Initial Norepinephrine Dosing for Severe Hypotension or Septic Shock
The initial dose of norepinephrine for treating severe hypotension or septic shock is 0.1-0.5 mcg/kg/min (which is 7-35 mcg/min in a 70-kg adult). 1
Norepinephrine as First-Line Vasopressor
- Norepinephrine is strongly recommended as the first-choice vasopressor for septic shock management 1, 2
- Norepinephrine has superior efficacy and safety profile compared to dopamine, with lower risk of mortality (relative risk 0.91) and significantly fewer arrhythmias 1
- Central venous access is required for norepinephrine administration, and arterial catheter placement is recommended for all patients requiring vasopressors 2
Initial Dosing and Titration Protocol
- Start with 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70-kg adult) 1
- Titrate to achieve a target mean arterial pressure (MAP) of 65 mmHg 1, 2
- Higher MAP targets may be appropriate for patients with pre-existing hypertension 1
- Continuous arterial blood pressure monitoring is essential for patients receiving vasopressors 2
Early Administration Benefits
- Early administration of norepinephrine is beneficial as profound and prolonged hypotension is an independent factor for increased mortality 3, 4
- Norepinephrine rapidly increases and better stabilizes arterial pressure compared to relying solely on fluid resuscitation 3
- Early norepinephrine administration increases cardiac output through increases in cardiac preload and cardiac contractility 5, 6
- It also improves microcirculation and tissue oxygenation while preventing fluid overload 6
Management of Refractory Hypotension
- If target MAP cannot be achieved with maximum doses of norepinephrine, consider adding vasopressin (up to 0.03 U/min) 1, 2
- Vasopressin should not be used as the single initial vasopressor, and doses higher than 0.03-0.04 U/min should be reserved for salvage therapy 1
- Epinephrine (0.1-0.5 mcg/kg/min) can be added to or substituted for norepinephrine when an additional agent is needed 1
- Obesity and hyperlactatemia are negatively associated with vasopressin response, while norepinephrine infusion rates ≥0.30 mcg/kg/min show positive odds of vasopressin response 7
Important Considerations and Precautions
- Adequate fluid resuscitation should ideally precede or accompany vasopressor therapy, but using vasopressors early is necessary in patients with severe shock 1
- Dopamine should only be used as an alternative to norepinephrine in highly selected patients with low risk of tachyarrhythmias or bradycardia 1
- Phenylephrine is not recommended except in specific circumstances, such as when norepinephrine causes serious arrhythmias 1
- Low diastolic arterial pressure (≤40 mmHg) or high diastolic shock index (heart rate/diastolic blood pressure ≥3) may indicate the need for earlier norepinephrine administration 3
- Norepinephrine and other catecholamines may cause tissue necrosis if extravasation occurs, so central line administration is preferred 1