What is the recommended starting dose and preparation of noradrenaline (norepinephrine) via infusion pump for a patient with severe hypotension or septic shock, specifically when mixed with 500 ml of saline?

Norepinephrine Preparation and Dosing for Severe Hypotension/Septic Shock

For a 500 mL saline preparation, add 4 mg (one 4 mL vial) of norepinephrine to create an 8 mcg/mL concentration, and start the infusion at 8-12 mcg/min (60-90 mL/hr on the pump), titrating every 2 minutes to achieve a mean arterial pressure (MAP) of 65 mmHg. 1

Standard Preparation Protocol

FDA-Approved Dilution Method

• The FDA recommends adding one 4 mg/4 mL vial of norepinephrine to 1,000 mL of 5% dextrose or dextrose-containing saline to produce a 4 mcg/mL concentration 1
• For 500 mL preparation (fluid-restricted patients): Add 4 mg (one vial) to 500 mL to create an 8 mcg/mL concentration 1
• Dextrose-containing solutions are strongly preferred over saline alone, as dextrose reduces potency loss from oxidation 1
• The diluted solution can be stored up to 24 hours at room temperature (20-25°C) when protected from light 1

Critical Pre-Administration Requirements

• Correct hypovolemia with at least 30 mL/kg crystalloid fluid resuscitation in the first 3 hours before or concurrent with norepinephrine initiation 2, 3, 4
• Establish central venous access whenever possible to minimize extravasation risk, though peripheral administration is acceptable in urgent situations 2, 1
• Place an arterial catheter for continuous blood pressure monitoring as soon as practical 2, 3

Initial Dosing Algorithm

Starting Dose

• Begin at 8-12 mcg/min (0.13-0.2 mcg/kg/min for a 70 kg patient) via continuous IV infusion 1
• For 8 mcg/mL concentration (500 mL bag): This equals 60-90 mL/hr on your infusion pump 1
• For 4 mcg/mL concentration (1000 mL bag): This equals 120-180 mL/hr on your infusion pump 1

Titration Protocol

• Monitor blood pressure every 2 minutes until MAP ≥65 mmHg is achieved 1
• Once target MAP is reached, monitor blood pressure every 5 minutes for the duration of infusion 1
• Target MAP of 65 mmHg for most patients; consider 70-75 mmHg for patients with chronic hypertension 2, 3, 4

Maintenance Dosing

• Typical maintenance dose is 2-4 mcg/min once hemodynamic stability is achieved 1
• For 8 mcg/mL concentration: This equals 15-30 mL/hr 1
• Maximum recommended dose before adding second vasopressor is approximately 15 mcg/min (0.2 mcg/kg/min) 2, 3

Escalation Strategy for Refractory Hypotension

When to Add Second Vasopressor

• Add vasopressin 0.03 units/min when norepinephrine requirements exceed 0.1-0.2 mcg/kg/min (approximately 7-14 mcg/min for a 70 kg patient) or when MAP target cannot be achieved 2, 3, 4
• Vasopressin acts on V1 receptors, providing complementary vasoconstriction through a different mechanism than norepinephrine's alpha-1 adrenergic effects 3
• Never exceed vasopressin 0.03-0.04 units/min except as salvage therapy, as higher doses cause cardiac, digital, and splanchnic ischemia 2, 3

Third-Line Options

• Add epinephrine 0.05-2 mcg/kg/min if hypotension persists despite norepinephrine plus vasopressin 2, 3
• Consider dobutamine 2.5-20 mcg/kg/min if persistent hypoperfusion exists despite adequate MAP, particularly when myocardial dysfunction is evident 2, 3
• Add hydrocortisone 200 mg/day (50 mg IV every 6 hours) for refractory shock after 4 hours of high-dose vasopressors 3, 4

Critical Monitoring Beyond Blood Pressure

Tissue Perfusion Markers

• Assess lactate clearance, urine output (target >0.5 mL/kg/hr), mental status, and capillary refill in addition to MAP 3, 4
• Continue fluid resuscitation as long as hemodynamic parameters improve using dynamic or static variables 4

Early Warning Signs

• A diastolic blood pressure ≤40 mmHg or diastolic shock index (heart rate/diastolic BP) ≥3 indicates profound vascular tone depression requiring urgent norepinephrine initiation 5, 6
• Early norepinephrine administration (concurrent with initial fluid resuscitation) should be considered in profound, life-threatening hypotension to avoid prolonged organ hypoperfusion 5, 7, 6

Common Pitfalls and How to Avoid Them

Administration Errors

• Never infuse into leg veins in elderly patients or those with peripheral vascular disease 1
• Avoid catheter-tie-in technique 1
• If extravasation occurs, immediately infiltrate the area with 10-15 mL saline containing 5-10 mg phentolamine 1
• Visually inspect solution before use—discard if pinkish, darker than slightly yellow, or contains precipitate 1

Discontinuation Protocol

• Reduce infusion rate gradually when discontinuing—never stop abruptly, as this causes marked rebound hypotension 1

Agents to Avoid

• Never use dopamine as first-line therapy—it increases mortality and arrhythmias compared to norepinephrine 2, 3, 4
• Never use low-dose dopamine for "renal protection"—this is strongly contraindicated and offers no benefit 2, 3, 4
• Avoid phenylephrine except when norepinephrine causes serious arrhythmias, cardiac output is high with persistent hypotension, or as salvage therapy 2, 3, 4

Drug Incompatibilities

• Avoid contact with iron salts, alkalis, or oxidizing agents 1
• Administer whole blood or plasma separately if needed for volume expansion 1
• Be aware that norepinephrine contains sodium metabisulfite, which may cause allergic reactions in susceptible patients 1

Cardiac Considerations

• Monitor for arrhythmias, particularly in patients with underlying heart disease or those receiving cardiac glycosides 1
• Norepinephrine increases myocardial oxygen demand—use cautiously in patients with ischemic heart disease, though this is not a contraindication 2
• Early norepinephrine administration actually increases cardiac output through increased preload and contractility in most septic shock patients, including those with reduced ejection fraction 8, 6