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. References

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

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