Norepinephrine Preparation in D5W
Yes, you can prepare norepinephrine 4mg in 250mL D5W, which creates a concentration of 16 mcg/mL—this is a standard and FDA-approved preparation method. 1
Standard Preparation Method
The FDA label explicitly describes this preparation 1:
- Add 4mg (one 4mL vial) of norepinephrine to 250mL of D5W
- Final concentration: 16 mcg/mL
- D5W is the preferred diluent as it protects against oxidation and loss of potency
- This solution is chemically stable for 7 days at room temperature under ambient light 2
Alternative Standard Concentration
The FDA also describes a more dilute preparation 1:
- Add 4mg to 1000mL D5W = 4 mcg/mL concentration
- This is useful when patients require larger fluid volumes
Clinical Indication
Norepinephrine is the first-choice vasopressor for septic shock and other forms of distributive shock 3. The Surviving Sepsis Campaign 2016 guidelines give this a strong recommendation with moderate quality evidence. It should be used to target a mean arterial pressure (MAP) of 65 mmHg 3.
Dosing Formula and Rate Calculation
Starting Dose
- Initial rate: 8-12 mcg/min (equivalent to 0.5-0.75 mL/min of the 16 mcg/mL solution) 1
- Titrate to achieve MAP ≥65 mmHg
Maintenance Dose
- Average: 2-4 mcg/min (0.125-0.25 mL/min of 16 mcg/mL solution) 1
- Dosing must be individualized based on hemodynamic response
Dose Calculation Formula
For 16 mcg/mL concentration (4mg in 250mL):
Rate (mL/hr) = Desired dose (mcg/min) × 60 ÷ 16
OR
Rate (mL/hr) = Desired dose (mcg/min) × 3.75Example calculations:
- For 8 mcg/min: 8 × 3.75 = 30 mL/hr
- For 12 mcg/min: 12 × 3.75 = 45 mL/hr
- For 4 mcg/min: 4 × 3.75 = 15 mL/hr
Weight-Based Dosing Formula
When dosing by weight (mcg/kg/min):
Rate (mL/hr) = Dose (mcg/kg/min) × Weight (kg) × 60 ÷ Concentration (mcg/mL)
For 16 mcg/mL:
Rate (mL/hr) = Dose (mcg/kg/min) × Weight (kg) × 3.75Example for 70kg patient:
- Low dose (0.05 mcg/kg/min): 0.05 × 70 × 3.75 = 13 mL/hr
- Moderate dose (0.2 mcg/kg/min): 0.2 × 70 × 3.75 = 52.5 mL/hr
- High dose (0.5 mcg/kg/min): 0.5 × 70 × 3.75 = 131 mL/hr
Dose Severity Classification
Recent evidence suggests specific cutoffs for norepinephrine dose severity 4:
- Low dose: <0.2 mcg/kg/min (mortality ~14%)
- Intermediate dose: 0.2-0.4 mcg/kg/min (mortality ~26%)
- High dose: >0.4 mcg/kg/min (mortality ~40%)
Doses >1.13 mcg/kg/min predict high early mortality (sensitivity 67%, specificity 80%) 5.
Critical Administration Guidelines
Route of Administration
- Preferred: Central venous catheter through a large vein 1
- Peripheral administration is acceptable when central access is delayed, using:
Important Caveats
Volume depletion must be corrected first 1. The FDA label explicitly states norepinephrine should not be used as a substitute for blood volume replacement. Occult hypovolemia should be suspected if extremely high doses are required.
Phentolamine is the antidote for extravasation: Inject 5-10mg diluted in 10-15mL saline into the extravasation site 1.
Salt vs. Base confusion: The vial contains norepinephrine bitartrate salt, but dosing is expressed as norepinephrine base. The 4mg/4mL vial contains 4mg of norepinephrine base—this is already accounted for in the labeling 1, 8.
Protect from light for extended storage: While stable for 7 days at room temperature, solutions protected from light maintain >90% concentration for 61 days at 4°C 9.