Lipid Therapy

[Praziquantel86]

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Hello everyone,

I recently had a question pop up regarding lipid use after accidental overdose of a local anesthetic, and I was hoping someone on this forum might be able to provide some info.

I was only able to find a very few cases regarding its successful use, mostly in animal models. I know it would be a decently rare scenario to have to use it, but does anyone here have any experience or heard of it being used?

Thanks for any responses!

 

[xjohns1]

lipidrescue.org

 

[Impromptu]

The aforementioned website is really the best collection of information. Lexi comp's toxicology program also recommends it for use following their same prescribed protocol.

I first heard about it during my interview at UIC. They consider it standard of care and believe it will be spreading throughout the United States, while right now it is mostly used in England right now.

I wanted to do a little presentation on it during my derm rotation, but they rarely use enough anesthetic to cause a problem that would require it's usage, maybe in babies or if there was some sort of titration error. I ended up broadening my presentation to encompass local anesthetic systemic toxicities. Anesthesiologists are the ones who would most likely need to use it.

The basic mechanism is simple enough. Local anesthetics are amphipathic, so a 20% lipid (2X what propofol comes in) infusion will provide a medium in the blood that absorbs the anesthetic, removing enough of it from sensitive areas (heart) that the levels left aren't above the toxic threshold.

 

[Bertelman]

There's an article in this month's Anesthesiology.

 

[Impromptu]

You're right, page 380 of February's journal. Intra-lipid appears to be the superior lipid emulsion,

 

[aphistis]

The aforementioned website is really the best collection of information. Lexi comp's toxicology program also recommends it for use following their same prescribed protocol.

I first heard about it during my interview at UIC. They consider it standard of care and believe it will be spreading throughout the United States, while right now it is mostly used in England right now.

I wanted to do a little presentation on it during my derm rotation, but they rarely use enough anesthetic to cause a problem that would require it's usage, maybe in babies or if there was some sort of titration error. I ended up broadening my presentation to encompass local anesthetic systemic toxicities. Anesthesiologists are the ones who would most likely need to use it.

The basic mechanism is simple enough. Local anesthetics are amphipathic, so a 20% lipid (2X what propofol comes in) infusion will provide a medium in the blood that absorbs the anesthetic, removing enough of it from sensitive areas (heart) that the levels left aren't above the toxic threshold.

A 20% solution of Intralipid is 20x the concentration of 1% propofol, not 2x.

 

[BLADEMDA]

The aforementioned website is really the best collection of information. Lexi comp's toxicology program also recommends it for use following their same prescribed protocol.

I first heard about it during my interview at UIC. They consider it standard of care and believe it will be spreading throughout the United States, while right now it is mostly used in England right now.

I wanted to do a little presentation on it during my derm rotation, but they rarely use enough anesthetic to cause a problem that would require it's usage, maybe in babies or if there was some sort of titration error. I ended up broadening my presentation to encompass local anesthetic systemic toxicities. Anesthesiologists are the ones who would most likely need to use it.

The basic mechanism is simple enough. Local anesthetics are amphipathic, so a 20% lipid (2X what propofol comes in) infusion will provide a medium in the blood that absorbs the anesthetic, removing enough of it from sensitive areas (heart) that the levels left aren't above the toxic threshold.

Many now conisider it the standard of care in the USA as well. The recommendation is to keep a $10 bottle of lipid in all locations where regional blocks are perfomed.

 

[Impromptu]

A 20% solution of Intralipid is 20x the concentration of 1% propofol, not 2x.

I was referring to the 10% lipid emulsion (soybean oil) that 1% propofol comes in, not that actual propofol. Thank you for letting me clarify.

Since most anesthesiologists have propofol readily at hand, there have been questions whether it would work just as well as intralipid, but the recommendations are that the lipid needs to be at least 20%, 2X the lipid concentration in propofol.

 

[BLADEMDA]

I was referring to the 10% lipid emulsion (soybean oil) that 1% propofol comes in, not that actual propofol. Thank you for letting me clarify.

Since most anesthesiologists have propofol readily at hand, there have been questions whether it would work just as well as intralipid, but the recommendations are that the lipid needs to be at least 20%, 2X the lipid concentration in propofol.

No. Propofol is the wrong drug for local anesthetic related cardiac arrest. Propofol is a cardiac depressant and should be avoided in this situation.
Is it better than "nothing" if that is all you have on hand? debatable.

 

[jwk]

No. Propofol is the wrong drug for local anesthetic related cardiac arrest. Propofol is a cardiac depressant and should be avoided in this situation.
Is it better than "nothing" if that is all you have on hand? debatable.

I think you're correct - it's NOT better than nothing. As already mentioned, every location should have it on hand. It's cheap and it works. We keep a bottle on every crash cart and every block cart.

 

[Praziquantel86]

Thanks for all the responses, it's definitely a good thing to be aware of.

It would be interesting to see if patients who are on high-lipid TPN would require higher than normal dosages to achieve the correct pharmacological response.

 

[nutmegs]

I don't remember the exact numbers, but the amount of propofol needed to a achieve the same amout of lipid is huge and would cause hemodynamic collapse in and of itself. There is no way to justfiy "I gave this coding patient propofol for the lipid". Don't do it.

 

[Gern Blansten]

Thanks for all the responses, it's definitely a good thing to be aware of.

It would be interesting to see if patients who are on high-lipid TPN would require higher than normal dosages to achieve the correct pharmacological response.

I suspect that if you ever had the occasion to do a nerve block on a patient on TPN, you would probably have to give a big whopping intravascular dose to get symptoms of toxicity.

 

[jwk]

I suspect that if you ever had the occasion to do a nerve block on a patient on TPN, you would probably have to give a big whopping intravascular dose to get symptoms of toxicity.

Why? Patients on TPN are getting their lipids at a slow infusion rate, not a whopping bolus all at one time.

 

[BADMD]

It would be interesting to see if patients who are on high-lipid TPN would require higher than normal dosages to achieve the correct pharmacological response.

There is a case report of a child on IV phenytoin and higher dose lipid who required significantly higher doses to maintain therapeutic levels. The report is extremely short and goes into a rat experiment to demonstrate the effect.

Staathof, DJ et al. "Influence of Intralipid Infusion on the Elimination of Phenytoin" Arch. Int. Pharmacodyn. 267, 180-186 (1984)

 

[Gern Blansten]

Why? Patients on TPN are getting their lipids at a slow infusion rate, not a whopping bolus all at one time.

http://www.ncbi.nlm.nih.gov/pubmed/9579517?ordinalpos=19&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 

[dfk]

There is a case report of a child on IV phenytoin and higher dose lipid who required significantly higher doses to maintain therapeutic levels. The report is extremely short and goes into a rat experiment to demonstrate the effect.

Staathof, DJ et al. "Influence of Intralipid Infusion on the Elimination of Phenytoin" Arch. Int. Pharmacodyn. 267, 180-186 (1984)

wouldn't this be b/c of the P450 induction/metabolism?

 

[BADMD]

wouldn't this be b/c of the P450 induction/metabolism?

I don't believe that lipid is a significant inducer of 2C9/19. Phenytoin exhibits Michalis-Menten kinetics. It would take a massive amount of induction to support a doubling of its dose.

The rat portion of the study definitely suggested that a significant amount of the drug was bound to liposomes. They have to go on and theorize how the phenytoin is cleared with the liposomes, however. There were some technical issues with their experiment and they had to repeat things to get over some problems.

Basically, the lipid sink theory is a more plausible mechanism.

 

[Impromptu]

Local anesthetic systemic toxicity comes in two main forms, CNS and cardiovascular. The seizures typically happen at lower dosages. From what I've been reading, one should avoid the use of phenytoin in treating those seizures, because it shares a similar mechanism with lidocaine, sodium channel blocker, and may potentiate its effects.

 

[Impromptu]

If a pre-infusion of lipids will lower the rate of cardio or CNS toxicity, maybe we should just give everyone a couple of Whoppers from Burger King before they have their regional blockade. Hardees/Carl's Jr has some monstrous burgers that might even turn their blood white, leaving no chance for any toxic levels to build up.

 

[Praziquantel86]

There is a case report of a child on IV phenytoin and higher dose lipid who required significantly higher doses to maintain therapeutic levels. The report is extremely short and goes into a rat experiment to demonstrate the effect.

Staathof, DJ et al. "Influence of Intralipid Infusion on the Elimination of Phenytoin" Arch. Int. Pharmacodyn. 267, 180-186 (1984)

I'm not able to access anything other than the abstract, does it mention a reason as to why the dosage was sub-therapeutic? If it is due to a significantly increased volume of distribution, it seems like the interaction would be something to look out for across all highly lipophilic drugs.

 

[BLADEMDA]

If a pre-infusion of lipids will lower the rate of cardio or CNS toxicity, maybe we should just give everyone a couple of Whoppers from Burger King before they have their regional blockade. Hardees/Carl's Jr has some monstrous burgers that might even turn their blood white, leaving no chance for any toxic levels to build up.

Aspiration Pnuemonia.

 

[BADMD]

I'm not able to access anything other than the abstract, does it mention a reason as to why the dosage was sub-therapeutic? If it is due to a significantly increased volume of distribution, it seems like the interaction would be something to look out for across all highly lipophilic drugs.

They did get a larger Vd, but they found that in both the lipid and control groups (in rats). They also had technical issues that leaves this part of the experiment somewhat questionable as they had to rely on a second set of testing when the first failed (recovering more than they put in F.ex). The only really consistent data they got was that phenytoin was more avidly contained in liposomes.

The human case report itself is ridiculously short and serves more as an intro to the rat experiment. Not a lot of data is given: 11 years old, 300 mg IV phenytoin q12, 8.7 ml/hr*21 hours/day of 20% lipid. All that is clear is that they had to give a very large amount of phenytoin once they started the patient on intralipid. So yes, I'd be concerned about using any lipophilic drug in a patient on a large infusion of lipid.

 

[BADMD]

Local anesthetic systemic toxicity comes in two main forms, CNS and cardiovascular. The seizures typically happen at lower dosages. From what I've been reading, one should avoid the use of phenytoin in treating those seizures, because it shares a similar mechanism with lidocaine, sodium channel blocker, and may potentiate its effects.

You should never use phenytoin to treat a toxic seizure. Phenytoin helps suppress propagation from an irritable focus. It does a very poor job putting the breaks on a generally irritable brain. Our neuro guys are recommending against giving it in status from non-toxic causes as well.

 

[Praziquantel86]

They did get a larger Vd, but they found that in both the lipid and control groups (in rats). They also had technical issues that leaves this part of the experiment somewhat questionable as they had to rely on a second set of testing when the first failed (recovering more than they put in F.ex). The only really consistent data they got was that phenytoin was more avidly contained in liposomes.

The human case report itself is ridiculously short and serves more as an intro to the rat experiment. Not a lot of data is given: 11 years old, 300 mg IV phenytoin q12, 8.7 ml/hr*21 hours/day of 20% lipid. All that is clear is that they had to give a very large amount of phenytoin once they started the patient on intralipid. So yes, I'd be concerned about using any lipophilic drug in a patient on a large infusion of lipid.

Thanks for the info, shame the case wasn't more detailed. This seems like something that might pop up from time to time, so it's definitely good to be aware of.

 

[ncdoc1974]

I don't remember the exact numbers, but the amount of propofol needed to a achieve the same amout of lipid is huge and would cause hemodynamic collapse in and of itself. There is no way to justfiy "I gave this coding patient propofol for the lipid". Don't do it.

I agree...
We do keep a bottle of intralipid on all regional block carts. I would recommend that anyone doing blocks or OB do the same...I hope to read as few case reports as possible! Use epi for PNBs & inject slowly...recognize an intravascular injection before you have the need to see if the intralipid really works or not!