Does epinephrine (EPi) cause more lactic acidosis than norepinephrine (norepi)?

Epinephrine Causes More Lactic Acidosis Than Norepinephrine

Yes, epinephrine causes significantly more lactic acidosis than norepinephrine, making norepinephrine the preferred vasopressor in most critical care scenarios. 1, 2, 3

Mechanisms of Lactic Acidosis with Vasopressors

• Epinephrine increases aerobic lactate production via stimulation of skeletal muscles' β2-adrenergic receptors, which can interfere with using lactate clearance as a resuscitation guide 1
• Epinephrine causes more pronounced splanchnic vasoconstriction, leading to tissue hypoperfusion and anaerobic metabolism, further contributing to lactic acidosis 4
• Norepinephrine primarily increases mean arterial pressure through vasoconstriction with minimal changes in heart rate and stroke volume, resulting in less metabolic derangement 1
• Catecholamines are catabolic hormones that can initiate metabolic processes including increased production of lactic acid, with epinephrine having a more pronounced effect than norepinephrine 5

Clinical Evidence

• In a randomized study comparing epinephrine to norepinephrine-dobutamine in cardiogenic shock, epinephrine was associated with increased lactate levels while lactate decreased in the norepinephrine-dobutamine group 2
• A 2018 randomized trial in cardiogenic shock after myocardial infarction found epinephrine caused significant lactic acidosis from 2-24 hours after administration compared to norepinephrine 3
• The same study was terminated early due to a higher incidence of refractory shock in the epinephrine group (37% vs 7% with norepinephrine, p=0.008) 3
• Even subcutaneous epinephrine administration has been associated with lactic acidosis, suggesting this is a consistent effect of the medication regardless of route 6

Hemodynamic and Metabolic Effects

• Epinephrine increases cardiac double product (heart rate × blood pressure) more than norepinephrine, potentially increasing myocardial oxygen demand 3
• Epinephrine is associated with higher heart rates and more arrhythmias compared to norepinephrine 2
• Tonometered PCO2 gap (a marker of splanchnic perfusion) increases with epinephrine while decreasing with norepinephrine, indicating worse visceral perfusion with epinephrine 2
• In experimental models, epinephrine decreases portal blood flow despite maintained total splanchnic blood flow, suggesting regional perfusion deficits 4

Clinical Recommendations

• Norepinephrine is recommended as the first-line vasopressor for septic shock based on evidence showing fewer adverse events compared to other agents 7, 1
• For cardiogenic shock, the combination of norepinephrine-dobutamine appears to be a more reliable and safer strategy than epinephrine alone 2
• In settings where norepinephrine is unavailable, epinephrine can be used as an alternative, but with careful monitoring for lactic acidosis 1
• When using epinephrine, clinicians should be aware that rising lactate levels may not necessarily indicate worsening tissue perfusion but could represent a pharmacologic effect of the drug 1, 5

Practical Considerations

• When monitoring patients on vasopressors, lactate trends should be interpreted differently depending on whether the patient is receiving epinephrine or norepinephrine 1
• Epinephrine-induced lactic acidosis can complicate clinical decision-making by masking improvements in tissue perfusion or falsely suggesting worsening shock 5
• The combination of norepinephrine with dobutamine (when inotropic support is needed) provides similar hemodynamic support to epinephrine but with less metabolic derangement 2