Thread by @maureviv

Basic thread about fingertip blood sampling for lactate levels 🧵#TheAcidTest

Lactic acid is a key molecule, part of our anaerobic fermentation, which is one way for cells to obtain energy (=ATP⚡).

Advantages:

1. Anaerobic metabolism means it doesn't need oxygen to work.
...

2. Lactate can go back to pyruvate->glucose (Cori cycle) to be included in the mitochondrial respiratory chain (using oxygen)

Disadvantage: anaerobic is much less efficient than the aerobic respiratory chain

➡️When we measure lactate we're usually interested in two things:

1- Lactate elevation due to tissue hypoperfusion:

It can be caused by complete occlusion of a large vessel followed by reperfusion, which releases lactate back into circulation.

Small vessel occlusions or capillary dysfunction may also lead to high lactate released in venules.

2a- Lactate as a byproduct of mitochondrial saturation: anaerobic metabolism provides increased energetic output when aerobic metabolism is *at capacity*.

2b-Lactate as compensation for impaired aerobic metabolism (anaerobic activates to compensate mitochondrial disease).

➡️After a brief overview of the lactate's role & meaning, a few bits about measurement

First, we're measuring "lactate" rather than "lactic acid"

Hence, the lactate we measure has been already compensated for in terms of pH (acids lower blood's pH, lactate itself does not).
...

To actually assess acid-base equilibrium we must study other parameters such as blood pH or base excess. 🧪🧫

(Although an elevated lactate will give a clue that something isn't right)

There are two main measurement sites for capillary blood: fingertips and earlobes.

We'll focus on fingertip lactate ☝️

➡️ Here are a few tips to optimise blood samples:

✅1. Get a pulse oximeter. Check with it that your finger has a pulse before obtaining the sample.
(...)

This is necessary because hands 🖐️(& feet) have special arteriovenous shortcuts that might exclude blood from fingers in situations like:

- Cold weather,
- Dysautonomia,
- Raynaud's flares,
Etc.

You would be measuring blood very high in lactate that wouldn't be representative.

✅2. Follow all device specifications (strip storage, calibration...)

✅3. Store the lactate value in a table (can be handwritten) where you write at least the date and time of your measurement (or any other parameter given by a study protocol)📋

➡️About portable lactate devices: 🧪

They use reactive strips, very much like glucose meters do.
They differ greatly in their specifications:

Here's a brief comparison of 3 different models (link translated into English by Google):

…ellelectromedicina-com.translate.goog/en/comparativa…

E.g. the Lactate-Pro-2 or the Accutrend don't need calibration and the reactive strips can be preserved at ambient temperature (0-30ºC)
(The link below contains also a -too brief- PDF leaflet)

arkray.eu/english/produc…

These portable devices use enzyme-based detection (lactate dehydrogenase) over an oxygen electrode (amperometric)

They usually obtain better results than plasma-based lactate assay.

Hemolysis can interfere the results (prick-obtained blood should have less risk of hemolysis)

With these biosensors, adequate handling of the reactive strip is the most important modifiable factor for measure accuracy.

Avoiding bumps and drops of the device will also lengthen its life.

Two common issues for many (if not most) measurements of physiological variables (which cannot be observed directly) is both the accuracy at extreme values* and inter-device agreement.

*approx. 0.5-20 mmol/L
⬇️

The same lactate level may not be comparable between individuals or devices:

Here, we can see that agreement between synchronic measurements becomes weaker at higher lactate levels
(Bland-Altman plot of Accutrend and Lactate Pro)

researchgate.net/figure/Bland-A…

https://twitter.com/maureviv/status/1652362512405340161?t=RlB_Ta637XU-Sn3KwppTKA&s=19

So, in a pooled data analysis, comparing "directly" a high level between 2 individuals isn't possible.

But of course, this and other challenges that may appear in further data processing can be dealt with by any data analyst with experience in physiological signals.

That brings us to the last (and actually most important) piece to interpret changes in a physiological variable that has to be measured (i.e. their "true value" is by definition unknown):

➡️ Control Subjects

Ensuring the highest possible number of controls will not only increase statistical power to detect changes. It is also a key part for external validity and reproducibility of the results.