Is norepinephrine (Levophed) the first-line pressor of choice?

Norepinephrine (Levophed) as First-Line Vasopressor

Norepinephrine is the recommended first-line vasopressor for fluid-refractory hypotensive shock in adults, particularly in septic shock, due to its reliable vasoconstrictor effects, minimal impact on heart rate, and mild inotropic properties. 1, 2, 3

Rationale for Norepinephrine as First Choice

• Mechanism of Action: Norepinephrine functions as a peripheral vasoconstrictor (alpha-adrenergic action) and provides inotropic stimulation of the heart with dilation of coronary arteries (beta-adrenergic action) 4

• Evidence Base:

  • The 2018 global perspective on vasoactive agents in shock from Intensive Care Medicine explicitly recommends norepinephrine as the first-line vasoactive drug in septic shock 1
  • Recent guidelines from Praxis Medical Insights state that norepinephrine should be initiated as the first-line vasopressor for patients with hypotension 2
  • Current evidence contradicts older notions that norepinephrine potentiates end-organ hypoperfusion 5

Clinical Application

Dosing and Administration

• Initial dose: 0.05-0.1 μg/kg/min
• Titration: Increase by 0.05-0.1 μg/kg/min every 5-15 minutes based on response 2
• Administration route: Should be given into a large vein via central venous access 4
• Preparation: Dilute in dextrose-containing solutions (typically 4 mg in 1000 mL of 5% dextrose) 4

Target Parameters

• Mean arterial pressure (MAP) ≥ 65 mmHg 2, 6
• In previously hypertensive patients, aim for MAP no higher than 40 mmHg below the preexisting systolic pressure 4
• Higher MAP targets may be appropriate in patients with chronic hypertension 6

Important Clinical Considerations

Fluid Status

• Critical Caveat: Blood volume depletion should always be corrected before or concurrently with vasopressor administration 4
• Norepinephrine should not be given to patients who are hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until volume replacement can be completed 4

Refractory Shock Management

When norepinephrine alone is insufficient:

1. Add Vasopressin: Consider adding vasopressin (up to 0.03 U/min) when shock is refractory to norepinephrine 1, 2, 6

   • Vasopressin's action is independent of catecholamine receptor stimulation and not affected by alpha-adrenergic receptor down-regulation 1

2. Consider Inotropic Support: Add dobutamine (2.5-20 μg/kg/min) if there is evidence of myocardial dysfunction or persistent hypoperfusion despite adequate blood pressure 2

3. Other Second-Line Agents:

   • Epinephrine may be considered as a second-line agent 1
   • Phenylephrine is another option but may reduce blood flow through increased SVR 1

Special Populations

• Pediatric Patients: The 2009 American College of Critical Care Medicine guidelines noted that dopamine was traditionally the first-line vasopressor for pediatric fluid-refractory hypotensive shock, but acknowledged evidence supporting norepinephrine's efficacy and safety 1

• Cardiogenic Shock: Norepinephrine is likely the vasoactive drug of choice for most patients with cardiogenic shock due to lower risk of adverse events than other catecholamine vasopressors 7

Monitoring

• Continuous blood pressure monitoring
• Heart rate, urine output, skin perfusion, mental status
• Lactate clearance
• Renal and liver function tests 2

Norepinephrine has demonstrated superior outcomes compared to high-dose dopamine or epinephrine in observational studies, with one study showing significantly lower hospital mortality (62% vs 82%) in patients treated with norepinephrine versus other vasopressors 5.