse reactions described in this section develop less quickly and, as it happens, are less frequent.
Methemoglobinemia: Nitroprusside infusions can cause problems in hemoglobin, such as methemoglobin.
The conversion process is usually rapid, and clinically significant methemoglobinemia (<10%) is rarely seen in nitroprusside patients.
Methemoglobin levels can be measured in most clinical laboratories.
The diagnosis should be suspected in patients who have received <10 mg/kg of nitroprusside and show signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2.
Classically, blood with methemoglobinemia is described as chocolate brown, with no change in color when exposed to air.
When methemoglobinemia is diagnosed, the treatment of choice is 1-2 mg/kg methylene blue, administered intravenously for several minutes.
In patients likely to have substantial amounts of cyanide bound to methemoglobin, such as cyanomethaemoglobin, the treatment of methemoglobinemia with methylene blue should be done with extreme caution.
Toxicity of thiocyanate: Most of the cyanide produced during nitroprusside metabolism is eliminated in the form of thiocyanate. When co-fusing thiosulfate, thiocyanate production increases and accelerate cyanide removal.
Thiocyanate is mildly neurotoxic (tinnitus, miosis, hyperreflexia) at serum levels of 1 mmol / L (60 mg / L). The toxicity of thiocyanate is potentially fatal when the groups are 3 or 4 times higher (200 mg / L).
The level of thiocyanate in a steady state after prolonged infusions of nitroprusside increases with a higher rate of information, and the average time of accumulation is 3-4 days.
To maintain the thiocyanate level at a steady-state below one mmol / L, a prolonged nitroprusside infusion should not be faster than three mcg/kg/min; in anuric patients, the corresponding limit is only one mcg/kg/min.
Thiocyanate levels should be measured daily when prolonged infusions are faster than these.
Physiological maneuvers (for example, those that alter urine pH) do not increase the elimination of thiocyanate. The clearance rates of thiocyanate during dialysis, on the other hand, may approximate the blood flow rate of the dialyzer.
Thiocyanate interferes with the uptake of iodine by the thyroid.
Abdominal pain, apprehension, diaphoresis, “dizziness,” headache, muscle spasms, nausea, palpitations, restlessness, nausea, and retrosternal discomfort have been observed when blood pressure dropped too quickly.
These symptoms quickly disappeared when the infusion slowed or stopped and did not reappear with slower (continued) information.
Other adverse reactions reported are:
Cardiovascular: bradycardia, electrocardiographic changes, tachycardia.
Dermatological: rashes.
Endocrine: hypothyroidism.
Gastrointestinal: ileum.
Hematologic: decreased platelet aggregation.
Neurological: increased intracranial pressure.
Miscellaneous: redness, vein streaks, irritation at the infusion site.
Drug interactions
The hypotensive effect of nitroprusside is increased by most other hypotensive drugs, including ganglionic blockers, damaging inotropic agents, and inhaled anesthetics.
Warnings
The principal risks of nitroprusside administration are excessive hypotension and excessive cyanide buildup.
Excessive hypotension: Small transient excesses in the rate of nitroprusside infusion can lead to excessive hypotension, sometimes at low levels that compromise the perfusion of vital organs.
These hemodynamic changes can lead to a variety of associated symptoms. Hypotension induced by nitroprusside will be self-limiting within 1-10 minutes after the interruption of the nitroprusside infusion.
During these few minutes, it may be helpful to place the patient in a head-down position to maximize venous return. If the hypotension persists more than a few minutes after the interruption of the nitroprusside infusion, then the nitroprusside is not the cause, and the actual cause must be sought.
Toxicity of cyanide: Infusions of nitroprusside at speeds above two mcg/kg/min generate cyanide ions (CN¯) faster than the body can generally eliminate.
When sodium thiosulfate is administered, the body’s ability to eliminate CN increases considerably.
The methemoglobin ordinarily present in the body can buffer a certain amount of CN¯, but the capacity of this system is exhausted.
This amount of nitroprusside is given in less than one hour when the medication is administered at ten mcg/kg/min (the maximum recommended rate). After that, the toxic effects of CN¯ can be rapid, severe, and even lethal.
The actual rates of clinically significant cyanide toxicity can not be assessed from spontaneous reports or published data.
Most patients who reported experiencing such toxicity received relatively long infusions.
The only patients whose deaths have been unequivocally attributed to cyanide toxicity induced by nitroprusside have been patients who received nitroprusside infusions at rates (30-120 mcg/kg/min) much higher than those now recommended.
However, sometimes elevated levels of cyanide, metabolic acidosis, and marked clinical deterioration have been reported in patients who received infusions at the recommended rates for only a few hours and, in one case, for only 35 minutes.
In some of these cases, the infusion of sodium thiosulfate caused a dramatic clinical improvement, supporting the diagnosis of cyanide toxicity.
Cyanide toxicity can manifest as venous hyperoxemia with bright red venous blood. The cells can not extract the oxygen supplied to them; metabolic acidosis (lactic acid); lack of air; confusion; and death.
Cyanide toxicity due to causes other than nitroprusside has been associated with angina pectoris and myocardial infarction, ataxia, seizures and stroke, and further diffuse ischemic damage.
Hypertensive patients and patients receiving concomitant antihypertensive medications may be more sensitive to the effects of nitroprusside than normal subjects.
Nitroprusside precautions
General: Like other vasodilators, it can cause increases in intracranial pressure. In patients whose intracranial pressure is already high, nitroprusside should be used only with extreme caution.
Hepatic: Exercise caution when administering nitroprusside to patients with hepatic impairment.
Use in anesthesia: When nitroprusside (or any other vasodilator) is used for controlled hypotension during anesthesia, the patient’s ability to compensate for anemia and hypovolemia may be diminished.
If possible, pre-existing anemia and hypovolaemia should be corrected before nitroprusside administration.
Hypotensive anesthetic techniques can also cause abnormalities in the pulmonary ventilation/perfusion relationship. Patients who can not tolerate these abnormalities may need a more significant fraction of inspired oxygen.
Extreme caution should be exercised in patients with especially low surgical risks.
Laboratory tests: The cyanide level test is technically tricky, and the levels of cyanide in bodily fluids other than red cell concentrates are difficult to interpret.
Cyanide toxicity will lead to lactic acidosis and venous hyperoxemia. Still, these findings may not be present for up to an hour or more after the cyanide capacity of the body’s red blood cell mass has been depleted.
Carcinogenesis, mutagenesis, and impaired fertility: No studies have been conducted in animals that evaluate the carcinogenicity and mutagenicity of nitroprusside. Similarly, nitroprusside has not been tested to determine the effects on fertility.
Pregnancy: There are no adequate and well-controlled studies of nitroprusside in laboratory animals or pregnant women. It is not known if nitroprusside can cause harm to the fetus when it is given to a pregnant woman or if it can affect reproductive capacity.
Nitroprusside should be given to a pregnant woman only if it is essential.
In three studies on pregnant sheep, nitroprusside was shown to cross the placental barrier. It was demonstrated that fetal cyanide levels are dose-related at the maternal levels of nitroprusside.
The metabolic transformation of sodium nitroprusside administered to pregnant sheep caused fatal levels of cyanide in fetuses. The infusion of 25 mcg/kg/min of nitroprusside for one hour in pregnant sheep resulted in the death of all fetuses.
Pregnant sheep infused with one mcg/kg/min of nitroprusside for one hour had normal lambs.
One researcher said a pregnant woman at 24 weeks of gestation was given nitroprusside to control gestational hypertension secondary to mitral valve disease.
Nitroprusside was infused at 3.9 mcg/kg/min for 3.5 mg/kg for 15 hours before the birth of a stillborn baby of 478 grams without any apparent abnormalities.
The levels of cyanide in the fetal liver were less than ten mcg/ml. It has been reported that toxic levels are more than 30-40 mcg / mL. The mother did not demonstrate cyanide toxicity.
The effects of the administration of sodium thiosulfate in pregnancy, alone or as a joint infusion with nitroprusside, are entirely unknown.
Nursing mothers: It is unknown whether nitroprusside and its metabolites are excreted in human milk.
Because many drugs are excreted in human milk, and due to the possibility of severe adverse reactions in infants by nitroprusside, the decision should be made to discontinue breastfeeding or discontinue the medication, taking into account the importance of the drug to the mother.
Pediatric use: The efficacy in the pediatric population was established based on trials in adults and supported by the dose range trial (Study 1) and an open infusion trial of at least 12 hours at a rate that achieved adequate MAP control (Study 2) with pediatric patients on nitroprusside.
No new safety issues were seen in these studies in pediatric patients.
Nitroprusside overdose
Overdose may manifest as excessive hypotension, cyanide toxicity, or thiocyanate toxicity.
The acute mean intravenous lethal doses of nitroprusside in rabbits, dogs, mice, and rats are 2.8, 5.0, 8.4, and 11.2 mg/kg, respectively.
Treatment of cyanide toxicity: many laboratories can measure cyanide levels, and blood-gas studies that can detect venous hyperoxemia or acidosis are widely available.
Acidosis may not appear for more than an hour after the appearance of dangerous levels of cyanide, and laboratory tests should not be expected. The reasonable suspicion of cyanide toxicity is sufficient reason to initiate the treatment.
The treatment of cyanide toxicity consists of:
- Suspend the administration of nitroprusside.
- Using sodium nitrite to convert as much hemoglobin into methemoglobin as the patient can safely tolerate.
- Infusion of sodium thiosulfate in sufficient quantity to convert the cyanide into thiocyanate.
The drugs needed for this treatment are found in commercially available cyanide antidote kits.
Hemodialysis is ineffective in removing cyanide, but it will eliminate most thiocyanate.
Cyanide antidote kits contain amyl nitrite and sodium nitrite to induce methemoglobinemia.
Amyl nitrite is supplied in inhalant ampoules for administration in environments where intravenous administration of sodium nitrite may be delayed.
In a patient who already has a patent intravenous line, the use of amyl nitrite does not confer any benefit that is not provided by the infusion of sodium nitrite.
Sodium nitrite is available in a 3% solution, and should be injected from 4 to 6 mg / kg (approximately 0.2 ml / kg) for 2-4 minutes.
This dose can convert approximately 10% of the patient’s hemoglobin to methemoglobin; This level of methemoglobinemia is not associated with any significant self-hazard.
Infusion of nitrite can cause transient vasodilatation and hypotension, and this hypotension should be routinely administered.
Sodium thiosulfate should be infused immediately after the infusion of sodium nitrite.
This agent is available in 10% and 25% solutions, and the recommended dose is 150-200 mg/kg; A typical amount for adults is 50 ml of the 25% solution.
Thiosulfate treatment of a patient with acute cyanide toxicity will increase thiocyanate levels, but not to a dangerous degree.
After two hours, the nitrite/thiosulfate regimen can be repeated at half the initial doses.
Contraindications
Nitroprusside should not be used to treat compensatory hypertension, where the primary hemodynamic lesion is aortic coarctation or arteriovenous shunt.
Nitroprusside should not be used to produce hypotension during surgery in patients with known inadequate cerebral circulation or in dying patients who attend emergency surgery.
Patients with congenital or amblyopic optic atrophy have unusually high cyanide/thiocyanate ratios.
These rare conditions are likely associated with defective or absent thiamine, and these patients should avoid nitroprusside.
Nitroprusside should not be used to treat acute congestive heart failure associated with reduced peripheral vascular resistance, such as high-output heart failure seen in endotoxic sepsis.
Clinical pharmacology
The principal pharmacological action of nitroprusside is the relaxation of vascular smooth muscle and the consequent dilation of peripheral arteries and veins.
Other smooth muscles (for example, uterine and duodenum) are not affected. Nitroprusside is more active in veins than in arteries, but this selectivity is much less marked than nitroglycerin.
Dilation of the veins promotes peripheral blood accumulation. It decreases venous return to the heart, which reduces the final diastolic pressure of the left ventricle and the pressure of the pulmonary capillary wedge.
Arteriolar relaxation reduces systemic vascular resistance, systolic blood pressure, and mean arterial pressure. Dilation of the coronary arteries also occurs.
In association with the decrease in blood pressure, nitroprusside administered intravenously to hypertensive and normotensive patients produces a slight increase in heart rate and a variable effect on cardiac output.
In hypertensive patients, moderate doses induce renal vasodilatation approximately proportional to the decrease in systemic blood pressure, so there is no appreciable change in renal blood flow or glomerular filtration rate.
In normotensive subjects, acute reduction in mean arterial blood pressure to 60-75 mm Hg by infusion of nitroprusside caused a significant increase in renin activity.
In the same study, ten renovascular hypertensive patients who received nitroprusside had significant increases in renin release from the affected kidney at mean arterial pressures of 90-137 mm Hg.
The hypotensive effect of nitroprusside is observed within a minute or two after the start of an adequate infusion and dissipates almost as quickly after an injection is interrupted.
