Norepinephrine Should Not Be Diluted with Normal Saline Alone
Norepinephrine should be diluted in dextrose-containing solutions (D5W or D5W with sodium chloride) rather than normal saline alone to prevent significant loss of potency due to oxidation. 1
Proper Dilution Guidelines
- Norepinephrine should be diluted in 5% dextrose injection (D5W) or 5% dextrose and sodium chloride injections, as these dextrose-containing fluids protect against significant loss of potency due to oxidation 1
- Standard adult concentration: Add 4 mg of norepinephrine to 250 mL of D5W to yield a concentration of 16 μg/mL 2
- Administration in saline solution alone is not recommended according to FDA labeling 1
Administration Route and Monitoring
- Central venous access is preferred for administration of norepinephrine to minimize risk of extravasation 3, 2
- If central access is unavailable or delayed, peripheral IV administration can be used temporarily, but requires strict adherence to protocols including:
- Appropriate catheter gauge selection
- Proper site selection
- Regular visual inspection every 2 hours 4
- Monitor blood pressure and heart rate every 5-15 minutes during initial titration 2
Complications and Precautions
- Norepinephrine and other catecholamines can produce tissue necrosis if extravasation occurs 3
- If extravasation develops, infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the site of extravasation as soon as possible to prevent tissue death and sloughing 3
- Adrenergic drugs should not be mixed with sodium bicarbonate or other alkaline solutions in the IV line, as there is evidence they are inactivated in alkaline solutions 3
Special Considerations
- While research suggests norepinephrine solutions may be chemically stable for up to seven days in both D5W and normal saline 5, 6, the FDA-approved labeling specifically recommends against using saline solution alone 1
- For specific clinical scenarios such as priapism treatment, phenylephrine (another sympathomimetic) is diluted with normal saline, but this is a different medication with different properties 3
- When peripheral administration is necessary, protocols for safe administration through peripheral IV have been developed, but these still require careful monitoring and should be limited to low doses for less than 24 hours 4
Dosing and Titration
- Initial infusion typically starts at 0.5 mg/h and is titrated up to 3 mg/h based on patient response 2
- Average maintenance dose ranges from 0.5 mL to 1 mL per minute (2-4 μg of base) 1
- Titrate according to the response of the patient, with significant individual variation in dose requirements 1
Despite some research suggesting stability of norepinephrine in normal saline 5, 6, clinical practice should follow FDA guidelines which explicitly state that administration in saline solution alone is not recommended 1. The dextrose in the recommended solutions provides protection against oxidation, which is critical for maintaining the potency of norepinephrine during administration.