What is the maximum recommended dose of a norepinephrine (levophed) drip?

Maximum Dosing of Norepinephrine (Levophed) Drip

The maximum recommended dose of norepinephrine is 3 mg/h (approximately 50 mcg/min or 0.7 mcg/kg/min in a 70 kg adult), though doses as high as 68 mg base per day have been reported in refractory cases where occult blood volume depletion has been excluded. 1

Standard Dosing Parameters

Starting and Titration Protocol:

• Initial dose: 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) 2, 1
• Titration increments: Increase by 0.5 mg/h every 4 hours as needed 2
• Standard maximum: 3 mg/h 2
• Target: Mean arterial pressure (MAP) ≥65 mmHg 2

Preparation and Concentration

Standard dilution: Add 4 mg of norepinephrine to 1000 mL of 5% dextrose solution to yield 4 mcg/mL concentration 1

• Each mL of this dilution contains 4 mcg of norepinephrine base 1
• Initial infusion rate: 2-3 mL/min (8-12 mcg/min) 1
• Maintenance range: 0.5-1 mL/min (2-4 mcg/min) 1

Alternative concentration: 16 mcg/mL can be prepared by adding 4 mg to 250 mL of D5W 2

Extreme Dosing Situations

When standard maximum doses fail:

• Doses as high as 68 mg base per day (17 vials) may be necessary in refractory hypotension 1
• Critical caveat: Before escalating to extreme doses, always suspect and correct occult blood volume depletion 1
• Central venous pressure monitoring is helpful in detecting hypovolemia 1

Weight-Based Dosing Considerations

Typical range in septic shock: 0.1-2 mcg/kg/min 2

Pediatric dosing:

• Starting dose: 0.1 mcg/kg/min 2
• Typical range: 0.1-1.0 mcg/kg/min 2
• Maximum: Up to 5 mcg/kg/min may be necessary in some children 2

Obesity consideration: Obese patients require lower weight-based doses but similar total (non-weight-based) doses compared to non-obese patients 3

Escalation Strategy for Refractory Hypotension

When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists:

• Add vasopressin 0.03-0.04 units/min as second-line therapy 2
• Consider adding epinephrine 0.1-0.5 mcg/kg/min 2
• Do NOT increase vasopressin above 0.03-0.04 units/min except for salvage therapy 2

For persistent hypoperfusion despite adequate vasopressors:

• Add dobutamine up to 20 mcg/kg/min, particularly if myocardial dysfunction is present 2

Critical Pre-Administration Requirements

Volume resuscitation is mandatory:

• Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 2
• In severe hypotension (systolic <70 mmHg), start norepinephrine as emergency measure while fluid resuscitation continues 2
• Pitfall to avoid: Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 2

Administration Route and Monitoring

Preferred access: Central venous line to minimize extravasation risk and tissue necrosis 2, 1

• If central access unavailable, peripheral IV can be used temporarily with strict monitoring 2

Monitoring requirements:

• Blood pressure and heart rate every 5-15 minutes during initial titration 2
• Place arterial catheter as soon as practical for continuous monitoring 2
• Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill 2

Extravasation Management

If extravasation occurs:

• Infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site immediately 2
• Pediatric dose: 0.1-0.2 mg/kg up to 10 mg 2

Important Contraindications and Precautions

Do NOT mix with:

• Sodium bicarbonate or other alkaline solutions, as norepinephrine is inactivated in alkaline solutions 2

Monitor for complications:

• Hypertension, arrhythmias, tissue ischemia 2
• Signs of excessive vasoconstriction: cold extremities, decreased urine output 2