Insulin overdose case/lactate question

[em06]

Had an insulin overdose case tonight. Apologies if any/all of the questions have already been answered on sdn...

50's male diabetic decides to inject himself (suicide attempt) with 1000 units of Humalog 70/30 in his deltoid (probably IM). Becomes symptomatically hypoglycemic and decides to drink sodas/eat sugary foods to save himself... EMS gives him 2 amps of D50, (unknown FS) and arrives in ED.

FS = 305 on arrival, pt somewhat lethargic, but arousable to loud voice. K never dropped below 3.3, monitored FS, which was ~200-250 over 3-4 hours.

My question concerns the lactate... On the ABG pH was 7.37, lactate was 5.4... Pt was not septic. Yes, he was also on metformin but he said he hadn't taken it since wednesday. Repeat lactates were 5.4, then 4.6 (pH 7.43) after lots of D5 fluid resuscitation. Pt is alert, oriented, in NAD, VS normal except for HR to 110's secondary to likely opioid withdrawal (takes 20 vicodin per day for arthritis pain, last took 2 days ago)

What is the reason for the elevated lactate?
As VBG lactates can reflect localized hypoperfusion, how much does that really matter, compared to ABG lactates?

thanks.

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[Painter1]

causes of high lactic include:

hypoperfusion
sepsis
metformin
methanol
INH
Iron
cynide
carbon monoxide

did he lie and ingest a bottle worth of metformin in his suicide attempt? did he ingest iron?

 

[USCDiver]

How long was his tourniquet on while the blood was being drawn?

 

[southerndoc]

How long was his tourniquet on while the blood was being drawn?

There was a study that cast doubt on the tourniquet time theory of increased lactates. Besides, this patient had an arterial lactate, which I believe to be real.

It's been a while since I studied biochemistry, but I think insulin uses lactate to perform gluconeogenesis. For some reason I think lactate production is increased due to shutting down of one of the TCA enzymes. I could be wrong. It's been 7.5 years since I learned (and forgot) this stuff. I thought they said we didn't need to really, really know biochemistry in emergency medicine? They lied, and I feel cheated!

 

[overthebars]

Although you still have to do your due diligence I'd think it probable that he took his Metformin too and is either a) lying or b) unreliable.

Goldfrank's has a cool secion on anti-diabetogenic OD.

Cool case.

 

[em06]

thanks for the replies...
I did check specifically about how long the tourniquet was on for the vbg, but it was a non issue since I drew the first abg myself to get quick lytes, K and pH, and any elevated lactate from minutes of tourniquetting on the vbg would not be reflected in the first abg I drew.

As far as the other causes of high lactate, wouldn't they be accompanied by acidosis? This guy's pH was 7.43, with a lactate of 5.4...

as far as other causes of elevated lactate levels, he was not septic, we did a utox which showed his vicodin he takes for pain (incidentally this guy was addicted to opioids, and he takes "20" vicodin a day for pain, which he gets both from legal and more nefarious sources)... last vicodin was 2 days prior per pt.

etoh level was 149. Did not check for toxic alcohols but asked both him and his wife specifically about them, which he denied. Had also done an AXR to look for the radiopaque ingestions, didn't see any.

anyway, the reason this question came up initially was because the MICU intensivist could not explain the lactate level, and the PMD wanted the pt admitted to the MICU b/c he couldn't explain the lactate either.

pt ended up going to tele, with q1h FS.

I'll check on the lactate/pt in a few days or so.

 

[southerndoc]

I did check specifically about how long the tourniquet was on for the vbg, but it was a non issue since I drew the first abg myself to get quick lytes, K and pH, and any elevated lactate from minutes of tourniquetting on the vbg would not be reflected in the first abg I drew.

My question concerns the lactate... On the ABG pH was 7.37, lactate was 5.4...

I'm confused. Did you do an ABG or a VBG? You said in your first post an ABG, and then you say both in your second post. Was it an arterial or venous lactate?

 

[em06]

I'm confused. Did you do an ABG or a VBG? You said in your first post an ABG, and then you say both in your second post. Was it an arterial or venous lactate?

Did both.
ABG on arrival 7.37, lactate 5.4
VBG a few hours later, lactate exactly same again, 5.4
VBG again, sent to the core lab, to run serum lactate... 4.5 or 4.6

 

[BADMD]

My question concerns the lactate... On the ABG pH was 7.37, lactate was 5.4... Pt was not septic. Yes, he was also on metformin but he said he hadn't taken it since wednesday. Repeat lactates were 5.4, then 4.6 (pH 7.43) after lots of D5 fluid resuscitation.

Here is a theory, not necessarily a good one, but one...

Lactate is usually metabolized to pyruvate via an enzymatic mechanism that converts NAD+ to NADH. He was very likely in a high energy state, given the amount of glycolysis that must have been occurring and thus had a significant amount of NADH. Without an available electron acceptor, NAD+, lactate remains (this is very much what happens in when alcoholics develop an elevated lactate). Thiamine is also required as a co-factor to help pyruvate enter the TCA cycle. If he had a relative thiamine deficiency, pyruvate may not have been moving and thus shifting the equilibrium toward lactate and not toward pyruvate.

If the above is true, there would be no acidosis and IV fluids would not help clear the lactate.

Metformin associated lactic acidosis is very rare, even in overdose. It is unusual in patients with normal kidney function and the patients get a huge acidosis (average pH in one case series was 6.9) that often requires exogenous bicarb or dialysis to correct. So metformin seems less likely, although it could just be mild.

As a side note, insulin receptor/transporter can get saturated in an area and, if this was a subq injection, could take days for him to fully absorb a dose of 1000 units.

 

[em06]

http://www.emedmag.com/html/pre/fea/features/038120044.asp

Lactate levels

Elevated arterial lactate levels are an early sensitive marker of tissue hypoperfusion, predicting both the severity of hemodynamic compromise and overall patient prognosis. Unlike the pH during cardiac arrest, interpreting a venous lactate level in relation to an arterial value could be useful in the workup and management of critically ill patients. Based on the available evidence, the correlation between arterial and venous lactate values appears to be quite close. A 1996 study by Younger of 48 emergency department patients in whom concurrent arterial and venous blood gas analyses were performed demonstrated that an abnormally elevated venous lactate level (1.6 mmol/L or greater) was 100% sensitive and 89% specific in predicting elevated arterial lactate levels. A 2000 study by Lavery bolstered these results, demonstrating a close correlation between arterial and venous lactate levels in a population of 375 hypovolemic trauma patients. A venous lactate level above 2 mmol/L predicted an elevated injury severity score, ICU admission, and length of stay.

The bottom line: Venous lactate levels are similar to those found in arterial samples. A normal venous lactate measurement predicts a normal arterial lactate reading, precluding the need to perform an arterial puncture.

 

[em06]

As a side note, insulin receptor/transporter can get saturated in an area and, if this was a subq injection, could take days for him to fully absorb a dose of 1000 units.

I'm assuming it was an IM injection, not SC, since the pt was etoh'ed to 149, and suicidal, he probably wasn't very precise on where he injected the insulin.

I guess if the depot of insulin was acting for too long, we could always do this:

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1499212&blobtype=pdf

... I think our residency requires that we do 3 insulin-depot-excision procedures to graduate.

 

[BADMD]

I'm assuming it was an IM injection, not SC, since the pt was etoh'ed to 149, and suicidal, he probably wasn't very precise on where he injected the insulin./QUOTE]

When you tack on the alcohol, I am far more convinced about my proposed mechanism. An elevated lactate in the face of significant alcohol use and thiamine deficiency (usually related to poor nutrition/chronic alcohol use) is quite common.

 

[southerndoc]

Here is a theory, not necessarily a good one, but one...

Lactate is usually metabolized to pyruvate via an enzymatic mechanism that converts NAD+ to NADH. He was very likely in a high energy state, given the amount of glycolysis that must have been occurring and thus had a significant amount of NADH. Without an available electron acceptor, NAD+, lactate remains (this is very much what happens in when alcoholics develop an elevated lactate). Thiamine is also required as a co-factor to help pyruvate enter the TCA cycle. If he had a relative thiamine deficiency, pyruvate may not have been moving and thus shifting the equilibrium toward lactate and not toward pyruvate..

Wouldn't an overdose of insulin cause gluconeogenesis instead of allowing glycolysis?

 

[em06]

Doesn't an acidosis go along with the elevated lactate in alcoholics? This guy was NOT acidotic. Plus, he didn't look like the typical, wasted alcoholic (he may have been wasted in the saturday-night-lets-go-clubbing vernacular, but not in the medical sense). LFT's and coags were fine, and he was obese.

http://www.anaesthesiamcq.com/AcidBaseBook/ab8_1.php

didn't have mesenteric ischemia.

Other theories I have are:

Cori cycle: I'm sure the huge amounts of glucose lying around in his bloodstream reduced gluconeogenesis... so, less glucose needed to be made from the lactate lying around, so the lactate level went up.

http://en.wikipedia.org/wiki/Cori_cycle

Or, maybe the shivering he had when he was hypoglycemic was the metabolic equivalent of anaerobic muscular exercise, thereby producing lactate, and the fact that he was not acidotic was b/c he was respiratorily compensating (although he wasn't that tachypneic)

 

[em06]

Wouldn't an overdose of insulin cause gluconeogenesis instead of allowing glycolysis?

Maybe you should just move this thread to the pre-allo forum and let them hash things out for a week or two
or the infernal medicine forum

 

[southerndoc]

Maybe you should just move this thread to the pre-allo forum and let them hash things out for a week or two
or the infernal medicine forum

They would certainly know better. I hardly remember my biochemistry I "learned" in medical school.

 

[BADMD]

Wouldn't an overdose of insulin cause gluconeogenesis instead of allowing glycolysis?

Intracellular tissue glycolysis. The cells are taking up a huge amount of glucose with all that insulin and something has to happen to it. Gluconeogenasis would be going on in the liver.

 

[BADMD]

Doesn't an acidosis go along with the elevated lactate in alcoholics? This guy was NOT acidotic. Plus, he didn't look like the typical, wasted alcoholic (he may have been wasted in the saturday-night-lets-go-clubbing vernacular, but not in the medical sense). LFT's and coags were fine, and he was obese.

You didn't mention his pCO2, so he may have been compensated. He may also have been volume contracted, so his acidosis might be masked. More likely, though, I wouldn't expect an acidosis. In alcoholics, the acidosis comes from ketoacids as a result of starvation. In this case, the guy is NADH replete, owning to alcohol metabolism and the massive amounts of glycolysis that is occurring, preventing lactate conversion to pyruvate. However, he still has lots of glucose to use as an energy source, especially as you are giving it to him IV.

I can't say this is exactly what was going on, but I think it is at least plausible.

 

[kungfufishing]

This thread is riveting. You guys sold me the whole seat, but I only needed the edge!

 

[WilcoWorld]

Insulin decreases gluconeogenesis / increases glcose utilization. Glucagon does the opposite.

Just think: Glucose stimulates insulin release (in healthy beta cells). Gluconeogenesis generates glucose. Thus if insulin stimulated gluconeogenesis it would thereby increase glucose & thus stimulate its own release in a positive feedback cycle, which would not be good. I'll admit that's teleologic reasoning, and thus not a great argument, but it helps me remember how it works.

 

[WilcoWorld]

This thread is riveting. You guys sold me the whole seat, but I only needed the edge!

LOL

 

[BADMD]

This thread is riveting. You guys sold me the whole seat, but I only needed the edge!

Becareful what you say...I'll post my most recent unusual acid-base-electrolytes disorder case. Trust me when I say I can pontificate on electrolytes like the medicine guys.

 

[geogil]

Wow. MS1 here and I can't believe what I'm reading. You mean the biochem block I just finished just might, maybe someday, come in handy! Huzzah!! of course, by the time I'm a resident it will probably be a distant memory, but thanks for at least showing the metabolism crap is actually relevant!

 

[southerndoc]

Insulin decreases gluconeogenesis / increases glcose utilization. Glucagon does the opposite.

Just think: Glucose stimulates insulin release (in healthy beta cells). Gluconeogenesis generates glucose. Thus if insulin stimulated gluconeogenesis it would thereby increase glucose & thus stimulate its own release in a positive feedback cycle, which would not be good. I'll admit that's teleologic reasoning, and thus not a great argument, but it helps me remember how it works.

If you say so. I'm still having a hard time comprehending it with my temp of 101 (hey, it's down from 103 the other day!).

 

[J-Rad]

What was the rest of his gas and what was the BMP? It's already been alluded to, but a normal pH does not rule out an acid-base abnormality. What was the gap and the delta gap?

 

[NinerNiner999]

Was there a reason for this patient to be alkalotic? What did his potassium levels do with all of that insulin? The lactate could be from tissue hypoperfusion in this case. Were there any signs of hemolysis?

 

[Dimoak]

I'm not an expert, but did the pt vomit? This could lead ABGs to show a slight alkalosis (7.43), and potentially obscure underlying lactacidosis?