What is the recommended initial dosing and infusion rate for vasopressors, such as norepinephrine (vasopressor), in critically ill patients with hypotension (low blood pressure) requiring vasopressor support?

Vasopressor Dosing and Infusion in Critically Ill Patients

Start norepinephrine at 2-3 mL/minute (8-12 mcg/minute of base) after diluting 4 mg in 1,000 mL of 5% dextrose, then titrate to maintain MAP ≥65 mmHg, with continuous arterial monitoring via central venous access. 1

Initial Norepinephrine Dosing Protocol

Preparation and Administration

• Dilute 4 mg (4 mL vial) of norepinephrine in 1,000 mL of 5% dextrose solution to create a concentration of 4 mcg/mL 1
• Administer through central venous access using a plastic intravenous catheter advanced centrally into a large vein 2, 1
• Place an arterial catheter for continuous blood pressure monitoring as soon as practical 2, 3
• Use an IV drip chamber or metering device to accurately measure flow rate in drops per minute 1

Starting Dose and Titration

• Begin with an initial infusion rate of 2-3 mL/minute (8-12 mcg/minute of base) 1
• Titrate rapidly to achieve and maintain MAP ≥65 mmHg 2, 3, 4
• The average maintenance dose ranges from 0.5-1 mL/minute (2-4 mcg/minute of base) 1
• In previously hypertensive patients, target MAP should be 70-75 mmHg or no higher than 40 mmHg below pre-existing systolic pressure 2, 1

Critical Timing Consideration

• Initiate norepinephrine early—as soon as hypotension persists after starting fluid resuscitation (minimum 30 mL/kg crystalloids in first 3 hours)—rather than waiting for complete fluid resuscitation 2, 3, 4, 5
• In life-threatening hypotension (diastolic BP ≤40 mmHg or diastolic shock index ≥3), start norepinephrine simultaneously with fluid resuscitation to prevent prolonged organ hypoperfusion 5

Escalation Protocol for Refractory Hypotension

Second-Line Agent: Vasopressin

• Add vasopressin at a fixed dose of 0.03 units/minute when norepinephrine alone fails to achieve target MAP 2, 3, 4
• Start vasopressin at 0.01 units/minute and titrate by 0.005 units/minute every 10-15 minutes up to maximum 0.03-0.04 units/minute 2
• Never use vasopressin as monotherapy—it must always be added to norepinephrine, not used as the sole initial vasopressor 2, 3, 4
• Do not exceed 0.03-0.04 units/minute except as salvage therapy, as higher doses cause cardiac, digital, and splanchnic ischemia 2, 3

Third-Line Agent: Epinephrine

• Add epinephrine at 0.05-2 mcg/kg/minute if target MAP is not achieved with norepinephrine plus vasopressin 2, 3
• Epinephrine should be added as a third agent rather than escalating vasopressin beyond 0.03-0.04 units/minute 2, 3
• Be aware that epinephrine causes transient lactic acidosis through β2-adrenergic stimulation, which interferes with lactate clearance as a resuscitation endpoint 2

Inotropic Support: Dobutamine

• Add dobutamine at 2.5-20 mcg/kg/minute if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident 2, 3, 4
• Dobutamine addresses inadequate cardiac output rather than vascular tone 2

High-Dose Norepinephrine Considerations

• Norepinephrine doses ≥15 mcg/minute indicate severe shock and warrant addition of vasopressin to spare norepinephrine 2
• Doses above 15 mcg/minute are associated with increased mortality and should prompt escalation to combination therapy rather than further dose increases 2
• Occasionally, very high doses (up to 68 mg base daily or 17 vials) may be necessary, but always suspect and correct occult blood volume depletion first 1
• Central venous pressure monitoring helps detect and treat ongoing hypovolemia in patients requiring high vasopressor doses 1

Monitoring Beyond Blood Pressure

• Assess tissue perfusion using lactate clearance, urine output, mental status, skin perfusion, and capillary refill—not just MAP 2, 3
• Continuous arterial blood pressure monitoring is essential for all patients receiving vasopressors 2, 3
• Monitor for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP 2

Critical Agents to Avoid

Dopamine

• Do not use dopamine as first-line therapy—it is associated with higher mortality and significantly more arrhythmias compared to norepinephrine 2, 3, 4
• Use dopamine only in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 2, 4
• Never use low-dose dopamine for "renal protection"—this is strongly contraindicated and offers no benefit 2, 3, 4

Phenylephrine

• Avoid phenylephrine except when norepinephrine causes serious arrhythmias, cardiac output is documented high with persistent hypotension, or as salvage therapy when all other agents have failed 2, 3, 4
• Phenylephrine may raise blood pressure numbers while actually worsening tissue perfusion through excessive vasoconstriction 2

Adjunctive Therapy for Refractory Shock

• Consider hydrocortisone 200 mg/day IV (50 mg every 6 hours) if hypotension remains refractory after 4 hours of norepinephrine ≥0.25 mcg/kg/minute or if hemodynamic stability cannot be achieved despite adequate fluid resuscitation and vasopressor support 2, 3

Common Pitfalls to Avoid

• Do not delay norepinephrine initiation waiting for complete fluid resuscitation if life-threatening hypotension is present 2, 5
• Do not rely solely on blood pressure targets—monitor markers of tissue perfusion (lactate, urine output, mental status) 2, 3
• Do not use vasopressin as initial monotherapy—always add it to norepinephrine 2, 3, 4
• Do not escalate vasopressin beyond 0.03-0.04 units/minute—add epinephrine instead 2, 3
• Avoid excessive vasoconstriction by titrating to adequate perfusion markers, not supranormal blood pressure targets 2