How to manage vasopressor-resistant septic shock?

Management of Vasopressor-Resistant Septic Shock

When norepinephrine alone fails to achieve a MAP ≥65 mmHg despite adequate fluid resuscitation, add vasopressin at 0.03 units/minute to either raise MAP to target or decrease norepinephrine requirements. 1, 2

Stepwise Escalation Algorithm

First-Line: Optimize Norepinephrine

• Start norepinephrine as the first-choice vasopressor, targeting MAP ≥65 mmHg 1, 2
• Ensure adequate fluid resuscitation (minimum 30 mL/kg crystalloids) has been initiated, but do not delay vasopressors waiting for complete fluid resuscitation if life-threatening hypotension exists 1, 2, 3
• Place arterial catheter for continuous blood pressure monitoring as soon as practical 1, 2
• Titrate norepinephrine upward to achieve target MAP 1

Second-Line: Add Vasopressin

When norepinephrine requirements remain elevated or target MAP is not achieved:

• Add vasopressin at 0.03 units/minute (do NOT use as monotherapy) 1, 2, 4
• The FDA-approved starting dose for septic shock is 0.01 units/minute, titrated up by 0.005 units/minute at 10-15 minute intervals 4
• Maximum recommended dose is 0.03-0.04 units/minute; higher doses should be reserved for salvage therapy only 1, 2
• Vasopressin reaches peak pressor effect within 15 minutes 4

Third-Line: Add Epinephrine or Dobutamine

If hypotension persists despite norepinephrine plus vasopressin:

• Add epinephrine to norepinephrine and vasopressin when additional agent is needed to maintain adequate blood pressure 1
• Consider dobutamine (up to 20 μg/kg/min) if there is evidence of persistent hypoperfusion despite adequate fluid loading and vasopressor use, particularly with myocardial dysfunction (elevated cardiac filling pressures, low cardiac output) 1, 2

Salvage Therapy Considerations

For truly refractory shock:

• Phenylephrine is NOT recommended except in specific circumstances: (a) norepinephrine causes serious arrhythmias, (b) cardiac output is known to be high with persistently low blood pressure, or (c) as salvage therapy when combined inotrope/vasopressor drugs and low-dose vasopressin have failed 1, 2
• Consider hydrocortisone 200 mg/day if adequate fluid resuscitation and vasopressor therapy cannot restore hemodynamic stability 1

Critical Monitoring Requirements

Hemodynamic Monitoring

• Continuous arterial blood pressure monitoring via arterial catheter 1, 2
• Monitor markers of tissue perfusion beyond MAP: lactate clearance, urine output, mental status, skin perfusion 2, 5
• Assess for signs of excessive vasoconstriction: digital ischemia, decreased urine output, rising lactate, worsening organ dysfunction despite adequate MAP 2

Vasopressor Weaning

• After target blood pressure is maintained for 8 hours without catecholamines, taper vasopressin by 0.005 units/minute every hour as tolerated 4
• Taper hydrocortisone when vasopressors are no longer required 1

Agents to AVOID

Dopamine

• Do NOT use dopamine as first-line therapy—it is associated with higher mortality and more arrhythmias compared to norepinephrine 1, 2, 6, 7
• Use dopamine only in highly selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia 1, 2
• Never use low-dose dopamine for renal protection—this is strongly discouraged with high-quality evidence showing no benefit 1, 2, 6

Other Contraindicated Approaches

• Do not use vasopressin as sole initial vasopressor 1, 2, 6
• Do not exceed vasopressin 0.03-0.04 units/minute except as salvage therapy 1, 2
• Avoid phenylephrine as routine therapy—it may raise blood pressure while actually worsening tissue perfusion through excessive vasoconstriction 1, 2

Common Pitfalls to Avoid

• Do not delay norepinephrine initiation waiting for complete fluid resuscitation if life-threatening hypotension exists 2, 3, 5
• Do not rely solely on MAP—monitor tissue perfusion markers (lactate, urine output, mental status) to guide therapy 2, 5
• Do not use vasopressin as monotherapy—it must always be added to norepinephrine, never used alone 1, 2, 6
• Do not escalate vasopressin beyond 0.03-0.04 units/minute—add epinephrine or dobutamine instead 1, 2
• Avoid excessive vasoconstriction—titrate to adequate perfusion markers, not supranormal blood pressure targets 2