What are the recommended vasopressors for refractory hypotension in septic shock?

Vasopressor Management for Refractory Hypotension in Septic Shock

Add vasopressin at 0.03 units/minute to norepinephrine when refractory hypotension persists despite adequate fluid resuscitation and initial norepinephrine therapy, targeting a mean arterial pressure (MAP) of 65 mmHg. 1, 2

First-Line Vasopressor Strategy

• Norepinephrine is the mandatory first-choice vasopressor for septic shock, initiated as soon as hypotension persists after fluid resuscitation (minimum 30 mL/kg crystalloid in first 3 hours). 1, 2
• Administer norepinephrine through central venous access with continuous arterial blood pressure monitoring via arterial catheter placed as soon as practical. 1, 2
• Target MAP of 65 mmHg in most patients; consider higher targets (80-85 mmHg) only in patients with documented chronic hypertension. 2, 3

Escalation Protocol for Refractory Hypotension

When norepinephrine alone fails to achieve target MAP despite adequate dosing, follow this algorithmic approach:

Second-Line Agent: Vasopressin (Preferred)

• Add vasopressin at 0.03 units/minute (range 0.01-0.03 units/min) to norepinephrine rather than escalating norepinephrine dose further. 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
• Never use vasopressin as monotherapy—it must always be added to norepinephrine, not used as the sole initial vasopressor. 2, 4
• Do not exceed 0.03-0.04 units/minute except as salvage therapy when all other options have failed. 2, 4
• Vasopressin acts on different vascular receptors (V1) than norepinephrine (α1-adrenergic), providing synergistic effect and norepinephrine-sparing properties. 5, 6

Alternative Second-Line Agent: Epinephrine

• Add epinephrine as an alternative to vasopressin when additional vasopressor support is needed. 1, 2
• FDA-approved dosing: 0.05-2 mcg/kg/min IV infusion, titrated every 10-15 minutes in increments of 0.05-0.2 mcg/kg/min to achieve desired MAP. 7
• Epinephrine carries higher risk of metabolic derangements (hyperglycemia, hyperlactatemia) and cardiac adverse effects compared to norepinephrine. 5

Third-Line Consideration: Dobutamine

• Add dobutamine (up to 20 mcg/kg/min) if persistent hypoperfusion exists despite adequate fluid loading and vasopressor therapy, particularly when myocardial dysfunction is evident. 1, 2
• Dobutamine provides inotropic support rather than additional vasoconstriction, addressing the cardiac component of shock. 1

Agents to Avoid in Refractory Septic Shock

Dopamine: Strongly Discouraged

• Use dopamine only in highly selected patients with low risk of tachyarrhythmias or absolute/relative bradycardia—it is associated with higher mortality and more arrhythmias compared to norepinephrine. 1, 2
• Never use low-dose dopamine for renal protection—this is a strong recommendation with high-quality evidence showing no benefit. 1, 2

Phenylephrine: Reserved for Specific Circumstances Only

• Do not use phenylephrine except when: (a) norepinephrine causes serious arrhythmias, (b) cardiac output is documented to be high with persistently low blood pressure, or (c) as salvage therapy when all other agents have failed. 1, 2
• Phenylephrine is a pure α1-agonist that may raise blood pressure numbers while actually compromising microcirculatory flow and tissue perfusion. 2

Critical Monitoring and Titration

• Monitor perfusion markers beyond blood pressure: lactate clearance, urine output, mental status, and skin perfusion to guide therapy. 3
• After target blood pressure is maintained for 8 hours without catecholamines, taper vasopressin by 0.005 units/minute every hour as tolerated. 4
• Wean epinephrine incrementally over 12-24 hours after hemodynamic stabilization, decreasing doses every 30 minutes. 7

Common Pitfalls to Avoid

• Do not delay norepinephrine initiation waiting to complete entire fluid resuscitation if life-threatening hypotension exists—early norepinephrine administration improves cardiac output, microcirculation, and avoids fluid overload. 6
• Do not escalate norepinephrine indefinitely without adding vasopressin—doses above 1 mcg/kg/min are associated with mortality rates exceeding 80%. 8
• Do not titrate to supranormal blood pressure targets—excessive vasoconstriction can compromise microcirculatory flow despite adequate MAP on the monitor. 2
• Do not use vasopressin analogs (terlipressin, selepressin) in septic shock—these agents are associated with higher rates of digital ischemia without proven mortality benefit. 5, 8