How does epinephrine (adrenaline) increase lactate levels?

How Epinephrine Drives Lactate Production

Epinephrine increases lactate levels primarily through stimulation of beta-adrenergic receptors, which activates glycogenolysis and glycolysis in skeletal muscle while simultaneously enhancing the Cori cycle, resulting in increased lactate production independent of tissue hypoperfusion. 1, 2

Mechanisms of Epinephrine-Induced Lactate Production

Beta-Adrenergic Effects on Skeletal Muscle

• Epinephrine stimulates beta-2-adrenergic receptors in skeletal muscle, activating glycogenolysis and glycolysis, leading to increased lactate production 1, 3
• At lower infusion doses (<0.3 μg/kg/min), epinephrine predominantly produces beta-adrenergic effects, including increased lactate production in peripheral tissues 1
• In skeletal muscle, beta-adrenergic stimulation activates glycogenolysis and increases lactate production due to the absence of glucose-6-phosphatase 1

Cori Cycle Activation

• Epinephrine enhances the Cori cycle, where lactate produced in peripheral tissues is transported to the liver as a substrate for gluconeogenesis 1, 3
• The drug increases the shuttle of lactate to the liver for glucose production, resulting in elevated plasma lactate concentrations 1
• Studies show that epinephrine administration activates gluconeogenesis and increases glucose utilization, with most utilized glucose being converted to lactate 3, 4

Metabolic Effects

• Epinephrine stimulates gluconeogenesis and glycogenolysis while inhibiting insulin action, leading to hyperglycemia 2, 1
• The drug increases blood glucose concentration and inhibits insulin release from the pancreas, contributing to elevated blood lactate levels 2
• Epinephrine-induced insulin resistance further contributes to lactate accumulation 5

Clinical Implications

Lactate Elevation Without Tissue Hypoperfusion

• Epinephrine can cause increased plasma lactate independent of changes in organ perfusion, making lactate a more difficult parameter to interpret in patients receiving epinephrine 1, 6
• In post-cardiopulmonary bypass patients, epinephrine administration has been shown to cause lactic acidosis without evidence of reduced tissue perfusion 6
• This phenomenon is associated with increased whole-body and lower limb blood flow and decreased oxygen extraction, not tissue hypoxia 6

Differential Effects from Other Vasopressors

• Unlike epinephrine, norepinephrine administration does not typically cause significant lactate elevation 6
• In comparative studies, epinephrine infusion produced a transient increase in serum lactate levels and decrease in arterial pH compared to norepinephrine 1

Monitoring Considerations

• When using epinephrine in clinical settings, particularly in septic shock, clinicians should be aware that elevated lactate may not necessarily indicate worsening tissue perfusion 1
• Lactate-guided resuscitation strategies should consider the direct metabolic effects of epinephrine when interpreting lactate levels 1

Dosage Considerations

• At lower doses (<0.3 μg/kg/min), epinephrine primarily causes beta-adrenergic effects with greater lactate production 1
• At higher doses (>0.3 μg/kg/min), alpha-adrenergic vasoconstriction becomes more prominent, though metabolic effects persist 1
• The degree of lactate elevation may vary based on individual patient factors and epinephrine dosing 1, 6