How to administer norepinephrine infusion?

Norepinephrine Infusion Administration

Dilute 4 mg of norepinephrine in 250 mL of D5W (yielding 16 mcg/mL concentration), administer through central venous access when possible, start at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min), and titrate every 5-15 minutes to achieve a target MAP of 65 mmHg while ensuring adequate fluid resuscitation with at least 30 mL/kg crystalloid bolus before or concurrent with initiation. 1, 2

Preparation and Concentration

• Standard adult concentration: Add 4 mg of norepinephrine to 250 mL of D5W to yield 16 mcg/mL 1, 2
• The FDA label specifies that norepinephrine must be diluted in dextrose-containing solutions (5% dextrose or 5% dextrose with sodium chloride) as these provide protection against oxidation 2
• Administration in saline solution alone is not recommended due to potency loss from oxidation 2
• Alternative concentration for specific scenarios: 1 mg in 100 mL saline (10 mcg/mL) can be used in anaphylaxis 1

Critical Pre-Administration Requirements

Address hypovolemia FIRST with a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation - vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 1, 3

• Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline 1
• In profound, life-threatening hypotension (systolic <70 mmHg or diastolic ≤40 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion 1, 3
• Early norepinephrine administration should be considered when diastolic shock index (heart rate/diastolic BP) is ≥3 3

Administration Route

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1, 2

• Insert a plastic IV catheter through a suitable bore needle well advanced centrally into the vein and securely fixed with adhesive tape 2
• If central access is unavailable or delayed, peripheral IV administration can be used temporarily with strict protocols 1, 4, 5:
  • Use large-bore catheter (≥20 gauge preferred) 4
  • Select antecubital or forearm sites (avoid hand, wrist, or small veins) 4
  • Limit to doses <0.25 mcg/kg/min and duration <24 hours 4, 5
  • Check IV site every 2 hours for signs of infiltration 4
  • Have phentolamine 5-10 mg immediately available 1

Initial Dosing and Titration

Starting dose: 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) 1, 2

• The FDA label recommends observing response to initial dose of 2-3 mL/min (8-12 mcg base/min), then adjusting to establish low normal blood pressure 2
• Titrate every 5-15 minutes during initial phase based on blood pressure and tissue perfusion markers 1
• Increase by 0.5 mg/h every 4 hours as needed, up to maximum of 3 mg/h 1
• Average maintenance dose: 0.5-1 mL/min (2-4 mcg base/min) per FDA label 2

Target Blood Pressure

Target MAP of 65 mmHg for most patients 1, 2

• In previously hypertensive patients, raise blood pressure no higher than 40 mmHg below pre-existing systolic pressure 2
• Patients with chronic hypertension or atherosclerosis may require higher MAP targets 1
• Titrate to both MAP and tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill, age-appropriate heart rate 1

Monitoring Requirements

• Blood pressure and heart rate every 5-15 minutes during initial titration 1
• Place arterial catheter as soon as practical for continuous monitoring 1
• Use IV drip chamber or metering device to permit accurate flow rate estimation 2
• Monitor for signs of excessive vasoconstriction: cold extremities, decreased urine output, elevated lactate 1
• Assess tissue perfusion continuously, not just blood pressure numbers 1

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 (do not increase above this dose) 1
• Alternative: Add epinephrine 0.1-0.5 mcg/kg/min 1
• For persistent hypoperfusion despite adequate vasopressors, add dobutamine up to 20 mcg/kg/min if myocardial dysfunction present 1
• Do NOT use dopamine as first-line agent - associated with higher mortality and arrhythmias 1
• Do NOT use phenylephrine as first-line - may raise blood pressure while worsening tissue perfusion 1

Management of Extravasation

If extravasation occurs, infiltrate phentolamine 5-10 mg diluted in 10-15 mL of saline intradermally at the site immediately to prevent tissue necrosis 1, 2

• Pediatric dose: 0.1-0.2 mg/kg up to 10 mg 1
• Recent studies show extravasation rate of 75.8 events/1,000 days of peripheral infusion, with most causing no or minimal tissue injury and no patients requiring surgical intervention 5

Pediatric Dosing

• Starting dose: 0.1 mcg/kg/min, titrated to 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 some children 1
• "Rule of 6" for simplified preparation: 0.6 × body weight (kg) = mg of norepinephrine diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min 1

Critical Pitfalls to Avoid

• Never mix with sodium bicarbonate or alkaline solutions - norepinephrine is inactivated in alkaline solutions 1, 2
• Avoid infusion pump loading dose errors - a case report documented cardiac arrest from inadvertent 1.8 mg bolus when pump reverted to historical rate of 999 mL/h 6
• Always verify pump settings and clear historical values before initiating infusion 6
• Do not rely solely on fluids to restore blood pressure in profound hypotension - this unduly prolongs hypotension and organ hypoperfusion 3
• Suspect occult blood volume depletion if requiring very high doses; central venous pressure monitoring helpful 2

Special Clinical Scenarios

Hepatorenal syndrome: Start at 0.5 mg/h, increase every 4 hours by 0.5 mg/h to maximum 3 mg/h, targeting MAP increase ≥10 mmHg and/or urine output >50 mL/h for at least 4 hours 1

Anaphylaxis refractory to epinephrine: Use only after epinephrine injections and volume resuscitation have failed; start at 0.05-0.1 mcg/kg/min 1

Pregnant patients with sepsis: Consider more restrictive initial boluses of 1-2 L due to lower colloid oncotic pressure and higher pulmonary edema risk; start norepinephrine at 0.02 mcg/kg/min with target MAP 65 mmHg 1