Norepinephrine Side Effects and Management of Hypotension
Norepinephrine should be administered through a central venous catheter at an initial dose of 0.1-0.5 mcg/kg/min for severe hypotension (systolic BP ≤70 mmHg) with low peripheral resistance, with careful monitoring for tissue extravasation and potential cardiovascular complications. 1
Major Side Effects of Norepinephrine
Cardiovascular Effects
- Arrhythmias: Norepinephrine can cause supraventricular arrhythmias (risk 7.25 times higher compared to vasopressin) 2
- Tachycardia: Though less common than with other vasopressors, tachyarrhythmias can occur even at low doses 3
- Increased myocardial oxygen consumption: May worsen ischemia in patients with coronary artery disease 2, 1
- Decreased cardiac output: In some patients, the increased afterload can reduce stroke volume 2
Vascular Effects
- Tissue necrosis from extravasation: Most serious complication with peripheral administration 2
- Renal and mesenteric vasoconstriction: Can impair perfusion to these organ systems, though this effect may be less pronounced in septic shock 2
- Digital ischemia: Peripheral vasoconstriction can lead to ischemia in extremities 2
Other Effects
- Drug interactions: Inactivation when mixed with alkaline solutions like sodium bicarbonate 2
- Variable effects on microcirculation: May impair microvascular flow in some patients 4
Management of Hypotension with Norepinephrine
Indications
- Severe hypotension (systolic BP ≤70 mmHg) with low peripheral resistance 2
- Septic shock after adequate fluid resuscitation 2
- Post-cardiac arrest care 2
Administration Protocol
- Correct hypovolemia first: Norepinephrine is relatively contraindicated in hypovolemic patients 2, 1
- Vascular access:
- Preferably administer through a central venous catheter 1
- If peripheral administration is necessary, use a large vein and monitor closely for extravasation
- Initial dosing: Start at 0.1-0.5 mcg/kg/min (7-35 mcg/min in a 70 kg adult) 2
- Titration: Adjust dose based on blood pressure response and target mean arterial pressure (MAP) of 65 mmHg 2
Monitoring
- Continuous arterial blood pressure monitoring 1
- Tissue perfusion markers (lactate levels, urine output, capillary refill time) 1, 5
- Cardiac output when possible 2
- Vigilant monitoring for extravasation at infusion site
Managing Complications
- Extravasation: Immediately infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline into the site 2
- Inadequate response: Consider adding vasopressin (up to 0.03 U/min) or epinephrine as a second agent 2
- Microcirculatory impairment: Consider continuous infusion rather than bolus administration, as this may better preserve microcirculation 4
Special Considerations
Patient-Specific Factors
- Cardiac disease: Use with caution in patients with ischemic heart disease due to increased myocardial oxygen demand 2, 1
- Vascular waterfall response: Approximately 63% of patients show improved tissue perfusion with norepinephrine (termed "vascular waterfall responders"), while others may not show the same benefits 5
- Septic shock: In this context, norepinephrine may actually improve renal blood flow and urine output despite its vasoconstrictor effects 2
Alternatives to Consider
- Epinephrine: First alternative to norepinephrine if needed, though it may increase lactate production 2
- Vasopressin: May be added at 0.03 U/min in patients requiring high-dose norepinephrine 2
- Phenylephrine: Consider only when norepinephrine causes serious arrhythmias, cardiac output is known to be high, or as salvage therapy 2
Practical Tips
- Never mix norepinephrine with sodium bicarbonate or other alkaline solutions 2
- For continuous infusions, prepare in standard concentrations to minimize dosing errors
- In post-cardiac surgery patients, continuous infusion may be preferable to bolus administration for maintaining both macro- and microcirculation 4
- Be aware that baseline parameters may not predict which patients will respond optimally to norepinephrine 5