norepinephrine (Rx)

Frequency Not Defined

Bradycardia

Hypertension

Arrhythmias

Confusion

Anxiety

Dyspnea, with or without respiratory difficulty

Headache

Nausea and vomiting

Sweating

Tremor

Restlessness

Urinary retention

Extravasation

Gangrene

Contraindications

Hypersensitivity

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

Peripheral vascular thrombosis (except for lifesaving procedures)

Concomitant use with some general anesthetics cyclopropane (not available in the US), halothane (not available in the US)

Cautions

If therapy is continuously administered to maintain blood pressure in absence of blood volume replacement, severe peripheral and visceral vasoconstriction, decreased renal perfusion and urine output, poor systemic blood flow despite “normal” blood pressure, tissue hypoxia, and lactate acidosis may occur

Use extreme caution with concurrent monoamine oxidase inhibitor (MAOI) use or antidepressants of the triptyline or imipramine types; severe, prolonged hypertension may result

Cyclopropane and halothane anesthetics increase cardiac autonomic irritability and seem to sensitize the myocardium to action of intravenously administered epinephrine or norepinephrine

Not for use in profound hypoxia or hypercarbia

Bitartrate injection contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people

Because of potency of drug and because of varying response to pressor substances, possibility always exists that dangerously high blood pressure may be produced with overdoses of this pressor agent; it is desirable, therefore, to record blood pressure every two min from time administration is started until desired blood pressure is obtained, then every five min if administration is to be continued; rate of flow must be watched constantly, and patient should never be left unattended while receiving therapy; headache may be a symptom of hypertension due to overdosage

When possible, infusions should be given into large vein, particularly an antecubital vein to reduce risk of necrosis of overlying skin from prolonged vasoconstriction; some authors have indicated that femoral vein is an acceptable route of administration; occlusive vascular diseases (for example, atherosclerosis, arteriosclerosis, diabetic endarteritis, Buerger’s disease) are more likely to occur in the lower than in the upper extremity; one should avoid the veins of the leg in elderly patients or in those suffering from such disorders; gangrene has been reported in a lower extremity when infusions were given in an ankle vein

Infusion site should be checked frequently for free flow; care should be taken to avoid extravasation of drug into tissues, as local necrosis might ensue due to vasoconstrictive action of drug; blanching along the course of the infused vein, sometimes without obvious extravasation, has been attributed to vasa vasorum constriction with increased permeability of vein wall, permitting some leakage

Antidote for extravasation ischemia

• To prevent sloughing and necrosis in areas in which extravasation has taken place, area should be infiltrated as soon as possible with 10 - 15 mL of saline solution containing from 5 mg to 10 mg of Regitine® (brand of phentolamine), an adrenergic blocking agent; a syringe with a fine hypodermic needle should be used, with the solution being infiltrated liberally throughout the area, which is easily identified by its cold, hard, and pallid appearance; sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours; therefore, phentolamine should be given as soon as possible after extravasation is noted.

Pregnancy category: C

Lactation: Not known if excreted into breast milk; avoid use during breastfeeding

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Strong beta1- and alpha-adrenergic effects and moderate beta2 effects, which increase cardiac output and heart rate, decrease renal perfusion and PVR, and cause variable BP effects

Absorption

Onset: 1-2 min

Duration: 1-2 min (vasopressor)

Metabolism

Metabolized by MAO and catechol-O-methyl transferase (COMT) in the adrenergic neuron

Metabolites: Normetanephrine, vanillylmandelic acid (inactive)

Elimination

Excretion: Urine (84-96%)

IV Incompatibilities

Additive: Aminophylline, pentobarbital

Not spec: Atropine, carbenicillin, cefazolin, diazepam

IV Compatibilities

Additive: Calcium gluconate, cimetidine, dobutamine, heparin, KCl, verapamil, vitamins B/C

Syringe: Heparin

Y-site: Amiodarone, epinephrine, esmolol, fentanyl, furosemide, heparin, hydrocortisone, KCl, vitamins B/C

Not spec: Tetracycline

IV Preparation

Solution: 4 mg in 1000 ml D5W (4 mcg/ml); 40 ml/hr (~3 mcg/min); dose may be titrated to patient response

IV Administration

Into large vein; central line required

Do not administer NaHCO3 through an IV line containing norepinephrine