Lactate: STAY ****ING CALM!

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Scenario: I'm on service and I get the dreaded page from the ED about an admit. I call them up and get sign out about a patient with possible "X" (pneumonia, cellulitis, the plague, etc) that looks clinically well but has a lactate of 3.2 that they want to admit because... well, the patient has a lactate of 3.2. I go down to the ED to check out the patient who's surrounded by loving co-workers.

The Office staff goes to visit Meredith in the hospital after being hit by a Michael in his car. Creed asks about the painkillers that Meredith might be taking. Watch full episodes at NBC.com, or on Thursdays 9/8c.

Good news, I have a ton of Palladone for you sir. Bad news ma'am, why are you here again? Oh right, you have a lactate of 3.2. In this case, I know I'm between a rock and a hard place. The Rock - they look clinically stable and could probably follow up the next day as an outpatient (if they're reliable). Probably. The Hard Place - the lactate is 3.2. For all of you familiar with the situation: you no argue the lactate. The lactate is scary and bad things can happen with an elevated lactate. You accept that fact and admit the patient for observation.  

Scenario 2: I get the same dreaded page but this time the patient looks pretty sick from the possible "X". Lactate is again 3.2. Then the scenario typically unfolds like the below video except substitute lactate for the fire and everyone in the hospital for the cast of The Office (maybe the ED doc can be Michael).

I get it. Lactate is important. But do we really need to freak out every time it's elevated? There are plenty of vending snacks for everyone. If you were one of the handful of people/bots that read my previous blog. You'd know that I'm more of a fan of clinical acumen than trending labs. I also have a pretty strong well bias I'm aware of. But in all seriousness, that was my question... 

How worried do I have to be about an elevated lactate when A) Someone appears to be clinically deteriorating and B) Someone appears to be clinically stable?

Looking back in the literature, lactate and sepsis have been tied together for ages. It's not a novel concept. A quick PubMed search for "lactate AND sepsis" shows the first papers being published in the mid-1960s. In medical years, that's pretty much the time right after these guys existed. This means two things: 1) I'm too lazy to actually get the physical copy from the Health Sciences building and 2) We have a ton of data. Physiologically, most of us have a good handle on lactate. It's the byproduct of anaerobic metabolism which starts to play a more prominent role during hypoxia. Which means the less oxygen your tissues get (whether it's exercise or sepsis) the more elevated your lactate levels get. There are also some more novel ideas surrounding lactate production which I'll touch on in a bit. I can't argue with the physiology but let's see what the data says.

Let's look at our sicker patient first. The answer to this one is fairly simple in the context of a greatly elevated lactate - be worried if it's high, especially > 4 mmol/L (aka severe sepsis land). There is no shortage of studies finding a linear relationship between lactate levels and mortality/complications in various settings from abdominal surgery to good ol' sepsis. Go ahead, take a look at here , hereor here. There’s a lot more where that came from. But I assume you already knew all that. 

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With sicker patients, the debate isn’t getting the initial lactate but whether it should be used as a surrogate for other markers of tissue hypoxia in sepsis, namely ScvO2. There was a point-counterpoint article in Chest a few years back that debated this exact topic and both sides made compelling arguments [Point, Counterpoint). They essentially debated the LACTATES trial which found using lactate clearance ( >10%) to be non-inferior to traditional ScvO2 goals ( >70%) in terms of mortality. Specifically, the lactate cohort drew an initial lactate then another at a minimum of 2 hours later. They then followed it hourly until the 6 hour mark to help guide resuscitation goals. 

The two authors then proceeded to go all hypothetical by discussing the kinetics of lactate and ScvO2. One side argued that lactate is a more robust marker of total body metabolism as it doesn't just reflect tissue hypoperfusion but may also reflect inflammatory stress. He cited the production of lactate in the lungs and WBCs as possibly playing this role. He also noted the fact that only lactate clearance has been shown to independently improve mortality rates while ScvO2 has not. [1] The counterpoint argued that ScvO2 is a more sensitive marker of early tissue hypoperfusion and that the kinetics of lactate are indeed too robust and complex to be used as a standardized marker. 

In the end, what I take from the debate is that I will still use ScvO2 to guide treatment until something comes along to either completely debunk or improve upon the landmark Rivers study in 2001 [2]. Twenty percent improvement in mortality is no joke. Also, what do most if not all of our ICU patients have? Central venous catheters. So if you have one in for fluids/pressors, why not use it to look at a variable? However, if I were in a situation where I didn't have a central line available, I would most assuredly use the lactate clearance goal of at least 10% after 6 hours (with an attempt to normalize after 24 hours) to help guide therapy. I'm also going to keep an eye out for this    bad boy to see if it shakes anything up.

One interesting wrench in the lactate arguments comes from Lee SW et al. (2008). In this particular prospective study (n=126) of either severe sepsis or septic shock patients, they found that there was no difference in mortality between patients with hyperlactemia and those with normal PH’s or normal lactates. There was however significant inpatient mortality found in patient’s who had lactic acidosis. One caveat would be that they only took samples at 0 and 4 hours of presentation. However, isn’t that the whole debate about lactate? It’s those initial lactates that should be elevated as an early marker of tissue hypo-perfusion that sets off the alarms. Not the one taken on day 3 when they are already sick in the ICU. [3]

Well what about the grey area? What I was looking for here is not the person who comes in with a lactate > 4 mmol/L and is rapidly deteriorating but the one who has either some indications of either sepsis, possibly severe sepsis or is clinically well appearing but has the lactate in the ballpark of 2-4 mmol/L. After a couple hours of digging I found the answer to that and it's not very robust.

Why? Because I can't find any studies on it.

Why? Because people probably don't care about it as much - like Stanley.

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I take that back, I found one.  Shapiro et al. (2005) [4] did a prospective cohort study that was kind of what I was looking for. They took roughly 1200 patients from the ED who had "infection related diagnoses" and looked at 3 and 28 day mortality while stratifying them by lactate level at time of admission. The "infection related diagnoses" portion was a bit messy as they had a single investigator (with another one checking 20% of the sample) choose which cases were "infection related". But I kind of like that for this study. It's messy and that's what we deal with in real life when trying to parcel out if someone is sick or not. They found the low (0-2.5 mmol/L), medium (2.5-4 mmol/L) and high (> 4mmol/L) groups to have 3 and 28 day mortality rates of 1.5%/4.9%, 4.5%/9%, and 22.4%/28.4%. Looking at it from sensitivity/specificity standpoint they found a serum lactate greater than or equal to 2.5 mmol/L 59% sensitive and 71% specific for death while lactate > 4 mmol/L was 36% sensitive and 92% specific for death. Now if this was a lab test like let's say.... BNP. Would 59%/71% sensitivity and specificity cut it for you? I'm guessing no. But 92% specificity? Yeah, I'll take that.

 

Overall the topic isn't as "sexy" as lactate in severe sepsis/septic shock patients because that's probably not where the most bang for your buck is in terms of preventing mortality. And that's really that's what everyone wants to think about. So when the data isn't robust, I tend to go to the old stand by, physiology. I came across a very nice interview with one Dr. Matthew Strehlow (Associate Professor of Surgery/Emergency Medicine, Stanford) on the ACEP website when looking for an answer and it really changed how I think about lactate. 

Whenever I see a clinically well patient with an odd lab, my first thought for better or worse is always false positive. Lactate can be falsely elevated in a number of scenarios including:

  • the tourniquet being on too long (> 2min)
  • diabetes
  • exercise
  • beta-agonists
  • dehydration
  • hyperthermia
  • NRTI meds such as AZT and 3TC causing mitochondrial toxicity in HIV patients
  • the lovable unicorn Metformin induced lactic acidosis.

So what's the best way to rule out a false elevated lactate per Dr. Strehlow?

Get another one in 30 minutes. 

What I failed to realize is that lactate has an incredibly short half life. Twenty minutes to be exact. By getting another one 30 minutes later, you'd be eliminating some of the potential causes of false positives. That is assuming that you corrected those things in the 30 minutes you waited (IVF, correcting hyperthermia, double checking the med list, not botching your blood draw again). Now it wouldn't eliminate all the possibilities but if it came down in that 30 minutes, that would be enough for me to send them home with close follow up. 

Wrapping up, here's what I learned. Lactate > 4 mmol/L = badness, no surprise. With lactates between 2.5-4 mmol/L I will continue to not freak out about them but may consider getting another soon after if I'm ruling out a false positive (30min) or don't have a central line in and want to monitor the initial progression (2h after initial, then hourly until the 6h mark). I can continue to use my clinical acumen though to guide me through this grey area and that's all I wanted to hear in the end.

And remember, stay ****ing calm. 

TL;DR: Lactates < 4 mmol/L don't merit a panic attack, lactates > 4 mmol/L do.