ANDROMEDA-SHOCK

[lymphocyte]

This was an interesting trial that borders on "too good to be true." Using peripheral capillary refill time instead of lactate clearance to guide resuscitation, it very nearly established a 8.5% absolute 28-day mortality reduction (P=.06, HR 0.75, 95% CI 0.55-1.02) and showed a significant reduction in SOFA at 72 hours (P=.045, mean difference -1.0).

After randomisation, patients either had their peripheral cap refill checked q30 minutes in a standardised way or lactate q2 hours for an 8 hour period. The goal was to get cap refill < 3 seconds or achieve lactate clearance of 30%. The sequence of intervention was fluids (20mLs/kg q 1hour loading than 500mLs every 30 minutes if deemed a fluid responder until a CVP safety limit), then NE (with a MAP target intially at 65 and then trialed at 80 in non-responders with chronic hypertension), then an inodilator challenge with either dobutamine or milrinone.

It's not really clear what drove the difference in mortality, but certainly more fluids and more vasoactive agents were given in the lactate group.

My take is that lactate clearance continues to be an inadequate resuscitation target with now a signal of harm. I have also started paying much closer attention to the peripheral cap refill time.

How do you structure your sepsis resuscitations? What targets do you use? Do you prefer NE + dobutamine or epinephrine? Routinely use vasopressin? If so, when do you start it? How do you determine fluid responsiveness?

Hernandez G 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. Effect on Septic Shock Mortality of Resuscitation Targeting Peripheral Perfusion vs Serum Lactate Levels

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[SurfingDoctor]

This was an interesting trial that borders on "too good to be true." Using peripheral capillary refill time instead of lactate clearance to guide resuscitation, it very nearly established a 8.5% absolute 28-day mortality reduction (P=.06, HR 0.75, 95% CI 0.55-1.02) and showed a significant reduction in SOFA at 72 hours (P=.045, mean difference -1.0).

After randomisation, patients either had their peripheral cap refill checked q30 minutes in a standardised way or lactate q2 hours for an 8 hour period. The goal was to get cap refill < 3 seconds or achieve lactate clearance of 30%. The sequence of intervention was fluids (20mLs/kg q 1hour loading than 500mLs every 30 minutes if deemed a fluid responder until a CVP safety limit), then NE (with a MAP target intially at 65 and then trialed at 80 in non-responders with chronic hypertension), then an inodilator challenge with either dobutamine or milrinone.

It's not really clear what drove the difference in mortality, but certainly more fluids and more vasoactive agents were given in the lactate group.

My take is that lactate clearance continues to be an inadequate resuscitation target with now a signal of harm. I have also started paying much closer attention to the peripheral cap refill time.

How do you structure your sepsis resuscitations? What targets do you use? Do you prefer NE + dobutamine or epinephrine? Routinely use vasopressin? If so, when do you start it? How do you determine fluid responsiveness?

Hernandez G 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. Effect on Septic Shock Mortality of Resuscitation Targeting Peripheral Perfusion vs Serum Lactate Levels

Good lord, these studies. I’m not sure where you got the impression that measuring lactate showed harm. You can’t be harmed by getting a blood test. This study doesn’t really make sense though. In the supplement there’s essentially no hemodynamic, treatment or lab measurements that differ between the groups. They had the same CVP, same Norepinephrine dose (though the lactate group got more Epinephrine and steroids), same MAP, heck they even had the same lactate for most of the study time points, and the lactate group had a cap refill of 3 seconds for most of the study. So what was actually different?! The lactate got more fluids, but why considering every other hemodynamic variable was essentially the same? I can’t find it, other than the cap refill group got physically reassessed every 30 minutes while the lactate group got assessed... once, never, who knows? I don’t think lactate is the end all be all of labs tests, but it is helpful to trend. But if the point of this study was that reassessing the patient more often is better than not reassessing them... well, I would hope so. Does keeping a closer eye on a patient lead to a 8% mortality reduction? Yeah, maybe, seem generous though and it wasn’t statically significant. In South America it apparently does. Though for whatever reason, the lactate group has a shorter hospital length of stay because whatever.

Also, what about warm shock with flash cap refill? They seem to ignore that population entirely.

Anyway, all I got from this was that lactate doesn’t tell you everything and that reassessing a sick patient is good... which is not a surprising outcome in the least.

Did love the trial name though...

 

[lymphocyte]

Good lord, these studies. I’m not sure where you got the impression that measuring lactate showed harm. You can’t be harmed by getting a blood test.

Yes, in fact, you can. Especially if that blood test guides therapy, as it does in this case.

It's like indiscriminately checking PSA -- there's demonstrable harm from just doing blood test, because of all the follow-on effects.

The point here is targeting lactate clearance is statistically associated with worse SOFA at 72 hours and a trend toward mortality harm at 28 days. You ask, why? And I think that's a fantastic question raised by this paper. More tailored and more frequent assessment might be a reason.

 

[SurfingDoctor]

Yes, in fact, you can. Especially if that blood test guides therapy, as it does in this case.

It's like indiscriminately checking PSA -- there's demonstrable harm from just doing blood test, because of all the follow-on effects.

The point here is targeting lactate clearance is statistically associated with worse SOFA at 72 hours and a trend toward mortality harm at 28 days. You ask, why? And I think that's a fantastic question raised by this paper. More tailored and more frequent assessment might be a reason.

Sorry, I’m not seeing harm. And the editorial by Derek Angus also states no harm. There is no cause and effect in any of the results or outcomes obtained and even the association is weak at best. All this data shows is that assessing the patient is no worse than measuring a blood test serially. That’s not really a shocking outcome.

And the SOFA scores went down faster at 72 hours in the CPT group, but that group of patients stayed in the hospital longer. That really doesn’t add up.

 

[jdh71]

I use NICOM. When the SVV < 12% I consider it a resuscitation end point from the perspective of initial IV fluids. Lactate clearance is a reassuring adjunct. I base ionotropes on my NICOM as well especially if I still notice smoldering residual lactic acidosis. I probably use dobuamine first as NE is my first choice pressor. I usually start vasopressin when the NE drip goes north of 0.2-0.25mcg/kg/min.

 

[lymphocyte]

Sorry, I’m not seeing harm. And the editorial by Derek Angus also states no harm. There is no cause and effect in any of the results or outcomes obtained and even the association is weak at best. All this data shows is that assessing the patient is no worse than measuring a blood test serially. That’s not really a shocking outcome.

And the SOFA scores went down faster at 72 hours in the CPT group, but that group of patients stayed in the hospital longer. That really doesn’t add up.

It's not about just doing blood tests, it's about what you do with the results, i.e. stop, relax, or augment your resuscitation.

You've misrepresented what the editorial was saying, which had do with adverse effects, not the trend toward mortality harm. If 8.5% more people die with a lactate-guided strategy, then there's a pretty fair signal of harm that needs further study, even with a p-value of 0.06. Ditto with worse SOFA scores.

The lactate-guided guided group may have had a shorter hospital LOS simply because the sick ones were more likely to die -- those data weren't censored, so it gets tricky to interpret.

Also, your point about vasodilatory shock -- all these patients still got vasoactive medications aiming for a MAP > 65 after judicious volume loading. The question was, then what? If the lactate were stagnant or the PCRT > 3 seconds, then they would either trial a MAP of 80 for hypertensive patients or commence an inodilator challenge.

 

[SurfingDoctor]

It's not about just doing blood tests, it's about what you do with the results, i.e. stop, relax, or augment your resuscitation.

You've misrepresented what the editorial was saying, which had do with adverse effects, not the trend toward mortality harm. If 8.5% more people die with a lactate-guided strategy, then there's a pretty fair signal of harm that needs further study, even with a p-value of 0.06. Ditto with worse SOFA scores.

The lactate-guided guided group may have had a shorter hospital LOS simply because the sick ones were more likely to die -- those data weren't censored, so it gets tricky to interpret.

Also, your point about vasodilatory shock -- all these patients still got vasoactive medications aiming for a MAP > 65 after judicious volume loading. The question was, then what? If the lactate were stagnant or the PCRT > 3 seconds, then they would either trial a MAP of 80 for hypertensive patients or commence an inodilator challenge.

Sorry, again, how specifically did measuring a blood level of lactate cause a 8% mortality? Because they got more fluid in the first 8 hours? Maybe. Again, I’m not suggesting a lactate is the panacea and no one parameter should ever drive clinical decisions, and this data just confirms that. And I still interpret these results that the real randomization was just the frequency of physical assessment, not a lab test. But I’m not going to go as far as to accept measuring or following lactates leads to a higher rate of death.

 

[deleted547339]

I use NICOM. When the SVV < 12% I consider it a resuscitation end point from the perspective of initial IV fluids. Lactate clearance is a reassuring adjunct. I base ionotropes on my NICOM as well especially if I still notice smoldering residual lactic acidosis. I probably use dobuamine first as NE is my first choice pressor. I usually start vasopressin when the NE drip goes north of 0.2-0.25mcg/kg/min.

I practice fairly similarly, but substitute a-lines and pvv. I’ll usually check an scvo2 if I’m thinking about ionotropes, although sometimes a smoldering lactic is enough (or enough for me to just stop checking it).

 

[jdh71]

Using peripheral capillary refill time

I mean, I work in the US, so I take care of a lot of vasculopaths. I think I'm worried I'd flood some of these poor circulation types if I went off of cap refill. Reading is hard and I've not looked at the paper itself yet, do they or an editorial talk about it?

 

[lymphocyte]

I mean, I work in the US, so I take care of a lot of vasculopaths. I think I'm worried I'd flood some of these poor circulation types if I went off of cap refill. Reading is hard and I've not looked at the paper itself yet, do they or an editorial talk about it?

Not addressed in the editorial or paper.

They took people across 25 ICUs in 5 countries, who, in aggregate, had a median Charleston Comorbidity Index of 3, so presumably including vasculopathic patients.

 

[jdh71]

Not addressed in the editorial or paper.

They took people across 25 ICUs in 5 countries, who, in aggregate, had a median Charleston Comorbidity Index of 3, so presumably including vasculopathic patients.

Which five countries? The vasculopathy we see in the US is pretty much a lifestyle phenomenon smoking and/or diabetes (insulin resistance from carbohydrate indulgence) which seems to be somewhat unique to the US as in even other western countries you don’t seem to see the same rates and the kind of thing you don’t see as much of in second and third world countries. I’m not trying to make any special pleading but I do wonder about the extrapolation to my patient population.

 

[deleted547339]

Which five countries? The vasculopathy we see in the US is pretty much a lifestyle phenomenon smoking and/or diabetes (insulin resistance from carbohydrate indulgence) which seems to be somewhat unique to the US as in even other western countries you don’t seem to see the same rates and the kind of thing you don’t see as much of in second and third world countries. I’m not trying to make any special pleading but I do wonder about the extrapolation to my patient population.

#peopleofwalmart

 

[jdh71]

#peopleofwalmart

most days these literally seem like 90% of my patient population

I'm not even trying to be a condescending elitist prick about it either - that's THE cohort in the US that regularly winds up in my ICU - socioeconomically below the national average with below average intelligence and all of the bad habits that go along with being poor and not very smart.

 

[vector2]

Say it with me (and Farkas): Lactate is not a marker of anaerobic metabolism or adequacy of oxygen delivery in septic shock. It is simply a marker of profoundly increased glycolysis and Cori cycle activity due to a shocky pt having significantly increased endogenous catecholamine circulation. It requires near-terminal status (some combo of Hgb 4-5 + cardiac index <=1 + hypoxemia + olympic athlete VO2) before the body goes globally anaerobic.

I'm skeptical of how profound the mortality difference was in the study, but there's no doubt in my mind that dumping in more crystalloid or jacking up the MAP with more levo just to treat a lactate number is detrimental (esp if the pt already has other signs of adequate perfusion)

 

[jdh71]

Say it with me (and Farkas): Lactate is not a marker of anaerobic metabolism or adequacy of oxygen delivery in septic shock. It is simply a marker of profoundly increased glycolysis and Cori cycle activity due to a shocky pt having significantly increased endogenous catecholamine circulation. It requires near-terminal status (some combo of Hgb 4-5 + cardiac index <=1 + hypoxemia + olympic athlete VO2) before the body goes globally anaerobic.

I'm skeptical of how profound the mortality difference was in the study, but there's no doubt in my mind that dumping in more crystalloid or jacking up the MAP with more levo just to treat a lactate number is detrimental (esp if the pt already has other signs of adequate perfusion)

So low(er) oxygen delivery during septic shock does not contribute to lactic acidosis? It’s all glycolysis and cori cycle?

I really hate these all or nothing proclamations because there are sure as **** plenty of patients in septic shock with relative low oxygen delivery to the tissues contributing to lactic acidosis.

 

[vector2]

So low(er) oxygen delivery during septic shock does not contribute to lactic acidosis? It’s all glycolysis and cori cycle?

I really hate these all or nothing proclamations because there are sure as **** plenty of patients in septic shock with relative low oxygen delivery to the tissues contributing to lactic acidosis.

Late, cold septic shock is a different story, but in regard to early, warm septic shock, oxygen delivery is not a problem in the vast, vast, vast majority of cases. When you first admit a patient in septic shock off the street, if you were to hypothetically throw in a PAC/a-line, shoot the numbers, and run an ABG you'd likely see a SvO2 > 65, cardiac output of 10L/min, Hgb > 10, SpO2 of 100%, a profoundly low SVR, and an elevated lactate. Ask yourself how on earth one can attribute the elevated lactate to "anaerobic metabolism" or "inadequate oxygen delivery" when we're looking at numbers like that.

Rather than oxygen delivery, it's usually a problem of oxygen utilization, as mitochondria are essentially poisoned in the septic milieu and cannot effectively continue oxidative phosphorylation. Glycolysis still continues when this happens, and a ton of pyruvate (which would've entered the Krebs cycle in a non-septic state) is converted to lactate, and thus when you measure it, it's elevated. Additionally, you may have some hepatic dysfunction while septic which prevents the liver from clearing the lactate as quickly.

"Hormonal activation is an early component of the inflammatory response to sepsis.36 Acute phase hormones such as adrenaline and cortisol prepare the body for stress, e.g., increasing cardiac output, diverting blood flow to appropriate organs involved in flight and fight (e.g., brain, heart, and muscle), modifying hepatic protein production toward acute phase proteins involved with defense and transport, and modulating metabolic activity. For example, they are counter-regulatory against insulin to increase glucose availability while, at the same time, altering cellular substrate utilization. Lactate release from muscle is enhanced by catecholamines to provide a ready fuel substrate for other organs such as brain, liver, and heart.37 At the same time, non-essential activities, i.e., those not immediately involved in dealing with the stressor such as general anabolic activities and DNA repair, are downscaled."

We also know that oxygen delivery is not the problem in sepsis because critical, rigorous evaluation of Rivers and other EGDT protocols showed that all the nonsense with dobutamine and CVP > 10-12 and tranfusing to a hct of 30 in an attempt to increase DO2 was totally futile.

 

[Beeftenderloin]

So low(er) oxygen delivery during septic shock does not contribute to lactic acidosis? It’s all glycolysis and cori cycle?

I really hate these all or nothing proclamations because there are sure as **** plenty of patients in septic shock with relative low oxygen delivery to the tissues contributing to lactic acidosis.

Unless they’re are PROFOUNDLY anemic, have **** lungs or a **** heart, oxygen delivery isn’t typically the problem. It’s a combination of glycolysis/krebs/cori being overwhelmed due to all the catechols (as noted above) AND impaired utilization of oxygen by the tissues. Most patients can get the oxygen where it needs to go well enough. The problem is the tissue can’t use it due to mitochondrial dysfunction. This is a huge part of the “dysregulated host response to infection” that’s in all the sepsis definitions. This is why patients go into organ failure.

Impaired oxygen utilization at the level of the mitochondria does further contribute to the “back log” in krebs/glycolysis and the shunting toward anaerobic metabolism and lactate production. But it’s not delivery that’s the problem. So lactate shouldn’t be used as a marker for O2 delivery.

 

[Beeftenderloin]

Late, cold septic shock is a different story, but in regard to early, warm septic shock, oxygen delivery is not a problem in the vast, vast, vast majority of cases. When you first admit a patient in septic shock off the street, if you were to hypothetically throw in a PAC/a-line, shoot the numbers, and run an ABG you'd likely see a SvO2 > 65, cardiac output of 10L/min, Hgb > 10, SpO2 of 100%, a profoundly low SVR, and an elevated lactate. Ask yourself how on earth one can prescribe the elevated lactate to "anaerobic metabolism" or "inadequate oxygen delivery" when we're looking at numbers like that.

Rather than oxygen delivery, it's usually a problem of oxygen utilization, as mitochondria are essentially poisoned in the septic milieu and cannot effectively continue oxidative phosphorylation. Glycolysis still continues when this happens, and a ton of pyruvate (which would've entered the Krebs cycle in a non-septic state) is converted to lactate, and thus when you measure it, it's elevated. Additionally, you may have some hepatic dysfunction while septic which prevents the liver from clearing the lactate as quickly.

"Hormonal activation is an early component of the inflammatory response to sepsis.36 Acute phase hormones such as adrenaline and cortisol prepare the body for stress, e.g., increasing cardiac output, diverting blood flow to appropriate organs involved in flight and fight (e.g., brain, heart, and muscle), modifying hepatic protein production toward acute phase proteins involved with defense and transport, and modulating metabolic activity. For example, they are counter-regulatory against insulin to increase glucose availability while, at the same time, altering cellular substrate utilization. Lactate release from muscle is enhanced by catecholamines to provide a ready fuel substrate for other organs such as brain, liver, and heart.37 At the same time, non-essential activities, i.e., those not immediately involved in dealing with the stressor such as general anabolic activities and DNA repair, are downscaled."

We also know that oxygen delivery is not the problem in sepsis because critical, rigorous evaluation of Rivers and other EGDT protocols showed that all the nonsense with dobutamine and CVP > 10-12 and tranfusing to a hct of 30 in an attempt to increase DO2 was totally futile.

Not only did you say what I wanted to say faster than I could, you also said it much better. Well done.

 

[jdh71]

Late, cold septic shock is a different story, but in regard to early, warm septic shock, oxygen delivery is not a problem in the vast, vast, vast majority of cases. When you first admit a patient in septic shock off the street, if you were to hypothetically throw in a PAC/a-line, shoot the numbers, and run an ABG you'd likely see a SvO2 > 65, cardiac output of 10L/min, Hgb > 10, SpO2 of 100%, a profoundly low SVR, and an elevated lactate. Ask yourself how on earth one can attribute the elevated lactate to "anaerobic metabolism" or "inadequate oxygen delivery" when we're looking at numbers like that.

Rather than oxygen delivery, it's usually a problem of oxygen utilization, as mitochondria are essentially poisoned in the septic milieu and cannot effectively continue oxidative phosphorylation. Glycolysis still continues when this happens, and a ton of pyruvate (which would've entered the Krebs cycle in a non-septic state) is converted to lactate, and thus when you measure it, it's elevated. Additionally, you may have some hepatic dysfunction while septic which prevents the liver from clearing the lactate as quickly.

"Hormonal activation is an early component of the inflammatory response to sepsis.36 Acute phase hormones such as adrenaline and cortisol prepare the body for stress, e.g., increasing cardiac output, diverting blood flow to appropriate organs involved in flight and fight (e.g., brain, heart, and muscle), modifying hepatic protein production toward acute phase proteins involved with defense and transport, and modulating metabolic activity. For example, they are counter-regulatory against insulin to increase glucose availability while, at the same time, altering cellular substrate utilization. Lactate release from muscle is enhanced by catecholamines to provide a ready fuel substrate for other organs such as brain, liver, and heart.37 At the same time, non-essential activities, i.e., those not immediately involved in dealing with the stressor such as general anabolic activities and DNA repair, are downscaled."

We also know that oxygen delivery is not the problem in sepsis because critical, rigorous evaluation of Rivers and other EGDT protocols showed that all the nonsense with dobutamine and CVP > 10-12 and tranfusing to a hct of 30 in an attempt to increase DO2 was totally futile.

Unless they’re are PROFOUNDLY anemic, have **** lungs or a **** heart, oxygen delivery isn’t typically the problem. It’s a combination of glycolysis/krebs/cori being overwhelmed due to all the catechols (as noted above) AND impaired utilization of oxygen by the tissues. Most patients can get the oxygen where it needs to go well enough. The problem is the tissue can’t use it due to mitochondrial dysfunction. This is a huge part of the “dysregulated host response to infection” that’s in all the sepsis definitions. This is why patients go into organ failure.

Impaired oxygen utilization at the level of the mitochondria does further contribute to the “back log” in krebs/glycolysis and the shunting toward anaerobic metabolism and lactate production. But it’s not delivery that’s the problem. So lactate shouldn’t be used as a marker for O2 delivery.

Ok. I see the disconnect. You are using utilization more specifically where I’m using the term “delivery” to also include that process. You both are correct if making a bit of pedantic point about the term itself. If UPS brings a package by my house, like drives by it, but doesn’t get out of the truck to drop it off at my house or if they do get out, leave, and someone comes along and steals it has the package been “delivered”? Anyway.

 

[vector2]

Ok. I see the disconnect. You are using utilization more specifically where I’m using the term “delivery” to also include that process. You both are correct if making a bit of pedantic point about the term itself. If UPS brings a package by my house, like drives by it, but doesn’t get out of the truck to drop it off at my house or if they do get out, leave, and someone comes along and steals it has the package been “delivered”? Anyway.

I would argue that the difference between DO2 and VO2 is not a "pedantic" point at all considering that Rivers/EGDT was a thing for 10+ years, and that sending a bazillion UPS trucks (all the central lines, scvo2s, inotropes, fluids, and blood administered) was at best neutral for septic patients, and at worst significantly increased morbidity and mortality. It's a shame because that was a time we could've been looking for the package thief instead of sending more packages. What's even more unfortunate is that we still have intensivists today who continue giving large volume, unnecessary crystalloid beyond 30cc/kg to bump up the preload/CO in an attempt to clear a lactate.

Again, you said "there are sure as **** plenty of patients in septic shock with relative low oxygen delivery to the tissues contributing to lactic acidosis." This statement is only correct if we are talking about septic cardiomyopathy- i.e. the pts with end stage sepsis who have cardiac outputs of like 1.2, cold extremities, not making any urine, multisystem organ failure etc. In these cases, you run a lactate level and it's 4, and you are absolutely correct that there is relatively low oxygen delivery, DO2 has hit a critical threshold, and much of the lactate is coming from tissue ischemia. In many cases, you start these pts on an epinephrine infusion, they start perfusing and looking better, you recheck a lactate and it's now 6! It's because of the phenomenon that I've hammering- catecholamines increase lactate in a non-pathologic manner.

An easier way to think about this entire thing- pts in distributive septic shock have no problems with cardiac output/DO2; pts in cardiogenic septic shock do have a problem with cardiac output/DO2. Both have elevated lactates, but the pathophysiology and the necessary treatment for each is significantly different.

 

[vector2]

Crazy that this was published in 1999
The pathogenesis of lactic acidosis in sepsis : Current Opinion in Critical Care

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Lactic acidosis is a common finding in critically ill patients during severe sepsis/septic shock, and a powerful predictor of mortality. Because of the knowledge that lactate is the end product of anaerobic glycolysis, the presence of hyperlactatemia in sepsis has been taken to indicate the development of anaerobic glycolysis within tissues. Such anaerobic glycolysis is understood to result from oxygen “debt” at cellular level. The metabolic acidosis frequently associated with hyperlactatemia has thus been ascribed to hydrogen ions released from adenosine triphosphate hydrolysis. This simplistic view of the pathogenesis and meaning of hyperlactatemia, however, is not supported by available data. Systemic oxygen transport is usually increased rather than decreased in septic patients. Whenever studied, tissue oxygenation is either preserved or increased in septic animals and humans. In addition, lactate levels may fluctuate in response to inotropic drugs and do not consistently decrease when tissue oxygen delivery is increased. Furthermore, there is strong evidence that large amounts of lactate can be produced and released under aerobic conditions and that the pathogenesis of hyperlactatemia in septic states is complex. Such pathogenesis may involve accelerated glycolytic fluxes, the inhibition of pyruvate dehydrogenase activity, and changes in intermediary metabolism. It may also involve the need to modulate the rate and efficiency of glycolytic flux by controlling the redox state of cytoplasm and mitochondria through lactate accumulation.

Furthermore, recent investigations have attempted to establish which organs are responsible for lactate production in septic humans and endotoxemic animals. These studies suggest that the lung may be a major source of much of the excess lactate produced under these circumstances. They also suggest that decreased lactate elimination is also an important component of the pathogenesis of hyperlactatemia. Finally, the pathogenesis of the metabolic acidosis associated with hyperlactatemia is most likely to be related to the effect of the lactate ion on the strong ion difference and subsequently on the dissociation of plasma water into hydrogen ions.

A great deal remains to be understood about the pathogenesis of lactic acidosis in sepsis. It is important, however, to understand that the concepts of “anaerobic glycolysis” and “unfettered adenosine triphosphate hydrolysis” are not convincingly supported by available evidence and probably represent an inaccurate and simplistic explanation of this complex phenomenon.

-----------------

 

[jdh71]

I would argue that the difference between DO2 and VO2 is not a "pedantic" point at all considering that Rivers/EGDT was a thing for 10+ years, and that sending a bazillion UPS trucks (all the central lines, scvo2s, inotropes, fluids, and blood administered) was at best neutral for septic patients, and at worst significantly increased morbidity and mortality. It's a shame because that was a time we could've been looking for the package thief instead of sending more packages. What's even more unfortunate is that we still have intensivists today who continue giving large volume, unnecessary crystalloid beyond 30cc/kg to bump up the preload/CO in an attempt to clear a lactate.

Again, you said "there are sure as **** plenty of patients in septic shock with relative low oxygen delivery to the tissues contributing to lactic acidosis." This statement is only correct if we are talking about septic cardiomyopathy- i.e. the pts with end stage sepsis who have cardiac outputs of like 1.2, cold extremities, not making any urine, multisystem organ failure etc. In these cases, you run a lactate level and it's 4, and you are absolutely correct that there is relatively low oxygen delivery, DO2 has hit a critical threshold, and much of the lactate is coming from tissue ischemia. In many cases, you start these pts on an epinephrine infusion, they start perfusing and looking better, you recheck a lactate and it's now 6! It's because of the phenomenon that I've hammering- catecholamines increase lactate in a non-pathologic manner.

An easier way to think about this entire thing- pts in distributive septic shock have no problems with cardiac output/DO2; pts in cardiogenic septic shock do have a problem with cardiac output/DO2. Both have elevated lactates, but the pathophysiology and the necessary treatment for each is significantly different.

Again. I was talking also about utilization when I was using the term delivery. Until my nespresso pods have gone into my house through my machine and into my belly, I would argue they have not been “delivered” regardless of how many laps said pods did through my town. Again. You are correct - at least more precise with the terminology. Being pedantic isn’t always a bad thing. Though it is this tedious, toxic “dunked on you!” way that critical care gets talked about here that seems unnecessary, especially in this forum. There appears to have been a misunderstanding of each other for a moment, one that appears remedied at this point. Maybe you’re not the smartest guy in the room, just in a room full of smart guys (and or gals and or anyone identifying as something nonbinary)? I don’t fault the EGDT folks too much. At least in the beginning. It was a nice first real attempt to bring something objective to the art of resuscitation. I only fault folks for holding onto for too long when it looked wrong. Science requires a lot of negative studies to advance.

 

[deleted547339]

So low(er) oxygen delivery during septic shock does not contribute to lactic acidosis? It’s all glycolysis and cori cycle?

I really hate these all or nothing proclamations because there are sure as **** plenty of patients in septic shock with relative low oxygen delivery to the tissues contributing to lactic acidosis.

Dude. You’ve been doing this long enough to know we have no clue what we’re doing. We give some fluids, and pressors, and antibiotics, then some stuff happens and people get better if they don’t. And of course vitamin C.

It’s all smoke and mirrors.

 

[vector2]

Again. I was talking also about utilization when I was using the term delivery. Until my nespresso pods have gone into my house through my machine and into my belly, I would argue they have not been “delivered” regardless of how many laps said pods did through my town. Again. You are correct - at least more precise with the terminology. Being pedantic isn’t always a bad thing. Though it is this tedious, toxic “dunked on you!” way that critical care gets talked about here that seems unnecessary, especially in this forum. There appears to have been a misunderstanding of each other for a moment, one that appears remedied at this point. Maybe you’re not the smartest guy in the room, just in a room full of smart guys (and or gals and or anyone identifying as something nonbinary)? I don’t fault the EGDT folks too much. At least in the beginning. It was a nice first real attempt to bring something objective to the art of resuscitation. I only fault folks for holding onto for too long when it looked wrong. Science requires a lot of negative studies to advance.

Dude, cmon. You come in totally disagreeing with something by saying that essentially an incorrect blanket statement has been made. I support what I said with what I think is the best argument for it. You're then like "oh yea that's what I was saying too." And I'm like "hmm, it doesn't sound like it was same thing, here's the difference"

I've done nothing but present my interpretation of what we know about the subject, and you've taken that as some sort of an affront when I couldn't care less about "dunking" on someone in a subform I infrequently visit and rarely post in. If this kind of back and forth is what's seen as "tedious and toxic" in a place that should have some pretty cerebral discussions then I can now understand why the traffic here is so low

 

[jdh71]

Dude, cmon. You come in totally disagreeing with something by saying that essentially an incorrect blanket statement has been made. I support what I said with what I think is the best argument for it. You're then like "oh yea that's what I was saying too." And I'm like "hmm, it doesn't sound like it was same thing, here's the difference"

I've done nothing but present my interpretation of what we know about the subject, and you've taken that as some sort of an affront when I couldn't care less about "dunking" on someone in a subform I infrequently visit and rarely post in. If this kind of back and forth is what's seen as "tedious and toxic" in a place that should have some pretty cerebral discussions then I can now understand why the traffic here is so low

I wasn’t actually totally disagreeing with you though. There was misunderstanding on both sides here. I promise I understand you (now). You initially said there was no anaerobic metabolism in septic shock causing lactate production and were not clear you were also talking about mitochondrial dysfunction until your later response. If the mitochondria aren’t working that cell will be in anaerobic metabolism. You then clarified further. I was then like, “oh we are talking about the same thing then, my term was not as precise as yours and here is why I think about it like that”. I guess if you aren’t trying to be toxic and dunk in here, and I’m happy to take you at your word you are not, then you can quit trying to tell me I was saying something I was not.

I promise those in this forum can handle the intellectual material in your posts. Post or don’t. It’s a free forum.

 

[jdh71]

Dude. You’ve been doing this long enough to know we have no clue what we’re doing. We give some fluids, and pressors, and antibiotics, then some stuff happens and people get better if they don’t. And of course vitamin C.

It’s all smoke and mirrors.

I’m definitely an EBM cynic after all I’ve seen in my relatively short time in medicine, from medical school onwards. But it still feels to me like “we” (someone - not me - I don’t have any funding) should continue to try to find the best path. How long did it take CVP to finally die? And now we have this 30cc/kg nonsense and the repeat lactates? Between the ED and the ICU we seem be scrambling to practice a lot of Voodoo to keep the suits happy.

But this current discussion is really about the basic science and physiology.

 

[vector2]

One thing I should've been more clear on in regard to anaerobic metabolism- we really need to be differentiate the so-called early and late shock states. When you are treating the early warm septic patient, there is no significant degree of any sort of anaerobic metabolism contributing to lactate generation, i.e. no significant problems with oxygen delivery or oxygen utilization. In the early state, oxygen delivery is fine and mitochondria are still functioning OK enough that any organ dysfunction is mild. The excess lactate when the pt is first admitted to the ICU exists because there is so much pyruvate being generated d/t catecholamine driven glycolysis that the mitochondria simply has too much pyruvate to keep up with even though it's running at full steam (same principle works the opposite way as to how ketones are generated when carbs/glucose are restricted and there's not enough oxaloacetate to keep up with all the acetyl coa churning through the TCA cycle, so acetyl coa from fatty acid metabolism goes to making ketones instead).

Some patients easily recover from this early warm state, some don't, and we all know it's possible to still be warm and die from sepsis. In these cases, multisystem organ dysfunction becomes worse and worse despite our best resuscitative efforts, and this is where we can really start talking about oxygen utilization, anaerobic metabolism, and mitochondrial dysfunction becoming a problem. Mitochondrial dysfunction supposedly happens because various reactive oxygen species, massive overproduction of NO, endotoxins etc are all pretty bad for them, and as they become more impaired, they gradually become unable to participate enough in oxphos and there is not enough ATP now generated to support the functions of the cell. Organs start failing badly and this is when we start putting in dialysis catheters, starting 3rd line pressors, proning the pt, and treating DIC etc. Indeed, only now have we reached the point where "anaerobic" lactate production is happening in the way that many think it is always happening in sepsis.

I feel like I've been typing forever, so the TL;DR version: In the first 48 hrs or so of warm septic shock, if your patient's vitals are stable or improving, organ function is stable or improving, and multiple surrogates of perfusion are stable or improving, do not escalate care based on a mild lactate increase.

 

[Radetzky]

Awesome insights here from the forum pros.

One thing that I've never had an adequate answer to is, if in the early stages of warm septic shock the cardiac output approaches 10 L/min, why would giving fluid, which might increase the CO to 10.3, have any beneficial effect at all? I do it, and the BP seems to get better, but I don't understand why it should.

Also, for the same reason, why the hell do we chase low urine output with endless fluid? I see it as the kidneys failing from mitochondrial dysfunction, cytokines, etc. but many people seem to still regard it as a sign of inadequate RBF?

The more I do medicine the more I realise how much we don't know.

 

[vector2]

Awesome insights here from the forum pros.

One thing that I've never had an adequate answer to is, if in the early stages of warm septic shock the cardiac output approaches 10 L/min, why would giving fluid, which might increase the CO to 10.3, have any beneficial effect at all? I do it, and the BP seems to get better, but I don't understand why it should.

Also, for the same reason, why the hell do we chase low urine output with endless fluid? I see it as the kidneys failing from mitochondrial dysfunction, cytokines, etc. but many people seem to still regard it as a sign of inadequate RBF?

The more I do medicine the more I realise how much we don't know.

Keep in mind, fluid responsiveness is not the same thing as requiring fluid. All of us sitting here right now would be fluid responsive and augment our numbers with a 1L bolus, but that doesn’t mean we were hypovolemic to start and actually required the fluid. It just means we were on the ascending part of the starling curve.

Even though 10L/min may be a bit of an exaggeration, don’t forget that early sepsis is a hypermetabolic state. Between the fever, protein synthesis, immune response, tachycardia, tachypnea, the BMR may reach 10,000 kcal/day in a robust, young pt. The CO needed to support this metabolism is tremendous, all the while the pt is profoundly vasodilated from both an arterial and vein standpoint and bunch of necessary preload is pooling in the veins. Giving a bit of a fluid bolus helps to fill up the veins and augment the preload, but mostly what needs to be treated is the underlying process (vasoplegia -> pressors)

 

[SurfingDoctor]

This discussion is also a great example of why 28 day or 90 day or whatever day mortality is a useless endpoint. People who die in the first 1 to 2 days aren’t dying from the same physiology as patients who die 2 weeks later.

Trying to rescue patients at both time points using the same physiological approach is unlikely to be successful.

 

[aafisahar]

https://www.nejm.org/doi/full/10.1056/NEJMoa0801581

Lactate measurements on Mt Everest. PaO2s in the 30s and normal lactate. Oxygenation is not the only thing that generates lactate and is probably overemphasized. I had an attending that reasoned lactate was a measure of catecholamines and not anaerobic metabolism due to this and many other pieces of data.

 

[jdh71]

https://www.nejm.org/doi/full/10.1056/NEJMoa0801581

Lactate measurements on Mt Everest. PaO2s in the 30s and normal lactate. Oxygenation is not the only thing that generates lactate and is probably overemphasized. I had an attending that reasoned lactate was a measure of catecholamines and not anaerobic metabolism due to this and many other pieces of data.

Yeah but all were acclimatized mountaineers/climbers. Hgb was supranormal. And they were otherwise healthy.

I mean it’s cool that they had adapted to the point where they didn’t make any lactate because they had optimized their physiology but I find it very confounding to try and then extrapolate that to a patient in septic shock.

 

[Hernandez]

So low(er) oxygen delivery during septic shock does not contribute to lactic acidosis? It’s all glycolysis and cori cycle?

I really hate these all or nothing proclamations because there are sure as **** plenty of patients in septic shock with relative low oxygen delivery to the tissues contributing to lactic acidosis.

But can I give it bicarb?

 

[Hernandez]

I would argue that the difference between DO2 and VO2 is not a "pedantic" point at all considering that Rivers/EGDT was a thing for 10+ years, and that sending a bazillion UPS trucks (all the central lines, scvo2s, inotropes, fluids, and blood administered) was at best neutral for septic patients, and at worst significantly increased morbidity and mortality. It's a shame because that was a time we could've been looking for the package thief instead of sending more packages. What's even more unfortunate is that we still have intensivists today who continue giving large volume, unnecessary crystalloid beyond 30cc/kg to bump up the preload/CO in an attempt to clear a lactate.

Again, you said "there are sure as **** plenty of patients in septic shock with relative low oxygen delivery to the tissues contributing to lactic acidosis." This statement is only correct if we are talking about septic cardiomyopathy- i.e. the pts with end stage sepsis who have cardiac outputs of like 1.2, cold extremities, not making any urine, multisystem organ failure etc. In these cases, you run a lactate level and it's 4, and you are absolutely correct that there is relatively low oxygen delivery, DO2 has hit a critical threshold, and much of the lactate is coming from tissue ischemia. In many cases, you start these pts on an epinephrine infusion, they start perfusing and looking better, you recheck a lactate and it's now 6! It's because of the phenomenon that I've hammering- catecholamines increase lactate in a non-pathologic manner.

An easier way to think about this entire thing- pts in distributive septic shock have no problems with cardiac output/DO2; pts in cardiogenic septic shock do have a problem with cardiac output/DO2. Both have elevated lactates, but the pathophysiology and the necessary treatment for each is significantly different.

I find your argument pedantic and arrogant and I love it. Where might I subscribe to your newsletter.

 

[Hernandez]

It’s all smoke and mirrors.

Chest thumping pendant arguments, voodoo and nutraceuticals....

 

[Hernandez]

I’m definitely an EBM cynic after all I’ve seen in my relatively short time in medicine, from medical school onwards. But it still feels to me like “we” (someone - not me - I don’t have any funding) should continue to try to find the best path. How long did it take CVP to finally die? And now we have this 30cc/kg nonsense and the repeat lactates? Between the ED and the ICU we seem be scrambling to practice a lot of Voodoo to keep the suits happy.

But this current discussion is really about the basic science and physiology.

Won’t someone show me the ebm behind ebm!?!?!

 

[deleted547339]

But can I give it bicarb?

I’m going to stab you.

 

[jdh71]

But can I give it bicarb?

wuts ur pH?

 

[jdh71]

Won’t someone show me the ebm behind ebm!?!?!

I'll show you my emb if you show me yours.

 

[McPoyle]

wuts ur pH?

No no it’s “what’s their base deficit?”

 

[vector2]

Had a couple patients today come up to the OR that made me think about this thread.

1. 26 yo M no PMH, looks like an athlete, s/p GSW to the anterior thigh. Minimal blood loss at the scene. No tourniquet, just a compression bandage. C/o of pain. Vitals HR 105, BP 158/83. Sp 100% on RA. H/H 14/43, normal chemistry.

Lactate: 8.8

2. 47yo M, hx of T6 paraplegia, HTN, morbidly obese with what appears to be developing fournier's / nec fasc. Vitals HR 92, BP 101/55. Sp O2 98% on RA. Febrile to 38.3. WBC 19.4. H/H 8/26. Na 129 from baseline 137. Glucose 340. Cr normal. Sed rate and CRP both very elevated.

Lactate: 1.3

 

[Siggy]

Had a couple patients today come up to the OR that made me think about this thread.

1. 26 yo M no PMH, looks like an athlete, s/p GSW to the anterior thigh. Minimal blood loss at the scene. C/o of pain. Vitals HR 105, BP 158/83. Sp 100% on RA. H/H 14/43, normal chemistry.

Lactate: 8.8

2. 47yo M, hx of T6 paraplegia, HTN, morbidly obese with what appears to be developing fournier's / nec fasc. Vitals HR 92, BP 101/55. Sp O2 98% on RA. Febrile to 38.3. WBC 19.4. H/H 8/26. Na 129 from baseline 137. Glucose 340. Cr normal. Sed rate and CRP both very elevated.

Lactate: 1.3

Obviously the first one is in septic shock and the second one is just fine because of lactate levels.
-The ED at both my residency hospital and my fellowship hospital.

 

[deleted547339]

Had a couple patients today come up to the OR that made me think about this thread.

1. 26 yo M no PMH, looks like an athlete, s/p GSW to the anterior thigh. Minimal blood loss at the scene. No tourniquet, just a compression bandage. C/o of pain. Vitals HR 105, BP 158/83. Sp 100% on RA. H/H 14/43, normal chemistry.

Lactate: 8.8

2. 47yo M, hx of T6 paraplegia, HTN, morbidly obese with what appears to be developing fournier's / nec fasc. Vitals HR 92, BP 101/55. Sp O2 98% on RA. Febrile to 38.3. WBC 19.4. H/H 8/26. Na 129 from baseline 137. Glucose 340. Cr normal. Sed rate and CRP both very elevated.

Lactate: 1.3

So you had a lactate or 9 and a normal anion gap?

 

[Colorado outliers]

Had a couple patients today come up to the OR that made me think about this thread.

1. 26 yo M no PMH, looks like an athlete, s/p GSW to the anterior thigh. Minimal blood loss at the scene. No tourniquet, just a compression bandage. C/o of pain. Vitals HR 105, BP 158/83. Sp 100% on RA. H/H 14/43, normal chemistry.

Lactate: 8.8

2. 47yo M, hx of T6 paraplegia, HTN, morbidly obese with what appears to be developing fournier's / nec fasc. Vitals HR 92, BP 101/55. Sp O2 98% on RA. Febrile to 38.3. WBC 19.4. H/H 8/26. Na 129 from baseline 137. Glucose 340. Cr normal. Sed rate and CRP both very elevated.

Lactate: 1.3

Interesting, I'll bite:

1. Localized tissue ischemia/trauma from GSW + strong Catecholamine response
2. Little muscle mass. CK? 'early' or actual nec fasc? If no real nec fasc/necrosis and not much muscle to begin with, and apparently still perfusing, would make sense that lactate is normal. Inadequate catecholamine response due to paraplegia. Did lactate increase after OR?

Your thoughts?

alternatively:

1. ICU
2. Stable for floor/Outpatient surgery center

 

[vector2]

So you had a lactate or 9 and a normal anion gap?

Actually had to go back and look. Bicarb was 20, na 137, cl 101, so I take that back, not a stone cold normal chemistry. But still, a lactate of almost 9.

Interesting, I'll bite:

1. Localized tissue ischemia/trauma from GSW + strong Catecholamine response
2. Little muscle mass. CK? 'early' or actual nec fasc? If no real nec fasc/necrosis and not much muscle to begin with, and apparently still perfusing, would make sense that lactate is normal. Inadequate catecholamine response due to paraplegia. Did lactate increase after OR?

Your thoughts?

alternatively:

1. ICU
2. Stable for floor/Outpatient surgery center

While I have to addend the full clinical picture of pt one, it still begs the question of the utility of lactate. Maybe there is some component of regional ischemia contributing to his acidosis and lactatemia, but his picture argues that the vast majority of the lactate production was related to a strong sympathetic response in a 20 something year old. After all, if we draw a lactate right after the 60 min tourniquet comes down in a total knee we dont see a lactate anywhere near this high.


With pt two, he had plenty of muscle mass. And the nec fasc and sepsis is def the real deal, he's going for another debridement today. Usually sympathetic NS is innervated from T1-T4 so a t6 injury is unlikely to have persistent sns problems. I honestly have no idea why he wouldn't have bumped his lactate at all as he did look pretty toxic on presentation

 

[deleted547339]

Actually had to go back and look. Bicarb was 20, na 137, cl 101, so I take that back, not a stone cold normal chemistry. But still, a lactate of almost 9.



While I have to addend the full clinical picture of pt one, it still begs the question of the utility of lactate. Maybe there is some component of regional ischemia contributing to his acidosis and lactatemia, but his picture argues that the vast majority of the lactate production was related to a strong sympathetic response in a 20 something year old. After all, if we draw a lactate right after the 60 min tourniquet comes down in a total knee we dont see a lactate anywhere near this high.


With pt two, he had plenty of muscle mass. And the nec fasc and sepsis is def the real deal, he's going for another debridement today. Usually sympathetic NS is innervated from T1-T4 so a t6 injury is unlikely to have persistent sns problems. I honestly have no idea why he wouldn't have bumped his lactate at all as he did look pretty toxic on presentation

I think it gives you a lot of information if you know what it means. The problem with lactic is that we want it to be a diagnostic and prognostic test as well as guide in management. It just can’t do three things well.

I think it adds data on many patients, but almost never the patients that my residents want to get it on. If you have a focal infiltrate on CXR, temp of 103, you’re tachy to the 120s and have a SBP in the 80s, I don’t need a lactic. In your patient, you don’t need a lactic. Now, it probably tells you that your septic patient is lower risk than someone with a similar picture and a lactic of 8, but you’ll only know in retrospect who will and won’t live. In someone who was found down and had a lactic of 12 that rapidly cleared to 1, that pretty much confirms a seizure. My residents and nurses like to order it on everyone who comes in the door. I don’t need to know that my otherwise stable 40yo banker with the flu has a lactic of 3 - that just obliges me to give them fluids they don’t need and recheck it to fix a number before discharge.

I like it, but I order it sparingly. Honestly, I find it most often useful in my icu patients who have marginal BPs to convince me (and everyone else) as one more piece of data that they don’t need pressors for low BPs.

Only a bad carpenter blames his tools

 

[vector2]

I think it gives you a lot of information if you know what it means. The problem with lactic is that we want it to be a diagnostic and prognostic test as well as guide in management. It just can’t do three things well.

I think it adds data on many patients, but almost never the patients that my residents want to get it on. If you have a focal infiltrate on CXR, temp of 103, you’re tachy to the 120s and have a SBP in the 80s, I don’t need a lactic. In your patient, you don’t need a lactic. Now, it probably tells you that your septic patient is lower risk than someone with a similar picture and a lactic of 8, but you’ll only know in retrospect who will and won’t live. In someone who was found down and had a lactic of 12 that rapidly cleared to 1, that pretty much confirms a seizure. My residents and nurses like to order it on everyone who comes in the door. I don’t need to know that my otherwise stable 40yo banker with the flu has a lactic of 3 - that just obliges me to give them fluids they don’t need and recheck it to fix a number before discharge.

I like it, but I order it sparingly. Honestly, I find it most often useful in my icu patients who have marginal BPs to convince me (and everyone else) as one more piece of data that they don’t need pressors for low BPs.

Only a bad carpenter blames his tools

The problem is that in the age of surviving sepsis/sepsis 3 and the various bundles out there, this kind of clinical judgement has mostly been outlawed. It's not fair to shade the arguments against lactate as "carpenters blaming tools" when there are millions of instances of intensivists using lactate clearance as a surrogate of improving perfusion in pts like your hypothetical pulmonary sepsis example (for which you say you don't need a lactate). My 26yo can likely handle the 6-8 liters of LR the trauma surgical ICU is going to throw at him when he comes out of the OR- someone a bit older or a little bit sicker might not be able to deal with the glycocalyx damage from that much fluid.

 

[Colorado outliers]

Actually had to go back and look. Bicarb was 20, na 137, cl 101, so I take that back, not a stone cold normal chemistry. But still, a lactate of almost 9.



While I have to addend the full clinical picture of pt one, it still begs the question of the utility of lactate. Maybe there is some component of regional ischemia contributing to his acidosis and lactatemia, but his picture argues that the vast majority of the lactate production was related to a strong sympathetic response in a 20 something year old. After all, if we draw a lactate right after the 60 min tourniquet comes down in a total knee we dont see a lactate anywhere near this high.


With pt two, he had plenty of muscle mass. And the nec fasc and sepsis is def the real deal, he's going for another debridement today. Usually sympathetic NS is innervated from T1-T4 so a t6 injury is unlikely to have persistent sns problems. I honestly have no idea why he wouldn't have bumped his lactate at all as he did look pretty toxic on presentation

Agree on questioning the clinical utility of lactate in that scenario and in many scenarios in the ICU where we 'trend' it, hoping it will normalize with our interventions. If you really wanted to prove this, you would measure serum epi and norepi levels in stable patients w/ elevated lactate levels and trend over time as the lactate resolves...seems likely someone could get money do to this study.

Still think a a T6 injury could dampen catecholamine response as the adrenal medulla is innervated by T5-T11. Whether that would really account for the lactate being normal, who knows. You would think the dead tissue alone would cause an elevated lactate.

From a reputable source (Brazil J Med Biol Res)...lol maybe
Catecholamine response to exercise in individuals with different levels of paraplegia. - PubMed - NCBI

Lactate not always elevated in nec fasc (up to 20%) in this Taiwanese cohort:
Lactate on emergency department arrival as a predictor of in-hospital mortality in necrotizing fasciitis: a retrospective study

Good stuff!

 

[leviathan]

Just a few points.

Lactate is up from both catecholamines but also tissue hypoxia - sometimes low cardiac output but other times from microcirculatory or mitochondrial dysfunction.

When the lactate is truly up from anaerobic metabolism, my experience is that those are the people with lactates >20. And usually part of it is their liver crapping out.

In my own experience, running people on epi infusions doesn't seem to increase the lactate, even at high doses, despite the theoretical reason it should rise.