Pharmacology. Norepinephrine is an endogenous catecholamine that stimulates mainly alpha-adrenergic receptors. It is used primarily as a vasopressor to increase systemic vascular resistance and venous return to the heart. Norepinephrine is also a weak beta1-adrenergic receptor agonist, and it may increase the heart rate and cardiac contractility in patients with shock. Norepinephrine is not effective orally and is absorbed erratically after subcutaneous injection. After intravenous administration, the onset of action is nearly immediate, and the duration of effect is 1–2 minutes after the infusion is discontinued.
Indications. Norepinephrine is used to increase blood pressure and cardiac output in patients with shock caused by venodilation, low systemic vascular resistance, or both. Hypovolemia, depressed myocardial contractility, hypothermia, and electrolyte imbalance should be corrected first or concurrently.
Norepinephrine is relatively contraindicated in patients who have peripheral arterial occlusive vascular disease with thrombosis or ergot poisoning (See Ergot Derivatives).
Severe hypertension, which may result in intracranial hemorrhage, pulmonary edema, or myocardial necrosis.
Aggravation of tissue ischemia, resulting in gangrene.
Tissue necrosis after extravasation.
Anxiety, restlessness, tremor, and headache.
Anaphylaxis induced by sulfite preservatives in sensitive patients. Use with extreme caution in patients with known hypersensitivity to sulfite preservatives.
Use with caution in patients intoxicated by chloral hydrate or halogenated or aromatic hydrocarbon solvents or anesthetics.
Use in pregnancy. This drug crosses the placenta; it can cause placental ischemia and reduce uterine contractions.
Drug or laboratory interactions
Enhanced pressor response may occur in the presence of cocaine and cyclic antidepressants owing to inhibition of neuronal reuptake.
Enhanced pressor response may occur in patients taking monoamine oxidase inhibitors owing to inhibition of neuronal metabolic degradation.
Alpha- and beta-blocking agents may antagonize the adrenergic effects of norepinephrine.
Anticholinergic drugs may block reflex bradycardia, which normally occurs in response to norepinephrine-induced hypertension, enhancing the hypertensive response.
Chloral hydrate overdose, cyclopropane, and halogenated or aromatic hydrocarbon solvents and anesthetics may enhance myocardial sensitivity to the arrhythmogenic effects of norepinephrine.
Dosage and method of administration
Caution: Avoid extravasation. The intravenous infusion must be free-flowing, and the infused vein should be observed frequently for signs of infiltration (pallor, coldness, or induration).
If extravasation occurs, immediately infiltrate the affected area with phentolamine (See Phentolamine), 5–10 mg in 10–15 mL of normal saline (children: 0.1– 0.2 mg/kg; maximum, 10 mg), via a fine (25- to 27-gauge) hypodermic needle; improvement is evidenced by hyperemia and return to normal temperature.
Alternatively, topical application of nitroglycerin paste and infiltration of terbutaline have been reported successful.
Intravenous infusion. Begin at 4–8 mcg/min (children: 1–2 mcg/min or 0.1 mcg/kg/min) and increase as needed every 5–10 minutes.
Formulations. Norepinephrine bitartrate is oxidized rapidly on exposure to air; it must be kept in its airtight ampule until immediately before use. If the solution appears brown or contains a precipitate, do not use it. The stock solution must be diluted in 5% dextrose or 5% dextrose-saline for infusion; usually, a 4-mg ampule is added to 1 L of fluid ...