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Toxicology In The Michael Jackson Manslaughter Trial
Witness testimony concerning the autopsy and toxicology results has begun in the trial of Dr. Conrad Murray for voluntary manslaughter in the death of Michael Jackson. This is likely the make or break area of testimony for the defense, who has claimed that Jackson caused his own death by self administering both oral lorazepam and oral and/or IV propofol. It is highly technical testimony, with large amounts of medical and scientific jargon and principles which cannot help but confuse the jury at times.
Law Med will go through the evidence and testimony in order to simplify and clarify what is becoming. in our view, intentionally muddled by the defense. We don’t blame them, since it may be their only hope of getting Murray off. The facts are certainly of little use towards that end. Even though we are ‘simplifying’ the information, it is still intensive to digest. Read some, take a break, come back to it. If you have any questions ask them using the comment form at the bottom of the article and we will answer them. Or contact us HERE. The lawyers on both sides have done their homework and appear to have a working knowledge of the pharmacology and toxicology of the drugs at issue in this case. If they can do it so can you…believe me. Smarter than us? Its not hard…so if you find an error let us know. Law Med has expertise in all of the drugs named and their administration, as well as interpretation of toxicology reports, but forensic toxicology is not our forte. If you are a juror of course, you should not be reading this so shame on you and stop now.
During the autopsy, blood samples were obtained from various areas in the body (more on the significance of these multiple samples later), as well as samples from the stomach (gastric) contents, the fluid in the eye (vitreous) and urine. All were tested for various drugs and reported in the final autopsy documents.
Drugs found in Jackson’s system were lorazepam (Ativan), midazolam (Versed), diazepam (Valium), nordiazepam (metabolite of diazepam). ephedrine, lidocaine and propofol (Diprivan). Significant to the case are the lorazepam and propofol results, and to a lesser extent the midazolam and lidocaine. Here they are:
Click to view enlarged document.
Diazepam, lorazepam and midazolam are all in the family of drugs known as benzodiazepines, which are sedative hypnotics. Each differs in it’s time to onset of action, duration of action, and metabolization time. Diazepam and lorazepam are common prescriptions in tablet form administered for anxiety and sometimes as a sleep aid. Both were found in pill form in Jackson’s house. Both also are available in IV form for hospital use, and IV lorazepam is sometimes used in surgery. Murray was ordering IV lorazepam in huge amounts, likely administering it IV on a near daily basis. IV administration of any benzodiazepine results in a much faster onset of action and a much more pronounced effect compared to oral administration.
Bezodiazepines have a low toxicity, despite their pronounced depressant effect on the central nervous system. In other words, while they make an individual very sleepy, even unconscious in large amounts, they rarely cause someone to stop breathing. Even in overdose they almost never cause death. In 2008, a total of 78,443 benzodiazepine single-substance exposures were reported to US poison control centers, of which 332 (0.4%) resulted in major toxicity and only 8 (0.01%) resulted in death. These drugs do however potentiate the effects of propofol, which means when administered together it takes much less propofol to reach a desired (or undesired) effect. This includes respiratory depression or apnea (breathing stops). All benzodiazepines are addictive and prolonged administration can result in tolerance requiring higher and higher amounts to cause the same effect.
Nordiazepam is a metabolite of diazepam, meaning it is formed in the body as diazepam is metabolized (broken down). Ephedrine is a common over the counter sinus medication. Aside from the fact that Murray told police that Jackson was administered a 10 mg valium tablet (relatively small dose) at 1:30 am on the morning of his death the drug plays no part in his death and the amount found in his system was just a trace. Ephedrine, was present in the urine. We will make no mention of either beyond this as they are simply not important.
The midazolam detected in the blood, as well as in the urine, was of a very small amount. Therapeutic blood levels of midazolam is 0.08-0.25 mcg/ml. Here, a plasma concentration of 0.0046 mcg/ml was found. This is a VERY small amount. It was also found in small amounts in the urine. From these results was can conclude that while Jackson received an administration of midazolam sometime in the previous 24-48 hours, he did not receive it the morning of his death and it played no part in his death. The amounts found are just too small. But Murray has claimed that he administered 2 mg IV midazolam at 3:00 am and again at 7:30 am. This appears to be false. Why he would claim this begs understanding, but there is no way it happened according to the blood and urine levels. Midazolam is metabolized and excreted in the urine fairly rapidly, but not THAT rapidly. The elimination ‘half life’, meaning the time it takes to excrete 50% of the drug, is 2-6 hrs. The most significant role midazolam plays, aside from Murray’s falsehood, is that Murray was ordering it in huge amounts, so it clearly was being administered frequently, just not on the morning in question.
Lidocaine is a common local anesthetic which is added to propofol prior to injection in order to minimize the burning sensation which propofol can cause. If you have ever had stitches or a root canal it is likely that you were injected with lidocaine first to numb the area. Lidocaine did not contribute to Jackson’s death. Its only significance is that wherever it is found in Jackson’s system, we also find propofol, as expected.
Lorazepam, a benzodiazepine as we have stated, was available in the Jackson home in both tablet and IV form. It bears pointing out that no patient, regardless of setting, should have access to pill forms of any medications they are also receiving IV. Jackson’s bedroom was littered with bottles of various bezodiazepines including in addition to diazepam and lorazepam, clonazepam (Klonipin) and temazepam (Restoril). A patient can potentially self administer any of these drugs causing dangerous potentiation of other medications, or cause an overdose when the care giver administers an IV medication not knowing about the oral dose.
This is one of the scenarios which the defense is claiming. It has become their position that Jackson took up to 8 lorazepam 2 mg tablets while Murray was out of the room. This is supposedly during the same 2 minutes Murray said he left the room prior to finding Jackson not breathing. Apparently they are inferring that this contributed to Jackson’s death. We can state that this is simply impossible. First, there were no pill fragments found in the stomach on autopsy. Second, absorption of lorazepam from the stomach takes far longer. Jackson would not have had ANY effect from an oral medication in the time frame specified. Third, IF Jackson had taken oral lorazepam in this quantity, one of two things would be seen: either no pills are in the stomach and there is a high blood level, or pills are found in the stomach and there is a low or no blood level. Instead we have no pills and a therapeutic blood level (neither high nor low, but rather the expected level from an appropriate dose). A therapeutic level of lorazepam in the blood is o.o1-0.2 mcg/ml. The blood level of lorazepam in this case is 0.169 mcg/ml, consistent with the IV administration by Dr. Murray (below), and is an expected, non-toxic, therapeutic level.
The coroner’s office did not test the gastric contents for an actual level of lorazepam, since the blood results which showed a low amount of lorazepam, any amount in the stomach would be irrelevant to the cause of death. The defense claims that the amount of lorazepam in the stomach was 4x the amount found in the blood according to subsequent testing they had done. This would not have affected Jackson however, since it is the amount in the bloodstream which affects the patient. Rather they are using this to claim that Jackson took oral lorazepam without Murray’s knowledge, apparently trying to bolster the claim that Jackson swallowed propofol without his knowledge. It seems a far stretch that even IF Jackson took oral lorazepam without Murray knowing (a medication he takes is prescribed and has taken orally many times before), that he would drink propofol (a medication never given to him orally before). Especially when he has someone willing to inject it into him every single night.
Murray has told the police that he administered 2 mg IV lorazepam at 2:00 am and then again at 5:00 am. This is consistent with the toxicology results and is likely the truth. In an average patient, the level of lorazepam in Jackson’s blood would produce noticeable central nervous system depression (very sleepy or sleeping) and would potentiate the effects of any propofol that was given. In Jackson however, who had been receiving benzodiazepines in significant amounts on a daily basis for some time, tolerance may be an issue. A “therapeutic” blood level in such patients is not therapeutic at all and higher blood levels are required to obtain a therapeutic effect. For all of these reasons, lorazepam played little if any role in the death of Michael Jackson.
Now we get down to it. Propofol is our killer here. To learn everything you need to know about the drug propofol, read Law Med’s posting “Propofol Explained: Factual Expert Answers On Jackson Case“.
Evaluation of post mortem blood levels of propofol is fraught with difficulties. This is primarily because of a lack of research into the subject as well as what can only be described as the strange behavior of propofol after a fatal dose. What we do know is gleaned from the handful of published cases of death from either self administered propofol during abuse, or in one case propofol used as a weapon in a homicide. These published cases had post mortem propofol levels which ranged from those lower than would be required to anesthetize a patient to levels which were much higher. It appears that a low post mortem blood level of propofol does not rule out propofol as a cause of death. At the same time there is no evidence of false high levels of propofol post mortem. In other words, levels may be found to be deceptively low even though propofol killed the individual, but they are predictive of propofol ingestion when high, though they can never be said to be indicative of the exact amount of propofol administered.
Baselt’s textbook The Disposition of Toxic Drugs and Chemicals in Man (7th edition) mentions that in 5 fatal cases of acute propofol poisoning, postmortem blood propofol levels ranged from 0.5 – 5.3 mcg/ml. The accepted therapeutic blood levels after a typical 2.5 mg/kg anesthesia induction dose of propofol are 1.3– 6.8 mcg/ml. As you can see, the are cases of fatal propofol administration where the blood levels were below those expected to anesthetize a patient and cause breathing to cease. Levels below 1.0 mcg/ml are considered sedation levels.
In this case, the following blood levels were found: Heart blood – 3.2 mcg/ml; Hospital blood – 4.1 mcg/ml; Femoral blood – 2.6 mcg/ml. This puts the propofol blood concentration in Jackson in the ‘therapeutic’ range for someone having a general anesthetic. For an individual who is not intended to be anesthetized to the point of cessation of breathing, the levels found in Jackson are FATAL. There is no doubt, JACKSON DIED FROM PROPOFOL INTOXICATION.
The total amount of propfol found in the stomach was 0.13 mg. Compare this to the amount of propofol necessary to be swallowed if the high blood levels seen are to be reached. If given IV, the dose would have to be an anesthetizing dose in the range of at least 150-200mg, since that is what the high blood levels indicate. That means that IF swallowing the same amount of propofol gave the same effect as injecting it then the amount swallowed would also have to be 150-200 mg. However, it takes MUCH more propofol when swallowed to reach the same blood levels as when given IV due to the manner in which propofol is absorbed in the stomach according to the limited information available in this area. Not a lot of research has been done regarding oral administration of propofol since it was never intended that it be swallowed.
What does this mean? The 0.13 mg of propofol found in the stomach is MINISCULE. Assuming, conservatively, that 200 mg would need to be swallowed to reach the blood levels seen, the 0.13 mg found is 0.065% of the amount swallowed. The amount which would have to be swallowed in order to reach the blood levels found, even when considering Dr. Murray’s admitted injection of 25 mg IV would be many times the 200mg amount however. This refutes the defense claim that Jackson swallowed propofol causing his own death, as much more propofol would be expected to be found in the gastric contents.
In addition, absorption into the blood stream when a medication is taken orally is MUCH slower than when given IV. Dr. Murray says he was out of the room for only 2 minutes and that when he returned Jackson was not breathing. It is IMPOSSIBLE for any amount of swallowed propofol to cause this in the time frame alleged. It is also impossible that all but 0.13 mg would have been absorbed into the blood stream in this period.
There is another far more plausible explanation for the small amount of propofol being found in the gastric contents. Postmortem redistribution (PMR) refers to the changes that occur in drug concentrations after death. It involves the redistribution of drugs into blood from solid organs such as the lungs, liver, and heart muscle. Postmortem drug concentrations do not necessarily reflect concentrations at the time of death, as drug levels may vary according to the sampling site and the interval between death and specimen collection. The recommended sample site for post mortem toxicology is the femoral vein due to its relative remoteness from solid organs. Vessels and locations closer to solid organs would be expected to have higher concentrations than the femoral vein. PMR can also take place into the stomach. This is the most likely cause of the small amount of propofol found in Jackson’s gastric contents.
Some drugs are more predisposed to PMR than others due to their particular makeup. We know that propofol does undergo some amount of PMR since blood taken from the heart (one of the organs which is know to leak drugs into the blood under PMR) contains more propofol than the femoral vein sample (3.2 vs 2.6 mcg/ml).
FINAL CONCLUSIONS: The evidence does not support the premise that Jackson drank propofol. Could Jackson have self injected propofol in the short time Murray claims he was out of the room? Yes. However, Jackson would not have been dead by the time Murray says he returned. He should easily have been resuscitated. If Jackson self administered propofol in his IV, the Murray remained out of the room for at least 8-10 minutes we estimate. The most likely scenario is that Murray started a propofol infusion after giving Jackson a bolus of propfol and after some amount of time passed Murray believed that Jackson was stable. Murray then left the room to chat on the phone and Jackson stopped breathing. Murray was gone for more than 5 minutes after breathing stopped, and likely much longer. Upon his return he immediately knew he had screwed up and that Jackson was dead. He removed the propofol infusion, hiding it for disposal later, which he did. This explains the delay in calling 911 as Murray panicked and thought about exactly what to do next. The only conclusions we can draw from the toxicology report are that Jackson did receive a dose of propofol sufficient to stop his breathing, and that it was given IV.
JACKSON AUTOPSY REPORT
Related Posts
- Propofol Explained: Factual Expert Answers On Jackson Case
- Jackson Received More Propofol Than Anyone In Medical History
- STUNNING Propofol Evidence In Jackson Physician Manslaughter Trial
- Jackson Propofol Homicide Trial Begins September 26
- Jackson’s Dr Murray Manslaughter Trial to be TV Event
There are some errors with the article above:
The half-life of midazolam is 2-6 hours in the average patient–this likely means he had received some within the past 24 hours, not 48 hours (use the rule of 5 half-lives for elimination). You are correct that Murray’s supposed timeline of administration is not correct concerning midazolam.
I think it is important to state some of the benzodiazepine prescriptions were from months prior and had excess tablets (ex. Restoril was from 12/2008 and had remaining capsules).
For lorazepam, the therapeutic level can range from as low as 10 ng/mL to as high as 300 ng/mL (depending on the source). However, what is not being taken into consideration is that 0.169 mcg/mL (169 ng/mL) far exceeds the amount that should have been given for insomnia. Given someone should be taking, for sleep, an oral dose of about 1-2 mg, that should give them a blood level of about 20 ng/mL, not 169 ng/mL. Tolerance or not, the fact that the propofol was fatal likely indicates this dose of lorazepam was causing some sort of respiratory depression in Jackson. It is rare for 100-200 mg of propfol (the estimated dose given the blood level) of propofol to be lethal. The blood level of 169 ng/mL does not correspond to Murray’s elaborate tale of times of administration, either. He admits to only giving 4 mg hours before Jackson’s death. There was likely about 11 mg (IV) of active lorazepam in MJ’s system at the time he died–assuming that blood level to be a peak. There is no excuse for this. Though it may not be lethal, it likely did play a role in his death, as the autopsy states it was a factor in the death. If one consider that, that this medication was sedating him, then why was the propofol given? I will leave that up to the reader to decide.
The bottle of propofol in the saline bag–that was a 1000 mg bottle. (FYI–a gravity-fed propofol drip would likely be fatal as a pump should always be used–Murray should have known this, too.) We have the two syringes–they can only deliver 100 mg at a time (not including lidocaine). The estimated blood level was between 100-200 mg. See where I am going? Jackson could not have administered over 100 mg to himself at one time.
Gigi~
Regarding midazolam: The blood level measured is so EXTREMELY small that I included up to 48 hrs. I also wonder if PMR is in play here.
Temazepam was indeed from 2008. However the clonazepam was from April 2009. Temazepam to Jackson would have been like taking tums….zero effect on his CNS. Jackson was a tremendous benzodiazepine addict with significant tolerance. How can I say this? Because of the amount of IV benzodiazepines (lorazepam and midazolam) being ordered monthly for Jackson.
See: http://lawmedconsultant.com/2458/stunning-propofol-evidence-in-jackson-physician-manslaughter-trial/
I agree that the 169 mcg/ml lorazepam level is likely too high for 4 mg IV in 2 doses over a number of hours. I also cannot imagine Jackson not popping a few oral lorazepam during this same period as he struggles with sleep.
I do have to disagree with “Tolerance or not, the fact that the propofol was fatal likely indicates this dose of lorazepam was causing some sort of respiratory depression in Jackson. It is rare for 100-200 mg of propfol (the estimated dose given the blood level) of propofol to be lethal.”
What has been lost on many in the medical community who have commented on propofol in this case (see http://lawmedconsultant.com/2532/), is that administration of 100-200mg IVP as a single rapid dose is FREQUENTLY fatal without some intervention to prevent an obstructed airway from relaxation and loss of protective reflexes, and/or artificial respiratory assistance. As I stated, if you administer 200 mg of propofol to a patient and then walk out of the room, you should EXPECT the patient to die. A live patient when you return 10 min later would be the exception rather than the rule.
In fact the amount of proopfol which in a single IVP dose is more likely than not to be fatal without respiratory intervention, is more than likely 100 mg or a bit less. Multiple deaths are reported annually in anesthesia professionals who were abusing propofol, and it is estimated that ~20% of abusers will suffer a fatal outcome. And these are propofol EXPERTS. Recovering propofol abusers relate 50 mg doses being typical. They are NOT administering 100-200mg, and the vast majority of deaths reported and published with toxicology results had no other drugs on board.
Also, for Jackson’s weight, 60-150 mg of propofol was a general anesthesia induction dose. which one should ALWAYS assume will cause breathing to stop.
See http://lawmedconsultant.com/2485/jackson-received-more-propofol-than-anyone-in-medical-history
So I jump on my soap box again and say that 100 mg or less of propofol, with or without lorazepam on board, could have killed Jackson…and it would not be surprising.
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.
And 0.13mg is 0.65% of 200mg. You seem to forget to multiply by 100%
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?
I do not think we can unequivocally state that temazepam had “zero effect” given the patient is not here to witness that lack of an effect. Furthermore, there is no evidence that he was a benzodiazepine “addict”. He did have a lot of prescriptions for benzos but he did not take them as prescribed. He had tempazepam left over from 12/2008, he had left clonazepam and lorazepam tablets from 04/2009, and then diazepam was written June 20th–he could take up to four a day–only three were missing over that 4 day period. Now, whether or not some tolerance occurred from what Murray was doing, that is very possible, but to what degree we do not know exactly. Today we learned that one of the tablets in the lorazepam bottle was halved–what kind of benzodiazepine “addict” halves a benzo tablet?
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.
Gigi~
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
Morinen~
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.
Morinen~
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).
Yes, I got the third number wrong too. The correct would be 0.065%, of course
Thank you for clarification regarding the blood levels, I got it now.