What considerations are necessary when administering norepinephrine (vasopressor)?

Norepinephrine Administration: Critical Considerations

Norepinephrine must be initiated with concurrent adequate fluid resuscitation (minimum 30 mL/kg crystalloid bolus), administered preferably through central venous access, and titrated to a mean arterial pressure target of 65 mmHg while monitoring for tissue perfusion and extravasation complications. 1, 2

Pre-Administration Requirements

Volume resuscitation is mandatory before or simultaneous with norepinephrine initiation. Administering norepinephrine to a hypovolemic patient causes severe organ hypoperfusion despite "normal" blood pressure readings because vasoconstriction in the setting of inadequate intravascular volume compromises tissue perfusion. 2

• Administer at least 30 mL/kg of crystalloid fluid bolus before or concurrent with starting norepinephrine 1, 2
• Balanced crystalloids (lactated Ringer's or Plasma-Lyte) are preferred over normal saline 2
• In profound, life-threatening hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while continuing fluid resuscitation rather than delaying for complete volume repletion 2

Dosing Protocol

Start at 0.1-0.5 mcg/kg/min (approximately 7-35 mcg/min in a 70 kg adult or 0.5 mg/h), titrating every 4 hours by 0.5 mg/h increments to a maximum of 3 mg/h. 2, 3

• Standard concentration: 4 mg norepinephrine in 250 mL D5W yields 16 mcg/mL 2
• Alternative concentration: 1 mg in 100 mL saline yields 10 mcg/mL for specific scenarios 2, 3
• Typical maintenance range in septic shock: 0.1-2 mcg/kg/min 2
• Pediatric dosing: start at 0.1 mcg/kg/min, titrate to effect, typical range 0.1-1.0 mcg/kg/min (maximum 5 mcg/kg/min may be necessary) 2, 3

Administration Route and Access

Central venous access is strongly preferred to minimize extravasation risk and tissue necrosis. 1, 2, 4

However, recent evidence supports temporary peripheral administration under specific conditions:

• Peripheral IV administration is acceptable for low doses (<0.5 mcg/kg/min) anticipated to run less than 24 hours 5
• Use large-bore peripheral IV (18-gauge or larger) in appropriate sites (antecubital preferred over hand/wrist) 2
• Intraosseous access can be used temporarily if central access is delayed 2
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1, 2, 4

Blood Pressure Targets

Target mean arterial pressure (MAP) of 65 mmHg for most patients. 1, 2, 4

• Patients with chronic hypertension may require higher MAP targets 2
• Titrate to both MAP and tissue perfusion markers: lactate clearance, urine output >50 mL/h, mental status, capillary refill, and normalization of heart rate 2
• Do not target supranormal blood pressure values, as excessive vasoconstriction compromises microcirculatory flow 4

Monitoring Requirements

Monitor blood pressure and heart rate every 5-15 minutes during initial titration. 2

Critical monitoring parameters include:

• Continuous arterial blood pressure via arterial catheter 1, 2, 4
• Signs of excessive vasoconstriction: cold extremities, decreased urine output, digital ischemia, rising lactate 2, 3
• IV site inspection every 2 hours for peripheral administration 5
• Tissue perfusion markers: urine output, mental status, capillary refill, lactate levels 2

Management of Refractory Hypotension

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

Escalation algorithm:

• Add vasopressin 0.03-0.04 units/min (do not exceed except as salvage therapy) 1, 2, 4
• Alternative: add epinephrine 0.1-0.5 mcg/kg/min if vasopressin unavailable 1, 2
• For persistent hypoperfusion despite adequate vasopressors, add dobutamine up to 20 mcg/kg/min if myocardial dysfunction is present 1, 2

Critical Complications and Management

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

• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg 2
• Norepinephrine causes severe tissue necrosis with extravasation due to intense vasoconstriction 2
• Watch for potential side effects: hypertension, arrhythmias, tissue ischemia 2

Drug Compatibility

Never mix norepinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as adrenergic agents are inactivated in alkaline solutions. 2, 3

Agents to Avoid

Do not use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine. 1, 4

• Dopamine should only be used in highly selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia 1
• Do not use low-dose dopamine for renal protection—it has no benefit 1, 4
• Phenylephrine is not recommended except when norepinephrine causes serious arrhythmias, cardiac output is documented high with persistent hypotension, or as salvage therapy 1, 4

Timing Considerations

Early administration of norepinephrine (simultaneously with fluid resuscitation) should be considered in profound hypotension, particularly when diastolic blood pressure ≤40 mmHg or diastolic shock index (heart rate/diastolic BP) ≥3. 6

• Prolonged hypotension is an independent factor for increased mortality 7, 6
• Early norepinephrine increases cardiac output, improves microcirculation, and avoids fluid overload 7, 6
• Consider early administration in patients at risk for fluid accumulation (ARDS, intra-abdominal hypertension) 6