What is the maximum dose of Levophed (norepinephrine)?

Maximum Dose of Levophed (Norepinephrine)

There is no absolute maximum dose of norepinephrine—doses as high as 68 mg base per day (17 vials) have been documented in the FDA label, though doses exceeding 0.6 μg/kg/min within 24 hours are associated with significantly increased mortality and may indicate refractory shock requiring additional interventions. 1, 2

Standard Dosing Range

• The FDA label specifies an average maintenance dose of 2-4 μg of base per minute (0.5-1 mL per minute of standard dilution), with initial dosing at 8-12 μg of base per minute 1
• The European Society of Cardiology guidelines recommend 0.2-1.0 μg/kg/min as the standard infusion range 3
• For a 70 kg adult, this translates to approximately 14-70 μg/min or 0.84-4.2 mg/hour 4

High-Dose Threshold and Mortality Risk

• A maximum norepinephrine dose of ≥0.6 μg/kg/min within 24 hours of ICU admission is associated with 7-day mortality (sensitivity 47%, specificity 93%) and should trigger consideration of refractory shock protocols 2
• The FDA label explicitly states that "occasionally much larger or even enormous daily doses (as high as 68 mg base or 17 vials) may be necessary if the patient remains hypotensive" 1
• However, the label emphasizes that occult blood volume depletion should always be suspected and corrected when high doses are required 1

Escalation Strategy When Approaching High Doses

• When norepinephrine reaches 0.25 μg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min as second-line therapy rather than continuing to escalate norepinephrine alone 4
• If hypoperfusion persists despite adequate vasopressors, add dobutamine up to 20 μg/kg/min for myocardial dysfunction 4
• Consider adding epinephrine 0.1-0.5 μg/kg/min if norepinephrine plus vasopressin are insufficient 4

Critical Considerations at High Doses

• Doses exceeding 0.6 μg/kg/min should prompt immediate reassessment for occult hypovolemia, inadequate source control, or other correctable factors 1, 2
• Central venous pressure monitoring is helpful in detecting and treating occult blood volume depletion when high doses are required 1
• The degree of dilution should be adjusted based on clinical fluid volume requirements—concentrations greater than 4 μg/mL may be necessary when large fluid volumes are clinically undesirable 1

Duration of High-Dose Therapy

• The FDA label documents cases requiring treatment for up to 6 days in vascular collapse due to acute myocardial infarction 1
• Infusions should be reduced gradually, avoiding abrupt withdrawal 1
• Continue infusion until adequate blood pressure and tissue perfusion are maintained without therapy 1

Common Pitfall to Avoid

• The most critical error is escalating norepinephrine to high doses without first ensuring adequate volume resuscitation—this causes severe organ hypoperfusion despite "normal" blood pressure readings 4, 1
• Always verify adequate fluid resuscitation (minimum 30 mL/kg crystalloid) before attributing hypotension to vasodilatory shock requiring extreme vasopressor doses 4