Lactate Levels cannot be corrected by Giving More Oxygen

I have covered lactate quite thoroughly over the last couple weeks but I still receive comments and questions from followers talking about oxygen deficiency to the cell causing elevated lactate and lactic acidosis. They ask "why don't you just increase the O2 that you're providing to the patient to help the cells out"? This question is not out of line with traditional thinking behind lactic acidosis being the byproduct of "tissue hypoxia" which I hope at this point you understand is NOT the cause of elevated lactate levels in septic shock patients (see many other posts for further details).

This study published in JAMA in 1993. The three key findings of their work include:

1. Critical O2 delivery was identified and is considerably lower than previously estimated. Increasing O2 delivery to supra-normal levels in critically ill patients in the hope of increasing O2 consumption may be inappropriate.

2. Sepsis was not associated with an increased critical O2 delivery

3. The increased concentration of arterial lactate at baseline was not associated with global tissue hypoxia, suggesting that lactate may not be a specific marker of tissue hypoxia in critically ill patients.

Hope this helps! A hat tip to the authors!

- EJ



Link to Article

Ronco JJ, Fenwick JC, Tweeddale MG, et al. Identification of the Critical Oxygen Delivery for Anaerobic Metabolism in Critically III Septic and Nonseptic Humans. JAMA. 1993;270(14):1724–1730.

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Can We Use Something Other Than Lactate To Guide Resuscitation?

Nurses: you see those orders. q1, q2, q4h lactates to help guide resuscitation in septic shock. You have to drop what you're doing and draw labs. Hopefully, if the patient is sick enough to need the labs, they have a central line. Hold off of titrating drips, hold off on the ever important charting you are required to do, let's trend lactates which I have previously discussed the utility of (or lack of utility). Along the way we contribute to iatrogenic anemia, spend a bunch of lab money, etc.

What if there was another option? Well, the ANDROMEDA-SHOCK trial proves that you can intelligently resuscitate patients without checking lactate levels. What they did was randomize >400pts to either have their resuscitation guided by lactate or this nifty little trick called Capillary Refill Time.

One of my favorite parts of the trial wasn't even the CRT vs. lactate component but their algorithm to determine fluid responsiveness which is a major interest of mine. I am not a fan of arbitrarily giving a pt liter after liter of fluid to "clear lactate" or improve the blood pressure. That just does not work and my body of work has data to prove that. I digress. Sometimes you need to read the supplementary materials in these articles as their algorithm was hidden in there.

Standard of care by CMS (the body that pays the hospitals and therefore us in the US) has mandated checking lactates despite no good evidence that trending it does much. This study shows that checking CRT is AT LEAST as good as checking lactate levels. The mortality was not statistically significant (p=0.06) but I wonder what would've happened if they would've had an additional 200pts in the trial. The CRT group had 34.9% mortality vs 43.4% in the lactate group. The CRT group also had fewer organ failures (p=0.045). Other fun facts include the fact that the lactate group received more fluids in the first 8h (p=0.01) but not overall. I don't know what to make of this.

All in all, even with its limitations, I feel this is a solid study. I really like it. I do not use CRT in my practice but I may be asking for a microscope slide to keep in my pocket in the upcoming weeks.

A hat tip to the authors

Hernandez G, Ospina‐Tascon GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, et al. Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28‐day mortality among patients with septic shock: the ANDROMEDA‐SHOCK randomized clinical trial. JAMA. 2019;321(7):654–64.

- EJ




Link to FULL FREE ARTICLE

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

How Does Lacate Turn Into Lactic Acid?

You have NO IDEA how much I banged my head against my desk looking for the answer to the question: how does lactate turn into lactic acid? Well, after many hours of searching for an answer, and you can think I'm a dummy for not find the answer sooner or knowing it like a useless fact off of the top of my head, I FOUND IT! It's honestly some information that's not readily available. Many articles play it off and don't mention specifics assuming that "it just happens". I am by no means a biochemist. I'm simply trying to understand all this. In my explanation, I purposefully will be oversimplifying things.

Here's how it works:
In the cytosol, pyruvate turns into lactate (rather than move towards acetyl-CoA) for a number of reasons, again that I'm not going to get into, via lactate dehydrogenase. That lactate (via shuttles) gets to the cytosol of the liver and kidneys where it eventually makes its way into the Cori/Lactic Acid Cycle. The Cori cycle eventually spits out glucose. So far so good, right? Glucose via glycolysis seems to be metabolized into lactate, ATP, and water. Said ATP gets hydrolyzed into ADP and inorganic phosphate which releases that very necessary proton (H+). When conditions get revved up, i.e. septic shock, and an excess of lactate is being produced, then the cell cannot handle the metabolism of lactate and guess what's also being overproduced? Said H+ which tags onto the lactate creating lactic acid.

The articles I've read tend to say that you start running into lactic acidosis territory when you have a lactate 5 with a concurrent acidosis (pH less than 7.35). 

Mad props to Amanda, my pharmacist teammate, for listening to me and helping me work through this while not making too much fun of me. 
<7 .35="" additional="" again.="" and="" any="" are....="" be="" better.="" biochemistry="" br="" can="" definitely="" did="" diving="" going="" help="" here="" i="" into="" knowledge="" me="" nbsp="" never="" of="" or="" others="" pointers="" provide="" think="" this="" to="" understand="" was="" we="" welcome="" you="">
Link to article (NOT FREE)

Fall P, Szerlip H. Lactic acidosis: from sour milk to septic shock. J Intensive Care Med 2005; 20: 255-71.

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Lactate in IVF Leads to Lactic Acidosis?

"Lactate in fluids, such as Ringer's lactate, causes a lactic acidosis". Ugh. How I cringe every time I hear or read that. You should take into account your patients organ failures since lactate is metabolized approximately 60% in the liver, 30% in the kidneys, and 10% elsewhere (including the heart, muscles, etc depending on your source).

There's no perfect trial to go ahead and prove this concept, but I have linked this study which FREE where they provided patients with a sodium lactate solution versus Hartmann's solution, aka Ringers Lactate. To provide some context, LR provides the patient with Sodium Lactate, 28mmol/L to be exact. The half-molar Sodium Lactate solution described in this article has 504mmol/L of Sodium Lactate. I struggled quite a bit to find that concentration but thankfully I found it in a Spanish (Spain) article.

I have attached the table to illustrate several points. First, if you notice the Sodium Lactate did not create an acidosis in any of the patient groups, on the contrary, they trended more so towards an alkalosis, even a statistically significant alkalosis in the case of the "lactate" group. Overall, there was no increase in lactate whatsoever in the LR group which means that there's no "lactic acidosis" created by LR. It does not make patients acidotic. If you have a functioning liver and kidneys, that lactate is metabolized into bicarbonate. Hope that all makes sense.

A hat tip to the authors.

-EJ

Link to Article

Link to FULL FREE PDF

Nalos, M., Leverve, X.M., Huang, S.J. et al. Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial. Crit Care 18, R48 (2014)

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Elevated Lactate Does Not Equal More Fluids

There is a law of diminishing returns when resuscitating patients with bolus after bolus of IV fluids.

Yes, lactate decreased with additional boluses by 1.3% per every 7.5mg/kg increase in fluids making the numbers look pretty, but does that mean we're treating the source of the lactate or are we just diluting it? This study shows that mortality actually increases as we keep providing more fluids.

I’m not saying that patients who are in septic shock do not need fluids. On the contrary, they need judicious use of IV fluids and 30cc/kg initial resuscitation is okay with me in the vast majority of patients. I had to read many articles to finally fall in line with that. Of course there are several patient populations where I’m against it. For example, severe pulmonary hypertension patients with right hearts living on a tight rope. I digress. But tagging along with my prior post discussing giving fluid boluses reflexively, this study shows that fluids don’t really “clear” lactate in the way we all hope and want them to. The correlation of having an elevated lactate to mortality is there. The correlation with more fluids making lactate decrease isn’t. The pathophysiology behind where lactate comes from explains why not. And as we all should know, fluids are not benign. The more fluids we give patients the higher the mortality per the 9000 that were assessed in this study.
A 🎩 tip to the authors. .

Liu V, Morehouse JW, Soule J, Whippy A, Escobar GJ. Fluid volume, lactate values, and mortality in sepsis patients with intermediate lactate values. Ann Am Thorac Soc. 2013;10:466–73.

FREE FULL ARTICLE

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Bicarbonate in Lactic Acidosis?

I would like to make this perfectly clear, this article has many nuisances to it. Many limitations and different components that need to be dissected carefully. Too carefully for what I can do on IG. Please attempt to obtain it and read it for yourself as it does not provide a black and white response to the question: can we treat lactic acidosis with bicarb?
The slides presented here are preliminary slides from my lectures that I am actively working on. I plan on explaining things in far more detail to my audience than what is on the slides. Is that enough of a disclaimer? Well then let's let it rip!
There exists a pendulum in many things medicine and providing bicarb in lactic acidosis patients is one of them. There's always been the question of whether it's beneficial, ineffective or harmful. If you look at the data pre-2000, it is almost entirely supportive of not providing bicarb for these patients. The data after 2001 is more lenient to where it is discussed in one paper that "bicarbonate might prolong survival sufficiently to allow treatment of the underlying cause of lactic acidosis". This is why I use the term "bicarb band-aid" whenever I put someone on a bicarb drip to buy some time to figure things out. 
Like everything in medicine, bicarb drips have their drawbacks. I know people LOVE to give amps of bicarb during ALCS but there's no data to do so. Much more to that than what I'm going to discuss here. Very broad topic. 
Getting back to the article. They took almost 400pts in France who were very sick, with a lactic acidosis, and randomized them to get either nothing or 4.2% bicarb gtt. They had some very strange outcomes which are a conversation for another day but ultimately, patients who had acute kidney injury did better, and this is even considering that 24% of the control group got bicarb. Nonetheless, the numbers are explained in the slides. 
Again, is this black and white? Nope. But it's the first large RCT in this patient population looking at this intervention and major hat tips to the authors. 

-EJ

PS: Can I take credit for the term "bicarb band-aid"? I'd like to but I feel that I'm not original enough to have come up with it. 





Link to Article

Jaber S, Paugam C, Futier E, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet 2018; 392:31.

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Don't give fluids just because the lactate is elevated.

Lactate is elevated? (without assessing the patient) Give a fluid bolus.

Wait, WHAT?!?!? Whyyyy? 😫

This is something I routinely see today. I routinely saw it at the Ivory Tower where I trained in fellowship. I routinely did it myself when I was a young whipper snapper of a resident and didn't know any better. Now, I'm here to tell you that you can do better.

I don't blame you for doing this, though. You've seen other clinicians do it. You were likely trained this way. The nurses have been trained this way. When the lactate is elevated, page the doctor and expect an order for a fluid bolus. It makes one feel all warm and fuzzy inside like "I did something". Everyone pats themselves on the back. Well I'm here to tell you that from now on, every time you do that, you're more likely to be wrong in your management that right.

This article which describes the "lacto-bolus reflex", i.e. to give a bolus of fluid for every elevated lactate. The authors are just as fed up about it as I am. IV fluid boluses are not benign. Fortunately, this article is completely free (I like finding you all full free articles) and it describes why the whole idea of patients developing a lactic acidosis due to cells not getting oxygen hypoperfusion is silly to the point where many of us need to be re-educated. I will admit, I had to be re-educated myself. I was not born knowing this stuff. I used to do it wrong. Now I'm trying to do it right.

The article is easy to read, for those of you who choose to dive further into it. Ultimately, they conclude that, although lactate levels are helpful for prognosis (plenty of data on that), and lactate not going away is helpful to know whether you have control of your patient or not, it ultimately does not help in any way, shape, or form, to guide fluid resuscitation. A 🎩 tip to the authors.

-EJ



Link to Article

Link to FULL FREE PDF

Spiegel R, Gordon D, Marik PE. The origins of the Lacto-Bolo reflex: the mythology of lactate in sepsis. J Thorac Dis 2020;12(Suppl 1):S48-S53.

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Lactate Measurements: Venous or Arterial Samples?

This is a question I remember asking myself quite a bit during my training when I used to check/trend lactate levels more than I do today. Does it really matter whether I check it from an arterial line or from a venous stick?

This study which was a prospective study of 100 patients who had both an arterial line and a central line. The authors compared the values during resuscitation. Short answer is no, there's no statistically significant difference.

Does this reflect the real world? Not really. As much as I would like to have an arterial line in all of my septic shock patients, this does not necessarily happen right away. Arterial lines, even for me who has put in hundreds, is not the easiest of procedures. I actually failed miserably on a patient in 5 different sites several weeks ago. I have excuses but I won't share them ;). Also, it is time consuming and causes the patient discomfort. That being said, when someone is sick sick, they get an arterial line from me or my trusty badass RT's.

The other real-world concern is the central line issue. There's data out there that you don't necessarily need a central line to run vasopressors, some of that data is my own data (my ONLY data out there haha). That being said, these patients will have their venous lactate checked via a peripheral stick, in many cases using a tourniquet. Using a tourniquet has its own problems as that could make the lactate levels unreliable.

Now, let's say that you have both an arterial line and a central line, then you can use this data more appropriately. Sort of. The authors did not specify whether they used the same point-of-care device to check the lactate levels in the venous nor arterial values. You know, some shops use POC for arterial, some have the fancy machine inside the ICU. Some could run the venous blood in that fancy machine, the POC, and some shops have to send it downstairs to the lab. This was not specified. Sigh.

Either way, I need to dissect the data regarding tourniquets for you.

-EJ



Link to Abstract

A. Mahmoodpoor, K. Shadvar, S. Sanaie, et al., Arterial vs venous lactate: Correlation and predictive value of mortality of patients with sepsis du..., Journal of Critical Care, https://doi.org/10.1016/j.jcrc.2019.05.019

Lactic Acidosis has a WIDE Differential (not just Sepsis)

There's a pendulum in medicine. Some things are over recognized and aggressively treated, some things are under appreciated (like subtle decreases in serum bicarb showing that the patient is becoming more acidotic and no one notices because the patient has obesity hypoventilation syndrome and their baseline bicarb is 34 and now has a bicarb of 22 and they look like poop).

At this time, all the rage is serum lactate and lactic acidosis. Every time someone says those words, with my biochemistry knowledge lagging far behind, everyone thinks "SEPSIS!! 30cc/kg IVF STAT!!!!" If you all knew how much this upsets me whenever I see it, you'd wonder how I'm still alive because I see it all the time. I bet you see it at your shop, too. It's very common because the pendulum has swung too far.

In order to correct this, I have embarked on discussing this topic ad nauseum in one of my lectures for Hawaii/Portland in 2020. The article linked below from the New England Journal of Medicine has a table that has been reproduced in many different forms. I will not break down the pathophysiology of each one of the etiologies, but I have been called for an ICU transfer for MANY of these.

Here are some examples where I have been called over the years where patients have received 30cc/kg of saline w/stable vital signs:
1. COPD patient receiving albuterol nebs. Lactic acid elevated because they're A. huffing and puffing, and B. receiving beta-2 agonists.
2. s/p seizure patients who are post-ictal
3. hypoglycemic diabetics
4. leukemia patients just watching TV
5. cocaine/chest pain patients in the ED
6. cardiogenic shock patients on an epinephrine gtt
7. HIV pt on Stauvidine (I should have written this one up)

I'm obviously not getting into the different subgroups of lactic acidosis at this time. Let's walk together before we run. Our job is to fix the underlying cause of the lactic acidosis, not dilute the number down with fluids.

-EJ




Link to Abstract

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Impact of Phlebotomy Tourniquet Use on Blood Lactate Levels in Acutely Ill Patients

https://www.ncbi.nlm.nih.gov/pubmed/27618976
https://www.researchgate.net/publication/295102634_Impact_of_Phlebotomy_Tourniquet_Use_on_Blood_Lactate_Levels_in_Acutely_Ill_Patients/download

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Plasma lactate measurement as an example of encountered gaps between routine clinical laboratory processes and manufactures' sample-handling instructions

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223191/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223191/pdf/main.pdf

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Lactate predicts in-hospital mortality

https://www.ncbi.nlm.nih.gov/pubmed/22202128
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292838/pdf/1757-7241-19-74.pdf

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Thiamine on Lactate Clearance and Mortality

https://journals.lww.com/ccmjournal/Citation/2018/11000/Effect_of_Thiamine_Administration_on_Lactate.5.aspx

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.