What is the recommended use and dosage of Levophed (norepinephrine) in patients with severe hypotension or septic shock?

Recommended Use and Dosage of Levophed (Norepinephrine) in Severe Hypotension or Septic Shock

Norepinephrine (Levophed) is strongly recommended as the first-choice vasopressor for patients with severe hypotension or septic shock, with an initial target mean arterial pressure (MAP) of 65 mmHg. 1

Indications and Timing

• Initiate vasopressor therapy when hypotension persists despite adequate fluid resuscitation
• Consider early administration of norepinephrine in cases of:
  • Profound hypotension (diastolic BP ≤ 40 mmHg) 2
  • High diastolic shock index (heart rate/diastolic BP ≥ 3) 2
  • Risk of fluid overload or when fluid accumulation would be particularly harmful 2

Dosing Protocol

1. Initial Dosing:

   • Begin with 0.05-0.1 μg/kg/min IV infusion
   • Titrate by 0.05-0.1 μg/kg/min every 5-15 minutes based on blood pressure response

2. Target MAP:

   • Maintain MAP ≥ 65 mmHg in most patients 1
   • Consider higher targets (70-80 mmHg) in patients with chronic hypertension 1, 3

3. Administration:

   • Administer through central venous access when possible
   • Place arterial catheter for continuous blood pressure monitoring as soon as practical 1
   • Average duration of infusion in septic shock is approximately 70.5 hours 4

Refractory Hypotension Management

If target MAP is not achieved with norepinephrine alone:

1. Add vasopressin (up to 0.03 U/min) to either:

   • Raise MAP to target, or
   • Decrease norepinephrine dosage 1

2. Add epinephrine as an alternative second agent when additional support is needed 1

3. Avoid phenylephrine except in specific circumstances:

   • Norepinephrine causes serious arrhythmias
   • Cardiac output is known to be high with persistent low blood pressure
   • As salvage therapy when other vasopressors have failed 1

Important Considerations

• Fluid resuscitation: Ensure adequate volume status before or concurrent with vasopressor initiation (minimum 30 mL/kg crystalloids) 1

• Monitoring: Assess not only blood pressure but also signs of tissue perfusion (lactate levels, skin perfusion, mental status, urine output) 1

• Weaning: Taper norepinephrine gradually as hemodynamic stability improves, continuing fluid resuscitation as needed 1

• Avoid dopamine as a first-line agent due to higher risk of arrhythmias; reserve for highly selected patients with low risk of tachyarrhythmias and relative bradycardia 1, 5

• Do not use low-dose dopamine for renal protection 1

Cautions and Pitfalls

• Extravasation can cause severe tissue necrosis; use central venous access whenever possible
• Excessive vasoconstriction may impair tissue perfusion despite adequate MAP
• Higher doses of norepinephrine may be required with increasing fluid administration 4
• Prolonged INR is associated with higher 28-day mortality in septic shock patients 4
• Avoid abrupt discontinuation of norepinephrine to prevent rebound hypotension

By following these evidence-based recommendations for norepinephrine administration in septic shock, clinicians can optimize outcomes while minimizing risks associated with both persistent hypotension and excessive vasopressor use.