Can I administer levophed (norepinephrine) with 3% saline simultaneously?

Compatibility of Levophed (Norepinephrine) with 3% Saline

Yes, you can administer levophed (norepinephrine) with 3% saline running simultaneously, but the FDA-approved preparation specifically requires dilution in dextrose-containing solutions, not saline alone. 1

Critical Preparation Requirements

The FDA label explicitly states that norepinephrine should be diluted in 5% dextrose injection or 5% dextrose and sodium chloride injections—administration in saline solution alone is NOT recommended. 1 This is because dextrose-containing fluids provide protection against significant loss of potency due to oxidation. 1

Standard Dilution Protocol

• Recommended preparation: Add 4 mg norepinephrine to 1,000 mL of 5% dextrose solution (yielding 4 mcg/mL concentration) 1
• Alternative concentration for specific situations: 1 mg in 100 mL saline for anaphylaxis (1:100,000 solution) 2
• The American Academy of Allergy, Asthma, and Immunology suggests 4 mg in 250 mL D5W for 16 μg/mL concentration 2

Simultaneous Administration Considerations

Separate Line Requirements

If you need to run both norepinephrine and 3% saline simultaneously, they should be administered through separate IV access points. The FDA label specifically warns that adrenergic drugs should not be mixed with alkaline solutions in the IV line, as they are inactivated in such solutions. 3

Access Route Priorities

• Central venous access is strongly preferred for norepinephrine administration to minimize extravasation risk 2, 3, 1
• If central access is unavailable or delayed, peripheral IV administration can be used temporarily with strict monitoring 2, 3
• The Society of Critical Care Medicine supports temporary peripheral or intraosseous administration when central access is not immediately available 2

Clinical Context: Why Both Might Be Running

Fluid Resuscitation in Septic Shock

The Surviving Sepsis Campaign guidelines provide the framework for understanding when both therapies are appropriate:

• Initial resuscitation requires crystalloid fluid boluses (minimum 30 mL/kg) BEFORE or concurrent with vasopressor initiation 4
• Norepinephrine is the first-choice vasopressor for septic shock (strong recommendation, moderate quality evidence) 4
• Crystalloids (including normal saline or balanced crystalloids) are recommended for initial resuscitation 4

Hypovolemia Must Be Addressed First

A critical pitfall: Never start norepinephrine in a hypovolemic patient without concurrent volume resuscitation. 3 Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure readings. 3 The FDA label emphasizes that blood volume depletion should always be corrected as fully as possible before any vasopressor is administered. 1

Practical Administration Strategy

If Using Y-Site or Separate Lines

• Run norepinephrine through one line (preferably central) diluted in D5W as per FDA requirements 1
• Run 3% saline through a separate line for volume resuscitation or hyponatremia correction
• Do NOT mix the two solutions in the same line or bag 3, 1

Monitoring Requirements

• Blood pressure and heart rate every 5-15 minutes during initial titration 2, 3
• Target MAP of 65 mmHg for septic shock 4
• Monitor for extravasation signs (cold extremities, decreased urine output) 2
• If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline at the site 2, 3

Special Consideration: 3% Saline Safety

Recent evidence demonstrates that 3% hypertonic saline can be safely administered peripherally at rates up to 50 mL/h through 16-20 gauge catheters with low complication rates (10.7% minor complications including infiltration and thrombophlebitis). 5, 6 This is relevant if you lack central access for either medication.

Common Pitfall to Avoid

Do not delay norepinephrine administration waiting for "perfect" central access in a profoundly hypotensive patient. The FDA label states that when intraaortic pressures must be maintained as an emergency measure to prevent cerebral or coronary ischemia, norepinephrine can be administered before and concurrently with blood volume replacement. 1 Use peripheral access temporarily if needed, with meticulous monitoring. 2