What is the maximum dose of Levophed (norepinephrine)?

Maximum Dose of Levophed (Norepinephrine)

There is no absolute maximum dose of norepinephrine—doses should be titrated to achieve adequate tissue perfusion, with reported doses ranging as high as 68 mg/day (approximately 3 mg/hour) in the FDA label, though real-world ICU practice shows some patients receiving doses exceeding 7 mcg/kg/min when necessary. 1, 2

Standard Dosing Framework

Initial and Typical Dosing

• Start norepinephrine at 0.5 mg/hour (approximately 0.1-0.5 mcg/kg/min) via continuous IV infusion 3, 1
• The average maintenance dose ranges from 0.5-1 mL per minute (2-4 mcg of base per minute) when using the standard dilution of 4 mg in 1000 mL 1
• Titrate by 0.5 mg/hour increments every 4 hours to achieve target mean arterial pressure 3

Target Blood Pressure Goals

• Target MAP of 65 mmHg for most patients with septic shock 3, 4
• In previously hypertensive patients, raise blood pressure no higher than 40 mmHg below the preexisting systolic pressure 1
• Titrate to both MAP and markers of tissue perfusion: lactate clearance, urine output >50 mL/hour, mental status, and capillary refill 3

High-Dose Considerations

FDA-Approved Upper Range

• 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
• This translates to approximately 3 mg/hour as a practical upper limit in many protocols 3

Real-World ICU Practice

• A 2025 retrospective study of 28,397 ICU admissions in Alberta showed the 90th percentile maximum dose was 0.7 mcg/kg/min, with a full range of 0.01-7.3 mcg/kg/min 2
• The 99th percentile reached 2.0 mcg/kg/min, demonstrating that substantially higher doses are used when clinically necessary 2
• Some patients received maximum combined vasopressor doses (norepinephrine-equivalents) well above typical ranges, with hospital survival of 31.6% even in the high-dose group 2

Critical Decision Points Before Escalating Dose

Rule Out Occult Hypovolemia First

• Always suspect and correct occult blood volume depletion when requiring high doses—this is the most common reason for apparent norepinephrine resistance 1
• Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 3
• Central venous pressure monitoring is usually helpful in detecting and treating inadequate volume resuscitation 1

Add Second-Line Agents Rather Than Escalating Indefinitely

• When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min as second-line therapy 3
• Consider adding epinephrine 0.1-0.5 mcg/kg/min for refractory shock 3
• For persistent hypoperfusion despite adequate vasopressors, add dobutamine up to 20 mcg/kg/min if myocardial dysfunction is present 3

Administration and Safety Requirements

Route of Administration

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 3, 1
• If central access is unavailable, peripheral IV or intraosseous administration can be used temporarily during initial resuscitation 3
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring when using high doses 3

Extravasation Management

• If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site immediately to prevent tissue necrosis 3
• Pediatric dose: 0.1-0.2 mg/kg up to 10 mg 3

Special Population Considerations

Obese Patients

• Obese patients (BMI ≥30) require lower weight-based doses (0.09 mcg/kg/min) compared to non-obese patients (0.13 mcg/kg/min), but similar total non-weight-based doses (approximately 9 mcg/min vs 8 mcg/min) 5
• Weight-based dosing in obese patients may lead to higher cumulative doses without achieving faster time to goal MAP 6

Pediatric Patients

• Pediatric dosing typically ranges from 0.1-1.0 mcg/kg/min, starting at the lowest dose 3
• Maximum doses up to 5 mcg/kg/min may be necessary in some children 3

Key Pitfalls to Avoid

• Never continue escalating norepinephrine indefinitely without reassessing volume status—occult hypovolemia is the most common cause of apparent vasopressor resistance 1
• Do not use dopamine as first-line agent—it is associated with higher mortality and more arrhythmias compared to norepinephrine 3
• Avoid phenylephrine as first-line therapy—it may raise blood pressure while worsening tissue perfusion 3
• Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as it becomes inactivated 3
• Plan for central line placement if norepinephrine will be needed beyond initial resuscitation, rather than prolonged peripheral administration 3