What is the typical starting dose of norepinephrine (vasopressor) for an adult with severe hypotension or septic shock?

Norepinephrine Starting Dose for Severe Hypotension/Septic Shock

Start norepinephrine at 0.1-0.5 mcg/kg/min (approximately 7-35 mcg/min in a 70 kg adult), which translates to 0.42-2.1 mL/hour using your 1 mg/mL concentration, and titrate to achieve a mean arterial pressure (MAP) of 65 mmHg. 1

Practical Dosing with 1 mg/mL Concentration

Since you have norepinephrine 1 mg/mL (1000 mcg/mL), you'll need to dilute this for safe administration:

• Standard dilution: Add 4 mg (4 mL of your 1 mg/mL solution) to 250 mL D5W to create a 16 mcg/mL concentration 1
• Starting infusion rate: 0.5-2 mL/hour of the diluted solution (16 mcg/mL) delivers approximately 0.1-0.5 mcg/kg/min for a 70 kg patient 1
• Titration: Increase by 0.5 mg/hour every 4 hours as needed, up to maximum 3 mg/hour 1

Critical Pre-Administration Requirements

Address hypovolemia FIRST with a minimum 30 mL/kg crystalloid bolus before or concurrent with norepinephrine initiation—vasoconstriction in a hypovolemic patient causes severe organ hypoperfusion despite "normal" blood pressure. 1, 2

• In profound hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion 1
• Early norepinephrine administration (within 93 minutes of emergency room arrival) significantly increases shock control by 6 hours compared to delayed administration (76.1% vs 48.4%, p<0.001) 3

Administration Route and Monitoring

• Central venous access is strongly preferred to minimize extravasation risk, though peripheral IV can be used temporarily if central access is delayed 1, 2
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring in all patients requiring vasopressors 2
• Monitor blood pressure and heart rate every 5-15 minutes during initial titration 1

Target Blood Pressure

• Primary target: MAP ≥65 mmHg 2, 1
• Patients with chronic hypertension may require higher MAP targets, while younger normotensive patients may tolerate lower pressures 1
• Titrate to both MAP AND tissue perfusion markers: lactate clearance, urine output >0.5 mL/kg/hour, mental status, and capillary refill 1, 3

Escalation Protocol for Refractory Hypotension

If target MAP is not achieved with norepinephrine alone:

1. Add vasopressin 0.03 units/min when norepinephrine reaches 0.25 mcg/kg/min or approximately 15-20 mcg/min 1, 4

   • Do NOT use vasopressin as monotherapy—it must be added to norepinephrine 4
   • Doses >0.03-0.04 units/min should be reserved for salvage therapy only 2, 4

2. Alternative: Add epinephrine as a second agent if vasopressin is unavailable 5

3. Add dobutamine (up to 20 mcg/kg/min) if persistent hypoperfusion exists despite adequate MAP and fluid loading, particularly with myocardial dysfunction 2, 5

Critical Pitfalls to Avoid

• Never use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine, and should only be used in highly selected patients with absolute bradycardia or low arrhythmia risk 2, 5
• Do NOT use low-dose dopamine for renal protection—this has no benefit and is strongly discouraged 2
• Avoid phenylephrine except when norepinephrine causes serious arrhythmias, cardiac output is documented high with persistent hypotension, or as salvage therapy 2, 5
• Watch for extravasation—if it occurs, immediately infiltrate phentolamine 5-10 mg diluted in 10-15 mL saline at the site to prevent tissue necrosis 1
• Do NOT mix with sodium bicarbonate or alkaline solutions—adrenergic agents are inactivated in alkaline solutions 1

Evidence Supporting Early Norepinephrine Use

The CENSER trial demonstrated that early norepinephrine administration (median 93 minutes from ER arrival) compared to standard treatment (median 192 minutes) resulted in:

• Higher shock control rate by 6 hours (76.1% vs 48.4%, p<0.001) 3
• Lower incidence of cardiogenic pulmonary edema (14.4% vs 27.7%, p=0.004) 3
• Lower incidence of new-onset arrhythmia (11% vs 20%, p=0.03) 3

Early administration should be particularly considered in patients with profound hypotension (diastolic BP ≤40 mmHg or diastolic shock index ≥3) or when fluid accumulation would be deleterious (ARDS, intra-abdominal hypertension) 6