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Propofol: Acute toxicity

daisydaisy said:
Yeah this is what I have thought since the Coroner's report was released.


The dose of propofol that Murray stated he gave Michael seems way off to me. Because Propofol has such a short half life a continous IV infusion is how it's normally used in clinical practice. So Murray saying he just gave 25mg seems kinda ridiculous to me.

http://www.mjjcommunity.com/forum/showthread.php?p=2155848

The following website is really good IMHO:

http://vam.anest.ufl.edu/simulations/propofolpharmacokinetics.php

It is a pharmacokinetic simulation of propofol in the human body. You have to register (free) before you can use it but is worth doing if you want to see estimates of what sorts of dosages of propofol are needed to give a blood level that are dangerous. IMO it is highly doubtful that 25mg can cause acute propofol toxicity.

Of course, 25mg could cause respiratory and cardiac problems which is why resus. and monitoring equipment should always be at hand. But, for the coroner to rule 'acute propofol toxicity' the levels must have been out of the normal blood range for this to be possible. If the blood level was within normal limits then how could this ruling be possible?

Hopefully the coroner has been able to estimate what dose was administered to Michael by working backwards from the blood levels.

I have thought for a long time that Murray may have set up the IV wrong, ie a whole large dose may have been administered in error due to setting the wrong flow rate or something.

The truth about what really happened when on that day needs to come out. I still can't believe all this happened with the hospital only minutes away-inexcusible.
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thank you :clapping::clapping:
 
williamorange1 said:
versed ? it is as risky as propofol and does not even have the propofol effect and on top of that VERY ADDICTIVE .

MJ calling Lee the person who refused to give him propofol five days before his death eventhough Murray was there for him , tells me it was MJ who realised taking that shit was not "as safe as he previously thought "
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you mean when he called about being hot on one side and cold on another.

yeah. :(

he should have taken himself to the hospital! oh mike.
 
williamorange1 said:
you know I'm reading about midazolam (versed) and it is a drug that provides sedation without loss of consciousness. add to that it is one hell of an addictive drug , why would murray use such a drug to "wean mj off propofol" ?

I know benzo are used usually before administring propofol , that's maybe the case here .

all this story about weaning mj off propofol does not make any sense to me at all .

those drugs were not given the way murray said at all , it just does not make sense. 2mg of versed would not have lasted long and from reading in some people it does not really work at all . AT ALL .
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Versed is usually used for short procedures. Given that he was using propofol for sleep, versed is another medication that causes sedation.

williamorange1 said:
I can understand that he used versed or lorazepam before administring propofol , because he administered propofol that NIGHT , not that morning as he claimed .

you use either one of them , why both ?

and no versed is not used to sleep, from reading about both versed and propofol, it seems to me administring versed is more absurd .
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In the hospital, we often use different drugs if you need to sedate someone. Ativan (lorazepam) and Versed (midazolam) are definitely within that class of meds. I think murray tried a few different agents, and none of them likely worked for very long.

daisydaisy said:
^^ I think what Murray meant by him 'weaning him off' propofol was that he didn't want to give it Michael anymore. Ie he was just trying other drugs that made more clinical sense ie benzodiazepines (BZDs) instead of propofol. Although the combo of BZDs he gave was not following protocol either. Murray, allegedly, had given Michael propofol on a number of nights before the 25th June since he was hired. He could have sensed it was wrong and risky to give propofol and wanted to stop so he tried BZDs instead.

Physical dependence on propofol does not occur like it does for opiates etc and Murray being a cardiologist would know this too. He probably said 'weaning' but chose the wrong word.
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I don't know what he said, but I can understand 'weaning off propofol.' I would definitely feel more comfortable giving 2 mg ativan versus propofol.

williamorange1 said:
"A total dose of up to 5 mg generally is adequate for conscious sedation in an average healthy adult younger than 60 years of age, and a total dose of up to 3.5 mg usually is adequate for patients 60 years of age or older, chronically ill and/or debilitated patients, and patients with decreased pulmonary reserve."


first it is 5 mg , second it is enogh for CONSCIOUS sedation . why would MJ want to "sleep" that way ?
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Why would he want to sleep with propofol?

Bottom line, none of these medications are standard practice for insomnia. Ativan is occasionally used, but no doctor wants to use it for insomnia.

All these different meds in a cocktail sounds like 'what was this guy doing? Obviously he's clueless and trying to kill the man' but Ativan and Versed are used commonly.

For example, if a patient dislocated his shoulder. I've seen some get Versed and fentanyl (an opiate pain med), become sedated, and the shoulder is put back in place. Done. Othertimes, patients require something stronger like propofol to be sedated. If the ativan or versed doesn't work, you can't fix the shoulder. And in that setting, you would give IV propofol (possibly 25 mg, depends on the case. but NOT a continuous infusion. continuous infusion propofol is used for surgery or in vented patients in the ICU typically). But even 25 mg can cause respiratory depression.

Michael may have been tolerant to the benzos and they probably didn't work. At that point, he probably asked for propofol. Maybe murray said 'okay, ativan didnt work, lets try versed' or something like that. And when the versed failed to work, he prob gave propofol.

Basically, we don't know what his INTENTIONS were. Speaking from a medical perspective, nothing in this thread has convinced me of malicious intent. Irresponsible, illegal, unethical, dangerous...yes.

We KNOW he is responsible for what happened. The question is, was this accidental or intended.
 
Dangerous21 said:
Versed is usually used for short procedures. Given that he was using propofol for sleep, versed is another medication that causes sedation.



In the hospital, we often use different drugs if you need to sedate someone. Ativan (lorazepam) and Versed (midazolam) are definitely within that class of meds. I think murray tried a few different agents, and none of them likely worked for very long.



I don't know what he said, but I can understand 'weaning off propofol.' I would definitely feel more comfortable giving 2 mg ativan versus propofol.



Why would he want to sleep with propofol?

Bottom line, none of these medications are standard practice for insomnia. Ativan is occasionally used, but no doctor wants to use it for insomnia.

All these different meds in a cocktail sounds like 'what was this guy doing? Obviously he's clueless and trying to kill the man' but Ativan and Versed are used commonly.

For example, if a patient dislocated his shoulder. I've seen some get Versed and fentanyl (an opiate pain med), become sedated, and the shoulder is put back in place. Done. Othertimes, patients require something stronger like propofol to be sedated. If the ativan or versed doesn't work, you can't fix the shoulder. And in that setting, you would give IV propofol (possibly 25 mg, depends on the case. but NOT a continuous infusion. continuous infusion propofol is used for surgery or in vented patients in the ICU typically). But even 25 mg can cause respiratory depression.

Michael may have been tolerant to the benzos and they probably didn't work. At that point, he probably asked for propofol. Maybe murray said 'okay, ativan didnt work, lets try versed' or something like that. And when the versed failed to work, he prob gave propofol.

Basically, we don't know what his INTENTIONS were. Speaking from a medical perspective, nothing in this thread has convinced me of malicious intent. Irresponsible, illegal, unethical, dangerous...yes.

We KNOW he is responsible for what happened. The question is, was this accidental or intended.
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who said Murray's intentions were to kill MJ that night? Not me at all . we are talking about what happened after he found mj in dire need of help , what he did then .


you are talking about "ok attivan did not work , lets try versed then propofol" like you do actually believe that what indeed happened that night , what murray said. WE DON'T . nobody here even believe mj was alive at 10:40 am that morning to begin with.
I don't believe murray had any intentions to stop giving propofol as he is claiming . I do understand you give lorazepam and midazolam before using propofol , but you use either of them , you don't use such a cocktail of drugs before administring propfol, especially without the medical equipment necessary .

one last thing , 2 mg of midazolam was the last benzo given to mj three hours before propofol , 2 mg of lorazepam were also given to mj 5 hours before propofol , and since both of the drugs are benzos and their adverse effects are alson very similar , why it was the lorazepam the one who contributed to the death not midazolam ?
ofcourse if you believe Murray's story that night , which I DON'T .
 
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murray is saying mj did not sleep at all that night . AT ALL . the 2 mg of midazolepam would not be enough to sedate a man like mj . on average you need 5 mg of midazolepam given over a period of time to "conscious sedate" someone . not even complete sedation . that's the point here .
 
and since both of the drugs are benzos and their adverse effects are alson very similar , why it was the lorazepam the one who contributed to the death not midazolam ?
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well i guess all u can think is because of the levels in mj.musth ave been far greater considering it was given b4 the midazolm.presumng Lor and Mid have the same side effects. its not like Loz is more dangerous than the other so it contributed more?
 
williamorange1 said:
murray is saying mj did not sleep at all that night . AT ALL . the 2 mg of midazolepam would not be enough to sedate a man like mj . on average you need 5 mg of midazolepam given over a period of time to "conscious sedate" someone . not even complete sedation . that's the point here .
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so why did he give it to him at all.if he only gave an amount that would do nothing. why the mixing?
 
he gave it before administring propofol , which is a very usual , but not INSTEAD of propofol like he is claiming . as for why lorazepam not midazolam contributed to the death ,another evidence Murray's story is so fucked up and can't be trusted at all .
 
he gave the mid b4 the dirpivan?. well maybe there wasnt an intention to give diprivan thats why he gave mid and all the others at low levels.( indiviually they wont do anything) but giving a mixture will. and it ended with him giving mj a low amount of diprivan.not wanting to give a large amount because of what he had already given mj? playing devils advocate here
 
you mean when he called about being hot on one side and cold on another.
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if murray's story is true that he wanted mj to 'wean off' propofol this could have been the reason .. he got scared after the incident on father's day when mj called nurse lee and told her he was feeling hot on one side and cold on the other side

what could have produced this effect? has there been any talk about this?
 
williamorange1 said:
thank you :clapping::clapping:
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You're welcome :) Did you check out the simulation?

sophie said:
if murray's story is true that he wanted mj to 'wean off' propofol this could have been the reason .. he got scared after the incident on father's day when mj called nurse lee and told her he was feeling hot on one side and cold on the other side

what could have produced this effect? has there been any talk about this?
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elusive moonwalker said:
he gave the mid b4 the dirpivan?. well maybe there wasnt an intention to give diprivan thats why he gave mid and all the others at low levels.( indiviually they wont do anything) but giving a mixture will. and it ended with him giving mj a low amount of diprivan.not wanting to give a large amount because of what he had already given mj? playing devils advocate here
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Yeah that's what I believe too. Like he was maybe having second thoughts about using propofol and wanted to try other routine drugs for insomnia. Then, perhaps as a last resort he gave propofol.

Can there be acute propofol toxicity where blood propofol levels are within 'normal' parameters?


Dangerous21 said:
Versed is usually used for short procedures. Given that he was using propofol for sleep, versed is another medication that causes sedation.

In the hospital, we often use different drugs if you need to sedate someone. Ativan (lorazepam) and Versed (midazolam) are definitely within that class of meds. I think murray tried a few different agents, and none of them likely worked for very long.

I don't know what he said, but I can understand 'weaning off propofol.' I would definitely feel more comfortable giving 2 mg ativan versus propofol.

Why would he want to sleep with propofol?

Bottom line, none of these medications are standard practice for insomnia. Ativan is occasionally used, but no doctor wants to use it for insomnia.

All these different meds in a cocktail sounds like 'what was this guy doing? Obviously he's clueless and trying to kill the man' but Ativan and Versed are used commonly.

For example, if a patient dislocated his shoulder. I've seen some get Versed and fentanyl (an opiate pain med), become sedated, and the shoulder is put back in place. Done. Othertimes, patients require something stronger like propofol to be sedated. If the ativan or versed doesn't work, you can't fix the shoulder. And in that setting, you would give IV propofol (possibly 25 mg, depends on the case. but NOT a continuous infusion. continuous infusion propofol is used for surgery or in vented patients in the ICU typically). But even 25 mg can cause respiratory depression.

Michael may have been tolerant to the benzos and they probably didn't work. At that point, he probably asked for propofol. Maybe murray said 'okay, ativan didnt work, lets try versed' or something like that. And when the versed failed to work, he prob gave propofol.

Basically, we don't know what his INTENTIONS were. Speaking from a medical perspective, nothing in this thread has convinced me of malicious intent. Irresponsible, illegal, unethical, dangerous...yes.

We KNOW he is responsible for what happened. The question is, was this accidental or intended.
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Thanks Dangerous, v good to read your info :) Interesting to know that propofol can be used as a 25mg bolus in some clinical situations. In these situations does the sedation only last a few minutes?

Have you ever seen ephedrine used in resus? This has been bugging me for a while now. I used to practice as a pharmacist and I've only heard of it being used in some cases for spinal anaesthesia not general anesthesia. Ephinephrine is what I would have expected to see on the coroner's report not ephedrine....
 
daisydaisy said:
Yeah that's what I believe too. Like he was maybe having second thoughts about using propofol and wanted to try other routine drugs for insomnia. Then, perhaps as a last resort he gave propofol.
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Versed is not a routine drug to treat insomnia neither is lorazepam especially through an IV , they are very dangerous alhough their adverse effect are not as dangerous as those of propofol but still should also be provided only with appropriate medical equipment .

the use of lorazepam and versed tells you murray was indeed planning on administring propofol that night, one of them is usually given before administring propofol , also mj had benzo pills why set an iv in the first place if you have no intentions of administring propofol .

Can there be acute propofol toxicity where blood propofol levels are within 'normal' parameters?
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no , "acute toxicity" is completely different from "normal" dose . although a normal dose could cause the same adverse effect an "acute toxicity" causes.

QUOTE]
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williamorange1 said:
Versed is not a routine drug to treat insomnia neither is lorazepam especially through an IV , they are very dangerous alhough their adverse effect are not as dangerous as those of propofol but still should also be provided only with appropriate medical equipment .

the use of lorazepam and versed tells you murray was indeed planning on administring propofol that night, one of them is usually given before administring propofol , also mj had benzo pills why set an iv in the first place if you have no intentions of administring propofol .

no , "acute toxicity" is completely different from "normal" dose . although a normal dose could cause the same adverse effect an "acute toxicity" causes.
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By more 'routine' drugs I just meant benzodiazepines as a class of drugs, ie BZDs are more commonly used to treat insomnia in the short term than general anaesthetics. Murray's choice of giving numerous types of BZD still perplexes me. I see your point about midazolam (versed) perhaps being used in preparation for propofol, but it can be used for short term insomnia as well (orally not IV). I reckon IV was given because IV drugs have a way faster onset of action than tablets. Tablets may take an hour or so to start workin=not ideal in insomnia.

Yeah what I'm basically wondering is how the coroner specifically defined acute propofol toxicity. I mean could someone have suffered from acute propofol toxicity even if their blood levels were in the acceptable range? Could lorazepam have lowered the usually 'safe' normal blood propofol limits, making toxicity possible with a seemingly 'normal' propofol dose? Or is it just defined by having a blood propofol level in excess of the 'normal' range?
 
versed is used for "conscious sedation" and he needed 5 mg given over a period of time of versed to create "conscious sedation" not even complete sedation , I doubt that what MJ wanted that night .

that's why I'm telling you murray's story does not make any sense . he could have decided to use versed instead of propofol that night but as with the propofol thing the amount he talked about 2mg was not enough to "conscious sedate " mj let alone make him go to sleep .

and yes benzos are used to treat short term insomnia but not through an IV .
 
there is not enough information on acute toxicity of propofol in humans , hell there is not even enough information on acute toxicity of benzos in humans . so I don't know how the coroner determined this was a case of "acute propofol toxicity"
 
williamorange1 said:
versed is used for "conscious sedation" and he needed 5 mg given over a period of time of versed to create "conscious sedation" not even complete sedation , I doubt that what MJ wanted that night .

that's why I'm telling you murray's story does not make any sense . he could have decided to use versed instead of propofol that night but as with the propofol thing the amount he talked about 2mg was not enough to "conscious sedate " mj let alone make him go to sleep .

and yes benzos are used to treat short term insomnia but not through an IV .
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williamorange1 said:
there is not enough information on acute toxicity of propofol in humans , hell there is not even enough information on acute toxicity of benzos in humans . so I don't know how the coroner determined this was a case of "acute propofol toxicity"
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Yeah the choice of specific BZDs do not make sense. You're right.....and why alternate lorazepam & midazolam? I don't get it either, but am trying to look at it from Murray's possible point of view.

Re. the route of administration, yes tablets are the norm but sometimes doctors deviate to suit the situation, ie quick onset needed. I forget, did Murray say he gave all the BZDs through the canula or just injection, maybe IM? Maybe the doses he gave were lower because they were through an IV? The equivalent IV dose of a 2mg tablet would probably be way lower than 2mg.
 
daisydaisy said:
Have you ever seen ephedrine used in resus? This has been bugging me for a while now. I used to practice as a pharmacist and I've only heard of it being used in some cases for spinal anaesthesia not general anesthesia. Ephinephrine is what I would have expected to see on the coroner's report not ephedrine....
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yeah , it is used and actually epherdine unlike Ephinephrine influence depth of sedation . epherdine from what I read increases the depth of sedation when propofol is used .
 
did Murray say he gave all the BZDs through the canula or just injection, maybe IM? Maybe the doses he gave were lower because they were through an IV? The equivalent IV dose of a 2mg tablet would probably be way lower than 2mg.
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he gave him first a 10 mg tab of valuim which is diazepam another benzo , then the rest through an IV 2 mg lorazepam, 2 mg midazolam, 2 mg lorazepam, 2mg midazolam then propofol .
 
ok, diazepam as pills is absorped within 1 to 2 hours . it has a long half life 45 hours , and it stays for many many days in the body before someone is completely clean . so mj could have taken diazepam 4 , 5 and sometimes even 10 days and the coroner could still detect it in his body . midazolam is much shorter , it disappears within 48 hours .so yeah the coroner listed the drugs contributed and the drugs detected but that does not mean all of those benzo were administered that night .
 
but why would murray admit he gave all these drugs that day if he did not ? why someone would incriminate himself even more , maybe to support his story about trying different methods to "wean mj off propofol" and administering it because mj was begging for it , and since I reread the search warrant I have to be fair to Murray and say that he told them "he felt that mj MAY HAVE BEEN forming an addiction to propofl" not that mj was addicted . big difference , still he killed mj and he is gonna pay for what he did that night.
 
Williamorange1, are you a doctor or work in the medical field? You seem to be very knowlegeable about these drugs.
 
no I'm studying IT , but I spend alot of time these days researching these drugs found in MJ's body .
 
wow reading all this and looking back on what Randy Phillips said in that interview makes me feel very scared of the outcome when the investigation is over, maybe Latoya was right and we will be very surprised and not in a pleasant way
and to think the main reason why Michael hired and trusted Murray was because he was James Brown's doctor he didn't even make a basic background check on him because of that why Michael? he always trusted the wrong people and look where it got him
 
I've said it before and I'll say it again :

We don't KNOW what Murray gave to MJ apart from the Propofol.

The doses of sedatives that you have quoted in your posts above were in the police affadavit NOT in Murray's statement. The doses of propofol were also not in Murray's statement.

We HAVEN'T HAD the coroners report yet. We only had a 'leak' and we have no idea how accurate that leak is.

I too want to know what Murray was doing between 10am, and noon on that morning. WHAT was he injecting MJ with and why? But getting upset over leaked documents that may be false is not helping me!

I also can't understand if Murray gave MJ an overdose, why hasn't he been arrested?

Nothing adds up, and I know you guys love him, but adding to the speculation doesn't help.
 
I also can't understand if Murray gave MJ an overdose, why hasn't he been arrested?
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the case is going to the D.A this week according to all reports

We don't KNOW what Murray gave to MJ apart from the Propofol.
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we know what he gave him but not the doses
 
slimblonde2 said:
I've said it before and I'll say it again :

We don't KNOW what Murray gave to MJ apart from the Propofol.

The doses of sedatives that you have quoted in your posts above were in the police affadavit NOT in Murray's statement. The doses of propofol were also not in Murray's statement.

We HAVEN'T HAD the coroners report yet. We only had a 'leak' and we have no idea how accurate that leak is.

I too want to know what Murray was doing between 10am, and noon on that morning. WHAT was he injecting MJ with and why? But getting upset over leaked documents that may be false is not helping me!

I also can't understand if Murray gave MJ an overdose, why hasn't he been arrested?

Nothing adds up, and I know you guys love him, but adding to the speculation doesn't help.
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:doh::doh:
you are joking right ?

do you realise if the detectives were not accurate when stating what Murray said in those affidavit to obtain a search warrant no evidence collected or recovered would ever be admissible in court ? :smilerolleyes:

in the search warrant obtained to raid murray's office and storage in Houston the drugs listed as found at mj's residence were not even the ones recovered on june 26 since someone called jeffers phillips handed them to the coroner assistant , they were not found by detectives , so they were a "tainted evidence" and the police did not want to jeopardise the whole investigation by obtaining a search warrant based on "tainted evidence" , they did not want to give any grounds to the defense to attack the way these search warrants were granted . obviously someone who goes to that length to ensure the investigation is not ruined would not list doses and names Murray did not admit to .

I can understand that Murray was not trustful which I do believe myself when he talked about the doses and the timing ...etc , but I can't accept that some fans believe the detectives would write complete lies or not accurately quoting murray to obtain a search warrant .
 
Thanks for clarifying that williamorange1.
The reason I'm questioning the affadavit is this :

"Much of what was in the search warrant affidavit is factual," said Mr Chernoff. "However, unfortunately, much is police theory. Most egregiously, the timeline reported by law enforcement was not obtained through interviews with Dr Murray, as was implied by the affidavit.

http://www.telegraph.co.uk/culture/...nies-leaving-singer-to-make-phone-calls.html#

So you can understand why I would question the WHOLE accuracy of the affadavit.
 
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