Lactate (since I’m currently in LA)

Big topic: Lactate or lactic acid (LA). Lactate is just lactic acid that is dissociated from a hydrogen ion. That being said I’m going to use these two terms interchangeably.

We measure lactate on our blood gases in order to check if our patients’ BPs are adequate enough for tissue perfusion. When I have an elevated level, I’m usually concerned that their hemodynamics are not sufficient enough to perfuse their tissues, whether it be from cardiogenic, septic, vasodilatory, or obstructive shock. When there is an issue with oxygen delivery (or utilization), tissues and cellular metabolism starts undergoing anaerobic respiration. Here is some quick biochemistry for all you nerds out there:

Glucose breaks down (through glycolysis) into pyruvate and NADH. When pyruvate meets oxygen, it enters aerobic metabolism via Kreb’s cycle and makes acetyl-CoA then you get your 34 ATP molecules inside the cell. When there is no oxygen, pyruvate enters anaerobic metabolism using LDH and becomes lactate (and NADH becomes NAD+H).

Frank Lodeserto, a pediatric critical care physician proposes differently. If I’m interpreting him right, he proposes that lactate production is not solely from anaerobic metabolism but from beta-2-adrenergic stimulation in the setting of shock. When someone is in shock, adrenaline is released causing beta-2 stimulation, which creates c-AMP (cyclic adenosine monophosphate). c-AMP activates PKA and up-regulates the break down of glucagon into glucose in the liver and then the pyruvate metabolism occurs. He states that the mitochondria cannot keep up with the production of pyruvate, even in the setting of adequate oxygen and some of it will still enter the anaerobic cycle and thus create lactate. So lactate is not synonymous with only inadequate oxygen perfusion but maybe increased endogenous or exogenous adrenaline. Important to note that a few articles I read that measured muscle lactate levels vs arterial lactate levels in setting of hypotension and shock had persistently higher levels of muscle lactate (which has a a lot of beta-2 receptors). *Remember beta-2 receptors are located on airway smooth muscle (don’t forget your albuterol!), cardiac muscle, parts of your liver and GI tract.

Oh, LA is metabolized mostly in the liver (70–80%) and some in the kidneys. LA is transported to the liver and metabolized back into the glucose (called gluconeogenesis). This is called the Cori cycle. Second to the liver, about 20% of total body lactate metabolism/uptake occurs in the kidney cortex (more from metabolism rather than physical excretion). Urinary excretion I think was only responsible for 10% of total. So if you have a problem with hepatocellular metabolism, it sounds like you’ll have issues with lactate clearance. The metabolism of LA in the kidney was researched in animal studies (including nephrectomies, sorry). I don’t want to get into iHD and CRRT and lactate clearance but using RRT does not clear lactate and if any, very minute amounts. It’s the bicarbonate buffer in HD that mitigates the metabolic acidosis. Lactic acidosis is NOT an indication for RRT. I got you, Dr. Yuriditsky :)

Type A and Type B LA

Type A LA is formed from inadequate oxygen and hypoperfusion and now I guess +/- beta-2 stimulation. These are your shock, mesenteric ischemia, and hypoxemic patients.

Type B LA is considered anything other than the above:

• epi IV/gtt
• high dose beta-agonist inhalers (for your severe bronchospasm patients)
• meformin use
• rare in leukemia, lymphoma and solid tumor
• propofol (need to look this up more since there are a lot of case reports — high propofol infusions can lead to impair mitochondrial metabolism and metabolic acidosis; sounds like early PRIS with rhabdo, acidosis, and cardiac failure)
• alcoholism (not necessarily from alcoholic fermentation but from decreased hepatic metabolism of the lactate)
• a lot of APAP (hepatocellular metabolism issue)
• drug-induced mitochondrial dysfunction (ie. HAART drugs)
• Linezolid??

I wonder if saying type 1 and 2 is interchangeable with type A and B…

Does this change how I interpret LA results?

More yes than no. I have tons of patients who make LA and fit in the clinical contexts of shock or are on an epi gtt. But for those patients who have good BPs and indices on or off inotropes/pressors and have a LA of 3–4 mmol/L it’ll make me think…did they just get albuterol (probably related if it’s upwards to 15mg)? Are they intubated and dysychronous with the vent? Maybe they have diaphragmatic fatigue and the muscle is creating more lactate? I think Dr. Lodeserto brings up a valid point but I wouldn’t be so quick to say that it’s a myth that lactate is created from anaerobic metabolism. In those patients who have good indices (say, CI>2) with a mild hyperlacticemia on dobutamine, do I need to go up on the dobutamine? No, maybe not just because they have a lactate. I’m going to use my physical exam (assess for warm extremities, CRT, mentation, etc). Maybe now I should over-interpret my liver function tests too. Maybe the liver is having trouble metabolizing the lactate. Time to break my thinking up into “is the elevated lactate still up due to a clearance issue rather than persistent tissue hypoxemia?” Up next, ANDROMEDA SHOCK trial? Maybe PE stuff.

Hope this post helps.

Dk