Norepinephrine (Levophed) Dosing for Sepsis Management
For sepsis management, norepinephrine should be initiated at 0.05-0.1 μg/kg/min and titrated by 0.05-0.1 μg/kg/min every 5-15 minutes to achieve a target mean arterial pressure (MAP) ≥65 mmHg. 1
Initial Dosing and Administration
- Norepinephrine is the first-choice vasopressor for septic shock management 1, 2
- Initial dosing parameters:
- Starting dose: 0.05-0.1 μg/kg/min
- Titration: Increase by 0.05-0.1 μg/kg/min every 5-15 minutes
- Target: MAP ≥65 mmHg 1
Timing of Norepinephrine Initiation
Recent evidence supports earlier administration of norepinephrine in septic shock:
- Traditional approach was to start vasopressors only after adequate fluid resuscitation
- However, early norepinephrine administration (simultaneously with fluid resuscitation) is now recommended, especially in cases of:
- Profound hypotension (e.g., diastolic BP ≤40 mmHg)
- High diastolic shock index (heart rate/diastolic BP ≥3)
- Risk of fluid overload 3
Early norepinephrine administration has several benefits:
- Rapidly increases and better stabilizes arterial pressure 3
- Increases cardiac output and improves microcirculation 2, 4
- Reduces administered fluid volume 3
- Increases shock control rate (76.1% vs. 48.4% in standard treatment) 5
- Lower incidence of cardiogenic pulmonary edema and new-onset arrhythmias 5
Blood Pressure Targets
- Standard target: MAP ≥65 mmHg 1, 2
- Consider higher MAP targets in patients with:
- Chronic hypertension 2
- Pre-existing cardiovascular disease
Management of Refractory Hypotension
When hypotension is refractory to norepinephrine:
- Add vasopressin (maximum dose: 0.03 U/min) 1, 2
- Vasopressin is relatively deficient during sepsis
- Acts on different vascular receptors than α1-adrenergic receptors
- Consider hydrocortisone (up to 300 mg/day) if escalating vasopressor doses are required, particularly with suspected relative adrenal insufficiency 1
- Consider dobutamine (2.5-20 μg/kg/min) if there is evidence of myocardial dysfunction or persistent hypoperfusion despite adequate blood pressure 1
Monitoring Parameters
Monitor the following during norepinephrine therapy:
- 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
- SpO₂ (target ≥95%) 1
Important Considerations and Cautions
- Higher doses of norepinephrine are associated with worse outcomes and lower perfusion index 6
- Excessive MAP targets (≥75 mmHg) may not provide additional benefit, especially in patients with poor cardiac contractility 4
- Norepinephrine has less risk of tachyarrhythmias compared to other vasopressors 1
- Continuous reassessment of fluid status is essential even when using early norepinephrine