When to Add Vasopressin to Norepinephrine in Shock Management
According to Rosen's Emergency Medicine guidelines, vasopressin (up to 0.03 U/min) should be considered as an adjunct to norepinephrine when norepinephrine is being used at doses of 0.2-1.0 μg/kg/min to raise mean arterial pressure or to decrease norepinephrine dosage requirements. 1
Vasopressor Management in Shock
The American College of Critical Care Medicine, European Heart Society, Society of Critical Care Medicine, and Surviving Sepsis Campaign recommend:
- Norepinephrine as the first-choice vasopressor in septic shock (Grade 1B recommendation)
- Initial norepinephrine dosing at 0.05-0.1 μg/kg/min
- Titration by 0.05-0.1 μg/kg/min every 5-15 minutes
- Target mean arterial pressure (MAP) ≥65 mmHg 1
Optimal Timing for Vasopressin Addition
Recent evidence suggests benefits to earlier vasopressin addition:
Adding vasopressin within 3 hours of norepinephrine initiation is associated with:
- Faster shock resolution (37.6 vs 60.7 hours)
- Decreased ICU length of stay (4.3 vs 5.3 days) 2
The most recent research (2025 OVISS study) indicates vasopressin should be initiated:
- Earlier than current clinical practice (median 4 hours vs 5 hours after shock onset)
- At lower norepinephrine doses than typically used (median 0.20 μg/kg/min vs 0.37 μg/kg/min) 3
Clinical Considerations and Caveats
High-dose norepinephrine (>1 μg/kg/min) is associated with mortality rates exceeding 80%, suggesting adjunctive strategies should be implemented before reaching this threshold 4
Vasopressin is relatively deficient during sepsis and acts on different vascular receptors than norepinephrine (non-adrenergic mechanisms) 5
Maximum vasopressin dose should not exceed 0.03 U/min 1
While vasopressin addition is recommended for refractory shock, it has not been shown to reduce overall mortality compared to norepinephrine alone in all patients with septic shock (28-day mortality: 35.4% vs 39.3%, P=0.26) 6
However, vasopressin may provide mortality benefit in less severe septic shock (26.5% vs 35.7%, P=0.05) 6
Practical Application
- Start norepinephrine at 0.05-0.1 μg/kg/min
- Consider adding vasopressin (up to 0.03 U/min) when:
- Norepinephrine dose reaches 0.2 μg/kg/min
- Within 3-4 hours of shock onset
- Before norepinephrine exceeds 1 μg/kg/min
- Continue to titrate both agents to maintain target MAP ≥65 mmHg
This approach aligns with the most recent evidence suggesting earlier and more frequent vasopressin use than traditional practice patterns, which is associated with improved outcomes 3.