Toxicology In The Michael Jackson Manslaughter Trial
October 08, 2011Witness 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:
Original anzeigen (0,2 MB)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 (0.004%) resulted in major toxicity and only 8 (0.0001%) 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 0.00065% 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.
http://lawmedconsultant.com/2575/toxicology-in-the-michael-jackson-manslaughter-trial