Levophed


norepinephrine bitartrate

Levophed, Noradrenaline (UK)

Pharmacologic class: Sympathomimetic

Therapeutic class: Alpha- and beta-adrenergic agonist, cardiac stimulant, vasopressor

Pregnancy risk category C

FDA Box Warning

If extravasation occurs, infiltrate area promptly with 10 to 15 ml of saline solution containing 5 to 10 mg phentolamine to prevent sloughing and necrosis. Use syringe with fine hypodermic needle, and infiltrate solution liberally throughout area. Give phentolamine as soon as possible; its sympathetic blockade causes immediate local hyperemic changes if area is infiltrated within 12 hours.

Action

Stimulates beta1 and alpha1 receptors in sympathetic nervous system, causing vasoconstriction, increased blood pressure, enhanced contractility, and decreased heart rate

Availability

Injection: 1 mg/ml

Indications and dosages

➣ Severe hypotension

Adults: 8 to 12 mcg/minute I.V.; then titrate based on blood pressure response. For maintenance, 2 to 4 mcg/minute.

Contraindications

• Concurrent cyclopropane or halo-thane anesthesia

• Hypotension caused by blood volume deficit (except in emergencies until blood volume replacement is completed), profound hypoxia or hypercarbia

• Mesenteric or peripheral vascular thrombosis

Precautions

Use cautiously in:

• sulfite sensitivity (some products), especially in asthmatic patients

• arterial embolism, cardiac disease, peripheral vascular disease, hypertension, hyperthyroidism

• patients receiving MAO inhibitors or tricyclic antidepressants concurrently

• elderly patients

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• Mix with dextrose 5% in water or dextrose 5% in normal saline solution.

• Inspect solution to make sure it's clear and colorless. Don't infuse if it's brown or pink.

• Administer through infusion pump. Titrate infusion rate to achieve and maintain low-normal systolic blood pressure (80 to 100 mm Hg).

• Continue infusion until adequate blood pressure and tissue perfusion persist without drug therapy.

• Gradually titrate dosage downward.

• To avoid extravasation, administer only into large vein (antecubital) or through central line. Don't use femoral vein in patients who are elderly or have occlusive vascular disorders.

To prevent delivery of large drug concentrations, avoid line stasis and flushing.

Adverse reactions

CNS: headache, anxiety

CV: bradycardia, severe hypertension, arrhythmias

Respiratory: respiratory difficulty

Skin: irritation with extravasation, necrosis

Other: ischemic injury

Interactions

Drug-drug. Alpha-adrenergic blockers: antagonism of norepinephrine effects Antihistamines, ergot alkaloids, guanethidine, MAO inhibitors, oxytocin, tricyclic antidepressants: severe hypertension Bretylium, inhalation anesthetics: increased risk of arrhythmias

Patient monitoring

Check blood pressure every 2 minutes until desired pressure is achieved. Recheck every 5 minutes for duration of infusion.

• Maintain continuous ECG monitoring and blood pressure monitoring.

Be aware that headache may signal extreme hypertension and overdose.

• Monitor infusion site for extravasation.

Watch for signs and symptoms of peripheral vascular insufficiency (decreased capillary refill, pale to cyanotic to black skin color).

Never leave patient unattended during infusion.

Patient teaching

• When patient is alert, explain why he's receiving drug.

• Reassure patient he'll be monitored continuously until he's stable.

norepinephrine

(nor-ep-i-nef-rin) norepinephrine,

Levophed

(trade name)

Classification

Therapeutic: vasopressors
Pregnancy Category: C

Indications

Produces vasoconstriction and myocardial stimulation, which may be required after adequate fluid replacement in the treatment of severe hypotension and shock.

Action

Stimulates alpha-adrenergic receptors located mainly in blood vessels, causing constriction of both capacitance and resistance vessels.Also has minor beta-adrenergic activity (myocardial stimulation).

Therapeutic effects

Increased BP.Increased cardiac output.

Pharmacokinetics

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 and Excretion: Taken up and metabolized rapidly by sympathetic nerve endings.Half-life: Unknown.

Time/action profile (effects on BP)

ROUTEONSETPEAKDURATION
IVimmediaterapid1–2 min

Contraindications/Precautions

Contraindicated in: Vascular, mesenteric, or peripheral thrombosis; Obstetric: ↓ uterine blood flow;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; Lactation: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • anxiety
  • dizziness
  • headache
  • insomnia
  • restlessness
  • tremor
  • weakness

Respiratory

  • dyspnea

Cardiovascular

  • arrhythmias
  • bradycardia
  • chest pain
  • hypertension

Genitourinary

  • ↓ urine output
  • renal failure

Endocrinologic

  • hyperglycemia

Fluid and Electrolyte

  • metabolic acidosis

Local

  • phlebitis at IV site

Miscellaneous

  • fever

Interactions

Drug-Drug interaction

Use with cyclopropane or halothaneanesthesia, cardiac glycosides, doxapram, or local use of cocaine may result in ↑ myocardial irritability.Use with MAO inhibitors, methyldopa, doxapram, or tricyclicantidepressants 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, ergonovine, methylergonovine, or oxytocin may result in enhanced vasoconstriction and hypertension.

Route/Dosage

Intravenous (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).Intravenous (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)

Injection: 1 mg/mL

Nursing implications

Nursing 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 physician 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 throughout infusion. A large vein should be used to minimize risk of extravasation, which may cause tissue necrosis. Phentolamine 5–10 mg may be added to each liter of solution to prevent sloughing of tissue in extravasation. If extravasation occurs, the site should be infiltrated promptly with 10–15 mL of 0.9% NaCl solution containing 5–10 mg of phentolamine to prevent necrosis and sloughing. If prolonged therapy is required or if blanching along the course of the vein occurs, change injection sites to provide relief from vasoconstriction.
    • If overdose occurs, discontinue norepinephrine and administer fluid and electrolyte replacement therapy. An alpha-adrenergic blocking agent (phentolamine 5–10 mg) may be administered intravenously to treat hypertension.

Potential Nursing Diagnoses

Decreased cardiac output (Indications)
Ineffective tissue perfusion (Indications)

Implementation

  • high alert: 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.
  • Volume depletion should be corrected, if possible, prior to initiation of norepinephrine.
    • Heparin may be added to each 500 mL of solution to prevent thrombosis in the infused vein, perivenous reactions, and necrosis in patients with severe hypotension following MI.
    • 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.
  • Intravenous Administration
  • pH: 3.0–6.5.
  • Continuous Infusion: 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. Do not use discolored solutions (pink, yellow, brown) or those containing a precipitate.
  • Rate: Titrate infusion rate according to patient response, using slowest possible rate to correct hypotension. Administer via infusion pump to ensure accurate dosage.
  • Y-Site Compatibility: alemtuzumab, alfentanil, amikacin, anidulafungin, argatroban, ascorbic acid, atracurium, atropine, aztreonam, benztropine, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftaroline, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, chrlopromazine, cisatracurium, cisplatin, clindamycin, cyanocobalamin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexamethasone, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doripenem, doxycycline, doxorubicin liposomal, enalaprilat, ephedrine, epinephrine, epirubicin, epoetin alfa, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hetastarch, hydrocortisone sodium succinate, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin calcium, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, meropenem, metaraminol, methotrexate, methoxamine, methyldopate, methylprednisolone, metoclopramide, metoprolol, metronidazole, micafungin, midazolam, milrinone, mitoxantrone, morphine, moxifloxacin, multivitamins, mycophenolate, nafcillin, nalbuphine, naloxone, nicardipine, nitroglycerin, nitroprusside, octreotide, ondansetron, oxacillin, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, papaverine, pemetrexed, penicillin G, pentamidine, pentazocine, phentolamine, phenylephrine, phytonadione, piperacillin/tazobactam, potassium acetate, potassium chloride, procainamide, prochlorperazine, promethazine, propofol, propranolol, protamine, pyridoxime, ranitidine, remifentanil, streoptokinase, succinylcholine, sufentanil, tacrolimus, telavancin, teniposide, theophylline, thiamine, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, vancomycin, vasorpessin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, vitamin B complex with C, voriconazole, zolendronic acid
  • Y-Site Incompatibility: aminophylline, amphotericin B colloidal, amphotericin B lipid complex, azathioprine, dantrolene, diazepam, diazoxide, folic acid, foscarnet, ganciclovir, indomethacin, pentobarbital, phenobarbital, phenytoin, sodium bicarbonate, thiopental, trimethoprim/sulfamethoxazole

Patient/Family Teaching

  • Instruct patient to report headache, dizziness, dyspnea, chest pain, or pain at infusion site promptly.

Evaluation/Desired Outcomes

  • Increase in BP to normal range.
    • Increased tissue perfusion.

Levophed

(lĕv′ə-fĕd′) A trademark for a drug preparation of norepinephrine.