For the management of blood pressure in selected acute hypotensive conditions such as pheochromocytomectomy, sympathectomy, poliomyelitis, spinal anesthesia, myocardial infarction, septicemia, blood transfusion reactions, and drug-induced reactions. It is also used as an adjunct in the treatment of cardiac arrest and severe hypotension.

Norepinephrine is a direct-acting sympathomimetic agent that stimulates both α- and β1-adrenergic receptors. Its α-adrenergic activity causes peripheral vasoconstriction, which increases systolic and diastolic blood pressure and may lead to reflex slowing of the heart rate.

An infusion of Norepinephrine should be given into a large vein. Restoration of Blood Pressure in Acute Hypotensive States. Blood volume depletion should always be corrected as fully as possible before any vasopressor is administered. When, as an emergency measure, intraaortic pressures must be maintained to prevent cerebral or coronary artery ischemia, Norepinephrine can be administered before and concurrently with blood volume replacement.

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 ampoule (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: 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 ampoules) may be necessary if the patient remains hypotensive, but occult blood volume 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.

Adjunctive Treatment in Cardiac Arrest: Infusions of Norepinephrine are usually administered intravenously during cardiac resuscitation to restore and maintain an adequate blood pressure after an effective heartbeat and ventilation have been established by other means. Norepinephrine powerful beta-adrenergic stimulating action is also thought to increase the strength and effectiveness of systolic contractions once they occur.

Average Dosage: To maintain systemic blood pressure during the management of cardiac arrest, Norepinephrine is used in the same manner as described under Restoration of Blood Pressure in Acute Hypotensive States. Do not use the solution if its color is pinkish or darker than slightly yellow or if it contains a precipitate. Avoid contact with iron salts, alkalis, or oxidizing agents.

Cyclopropane and halothane anesthesia increase cardiac excitability and may sensitize the heart to the effects of intravenously administered epinephrine or norepinephrine. Therefore, the use of norepinephrine during these anesthetics is generally contraindicated due to the risk of ventricular tachycardia or fibrillation. Similar arrhythmias may also occur in patients with severe hypoxia or hypercarbia. Extreme caution is required when norepinephrine is used in patients receiving monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants such as amitriptyline or imipramine, as it may cause severe and prolonged hypertension.

Norepinephrine should not be used in patients with hypotension due to low blood volume unless as an emergency measure to maintain coronary and cerebral perfusion until volume replacement is completed. Prolonged use without correcting blood volume may lead to severe vasoconstriction, reduced kidney perfusion, low urine output, tissue hypoxia, and lactic acidosis despite normal blood pressure. It is also contraindicated in patients with mesenteric or peripheral vascular thrombosis due to the risk of worsening ischemia and expanding infarction, unless life-saving use is required. Use during cyclopropane or halothane anesthesia is contraindicated due to risk of life-threatening arrhythmias. Severe hypoxia or hypercarbia also increases this risk.

General: Tissue ischemia due to strong vasoconstriction and reduced oxygen supply.

Cardiovascular: Reflex bradycardia, arrhythmias.

Nervous system: Anxiety, temporary headache.

Respiratory: Breathing difficulty.

Skin: Local tissue necrosis at injection site due to extravasation. Prolonged use may reduce plasma volume, requiring fluid and electrolyte correction. If not corrected, hypotension may recur after discontinuation or cause poor tissue perfusion, hypoxia, and lactic acidosis. Rarely, gangrene of extremities may occur. Overdose or sensitivity (e.g., hyperthyroidism) may cause severe hypertension, headache, light sensitivity, chest pain, sweating, vomiting, and pallor.

Pregnancy Category C. Animal studies have not been performed, and its safety in pregnancy is not established. It is unknown whether norepinephrine can harm the fetus or affect reproductive capacity; therefore, it should only be used during pregnancy if clearly necessary. It is also unknown whether the drug passes into breast milk. Since many drugs are excreted in human milk, caution is advised when administering norepinephrine to breastfeeding mothers.

Due to the strong vasopressor effect of norepinephrine and variable patient sensitivity, there is a risk of severe hypertension if overdosed. Blood pressure should be monitored every 2 minutes after starting infusion until the desired level is achieved, then every 5 minutes if treatment continues. Infusion rate must be continuously observed, and the patient should never be left unattended. Headache may indicate excessive blood pressure.

Infusion should preferably be given through a large vein, especially an antecubital vein, to reduce the risk of local skin necrosis from prolonged vasoconstriction. Femoral vein may also be used. Catheter tie-in techniques should be avoided if possible due to risk of blood flow obstruction and drug concentration buildup. Lower limb veins should be avoided in elderly patients or those with vascular disease, as they have higher risk of ischemic complications; gangrene has been reported with ankle vein infusion.

The infusion site must be checked frequently to ensure free flow and avoid extravasation, which may cause local tissue necrosis. Even without visible leakage, blanching along the vein may occur due to vasoconstriction and may progress to superficial skin damage, especially in elderly or patients with vascular disease. If blanching occurs, changing the infusion site is recommended.

For extravasation-induced ischemia, the affected area should be infiltrated promptly with 10–15 mL saline containing 5–10 mg phentolamine. This adrenergic blocker should be injected throughout the affected area, which appears cold, pale, and firm. If given within 12 hours, phentolamine can rapidly reverse local ischemia.

Pediatric use: Safety and efficacy in children and adolescents have not been established.

Geriatric use: Limited clinical data exist in patients aged 65 and above. Elderly patients may have reduced liver, kidney, or heart function and are more likely to have coexisting diseases or medications; therefore, dosing should start at the lower end of the range. Infusions should not be given into leg veins in elderly patients.

Carcinogenesis, mutagenesis, and fertility studies have not been performed.

Overdose may cause severe hypertension, headache, reflex bradycardia, increased peripheral resistance, and reduced cardiac output. If overdose occurs, norepinephrine infusion should be stopped immediately until the patient stabilizes.

Alpha and beta adrenergic agonist

Store below 30°C in a dry place and protect from light.