How do you calculate a norepinephrine (vasopressor) drip dose?

How to Calculate Norepinephrine Drip Dose

The standard norepinephrine drip is prepared by adding 4 mg of norepinephrine to 250 mL of D5W, yielding a concentration of 16 mcg/mL, with initial dosing starting at 0.1-0.5 mcg/kg/min (or 7-35 mcg/min in a 70 kg adult) and titrated to achieve a mean arterial pressure of 65 mmHg. 1, 2

Standard Concentration Preparation

• Add 4 mg (4 mL) of norepinephrine to 1,000 mL of 5% dextrose solution to create a concentration of 4 mcg/mL 2
• Alternatively, add 4 mg of norepinephrine to 250 mL of D5W to yield a more concentrated solution of 16 mcg/mL 1
• Dextrose-containing solutions are essential as they protect against significant loss of potency due to oxidation; administration in saline alone is not recommended 2
• Solutions remain chemically stable for seven days at room temperature under ambient light when diluted in either D5W or normal saline 3

Initial Dosing and Titration

• Start at 2-3 mL/min (8-12 mcg/min) using the 4 mcg/mL concentration, then titrate to maintain systolic blood pressure of 80-100 mmHg 2
• Using weight-based dosing: initiate at 0.1-0.5 mcg/kg/min, which translates to 7-35 mcg/min in a 70 kg adult 1
• The average maintenance dose ranges from 0.5-1 mL/min (2-4 mcg/min of base) using the standard 4 mcg/mL concentration 2
• Titrate dose every 4 hours as needed, increasing by 0.5 mg/h increments up to a maximum of 3 mg/h 1

Target Blood Pressure Goals

• Target mean arterial pressure (MAP) of 65 mmHg for septic shock 1
• In previously hypertensive patients, raise blood pressure no higher than 40 mmHg below the pre-existing systolic pressure 2
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1

Critical Pre-Administration Requirements

• Address hypovolemia FIRST with a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1
• In severe hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues, rather than waiting for complete volume repletion 1
• Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 1

Administration Route and Safety

• Central venous access is strongly preferred to minimize extravasation risk 1, 2
• If central access is unavailable or delayed, peripheral IV can be used temporarily with strict monitoring 1
• Insert a plastic IV catheter well advanced centrally into the vein and securely fixed with adhesive tape 2
• Use an IV drip chamber or metering device to permit accurate estimation of flow rate in drops per minute 2

Extravasation Management

• If extravasation occurs, immediately infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline at the site to prevent tissue necrosis 1, 2
• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg 1

Special Dosing Considerations

Pediatric Dosing

• Standard pediatric dosing ranges from 0.1-1.0 mcg/kg/min, starting at the lowest dose and titrating to effect 1
• Doses as high as 5 mcg/kg/min may be necessary in children 1
• "Rule of 6" for pediatric infusions: 0.6 × body weight (kg) = number of milligrams diluted to total 100 mL of saline; then 1 mL/h delivers 0.1 mcg/kg/min 1

Obese Patients

• Obese patients require lower weight-based doses (0.09 mcg/kg/min) compared to non-obese patients (0.13 mcg/kg/min) 4
• However, total non-weight-based doses are similar between obese and non-obese patients (approximately 8-9 mcg/min) 4

Alternative Concentration for Anaphylaxis

• For anaphylaxis requiring continuous infusion: add 1 mg of norepinephrine to 100 mL of saline to create a 1:100,000 solution (10 mcg/mL) 1
• Administer at an initial rate of 30-100 mL/h (5-15 mcg/min), titrated based on clinical response 1

Monitoring and Titration Endpoints

• Titrate to achieve target MAP and markers of tissue perfusion including lactate clearance, urine output (>50 mL/h), mental status, and capillary refill 1
• When norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, add vasopressin (0.03-0.04 units/min) as second-line therapy rather than continuing to escalate norepinephrine alone 1
• Place an arterial catheter as soon as practical for continuous monitoring 1

Important Precautions

• Do not mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as adrenergic agents are inactivated in alkaline solutions 1, 2
• Watch for potential side effects including hypertension, arrhythmias, tissue ischemia, cold extremities, and decreased urine output 1
• Reduce infusion gradually when discontinuing; avoid abrupt withdrawal 2
• Great individual variation occurs in required doses; occasionally doses as high as 68 mg base (17 vials) daily may be necessary, but always suspect and correct occult blood volume depletion 2