Does vasopressin increase lactate levels in patients with septic shock?

Vasopressin and Lactate Levels in Septic Shock

Vasopressin does increase lactate levels in patients with septic shock, but this effect is clinically modest and should not prevent its use as an adjunctive vasopressor when indicated. 1

Evidence for Vasopressin-Associated Lactate Elevation

The most direct evidence comes from a 2020 observational study demonstrating that vasopressin administration was associated with rising serum lactate levels in septic patients:

• Patients receiving vasopressin were 6.6 times more likely to have rising lactate levels (95% CI: 3.0-14.6) compared to matched controls who did not receive vasopressin 1
• The median lactate increase was 0.3 mmol/L in vasopressin-treated patients, while controls had a median decrease of 0.7 mmol/L over 24 hours 1
• This association remained significant even when accounting for norepinephrine initiation timing 1

Mechanism and Clinical Context

Unlike epinephrine, vasopressin does not directly stimulate metabolic lactate production through β2-adrenergic receptors. 2, 3 The lactate elevation with vasopressin likely reflects:

• Microcirculatory effects at higher doses: Vasopressin can impair splanchnic perfusion, particularly at doses above 0.03 U/min, potentially causing tissue hypoperfusion 2
• Dose-dependent vasoconstriction: At low doses, vasopressin has modest effects on splanchnic circulation, but at high doses it markedly impairs regional perfusion 2

Paradoxical Findings on Lactate Clearance

Interestingly, one randomized trial found vasopressin improved 24-hour lactate clearance (46% vs. 20%, p=0.048) compared to norepinephrine alone, despite the observational data showing lactate increases 4. This suggests:

• The lactate effect may be related to vasopressin's catecholamine-sparing properties 4
• Microcirculatory improvements may occur at appropriate doses 4
• The relationship between vasopressin and lactate is complex and potentially dose-dependent

Critical Distinction from Epinephrine

This is fundamentally different from epinephrine-induced lactate elevation: 2, 3

• Epinephrine increases aerobic lactate production via β2-adrenergic stimulation of skeletal muscle glycogenolysis 2, 3
• Epinephrine's lactate elevation is a direct metabolic effect independent of tissue perfusion 3
• Vasopressin has no evidence of direct metabolic effects on lactate production 2

Clinical Implications for Practice

Do not withhold vasopressin due to concerns about lactate elevation. The guideline-recommended approach remains:

• Use vasopressin at 0.03 U/min as an adjunctive agent when norepinephrine alone is insufficient to maintain MAP ≥65 mmHg 2
• Monitor lactate trends in context: Rising lactate with vasopressin may reflect inadequate resuscitation or excessive dosing rather than a benign metabolic effect 1
• Avoid doses >0.04 U/min due to increased risk of cardiac, digital, and splanchnic ischemia 2, 5

Practical Monitoring Strategy

When using vasopressin in septic shock:

• Complement lactate monitoring with other perfusion markers: urine output, skin perfusion, mental status, and mixed/central venous oxygen saturation 2
• Consider the timing and magnitude of lactate changes: A modest 0.3 mmol/L increase is clinically different from progressive lactate elevation suggesting worsening shock 1
• Wean vasopressin after norepinephrine during de-escalation, as withdrawing vasopressin first causes more hemodynamic instability 2

Key Caveat

The observational nature of the primary evidence linking vasopressin to lactate elevation limits causal inference. 1 Patients receiving vasopressin typically have more severe shock, which itself drives lactate elevation. The association may reflect disease severity rather than a direct drug effect, though the matched design attempted to control for this confounding.