What is the recommended dosing for norepinephrine (vasopressor) in treating hypotension?

Norepinephrine Dosing for Hypotension

Start norepinephrine at 8-12 mcg/min (0.1-0.5 mcg/kg/min for a 70 kg adult) via continuous IV infusion, targeting a mean arterial pressure of 65 mmHg, with central venous access strongly preferred. 1, 2

Preparation and Concentration

• Standard dilution: Add 4 mg norepinephrine to 250 mL of 5% dextrose solution to yield 16 mcg/mL concentration. 1, 3
• Dextrose-containing solutions are essential to prevent oxidation and loss of potency; administration in saline alone is not recommended. 1
• Alternative concentration for specific scenarios: 1 mg in 100 mL saline (10 mcg/mL) may be used in anaphylaxis cases. 2

Critical Pre-Administration Requirements

Administer a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation to avoid severe organ hypoperfusion from vasoconstriction in hypovolemic patients. 4, 2, 3

• Balanced crystalloids (lactated Ringer's or Plasma-Lyte) are preferred over normal saline for fluid resuscitation. 4
• In life-threatening hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion. 2

Initial Dosing

• Begin infusion at 8-12 mcg/min (equivalent to 2-3 mL/min of standard 4 mcg/mL dilution). 1
• Weight-based dosing: 0.1-0.5 mcg/kg/min for adults, with most patients starting at 0.02 mcg/kg/min in septic shock. 4, 2
• For hepatorenal syndrome specifically: Start at 0.5 mg/h (8.3 mcg/min), increase by 0.5 mg/h every 4 hours to maximum 3 mg/h. 2, 3

Administration Route

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 4, 5, 3

• If central access is unavailable or delayed, peripheral IV administration can be used temporarily with strict monitoring protocols. 4, 2
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors. 2, 5

Target Blood Pressure and Monitoring

• Target mean arterial pressure (MAP) of 65 mmHg for most patients with septic shock. 4, 2, 5
• In previously hypertensive patients, raise blood pressure no higher than 40 mmHg below pre-existing systolic pressure. 1
• Monitor blood pressure every 5-15 minutes during initial titration. 2, 3
• Assess tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill. 2, 3

Titration Strategy

• Maintenance dose typically ranges from 2-4 mcg/min (0.5-1 mL/min of standard dilution). 1, 3
• Titrate according to patient response; great individual variation exists in required doses. 1
• For hepatorenal syndrome: Increase by 0.5 mg/h every 4 hours as needed, targeting MAP increase ≥10 mmHg or urine output >50 mL/h. 2, 3

Escalation for Refractory Hypotension

When norepinephrine reaches 0.1-0.25 mcg/kg/min and hypotension persists, add vasopressin 0.03-0.04 units/min as second-line therapy rather than continuing to escalate norepinephrine alone. 4, 2, 3

• Alternative second agents: Epinephrine 0.1-0.5 mcg/kg/min may be added if vasopressin is unavailable or contraindicated. 2
• For persistent hypoperfusion despite adequate vasopressors with myocardial dysfunction: Add dobutamine up to 20 mcg/kg/min. 2
• High doses (up to 68 mg base daily or 17 vials) may occasionally be necessary, but occult blood volume depletion should always be suspected and corrected. 1

Special Populations

Pregnant Patients

• Start at 0.02 mcg/kg/min targeting MAP 65 mmHg. 4, 3
• Consider more restrictive initial fluid boluses (1-2 L) due to lower colloid oncotic pressure and higher pulmonary edema risk. 4
• Add vasopressin 0.04 units/min for refractory shock with appropriate fetal monitoring. 4

Pediatric Patients

• Start at 0.1 mcg/kg/min, titrate to clinical effect with typical range 0.1-1.0 mcg/kg/min. 2
• Maximum doses up to 5 mcg/kg/min may be necessary in exceptional circumstances. 2
• "Rule of 6" for simplified dosing: 0.6 × body weight (kg) = mg diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min. 2

Patients on Beta-Blockers

• May require glucagon 1-5 mg IV over 5 minutes followed by infusion for refractory cardiovascular effects. 3

Management of Extravasation

If extravasation occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline intradermally at the site to prevent tissue necrosis. 2, 5, 3

• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg diluted in 10 mL of 0.9% sodium chloride. 2

Critical Pitfalls to Avoid

• Never start norepinephrine without addressing hypovolemia first—vasoconstriction in hypovolemic patients causes severe organ hypoperfusion despite "normal" blood pressure. 2, 5
• Do not mix with sodium bicarbonate or other alkaline solutions in the IV line, as norepinephrine is inactivated in alkaline solutions. 2, 5
• Avoid using dopamine as first-line agent; it is associated with higher mortality and more arrhythmias compared to norepinephrine. 2, 5
• Do not use low-dose dopamine for renal protection—it has no benefit. 2
• Phenylephrine should not be used as first-line therapy; it may raise blood pressure while worsening tissue perfusion. 2

Weaning Protocol

• Reduce gradually, avoiding abrupt withdrawal. 1
• Decrease by 25% of current dose every 30 minutes as tolerated. 5
• Continue infusion until adequate blood pressure and tissue perfusion are maintained without therapy. 1
• Treatment duration varies; some cases of vascular collapse may require up to 6 days. 1

Monitoring for Adverse Effects

• Watch for arrhythmias, particularly at higher doses. 5, 3
• Monitor for excessive vasoconstriction: cold extremities, decreased urine output, poor capillary refill. 2, 3
• Assess for increased myocardial oxygen consumption, especially in patients with ischemic heart disease. 5, 3
• Higher doses (>10 mcg/min) are associated with increased mortality and should be avoided if possible. 5