When should I consider adding another vasopressor (pressor) to a patient with hypotension?

When to Add a Second Vasopressor

Add a second vasopressor (vasopressin 0.03 units/min) when norepinephrine reaches 0.1-0.2 mcg/kg/min (approximately 7-14 mcg/min in a 70kg patient) and fails to maintain MAP ≥65 mmHg despite adequate fluid resuscitation. 1, 2

Initial Vasopressor Strategy

• Start with norepinephrine as the sole first-line agent at 0.02 mcg/kg/min and titrate upward to achieve MAP ≥65 mmHg 1, 2
• Ensure adequate fluid resuscitation first: minimum 30 mL/kg crystalloid bolus within the first 3 hours 1, 2
• Place an arterial catheter as soon as practical for continuous blood pressure monitoring 1, 2, 3
• Never start multiple vasopressors simultaneously—there is no evidence supporting this approach 2

Threshold for Adding Second Vasopressor

The critical decision point occurs when norepinephrine reaches low-to-moderate doses (0.1-0.2 mcg/kg/min) without achieving target MAP. 1, 2 At this threshold:

• Add vasopressin 0.03 units/min to either raise MAP to target or decrease norepinephrine requirements 1, 2, 3
• Vasopressin should never be used as initial monotherapy—only as an adjunct to norepinephrine 1, 2, 3
• Do not escalate vasopressin beyond 0.03-0.04 units/min, as higher doses cause cardiac, digital, and splanchnic ischemia 3

Critical Pitfall to Avoid

Do not wait until norepinephrine exceeds 0.2 mcg/kg/min (approximately 15 mcg/min in a 70kg patient) before adding a second agent. 1, 3 Norepinephrine doses above 15 mcg/min are associated with significantly increased mortality and indicate severe shock requiring immediate escalation of therapy. 3

Third Vasopressor Selection

If hypotension persists despite norepinephrine plus vasopressin:

• Add epinephrine (0.05-2 mcg/kg/min) as the third vasopressor, particularly when myocardial dysfunction is present due to its inotropic effects 1, 2, 3
• Alternatively, consider adding dobutamine (2.5-20 mcg/kg/min) if persistent hypoperfusion exists despite adequate MAP, especially when low cardiac output is evident 1, 2, 3

Important Consideration with Epinephrine

Epinephrine increases the risk of serious cardiac arrhythmias (ventricular arrhythmias RR 0.35; 95% CI 0.19-0.66) and causes transient lactic acidosis through β2-adrenergic stimulation, which interferes with lactate clearance as a resuscitation endpoint. 3, 4 Monitor closely for arrhythmias and do not rely solely on lactate trends when epinephrine is used. 3, 4

Agents to Avoid

• Never use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine 1, 2, 3
• Dopamine should only be considered in highly selected patients with absolute bradycardia and low risk of tachyarrhythmias 1, 2, 5
• Do not use dopamine for "renal protection"—this is strongly discouraged and provides no benefit 1, 2, 3
• Avoid phenylephrine except in specific circumstances: 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

Monitoring Beyond MAP Targets

MAP ≥65 mmHg alone is insufficient—assess tissue perfusion using: 1, 2, 3

• Lactate clearance (repeat within 6 hours if initially elevated) 1
• Urine output 1, 2, 3
• Mental status 1, 2, 3
• Skin perfusion and capillary refill 1, 2, 3

Special Considerations for Obstetric Patients

In maternal sepsis with persistent hypotension after 1-2L fluid bolus:

• Start norepinephrine at 0.02 mcg/kg/min to maintain MAP ≥65 mmHg 1
• Add vasopressin 0.04 units/min if MAP remains inadequate despite low-moderate dose norepinephrine (0.1-0.2 mcg/kg/min) 1
• Consider epinephrine in patients with cardiac dysfunction and persistent hypoperfusion despite adequate volume status and arterial pressure 1
• Start low-dose steroids (hydrocortisone 200 mg/day) if no response to norepinephrine or epinephrine ≥0.25 mcg/kg/min for at least 4 hours 1

Adjunctive Therapy for Refractory Shock

If hypotension remains refractory despite multiple vasopressors:

• Consider low-dose corticosteroids (hydrocortisone 200 mg/day IV) for shock reversal 3
• This is indicated when vasopressor requirements remain high despite combination therapy 1, 3