Teaching Points: Propofol and Lidocaine

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LostTommyGuns

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At my home institution there seems to be some debate regarding the use of Lidocaine before or combined with Propofol during induction. There seems to be general agreement that lidocaine (as well as Fentanyl) is used for blunting the sympathetic response and maintaining more steady pulse and blood pressures. The debate is whether to give Lidocaine mixed with Propofol or Lidocaine then propofol.

I am interested in hearing people's experiences and thoughts but particularly anything evidenced based. The article below was mentioned by a faculty member as one of the few pieces of evidence they were aware of and is for your enjoyment and discussion.

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Anaesth Intensive Care. 2004 Aug;32(4):482-4.
Preventing pain on injection of propofol: a comparison between lignocaine pre-treatment and lignocaine added to propofol.

A randomized double-blind study compared two methods of preventing the pain from injection of propofol, lignocaine pre-treatment followed by propofol and lignocaine added to propofol. One hundred patients received a 4 ml solution intravenously with a venous tourniquet for 1 minute, followed by propofol mixed with 2 ml of solution. Patients were divided into two treatment groups of 50 patients each: 4 ml 1% lignocaine pre-treatment followed by propofol and 2 ml saline, or 4 ml saline followed by propofol and 2 ml 2% lignocaine. Pain was assessed with a 100 mm visual analogue scale after induction and in recovery. The incidence of injection pain was 8% in the propofol mixed with lignocaine group, and 28% in the lignocaine pre-treatment group. This difference is statistically significant (P=0.017). For those patients who had pain, the mean pain score was 26.5 on induction for the propofol with lignocaine group (n =4), while the mean score was 44.4 for the pre-treatment group (n=13). The difference was not statistically significant (P=0.25). None of the propofol mixed with lignocaine group recalled pain, while 13 of the pre-treatment group did so. Lignocaine pre-treatment does not improve the immediate or the recalled comfort of patients during propofol induction when compared to lignocaine added to propofol. It is recommended that lignocaine should be added to propofol for induction rather than given before induction.

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curious to see the time between lidocaine injection and propofol injection?

i always give 80-100mg of 2% lido about 15 secs before I give the propofol induction dose. sometimes they complain of irritation, sometimes not. maybe i'll switch it up and premix it...

but if you think about it, premixing seems counterintuitive as we all know lidocaine takes some time to "set in" and work, right? so mixing it with the propofol theoretically should not have time to work to prevent injection discomfort. when using lido as a LA, we don't inject through a 14g angiocath as we're placing the IV? maybe lido is reducing the incidence of discomfort not by being a LA but rather changing the acid/base nature of the propofol - i don't remember offhand the pH of propofol

tomorrow, i'll try premixing....
 
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curious to see the time between lidocaine injection and propofol injection?

i always give 80-100mg of 2% lido about 15 secs before I give the propofol induction dose. sometimes they complain of irritation, sometimes not. maybe i'll switch it up and premix it...

but if you think about it, premixing seems counterintuitive as we all know lidocaine takes some time to "set in" and work, right? so mixing it with the propofol theoretically should not have time to work to prevent injection discomfort. when using lido as a LA, we don't inject through a 14g angiocath as we're placing the IV? maybe lido is reducing the incidence of discomfort not by being a LA but rather changing the acid/base nature of the propofol - i don't remember offhand the pH of propofol

tomorrow, i'll try premixing....

I always thought it was the benzyl alcohol in propofol that caused the irritation, not the pH. What do I know though, just trying to take all this info in.
 
microemulsion propofol, when available (someday), will put an end to all of this.
 
I could be wrong, but I thought only the generic propofol had benzyl alcohol, and Diprivan brand propofol had a different preservative (yet both are irritating when injected). I had one attending that instructed me to add NaHCO3 to my propofol, others that had me add lidocaine, and still others who prefer to inject 40-60 mg lidocaine a few seconds prior to propofol. Anecdotally, the last approach seems to be the most comfortable. I also believe I was once told that 40-60 mg of IV lidocaine may provide some laryngeal analgesia which may decrease stimulation from DL. Haven't noticed if this is meaningful or true.
 
I could be wrong, but I thought only the generic propofol had benzyl alcohol, and Diprivan brand propofol had a different preservative (yet both are irritating when injected). I had one attending that instructed me to add NaHCO3 to my propofol, others that had me add lidocaine, and still others who prefer to inject 40-60 mg lidocaine a few seconds prior to propofol. Anecdotally, the last approach seems to be the most comfortable. I also believe I was once told that 40-60 mg of IV lidocaine may provide some laryngeal analgesia which may decrease stimulation from DL. Haven't noticed if this is meaningful or true.

A little versed and it doesnt matter anyway.
 
I have always mixed 100 mg lido with 20 cc's propofol. I have found that pretreatment injection of lido has been less successful.

Blunting of airway reflexes is just a bonus.
 
Actually, the reason for mixing a few cc's of lidocaine into your propofol syringe is to drop the pH of the propofol, and thus decrease the burning sensation on injection. The veins are very sensitive to basic substances and less so to acidic substances. This was alluded to above. It's a common misconception that the lidocaine "numbs" the veins before injection.

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TIVA expresses what I have come to believe which is that it is a common misconception that lidocaine numbs the vein. When you look at the study that I posted you'll notice that pre-propofol injection lidocaine appeared to be less effective at removing pain, and when combined with the fact that they had a tourniquet on for a minute before giving the propofol it makes me think lidocaine is even more useless at numbing veins.

There have been a number of articles that compared long-chain propfol to medium-chain propofol to long-chain/medium-chain propofol (I don't know as much about this) and it appeared that there was a substantial difference in terms of discomfort upon injection. I expect that this is what VolatileAgent is talking about.
 
I had an attending who mixed 2-3 cc's of pentothal with 20 of propofol. He said it was a pH thing too.
 
fentanyl 250mcg about 2 minutes prior to injection seems to do the trick...:)
 
pH of propofol is 8 and change...

Package insert:

Propofol is very slightly soluble in water, and thus, forumulated in a white, oil-in-water emulsion. The pKa is 11. The octanol / water pertition coefficient for propofol is 6761:1 at a pH of 6-8.5.

The addition to to the active component, propofol, the formulation also contains soybean oil, glycerol, egg yolk phospholipid ad sodium metabisulfite, with sodium hyroxide to adujst pH. Propofol injectable emulsion is isotonic and has a pH of 4.5 - 6.6.
 
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pH of 4.5 - 6.6.[/U]

That's a 100 fold H+ concentration difference, why such variation?? From what i could find unbuffered lidocaine has a pH around 6.1 so it wouldn't change the pH of propofol if it's in the same range... :confused:
 
That's a 100 fold H+ concentration difference, why such variation?? From what i could find unbuffered lidocaine has a pH around 6.1 so it wouldn't change the pH of propofol if it's in the same range... :confused:


My guess is the mfg is playing it safe allowing for diffences in production (and perhaps minute concentration differences in the soybean oil, gylcerol, egg yolk, sodium metabisulfite, and sodium hydroxide) and also playing it safe with regards to legality...But I agree that you should expect a pharmaceutical company to be able to exert tighter control over an injected drug.

The trend here is pointing to the pH of propofol being basic (8 or so) and that is why lidocaine helps...by adjusting the pH. From the mfg, the pH is not basic. Now what?
 
cchoukal - I noticed today that our midazolam has benzyl alcohol in it, so I doubt that is the cause of the irritation.
 
Package insert:

Propofol is very slightly soluble in water, and thus, forumulated in a white, oil-in-water emulsion. The pKa is 11. The octanol / water pertition coefficient for propofol is 6761:1 at a pH of 6-8.5.

The addition to to the active component, propofol, the formulation also contains soybean oil, glycerol, egg yolk phospholipid ad sodium metabisulfite, with sodium hyroxide to adujst pH. Propofol injectable emulsion is isotonic and has a pH of 4.5 - 6.6.

This must be for Diprivan brand propofol, because the package for generic propofol lists pH adjusted to 7-8.5.
 
This must be for Diprivan brand propofol, because the package for generic propofol lists pH adjusted to 7-8.5.


I used the word propofol for a reason. I did not mean Diprivan. Baxter lists the pH of propofol as 4.5 - 6. Package insert for generic propofol link is listed below.

http://www.baxter.com/products/anesthesia/anesthetic_pharmaceuticals/downloads/propofol.pdf

However, it seems that trade product DIPRIVAN has a pH of 7.0-8.5.
http://www.diprivan.com/sedation/index.asp
http://www.astrazeneca-us.com/pi/diprivan.pdf

In looking at both Abbott for generic propofol and AstraZeneca for trade DIPRIVAN, both drugs contain:
propofol (1%), soybean oil (100mg/ml), glycerol (22.5 mg/ml), egg lecithin or egg yolk phospholipid (12 mg/ml) and both contain sodium hydroxide (amount not given) to "adjust for pH". We all know the generic has a bilsulfite, listed as sodium metabisulfite (0.25 mg/ml) and trade DIPRIVAN elected to use disodium edetate (EDTA) at a concentration of (0.005%). Perhaps it is the unknown concentration of sodium hydroxide that accounts for the pH difference. Neither drug insert listed the amount or concentration of the sodium hydroxide used in either preparation. The only other difference is the sodium metabisulfite vs EDTA in the recepies.
 
I had one attending (very ANA L) tell me that she mixed 50 mg (5 ml) of 1% lidocaine and 50 mg (5 ml) of propofol ina 10 cc syringe. She first injected this and then the remaining does of propofol(plain). She said that she heard it in a meeting .... somewhere....

Initially I thought that it was bogus because it just did not make sense. Still tried it about a year ago and sice then have never had any patient complain. It does not matter how small the vein is etc etc.... no pain during injection or recall of pain in PACU.

Again, I do not have answers regarding pH etc.... but this has really worked for me.

Let me know what you guys think
 
nobody really knows why it burns...

however in pediatric studies (where it matters a bit more), small doses of ephedrine or labetalol have been shown to decrease the burning sensation... interesting....

i used to dose ephedrine at 30mcg/kg and saw good results, and then all of a sudden 3 studies come out in the last year showing that ephedrine statistically doesn't make a difference...

bottom line
1) choose the biggest vein possible for your induction w/ propofol
2) pre-treat the pt w/ touch of fentanyl/midazolam
3) quick bier block w/ lidocaine (100mg injected while keeping the IV tourniquet tight (proximal to the angiocath tip)
4) push propofol

and odds are some patients will still bitch and moan...
 
The pH is not a factor (it is within physiologic limits & altering it does not change the pain).

Isotonicity is not related to pH at all & is a function of the osmotic pressure the solution exerts - propofol is isotonic.

The preservatives also are not the issue - changing them has not been shown to alter the irritation.

The studies have identified that propofol emulsion induces pain by multiple mechanisms. The lipid solvent activates the plasma kallikrein-kinin system & produces bradykinin. Propofol itself also does this, but to a lesser degree than the lipid solvent, possibly because the the weak negative charge of the solvent which is not present as much with propofol.

The bradykinin modifies the vein by vasodilating & allowing it to become hyperpermeable. This modification in the vein increases contact between the aqueous phase of propofol & the free nerve endings. Because propofol is a substituted phenol..it is irritating to all tissues - epidermis, mucous membranes & venous intema.

Lidocaine has been shown to inhibit bradykinin to a certain degree, but since the half life of bradykinin is so short (15 sec), studies have not been done to determine exactly if this is the mechanism for why lidocaine appears to help. Other work has been done to modify both the bradykinin production & lessening the ability of the aqueous propofol phase to contact the afferent nerve endings, but nothing has been shown yet to significantly make a change.

There have been a couple of studies on this - one reported in the British Journal of Anesthesia in 1999 & one in Japan, but I don't have that citation.
 
Props to LostTommyGuns for his Teaching Points series from this MS-4. :thumbup:

Noyacs' explanantion of the pain mechanism is excellent and the most thorough I've heard. It does make sense that a substituted phenol would be irritating to the tissues and that this irritation is the cause of the burning sensation. Noyac gives a tantalizing hint (inhibiting bradykinin locally) of the possible mechanism of Lido blocking the burning, but does anyone have more info/alt theory on this mechanism?
 
versed up front and nobody remembers that 2-10 second burn.

If you are truely worried about its impact on a patient's experience just put the IV (hopefully bigger than a 22g) proximal to the hand. No more burn.
 
Yeah - I realize that the versed pretty well keeps them from remembering it, I guess I brought it up more as a theoretical than to induce practice changes. :D

Vent: If you have an IV (larger than 22G and preferably without the cute little ER pigtails :rolleyes: ) proximal to the hand why do you get less burn? Bigger veins?
 
Props to LostTommyGuns for his Teaching Points series from this MS-4. :thumbup:

Noyacs' explanantion of the pain mechanism is excellent and the most thorough I've heard. It does make sense that a substituted phenol would be irritating to the tissues and that this irritation is the cause of the burning sensation. Noyac gives a tantalizing hint (inhibiting bradykinin locally) of the possible mechanism of Lido blocking the burning, but does anyone have more info/alt theory on this mechanism?

If you want more on lidocaine & bradykinin....in short, so far, we know that bradykinin induces activation of phospholipase D via the B2 receptors in neuronal cells. Most local anesthetics affect phospholipase C, protein tyrosine kinase & extracellular signal-regulated kinase, which are the molecules upstream of phospholipase D. Some potentiate some of the molecules...others depress them & they are different intracellularly & extracellularly.

Somehow...the local anesthetics depress bradykinin-induced signaling pathway or pathways - not sure how many there are...I don't think researchers know how many there are...

Researchers are attemping to understand the molecular mechanisms of how these drugs provide anesthesia & analalgesia by working out the pathways involved. But...there is still a lot unknown.

There is also work being done on how bradykinin is involved in vascular spasm associated with vascular surgery & the mechanism of how topical lidocaine affects this. Apparently - this is a completely different effect of bradykinin - the stimulation of basal endothelium-dependent platelet aggregation. Lidocaine itself failed to induce platelet aggregation, but it did inhibit bryadykinin-stimulated antiaggregation in a concentration-dependent manner.
 
Anyone want to comment on preventing pain with the injection of propofol? I've been using this drug for almost 20 years and I still can't say for certain that anything works well on a consistent basis.
 
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I can't think of a less interesting discussion than preventing pain upon injection of propofol. All you are doing with maneuvers like lidocaine or fentanyl is treating the OR nurses, and who gives a **** what they think. With midazolam on board, it really makes no difference. And the patients who I don't give midazolam to or underdose it (dialysis patients, some cranis, the very elderly) have been through enough that a little burning with propofol is nothing to them. I do remember what propofol feels like and there are much worse things.
 
I can't think of a less interesting discussion than preventing pain upon injection of propofol. All you are doing with maneuvers like lidocaine or fentanyl is treating the OR nurses, and who gives a **** what they think. With midazolam on board, it really makes no difference. And the patients who I don't give midazolam to or underdose it (dialysis patients, some cranis, the very elderly) have been through enough that a little burning with propofol is nothing to them. I do remember what propofol feels like and there are much worse things.

I think some of the Residents still are curious as to why some attendings do what they do before giving propofol.
 
OK.

I had one attending in residency who liked doing the things mentioned previously (mini-Bier block, big vein, etc) but he added his own twist. He liked to inject the propofol very slow. Like an induction dose over the course of a full 60-80 seconds. And he'd massage the vein that the IV was in while he was doing it. As I said, with most inductions, I couldn't care less, but every once in a while, I inject the propofol REALLY slow and gently pat their hand where I'm injecting.

Works every time. :laugh:
 
Not surprised. The package insert for propofol recommends 40mg q 10 seconds until induction. That's exactly how I give it in a non-RSI induction. I've found that giving it 40 mg at a time and letting the free flow IV run it in rarely causes any pain. I don't think lido or massaging the vein does much.
 
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I don't think I've ever seen pain on injection of propofol when I've mixed in lidocaine 5mg/ml to the propofol, regardless of the injection site.

I've seen plenty of pain with bolusing of propofol proximal to the hand.
 
Anyone want to comment on preventing pain with the injection of propofol? I've been using this drug for almost 20 years and I still can't say for certain that anything works well on a consistent basis.

Propofol bier blocks are uncomfortable, make sure the BP cuff isn't up on the arm with the IV. :)
 
i have a very soothing voice which I frequently use during induction. i also give lidocaine with my inductions, because I believe it has some effects as a general anesthetic.
 
Not surprised. The package insert for propofol recommends 40mg q 10 seconds until induction. That's exactly how I give it in a non-RSI induction. I've found that giving it 40 mg at a time and letting the free flow IV run it in rarely causes any pain. I don't think lido or massaging the vein does much.

I find this difficult to do on busy days and/or when the surgeon is in the room ready to pounce after induction.
 
I find this difficult to do on busy days and/or when the surgeon is in the room ready to pounce after induction.

I pretty much do the same thing proman does. Inject my induction over maybe 30-45 seconds. You can save that time somewhere else, unless you are already practicing like the Road Runner.

If the surgeon is bugging, push it fast in a small vein on a little old lady, watch her complain for 30 seconds, and tell him that's why you inject slowly. Because you're there for patient comfort.
 
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I find this difficult to do on busy days and/or when the surgeon is in the room ready to pounce after induction.

That means it's time to slow down even more. :smuggrin:
 
On healthy folks. 5cc propofol and 5cc 2% lido while moving to OR table. Place and cycle BP cuff. Place SpO2 and ECG. Preox PRN. 10-15cc propofol +/- NMB. Airway.

Adjust downward based on age/ health.

No sting in 97% of patients. 2% experience sting only with the full strength propofol but don't remember it. 1% or less have mild stinging with the first dose. 5 min door to done.

- pod
 
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On healthy folks. 5cc propofol and 5cc 2% lido while moving to OR table. Place and cycle BP cuff. Place SpO2 and ECG. Preox PRN. 10-15cc propofol +/- NMB. Airway.

Adjust downward based on age/ health.

No sting in 97% of patients. 2% experience sting only with the full strength propofol but don't remember it. 1% or less have mild stinging with the first dose. 5 min door to done.

- pod

8% sevo for 2 minutes prior to propofol = 100% effective. JK
Actually I sometimes give N2O and switch to 100% O2 just before injecting propofol. Seems to help and etO2 is plenty high when they stop SV. I don't do it with concern for difficult mask though.
 
With an adequate mini Bier Block it really shouldn't matter if it is 2% lidocaine or 0.5% lidocaine.
 
Draw up 40mg lido in 200mg PPF. I tell the pt you might feel a warm feeling in your IV, it may even sting. If it hurts, I push and flush faster.
 
I can't think of a less interesting discussion than preventing pain upon injection of propofol. All you are doing with maneuvers like lidocaine or fentanyl is treating the OR nurses, and who gives a **** what they think. With midazolam on board, it really makes no difference. And the patients who I don't give midazolam to or underdose it (dialysis patients, some cranis, the very elderly) have been through enough that a little burning with propofol is nothing to them. I do remember what propofol feels like and there are much worse things.
Propofol with or without lidocaine is all I generally give anyone in the endo suite - never versed. No burn is always better. Premixed lido seems better than no lido. Based on above comments I am going to start paying attention to whether or not I am using diprivan or propofol...
 
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I like to give lidocaine 1-1.5 mg/kg in order to blunt the laryngeal response.
 
Anyone want to comment on preventing pain with the injection of propofol? I've been using this drug for almost 20 years and I still can't say for certain that anything works well on a consistent basis.

because it does not.
 
because it does not.

Well i disagree completely.
Just the other day a friend of my who went under told me how horrible the pain was from the propofol and he's not the type to complain much.

If it's too much to ask to put 2cc of lido in the propofol stick then you're one lazy MF. Personally i hate it when the patient starts to wiggle on the table from the propofol pain not very smooth looking either.
 
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