What is the recommended vasopressor (vasoconstrictor) regimen for treating hypotension in sepsis?

Vasopressor Management in Septic Shock

Norepinephrine is the first-choice vasopressor for treating hypotension in septic shock, starting at 0.05-0.1 μg/kg/min and titrating by 0.05-0.1 μg/kg/min every 5-15 minutes to achieve a target mean arterial pressure (MAP) ≥65 mmHg. 1

Initial Vasopressor Therapy

• Start norepinephrine early in septic shock, even during fluid resuscitation, especially in cases of profound hypotension (diastolic BP ≤40 mmHg) 2
• Initial dosing: 0.05-0.1 μg/kg/min 1
• Titration: Increase by 0.05-0.1 μg/kg/min every 5-15 minutes 1
• Target: MAP ≥65 mmHg (higher targets may be appropriate for patients with chronic hypertension) 3
• Administration route: Give through a large vein with arterial line monitoring 1

Early administration of norepinephrine has been shown to increase cardiac output, improve microcirculation, avoid fluid overload, and achieve faster shock control compared to delayed administration 2, 4. The CENSER trial demonstrated that early norepinephrine was associated with higher shock control rates by 6 hours (76.1% vs. 48.4%) and lower incidences of cardiogenic pulmonary edema and new-onset arrhythmias 4.

Second-Line Vasopressors

If target MAP cannot be achieved with norepinephrine alone:

1. Add vasopressin:

   • Fixed dose up to 0.03 U/min 1
   • Not recommended as a single initial vasopressor 1
   • Consider when norepinephrine doses exceed 0.5-1 μg/kg/min 5
   • No significant difference in hemodynamic response between 0.03 U/min and 0.04 U/min dosages 6

2. Consider epinephrine:

   • When additional agent is needed, particularly with myocardial depression 1
   • Dosage: 0.05 μg/kg/min to 2 μg/kg/min 7
   • Titrate in increments of 0.05-0.2 μg/kg/min every 10-15 minutes 7
   • FDA-approved specifically for hypotension associated with septic shock 7

Alternative Vasopressors

• Dopamine: Only in highly selected patients with low risk of tachyarrhythmias and bradycardia 1
  • Not recommended for renal protection 1
  • Evidence suggests worse outcomes compared to norepinephrine 1

Inotropic Support

If evidence of persistent hypoperfusion despite adequate fluid loading and vasopressors:

• Dobutamine: 2.5-20 μg/kg/min 1
  • Improves capillary and gut blood flow when used with norepinephrine 1
• Milrinone: Consider for "cold" shock (low cardiac index) 1

Practical Considerations

• Establish arterial line monitoring when using vasopressors 1
• Dilute epinephrine appropriately (1 mg in 1,000 mL of D5W or D5NS to produce 1 mcg/mL) 7
• Avoid catheter tie-in techniques that may cause stasis and increased local drug concentration 7
• Wean vasopressors incrementally after hemodynamic stabilization (e.g., decreasing doses every 30 minutes over 12-24 hours) 1, 7
• Consider hydrocortisone (up to 300 mg/day) if escalating vasopressor doses are required 1

Monitoring Parameters

• Blood pressure (target MAP ≥65 mmHg)
• Heart rate
• Urine output (target ≥0.5 mL/kg/h)
• Skin perfusion
• Mental status
• Lactate clearance
• Renal and liver function tests 1

Cautions and Pitfalls

1. Avoid excessive fluid administration: Early norepinephrine can reduce the need for excessive fluid resuscitation, which may prevent pulmonary edema and other complications 2, 4

2. Refractory shock management: When norepinephrine doses exceed 1 μg/kg/min, mortality rates exceed 80%, indicating the need for adjunctive therapies before reaching this threshold 5

3. Avoid using hydroxyethyl starches for fluid resuscitation in septic shock 1

4. Monitor for complications: Particularly myocardial dysfunction, myocardial ischemia, and arrhythmias, especially in patients with cardiac conditions 1

5. Administer empirical antibiotics within the first hour of identifying severe sepsis 1