Is noradrenaline (norepinephrine) compatible with normal saline?

Norepinephrine Compatibility with Normal Saline

Norepinephrine is fully compatible with normal saline (0.9% sodium chloride) for dilution and administration, though dextrose-containing solutions are preferred when available to reduce oxidative potency loss. 1

FDA-Approved Dilution Guidelines

The FDA label explicitly permits normal saline as a diluent for norepinephrine, with the following specifications: 1

• Standard dilution: Add 4 mg norepinephrine to 1,000 mL of either 5% Dextrose Injection or Sodium Chloride solutions containing 5% dextrose to produce a 4 mcg/mL concentration 1
• Saline-only solutions: While administration in saline solution alone is "not recommended" as the preferred option, it is explicitly listed as an acceptable alternative when dextrose solutions are unavailable 1
• The FDA notes that dextrose reduces loss of potency due to oxidation, which is why dextrose-containing solutions are preferred over saline alone 1

Chemical Stability Evidence

Norepinephrine maintains excellent chemical stability in normal saline for extended periods. A prospective stability study demonstrated: 2

• No significant decrease in norepinephrine concentration when diluted in normal saline at both 4 mcg/mL and 16 mcg/mL concentrations over 7 days 2
• 96.4% concentration retention at 168 hours for both tested concentrations in normal saline 2
• Stability maintained at room temperature under ambient light conditions 2
• Comparable stability between normal saline and D5W solutions 2

Clinical Practice Recommendations

For peripheral administration specifically, 0.9% saline is recommended as the default diluent. Recent systematic reviews analyzing peripheral norepinephrine administration concluded: 3, 4

• Normal saline (0.9%) should be used as the standard diluent for peripheral norepinephrine infusions 3, 4
• This recommendation applies particularly to early resuscitation scenarios where peripheral access may be used temporarily 3, 4

Alternative Dilution Protocols from Guidelines

Multiple guideline-based protocols confirm normal saline compatibility: 5

• For anaphylaxis: 1 mg norepinephrine in 100 mL saline creates a 1:100,000 solution, administered at 30-100 mL/h 5
• Vasopressin combination: Vasopressin can be diluted as 25 U/250 mL in either 5% dextrose water or normal saline 6

Critical Incompatibilities to Avoid

Never mix norepinephrine with alkaline solutions in the same IV line. 5

• Adrenergic drugs are inactivated in alkaline solutions 5
• Specifically avoid contact with sodium bicarbonate 5, 1
• Avoid contact with iron salts, alkalis, or oxidizing agents 1

Practical Storage Considerations

Once diluted in normal saline: 1

• Store for up to 24 hours at room temperature [20°C to 25°C (68°F to 77°F)] 1
• Protect from light during storage 1
• Visually inspect before use—solution should be colorless to slightly yellow; discard if pinkish or darker or if precipitate present 1