What is the recommended preparation and dosage for a norepinephrine drip?

Norepinephrine Drip Preparation and Administration

For standard adult preparation, add 4 mg of norepinephrine to 250 mL of D5W to create a concentration of 16 μg/mL, and initiate the infusion at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min), titrating to achieve a mean arterial pressure of 65 mmHg. 1, 2

Standard Preparation Protocol

Adult Concentration:

• Add 4 mg norepinephrine (one 4 mL vial) to 250 mL of 5% dextrose in water (D5W) to yield 16 μg/mL 1, 2
• The FDA label specifies that dextrose-containing solutions protect against significant potency loss due to oxidation 2
• Do not use normal saline alone as the diluent - the FDA explicitly states "administration in saline solution alone is not recommended" 2
• Solutions remain chemically stable for 7 days at room temperature under ambient light in either D5W or normal saline, though D5W is preferred per FDA guidance 3, 2

Alternative Concentrations:

• For anaphylaxis scenarios: 1 mg norepinephrine in 100 mL saline creates a 10 μg/mL solution (1:100,000), administered at 30-100 mL/h 1
• For pediatric patients using "Rule of 6": 0.6 × body weight (kg) = mg of norepinephrine, diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min 1

Initial Dosing and Titration

Starting Dose:

• Begin at 0.5 mg/h (8-12 mcg/min or 0.1-0.5 mcg/kg/min) via continuous IV infusion 1, 2
• The FDA label recommends an initial test dose of 2-3 mL/min (8-12 mcg/min) to observe response before establishing maintenance rate 2

Titration Strategy:

• Increase by 0.5 mg/h every 4 hours as needed, up to maximum 3 mg/h 1
• Target MAP of 65 mmHg for most patients with septic shock 1
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1

Escalation 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 1
• Consider adding epinephrine 0.1-0.5 mcg/kg/min if vasopressin is insufficient 1
• Do not use dopamine as first-line agent - it is associated with higher mortality and arrhythmias compared to norepinephrine 1

Administration Route and Access

Preferred Access:

• Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1, 2
• The FDA label states to "insert a plastic intravenous catheter through a suitable bore needle well advanced centrally into the vein" 2

Temporary Alternatives:

• Peripheral IV can be used temporarily if central access is unavailable or delayed, with strict monitoring 1
• Intraosseous (IO) administration is acceptable in emergency situations, particularly after 40-60 mL/kg fluid resuscitation in children with septic shock 1
• All medications given via IO should be followed by saline flush and may require manual pressure or infusion pump 1

Critical Pre-Administration Requirements

Fluid Resuscitation First:

• Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1
• The FDA label emphasizes "blood volume depletion should always be corrected as fully as possible before any vasopressor is administered" 2
• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 1
• Vasoconstriction without adequate volume causes severe organ hypoperfusion despite "normal" blood pressure 1

Exception for Severe Hypotension:

• In life-threatening hypotension (systolic <70 mmHg), start norepinephrine as emergency measure while fluid resuscitation continues, rather than waiting for complete volume repletion 1
• Recent evidence supports early norepinephrine administration in profound hypotension (diastolic ≤40 mmHg or diastolic shock index ≥3) to prevent prolonged hypotension and organ damage 4

Monitoring Requirements

Hemodynamic Monitoring:

• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1
• Monitor MAP, heart rate, and tissue perfusion markers (lactate clearance, urine output >50 mL/h, mental status, capillary refill) 1

Target Parameters:

• MAP ≥65 mmHg for most patients 1
• Patients with chronic hypertension may require higher MAP targets 1
• In hepatorenal syndrome, target MAP increase ≥10 mmHg and/or urine output >50 mL/h for at least 4 hours 1

Extravasation Management

Immediate Treatment:

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

Pediatric Dosing

Standard Pediatric Range:

• Start at 0.1 mcg/kg/min, titrating to desired clinical effect 1
• Typical range: 0.1-1.0 mcg/kg/min 1
• Maximum doses up to 5 mcg/kg/min may be necessary in exceptional circumstances, mandating central line placement 1

Critical Pitfalls to Avoid

Drug Incompatibilities:

• Never mix norepinephrine with sodium bicarbonate or other alkaline solutions - adrenergic agents are inactivated in alkaline solutions 1, 2

Fluid Selection Errors:

• Do not use hydroxyethyl starch (HES) for fluid resuscitation with norepinephrine - it increases mortality (51% vs 43%, p=0.03) and renal injury 1
• Avoid gelatin and dextran solutions 1

Dosing Errors:

• Do not use low-dose dopamine for renal protection - it has no benefit and is strongly discouraged 1
• Do not use phenylephrine as first-line therapy - it may raise blood pressure while worsening tissue perfusion 1

Volume Status Errors:

• Do not start norepinephrine without addressing hypovolemia first, except in life-threatening hypotension 1, 2
• Excessive fluid resuscitation should also be avoided - use conservative strategy after initial 30 mL/kg bolus 1