In a septic shock patient with worsening hypotension despite high‑dose norepinephrine and moderate‑dose dopamine and dobutamine, how should vasopressor and inotropic therapy be adjusted?

Immediate Vasopressor Adjustment in Refractory Septic Shock

Stop dopamine immediately and discontinue dobutamine, add vasopressin at 0.03 units/minute to your high-dose norepinephrine, and prepare to add epinephrine as a third vasopressor if hypotension persists. 1, 2

Critical First Steps: Eliminate Harmful Agents

Dopamine must be discontinued now — it increases mortality by 11% absolute risk reduction compared to norepinephrine and causes significantly more arrhythmias (53% increased risk of supraventricular arrhythmias, 65% increased risk of ventricular arrhythmias). 1, 3 The Society of Critical Care Medicine strongly discourages dopamine use except in highly selected patients with bradycardia and low arrhythmia risk. 1

Discontinue dobutamine immediately unless you have documented myocardial dysfunction with persistent hypoperfusion despite adequate MAP. 1, 2 In refractory shock with worsening hypotension, dobutamine's inotropic effects increase myocardial oxygen demand without addressing the primary problem of severe vasodilatory collapse. 1

Vasopressor Escalation Algorithm

Step 1: Add Vasopressin (Do This Now)

• Start vasopressin at a fixed dose of 0.03 units/minute immediately. 1, 2
• Vasopressin works through V1 receptors (different from alpha-adrenergic receptors), providing complementary vasoconstriction when catecholamine receptors are downregulated in septic shock. 2, 4
• Never exceed 0.03-0.04 units/minute except as salvage therapy — higher doses cause cardiac, digital, and splanchnic ischemia. 1, 2
• The pressor effect peaks within 15 minutes and fades within 20 minutes after stopping. 4

Step 2: If Hypotension Persists, Add Epinephrine

• If target MAP ≥65 mmHg is not achieved after adding vasopressin, add epinephrine at 0.05 mcg/kg/min (approximately 3.5 mcg/min for a 70 kg patient). 1, 2
• Titrate epinephrine in increments of 0.03 mcg/kg/min up to a maximum of 0.3 mcg/kg/min (21 mcg/min for 70 kg patient). 1
• Epinephrine is recommended as the third vasopressor agent rather than escalating norepinephrine or vasopressin beyond recommended limits. 1, 2

Step 3: Consider Hydrocortisone for Refractory Shock

• Add hydrocortisone 200 mg/day IV (50 mg every 6 hours) if hypotension persists despite norepinephrine, vasopressin, and epinephrine. 1, 2, 5
• The Surviving Sepsis Campaign recommends steroids for shock reversal when hemodynamic stability cannot be achieved despite adequate fluid resuscitation and vasopressor therapy. 5
• Taper hydrocortisone when vasopressors are no longer required. 5

Essential Monitoring Requirements

• Verify central venous access for safe vasopressor administration. 1, 2
• Place arterial catheter if not already present for continuous blood pressure monitoring. 1, 2
• Monitor tissue perfusion markers beyond MAP: lactate clearance every 2-4 hours, urine output ≥0.5 mL/kg/h, mental status, capillary refill, and skin perfusion. 1, 2

Critical Pitfalls to Avoid

Do not escalate norepinephrine indefinitely — doses above 15 mcg/min are associated with increased mortality and indicate the need for additional vasopressor agents with different mechanisms of action. 1

Do not use phenylephrine — it may raise blood pressure numbers on the monitor while actually worsening tissue perfusion through excessive vasoconstriction without cardiac output support. 1

Do not combine dopamine with epinephrine — this creates additive adverse effects and significantly increases arrhythmia risk. 1

Do not use vasopressin as monotherapy — it must always be added to norepinephrine, never used alone. 1, 2

Reassess for Myocardial Dysfunction

Only reintroduce dobutamine (2.5-20 mcg/kg/min) if you achieve adequate MAP with the above vasopressor regimen but persistent hypoperfusion continues with documented myocardial dysfunction (low cardiac output on echocardiography or cardiac output monitoring). 1, 2 In this scenario, the problem is cardiac output rather than vascular tone, making inotropic support appropriate. 1