II. Definitions

  1. Norepinephrine
    1. Natural Catecholamine, released from Adrenal Medulla as a stress response (along with Epinephrine)
    2. Also the primary postganglionic Neurotransmitter of the Sympathetic Nervous System
    3. Strong Vasoconstriction and increased arterial pressure (a1) and reflex Bradycardia
    4. Unlike Epinephrine, only small effects on contractility and NO beta effect (no bronchodilation or metabolic effects)

III. History

  1. Ulf Von Euler won 1970 Nobel Prize for its discovery
    1. Swedish Chemist also discovered Prostaglandins

IV. Mechanism

  1. Naturally occurring Catecholamine
  2. Potent Alpha Adrenergic ReceptorAgonist
    1. Potent arterial and venous Vasoconstriction
  3. Weak Beta 1 Adrenergic ReceptorAgonist
    1. Only small effects on contractility (contrast with Epinephrine which increases contractility)
    2. Reflex Bradycardia (contrast with Epinephrine, which increases Heart Rate)
  4. No Beta 2 Adrenergic Receptor Activity
    1. No bronchodilation or metabolic effects (contrast with Epinephrine)

V. Indications

  1. First line Vasopressor in fluid refractory, hemodynamically significant Hypotension (esp. Septic Shock)
    1. Useful in Low Systemic Vascular Resistance (e.g. Septic Shock, Neurogenic Shock)

VI. Contraindications: Relative

  1. Acute Myocardial Infarction
    1. Risk of worsening coronary perfusion

VII. Monitoring

  1. Monitor Blood Pressure accurately
    1. Consider Arterial Line with continuous monitoring
    2. Blood Pressure cuff monitoring every 5 minutes
  2. Consider advanced hemodynamic monitoring
    1. Cardiac Output
    2. Pulmonary wedge pressure
    3. Peripheral arterial resistance

VIII. Precautions

  1. Maximize management of other Hypotension Causes first
    1. Maximize fluid Resuscitation in Sepsis
    2. Replace Blood Products in Trauma
  2. Use with caution in Myocardial Ischemia
    1. Increases myocardial oxygen requirements
    2. No compensatory increase in coronary perfusion
  3. Observe for Arrhythmias
    1. Volume depleted patents
    2. Limited myocardial reserve
  4. Norepinephrine is safest to use via central venous catheter
    1. However reliable large bore peripheral IV may be used safely with caution initially (e.g. first 24 hours)
      1. Nguyen (2020) Am J Emerg Med +PMID: 31959524 [PubMed]
    2. Extravasation may cause severe local tissue damage
    3. Antidote for extravasation
      1. Phentolamine 5-10 mg diluted in 10-15 ml NS
      2. Infiltrate area of extravasation with Phentolamine

IX. Preparation

  1. Start with Norepinephrine (1 mg/ml) 4 ml ampule
  2. Option 1: Mix 4 mg (4 ml) Norepinephrine in 500 ml D5W or Normal Saline
    1. Final Concentration: 8 mcg/ml Norepinephrine (rate 22.5 ml/h delivers 3 mcg/min)
  3. Option 2: Mix 4 mg (4 ml) Norepinephrine in 250 ml D5W or Normal Saline
    1. Final Concentration: 16 mcg/ml Norepinephrine (rate 11.25 ml/h delivers 3 mcg/min)

X. Dosing: Infusion via Central Venous Catheter

  1. May start via reliable large bore peripheral line during stabilization, but should be transitioned to Central Line within hours (<24 hours)
  2. Child (off label)
    1. Start 0.05 to 0.1 mcg/kg/min IV
    2. Titrate to mean arterial pressure or systolic Blood Pressure target up to max rate (2 mcg/kg/min)
  3. Adult: Weight Based (preferred, adults)
    1. Start at 0.05 mcg/kg/min
    2. Unlikely to benefit from titration above 0.3 mcg/kg/min
  4. Adult: Non-weight based
    1. Start at 5 mcg/min up to 8 to 12 mcg/min
    2. Typical dose range (adults): 2 to 4 mcg/min (up to 30 mcg/min or 0.3 mcg/kg/min)
  5. Adult: Titrate to Systolic Blood Pressure >90 mmHg or MAP >65 mmHg
    1. Average Adult Dose: 2 to 12 mcg/min
    2. Refractory Shock: up to 30 mcg/min

XI. Adverse Effects

  1. Tissue extravasation
    1. Risk of tissue ischemia, necrosis, gangrene
    2. Infuse via central venous catheter
      1. May use reliable large bore peripheral IV initially during stabilization

XII. Resources

XIII. References

  1. McCollum in Herbert (2019) EM:Rap 19(7):4-6

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Related Studies

Ontology: Norepinephrine (C0028351)

Definition (NCI) A naturally occurring catecholamine hormone that functions as a neurotransmitter in the sympathetic nervous system. Norepinephrine directly stimulates adrenergic receptors. Stimulation of alpha-adrenergic receptors causes vasoconstriction of the radial smooth muscle of the iris, arteries, arterioles, veins, urinary bladder, and the sphincter of the gastrointestinal tract. Stimulation of beta-1 adrenergic receptors causes an increase in myocardial contractility, heart rate, automaticity, and atrioventricular (AV) conduction while stimulation of beta-2 adrenergic receptors causes bronchiolar and vascular smooth muscle dilatation.
Definition (NCI_NCI-GLOSS) A chemical made by some nerve cells and in the adrenal gland. It can act as both a neurotransmitter (a chemical messenger used by nerve cells) and a hormone (a chemical that travels in the blood and controls the actions of other cells or organs). Noradrenaline is released from the adrenal gland in response to stress and low blood pressure.
Definition (NCI) A synthetic phenylethylamine that mimics the sympathomimetic actions of the endogenous norepinephrine. Norepinephrine acts directly on the alpha- and beta-adrenergic receptors. Clinically, norepinephrine is used as a peripheral vasoconstrictor that causes constriction of arterial and venous beds via its alpha-adrenergic action. It is also used as a potent inotropic and chronotropic stimulator of the heart mediated through its beta-1 adrenergic action.
Definition (MSH) Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.
Definition (CSP) precursor of epinephrine; widespread central and autonomic neurotransmitter, principal transmitter of most postganglionic sympathetic fibers; secreted by the adrenal medulla; used pharmacologically as a sympathomimetic.
Concepts Pharmacologic Substance (T121) , Neuroreactive Substance or Biogenic Amine (T124) , Organic Chemical (T109)
MSH D009638
SnomedCT 111130009, 386986004, 349918005, 45555007
LNC LP15271-7, MTHU003447
English Levarterenol, Levonorepinephrine, Noradrenaline, Norepinephrine, norepinephrine, 1,2-Benzenediol, 4-(2-amino-1-hydroxyethyl)-, (R)-, Arterenol, l-Noradrenaline, l-Norepinephrine, levarterenol, Noradrenaline preparation, norepinephrine (medication), vasopressors norepinephrine, noradrenalin, Norepinephrine [Chemical/Ingredient], norepinephrines, noradrenaline, NOREPINEPHRINE, (+/-)-Noradrenaline, l-Arterenol, l-3,4-Dihydroxyphenylethanolamine, (-)-alpha-(aminomethyl)-3,4-dihydroxybenzyl Alcohol, Norepinephrine, DL-, 1,2-benzenediol, 4-(2-amino-1-hydroxyethyl)-, (+/-)-, Noradrenaline product (product), Norepinephrine preparation (substance), (.+-.)-Norepinephrine, NOREPINEPHRINE, DL-, (.+-.)-Noradrenaline, (R)-4-(2-Amino-1-hydroxyethyl)-1,2-benzenediol, Noradrenaline product, Norepinephrine preparation, NA - Noradrenaline, NA - Norepinephrine, Norepinephrine (substance), Norepinephrine preparation (product), Norepinephrine product, Noradrenaline product (substance)
Swedish Noradrenalin
Czech noradrenalin
Finnish Noradrenaliini
French Norépinéphrine, Noradrénaline
Russian NORADRENALIN, LEVONOREPINEFRIN, ARTERENOL, LEVARTERENOL, NOREPINEFRIN, АРТЕРЕНОЛ, ЛЕВАРТЕРЕНОЛ, ЛЕВОНОРЭПИНЕФРИН, НОРАДРЕНАЛИН, НОРЭПИНЕФРИН
Japanese アルテレノール, ノルエピネフリン, レボノルエピネフリン, レバルテレノール, ノルエピネフリン酒石酸塩, 酒石酸水素ノルアドレナリン, 酒石酸ノルアドレナリン, ノルアドレナリン酒石酸塩, ノルアドレナリン塩酸塩, 塩酸ノルアドレナリン, ノルアドレナリン, 酒石酸ノルエピネフリン, 塩酸ノルエピネフリン, 4-(2-アミノ-1-ヒドロキシエチル)-1,2-ベンゼンジオール, 酒石酸水素ノルエピネフリン, ノルエピネフリン塩酸塩
Spanish norepinefrina, norepinefrina (producto), preparado con norepinefrina, producto con noradrenalina (producto), levarterenol, producto con noradrenalina, preparado con noradrenalina, noradrenalina, producto (producto), preparado de noradrenalina (sustancia), preparado de noradrenalina, noradrenalina, producto, noradrenalina (sustancia), noradrenalina, producto (sustancia), noradrenalina, preparado de noradrenalina (producto), preparado de norepinefrina, Norepinefrina, Levarterenol, Levonorepinefrina, Noradrenalina
Croatian NOREPINEFRIN
Polish Norepinefryna, Noradrenalina, Levarterenol, Układ noradrenergiczny
German Levarterenol, Levonorepinephrin, Noradrenalin, Norepinephrin
Italian Norepinefrina
Portuguese Norepinefrina, Levarterenol, Levonorepinefrina, Noradrenalina

Ontology: Levophed (C0733815)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D009638
English Bitartrate, Levophed, Levophed Bitartrate, levophed, Abbott Brand of Levophed Bitartrate, Levophed