How to calculate and administer norepinephrine for hypotension?

Norepinephrine Dosing and Administration for Hypotension

For hypotension management, norepinephrine should be administered as a continuous infusion through a central venous line when possible, with standard adult concentration prepared by adding 4 mg of norepinephrine to 250 mL of D5W to yield a concentration of 16 μg/mL, and titrated to achieve a target mean arterial pressure of 65-100 mmHg. 1, 2

Preparation and Concentration Options

• Standard adult concentration: Add 4 mg norepinephrine to 250 mL of D5W to yield 16 μg/mL 2
• Alternative concentration for anaphylaxis: Add 1 mg norepinephrine to 100 mL of saline (1:100,000 solution) 2
• For pediatric patients, use the "rule of 6": 0.6 × body weight (kg) = number of milligrams diluted to total 100 mL of saline; then 1 mL/h delivers 0.1 mcg/kg/min 2

Administration Route

• Central venous access is strongly preferred to prevent tissue necrosis from extravasation 1, 2
• If central access is unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily while central access is being established 2

Initial Dosing and Titration

• Start at 0.5 mg/h (approximately 0.05-0.1 μg/kg/min) and titrate based on response 1, 2
• For severe hypotension in anaphylaxis, consider the following dosing based on severity:
  • Grade II reactions (moderate hypotension): Administer IV epinephrine 20 μg initially, then escalate to 50 μg if unresponsive after 2 minutes 3
  • Grade III reactions (life-threatening hypotension): Administer IV epinephrine 50-100 μg initially, then escalate to 200 μg if unresponsive after 2 minutes 3
  • If hypotension persists after 10 minutes despite epinephrine, add norepinephrine infusion at 0.05-0.5 μg/kg/min 3

Monitoring and Titration Protocol

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 2
• Titrate to achieve target MAP of 65-100 mmHg or sufficient to maintain vital organ perfusion 1
• Increase dose by 0.5 mg/h every 4 hours as needed, to a maximum of 3 mg/h 2
• For refractory hypotension, consider escalating the dose or adding alternative vasopressors 1
• Monitor for signs of excessive vasoconstriction (cold extremities, decreased urine output) 2

Managing Extravasation

• If extravasation occurs, infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the site to prevent tissue necrosis 1, 2
• For pediatric patients, use phentolamine 0.1-0.2 mg/kg (up to 10 mg) diluted in 10 mL of 0.9% sodium chloride 2

Special Considerations

• Always correct volume depletion before or concurrently with norepinephrine administration 1
• Use cautiously in patients with ischemic heart disease as it may increase myocardial oxygen requirements 1
• Continuous infusion of norepinephrine has shown better effects on microcirculation compared to bolus administration 4
• Variable-rate infusion has demonstrated lower incidence of maternal hypotension (9%) compared to fixed-rate infusion (30%) during cesarean delivery under spinal anesthesia 5

Weaning Protocol

• Once the patient is hemodynamically stable, decrease the norepinephrine dose by 25% of the current dose every 30 minutes as tolerated 1

Potential Adverse Effects

• Increased myocardial oxygen consumption 1
• Tissue necrosis if extravasation occurs 1
• Arrhythmias at higher doses 1
• Excessive vasoconstriction leading to end-organ hypoperfusion 1

Early administration of norepinephrine in severely hypotensive septic patients has been shown to increase cardiac output through an increase in cardiac preload and cardiac contractility, even in patients with poor cardiac contractility 6.