Thread by @erikrtn

1/ Why is lactate elevated in sepsis or septic shock?

@dolan_russell & I explore this common #ICU pimp question via #tweetorial.

We're taught that ↓O2 revs up anaerobic metabolism causing ↑ lactate. But wait, there's more...

#medtwitter #FOAMed #meded #FOAMcc #criticalcare

2/ In homeostasis, lactate is continually produced and metabolized; serum concentration is at steady state.

Which of the following organs is responsible for the majority lactate consumption and metabolism?

3/ The liver is responsible for ~70% of lactate metabolism.

Patients with hepatic dysfunction can have ↑ lactate 2/2 ↓ clearance or ↑ production. Also, cirrhotics are more prone to hyperlactatemia in setting of sepsis.

Diving deeper, how does the liver metabolize lactate?

4/ Hepatocytes metabolize 70% of lactate via gluconeogenesis & to a lesser extent, oxidation.

Outside of the liver, mitochondria-rich skeletal & cardiac myocytes & proximal tubule cells remove the rest of the lactate by converting it to pyruvate.

Ref: sciencedirect.com/science/articl…

5/ Patients w/ hepatic dysfx have ↑ lactate 2/2 ↓ clearance or ↑ production. Why?

↑ lactate may be 2/2 accelerated glycolysis in the splanchnic region: tandfonline.com/doi/abs/10.310…

Also, cirrhotics are more prone to hyperlactatemia in setting of sepsis.

6/ Other causes of ↑ lactate in the cirrhotic patient:

+ Lactated Ringers
+ Albuterol or other β2 adrenergic stimulation (seen in asthmatics or pt on epi drip; h/t @ASundaralingam)
+ Metformin, especially in setting of renal impairment; rare

7/ Let’s return to sepsis.

We are taught that lactate rises as a result of ↓O2 delivery, hypoperfusion, tissue hypoxia, and anaerobic glycolysis: uptodate.com/contents/sepsi…

Unfortunately, this may be an oversimplification.

What are other causes of ↑ lactate in sepsis?

8/ ↑ lactate often does not correlate w/ traditional indicators of perfusion, nor does it diminish with ↑ O2 delivery: thelancet.com/journals/lance… and
ncbi.nlm.nih.gov/pmc/articles/P…

9/ In sepsis, systemic inflammation and endothelial activation causes microcirculatory and mitochondrial dysfunction: onlinelibrary.wiley.com/doi/full/10.11…

Also, despite high CO and low SVR, peripheral O2 extraction is low. These factors shunt pyruvate into lactate.

10/ β2 adrenergic stimulation → ↑ aerobic glycolysis in skeletal muscle, shunting excess pyruvate into lactate (c/w sepsis = hypermetabolic state): ccforum.biomedcentral.com/articles/10.11… and journals.lww.com/co-criticalcar…

This also explains the ↑ lactate in patients given albuterol or epi drip!

11/ Thiamine (vit B1) deficiency can shunt pyruvate to lactate, and may play a role.

B1 can be deficient in sepsis: sciencedirect.com/science/articl…

Giving B1 *may* improve lactate clearance: journals.lww.com/ccmjournal/Cit…

...but this RCT suggests it does not help: journals.lww.com/ccmjournal/Abs…

12/ To summarize, ↑ lactate in sepsis septic shock is 2/2:

+ ↓ O2 extraction 2/2 inflammation, microcirculatory & mitochondrial dysfx
+ β2 adrenergic stim. & hypermetabolic state, shunting pyruvate → lactate
+ Thiamine deficiency (maybe)

Thanks @tony_breu for inspiring!

Related: amazing BST mode (cc @gradydoc) talk by @maxhockstein at #CCS19 on five causes of lactic acidosis. Elevated lactate is not always sepsis!

Check out @SummitCritCare, hopefully talks will be uploaded to YouTube.