Maximum Dose of Norepinephrine
There is no absolute maximum dose of norepinephrine established in guidelines, though typical dosing ranges from 0.1-2 mcg/kg/min in adults, with doses occasionally exceeding this range in refractory shock requiring escalation to additional vasopressors rather than arbitrary dose capping. 1
Standard Adult Dosing Parameters
Initial and typical dosing:
- Start at 0.5 mg/h (approximately 0.1-0.5 mcg/kg/min) via continuous IV infusion 1
- Titrate every 4 hours by 0.5 mg/h increments targeting mean arterial pressure (MAP) ≥65 mmHg 1
- Typical therapeutic range: 0.1-2 mcg/kg/min for most patients with septic shock 1
Practical upper limits referenced in protocols:
- Maximum of 3 mg/h cited in hepatorenal syndrome protocols (approximately 0.7 mcg/kg/min in a 70 kg adult) 1
- However, this represents a protocol-specific ceiling rather than a physiologic maximum 1
Escalation Strategy When High Doses Are Required
Rather than continuing to escalate norepinephrine indefinitely, guidelines recommend adding second-line agents:
- Add vasopressin 0.03-0.04 units/min when norepinephrine reaches 0.25 mcg/kg/min and hypotension persists, rather than continuing to increase norepinephrine alone 1, 2
- Alternatively, add epinephrine 0.1-0.5 mcg/kg/min if vasopressin is unavailable 1
- For persistent hypoperfusion despite adequate vasopressors, add dobutamine up to 20 mcg/kg/min if myocardial dysfunction is present 1
The rationale for combination therapy rather than dose escalation:
- Early addition of vasopressin (within 3 hours) leads to faster shock resolution (37.6 vs 60.7 hours) and decreased ICU length of stay 2
- Vasopressin acts on different vascular receptors than α1-adrenergic receptors and addresses relative vasopressin deficiency in sepsis 3
Pediatric Dosing
Standard pediatric parameters:
- Starting dose: 0.1 mcg/kg/min, titrated to desired clinical effect 1
- Typical range: 0.1-1.0 mcg/kg/min 1
- Maximum doses up to 5 mcg/kg/min may be necessary in some children, though this requires central venous access and represents exceptional circumstances 1
Older Adults
No specific dose adjustments are recommended based solely on age 1. However:
- Patients with chronic hypertension may require higher MAP targets (>65 mmHg) to maintain adequate organ perfusion 1
- Titration should be guided by tissue perfusion markers (lactate clearance, urine output, mental status, capillary refill) rather than blood pressure alone 1
Critical Administration Requirements
Route of administration:
- Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis 1
- Peripheral IV or intraosseous administration can be used temporarily if central access is unavailable, with strict monitoring protocols 1
Monitoring during high-dose therapy:
- Blood pressure and heart rate every 5-15 minutes during initial titration 1
- Arterial catheter placement as soon as practical for continuous monitoring 1
- Assess tissue perfusion markers: lactate, urine output >50 mL/h, mental status, capillary refill 1
- Watch for signs of excessive vasoconstriction: cold extremities, decreased urine output 1
Common Pitfalls to Avoid
Inadequate volume resuscitation:
- Administer minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation 1
- Vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure 1
Delaying combination therapy:
- Do not continue escalating norepinephrine beyond 0.25 mcg/kg/min without adding vasopressin 1, 2
- Earlier vasopressin addition (within 3 hours) improves outcomes compared to later addition 2
Using dopamine instead:
- Dopamine is associated with higher mortality and more arrhythmias compared to norepinephrine and should not be used as first-line therapy 1
Extravasation management: