Simultaneous Administration of Norepinephrine and Adrenaline
The simultaneous administration of norepinephrine and adrenaline is appropriate in specific clinical scenarios such as refractory shock, with norepinephrine as the first-line agent and adrenaline added when additional vasopressor support is needed to maintain adequate blood pressure. 1
Clinical Indications for Combined Therapy
Refractory Shock
- Norepinephrine should be initiated as the first-line vasopressor for patients with hypotension 1, 2
- Adrenaline (epinephrine) should be added when norepinephrine alone fails to maintain target mean arterial pressure (MAP) 1
- This combination is particularly valuable in:
Dosing Guidelines
Norepinephrine:
- Initial dose: 0.05-0.1 μg/kg/min 2
- Titration: Increase by 0.05-0.1 μg/kg/min every 5-15 minutes 2
- Maximum dose: Up to 3 μg/h for hepatorenal syndrome 1
Adrenaline (Epinephrine):
- Initial dose: 0.05-0.5 μg/kg/min when added to norepinephrine 1
- For anaphylaxis: 50 μg IV for Grade II reactions, 100-200 μg for Grade III reactions 1
- For cardiac arrest: 1 mg IV per resuscitation protocols 1
Hemodynamic Effects and Monitoring
The combination therapy leverages complementary mechanisms:
- Norepinephrine: Predominantly alpha-adrenergic effects (vasoconstriction)
- Adrenaline: Both alpha and beta-adrenergic effects (vasoconstriction, increased heart rate, bronchodilation)
When administered together:
- Mean arterial pressure increases more effectively than with either agent alone 3
- Cardiac output may be better maintained compared to norepinephrine alone 4
- Heart rate tends to increase more than with norepinephrine alone 4
Required Monitoring:
- Continuous arterial blood pressure monitoring (arterial line recommended) 2
- Continuous ECG monitoring for arrhythmias 4
- Urine output (target >0.5 ml/kg/h) 2
- Lactate levels to assess tissue perfusion 2, 4
- Assessment of peripheral perfusion (skin temperature, capillary refill) 2
Potential Complications and Precautions
Adverse Effects:
- Tachyarrhythmias (more common with adrenaline) 4
- Myocardial ischemia due to increased oxygen demand 4
- Lactic acidosis (particularly with adrenaline) 4
- Digital/peripheral ischemia 1
- Splanchnic hypoperfusion (more pronounced with adrenaline) 4
Important Precautions:
- Ensure adequate fluid resuscitation before or concurrent with vasopressor therapy 2
- Use through central venous access whenever possible to avoid extravasation
- Monitor for signs of tissue ischemia, particularly with prolonged use
- Consider adding vasopressin (up to 0.03 U/min) as an alternative to escalating catecholamine doses 1
- In patients on beta-blockers, consider glucagon (1-2 mg IV) to counteract resistance to catecholamines 1
Special Considerations
Pediatric Patients:
- Dosing must be weight-based and concentration-appropriate 1
- For cardiopulmonary resuscitation in infants/children: 0.01 mg/kg of 1:10,000 solution (maximum: 1 mg) 1
Anaphylaxis Management:
- For Grade III reactions: Initial IV epinephrine 50 μg, escalating to 200 μg if unresponsive 1
- Consider epinephrine infusion when more than three boluses are required 1
- Norepinephrine may be added if persistent hypotension despite epinephrine 1
Cardiogenic Shock:
- The combination of norepinephrine with dobutamine may be preferable to epinephrine alone for better splanchnic perfusion and less lactic acidosis 4
Conclusion
The simultaneous use of norepinephrine and adrenaline requires careful titration, appropriate monitoring, and awareness of potential complications. This combination therapy should be reserved for situations where single-agent therapy is insufficient to maintain adequate tissue perfusion, with norepinephrine as the foundation and adrenaline added for additional support when needed.