What are the expected lactate levels in patients on vasopressors, such as norepinephrine (Levophed) or epinephrine (Adrenalin)?

Expected Lactate Levels in Patients on Vasopressors

In patients requiring vasopressors for septic shock, lactate levels are typically elevated (≥2 mmol/L), but nearly half of patients on vasopressors may present with normal lactate levels (<2 mmol/L), and this does not exclude severe illness or predict lower mortality.

Defining Septic Shock and Expected Lactate

• Septic shock is clinically defined by the requirement for vasopressors to maintain MAP ≥65 mmHg AND serum lactate >2 mmol/L in the absence of hypovolemia 1
• Outside of labor or immediate postpartum, expected normal lactate values are below 2 mmol/L 1
• The threshold of 2 mmol/L represents the cutoff where tissue hypoperfusion becomes clinically significant and warrants investigation 2

The Reality: Wide Variability in Lactate Levels on Vasopressors

Lactate Distribution in Vasopressor-Dependent Patients

• Approximately 45% of patients with vasopressor-dependent septic shock present with normal lactate levels (≤2.4 mmol/L), despite requiring vasopressors 3
• Among vasopressor-dependent patients, lactate levels distribute across a wide spectrum: some with lactate <2 mmol/L, others 2-4 mmol/L, and many >4 mmol/L 4, 3
• Higher lactate levels (≥4 mmol/L) are associated with more aggressive vasopressor requirements, including combination therapy with norepinephrine plus vasopressin (55% vs 26%) and triple-agent regimens (17% vs 0%) 4

Prognostic Significance Across the Lactate Spectrum

• Even lactate levels within the "normal" range (1.4-2.3 mmol/L) are prognostic in septic shock, with mortality increasing significantly above 1.4 mmol/L 5
• Patients with lactate 1.4-2.3 mmol/L have mortality and organ dysfunction rates as severe as those with lactate 2.3-4.4 mmol/L 5
• Mortality increases in stepwise fashion: 39% with lactate <5 mmol/L, 67% with lactate 5-10 mmol/L, and 92% with lactate ≥10 mmol/L in cardiac arrest survivors requiring vasopressors 6
• Patients on vasopressors with elevated lactate have significantly higher mortality (80%) compared to those without vasopressors (52%) 6

Mechanisms of Lactate Elevation on Vasopressors

Tissue Hypoperfusion vs. Medication Effects

• Tissue hypoperfusion and hypoxia from inadequate oxygen delivery is the most common cause of elevated lactate in shock states 2
• Epinephrine specifically causes elevated lactate through beta-2-adrenergic receptor stimulation in skeletal muscle, activating glycogenolysis and glycolysis independent of tissue perfusion 2
• Norepinephrine can cause severe peripheral and visceral vasoconstriction, decreased renal perfusion, poor systemic blood flow despite "normal" blood pressure, tissue hypoxia, and lactate acidosis when administered continuously without adequate volume replacement 7

Factors Associated with Lactate Expression

• Acute liver injury, history of liver disease, and bacteremia are associated with elevated lactate levels in vasopressor-dependent septic shock 3
• Almost half of patients with vasopressor-dependent septic shock do not express elevated lactate on presentation, despite high mortality rates 3

Clinical Application and Monitoring

Initial Assessment

• Measure serum lactate immediately in all patients with suspected sepsis requiring vasopressors 1
• Do not rely on lactate as the sole indicator of illness severity—normal lactate does not exclude severe septic shock requiring vasopressors 3
• Target MAP ≥65 mmHg as the initial hemodynamic goal during vasopressor therapy 1

Serial Monitoring Strategy

• Repeat lactate every 2-6 hours during acute resuscitation to assess treatment response 2
• Target lactate clearance of at least 10% every 2 hours during the first 8 hours 2
• Normalization of lactate within 24 hours is associated with 100% survival in trauma patients, dropping to 77.8% if normalization occurs within 48 hours, and to 13.6% if levels remain elevated beyond 48 hours 2
• If lactate is elevated, repeat within 6 hours as part of the septic shock bundle 1

Treatment Implications

• Guide resuscitation to normalize lactate in patients with elevated levels as a marker of tissue hypoperfusion 1
• Patients with lactate ≤1.4 mmol/L may benefit more from vasopressin compared to norepinephrine 5
• Consider medication effects when interpreting elevated lactate, particularly with epinephrine use 2

Critical Pitfalls to Avoid

• Never dismiss a patient as "stable" based solely on normal lactate when vasopressors are required—mortality remains high regardless of lactate level 3
• Do not use lactate as the sole end point of resuscitation; incorporate clinical examination, hemodynamic variables, and other markers of perfusion 1
• Recognize that failure to normalize lactate within 24-48 hours dramatically worsens prognosis and should prompt escalation of care 2