Potency of Propofol with Lidocaine

[PCSOM]

Does anyone know by how much the potency of Propofol (200mg) is decreased if it is mixed with 2% Lidocaine (60mL) and is administered?

I know for sure that the potency is decreased if premixed, due to pH alteration.

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[Planktonmd]

Does anyone know by how much the potency of Propofol (200mg) is decreased if it is mixed with 2% Lidocaine (60mL) and is administered?

I know for sure that the potency is decreased if premixed, due to pH alteration.

did you say that you want to mix Propofol 200 mg with 60 cc of Lidocaine 2 %????
Why would you do something like that?

 

[UTSouthwestern]

Does anyone know by how much the potency of Propofol (200mg) is decreased if it is mixed with 2% Lidocaine (60mL) and is administered?

I know for sure that the potency is decreased if premixed, due to pH alteration.

With that mixture, I'd say dilution is the biggest factor decreasing the potency.

Did you really intend to give 1200 mg of lidocaine with 200 mg of propofol?

 

[Mman]

I'm assuming that the question refers to mixing 3 ml of 2% lidocaine (60 mg) with 200 mg of Propofol. I'm not sure of the answer as to what that does to the potency of the propofol.

 

[VentdependenT]

With that mixture, I'd say dilution is the biggest factor decreasing the potency.

Did you really intend to give 1200 mg of lidocaine with 200 mg of propofol?

Why not just infuse interlipid in the other arm at the same time.

 

[PCSOM]

I'm assuming that the question refers to mixing 3 ml of 2% lidocaine (60 mg) with 200 mg of Propofol. I'm not sure of the answer as to what that does to the potency of the propofol.

Yes, I am talking about mixing 3cc (20mg/mL) of Lidocain with 20cc (10mg/mL) of Propofol. Sorry for the confusion.

Well, I just want to find out by how much Propofol efficay is decreased when mixed with Lidocaine in the same syringe? I hope this will clear some confusion by me. For example, 1cc (20mg/mL) of Lidocain would decrease Propofol efficacy by ________mg/mL or by _______%?

 

[UTSouthwestern]

Yes, I am talking about mixing 3cc (20mg/mL) of Lidocain with 20cc (10mg/mL) of Propofol. Sorry for the confusion.

Well, I just want to find out by how much Propofol efficay is decreased when mixed with Lidocaine in the same syringe? I hope this will clear some confusion by me. For example, 1cc (20mg/mL) of Lidocain would decrease Propofol efficacy by ________mg/mL or by _______%?

I believe that the only study I have heard of addressing this issue was in the laboratory with rats.

The proposed hypothesis was that the presence of lidocaine causing lower pH altered the concentration of the total amount of propofol present in the aqueous phase of the emulsion of propofol, effectively reducing pain on injection caused by propofol.

The study did validate an increased amount of propofol required to induce anesthesia when compared to rats receiving lidocaine and propofol as separate injections, without elucidating a clear mechanism for this finding.

This study says the above study is not accurate, therefore this is an ongoing argument.

http://www.anesthesia-analgesia.org/cgi/content/full/97/2/461

 

[sdn1977]

Yes, I am talking about mixing 3cc (20mg/mL) of Lidocain with 20cc (10mg/mL) of Propofol. Sorry for the confusion.

Well, I just want to find out by how much Propofol efficay is decreased when mixed with Lidocaine in the same syringe? I hope this will clear some confusion by me. For example, 1cc (20mg/mL) of Lidocain would decrease Propofol efficacy by ________mg/mL or by _______%?

UT really gave you the best study looking at this to date.

The issue really is not so much the pH - it has more to do with the stability of the emulsion. The only way the propofol is active is when it is infused in a form in which it can be active. It is a lipophillic substance. When you mix it with a hydrophillic substance, it is not so much a situation of pH difference - rather a situation of altering or "breaking" the emulsion which then presents the drug in a form in which it cannot be effective. I could look & find out what volume of a hydrophillic substance will dilute the propofol to break the emulsion if you want.

This same issue occurs when we infuse diazepam infusions (which are solubilized in propylene glycol). If you decrease the propylene glycol concentration, the active drug - diazepam precipates out & the infusion becomes ineffective.

This is why we infuse Intralipid in an alternate site - as VentDependent suggested. I'm not sure exactly why or how you're using the lidocaine, but you could push the lidocaine, flush then run your propofol.

Or, alternatively, you could use a dual lumen lumen (or better yet!) a triple lumen catheter.

 

[tussionex]

UT really gave you the best study looking at this to date.

Or, alternatively, you could use a dual lumen lumen (or better yet!) a triple lumen catheter.

i second that. triple lumen.

i dont like mixing things with lipid-based formulations; the opacity can prevent easy visualization of precipitates.

 

[PCSOM]

I believe that the only study I have heard of addressing this issue was in the laboratory with rats.

The proposed hypothesis was that the presence of lidocaine causing lower pH altered the concentration of the total amount of propofol present in the aqueous phase of the emulsion of propofol, effectively reducing pain on injection caused by propofol.

The study did validate an increased amount of propofol required to induce anesthesia when compared to rats receiving lidocaine and propofol as separate injections, without elucidating a clear mechanism for this finding.

This study says the above study is not accurate, therefore this is an ongoing argument.

http://www.anesthesia-analgesia.org/cgi/content/full/97/2/461

Thank you for your responce back. I did happen to read both of these articles (one about the rats and the other one you have posted) but I never found out the anwer to my questions. I had infused Lido with Propo the other day and my attending did not like that mix. So, I was pimped to find out. After spending a good significant time into this, I was unable to find so I thought that I try here and see any of you experts can help me out.

 

[sdn1977]

Thank you for your responce back. I did happen to read both of these articles (one about the rats and the other one you have posted) but I never found out the anwer to my questions. I had infused Lido with Propo the other day and my attending did not like that mix. So, I was pimped to find out. After spending a good significant time into this, I was unable to find so I thought that I try here and see any of you experts can help me out.

The "rule of thumb" is - don't dilute an emulsion (something that is solubilized in anything other than a hydrophillic base.)

The best case is you will have decreased effectiveness. The worst case, is you can get deposition of unsolublized drug in places you don't want (lungs, carotids, etc...)

But...as UT pointed out - there are is continuing work on stuff like this.

Good luck!

 

[UTSouthwestern]

The "rule of thumb" is - don't dilute an emulsion (something that is solubilized in anything other than a hydrophillic base.)

The best case is you will have decreased effectiveness. The worst case, is you can get deposition of unsolublized drug in places you don't want (lungs, carotids, etc...)

But...as UT pointed out - there are is continuing work on stuff like this.

Good luck!

I'm suprised that there hasn't been a formulation created with a precise or tolerable amount of local anesthetic built into the formulation. Given the frequency of use of propofol, it would definitely be a profitable endeavor, although it may not be feasible with the pharmacodynamic profile of propofol. Then again, a tolerable amount in the formulation may do absolutely nothing to decrease pain on injection so the makers may just leave it up to us to inject a little local just prior to injecting the propofol.

I remember in 2003 at Southwestern, we were testing Ampofol, a propofol preparation with less lipid concentration designed to minimize the impact an infusion of propofol could have on triglyceride levels, microbial contamination, etc. Unfortunately, it caused MORE pain on injection than any of the currently utilized propofol formulations:

http://www.asaabstracts.com/strands...944805A946114D4?year=2003&index=2&absnum=1000

 

[jwk]

The "rule of thumb" is - don't dilute an emulsion (something that is solubilized in anything other than a hydrophillic base.)

The best case is you will have decreased effectiveness. The worst case, is you can get deposition of unsolublized drug in places you don't want (lungs, carotids, etc...)

But...as UT pointed out - there are is continuing work on stuff like this.

Good luck!

I think the rule of thumb is don't mix propofol with anything, lidocaine or otherwise.

Mixing lidocaine with propofol has a negligible effect on the pain of injection. Giving lidocaine prior to injection of propofol doesn't seem to help much either. Using a larger and faster flowing IV catheter in a vein that's NOT in the back of the hand goes a long way towards easing that pain.

 

[Intubate]

I think the rule of thumb is don't mix propofol with anything, lidocaine or otherwise.

Mixing lidocaine with propofol has a negligible effect on the pain of injection. Giving lidocaine prior to injection of propofol doesn't seem to help much either. Using a larger and faster flowing IV catheter in a vein that's NOT in the back of the hand goes a long way towards easing that pain.

I agree... Placing a tourniquet prior to giving lidocaine (a mini bier block) is effective, but a pain in the ass.

 

[leaverus]

I've never really understood the practice of administering lido w/ propofol induction. IMO, it doesn't seem to work for decreasing the pain of injection. In any case, although we should try to minimize the patients discomfort as much as possible, i don't see the point since the burning stops as soon as the patient is asleep and they won't remember it anyway.

 

[sensoricaine]

I'm suprised that there hasn't been a formulation created with a precise or tolerable amount of local anesthetic built into the formulation. Given the frequency of use of propofol, it would definitely be a profitable endeavor, although it may not be feasible with the pharmacodynamic profile of propofol. Then again, a tolerable amount in the formulation may do absolutely nothing to decrease pain on injection so the makers may just leave it up to us to inject a little local just prior to injecting the propofol.

I remember in 2003 at Southwestern, we were testing Ampofol, a propofol preparation with less lipid concentration designed to minimize the impact an infusion of propofol could have on triglyceride levels, microbial contamination, etc. Unfortunately, it caused MORE pain on injection than any of the currently utilized propofol formulations:

http://www.asaabstracts.com/strands...944805A946114D4?year=2003&index=2&absnum=1000

we touched on this very briefly at grand rounds two weeks ago, ie Propofol + lidocaine mixture: conc. of propofol decreases linearly (after 30 mins) and that this is a time-dependent effect. Also an unstable emulsification at least on a microscopic level..

check out http://www.anesthesia-analgesia.org/cgi/content/full/90/4/989

perhaps this is the relationship the OP's attending was trying to get at?

 

[Fastrach]

I've never really understood the practice of administering lido w/ propofol induction. IMO, it doesn't seem to work for decreasing the pain of injection. In any case, although we should try to minimize the patients discomfort as much as possible, i don't see the point since the burning stops as soon as the patient is asleep and they won't remember it anyway.

The IV Lido is to decrease airway reactivity. The bit about it being given to help with the burning is BS.

 

[leaverus]

The IV Lido is to decrease airway reactivity. The bit about it being given to help with the burning is BS.

That's what the NMB is for, so why do we still need the lido?

 

[huktonfonix]

I disagree. lido given before propofol can decrease pain on injection if done correctly. You can use a tourniquet or inject some lido, use your finger to block the vein proximally for a bit, then give propofol. I usually only do this for MACs that are complaining of burning with propofol and it almost always stops the burning.

 

[PCSOM]

we touched on this very briefly at grand rounds two weeks ago, ie Propofol + lidocaine mixture: conc. of propofol decreases linearly (after 30 mins) and that this is a time-dependent effect. Also an unstable emulsification at least on a microscopic level..

check out http://www.anesthesia-analgesia.org/cgi/content/full/90/4/989

perhaps this is the relationship the OP's attending was trying to get at?

WOW! Thanks, it is a fantastic study. I see that in the first hour or so, according to the graph, propofol concentration is deceased by almost 3% or more. I know many CRNAs at my place (and pretty sure at other places too) mix this combo an hour or may be more before the next case. I mean, propofol to begin with is not as potent as Diprivan and now mixing it does change the [ ] significantly. Great study to share.

 

[PCSOM]

That's what the NMB is for, so why do we still need the lido?

how about LMA cases? Do you use NMB? studies do show that using lidocain prior to propofol does decrease pain/burning sensation in patients. i mean cm'on, it's a local anesthetic and if you use in a significant amount, (i usually use 3mL 2% Lido) then it should do what it is suppose to do - decrease pain/burning sensation.

 

[Fastrach]

how about LMA cases? Do you use NMB? studies do show that using lidocain prior to propofol does decrease pain/burning sensation in patients. i mean cm'on, it's a local anesthetic and if you use in a significant amount, (i usually use 3mL 2% Lido) then it should do what it is suppose to do - decrease pain/burning sensation.

Clarification: I agree it decreases burning when added to the Propofol in advance, as mentioned before, like you might do in a MAC case. But I've found it is NOT helpful for this purpose when given separately from and immediately before the Propofol; its primary purpose, as I said earlier, is for reducing airway reactivity.

 

[milrisome]

I can see four possible reasons for giving IV lidocaine prior to induction:
1) Reduce pain of propofol injection. I don't see how mixing it with the propofol helps, last time I checked lidocaine takes some time to take effect. It doesn't work immedately. I'm sure we've all had the experience of giving a local for an IV or block and then starting 5 seconds later, the patient says ouch. So I can't see mixing it unless there's something about it other than numbing the vein.

2) reduce hemodynamic effects of intubation. No reasons to mix it here. Should work just as well separately. Not sure this works anyway, at least in a couple of studies I found. Fentanyl works better if you give it enough time, and they probably won't complain about the burning if the fentanyl has taken effect.

3) reduce arrhythmias with intubation. Shown in one study I found. Again, giving it separately should be fine.

4) Reduce airway irratability. No reason to mix it here.

Bottom line, I don't see how mixing the lidocaine in the propofol is helpful. And it comes with possible problems like reduction of efficacy or molecular changes. I'd rather stay away from that type of unknown.

 

[dhb]

1) I find that lidocaine does make a difference when mixed with propofol: i rarely have patients complaining
2) Lidocaine doesn't numb the vein it acts by inhibiting the kinin pathway that is activated by propofol

Here's a thread that already dealt with the issue:
http://forums.studentdoctor.net/showthread.php?t=314396

 

[Mman]

Some attendings I work with swear by mixing in 3 ml of lidocaine with a 20 ml syringe of propofol and I will admit that the patients seem to complain a lot less about burning. Purely anecdotal, but it seems like a pretty strong effect.

 

[Noyac]

So what happens to drugs like fentanyl when mixed with propofol? Any ideas?

SDN?

 

[joncmarkley]

I see a lot of people at work using 2% lido w preservative (multidose vial) with the propofol.

I think this is inappropriate and I use preservative free....any insight to this issue (ie can the multidose be give iv?)

 

[loveumms]

I can see four possible reasons for giving IV lidocaine prior to induction:
1) Reduce pain of propofol injection. I don't see how mixing it with the propofol helps, last time I checked lidocaine takes some time to take effect. It doesn't work immedately. I'm sure we've all had the experience of giving a local for an IV or block and then starting 5 seconds later, the patient says ouch. So I can't see mixing it unless there's something about it other than numbing the vein.

I was under the assumption that lidocaine didn't actually anesthetize the vein but, actually changed the pH of the propofol to decrease the pain on injection.

 

[Noyac]

I see a lot of people at work using 2% lido w preservative (multidose vial) with the propofol.

I think this is inappropriate and I use preservative free....any insight to this issue (ie can the multidose be give iv?)

What exactly is inappropriate?

 

[huktonfonix]

It would be inappropriate if going neuraxial........hmmm propofol in the epidural space.....

 

[milrisome]

1) I find that lidocaine does make a difference when mixed with propofol: i rarely have patients complaining
2) Lidocaine doesn't numb the vein it acts by inhibiting the kinin pathway that is activated by propofol

Here's a thread that already dealt with the issue:
http://forums.studentdoctor.net/showthread.php?t=314396

Thanks, that's very helpful. Nice explanation of why propofol hurts and how lidocaine prevents it.

I must admit to laboring under the false impression that the reason for giving the lidocaine was to anesthetize the vein. And I specifically remember one of my attendings telling me so.

 

[PCSOM]

I was under the assumption that lidocaine didn't actually anesthetize the vein but, actually changed the pH of the propofol to decrease the pain on injection.

i was under the impression that lidocain actually anesthetizes the vein b/c lidocain mixed with propofol (pH 4.5 – 6.4 and for Diprivan pH 7 – 8.5)
decreases the pH further hence making it more acidotic. any suggestions???

 

[OldManDave]

I've never really understood the practice of administering lido w/ propofol induction. IMO, it doesn't seem to work for decreasing the pain of injection. In any case, although we should try to minimize the patients discomfort as much as possible, i don't see the point since the burning stops as soon as the patient is asleep and they won't remember it anyway.

Easy solution - give them sufficient benzos such that they do not remember the propofol burning them!

 

[milrisome]

Easy solution - give them sufficient benzos such that they do not remember the propofol burning them!

Or enough narcs that they don't notice the burn!

 

[Kaptain Krunch]

I just give propofol straight. Does this make me a bad person? If so, at least the lidocaine will take the feeling away.