Lorazepam-I pray this is not being overlooked

The cause of death is listed as acute propofol intoxication with benzodiazepine effect.

When the COD was first released I expected they had found normal benzodiazepine levels in his system and it was the synergistic respiratory depression between a normal dose of benzodiazepine and propofol, along with the blatant incompetence and lack of monitoring, that caused this tragedy. However, now it seems the benzodiazepine levels found seem to be a lot more than 'normal' levels.

The femoral blood level was 169ng/ml. According to the FDA in relation to IV lorazepam:

"A 4-mg dose provides an initial concentration of approximately 70 ng/mL."

And in relation to IM lorazepam:

"A 4-mg dose provides a Cmax of approximately 48 ng/mL. " NB Cmax is peak plasma level.

Tablets give a way lower plasma level than this.

http://www.drugs.com/pro/ativan.html

Assuming a proportional relationship between plasma levels and dose, as is true for lorazepam, then by my reckoning the dose of lorazepam given was close to 10mg.

In the Coroner's Report it seems like lorazepine data is being held back. For example, there is no mention of urine sample results or hospital blood results.

In regards to the bigger picture, the amount of propofol found in the blood samples again reflects a dose greater than 25mg being given. How can Murray possibly justify giving a wacking dose of lorazepam? How can he then justify that Michael still could not sleep, as he could already have been in a coma? So how can he justify the need for giving propofol?

are you saying he might've injected Michael with propofol when he was already unconscious?
the way I see it now anything is possible with Murray anything

IDK anything is possible. The blood levels are factual and they speak for themselves. The lorazepam level found was very high indeed compared to the FDA's figures. Murray only stated he gave two lots of 2mg injections, the last one being at 5am. This does not sit right with the levels found. I think, with a blood level that high, how could he still be awake or unable to sleep?

daisydaisy said:

IDK anything is possible. The blood levels are factual and they speak for themselves. The lorazepam level found was very high indeed compared to the FDA's figures. Murray only stated he gave two lots of 2mg injections, the last one being at 5am. This does not sit right with the levels found. I think, with a blood level that high, how could he still be awake or unable to sleep?

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This is something I am sure they are aware of BUT as I mentioned before there was Lorazepam left in the tubing that was in the IV that was in his leg.

This amount that was left in the tubing was likely pushed through with the Propofol when he injected that through that same line.

The IV line (The Y Tubing) that was in his leg holds a certain amount of fluid and as a nurse I can tell you that we flush that line after we are done with Normal Saline to clear that line. If that was not done there was drug left in the line. If you come along after that and push more drug into the line you are pushing both the last drug and the new drug into the same line.

I don't know how long the tubing was or how much was in there or the concentration of the drug he used but this is an explanation of why he received too much Lorazepam with the Propofol if that makes sense.

True that there could have been some lorazepam left over in the tubing (v bad practice) but the amount femoral blood does not correlate with Murray's stated dosage by more than this.

If Murray drew 2mg worth of liquid (don't know what concentration injection he used) and pushed it into the IV, then the amount left in the tubing would come from this 2mg dose. So any extra given with propofol would come out of the original 2mg dose. The discrepency is too large for this. The dose is milligrams out not just a little bit of liquid.

Beachlover said:

This is something I am sure they are aware of BUT as I mentioned before there was Lorazepam left in the tubing that was in the IV that was in his leg.

This amount that was left in the tubing was likely pushed through with the Propofol when he injected that through that same line.

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Do we know for sure that there was Lorazepam left in the tubing? I checked the autopsy report and couldn't find mention of it. I could have missed it though.

Lorazepam injection is clear and colourless, but I don't know for sure if it was found or not in the tubes. Even if it was this is not an excuse because you draw the dose then push it in the IV tubing. Whatever is drawn minus the amount left in the tubing is the dose administered.

daisydaisy said:

Lorazepam injection is clear and colourless, but I don't know for sure if it was found or not in the tubes. Even if it was this is not an excuse because you draw the dose then push it in the IV tubing. Whatever is drawn minus the amount left in the tubing is the dose administered.

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Thank you. So if Murray had drawn 2mg of Lorazepam and some was left over in the tube after he administered it to MJ, then the amount left over would be less than 2mg. And less than 2mg isn't enough to result in the amount of Lorazepam found in the heart blood. Am I understanding correctly?

daisydaisy said:

Lorazepam injection is clear and colourless, but I don't know for sure if it was found or not in the tubes. Even if it was this is not an excuse because you draw the dose then push it in the IV tubing. Whatever is drawn minus the amount left in the tubing is the dose administered.

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Yes I understand that but I have long given up on what the search warrants have 'stated' as being dosed. Regardless of whether it was found in the tubes, it had to have been administered through them if it was found in his system and it was.

Whether it was left in the tubing or not, I don't know but I strongly suspect he was tired and didn't clear his lines when he was done. This could just be an explanation as to why the Lorazepam was found in such high concentration at the time of the blood draw.

We really don't know what he gave and what times he gave it. We don't know what he gave the other nights either. We have limited resources to check from.

curlybrat said:

Do we know for sure that there was Lorazepam left in the tubing? I checked the autopsy report and couldn't find mention of it. I could have missed it though.

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Just to explain this though. By the time they check the 'y' tubing it had already been used for flumazenil. That was found in the tubing and it was yellow colored.

Beachlover said:

Yes I understand that but I have long given up on what the search warrants have 'stated' as being dosed. Regardless of whether it was found in the tubes, it had to have been administered through them if it was found in his system and it was.

Whether it was left in the tubing or not, I don't know but I strongly suspect he was tired and didn't clear his lines when he was done. This could just be an explanation as to why the Lorazepam was found in such high concentration at the time of the blood draw.

We really don't know what he gave and what times he gave it. We don't know what he gave the other nights either. We have limited resources to check from.

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So what you're speculating is that Murray gave more than 2mg (which I would speculate as well since the Propofol amount seems to be more than what Murray stated), left some of it the tube and then that was pushed into the I.V. along with the Propofol.

It does make me wonder how much would have had to have been left in the tubing for it to result in the amounts cited in the autopsy report. And if there was that much left in the tubing, then how much was originally given. I'm not a medical expert so I don't know if the amount found in the heart blood was high, normal or low.

curlybrat said:

So what you're speculating is that Murray gave more than 2mg (which I would speculate as well since the Propofol amount seems to be more than what Murray stated), left some of it the tube and then that was pushed into the I.V. along with the Propofol.

It does make me wonder how much would have had to have been left in the tubing for it to result in the amounts cited in the autopsy report. And if there was that much left in the tubing, then how much was originally given. I'm not a medical expert so I don't know if the amount found in the heart blood was high, normal or low.

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This can cause your head to spin because first we need the concentration of the drug he used, then we need to know how much could have been left in the tubing....and we would have to know if in fact he did not flush the line.

Many variables here.

Just for clarification here. I am not sure whether there was Lorazepam left in the tubing at the time he pushed the Propofol. I strongly suspect that but I don't know.

Thanks beachlover. It does make ones head spin. I almost went on the internet to research Lorazepam and half-life and dosage and blood concentrations....but I need to clean my kitchen. LOL. I will take that on later.

I guess in the end though Murray had to have given more Lorazepam than he stated and at the time he stated that he gave it in order to have the heart blood concentration that was reported. I would speculate that regardless of whether or not it was pushed in with the Propofol there at the end, the amount was entirely too much.

ETA: Just reread Daisy's post about the levels and concentration in relation to Lorazepam. This makes me wonder if 10mg of Lorazepam would have amounted to enough leftover fluid in the tubing to cause the high concentration that was found.

According to the search warrant, Murray stated that he gave Lorazepam at 5am then Midazolam at 7:30am then the Propofol. So wouldn't any leftover Lorazepam have been pushed in when the Midazolam was administered?

curlybrat said:

According to the search warrant, Murray stated that he gave Lorazepam at 5am then Midazolam at 7:30am then the Propofol. So wouldn't any leftover Lorazepam have been pushed in when the Midazolam was administered?

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Yes, if you are to believe him. I am now beginning to question what he stated he gave. As time goes on and the more we know it seems even more confusing.

Forensic medicine is not the same as when people are living so it is a little out of my league.

curlybrat said:

Thank you. So if Murray had drawn 2mg of Lorazepam and some was left over in the tube after he administered it to MJ, then the amount left over would be less than 2mg. And less than 2mg isn't enough to result in the amount of Lorazepam found in the heart blood. Am I understanding correctly?

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Exactly. There is no way the amount left over could have been enough to cause blood levels this high if the dose was 2mg. It's standard practice to draw the dose then push through in the IV, and whatever gets left over is left over from the drawn dose.

COD listed Loz as a contributing factor so i dont see it being overlooked. its listed as being more important then the other benzos

thank you daisy , this is what I have been looking for since they said Lorazepam was a contribuing factor .

How much lorazepam did that monester give MJ before his death we don't know but it was certainly much more than 4 mg . and if you want to believe his story that he gave 2 mg at 3 am and another 2mg at 5 am , then lorazepam would have been detected in his liver . and noway the concentration would be near 162 if it was given that early .

No lorazepam was detected in any part of the IV system , and if indeed no lorazepam was detected in hospital blood then I'm bound to believe he injected him with lorazepam immediatley before his death and not into the IV . I said it before and I'll say it again , Murray needed an apparent cause of death because he believed propofol would disappear and lorazepam was it . He pointed all the fingers at it and then tried to downplay its role in his interview with the police by lying and claiming he gave it for three nights before and earlier that night . He knew what he did .

More like 10mg was administered. That is crazy! There is no innocent explanation for this. What you suggested is a definite possibility, but IDK how he expected all the propofol to be gone out of his system?

he waited for more than hour

If Michael had already passed then it wouldn't have been metabolised anymore, so I don't get it...There could be truth to what you are saying though.

daisydaisy said:

If Michael had already passed then it wouldn't have been metabolised anymore, so I don't get it...There could be truth to what you are saying though.

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There has to be some metabolized from the night before and the night before that. It isn't just what was pushed that same night that is going to show up. There is a cumulative effect of this and all drugs.

Do medications clear the body at different rates? I mean, depending on the type of drug it is, and the metabolism of the person who's had the drug? I'm assuming that they do, and this would be part of the forensic evidence? So, a "cumulative" effect, or not, would depend on knowing this? Also, I'm assuming that when a person dies, that the process of "clearing the drugs from the body" stops? Or do the drugs continue to dissipate even after death?

Victoria83 said:

Do medications clear the body at different rates? I mean, depending on the type of drug it is, and the metabolism of the person who's had the drug? I'm assuming that they do, and this would be part of the forensic evidence? So, a "cumulative" effect, or not, would depend on knowing this? Also, I'm assuming that when a person dies, that the process of "clearing the drugs from the body" stops? Or do the drugs continue to dissipate even after death?

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You are assuming correctly. Pharmacology and how drugs work and how long they last are a science all by themselves. Drugs have a 'half life' and things of that nature that mean for example, you can take 2 Aspirin for a headache and in another 4 hours take 2 more Aspirin but the first have not stopped working. Aspirin is also a blood thinner as well as an anti inflammatory drug. Many people were taking these for arthritis and ended up having severe bleeding problems. This is just an example of an unwanted side effect of one drug.

There are side effects of long term use of Propofol as well. Since Propofol is not often used 'continuously' for a long time, or used even 'daily' by many, it is unpredictable simply because there is a lot they still don't know about long term use. Lorazepam has a half life of 9 - 16 hours. Over time our bodies build up a tolerance to many drugs also and we need more of them to achieve the desired results. BUT that doesn't mean they don't produce the unwanted side effects as well. Midazolam has a half life of 1.8 to up to 7 hours.

I do know that we can give a patient a pain killer and they are still awake and complaining of pain and we give just a little more and after an amount of time their respiration's start to slow and they start showing signs of overdose. Sometimes it takes time before the drugs start to work on certain people and the cumulative effect is too much for them.

This is why it is difficult for us to give any accurate answers. We know some things for sure but there are other things that we have to 'estimate' and guess at. What I am saying is that it is a very individual thing.

We can't say for sure what dose will work for a person even if they go by body weight. We use that as a starting point but it is not exact.

Now, as far as drugs crossing over membranes after death, some do. For the most part though, these bloods and urines were done fairly quickly so that should not present a major problem.

But OH...I forgot one of the things you were asking. They don't continue to 'move' though the body as in metabolism. In other words, the urine concentration would not change drastically. Each drug does get to certain body parts at different rates and would show up in the urine at a different rate depending on the drug. Some drugs change while going through metabolism, such as Diazepam which turns to Nordiazepam (Valium)

Wow...a lof of this medical jargon and information went right over my head, but after reading through it all a couple of times, I think I have a better understanding. Thanks for all who contributed here...it is very interesting. I agree that whatever Murray stated as his dosages and times in the affidavit is highly suspect. None of this adds up according to his initial statements.

TinaG said:

Wow...a lof of this medical jargon and information went right over my head, but after reading through it all a couple of times, I think I have a better understanding. Thanks for all who contributed here...it is very interesting. I agree that whatever Murray stated as his dosages and times in the affidavit is highly suspect. None of this adds up according to his initial statements.

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Well, the drugs he mentioned are in there. That much is true. Regarding the doses, no, but the drugs themselves are there and nothing else was.

Beachlover said:

There has to be some metabolized from the night before and the night before that. It isn't just what was pushed that same night that is going to show up. There is a cumulative effect of this and all drugs.

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Are you referring to propofol or lorazepam, or both? I think I read somewhere that propofol is nearly all cleared from the blood within approx 24 hours......so after a few hours there will be some negligable levels of propofol in the blood but the level would be a lot under the clinical / therapeutic level, so not really relevant here.

Victoria83 said:

Do medications clear the body at different rates? I mean, depending on the type of drug it is, and the metabolism of the person who's had the drug? I'm assuming that they do, and this would be part of the forensic evidence? So, a "cumulative" effect, or not, would depend on knowing this? Also, I'm assuming that when a person dies, that the process of "clearing the drugs from the body" stops? Or do the drugs continue to dissipate even after death?

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Yes, each drug has it's own metabolism rate and clearance rate and this does depend on a number of parameters, and also varies to a certain extent between individuals. A series of equations are used to model and estimate this. A toxicologist / pharmacologist can work these out and should have forwarded their findings and calculations to the DA, and hopefully made predictions as to what they think was administered when, including any possible cumulative effect. In my honest opinion, I doubt a cumulative effect would have caused these high blood levels, but it's hard to say for sure without all the results. It does seem like they are holding back lots of information, which could be a good thing at this stage.

I think metabolism and clearance does stop pretty much straight away after death, but what can occur is a kind of redistribution with some drugs in different tissues, but think I read in another thread that lorazepam does not do this to a great level.

daisydaisy said:

Are you referring to propofol or lorazepam, or both? I think I read somewhere that propofol is nearly all cleared from the blood within approx 24 hours......so after a few hours there will be some negligable levels of propofol in the blood but the level would be a lot under the clinical / therapeutic level, so not really relevant here.

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I was speaking somewhere earlier about the urine found at the bedside which had a very small amount of Propofol, and knowing what we know now it was probably from the night before use because he was definitely awake when he produced that urine.