How to Give Norepinephrine
Norepinephrine must be administered as a continuous intravenous infusion through a large vein, preferably via central venous catheter, at an initial dose of 0.05-0.1 mcg/kg/min (or 2-12 mcg/min in adults), titrated to achieve a mean arterial pressure of ≥65 mmHg.
Route of Administration
Norepinephrine should be given through a central venous catheter whenever possible 1, 2. The 2017 Surviving Sepsis Campaign guidelines recommend norepinephrine as the first-choice vasopressor and suggest arterial catheter placement for all patients requiring vasopressors 1.
However, peripheral administration through a large-bore (16-20 gauge) IV catheter in the mid-to-upper arm is acceptable when central access is not immediately available or would cause treatment delays 3, 4. Recent evidence demonstrates that peripheral norepinephrine administration can safely avoid central line placement in approximately 50% of patients, with extravasation rates of 75.8 events per 1,000 catheter-days and no patients requiring surgical intervention 3. The key is using a dedicated peripheral line in a proximal vein with vigilant monitoring.
Preparation and Dilution
Standard dilution: Add 4 mg of norepinephrine to 1,000 mL of 5% dextrose solution to yield 4 mcg/mL 2. This is the FDA-approved preparation method. Dextrose-containing solutions are essential as they protect against oxidation and loss of potency 2.
Do not use saline alone as the diluent 2.
Alternative concentration for infusion pumps: 1 mg in 100 mL saline (10 mcg/mL) can be used when tighter volume control is needed 5.
Initial Dosing
Adults:
- Start at 2-3 mL/min of the standard dilution (8-12 mcg/min) 2
- Alternative weight-based approach: 0.05-0.1 mcg/kg/min 6
- Titrate to achieve MAP ≥65 mmHg 1
Pediatrics:
- 0.1-1.0 mcg/kg/min, starting at the lowest dose 6
- Maximum doses up to 5 mcg/kg/min may be necessary 6
Titration Strategy
Adjust the infusion rate based on blood pressure response, not arbitrary dose limits 2. The average maintenance dose ranges from 0.5-1 mL/min (2-4 mcg/min) of standard dilution 2.
There is no absolute maximum dose - doses as high as 68 mg/day (approximately 47 mcg/min) have been used safely, though such high requirements should prompt investigation for occult hypovolemia 2. Recent survey data shows wide variability in institutional "maximum doses," ranging from 20-400 mcg/min, reflecting lack of evidence-based limits 7.
Critical principle: If escalating doses are required, always reassess for inadequate volume resuscitation first 2. Fluid-refractory hypotension may warrant adding vasopressin (0.03 units/min) or epinephrine rather than continuing to escalate norepinephrine alone 1.
Monitoring Requirements
Measure blood pressure and heart rate every 5-15 minutes during infusion 8. Continuous hemodynamic monitoring is essential when available 5.
For peripheral administration:
- Inspect the IV site frequently (every 15-30 minutes) for signs of extravasation 3
- Use infusion pumps when available for precise dosing 2
- Limit peripheral infusion to ≤24 hours when possible 4
Management of Extravasation
If extravasation occurs, immediately stop the infusion and inject phentolamine 0.1-0.2 mg/kg (up to 10 mg) diluted in 10 mL of 0.9% sodium chloride intradermally at the extravasation site 6. This counteracts dermal vasoconstriction and prevents tissue necrosis.
Special Considerations
Obesity: Use actual body weight for weight-based dosing. Obese patients require lower weight-based doses (0.09 vs 0.13 mcg/kg/min) but similar total doses compared to non-obese patients 9.
Timing: Early initiation is critical. Do not delay norepinephrine while waiting for central access - start peripherally if needed 3, 4. Time to hemodynamic stabilization directly impacts outcomes in septic shock.
Transition to central access: If norepinephrine is expected to be needed for >24 hours or doses exceed moderate levels, transition to central venous administration 4.
Avoid common pitfalls: