In this episode, I’ll discuss how lactate clearance in sepsis isn’t as straightforward as the guidelines make it seem.
The surviving sepsis guidelines state:
We suggest guiding resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion (weak recommendation, low quality of evidence).
When sepsis leads to hypoperfusion, the resulting tissue hypoxia causes an increased serum lactate. But the reverse is not necessarily always true. An increased serum lactate is not a direct measurement of tissue hypoperfusion.
There are several aspects of lactate that confound its ability to correlate to tissue perfusion.
Clearance
A decrease in the blood level of lactate may indicate decreased production. However, it also may indicate increased lactate metabolism, conversion to glucose, or excretion.
Liver function
The liver is responsible for more than half of the systemic metabolism of lactate. As such, alterations in liver function may account for increases or decreases in serum lactate, and these alterations may or may not be due to sepsis-related effects on perfusion.
Catecholamines
The administration of catecholamine-based vasopressors is necessary for septic shock. However, a side effect of these medications is an increase in lactate production. Other causes of increased glucose metabolism, such as alkalosis, may also be responsible for changes in lactate levels.
The sepsis guidelines state:
Human and animal studies suggest that the infusion of epinephrine may have deleterious effects on the splanchnic circulation and produces hyperlactatemia. However, clinical trials do not demonstrate worsening of clinical outcomes…Epinephrine may increase aerobic lactate production via stimulation of skeletal muscle β2-adrenergic receptors and thus may preclude the use of lactate clearance to guide resuscitation.
Prediction of mortality
Regardless of the different causes of elevated lactate, it is clearly a marker of illness severity. In the ARISE trial, patients with elevated lactate had almost double the risk of 90-day mortality than patients with hypotension.
Physical examination and urine output also provide clues to tissue hypoperfusion in sepsis, but lactate has an advantage being that it is an objective laboratory test.
Despite the potential pitfalls in using lactate as a measure of tissue perfusion, an analysis of five randomized trials with over 600 patients demonstrated a significant reduction in mortality with lactate-guided resuscitation compared to resuscitation without lactate monitoring.
In summary, while lactate-guided resuscitation may be useful, there are many nuances to interpreting lactate levels in patients with sepsis. Pharmacists should be especially aware of the potential for catecholamine vasopressors to interfere with the clinical utility of trending serum lactate levels in some patients with septic shock.
Members of my Hospital Pharmacy Academy have access to over 35 in-depth audio/video trainings, including the treatment of septic shock, vasopressor use, and the interpretation of laboratory values in the ICU. To find out more, go to pharmacyjoe.com/Academy.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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