From the Guidelines
Epinephrine (adrenaline) causes Type B lactic acidosis through its effects on metabolism, as evidenced by its ability to stimulate glycolysis and increase glucose production, leading to increased lactate production even in the absence of tissue hypoxia. This is supported by the study 1, which notes that epinephrine can aggravate lactic acidosis, and suggests that norepinephrine should be preferred over epinephrine when available. The mechanism by which epinephrine causes Type B lactic acidosis involves the activation of beta-2 adrenergic receptors, which stimulates glycolysis and increases glucose production through glycogenolysis, leading to increased pyruvate production and subsequent conversion to lactate.
Key points to consider include:
- Epinephrine's stimulation of Na+/K+ ATPase activity, which increases energy demands and further promotes lactate production 1
- The importance of monitoring patients receiving epinephrine infusions for signs of lactic acidosis, particularly in resource-limited settings where access to diagnostic tools may be limited 1
- The potential for epinephrine to cause Type B lactic acidosis even in the absence of tissue hypoxia, highlighting the need for careful patient monitoring and management 1
It is also worth noting that while other studies, such as 1, discuss the use of epinephrine in the treatment of anaphylaxis, they do not provide direct evidence regarding the mechanism by which epinephrine causes Type B lactic acidosis. Therefore, the study 1 remains the most relevant and highest-quality evidence for this specific question.
From the FDA Drug Label
Epinephrine increases glycogenolysis, reduces glucose up take by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid [see Warnings and Precautions 5-(5.3)]. Epinephrine causes Type B lactic acidosis by:
- Increasing glycogenolysis
- Reducing glucose uptake by tissues
- Inhibiting insulin release in the pancreas, resulting in hyperglycemia and increased blood lactic acid 2
From the Research
Epi-Induced Type B Lactic Acidosis
- Type B lactic acidosis is a condition where lactic acid builds up in the blood due to non-hypoxic causes, such as metabolic disorders or certain medications 3, 4, 5, 6.
- Epinephrine (epi) administration has been shown to cause Type B lactic acidosis in some patients, particularly in the context of cardiopulmonary bypass 3 and anaphylactic shock 5, 6.
- The mechanism of epi-induced lactic acidosis is thought to be related to the beta-mediated effects of epinephrine, which increase whole-body and lower limb blood flow, and decrease whole-body and transfemoral oxygen extraction 3.
- Studies have also shown that epinephrine perfusion directly increases local leg lactate release, stimulates lipolysis, and induces insulin resistance, which can contribute to the development of lactic acidosis 4.
- The increase in lactate levels due to epinephrine administration can be transient and resolve after discontinuation of the drug, highlighting the importance of careful monitoring and nuanced interpretation of lactate dynamics 5, 6.
- Clinicians must differentiate between lactate elevations due to tissue hypoperfusion and those arising from epinephrine's pharmacologic effects to optimize patient care 5, 6.