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  1. Pharmacology. Norepinephrine, an endogenous catecholamine, is a potent alpha1-adrenergic receptor agonist with some beta1-adrenergic receptor activity. It is used primarily as a vasopressor to increase systemic vascular resistance and venous return to the heart. It also may increase heart rate and cardiac contractility because of its beta1 effects. 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.

  2. 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.

  3. Contraindications

    1. Uncorrected hypovolemia.

    2. Norepinephrine is relatively contraindicated in patients who have mesenteric or peripheral arterial occlusive vascular disease with thrombosis, or ergot poisoning.

    3. Use with caution in patients intoxicated with chloral hydrate or halogenated or aromatic hydrocarbon solvents or anesthetics.

  4. Adverse effects

    1. Severe hypertension, which may result in intracranial hemorrhage, pulmonary edema, or myocardial necrosis.

    2. Reflex bradycardia.

    3. Ventricular dysrhythmias.

    4. Aggravation of tissue ischemia, resulting in gangrene.

    5. Tissue necrosis after extravasation.

    6. Anxiety, restlessness, tremor, and headache.

    7. Anaphylaxis induced by sulfite preservatives in sensitive patients. Use with extreme caution in patients with known hypersensitivity to sulfite preservatives.

    8. Increased cardiac irritability due to myocardial sensitization of catecholamines in the setting of exposures to halogenated hydrocarbons, such as certain anesthetics, solvents, and medications.

    9. Use in pregnancy. FDA category C. This drug crosses the placenta; it can cause placental ischemia and reduce uterine contractions.

  5. Drug or laboratory interactions

    1. Enhanced vasopressor response may occur in the presence of cocaine and cyclic antidepressants (owing to inhibition of neuronal reuptake) or with other vasoactive drugs (eg, dihydroergotamine).

    2. Enhanced vasopressor response may occur in patients taking monoamine oxidase inhibitors or COMT inhibitors owing to inhibition of neuronal metabolic degradation.

    3. Alpha- and beta-blocking agents may antagonize the adrenergic effects of norepinephrine.

    4. Anticholinergic drugs may block reflex bradycardia, which normally occurs in response to norepinephrine-induced hypertension, enhancing the hypertensive response.

    5. Chloral hydrate overdose, cyclopropane, and halogenated or aromatic hydrocarbon solvents and anesthetics may enhance myocardial sensitivity to the arrhythmogenic effects of norepinephrine.

  6. Dosage and method of administration

    1. Black box warning: 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).

      1. If extravasation occurs, immediately infiltrate the affected area with phentolamine, 5–10 mg in 10–15 mL of normal saline (children: 0.1- 0.2 mg/kg; maximum, 10 mg), via a fine (25-27-gauge) hypodermic needle; improvement is evidenced by hyperemia and return to normal temperature.

      2. Alternatively, nitroglycerin topical 2% ointment can be applied to the affected area. Infiltration of terbutaline has been reportedly successful; 1 mg diluted in 10 mL of normal saline for a large extravasation site or 1 mg diluted in 1-mL normal saline for a small site.

    2. Intravenous infusion. Initial dose ...

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