What is the recommended starting dose of Levophed (norepinephrine) for treating hypotension?

Norepinephrine Dosing for Hypotension

Start norepinephrine at 0.5-1 mL/min (2-4 mcg/min of base) after diluting 4 mg in 1000 mL of 5% dextrose, and titrate to achieve a mean arterial pressure of 65 mmHg or systolic blood pressure of 80-100 mmHg. 1

Preparation and Dilution

• Dilute 4 mg (one 4 mL vial) of norepinephrine in 1000 mL of 5% dextrose solution to create a concentration of 4 mcg/mL 1
• Use 5% dextrose injection or 5% dextrose with sodium chloride; these dextrose-containing fluids protect against potency loss from oxidation 1
• Saline solution alone is not recommended for dilution 1
• Alternative concentration: 16 mcg/mL can be prepared by adding 4 mg to 250 mL of D5W 2

Initial Dosing

• Begin with 2-3 mL/min (8-12 mcg/min of base) and observe the initial response 1
• After assessing response, adjust to maintenance range of 0.5-1 mL/min (2-4 mcg/min of base) 1
• Alternative starting approach: 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70 kg adult) 2

Administration Route

• Administer through a large central vein whenever possible using a plastic intravenous catheter advanced centrally and securely fixed 1
• If central access is unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily with strict monitoring 3, 2
• Use an IV drip chamber or metering device to accurately measure flow rate in drops per minute 1

Blood Pressure Targets

• Target mean arterial pressure (MAP) of 65 mmHg for septic shock 3, 2
• For general hypotension, maintain systolic blood pressure of 80-100 mmHg 1
• In previously hypertensive patients, raise blood pressure no higher than 40 mmHg below the pre-existing systolic pressure 1

Critical Pre-Administration Requirements

• Correct blood volume depletion as fully as possible before starting norepinephrine 1
• Administer crystalloid fluid boluses (minimum 30 mL/kg) before or concurrent with vasopressor initiation in septic shock 2
• When intraaortic pressures must be maintained emergently to prevent cerebral or coronary ischemia, norepinephrine can be given before and concurrently with volume replacement 1

Titration and Monitoring

• Titrate dose according to individual patient response to achieve and maintain adequate blood pressure 1
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 3, 2
• Place an arterial catheter as soon as practical in all patients requiring vasopressors 3
• Assess peripheral perfusion regularly (skin temperature, capillary refill) 3

High-Dose Considerations

• Great individual variation exists in required dosing; occasionally much larger doses may be necessary 1
• Doses as high as 68 mg base (17 vials) daily have been used in refractory hypotension 1
• If the patient remains hypotensive on high doses, always suspect and correct occult blood volume depletion 1
• Central venous pressure monitoring is helpful in detecting and treating volume depletion 1
• Higher doses (>10 mcg/min) are associated with increased mortality and should be avoided if possible 3

Duration and Weaning

• Continue infusion until adequate blood pressure and tissue perfusion are maintained without therapy 1
• Reduce infusions gradually, avoiding abrupt withdrawal 1
• Decrease dose by 25% of current dose every 30 minutes as tolerated 3
• Treatment may be required for up to 6 days in cases of vascular collapse from acute myocardial infarction 1

Extravasation Management

• If extravasation occurs, immediately infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the affected site to prevent tissue necrosis 3, 2
• Norepinephrine can cause severe tissue necrosis and sloughing if extravasation occurs 3

Drug Compatibility

• Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as it becomes inactivated in alkaline solutions 2
• Administer whole blood or plasma separately (using a Y-tube with individual containers if given simultaneously) 1

Special Clinical Situations

• Norepinephrine is the first-choice vasopressor for septic shock over dopamine, epinephrine, or phenylephrine (strong recommendation, moderate quality evidence) 3, 2
• For cardiogenic shock, use cautiously and only transiently due to risk of increasing afterload and decreasing end-organ blood flow 3
• Typical dosage range for acute heart failure: 0.2-1.0 mcg/kg/min 3
• For beta-blocker toxicity, norepinephrine is more effective than dopamine 2

Common Pitfalls to Avoid

• Never start norepinephrine in a hypovolemic patient without concurrent volume resuscitation, as vasoconstriction in hypovolemia causes severe organ hypoperfusion despite "normal" blood pressure 2
• Avoid using saline alone for dilution; always use dextrose-containing solutions 1
• Do not attempt to achieve "normal" blood pressure in all patients; target is adequate organ perfusion, not normalization 1