How do you escalate to adding multiple vasopressors (pressors) in a patient with hypotension?

Vasopressor Escalation Strategy for Refractory Hypotension

Start with norepinephrine as your first-line vasopressor, and when it fails to achieve a MAP of 65 mmHg, add vasopressin at 0.03 units/minute as your second agent, followed by epinephrine if hypotension persists—never escalate beyond moderate doses of a single agent before adding a second vasopressor. 1, 2, 3

Initial Vasopressor: Norepinephrine

• Begin norepinephrine at 0.1-0.5 mcg/kg/min (approximately 8-12 mcg/min for a 70 kg patient) through central venous access, targeting a MAP of 65 mmHg 1, 3, 4
• Titrate norepinephrine upward based on blood pressure response, but recognize that doses exceeding 15 mcg/min indicate severe shock and trigger the need for a second agent 1
• Place an arterial catheter for continuous blood pressure monitoring as soon as practical when any vasopressor is initiated 5, 1, 3

Second Vasopressor: Add Vasopressin

When norepinephrine alone fails to maintain MAP ≥65 mmHg, add vasopressin at a fixed dose of 0.03 units/minute rather than continuing to escalate norepinephrine 1, 2, 3

• Vasopressin should never be used as monotherapy—it must be added to norepinephrine, not substituted for it 1, 6
• The standard dose is 0.03 units/minute; do not exceed 0.03-0.04 units/minute except as salvage therapy, as higher doses cause cardiac, digital, and splanchnic ischemia 5, 1, 6
• After adding vasopressin, you can either raise MAP to target or decrease norepinephrine requirements while maintaining hemodynamic stability 1, 3

Third Vasopressor: Add Epinephrine

If hypotension persists despite norepinephrine plus vasopressin, add epinephrine at 0.05-0.5 mcg/kg/min as your third agent 1, 2, 3

• Epinephrine should be added rather than escalating vasopressin beyond 0.03-0.04 units/minute 1
• Be aware that epinephrine causes transient lactic acidosis through β2-adrenergic stimulation of skeletal muscle, which interferes with using lactate clearance as a resuscitation endpoint 1
• Monitor closely for arrhythmias, as epinephrine increases myocardial oxygen consumption more than norepinephrine and carries higher risk of ventricular arrhythmias 1

Critical Thresholds and Decision Points

When to Add the Second Agent

• Add vasopressin when norepinephrine reaches approximately 15 mcg/min (0.2 mcg/kg/min) without achieving target MAP 1
• Do not wait until norepinephrine doses become extreme—patients requiring ≥15 mcg/min already have severe shock with elevated mortality 1

When to Add the Third Agent

• Add epinephrine when norepinephrine plus vasopressin 0.03 units/minute fails to maintain MAP ≥65 mmHg 1, 2
• Consider adding dobutamine (up to 20 mcg/kg/min) instead of a third vasopressor if there is evidence of myocardial dysfunction with persistent hypoperfusion despite adequate MAP 5, 1, 3

Agents to Avoid During Escalation

Do not use dopamine as a first-line agent—it is associated with higher mortality and more arrhythmias compared to norepinephrine 5, 1, 2

• Dopamine should only be considered in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia 5, 1
• Do not use low-dose dopamine for "renal protection"—this practice is strongly discouraged and provides no benefit 5, 1

Avoid phenylephrine except in specific circumstances 1, 2

• Phenylephrine is a pure alpha-agonist that may raise blood pressure numbers while actually worsening tissue perfusion through excessive vasoconstriction 1
• Reserve phenylephrine only for situations where norepinephrine causes serious arrhythmias, cardiac output is documented to be high with persistent hypotension, or as salvage therapy when all other agents have failed 1, 2

Adjunctive Therapies for Refractory Shock

Corticosteroids

• Consider hydrocortisone 200 mg/day IV (or 50 mg every 6 hours) for shock reversal if hypotension remains refractory despite multiple vasopressors 1, 3
• This is particularly relevant in septic shock when adequate fluid resuscitation and vasopressor therapy fail to restore hemodynamic stability 5

Inotropic Support

• Add dobutamine 2-20 mcg/kg/min if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is evident 5, 1, 3
• Dobutamine should be used when there is low cardiac output with adequate filling pressures, not simply for refractory hypotension 5

Common Pitfalls to Avoid

Never escalate a single vasopressor to extreme doses before adding a second agent 1

• Doses of norepinephrine exceeding 175 mcg/min (2.5 mcg/kg/min in a 70 kg patient) represent more than 10 times the threshold for severe shock and indicate irreversible circulatory failure 1
• Such extreme doses suggest occult blood volume depletion that must be corrected, or the need for mechanical circulatory support rather than further pharmacologic escalation 1, 4

Do not use vasopressin doses above 0.03-0.04 units/minute routinely 5, 1, 6

• Higher vasopressin doses are associated with cardiac, digital, and splanchnic ischemia and should be reserved only for salvage therapy when other vasopressors have failed 5, 1

Ensure adequate fluid resuscitation before and during vasopressor therapy 5, 3, 4

• Blood volume depletion should always be corrected as fully as possible before any vasopressor is administered 4
• In trauma patients without TBI, target systolic blood pressure of 80-90 mmHg with restricted fluid replacement; only use vasopressors if severe hemorrhage-induced hypotension with systolic BP <80 mmHg occurs 5

Monitor for signs of excessive vasoconstriction 1

• Watch for digital ischemia, decreased urine output, rising lactate, or worsening organ dysfunction despite adequate MAP 1
• Titrate to adequate perfusion markers, not to supranormal blood pressure targets 1

Special Considerations by Shock Type

Septic Shock

• Follow the standard escalation pathway: norepinephrine → add vasopressin → add epinephrine 1, 2, 3
• Target MAP of 65 mmHg initially, considering higher targets only in patients with chronic hypertension 1, 3

Cardiogenic Shock

• Norepinephrine remains first-line, but consider earlier addition of inotropes (dobutamine or milrinone) rather than multiple vasopressors 5, 3
• In cardiogenic shock specifically, milrinone may be associated with better prognosis compared to other vasoactive agents 7
• Use vasopressors cautiously as they increase afterload and myocardial oxygen demand 5

Hemorrhagic/Trauma Shock

• Prioritize bleeding control and blood product resuscitation over vasopressors 5
• Use permissive hypotension (systolic BP 80-90 mmHg) until bleeding is controlled, except in patients with TBI or spinal injury 5
• Only use transient norepinephrine if systolic BP falls below 80 mmHg despite restricted volume replacement 5
• Consider low-dose vasopressin (bolus of 4 IU followed by 0.04 IU/min) in hemorrhagic shock, as it may decrease blood product requirements 5