What is the recommended dilution for NorAdrenaline (Norepinephrine)?

Norepinephrine Dilution Guidelines

The standard adult dilution for norepinephrine is 4 mg added to 250 mL of 5% dextrose (D5W), yielding a concentration of 16 mcg/mL, which should be administered via continuous infusion starting at 0.5 mg/h (approximately 8-12 mcg/min) and titrated to effect. 1, 2

Standard Preparation and Concentration

Adult Dilution

• Add 4 mg of norepinephrine to 1000 mL of 5% dextrose solution to create a 4 mcg/mL concentration (this is the FDA-approved standard dilution) 2
• Alternatively, add 4 mg to 250 mL of D5W for a more concentrated 16 mcg/mL solution, which is commonly used in clinical practice 1
• Dextrose-containing solutions are essential as they protect against significant loss of potency due to oxidation; saline solution alone is not recommended 2

Alternative Concentrations

• For anaphylaxis requiring continuous infusion: 1 mg norepinephrine in 100 mL saline creates a 1:100,000 solution (10 mcg/mL), administered at 30-100 mL/h 1
• The concentration can be adjusted based on fluid volume requirements, but more dilute solutions than 4 mcg/mL should be used if large fluid volumes are needed 2

Pediatric Dilution Methods

Rule of 6 Method

• Multiply 0.6 × body weight (kg) = number of milligrams of norepinephrine to add to 100 mL of saline 1
• With this dilution, 1 mL/h delivers 0.1 mcg/kg/min 1
• This simplified approach facilitates accurate dosing in pediatric patients 1

Standard Pediatric Dosing

• Starting dose: 0.1 mcg/kg/min, titrated to desired clinical effect 3, 1
• Typical range: 0.1-1.0 mcg/kg/min 3, 1
• Maximum doses up to 5 mcg/kg/min may be necessary in some children 3, 1

Administration Route and Safety

Preferred Access

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1, 2
• The catheter should be well advanced centrally into the vein and securely fixed 2

Peripheral Administration

• If central access is unavailable or delayed, peripheral IV or intraosseous administration can be used temporarily 1, 4
• In pediatric studies, peripheral or intraosseous routes were used safely for a median duration of 3 hours without adverse effects 4
• Strict monitoring for extravasation is mandatory with peripheral administration 1

Critical Precautions

Extravasation Management

• If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site to prevent tissue death and sloughing 1, 2
• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg diluted in 10 mL of 0.9% sodium chloride 3, 1

Drug Compatibility

• Never mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as adrenergic agents are inactivated in alkaline solutions 1, 2

Volume Resuscitation Requirements

• Address hypovolemia first with minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1
• In severe hypotension (systolic <70 mmHg), norepinephrine may be started as an emergency measure while fluid resuscitation continues 1
• Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 1

Dosing and Titration

Initial Dosing

• Adults: Start at 8-12 mcg/min (2-3 mL/min of 4 mcg/mL solution), then titrate 2
• Alternative starting range: 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70 kg adult) 1

Maintenance and Maximum Doses

• Average maintenance: 2-4 mcg/min (0.5-1 mL/min of 4 mcg/mL solution) 2
• Titrate by 0.5 mg/h every 4 hours as needed, up to maximum 3 mg/h 1
• Occasionally, much higher doses (up to 68 mg base daily) may be necessary if hypotension persists, though occult blood volume depletion should always be suspected 2

Target Blood Pressure

• 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 pre-existing systolic pressure 2
• Titrate to both MAP and tissue perfusion markers (lactate clearance, urine output >50 mL/h, mental status, capillary refill) 1

Monitoring Requirements

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1
• Use an IV drip chamber or metering device to permit accurate flow rate estimation 2
• Watch for signs of excessive vasoconstriction: cold extremities, decreased urine output 1
• Consider arterial catheter placement for continuous monitoring 1