What is the alternative to increasing the dose of noradrenaline (norepinephrine) in patients with hypotension?

Vasopressin as Second-Line Vasopressor in Septic Shock

Add vasopressin at 0.03 units/minute when norepinephrine requirements exceed 0.25 mcg/kg/min, rather than continuing to escalate norepinephrine doses. 1

When to Add Vasopressin

The most recent high-quality guideline (AASLD 2024) explicitly recommends vasopressin as a second-line agent when increasing doses of norepinephrine are required. 1 This represents a shift from simply escalating norepinephrine, which at high doses may cause:

• Increased cardiac arrhythmias 2
• Immunological adverse effects 3
• Poorer patient outcomes at doses >0.25-0.50 mcg/kg/min 3

The Surviving Sepsis Campaign guidelines support adding vasopressin rather than increasing norepinephrine beyond moderate doses, specifically when norepinephrine reaches 0.25 mcg/kg/min and hypotension persists. 2

Vasopressin Dosing Protocol

Standard dose: 0.03 units/minute as continuous IV infusion 2, 4

• Do NOT use vasopressin as monotherapy—it must be added to norepinephrine, never used alone 2
• Do NOT exceed 0.03-0.04 units/minute except as salvage therapy when all other options have failed 2, 3
• Doses above 0.04 units/minute are associated with cardiac, digital, and splanchnic ischemia 2

Critical Pre-Administration Requirements

Before initiating vasopressin:

• Ensure adequate fluid resuscitation with minimum 30 mL/kg crystalloid bolus 4
• Verify norepinephrine is running at ≥0.25 mcg/kg/min 4
• Exclude persistent hypovolemia and cardiac dysfunction 3
• Establish central venous access (strongly preferred) 4
• Place arterial catheter for continuous blood pressure monitoring 2

Physiologic Rationale

Up to one-third of patients with septic shock have vasopressin deficiency, which contributes to refractory shock. 3 Vasopressin works through V1 receptors, providing vasoconstriction through a non-catecholaminergic pathway—this is the concept of "decatecholaminization." 3 This norepinephrine-sparing effect may reduce complications from high-dose catecholamines. 3

Alternative Escalation Strategy

If vasopressin is unavailable or contraindicated, consider adding epinephrine 0.1-0.5 mcg/kg/min as an alternative second-line agent. 2 However, epinephrine causes more metabolic adverse effects (transient lactic acidosis) and cardiac arrhythmias compared to the norepinephrine-vasopressin combination. 2

Common Pitfalls to Avoid

• Never escalate vasopressin beyond 0.03-0.04 units/minute—this causes severe ischemic complications 2, 3
• Never use vasopressin as sole initial vasopressor—norepinephrine must be first-line 2
• Do not add vasopressin before adequate fluid resuscitation—this causes severe organ hypoperfusion from excessive vasoconstriction in hypovolemic patients 5
• Avoid dopamine entirely—it is associated with higher mortality and more arrhythmias compared to norepinephrine 2
• Do not use phenylephrine as first-line—it may raise blood pressure numbers while actually worsening tissue perfusion 2

Target Blood Pressure

Maintain mean arterial pressure (MAP) ≥65 mmHg while monitoring tissue perfusion markers:

• Lactate clearance 5
• Urine output >50 mL/h 5
• Mental status 5
• Capillary refill 5

Patients with chronic hypertension may require higher MAP targets, but titrate to adequate perfusion markers, not supranormal blood pressure. 2