Local Anesthetics are confusing

[propofabulous]

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CA1 here having some trouble with local anesthetic onset of action, peak effect, duration of action, and toxicity. My issue is that whenever toxic doses or onset/duration are listed, I don't know what type of delivery they are referring to (or if it matters).

For example, I've read that ~max toxic dose for lidocaine is 4.5 mg/kg, 7 mg/kg with epi. And it is ~3 mg/kg for bupi/ropivacaine. But is this referring to IV injection, subQ injection, peripheral nerve block, spinal or epidurals? I'm guessing IV, because I know that LAST risk exists in this order: IV > Tracheal > Intercostal > Caudal > Paracervical > Epidural > Brachial > Sciatic > SubQ?

Also, my understanding is that IV lidocaine duration of action is 10-20 minutes, while lidocaine used as a local anesthetic subQ has duration of action 45-90 minutes (based on the table from open anesthesia keword for Local Anesthetics:Systemic toxicity, SDN not allowing me to link). Does this duration of action change when lidocaine is given intrathecally? What about as an initial bolus when given as an epidural?

Any help would be greatly appreciated. Thank you all very much in advance

 

[T-burglar]

The toxic dose is affected by patient comorbities, injection site, epinephrine usage, cardiac conduction system reserve.

Essentially it’s a made up number but the most important thing to do is make sure when you pick up a vial you stare at the concentration and be sure you’re using the concentration you want

 

[Shimmy8]

Always assume the drug could potentially have been absorbed IV whether truly injected there, inadvertently, etc. So same "dose" no matter the route.

 

[Iso4ane]

I’m bad at history, but if I recall correctly, the toxic dose of most of the common local anesthetics were discovered in a dog model with IV injection and that the toxic dose in humans is extrapolated from that.

It is always the the safest asssumption that all you medication will be instaneously intravascile regardless of delivery site. Although, we probably could get away with a slightly higher dose in those alternate locations, how much higher I don’t think anyone knows.

 

[CopaceticOne]

For example, I've read that ~max toxic dose for lidocaine is 4.5 mg/kg, 7 mg/kg with epi. And it is ~3 mg/kg for bupi/ropivacaine. But is this referring to IV injection, subQ injection, peripheral nerve block, spinal or epidurals? I'm guessing IV, because I know that LAST risk exists in this order: IV > Tracheal > Intercostal > Caudal > Paracervical > Epidural > Brachial > Sciatic > SubQ?

20cc of 0.5% bupi given IV bolus to a 70kg patient = big, huge, badness.

 

[Iso4ane]

20cc of 0.5% bupi given IV bolus to a 70kg patient = big, huge, badness.

But, that’s not near the toxic dose in any regards

 

[daneeka]

The maximum safe dose is an estimate of the amount of drug, deposited into a tissue (i.e. not IV!), that maintains a plasma concentration less than toxic levels. The plasma concentration is what matters - but cannot be reliably estimated for all comers. It depends on many factors - protein binding, volume of distribution, rate of uptake from the tissue site etc. Additionally, the effects of toxicity for the drugs differ - lignocaine might cause some perioral tingling or seizures if unlucky, while bupivucaine causes cardiovascular collapse.

Obviously, an intravenous dose will have a peak concentration far higher than an epidural dose which is gradually absorbed into the plasma, for example.

 

[CopaceticOne]

But, that’s not near the toxic dose in any regards

That is my exact point.

 

[DM27]

As some people mentioned earlier, try your best to find the literature behind the toxic dosing guidelines because it is close to nonexistent. The studies are old and they do not describe the route and actual toxic dosing for anesthetics well at all. The numbers we go by are essentially dogma. Once you start trying to determine toxic doses for different routes (i.e. nerve block vs. topicalizing the airway) you can basically find, at best, general rules of thumb without any real evidence behind them (such as the ranking of absorption you posted).

 

[deleted171991]

As some people mentioned earlier, try your best to find the literature behind the toxic dosing guidelines because it is close to nonexistent. The studies are old and they do not describe the route and actual toxic dosing for anesthetics well at all. The numbers we go by are essentially dogma. Once you start trying to determine toxic doses for different routes (i.e. nerve block vs. topicalizing the airway) you can basically find, at best, general rules of thumb without any real evidence behind them (such as the ranking of absorption you posted).

So IV is clearly the fastest, and intratracheal has been proven during CPR. And anybody who has done an intercostal block with bupivacaine can attest that it wears off in less than 2 hours. Also we know that an epidural wears off faster than a spinal block. We see it all the time.

So a good part of the ranking of absorption one can see in real life, without any studies.

 

[facted]

The dose recommendations are indeed a bit of voodoo, and really unclear where it comes from. I've done quite a bit of searching, and also read that much of it comes from animal studies.

I think the dosing guidelines are fine any of the PNB or infiltration, but clearly nowhere near acceptable for IV use. Interestingly never mentioned, it appears that fascial plane blocks actually carry one of highest risks for LAST, likely secondary to increased surface area for local absorption. There are quite a few case reports about this. Don't go crazy with the local for your facial plane blocks (ie: stay within the recommended dose)

 

[drmwvr]

About 3 to 4 clinically useful LA's and modalities commonly at hand. 3 potential out comes: anesthesia (the most common), nothing (second most common), toxicity (very rare). Of these 3, the last (pun intended) is the most easily and readily recognizable.

At the end of the day, seizures or pulselessness means stop injecting and call for help.

Checklist for Treatment of Local Anesthetic Systemic Toxicity

 

[deleted59964]

peak [LA] at the tissue of interest is what determines toxicity to that tissue.
this is why very small amounts of local (eg. 1 mL of 0.5% bupivicaine) injected into the carotid (think CEA under local) will cause a seizure.

The numbers typically learnt are maximum safe doses. The context is important - ie. where is local going, and who is it going in ...

 

[Mman]

At the end of the day, seizures or pulselessness means stop injecting and call for help.

I think that's pretty easy for everybody to understand. The thing to always keep in the back of your mind is the potential delay between the injection and the toxicity. You could be 15-30 minutes after the block and then see the seizures or lack of pulse.

 

[kmurp]

I think that's pretty easy for everybody to understand. The thing to always keep in the back of your mind is the potential delay between the injection and the toxicity. You could be 15-30 minutes after the block and then see the seizures or lack of pulse.

I think I remember reading for a plexus block, that peak plasma concentrations are at around 30 minutes. That’s why block patients need to stay on monitor.

 

[Mman]

I think I remember reading for a plexus block, that peak plasma concentrations are at around 30 minutes. That’s why block patients need to stay on monitor.

I think it's extremely variable as to when peak plasma concentrations occur.