Last week I used IFE (not for local anesthetic toxicity) after other measures failed. I was stuck scrambling for a dose and ended up taking an example protocol from a reputable website.

Since anesthesiologist are most likely to have thought this out, I'm curious what dose and dosing schedule you all use. Is there any provision for a second dose if there is a temporary response to first dose? Ceiling dose?

Thanks.

I think lipidrescue.org is pretty much the authority for this. They recommend the following:

20% Intralipid:

1.5 mL/kg as an initial bolus, followed by

0.25 mL/kg/min for 30-60 minutes

Bolus could be repeated 1-2 times for persistent asystole

Infusion rate could be increased if the BP declines.


This is the exact protocol we use at our institution.

I think lipidrescue.org is pretty much the authority for this. They recommend the following:

Lipidrescue is where I found the sample dosing. They don't actually "recommend" that dose as use it as an example protocol. The two human case reports used different dosing, so they kind of came up with a middle ground.

I know I was being deliberately vague, but here is the problem I ran into. The first dose/infusion of lipid pulled the guy out of shock: bp increased and he started having urine output. About 12 hours later he declines and is shocky again. He gets another round and it worked, but the effect diminished when the infusion stopped and he slid downhill until ~4 hours post infusion when he was clinically back in shock. He had received about 2.4 liters of lipid at this point in less than 24 hours.

A discussion ensued about restarting lipid and how, versus other interventions.

Thus I am curious what other hospitals have decided upon for their protocols. I know I'm in uncharted territory (and the discussion is mostly academic at this point). As a note, I'm already starting to write the case report.

Any thoughts, or does everyone pretty much follow the Lipidrescue sample dosing.

A total maximum of 8cc/kg is recommended. (www.lipidrescue.org)

I think the 8 ml/kg ceiling is pretty much made up. The only place I can find that mention is on a "sample label" included to guide making up a kit.

It will be interesting to see if this dosing and ceiling become standard, even though the authors state that they basically pulled the dosing out of air.

What was the cause of the shock state? What were you treating? You said it was not local toxicity.

I am not aware of any indication for lipids to treat shock other than the specific situation of asystole caused by local anesthetic toxicity.
Could you educate us please?

What was the cause of the shock state? What were you treating? You said it was not local toxicity.

Verapamil OD. There have been a couple of studies in animals. He was already on multiple pressors, calcium, and high dose insulin along with a pacer, without improvement. This was a large topic of discussion at the North American Congress of Clinical Toxicology meeting a few weeks ago.

Verapamil OD. There have been a couple of studies in animals. He was already on multiple pressors, calcium, and high dose insulin along with a pacer, without improvement. This was a large topic of discussion at the North American Congress of Clinical Toxicology meeting a few weeks ago.
Interesting.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17766009&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum

Plus, animal studies have shown success with treatment of TCA and Ca++ channel blocker overdose.

The above case report with bupropion and lamotrigine is pretty darned impressive. She was down for 70 minutes while they scrambled with standard ACLS and eventually tried intralipid with very quick results and full recovery. No apparent neurologic sequelae.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17766009&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum

Plus, animal studies have shown success with treatment of TCA and Ca++ channel blocker overdose.

The above case report with bupropion and lamotrigine is pretty darned impressive. She was down for 70 minutes while they scrambled with standard ACLS and eventually tried intralipid with very quick results and full recovery. No apparent neurologic sequelae.

I've read the report and one of the docs involved was at NACCT. I'm not sure what to make of it. It is an interesting case, although to play devil's advocate, they tried a lot of therapies over that 70 minutes. While the temporal relationship between the lipid and ROSC is quite tight, the other therapies or even just prolonged CPR might have had the same effect. I'm not ready to throw lipid at a bupropion OD unless we are talking refractory pulselessness. The number of times that bupropion has actually killed is pretty small, so mostly I worry about managing the seizures associated with it. I'll certainly keep IFE as thought in the back of my head.

Same goes with TCAs, although I think I have a better body of data. Bicarb and 3% sodium work pretty well for resucitaiton. Rapid application of bicarb is probably the best way to go. Again, IFE goes to the back of the head for consideration.

My issue with the CCBs, and verapamil especially, is that when a person really ODs, there comes a point where I don't have good therapy. CCBs effectively block the end of the signally cascade and main trigger for muscle contraction. In an ideal world, I might shove the really sick ones on ECMO, but most places don't have that lying around and the patients are often too unstable to transport any significant distance. So IFE looks like a promising therapy where I've got nothing else of significant benefit to offer.

hey,
this is an important case. you should write it up.

to play devil's advocate, they tried a lot of therapies over that 70 minutes. While the temporal relationship between the lipid and ROSC is quite tight, the other therapies or even just prolonged CPR might have had the same effect. I'm not ready to throw lipid at a bupropion OD unless we are talking refractory pulselessness. The number of times that bupropion has actually killed is pretty small, so mostly I worry about managing the seizures associated with it.

Okay, I will play devil's advocate too. First, how many times have you seen CPR go for 70 minutes? If you have seen it go for that long, how many survived? What makes you think that suddenly the patient just all of a sudden got better from CPR? A pretty good body of evidence is developing to support lipid therapy for overdose of multiple lipid soluble medications. Besides that, what have you lost if you try it early? You mention that you would be more worried about treating the seizures. I believe that by putting the drug into a lipid phase, you would effectively treat the neurologic symptoms as well as the cardiac symptoms. I would not hesitate to treat toxicity of a lipid soluble drug early as opposed to late.

Last week I used IFE (not for local anesthetic toxicity) after other measures failed. I was stuck scrambling for a dose and ended up taking an example protocol from a reputable website.

Since anesthesiologist are most likely to have thought this out, I'm curious what dose and dosing schedule you all use. Is there any provision for a second dose if there is a temporary response to first dose? Ceiling dose?

Thanks.

was this a last ditch effort or something to try and decrease supportive care efforts?

How bad was this guy doing?

What makes you think that suddenly the patient just all of a sudden got better from CPR?

Many of these patients get better once the drug redistributes out of the blood compartment. Often times they only need to get through the acute episode (measured in hours) in order to be survivors. When you look at it from that prespective, maintaining circulation and allowing redistribution may be what saved the patient. A drug induced cardiac arrest is a different beast than one cause by MI/PE.


A pretty good body of evidence is developing to support lipid therapy for overdose of multiple lipid soluble medications.

No argument.

Besides that, what have you lost if you try it early? You mention that you would be more worried about treating the seizures. I believe that by putting the drug into a lipid phase, you would effectively treat the neurologic symptoms as well as the cardiac symptoms.

Depends on what dose you are planning to use. No one knows how to dose the IFE and the only doses that have been tried are HUGE. There is potential morbidity associated with giving this much IFE so rapidly. I'm also not conviced that by creating a lipid based blood compartment, that I will reduce CNS toxicity, as the drug has already crossed the BBB. Given that the main toxicity of bupropion is seizures, I know that with liberal application of Benzo I can treat the problem without filling the patient's veins with soybean oil.

As a treatment for cardiac arrest, I'll use it. For the treatment of a symptomatic bupropion or lamotrigine OD, I'm reaching for standard therapies.

was this a last ditch effort or something to try and decrease supportive care efforts?

How bad was this guy doing?

Rescue therapy, as the next step would be balloon pump or ECMO. To call him sick, would be minimizing the situation.

Iatrogenic verapamil OD, drug error in house, suicide attempt? Again, just curious.

Given that the main toxicity of bupropion is seizures, I know that with liberal application of Benzo I can treat the problem without filling the patient's veins with soybean oil.

As a treatment for cardiac arrest, I'll use it. For the treatment of a symptomatic bupropion or lamotrigine OD, I'm reaching for standard therapies.

Point taken, but we fill patients with "soybean oil" every day without much problem. Worried about fatty liver or something? I think a short term use is not going to be an issue. Patients get TPN infusions all of the time. We use propofol all of the time and I never hear of complications due to the lipid carrier. Maybe I am out of the loop on how big a problem that may be.

With regards to standard therapies, I think if we give this a couple of years, lipid therapy will be considered standard therapy. I think the potential benefits far outweigh the potential downsides to a trial in a neurologically or cardiovascularly unstable patient following overdose of a lipid soluble drug.

Worried about fatty liver or something? I think a short term use is not going to be an issue. Patients get TPN infusions all of the time. We use propofol all of the time and I never hear of complications due to the lipid carrier. Maybe I am out of the loop on how big a problem that may be.

I believe one of the dogs in a study developed a lipid embolism during one of the infusions. I'd be afraid of pancreatitis as well.

The dose of IFE for nutrition and for rescue are significantly different. Usually I see 1-2/kg/day. If you use the Lipid Rescue 30 minute example protocol, you are giving about 3 times that (6.3 g /kg) in 30 minutes. Propofol appears to be about 10%. I don't use the drug, so I'm not familiar with it. From what I can find, given an induction dose of 4 mg /kg, you'd give .04 g /kg of fat emulsion. If the maintanance infusion is 2 mg/kg/min, after 30 minutes, you'd only give .6 of a g/kg. I may not have the propofol dosing quite right, but unless I've made a 10 fold error, the dosages are still pretty different.

With regards to standard therapies, I think if we give this a couple of years, lipid therapy will be considered standard therapy. I think the potential benefits far outweigh the potential downsides to a trial in a neurologically or cardiovascularly unstable patient following overdose of a lipid soluble drug.

That is certainly a possibilty. It would be nice to have a new, reliable antidote for a broad range of toxic ingestions.

I would like know more about how it works exactly. If the lipid sink/spounge theory is correct, then I am somewhat worried about what will happen once the lipid is metabolized. Hopefully slow distribution of the solubilized drug will keep a person from becoming toxic again. Maybe someone can throw me some cash and I'll try out a few lipid protocols on some rats and see if I can figure it out. :)

[quote=BADMD;5846948]I believe one of the dogs in a study developed a lipid embolism during one of the infusions. I'd be afraid of pancreatitis as well.

i'm siding with Gern on this....
i've not heard of any complications in experimental animals or patients.
there are several reports (at the website) of reversal of CNS toxicity alone or combined with cardiac arrhythmias
by the way....good thread, guys

This is nice

Yes, so very nice.

Talked to resident candidate the other day who is doing some pretty interesting things in his lab with intralipid...
http://hyper.ahajournals.org/content/early/2011/07/08/HYPERTENSIONAHA.110.168781