Propofol & SZ...

[chbare]

Nate, here is a little information I was able to dig up.

Author: S Najjar, O Devinsky, and AD Rosenberg

During induction with propofol, spontaneous movements can occur without associated epileptiform abnormalities. These movements may include:

dystonia

chorea

athetosis

twitches

opisthotonus

Abnormal movements may mimic tonic and clonic movements during seizures, especially during the postoperative period.76 In several cases, cortical epilepsy was activated during electrocorticography, with epileptiform activity beginning 20–30 seconds after a bolus of intravenous propofol.77 Seizures may recur for 7 to 23 days after propofol anesthesia, suggesting a proconvulsant metabolite.78,79

Propofol also has anticonvulsant properties in animals80 and humans.81 Continuous propofol infusion can terminate status epilepticus refractory to other therapies.82

In epilepsy patients who underwent dental procedures, administration of propofol in subanesthetic doses to achieve conscious sedation did not provoke seizures or enhance any interictal epileptiform activity.45

One study showed that administration of calcium chloride minimizes the hemodynamic effects of propofol in patients who undergo coronary artery bypass grafting, and thereafter it may potentially reduce postoperative epileptic paroxysms in these patients.9 Recent studies indicate that the synergetic sedation with propofol and midazolam in intensive care patients after coronary artery bypass grafting reduces hemodynamic impairment, which is implicated in the pathogenesis of postoperative seizures.83

Adapted from: Najjar S, Devinsky O, Rosenberg AD, et al. Procedures in epilepsy patients. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;499–513.

With permission from Elsevier (www.elsevier.com).

Reviewed and revised April 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.

Let me know if this was helpful.

Take care,

chbare.

[Nate]

Yes it was, I'm waiting for this tox "expert" to email me back with some more info.

[Spock]

Sorry not to have answered sooner but I've been working late recently and golfed on Sunday (my birthday!).

I administer propofol almost every day I work. It is the induction agent of choice in our operating room for general anesthesia and is used as an infusion for sedation cases (we call them a MAC case). We use propofol because it is cost effective (it came off patent a few years ago) and is thought to have antiemetic effects. It wears off quicker and leaves no hang over effects that you saw with pentothal. We use etomidate for patients with impaired left ventricular heart function and fentanyl for CABG patients. Patients frequently report very pleasant dreams while receiving propofol many of them of a sexual nature. More than one patient has asked if they could take some home!

I have never seen seizures from propofol. Some will use propofol to terminate a seizure but the text state it has no anticonvulsant properties. Tonic movements have been reported but I have never seen them with a bolus or infusion. A bolus of propofol is always followed by a muscle relaxant such as succinylcholine or rocuronium. The muscle fasciculations we see with suxs may also be caused by the propofol but we would have no way to differentiate. I have never seen the tonic movements when roc is given.

One thing that commonly happens with propofol is a dysphoria or agitation seen when not enough is given. There is a gray area (I call it the DMZ) between sedate and unconscious that is very unpleasant for all. The pt will be wild and almost uncontrollable. The solution is to given more or less in order to get them out of the DMZ.

This is adapted from Clinical Anesthesiology by Morgan and Mikhail second edition pages 144-155.

"Propofol decreases cerebral blood flow and ICP. In patients with elevated ICP, propofol can cause a critical reduction in cerebral perfusion pressure (<50mm Hg) unless steps are taken to support mean arterial BP. Propofol and thiopental probably provide a similar degree of cerebral protection during focal ischemia. A unique characteristic of propofol is its antiemetic and antipruritic properties. Propofol does not have anticonvulsant properties. Induction is occasionally accompanied by excitatory phenomena such as muscle twitching, spontaneous movement, or hiccuping. Propofol decreases intraocular pressure."

Propofol works by facilitation of inhibitory neurotransmission mediated by gamma aminobutyric acid. Its high lipid solubility accounts for its rapid onset. Metabolism is through the liver although clearance exceeds hepatic blood flow which means it goes away quickly. The metabolites of propofol are inactive and renal failure does not impede excretion.

Propofol is not water soluble and is available in an emulsion containing soybean oil, glycerol, and egg lecithin which accounts for its milk white appearance (we call it milk of amnesia). A common misconception is that patients allergic to eggs can not receive propofol: they can.

OK, sorry for the pharmacology 101 lecture. Nate, I'm not sure what happened with your patient but the seizure you saw might have been from either a contaminant or the DMZ I spoke of. Propofol has no preservative and must be drawn up and administered aseptically within six hours. Sepsis and death have resulted from contaminated propofol. Could this have been the issue or was he in the DMZ? What else was given and the same time and what were the circumstances surrounding the seizure? I understand if you can't answer these questions.

Might I add it is a pleasure to converse with all the folks on EMT City. The questions and comments are for the most part very intelligent and insightful. Much better than our local forums here in the Steel City home of the Super Bowl Champion Pittsburgh Steelers! Sorry, just had to toss that in.

Live long and prosper.

Spock

[Nate]

OK, sorry for the pharmacology 101 lecture. Nate, I'm not sure what happened with your patient but the seizure you saw might have been from either a contaminant or the DMZ I spoke of. Propofol has no preservative and must be drawn up and administered aseptically within six hours. Sepsis and death have resulted from contaminated propofol. Could this have been the issue or was he in the DMZ? What else was given and the same time and what were the circumstances surrounding the seizure? I understand if you can't answer these questions.

I believe it could have been the DMZ you spoke of, but I'm actually leaning more towards contamination. The reason being is that the patient was being treated at a local LTAC for respiratory failure. He was doing well, but then went outside with his wife for some sunlight. He came back and started to go down hill and was intuabted and placed on a vent. They staff believes that the patient might have taken or given crack cocaine by the wife.

[medik8]

Hmmm....no knowledge of it myself...but according to this....it can.....

http://www.ncbi.nlm.nih.gov/entrez/query.f...p;dopt=Abstract

Convulsive/seizure phoenomena? :-k

xoxo

8

[chbare]

Medik8, that is an interesting article. Thanks for posting it.

Spock, thank you for your post, and happy birthday. I agree that there are allot of intelligent posts on this site. I like the fact that there are so many experienced people on this site in addition to docs and advanced practitioners.

Take care everybody,

chbare.

[Spock]

What is an LTAC? The abstract Medik8 posted is indeed interesting but one item from 1994 is not an indictment of propofol. I would say that seizures from propofol are rare to nonexistent. Cocaine and seizures are very common.

One other thing about propofol is that it burns very badly if given through a small peripheral IV. We usually administer lidocaine 1mg/kg just prior to propofol as a venous local anesthetic.

Live long and prosper.

Spock

[medik8]

ACK! #-o You did it to me again!....I have now been researching this drug for the last two days to see what I could find. The overall consensus of all the studies done thus far (that I have read) seem to point to the same thing. It, obviously, DOES help seizures. However, there have been many cases where it has appeared to cause them. The idea of whether it helps/hurts appears to be simply situational. Although I'm sure the benefits outweigh the risks....

You're right, Spock. One report from 1994 does not prove anything. However, I'm finding repetitive reports that basically say that during induction with propofol, spontaneous movements can occur without associated epileptiform abnormalities. The movements can/do include dystonia, chorea, athetosis, twitches, opisthotonus, and abonormal movements that may mimic tonic and clonic movements during seizures, (especially during the postoperative period.)...

The case studies also stated that cortical epilepsy was activated during electrocorticography, with epileptiform activity beginning 20–30 seconds after a bolus of intravenous propofol. Seizures generally were recurring for about 7 to 23 days after propofol anesthesia.... suggesting a proconvulsant metabolite. This was basically already posted before by someone else. Probably the same study....

However, the studies also stated that Propofol had anticonvulsant effects in animals and humans (duh, we already knew this :roll: )....and that continuous propofol infusion terminated status epilepticus.

I'm not sure I really have an opinion either way. Especially after everything I have read so far. It sounds like it's still up in the air, although...it's obvious it can cause seizures in some cases/situations...and not at all in others.

?? I'm still looking...and will report back if I find anything really interesting... (since all I do is work and in between...I have lots of time on my hands. LMAO.)

I have a few other links where I found some of the same information supporting what I had written above...I will post them as well... At this point, I'm looking for some actual percentage numbers. I would be interested to see those...

Thanks, Nate....for starting this discussion. I have a great interest in drugs/medications....

PS...LTAC is a Long Term Acute Care hospital....

xoxoxo :wink:

Luv,

8

[Nate]

LTAC hospitals here (Houston) range from a small rehab facility (similar to a nursing home) to an actual hospital (Triump, Kindred, Memorial Hermann Cont. Care. Some have ICU's, OR's, labs, etc. They ALL lack an ER.

[Spock]

We have a Kindred here in Pittsburgh and a former student of mine is the CEO but I just never saw the abbreviation LTAC before.

Very interesting discussion here. One thing to remember about medications is that we frequently only have theories of how and why they work even though we use them commonly. Propofol has been around for quite some time but it was very expensive so most people didn't use it until it came off patent around 1999 (not sure of the exact date). The text I cited has been updated so it may now say that propofol does have anticonvulsant properties. I suppose I should update my library. Anyway, the common perception is that it does stop seizures although benzodiazepines are the drug of choice to terminate a seizure. Propofol goes away so quickly that the seizure would easily reoccur. The tonic movements seen with propofol could easily be confused with seizures so the only way to know what is really going on is to monitor EEG during the event. My experience over nine years as a CRNA tells me that the tonic movements occur rarely because I can't ever remember seeing it. That doesn't mean it does not happen but I have just not seen it.

I monitor EEG during general anesthesia with my BIS monitor which is a gauge of anesthetic depth. I usually do not apply the monitor until after the patient is asleep but I may start putting it on prior to induction and look for EEG activity consistent with a seizure upon propofol administration.

Live long and prosper.

Spock