Exparel versus intralipid

[ArMed]

Based on my rudimentary understanding of how intralipid works, I can't imagine it would work to neutralize an a drug encased in a liposome...given the whole hydrophilic center thing.
The package insert for Exparel warns against the usual bupivicaine toxicities one could expect from an overdose, and it offers intralipid as a suggestion. But it also notes that intralipid is not supported by any trials for the treatment of an Exparel overdose.
Thoughts?

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[deleted126335]

If you run into local anesthetic toxicity from exparel, why not give intralipid?
Like the old joke:

Moments before a famous Shakespearean actor was to perform Hamlet to a packed house in New York, he dropped dead. The house manager solemnly went onstage and announced, "We are sorry to bring you this news, but our performance tonight has been canceled due to the untimely demise of our featured performer."

From the back of the theater a voice cried out, "Give him some chicken soup!"

Startled, the stage manager cleared his throat and replied, "I apologize if in my grief I have not made my solemn message clear. The man is deceased."

Once again, but more emphatically the voice rang out, "Give him some chicken soup!"

Having had quite enough, the manager bellowed back, "Sir, the man is dead! Giving him chicken soup couldn't possibly help."

To which the voice replied, "Well, it couldn't hurt!"

 

[Drachfar]

I would think that intralipid sequesters the drug into the serum so less crosses the BBB. If I'm not mistaken, serum triglycerides and amide anesthetics are highly metabolized in the liver, which is preferable to brain/heart.

 

[Mman]

I would think that intralipid sequesters the drug into the serum so less crosses the BBB. If I'm not mistaken, serum triglycerides and amide anesthetics are highly metabolized in the liver, which is preferable to brain/heart.

I'm far less concerned about a seizure from CNS toxicity than I am by the potentially lethal arrhythmias from high serum levels.

If I had a patient showing signs of toxicity from Exparel, I'd give intralipid as part of my ACLS resuscitation. It can't hurt. It probably helps. My assumption is that the local that is causing the toxicity has already been released from the liposome so it's free in the serum. Doesn't the whole liposomal preparation just delay the release of the local?

 

[Drachfar]

You're right, IMO arrhythmias are far more scary. Fortunately, I think the concentration that causes cardiac side effects is 3x the concentration that will give you seizures so you know what to look for/expect.

The intralipid should theoretically sequester/compete for the lipophilic bupivicaine into the serum lipids and away from the heart and brain. I still think the moa is reduction of drug bioavilability followed by metabolism by the liver.

 

[epidural man]

Based on my rudimentary understanding of how intralipid works, I can't imagine it would work to neutralize an a drug encased in a liposome...given the whole hydrophilic center thing.
The package insert for Exparel warns against the usual bupivicaine toxicities one could expect from an overdose, and it offers intralipid as a suggestion. But it also notes that intralipid is not supported by any trials for the treatment of an Exparel overdose.
Thoughts?

As someone mentioned, any bupivicaine from Exparel causing toxicity will be free bupivicaine (not encapsulated in the liposome) which should respond the same to intralipid.

 

[ArMed]

So is the toxic event a one-time thing? How often are we re-dosing intralipid? Are we expecting recurrent cardiac arrest up until the plasma concentrations of Exparel drop? I don't think these are unreasonable considerations. I've seen surgeons crack multiple vials of the stuff to inject post-op.

 

[Mman]

So is the toxic event a one-time thing? How often are we re-dosing intralipid? Are we expecting recurrent cardiac arrest up until the plasma concentrations of Exparel drop? I don't think these are unreasonable considerations. I've seen surgeons crack multiple vials of the stuff to inject post-op.

I will assume the answer is "nobody knows" because it hasn't been around long enough to have data to help make that decision. Maybe a prudent thing would be to admit patient to hospital for 3 days and have a low dose intralipid infusion running prophylactically.

 

[epidural man]

The data available shows that IV exparel is much more safe than IV bupivicaine.

Also, think about this. Exparel is really really low dosing - and probably why it doesn't work great for nerve blocks (my experience on femoral nerve for painful surgeries).

If I run a femoral nerve catheter for 3 days - 0.125% at 10cc/hr (6cc/hr + 2cc bolus q 30min), that is 300mg/day and 900mg in 72 hrs.

If I inject full strength exparel all 20cc's on the nerve - that is 266mg/3 or 88mg/day. Less than 10% the dose one gives as a standard infusion on the nerve.

 

[epidural man]

Actually the number is worse than 88mg/day, because some of the 266mg is quick released from the initial bolus.