What is the third-line recommended vasopressor for a patient in septic shock with global hypokinesia and an ejection fraction (EF) of 25-30%?

Third-Line Vasopressor in Septic Shock with Severe Myocardial Dysfunction

Epinephrine (0.05-2 mcg/kg/min) is the recommended third-line vasopressor for this patient with septic shock and severe cardiac dysfunction (EF 25-30% with global hypokinesia). 1

Vasopressor Escalation Algorithm for This Clinical Scenario

First-Line: Norepinephrine

• Norepinephrine remains the mandatory first-line vasopressor, targeting MAP ≥65 mmHg after adequate fluid resuscitation (minimum 30 mL/kg crystalloid). 1
• Administer through central venous access with continuous arterial blood pressure monitoring. 1

Second-Line: Vasopressin

• Add vasopressin at 0.03 units/minute when norepinephrine alone fails to maintain adequate MAP despite appropriate fluid resuscitation. 1, 2
• Critical ceiling: Do not exceed 0.03-0.04 units/minute for routine use, as higher doses cause cardiac, digital, and splanchnic ischemia without additional benefit. 1
• Vasopressin should never be used as monotherapy—it must be added to norepinephrine. 1

Third-Line: Epinephrine (The Answer for This Patient)

• Add epinephrine at 0.05-2 mcg/kg/min when target MAP is not achieved with norepinephrine plus vasopressin. 1, 2
• For a 70 kg patient, this translates to starting at 3.5 mcg/min and titrating up to a maximum of 140 mcg/min (though typically much lower doses suffice). 1
• Epinephrine is particularly appropriate in this patient because it provides both vasopressor support AND inotropic support for the severely depressed myocardium (EF 25-30%). 1, 3

Why Epinephrine Over Other Options in This Patient

Cardiac Dysfunction Makes Epinephrine Ideal

• The global hypokinesia with EF 25-30% indicates significant myocardial dysfunction requiring both vasopressor AND inotropic support. 1
• Epinephrine provides combined alpha-adrenergic vasoconstriction and beta-1 adrenergic cardiac stimulation, addressing both the vasodilatory shock and cardiac dysfunction simultaneously. 3

Alternative Consideration: Dobutamine

• Dobutamine (2.5-20 mcg/kg/min) should be added if persistent hypoperfusion exists despite adequate MAP and vasopressor therapy, particularly when myocardial dysfunction is the primary problem. 1, 4
• However, dobutamine is an inotrope, not a vasopressor—it addresses cardiac output but does not raise MAP. 1
• In this scenario where you need a third-line vasopressor (implying inadequate MAP despite norepinephrine + vasopressin), epinephrine is superior because it provides both vasopressor and inotropic effects. 1, 3

Critical Monitoring and Safety Considerations

Epinephrine-Specific Risks

• Increased risk of cardiac arrhythmias, particularly ventricular arrhythmias, though still lower than dopamine (RR 0.35; 95% CI 0.19-0.66 compared to dopamine). 1
• Transient lactic acidosis through β2-adrenergic stimulation of skeletal muscle—this interferes with lactate clearance as a resuscitation endpoint, so do not rely solely on lactate trends. 1
• Increased myocardial oxygen consumption more than norepinephrine, making continuous cardiac monitoring essential in this patient with pre-existing cardiac dysfunction. 1

What NOT to Do

• Do not use dopamine—it is strongly discouraged due to higher mortality and significantly more arrhythmias (53% increased risk of supraventricular arrhythmias, 65% increased risk of ventricular arrhythmias). 1, 4
• Do not escalate vasopressin beyond 0.03-0.04 units/minute—reserve higher doses only for salvage therapy when all other options have failed. 1
• Do not use phenylephrine except in specific circumstances (norepinephrine-induced arrhythmias, high cardiac output with persistent hypotension, or salvage therapy). 1

Adjunctive Therapy for Refractory Shock

Corticosteroids

• Consider hydrocortisone 200 mg/day IV for shock reversal if hypotension remains refractory to vasopressors. 1, 2
• This is particularly important if the patient has been on high-dose vasopressors for >4 hours. 5

Monitoring Beyond MAP

• Assess tissue perfusion using lactate clearance (with caveat about epinephrine effect), urine output ≥0.5 mL/kg/hr, mental status, capillary refill, and skin temperature. 1, 5
• Do not focus solely on MAP numbers—tissue perfusion markers are equally critical. 1

Common Pitfalls to Avoid

• Delaying epinephrine addition: If norepinephrine plus vasopressin at appropriate doses fail to achieve target MAP, do not continue escalating norepinephrine to dangerous levels—add epinephrine. 1
• Ignoring the cardiac dysfunction: This patient's EF 25-30% means they need inotropic support in addition to vasopressor support, making epinephrine particularly appropriate. 1
• Using dopamine: Despite its inotropic properties, dopamine is associated with 11% absolute increase in mortality and should be avoided. 1, 6