What is the recommended dosage of norepinephrine for adults with septic shock or severe hypotension?

Norepinephrine Dosage for Adults with Septic Shock or Severe Hypotension

For adults with septic shock or severe hypotension, norepinephrine should be initiated at 0.05-0.1 μg/kg/min (approximately 3.5-7 μg/min for a 70kg adult) and titrated every 5-15 minutes to achieve a target mean arterial pressure (MAP) of at least 65 mmHg. 1, 2

First-Line Vasopressor Selection

Norepinephrine is strongly recommended as the first-choice vasopressor for septic shock based on the following evidence:

• The Surviving Sepsis Campaign guidelines provide a strong recommendation with moderate quality evidence for norepinephrine as first-line therapy 1
• Norepinephrine has predominantly alpha-1 adrenergic effects, making it a potent vasoconstrictor with minimal tachycardia 2
• Early administration of norepinephrine has been shown to increase shock control rate and improve outcomes 3, 4

Dosing Protocol

1. Initial dosing: 0.05-0.1 μg/kg/min (3.5-7 μg/min for a 70kg adult) 1, 2
2. Titration: Increase by 0.05-0.1 μg/kg/min every 5-15 minutes 2
3. Administration route: Preferably through a central venous catheter to reduce extravasation risk 2
4. Target MAP: ≥65 mmHg for most patients 1, 5
   • Consider higher targets (75-85 mmHg) for patients with chronic hypertension 4

Refractory Hypotension Management

If target MAP is not achieved despite adequate fluid resuscitation and increasing norepinephrine doses:

1. Add vasopressin up to 0.03 U/min to either raise MAP or decrease norepinephrine requirements 1, 2
2. Consider epinephrine as an alternative second agent (weak recommendation, low quality evidence) 1
3. For persistent hypoperfusion despite adequate MAP and fluid resuscitation, add dobutamine up to 20 μg/kg/min 1

Practical Considerations

• Early initiation: Recent evidence supports starting norepinephrine early in resuscitation, especially in patients with profound hypotension (diastolic BP ≤40 mmHg) 3, 6
• Monitoring: All patients requiring vasopressors should have an arterial catheter placed as soon as practical 1
• Fluid status: Ensure adequate fluid resuscitation before or during vasopressor therapy 2
• High-dose therapy: In cases of refractory hypotension, norepinephrine doses up to 1 μg/kg/min may be considered before adding other agents 5

Important Cautions

• Extravasation risk: Administer through central line whenever possible; if extravasation occurs, infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the site 1
• Drug interactions: Do not mix adrenergic drugs with sodium bicarbonate or other alkaline solutions in the IV line 1
• Contraindications: Norepinephrine is relatively contraindicated in hypovolemic patients; ensure adequate volume status first 1
• Avoid low-dose dopamine: Not recommended for renal protection (strong recommendation, high quality evidence) 1

By following this evidence-based approach to norepinephrine dosing in septic shock, clinicians can optimize tissue perfusion while minimizing adverse effects, ultimately improving patient outcomes.