Norepinephrine Tartrate

Approved Indications:

• Acute Hypotension and Shock:
• Treatment of life-threatening hypotension due to:
• Septic shock
• Neurogenic shock
• Cardiogenic shock
• Hypotension during anesthesia
• Cardiac Arrest (as adjunct):
• For restoration and maintenance of blood pressure during cardiopulmonary resuscitation when hypotension persists after adequate fluid resuscitation

Clinically Accepted Off-label Uses:

• Spinal or Epidural Anesthesia-induced Hypotension:
• Prophylactic use in cesarean section under spinal anesthesia
• Traumatic Brain Injury (TBI):
• To maintain cerebral perfusion pressure
• Refractory Anaphylaxis:
• As second-line vasopressor when epinephrine fails

Adults:

• Initial Dose:
  8–12 mcg/min IV infusion
• Maintenance Dose:
  2–4 mcg/min IV, titrated based on patient response
• Maximum Dose:
  No absolute ceiling; doses >30 mcg/min require extreme caution due to risk of ischemia

Pediatrics:

• Initial Dose:
  0.05–0.1 mcg/kg/min IV infusion
• Titrate gradually to effect under intensive care supervision

Elderly:

• Start at lower end of dosing range; monitor closely for cardiac and ischemic complications

Special Populations:

• Renal or Hepatic Impairment:
  No specific dosage adjustment needed, but use with caution

Administration Route:

• Intravenous infusion only
• Preferably through a central venous catheter
• Use an infusion pump for accurate delivery
• Never administer via IV bolus

Duration:

• Continue infusion as long as hypotension persists
• Taper gradually to avoid rebound hypotension

Norepinephrine acts predominantly as a potent alpha-adrenergic agonist with minor beta-1 adrenergic activity. It causes peripheral vasoconstriction through α1 receptor stimulation, increasing systemic vascular resistance and blood pressure. It also activates β1 receptors in the heart, resulting in a modest increase in myocardial contractility and cardiac output. However, baroreceptor reflex may induce reflex bradycardia, limiting heart rate elevation. The net effect is an increase in mean arterial pressure (MAP) with a balanced cardiac workload, making it the vasopressor of choice in most shock states.

• Absorption:
  Rapid onset with IV infusion (1–2 minutes)
• Distribution:
  Limited to extracellular space; does not cross the blood-brain barrier significantly
• Metabolism:
  Primarily by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) in liver and other tissues
• Half-life:
  Approximately 2.5 minutes
• Elimination:
  Metabolites excreted via urine (as vanillylmandelic acid, metanephrine, normetanephrine)
• Onset of Action:
  Within 1–2 minutes after IV infusion begins
• Duration of Action:
  Short; persists only during continuous infusion

• Pregnancy:
  Category C (US FDA)
• Use only if clearly indicated. May reduce uterine blood flow and oxygen delivery to the fetus. Exercise caution, particularly during labor or cesarean delivery.
• Lactation:
• Unknown if excreted into human breast milk
• Systemic exposure to nursing infants is unlikely due to poor oral absorption
• Use caution if administered to lactating women

• Primary Class: Vasopressor
• Subclass: Sympathomimetic amine / Catecholamine
• Receptor Activity: Predominantly α1 agonist, partial β1 agonist, minimal β2 activity

• Known hypersensitivity to norepinephrine or any component of the formulation
• Hypotension due to blood volume deficit (uncorrected hypovolemia)
• Mesenteric or peripheral vascular thrombosis
• Profound hypoxia or hypercapnia
• Use in patients without access to central venous administration (due to extravasation risk)

• Extravasation Risk (Black Box Warning):
• Severe local tissue necrosis and gangrene may occur if extravasation happens
• Administer via central line whenever possible
• In case of extravasation, infiltrate area with phentolamine
• Tissue Ischemia:
• Risk of peripheral, mesenteric, and renal ischemia at high doses
• Cardiac Complications:
• May precipitate arrhythmias or myocardial ischemia, especially in patients with pre-existing cardiovascular disease
• Reflex Bradycardia:
• May occur due to baroreceptor stimulation
• Hyperglycemia & Lactic Acidosis:
• Possible in patients with prolonged or high-dose use, particularly in sepsis
• Clinical Monitoring Required:
• Continuous monitoring of BP, ECG, urine output, and peripheral perfusion

Common (≥1%):

• Cardiovascular:
• Hypertension, reflex bradycardia, tachycardia, arrhythmias
• Local:
• IV site pain, blanching, phlebitis
• Neurologic:
• Anxiety, restlessness, headache, dizziness

Serious (Rare):

• Tissue necrosis from extravasation
• Myocardial infarction
• Renal failure due to prolonged vasoconstriction
• Limb ischemia and gangrene
• Pulmonary edema (especially in fluid-overloaded states)

Timing:

• Onset is rapid (1–2 minutes); adverse effects are often dose-dependent

• Monoamine Oxidase Inhibitors (MAOIs):
• Potentiates hypertensive effects; contraindicated
• Tricyclic Antidepressants (TCAs):
• Enhance vasopressor effect; increased risk of severe hypertension
• General Anesthetics (e.g., halothane):
• May increase risk of cardiac arrhythmias
• Beta-blockers:
• Can exacerbate peripheral vasoconstriction due to unopposed alpha activity
• Ergot Alkaloids or Oxytocics:
• Additive vasoconstrictive effect; avoid concurrent use
• CYP450 Interactions:
• Not metabolized by CYP enzymes; minimal involvement in hepatic microsomal systems

• Surviving Sepsis Campaign (2021–2024):
• Confirms norepinephrine as first-line vasopressor in septic shock
• Recommends initiating vasopressors early (within 1 hour) to maintain MAP ≥65 mmHg
• WHO Essential Medicines List (Current):
• Listed as a critical emergency medicine for managing acute hypotension and shock
• Recent Research Trends:
• Early vasopressor initiation associated with better outcomes in shock
• Investigations ongoing for alternative routes (e.g., low-dose peripheral infusions in emergencies)

• Temperature:
  Store between 20°C to 25°C (68°F to 77°F); brief excursions between 15°C and 30°C are permitted
• Light Protection:
  Keep in the original outer packaging to protect from light
• Freezing:
  Do not freeze
• After Dilution:
  Use immediately after preparation
  If necessary, store refrigerated at 2°C to 8°C for up to 24 hours
• Infusion Compatibility:
• Compatible with 0.9% sodium chloride or 5% dextrose
• Do not mix with alkaline solutions
• Handling:
  Use an infusion pump; inspect solutions for particulate matter and discoloration prior to use