Norepinephrine Dosing for Hypotension
Norepinephrine should be initiated at 0.1-0.5 mcg/kg/min (approximately 7-35 mcg/min in a 70 kg adult) and titrated to achieve a mean arterial pressure (MAP) of 65 mmHg, with typical maintenance doses ranging from 2-4 mcg/min (0.03-0.06 mcg/kg/min). 1, 2, 3
Initial Dosing and Preparation
Standard concentration: Add 4 mg of norepinephrine to 250 mL of D5W to yield 16 mcg/mL. 2
Starting dose ranges:
- FDA-approved initial dose: 0.25-0.375 mL/min (8-12 mcg/min of base) 3
- Contemporary guideline recommendation: 0.1-0.5 mcg/kg/min (7-35 mcg/min in 70 kg adult) 1, 2
- Average maintenance dose: 2-4 mcg/min (0.03-0.06 mcg/kg/min) 3
Target Blood Pressure
Primary target: MAP ≥65 mmHg 4, 1, 2
The 65 mmHg MAP target has been validated to preserve tissue perfusion in septic shock. 4 However, patients with chronic hypertension or atherosclerosis may require higher targets, while younger normotensive patients may tolerate lower pressures. 4, 5 Titration should be guided by both MAP and markers of tissue perfusion including lactate clearance, urine output (>0.5 mL/kg/h), mental status, and capillary refill. 4, 1
Dose Escalation and Maximum Doses
Titration protocol:
- Increase by 0.5 mg/h every 4 hours as needed 2
- Maximum recommended dose: 3 mg/h 2
- Typical range in septic shock: 0.1-2 mcg/kg/min 2
- Higher doses (up to 2.5 ± 2.2 mcg/kg/min) may be necessary in severe cases 6
When norepinephrine reaches 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, 7
Timing of Initiation
Early administration is critical. Norepinephrine should be started during or immediately after initial fluid resuscitation, particularly in patients with profound hypotension. 1, 8, 9
Indications for early initiation:
- Systolic blood pressure <70 mmHg despite fluid resuscitation 1
- Diastolic blood pressure ≤40 mmHg (indicating very low arterial tone) 8
- Diastolic shock index (heart rate/diastolic BP) ≥3 8
- Life-threatening hypotension where delaying vasopressors would prolong organ hypoperfusion 8
A randomized trial demonstrated that early norepinephrine (median 93 minutes from ER arrival) achieved shock control by 6 hours in 76.1% of patients versus 48.4% with standard delayed administration, and reduced cardiogenic pulmonary edema (14.4% vs 27.7%) and arrhythmias (11% vs 20%). 9
Fluid Resuscitation Requirements
Minimum 30 mL/kg crystalloid bolus should be administered before or concurrent with norepinephrine initiation. 4, 2 However, in severe hypotension (systolic <70 mmHg), norepinephrine should be started as an emergency measure while fluid resuscitation continues, rather than waiting for complete volume repletion. 4, 1
Administration Route and Safety
Central venous access is strongly preferred to minimize extravasation risk. 1, 2, 3
Peripheral or intraosseous administration can be used temporarily if central access is unavailable, with strict monitoring. 1, 2 Pediatric data shows peripheral administration for median 3 hours was safe without adverse effects. 6
If extravasation occurs: Immediately infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline into the affected area to prevent tissue necrosis. 1, 2, 3
Monitoring Requirements
- Blood pressure and heart rate every 5-15 minutes during initial titration 2
- Arterial catheter placement for continuous monitoring in all vasopressor-dependent patients 2, 7
- Monitor for signs of excessive vasoconstriction: cold extremities, decreased urine output, arrhythmias 2
- Assess tissue perfusion markers: lactate, mental status, urine output, capillary refill 4, 1
Pediatric Dosing
Starting dose: 0.1-1.0 mcg/kg/min, beginning at the lowest dose and titrating to effect 2
Maximum doses: Up to 5 mcg/kg/min may be necessary in children 2
"Rule of 6" for preparation: 0.6 × body weight (kg) = mg of norepinephrine diluted to 100 mL saline; then 1 mL/h delivers 0.1 mcg/kg/min 2
Critical Precautions
Do not mix with sodium bicarbonate or alkaline solutions in the IV line, as norepinephrine is inactivated in alkaline environments. 2, 3
Avoid abrupt discontinuation: Gradually reduce infusion rate to prevent rebound hypotension. 1, 3
Use cautiously in ischemic heart disease as norepinephrine increases myocardial oxygen demand. 1, 2
Dose-Mortality Relationship
Recent data establishes severity cutoffs based on mortality risk:
- Low dose: <0.2 mcg/kg/min (14% hospital mortality)
- Intermediate dose: 0.2-0.4 mcg/kg/min (26.4% hospital mortality)
- High dose: >0.4 mcg/kg/min (40.2% hospital mortality) 10
These cutoffs help quantify circulatory failure severity and guide decisions about adding second-line agents.