Does a continuous intravenous epinephrine infusion raise serum lactate and blood glucose levels?

Epinephrine Infusion Raises Both Lactate and Blood Glucose

Yes, continuous intravenous epinephrine infusion significantly elevates both serum lactate and blood glucose levels through distinct metabolic mechanisms that are independent of tissue perfusion status.

Mechanism of Lactate Elevation

Epinephrine increases plasma lactate concentrations through stimulation of gluconeogenesis via the Cori cycle, making lactate a less reliable marker of tissue hypoperfusion in patients receiving epinephrine infusions. 1

• Epinephrine increases the shuttle of lactate to the liver as a substrate for glucose production through the Cori cycle, resulting in elevated plasma lactate concentrations independent of changes in organ perfusion 1
• This metabolic effect makes lactate "somewhat more difficult to interpret in children with septic shock" receiving epinephrine, as the elevation does not necessarily indicate inadequate tissue oxygenation 1
• Lactate serves as the predominant precursor for epinephrine-stimulated gluconeogenesis in both liver and kidney, with renal and hepatic gluconeogenesis from lactate increasing 4- to 6-fold during epinephrine infusion 2
• Blood lactate levels can rise substantially (1.5-4.6 mmol/L) during epinephrine infusions despite increases in hepatic lactate uptake, demonstrating the powerful peripheral mobilization effect 3

Mechanism of Hyperglycemia

Epinephrine stimulates gluconeogenesis and glycogenolysis while simultaneously inhibiting insulin action, leading to marked increases in blood glucose concentrations. 1

• Epinephrine increases glycogenolysis, reduces glucose uptake by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia 4
• Blood glucose typically rises 40-60% during epinephrine infusion, with plasma insulin increasing 30-40% in a compensatory but insufficient response 5
• The initial epinephrine-induced rise in glucose production is largely due to activation of glycogenolysis, but thereafter epinephrine-stimulated gluconeogenesis becomes the major factor maintaining hepatic glucose production 5
• Epinephrine produces dose-dependent increments in overall glucose production, with progressive stimulation of both glycogenolysis (immediate effect) and gluconeogenesis (sustained effect) 3

Clinical Implications for Monitoring

When managing patients on epinephrine infusions, clinicians must recognize that elevated lactate does not automatically indicate shock or inadequate resuscitation, and hyperglycemia requires active management.

• Monitor glucose and lactate levels as part of routine assessment, but interpret elevated lactate in the context of other perfusion markers (capillary refill, urine output, mental status, ScvO2) rather than as an isolated indicator of inadequate resuscitation 1
• Appropriate glucose delivery can be attained by giving a D10% containing isotonic IV solution at fluid maintenance rate, with insulin infusion titrated to reverse hyperglycemia (keep glucose ≤150 mg/dL) while carefully monitoring to avoid hypoglycemia (keep glucose ≥80 mg/dL) 1
• The use of lesser glucose infusion rates (e.g., D5% or lower volumes of D10%) will not provide adequate glucose delivery requirements during the stress response 1

Dose-Response Relationship

The metabolic effects of epinephrine on lactate and glucose are dose-dependent:

• At lower infusion doses (<0.3 μg/kg/min), epinephrine has greater beta-2-adrenergic effects with less alpha-adrenergic effect, but metabolic effects on glucose and lactate still occur 1
• Higher epinephrine levels produce progressively greater increases in both glycogenolysis and gluconeogenesis, with intrahepatic gluconeogenic efficiency increasing by 77-136% 3
• The conversion of labeled alanine and lactate into glucose can increase fourfold and remain elevated throughout epinephrine infusion, even as the glycogenolytic effect wanes 5

Critical Pitfall to Avoid

Do not interpret elevated lactate as treatment failure or inadequate resuscitation in patients receiving epinephrine without considering other markers of tissue perfusion. The lactate elevation is a predictable metabolic consequence of epinephrine's mechanism of action, not necessarily an indicator of ongoing shock 1. Similarly, hyperglycemia should be anticipated and managed proactively rather than attributed solely to stress or inadequate insulin 4, 5.