Thank you for clarification regarding the blood levels, I got it now.

I HATE math and I admittedly suck at it. Am I nuts or are we BOTH not actually correct on this one?

0.13mg is in fact 0.065% of 200mg
13 mg would be 6.5%
1.3 mg would be 0.65%

Regarding postmoretm propofol levels: We have a handful of cases where we KNOW that the person died from a self administered dose of propofol and no other drugs were involved. In those cases the blood levels on autopsy ranged from 0.53 mcg/ml to more than 6.0 mcg/ml. In other words, there are cases where the propofol level is subtherapeutic…one would not expect that the person would be asleep much less dead from the amount seen in the blood. Clearly these levels are not accurate. Except for one thing….IF THEY ARE HIGH then they do indicate that at least that amount of propofol was administered. While the levels can be falsely low after death they CANNOT be falsely high, at least not to any significant extent (since PMR could elevate the level slightly).

Thanks for commenting! Well, we are both a bit off:

“332 cases out of 78,443 is not 0.004%, it’s 0.4%.
And 8 cases is 0.01%, which is not that small.”

Indeed it should! However 0.01% in the world of statistics is very, very, very small in fact. So small that it is not statistically significant. It is as if such cases simply do not exist. The statement “Benzodiazepine overdoses are not fatal” is, in light of this data, accurate.

Thanks for you comments! I agree with your take on the events. Murray did his usual propofol infusion and left the room thinking Jackson was fine. Jackson stopped breathing. I would say that Murray returned at least 15 min after Jackson stopped breathing…or at least 10 min after Jackson’s heart stopped. He then went into damage control mode.

As for tolerance to propofol, we actually have quite a lot of evidence both from research and clinical anecdotes, that tolerance to propofol does develop.

http://www.anesthesia-analgesia.org/content/103/2/359.full

http://journals.lww.com/ejanaesthesiology/Citation/2009/09000/Increase_of_propofol_requirement_after_repeated.19.aspx

Thank you for an excellent response. First, what evidence do we have that Jackson was a benzodiazepine addict? Outside of the three months in which Murray was involved in the care of Jackson, I do recall coming across statements of individuals close to Jackson which revealed that he took large amounts of benzodiazepines in an attempt to induce sleep. I will search for information posted here. I believe one of the sources was Jackson’s friend Deepak Chopra.

Focusing only on the three months that Murray was involved in Jackson’s care we have only Murray’s statements that on a nightly basis he administered propofol to induce sleep in Jackson. However we also have the undisputed records of the medications Murray purchased on a monthly basis for use in his treatment of Jackson. The fact he purchased them monthly is significant in that one would not keep purchasing stocks of intravenous controlled substances unless presumably one was administering them. Especially when the purchase is in such large quantities.

Murray ordered, in total, 40 10 mL vials of midazolam 1 mg/mL, and 20 10 mL vials of lorazepam 2mg/ml over the course of three months in three divided orders. Any addictionologist will tell you that if an individual is given nightly intravenous doses of these benzodiazepines at a therapeutic level for more than two months this alone is likely to result in physical dependence. Granted I am making the assumption that Murray was administering these medications to Jackson and not throwing them away or diverting them for other purposes. Should Jackson have been taken off benzodiazepines cold turkey I think the argument that he would not have had withdrawal symptoms is the more difficult one to support.

As for the half tablet, we do not know who broke it in half. It is not particularly surprising that the oral benzodiazepines were not overused when we have a physician administering IV lorazepam on a nightly basis and the drug has a 12 to 16 hour half-life. the defense is claiming that Jackson ingested 6 to 8 lorazepam tablets the morning of his death. Apparently there is more lorazepam in tablet form at play here then the single prescription you allude to.

Propofol has very similar effects in the brain as other more common drugs of abuse such as benzodiazepines, opiates, and alcohol. Studies in animals and humans have shown that the addiction potential of propofol is similar to these drugs. It affects the dopaminergic reward system in the prefrontal cortex and the nucleus acumbens in the same way. There is indeed a withdrawal syndrome associated with propofol as well as tolerance in patients in an ICU setting who have been sedated with propofol for extended periods of time (mere weeks, not months). This phenomenon has not been well studied in individuals who have abused propofol.

The first source I rely on in my statement that 200 mg dose of propofol administered to a patient is expected to be lethal if one does nothing to support the patient’s respirations but instead merely walks out of the room is my own 20 years of administering anesthesia, specifically administering propofol in similar doses on what has to be more than 10,000 occasions. Any anesthesia professional will tell you that if you administer an induction dose of propofol and then do nothing you should expect that you have just killed your patient. These patients stop breathing. The notion that the short duration of action of propofol results in the patient waking up in time to gasp for air and save themselves is absurd. Any “experts” who opine that it is thus impossible to self administer an induction dose of propofol and cause your own demise are, when one looks at whether they have any experience with the drug being used to induce anesthesia, revealed as being far from experts at all. And I have not even taken into account the co-administration of potentiating drugs like benzodiazepines which only reinforce this lethality.

I am unaware of ‘experts’ who thought that self administration of 200 mg of propofol could not be fatal until some deaths were seen. I am very familiar with just about every study, research paper and published account of propofol abuse and addiction and have never come across such a claim. Deaths from accidental overdose during self administration of propofol has been reported around the world for more than a decade. In a handful of individuals postmortem has revealed pulmonary edema presumably from cardiovascular collapse, however the majority of individuals have no such finding and the presumed mechanism of death is respiratory depression leading to cardiac arrest. Respiratory depression and respiratory arrest are the causes of death in the majority of these cases. It is not cardiovascular collapse from rapid administration.

In fact when propofol is administered in operating room by anesthesia professionals cardiovascular collapse from rapid administration is not a paramount concern. Certainly when administered to the elderly or those with underlying cardiovascular disease the more rapid the administration the greater the expected drop in blood pressure. Thus administration is accomplished over a minute or two. But cardiovascular collapse is an extremely rare event. Administration of an induction dose of propofol which results in the induction of a plane of general anesthesia regardless of the speed at which it is administered produces profound respiratory depression which if not treated far more often than not results in a fatal outcome. Not to mention cerebral ischemia in those that do survive a prolonged lack of adequate respiratory function and oxygenation of the brain.

Of COURSE bolus dosing is used in procedures….but NOT at induction doses with the idea that no respiratory support will be required. Also keep in mind that surgical/procedural stimulation lightens anesthesia greatly and a dose of propofol is a very different thing when it is immediately followed by an incision or reduction of a fracture. Propofol infusions in unintubated patients are used all the time…..but not at doses which maintain general anesthesia. Sedation doses are used, and the patient continues to breath.

I would be VERY interested in reading the cases of individuals who were self administering “100-200 mg or more” at a pop. Post any links you may have.

For some insight into my background in this area and a number of links to published research see:

http://lawmedconsultant.com/2532/propofol-explained-factual-expert-answers-on-jackson-case

Why would you jump to the conclusion that Jackson “popped” pills on June 25th when apparently he did not “pop” them anytime before?

Just because Murray was ordering these supplies does not mean he used them all as he ordered them. We see there was not a high level of midazolam at death (it was inactive). Diazepam was inactive. Lorazepam was active, the only benzo active. He could have continued with benzos which have a safer profile than propofol, especially if we are considering home use, though none of these medications are safe in a home. We have two used IV vials of 10 mL of lorazepam. We have an MD who admits to giving IV lorazepam. We know he lied about how much propofol he administered, too, among many other lies. Two syringes used for 25 mg? I do not think so.

Murray himself stated that Jackson slept fine the night before on (and possibly a few other nights before) on benzos alone. Then, he jumps to the conclusion the benzos stopped working because of propofol withdrawal–wrong, there is no physical withdrawal from propofol.

I would like to know what studies you referenced to say that 200 mg should kill a patient if one walks out of a room. Experts thought it was impossible for someone to die self-administering 200 mg until there were a few deaths from propofol abuse and this was the suspected dose. In fact, it is not the amount but the rapidity of the dosing, at 200 mg, that caused death and it is an instant death do to cardiovascular collapse. If 200 mg is not pushed rapidly, it should not kill someone healthy, typically. Of course, precautions should be in place given there are always risks.

The typical induction bolus dose for general anesthesia is 2-2.5 mg/kg. Assuming a weight of 60 kg that is about 120-150 mg. That should not be lethal unless it is given too rapidly. There are many instances were bolus dosing is given for a rapid procedure in which the patient is fine. There are even instances there the medication can be given by a controlled drip and the patient not be intubated (ex. dentistry). I have actually read a few cases of propofol abuse was 100-200 mg doses or more. In one case a medical student abused 100 mg approximately 100 times a day. He was alive when the article was written.

As I assume this argument will continue so I think it is safe to agree to disagree on certain terms.

I have a question. Regarding the propofol you are saying,
“[levels] can never be said to be indicative of the exact amount of propofol administered.” So, does that mean that based on the blood level you cannot say how much the person was given? But later on you say that it must have been at least 100-200 mg based on the blood level – so you can make that estimation. How precise is it? Can Murray be telling the truth that he only gave Michael 25 mg?

It’s just very hard to explain why he suddently gave him 100mg when he used to give him 50mg in prev. nights (unless it was a planned murder). Or is it possible that he lied, and he had actually been giving Michael 100mg each night? But then his breathing should have stopped earlier, shouldn’t it?