Norepinephrine (Noradrenaline) is a beta-1 and alpha receptors agonist. It improves myocardial contractility and vasoconstriction.

Norepinephrine (Noradrenaline) Uses:

• Hypotension/shock:

  • Shock treatment which persists after adequate fluid volume replacement.
  • Severe hypotension

Guideline recommendations:

• Cardiogenic shock:

  • It is recommended by The 2017 American Heart Association (AHA) scientific statement for the Contemporary Management of Cardiogenic Shock norepinephrine as the vasopressor of choice for initial management in patients with hemodynamic instability (eg, systolic blood pressure <90 mm Hg or evidence of end-organ hypoperfusion) or the following etiologies of cardiogenic shock:
    • right ventricular failure,
    • mitral regurgitation,
    • ventricular septal defect after myocardial infarction, or
    • pericardial tamponade (AHA [van Diepen 2017]).

• Septic shock:

  • The 2016 Surviving Sepsis Campaign:
  • It is recommended by the International Guidelines for Management of Sepsis and Septic Shock norepinephrine as the first-choice vasopressor for management of septic shock.

Norepinephrine (Noradrenaline) Dose in Adults

Note:

• The dose is stated in terms of the norepinephrine base.

Norepinephrine (Noradrenaline) Dose in the treatment of Hypotension/shock:

• Continuous IV infusion:

  • Initial:
    • 8-12 mcg/min.
    • Titrate to the desired response.
  • Usual maintenance range:
    • 2-4 mcg/min,
    • Depending on the clinical situation, the dosage range varies greatly.
    • Despite large doses, if the patient remains hypotensive, evaluate for occult hypokalemia, and provide fluid resuscitation as appropriate.
  • ACLS dosing range (weight-based dosing):
    • Post cardiac arrest care:
    • Initial:
    • 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70 kg patient).
    • Titrate to desired response (AHA 2010)

Norepinephrine (Noradrenaline) Dose in the treatment of Cardiogenic shock (off-label dose):

• 05-0.4 mcg/kg/min.

Norepinephrine (Noradrenaline) Dose in the treatment of Sepsis and septic shock (weight-based dosing):

• Range from clinical trials:
• 0.01-3 mcg/kg/min (0.7-210 mcg/min in a 70 kg patient).

Norepinephrine (Noradrenaline) Dose in Childrens

Note:

• Dose stated in terms of norepinephrine base.

Norepinephrine  (Noradrenaline) Dose in the treatment of Hypotension/ shock:

• Continuous IV infusion:

  • Initial:
    • 0.05-0.1 mcg/kg/min, titrate to the desired effect.
  • Usual max dose:
    • 2 mcg/kg/min.
    • The max individual reported rate: 10.5 mcg/kg/min.

Pregnancy Risk Category: C

• Norepinephrine, an endogenous catecholamine, crosses the placenta.
• Pregnancy has the same medications for cardiac arrest as a nonpregnant.
• Appropriate medication should not be withheld due to concerns about fetal teratogenicity.
• Norepinephrine may be used in the post-resuscitation period.
• The effects of vasoactive medication on the fetus should be considered.
• Follow the current Advanced Cardiovascular Life Support Guidelines for indications and dosages.

Use of norepinephrine while breastfeeding

• It is unknown if breast milk contains norepinephrine or not.
• Manufacturers recommend that breastfeeding mothers be cautious when giving norepinephrine.

Dose in Kidney Disease:

• In the manufacturer's labeling, there are no dosage adjustments provided.

Dose in Liver Disease:

• In the manufacturer's labeling, there are no dosage adjustments provided.

Side effects of Norepinephrine (Noradrenaline):

• Cardiovascular:

  • Bradycardia
  • Cardiac Arrhythmia
  • Cardiomyopathy (Stress)
  • Peripheral Vascular Insufficiency

• Central Nervous System:

  • Anxiety
  • Transient Headache

• Respiratory:

  • Dyspnea

Contraindications to Norepinephrine (Noradrenaline):

• To maintain cerebral and coronary perfusion, hypotension is an emergency measure that can be used to replace volume.
• If it is not life-saving, mesenteral or peripheral vascular embolism can occur. Anesthesia with cyclopropane or halothane, which are not available in the US, may be used.
• Limited documentation exists on allergenic cross-reactivity of vasopressors.
• Cross-sensitivity cannot be excluded because of similar chemical structures and pharmacologic activities.

Warnings and precautions

• Extravasation:

  • Vesicant.
  • Before and during infusion, make sure you have the proper needle/catheter placement.
  • Avoid extravasation.
  • If possible, infuse into a large vein.
  • Avoid infusion of leg veins
  • Pay attention to the IV site.
  • [US Boxed Warning]
    • If extravasation is possible, infiltrate the area using diluted phentolamine (5-7 mg in saline).
    • Phentolamine should only be administered if extravasation has been confirmed to prevent sloughing/necrosis.

• Hypoxia/hypercarbia

  • Patients with severe hypoxia or hypercarbia might experience ventricular fibrillation or tachycardia.
  • Extreme caution is advised.

Norepinephrine (noradrenaline): Drug Interaction

Monitoring Parameters:

• Blood pressure (or mean arterial pressure), heart rate.
• Cardiac output (as appropriate), intravascular volume status, pulmonary capillary wedge pressure (as appropriate),
• Urine output, peripheral perfusion.
• Examine the infusion site closely
• Consult individual institutional policies and procedures.

How to administer Norepinephrine?

• IV Via an infusion pump, administer as a continuous infusion.
  • Dilute prior to use.
  • Central line administration is preferred.
  • Extravasation may cause severe ischemic necrosis.
  • Through an IV line containing norepinephrine, do not administer sodium bicarbonate (or any alkaline solution).
  • Inactivation of norepinephrine may occur.
  • Vesicant.
  • Prior to and during infusion, ensure proper needle or catheter placement.
  • Avoid extravasation.

Extravasation management:

• Stop infusion immediately and disconnect, if extravasation occurs (leave cannula/needle in place).
• Gently aspirate extravasated solution (do NOT flush the line).
• Remove needle/cannula elevate extremity.
• Initiate phentolamine (or alternative) antidote.
• Apply dry warm compresses (Hurst 2004; Reynolds 2014).

Phentolamine:

• • After extravasation, dilute 5-10 mg in 10-20 mL NS & administer it into the extravasation site as soon as possible.
  • May readminister if the patient remains symptomatic (Reynolds 2014) or dilute 5-10 mg in 10 mL NS and administer into extravasation area (within 12 hours of extravasation).
  • Alternatives to phentolamine:

Nitroglycerin topical 2 percent ointment (based on limited data):

•  To the site of ischemia, apply a 1-inch strip.
•  May repeat every 8 hours as necessary.

Terbutaline (based on limited case reports):

• Using a solution of terbutaline 1 mg diluted in 10 mL NS (large extravasation site, administration volume varied from 3 to 10 mL) or 1 mg diluted in 1 mL NS, infiltrate extravasation area (small/distal extravasation site, administration volume varied from 0.5 to 1 mL).

Mechanism of action of Norepinephrine:

• Stimulates alpha-adrenergic and beta-1 adrenergic receptors, causing increased contractility as well as heart rate. This causes an increase in systemic blood pressure and coronary flow.
• Clinically, alpha effects (vasoconstriction), are more powerful than beta effects (inotropic or chronotropic effects).

Onset of action:

• Very rapid acting

Duration:

• Vasopressor:
• 1-2 mins

Metabolism:

• Via catechol-o-methyltransferase (COMT) & monoamine oxidase (MAO)

Excretion:

• Urine (as inactive metabolites)

International Brands of Norepinephrine:

• Levophed
• Adine
• Adrenor
• Adronis
• Aficard
• Arespin
• Arterenol
• Cardiamed
• Efrala
• Efrinalin
• Epinor
• Fioritina
• Levonor
• Levophed
• Levophed Bitartrate
• Mephrin
• N-Epi
• Nodresol
• Norad
• Noradrenalina Tartrato
• Noradrenaline
• Noradrenaline Aguettant
• Norages
• Noralin
• Norene
• Norepin
• Norepine
• Norphed
• Norpin
• Pridam
• Radrenit
• Rhinopront
• Vascon

Norepinephrine Brand Names in Pakistan: