norepinephrine

Absorption: IV administration results in complete bioavailability.

Distribution: Concentrates in sympathetic nervous tissue. Does not cross the blood-brain barrier but readily crosses the placenta.

Metabolism/Excretion: Taken up and metabolized rapidly by sympathetic nerve endings.

Half-Life: Unknown.

Time/Action Profile ⬆ ⬇

(effects on BP)

ROUTE	ONSET	PEAK	DURATION
IV	immediate	rapid	1–2 min

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Vascular, mesenteric, or peripheral thrombosis;
Hypoxia;
Hypercarbia;
Hypotension secondary to hypovolemia (without appropriate volume replacement);
Hypersensitivity to bisulfites.

Use Cautiously in:

Hypertension;
Concurrent use of MAO inhibitors, tricyclic antidepressants, or cyclopropane or halothane anesthetics;
Hyperthyroidism;
Cardiovascular disease;
OB: May uterine blood flow in pregnancy;
Lactation: Safety not established in breastfeeding.

Adv. Reactions/Side Effects ⬆ ⬇

CV: arrhythmia, bradycardia, chest pain, hypertension

Endo: hyperglycemia

F and E: metabolic acidosis

GU: ↓urine output, renal failure

Local: phlebitis at IV site

Neuro: anxiety, dizziness, headache, insomnia, restlessness, tremor, weakness

Resp: dyspnea

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Use with cyclopropane or halothane anesthesia, digoxin, doxapram, or local use of cocaine may result in ↑ myocardial irritability.
Use with MAO inhibitors, doxapram, or tricyclic antidepressants may result in severe hypertension.
Alpha-adrenergic blockers can prevent pressor response.
Beta blockers may exaggerate hypertension or block cardiac stimulation.
Concurrent use with ergot alkaloids (ergotamine, methylergonovine, or oxytocin) may result in enhanced vasoconstriction and hypertension.

Route/Dosage ⬆ ⬇

IV (Adults ): 0.5–1 mcg/min initially, followed by maintenance infusion of 2–12 mcg/min titrated by BP response (average rate 2–4 mcg/min, up to 30 mcg/min for refractory shock have been used).
IV (Children ): 0.1 mcg/kg/min initially; may be followed by infusion titrated to BP response, up to 1 mcg/kg/min.

Availability ⬆ ⬇

(Generic available)

Premixed infusion: 4 mg/250 mL D5W or 0.9% NaCl; 8 mg/250 mL D5W or 0.9% NaCl; 16 mg/250 mL 0.9% NaCl
Solution for injection: 1 mg/mL

Assessment ⬆ ⬇

Monitor BP every 2–3 min until stabilized and every 5 min thereafter. Systolic BP is usually maintained at 80–100 mm Hg or 30–40 mm Hg below the previously existing systolic pressure in previously hypertensive patients. Consult health care professional for parameters. Continue to monitor BP frequently for hypotension following discontinuation of norepinephrine.
ECG should be monitored continuously. CVP, intra-arterial pressure, pulmonary artery diastolic pressure, pulmonary capillary wedge pressure (PCWP), and cardiac output may also be monitored.
Monitor urine output and notify health care professional if it decreases to <30 mL/hr.
Assess IV site frequently during infusion. A large vein should be used to minimize risk of extravasation, which may cause tissue necrosis. If prolonged therapy is required or if blanching along the course of the vein occurs, change injection sites to provide relief from vasoconstriction.

Toxicity and Overdose:

If overdose occurs, discontinue norepinephrine and administer fluid and electrolyte replacement therapy. An alpha-adrenergic blocking agent may be administered intravenously to treat hypertension.

Implementation ⬆ ⬇

Vasoactive medications are inherently dangerous. Have second practitioner independently check original order, dose calculations, and infusion pump programming. Establish maximum dose limits. Norepinephrine overdose can result in severe peripheral vasoconstriction with resultant ischemia and necrosis of peripheral tissue. Assess peripheral circulation frequently.
Correct volume depletion, if possible, prior to initiation of norepinephrine.
- Norepinephrine may deplete plasma volume and cause ischemia of vital organs, resulting in hypotension when discontinued, if used for prolonged periods. Prolonged or large doses may also decrease cardiac output.
- Infusion should be discontinued gradually, upon adequate tissue perfusion and maintenance of BP, to prevent hypotension. Do not resume therapy unless BP falls to 70–80 mm Hg.

IV Administration:

Diluent: Dilute 4 mg in 1000 mL of D5W or D5/0.9% NaCl. Do not dilute in 0.9% NaCl without dextrose.Concentration: 4 mcg/mL. Solution is colorless. Do not use discolored solutions (pink, yellow, brown) or those containing a precipitate. Solution is stable for 24 hr at room temperature. Protect from light.
Rate: Titrate infusion rate according to patient response, using slowest possible rate to correct hypotension. Administer via infusion pump to ensure accurate dose. Typical maintenance IV dose is 2 to 4 mcg per min.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇