How to safely increase norepinephrine (NORAD) dosage?

Safe Titration of Norepinephrine (NORAD) Dosage

For patients requiring norepinephrine for shock, start with a dose of 0.05-0.1 μg/kg/min and titrate by 0.05-0.1 μg/kg/min every 5-15 minutes to achieve target mean arterial pressure (MAP) of at least 65 mmHg. 1

Preparation and Administration

Dilution

• Add 4 mg (4 mL) of norepinephrine to 1,000 mL of 5% dextrose solution
• This creates a concentration of 4 μg/mL 2
• Important: Always use dextrose-containing solutions (5% dextrose or 5% dextrose with sodium chloride) to protect against oxidation and potency loss 2

Administration Route

• Administer through a central venous catheter whenever possible
• For emergency situations, peripheral venous access or intraosseous route can be used temporarily (up to 3-4 hours) while central access is being established 3
• Secure IV catheter well to prevent extravasation

Dosing Protocol

Initial Dosing

1. Start at 0.05-0.1 μg/kg/min (approximately 2-4 μg/min for an average adult) 1
2. Observe response to initial dose for 5-15 minutes

Titration

• Increase by 0.05-0.1 μg/kg/min every 5-15 minutes until target MAP is achieved 1
• Target MAP should be ≥65 mmHg (consider higher target if patient has chronic hypertension) 1
• Average maintenance dose ranges from 2-4 μg/min (0.5-1 mL/min of the standard dilution) 2

Maximum Dosing

• No absolute maximum dose is established
• In refractory shock, doses as high as 2.5 μg/kg/min may be required 3
• Some cases may require even higher doses (up to 68 mg total daily dose in extreme cases) 2

Monitoring During Titration

• Continuous arterial blood pressure monitoring is strongly recommended 1
• Monitor for signs of adequate tissue perfusion:
  • Lactate clearance
  • Urine output (target >0.5 mL/kg/hr)
  • Skin perfusion (capillary refill)
  • Mental status 1
• Watch for signs of excessive vasoconstriction:
  • Peripheral ischemia
  • Decreased urine output despite adequate MAP

Refractory Hypotension Management

If inadequate response to norepinephrine after 10 minutes:

1. Escalate norepinephrine dose by doubling the current rate 4
2. Consider adding a second vasopressor:
   • Vasopressin (up to 0.03 U/min) to help decrease norepinephrine requirements 1
   • Epinephrine (0.05-2 μg/kg/min) if additional support is needed 1
3. Consider IV glucagon (1-2 mg) if patient is on beta-blockers 4

Potential Complications

• Extravasation: Can cause severe tissue injury
  • Management: Phentolamine (0.1-0.2 mg/kg up to 10 mg diluted in 10 mL of 0.9% sodium chloride) injected intradermally at extravasation site 4
• Arrhythmias: Monitor cardiac rhythm continuously
• Hypertension: May require dose reduction 3
• Tissue ischemia: At higher doses, monitor for signs of peripheral, renal, and splanchnic vasoconstriction 4

Weaning Protocol

1. Once the underlying cause of shock is resolving, gradually decrease the infusion rate
2. Reduce by 0.05 μg/kg/min every 15-30 minutes as tolerated
3. Monitor for hypotension during weaning process

Special Considerations

• Volume status: Always ensure adequate volume resuscitation before and during vasopressor therapy 2
• Occult hypovolemia: Consider if unusually high doses are required 2
• Pediatric dosing: Similar principles apply, but with weight-based calculations 4, 3
• Renal function: Monitor closely, especially with prolonged administration

Remember that norepinephrine is a potent vasopressor and requires careful titration and continuous monitoring to achieve optimal outcomes while minimizing adverse effects.