Epinephrine Administration Increases Lactic Acid Levels Through Direct Metabolic Effects
Epinephrine administration causes elevated lactic acid levels independent of tissue perfusion status, primarily through beta-2-adrenergic stimulation of skeletal muscle glycolysis, making lactate an unreliable marker of tissue hypoperfusion in patients receiving this medication. 1, 2
Mechanism of Lactate Production
Epinephrine increases lactate through direct metabolic pathways rather than tissue hypoxia:
Beta-2-adrenergic receptor stimulation in skeletal muscle activates glycogenolysis and glycolysis, directly producing lactate even when tissue perfusion is adequate. 1 This occurs because skeletal muscle lacks glucose-6-phosphatase, forcing glycolytic products toward lactate production. 1
At lower infusion doses (<0.3 μg/kg/min), beta-adrenergic effects predominate, causing greater lactate production in peripheral tissues. 1 The FDA label confirms that epinephrine increases glycogenolysis, reduces glucose uptake by tissues, inhibits insulin release, and increases blood lactic acid. 2
At higher doses (>0.3 μg/kg/min), alpha-adrenergic vasoconstriction becomes more prominent, though metabolic lactate production persists. 1
Clinical Evidence from Comparative Studies
In randomized trials comparing epinephrine to norepinephrine after cardiopulmonary bypass, 6 of 19 patients (32%) receiving epinephrine developed lactic acidosis, while zero patients receiving norepinephrine developed this complication. 3
Key findings from this high-quality evidence:
Lactate concentrations increased significantly at 1 hour and 6-10 hours after epinephrine infusion (p=0.01), while pH and base excess decreased (p≤0.01). 3
Patients receiving epinephrine had higher femoral venous lactate concentrations (p=0.03), increased lower limb blood flow (p=0.05), and increased femoral venous oxygen saturations (p=0.04). 3 This demonstrates that lactate elevation occurred despite improved, not worsened, tissue perfusion.
The phenomenon was associated with increased whole-body blood flow and decreased oxygen extraction, confirming this was not related to reduced tissue perfusion. 3
Critical Clinical Implications for Practice
The American College of Critical Care Medicine explicitly states that epinephrine may prevent the use of lactate clearance to guide resuscitation because elevated lactate does not necessarily indicate worsening tissue perfusion. 1 This has profound implications for clinical decision-making:
Do not interpret rising lactate as treatment failure or worsening shock in patients receiving epinephrine. 1 The lactate elevation is a direct pharmacologic effect, not a marker of inadequate resuscitation.
Lactate-guided resuscitation strategies should not be applied to patients receiving epinephrine infusions. 1 Use alternative markers of perfusion adequacy (mental status, urine output, skin perfusion, mixed venous oxygen saturation).
When choosing vasopressors for septic shock, norepinephrine is recommended as first-line therapy, with epinephrine as the first alternative only when norepinephrine is unavailable or ineffective. 1 This recommendation is based partly on the confounding effect of epinephrine on lactate monitoring.
Common Pitfalls to Avoid
The most dangerous error is misinterpreting epinephrine-induced lactate elevation as evidence of inadequate resuscitation or worsening shock, leading to unnecessary escalation of therapy. 1, 3
Subcutaneous epinephrine administration (as used in anaphylaxis or asthma) can also cause lactic acidosis. 4 A case report documented lactate rising to 9.5 mmol/L six hours after subcutaneous epinephrine for status asthmaticus, resolving within 15 hours without hypotension, hypoxemia, or sepsis. 4
The lactic acidosis associated with epinephrine does not carry the poor prognosis of lactate elevation from shock states. 3 Recognize this as a benign metabolic effect rather than a marker of mortality risk.
Blood glucose concentration is also elevated by epinephrine through the same beta-adrenergic mechanisms. 2, 3 Expect hyperglycemia as a concurrent finding.
Practical Monitoring Approach
When epinephrine is being administered:
Monitor hemodynamic parameters directly: blood pressure, cardiac output, mixed venous oxygen saturation, and clinical perfusion markers (mental status, urine output, capillary refill). 5, 3
If lactate is measured, interpret trends cautiously and in context with other perfusion markers. 1 A rising lactate with improving blood pressure, urine output, and mental status likely represents the metabolic effect rather than worsening shock.
Consider switching to norepinephrine if lactate monitoring is essential for guiding therapy. 1 Norepinephrine does not produce the same degree of metabolic lactate elevation. 3