For blood pressure control in certain acute hypotensive states (e.g.,pheochromocytomectomy, sympathectomy,poliomyelitis,spinal anesthesia,myocardial infarction,septicemia,blood transfusion,and drug reactions). As an adjunct in the treatment of cardiac arrest and profound hypotension.
Norepinephrine is a direct-acting sympathomimetic which stimulates β1- and α-adrenergic receptors. Its α-agonist effects cause vasoconstriction, thereby raising systolic and diastolic BP with reflex slowing of heart rate.
Diluent: Norepinephrine should be diluted in 5 percent dextrose injection or 5 percent dextrose and sodium chloride injections. These dextrose containing fluids are protection against significant loss of potency due to oxidation. Administration in saline solution alone is not recommended. Whole blood or plasma,if indicated to increase blood volume,should be administered separately (for example,by use of a Y-tube and individual containers if given simultaneously). Average Dosage: Add the content of the vial (4 mg/4 mL) of Norepinephrine to 1,000 mL of a 5 percent dextrose containing solution. Each mL of this dilution contains 4 mcg of the base of Norepinephrine. Give this solution by intravenous infusion. Insert a plastic intravenous catheter through a suitable bore needle well advanced centrally into the vein and securely fixed with adhesive tape,avoiding,if possible,a catheter tie-in technique as this promotes stasis. An IV drip chamber or other suitable metering device is essential to permit an accurate estimation of the rate of flow in drops per minute. After observing the response to an initial dose of 2 mL to 3 mL (from 8 mcg to 12 mcg of base) per minute,adjust the rate of flow to establish and maintain a low normal blood pressure (usually 80 mm Hg to 100 mm Hg systolic) sufficient to maintain the circulation to vital organs. In previously hypertensive patients,it is recommended that the blood pressure should be raised no higher than 40 mm Hg below the preexisting systolic pressure. The average maintenance dose ranges from 0.5 mL to 1 mL per minute (from 2 mcg to 4 mcg of base). High Dosage: Great individual variation occurs in the dose required to attain and maintain an adequate blood pressure. In all cases,dosage of Norepinephrine should be titrated according to the response of the patient. Occasionally much larger or even enormous daily doses (as high as 68 mg base or 17 vials) may be necessary if the patient remains hypotensive,but occult blood volume EN-1544 Page 5 of 5 depletion should always be suspected and corrected when present. Central venous pressure monitoring is usually helpful in detecting and treating this situation. Fluid Intake: The degree of dilution depends on clinical fluid volume requirements. If large volumes of fluid (dextrose) are needed at a flow rate that would involve an excessive dose of the pressor agent per unit of time,a solution more dilute than 4 mcg per mL should be used. On the other hand,when large volumes of fluid are clinically undesirable,a concentration greater than 4 mcg per mL may be necessary. Duration of Therapy: The infusion should be continued until adequate blood pressure and tissue perfusion are maintained without therapy. Infusions of Norepinephrine should be reduced gradually, avoiding abrupt withdrawal. In some of the reported cases of vascular collapse due to acute myocardial infarction,treatment was required for up to six days.
Cyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of intravenously administered epinephrine or norepinephrine. Hence, the use of Norepinephrine during cyclopropane and halothane anesthesia is generally considered contraindicated because of the risk of producing ventricular tachycardia or fibrillation. The same type of cardiac arrhythmias may result from the use of Norepinephrine in patients with profound hypoxia or hypercarbia. Norepinephrine should be used with extreme caution in patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types, because severe, prolonged hypertension may result.
Norepinephrine should not be given to patients who are hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed. If Norepinephrine is continuously administered to maintain blood pressure in the absence of blood volume replacement,the following may occur: severe peripheral and visceral vasoconstriction,decreased renal perfusion and urine output,poor systemic blood flow despite ?normal? blood pressure,tissue hypoxia,and lactate acidosis. Norepinephrine should also not be given to patients with mesenteric or peripheral vascular thrombosis (because of the risk of increasing ischemia and extending the area of infarction) unless, in the opinion of the attending physician,the administration of Norepinephrine is necessary as a lifesaving procedure. Cyclopropane and halothane anesthetics increase cardiac autonomic irritability and therefore seem to sensitize the myocardium to the action of intravenously administered epinephrine or norepinephrine. Hence,the use of Norepinephrine during cyclopropane and halothane anesthesia is generally considered contraindicated because of the risk of producing ventricular tachycardia or fibrillation. The same type of cardiac arrhythmias may result from the use of Norepinephrine in patients with profound hypoxia or hypercarbia. Norepinephrine should be used with extreme caution in patients receiving monoamine
Body As A Whole: Ischemic injury due to potent vasoconstrictor action and tissue hypoxia. Cardiovascular System: Bradycardia,probably as a reflex result of a rise in blood pressure, arrhythmias. Nervous System: Anxiety,transient headache. Respiratory System: Respiratory difficulty. Skin and Appendages: Extravasation necrosis at injection site.
Pregnancy Category C: Animal reproduction studies have not been conducted with Norepinephrine. It is also not known whether Norepinephrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Norepinephrine should be given to a pregnant woman only if clearly needed. Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk,caution should be exercised when Norepinephrine is administered to a nursing woman.
Overdosage with Norepinephrine may result in headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance, and decreased cardiac output. In case of accidental overdosage, as evidenced by excessive blood pressure elevation, discontinue Norepinephrine until the condition of the patient stabilizes.
Store at a temperature not exceeding 30°C in a dry place. Protect from light.
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