From the Guidelines
Lactate elevations above 4 mmol/L in patients on epinephrine infusions should raise concern, as they may indicate tissue hypoperfusion or other causes of lactate elevation. The interpretation of lactate levels in patients on epinephrine infusions requires consideration of the baseline and rate of increase rather than an absolute threshold 1. Epinephrine naturally increases lactate levels through its beta-adrenergic effects, which enhance glycolysis and inhibit pyruvate dehydrogenase, leading to increased lactate production even in well-perfused tissues 1. This phenomenon, called Type B lactic acidosis, is different from the hypoperfusion-related lactate elevation (Type A) seen in shock states. For patients on epinephrine, serial measurements are more valuable than single readings, with rapidly rising levels or those exceeding 4 mmol/L warranting closer evaluation of tissue perfusion and possible adjustment of therapy. Some key points to consider in the management of patients on epinephrine infusions include:
- Other clinical parameters like blood pressure, urine output, mental status, and peripheral perfusion should be assessed alongside lactate levels 1.
- If lactate continues rising despite adequate perfusion markers, consider reducing the epinephrine dose if hemodynamically feasible or evaluating for other causes of lactate elevation such as liver dysfunction, seizures, or other medications 1.
- The Surviving Sepsis Campaign recommends guiding resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion, although this is a weak recommendation with low quality of evidence 1.
- A recent study suggests that lactate clearance may be a useful target for resuscitation in septic patients, although the evidence is still limited 1. Overall, the management of patients on epinephrine infusions requires careful consideration of lactate levels and other clinical parameters to ensure optimal tissue perfusion and minimize the risk of adverse outcomes.
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. The degree of lactate elevation that is concerning in patients on epinephrine infusion is not explicitly stated in the drug label.
- Lactate elevation is expected as a result of epinephrine administration due to its effects on glucose metabolism.
- The FDA label does not provide a specific threshold for concerning lactate levels in this context 2.
From the Research
Lactate Elevation in Patients on Epinephrine Infusion
The degree of lactate elevation concerning in patients on epinephrine infusion can be evaluated based on several studies.
- Lactate levels are a useful marker for disease mortality and severity, but an unreliable marker of tissue hypoxia/hypoperfusion in critically ill patients 3.
- Epinephrine can induce tissue perfusion deficit and increase lactate levels, even in the absence of tissue hypoxia 4, 5.
- A lactate level greater than 4 mmol/L is associated with increased mortality in patients with sepsis-induced tissue hypoperfusion 6.
Concerning Lactate Levels
- Lactate levels greater than 4 mmol/L, in conjunction with hypotension, are significantly associated with increased mortality 6.
- Elevated lactate levels are highly associated with in-hospital mortality, but only patients with lactate values greater than 4 mmol/L are significantly associated with increased risk 6.
- The use of epinephrine may increase lactate levels due to aerobic glycolysis, rather than tissue hypoxia 5.
Clinical Implications
- Lactate measurements should be interpreted with caution in patients on epinephrine infusion, as they may not accurately reflect tissue hypoxia 3, 5.
- The Surviving Sepsis Campaign guidelines recommend obtaining a serum lactate measurement within 6 hours of presentation for all patients with suspected severe sepsis or septic shock 6.
- Bicarbonate therapy may be considered in patients with septic shock and elevated blood lactate levels, but its effectiveness is still a topic of debate 7.