How to initiate a noradrenaline (norepinephrine) infusion?

How to Initiate Norepinephrine Infusion

Start norepinephrine at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) via continuous IV infusion, preferably through central venous access, while simultaneously ensuring adequate fluid resuscitation with at least 30 mL/kg crystalloid bolus. 1

Critical Pre-Administration Requirements

Address hypovolemia FIRST before or concurrent with norepinephrine initiation. 1 Administer a minimum 30 mL/kg crystalloid bolus—this is non-negotiable. 1 Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure readings. 1 Use balanced crystalloids (lactated Ringer's or Plasma-Lyte) preferentially over normal saline. 1

Common pitfall: Starting norepinephrine without adequate volume resuscitation will raise blood pressure numbers while worsening tissue perfusion. 1

Preparation and Concentration

The standard adult concentration is prepared by adding 4 mg of norepinephrine to 250 mL of D5W, yielding 16 μg/mL. 1 The FDA-approved initial dose is 0.25-0.375 mL per minute (8-12 mcg of base per minute). 2

Alternative concentration: Add 1 mg norepinephrine to 100 mL saline for a 10 μg/mL solution, useful in fluid-restricted situations. 1

Pediatric dosing: Start at 0.1 mcg/kg/min, titrating to effect within a typical range of 0.1-1.0 mcg/kg/min. 1 Maximum doses up to 5 mcg/kg/min may be necessary in exceptional circumstances. 1 Use the "Rule of 6" for simplified preparation: 0.6 × body weight (kg) = milligrams diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min. 1

Administration Route

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 2 However, if central access is unavailable or delayed, peripheral IV administration can be used temporarily with strict protocols. 1

For peripheral administration:

• Use large-bore IV (18-20 gauge minimum) 1
• Proper site selection (avoid hand/wrist; prefer antecubital fossa) 1
• Visual inspection and evaluation every 2 hours 3
• Limit to low doses (<0.5 mcg/kg/min) and duration <24 hours 3
• Maximum dose adherence critical for safety 3

If extravasation occurs: Infiltrate 5-10 mg phentolamine diluted in 10-15 mL 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

Target Blood Pressure and Titration

Target mean arterial pressure (MAP) of 65 mmHg for most patients with septic shock. 1 This is the evidence-based standard with strong recommendation and moderate quality evidence. 1

Titration protocol:

• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1
• Increase dose by 0.5 mg/h every 4 hours as needed, to maximum of 3 mg/h 1
• FDA-approved average maintenance dose: 2-4 mcg/min (0.0625-0.125 mL per minute) 2
• Place arterial catheter as soon as practical for continuous monitoring 1

Assess tissue perfusion markers beyond MAP alone:

• Lactate clearance 1
• Urine output >50 mL/h for at least 4 hours 1
• Mental status 1
• Capillary refill and skin perfusion 1

Special consideration: Patients with chronic hypertension may require higher MAP targets, while younger normotensive patients may tolerate lower pressures. 1 However, 65 mmHg remains the initial target. 1

Monitoring Requirements

• Blood pressure every 5-15 minutes initially 1
• Continuous cardiac monitoring for arrhythmias 2
• Signs of excessive vasoconstriction: cold extremities, decreased urine output 1
• Watch for hypertension, arrhythmias, and tissue ischemia 1

Critical safety note: Never mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line—adrenergic agents are inactivated in alkaline solutions. 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 1
• Do NOT increase vasopressin above 0.04 units/min except for salvage therapy 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

What NOT to do:

• Do NOT use dopamine as first-line agent—associated with higher mortality and more arrhythmias 1
• Do NOT use low-dose dopamine for "renal protection"—no benefit and strongly discouraged 1
• Do NOT use phenylephrine as first-line therapy—may raise blood pressure while worsening tissue perfusion 1

Discontinuation

Reduce infusion rate gradually when discontinuing—sudden cessation may result in marked hypotension. 2 The pressor action stops within 1-2 minutes after infusion is discontinued due to rapid uptake and metabolism. 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: Add norepinephrine at 0.05-0.1 mcg/kg/min for persistent hypotension after 10 minutes despite epinephrine boluses and volume resuscitation. 1

Pregnant patients: Start at 0.02 mcg/kg/min with target MAP 65 mmHg; consider more restrictive initial boluses of 1-2 L due to lower colloid oncotic pressure. 1

Beta-blocker toxicity: Norepinephrine is more effective than dopamine for hypotension in this context. 1