This is Part 1 of 3 of Dr Steve Shafer's answers to MJJCommunity questions. In this first instalment, Dr Shafer will be answering questions about Michael Jackson, himself (Dr Shafer) and Conrad Murray trial in general.
MJJC: While watching the trial it felt like there’s an animosity or fall out between you and Dr White. Are we correct about this? If yes did this fall out stem from the events of the trial or is there a history to this?
Dr Steve Shafer: Paul has been a friend for nearly three decades. The Paul White you saw on television was not the Paul White that I have known since medical school. He has made many contributions to our speciality. It is my hope that his contributions are his permanent legacy, not his defence of Conrad Murray.
Paul has been a cherished mentor since I was a medical student. I was not his “student” as Chernoff stated, and I did not appreciate the implication that Paul taught me what I knew about propofol. However, Paul has given me counsel on everything from medical school to romance. I was expecting Chernoff to ask “Hasn’t Dr White been a mentor to you?” I was ready to say “yes”.
MJJC: What did you think of Dr White’s testimony and his behaviour? Did anything he said change your opinion about your colleague? Were you surprised by the things he said and things he did (such as his comments to the media) or didn’t do (such as not doing his own charts, not overseeing the Beagle experiment)?
Dr Steve Shafer: There were factual errors in Paul’s testimony. Paul is capable of outstanding scholarship. I don’t know the dynamics of his relationship to the defence team that led to him not doing the heavy lifting that he usually does when it comes to checking the literature. I wish he had contacted me in advance. I would have been happy to help him review the literature and explain the science.
The different approaches of science and law to discerning the truth failed Paul. If this had been an argument over a scientific manuscript, Paul and I would have spoken directly, without attorneys trying to discredit either one of us. We would have lined up papers, and arguments, and “duked it out” by e-mail, or perhaps over an extended lunch at one of our favourite Mexican restaurants. That would have worked and the science would be right (at least as “right” as we could get it). There would be no adverse consequences for either of us. As scientists collaborating to “get it right” we would have done well. The criminal justice system isn’t set up to allow scientists representing opposing sides to collaborate in an effort to find the truth.
MJJC: Are you still friends with Dr White?
Dr Steve Shafer: There may be some bruised feelings, but we will get past it. We have a lot of shared history.
MJJC: You worked with Dr White and you are/were friend with him. So how it's possible to have 2 completely different opinions about what happened the night of 25 June 2009 from two close people?
Dr Steve Shafer: Paul White admitted in court that he only considered self-injection scenarios. This severely limited the scenarios he considered.
MJJC: What do you think of your colleague Dr White going out of his way to justify Conrad Murray's actions, from a medical point of view?
Dr Steve Shafer: I don’t understand it at all.
Questions about Dr Murray
MJJC: Did you purposely NOT refer to Conrad Murray as a doctor during your testimony? Have you heard the news reports about how furious it made him?
Dr Steve Shafer: I was not aware of that. It would be very unlike me to refer to him as “Mr Murray,” as my habit is to be respectful. I probably referred to him simply as “Conrad Murray”. If I never said “Dr Conrad Murray”, then this is indeed a Freudian slip. I don’t see him as a doctor.
MJJC: Viewers at home could see Murray losing his temper when you started the IV demonstration, was that temper flare up noticeable to you from where you were positioned in the courtroom?
Dr Steve Shafer: I read about it, but I didn’t personally observe it. I was focused on the jury.
MJJC: If so, were you fearful of what Murray may do (i.e. did you think there was a possibility that he would physically attack you)?
Dr Steve Shafer: Not at all.
MJJC: What are your thoughts on Murray as a doctor?
Dr Steve Shafer: I believe he violated the fundamental trust between doctors and patients, and that he did so not in an isolated incident under duress, but intentionally and repeatedly. That is not something a doctor would do.
MJJC: Did you hear about and/or watch the Conrad Murray documentary.
Dr Steve Shafer: No, I just heard about it.
MJJC: If so what are your thoughts about it. Do you feel that his participation in this documentary further proves Murray's lack of professional ethics and an unsuitable candidate for the medical profession?
Dr Steve Shafer: I can’t imagine why he would participate in a documentary that would be shown prior to sentencing. Evidently, they filmed the attorneys swearing at each other, with Paul White and Conrad Murray on a couch in Flanagan’s home. It seems reckless for everyone involved.
Questions about the role of propofol in Michael Jackson’s death
MJJC: Based on everything you know, what do you think happened on June 25, 2009?
Dr Steve Shafer: Michael Jackson died from respiratory arrest (his breathing stopped) while receiving propofol, exactly as the coroner reported. There was a contribution of the lorazepam, also as reported by the coroner. The coroner got it right.
MJJC: How convinced are you that MJ was on a drip that night?
Dr Steve Shafer: I’m completely convinced. Murray admitted to using a drip every night. He said he was trying to wean Michael Jackson. I don’t believe him. The urine propofol levels suggest massive doses, more than 2000 mg, as I explained in my rebuttal testimony. The blood levels show anaesthetic concentrations of propofol. It all fits with an infusion (drip).
MJJC: If we disregard Murray's police interview, in your professional opinion, how long was MJ gone before Murray finally found him? Some experts are under the impression that the delay in calling 911 can only be explained by him knowing MJ was already dead.
Dr Steve Shafer: I think he was already dead, but that is really speculative. I don’t believe anything Conrad Murray says, and there are no records. My guess that he was dead is based on the limited window between stopping breathing and death (10-20 minutes). Murray would have to observe him in that window to have a chance to revive him.
MJJC: There are some rumours that Michael actually ate a meal the night he died in Murray's so-called "care". Do you think Michael was fasting for the required time? Or was this yet one more deviation from the standard of care by Murray? What are your thoughts on this?
Dr Steve Shafer: I’m not aware of any data suggesting Michael Jackson ever fasted. It doesn’t come up anywhere in the record. My guess is that he ate, because he would likely be hungry after a vigorous rehearsal.
MJJC: What do you think about June 19th (Kenny Ortega's email describing Michael- chills, seeming lost), and June 21st (hot and cold symptoms described by Cherylin Lee). What could those symptoms come from?
Dr Steve Shafer: It is hard to know. The defence proposed that those might be withdrawal from Demerol, and that is correct. It might also be withdrawal from lorazepam. Propofol withdrawal hasn’t been described, because nobody other than Michael Jackson has ever received propofol night after night for insomnia. However, at least in theory, it could be propofol withdrawal.
However, it could also be the usual sort of illness: the “stomach flu” or a bad cold. There is no way of knowing.
MJJC: Do you have an opinion about June 23rd and 24th, when Michael seemed to be feeling great? What could this improvement come from?
Dr Steve Shafer: I don’t know. After the trial, I watched “This is It.” There was obvious excitement and exuberance as rehearsals were nearing the end, and the tour was approaching. It could simply be excitement and exuberance in expectation of the tour.
MJJC: Does it surprise you MJ didn't die sooner than June 25th after finding out Murray was given MJ Propofol without proper equipment for 2 months (according to Murray) prior to MJ's death?
Dr Steve Shafer: Yes. I think that is quite surprising. We don’t know if there were prior close calls, because there are no records.
MJJC: May 2009 audio recording of Michael in which he was slurring his words attracted a lot of attention. In an interview, Dr. Murray said Michael was under the influence of Propofol during that recording. However, some people say Propofol does not cause slurred speech. What do you think about that recording? Any idea what drugs can cause that speech?
Dr Steve Shafer: Sedatives cause slurred speech. This could have been caused by midazolam, lorazepam, or propofol.
MJJC: Do you think there was a chance for Michael to be in good health and to continue normal usual life after such long respiratory arrest even if paramedics could reanimate him?
Dr Steve Shafer: Definitely, if they arrived in time.
MJJC: This is a hard question but we have to ask. When there is an overdose of Propofol and it causes death like it happened to Michael, does the person suffer? Do they feel pain? Or is it like dying in your sleep that you feel nothing?
Dr Steve Shafer: It is an easy question to answer: there is no suffering from a propofol overdose. The person falls asleep quickly and comfortably. The brain is deeply depressed, and the brain never returns to consciousness.
MJJC: If Michael had been your patient and asked you for Propofol to help him sleep, how would you have responded? What would you suggest to him? Would you have recommended he see a sleep specialist?
Dr Steve Shafer: Absolutely the right question to ask! I would have referred him to a sleep specialist. He had a very serious sleep disorder that was threatening his tour, his ability to perform, his ability to create music, and potentially his life. It needed urgent care from someone who knows what he or she is doing.
MJJC: Do you know what the long-term effects of using Propofol would be? Murray has indicated that MJ was using Propofol for 6 weeks, apparently for sleeping 8 hours or so a night. Have you ever read about case studies of patients doing this or, as it was put forward in the trial, was MJ an experiment?
Dr Steve Shafer: This was an experiment. I don’t think any other patient in the world has ever received this. There may be long-term effects – that is a question that can’t be answered without clinical research. I don’t know what effects to expect, but it seems likely that tolerance and dependence would develop.
MJJC: How about even longer terms such as months or even years taking of deep sedation of Propofol, could it affect human health and any organs? Is it possible to take Propofol for a long time and don’t have any associated negative side effect?
Dr Steve Shafer: We don’t know – the studies have not been done.
MJJC: There might not be enough information to have a clear picture of what was going on, but we would like to know your opinion about what Murray was prescribing to Michael (from late 2006), the amounts of midazolam, lorazepam and flumazenil Murray was buying, and the possible consequences of such a treatment.
Dr. Steve Shafer: I am not sure what amounts you are referring to. I am aware of the drugs that Murray purchased in 2009, but I did not review his previous treatment of Michael Jackson, because it didn’t relate directly to the questions I was trying to answer at the trial.
MJJC: According to his police interview, it seems that Murray knew he shouldn't mix Lorazepam and Propofol, so we are confused about their use together. Why would Dr Murray or anyone mix those together?
Dr Steve Shafer: There is nothing wrong with giving lorazepam and propofol at more or less the same time. Anesthesiologists routinely give midazolam at the start of an anaesthetic, and propofol a few minutes later. Midazolam and lorazepam are closely related. You just have to know that the effects are “synergistic”, meaning that you need to reduce the dose of propofol when you give a lot of midazolam or lorazepam.
MJJC: Do you have any idea about how much lorazepam had he been given and when?
Dr Steve Shafer: Yes, he gave a lot. The lorazepam levels in the blood were high enough to contribute to the cause of death, as stated in the coroner’s report, and as emphasized by the defence. As accurately stated by the defence, the lorazepam concentration in his blood was enough to put most of us to sleep. There were 8.4 milligrams of lorazepam in his autopsy urine, and another 5.8 milligrams of lorazepam in the urine that was recovered at the scene, which presumably was from the same night. So Michael Jackson received a lot of lorazepam. However, because there are no records, and I don’t trust what Conrad Murray says, it is hard to be more precise.
MJJC: Dr Kamangar said that dependency would be faster if benzos were given IV. Now was this a "treatment" that would have made him highly dependent on benzodiazepines? If Michael had survived, would he have been able to recover from this?
Dr Steve Shafer: Yes to both questions. Intravenous drug use typically results in faster dependence. Regardless of the degree of dependency, one can recover from it with appropriate treatment. The big problem for Michael Jackson would have been whether he would be willing to stay away from intravenous sedatives for the rest of his life. Without a change in life priorities, it is often very hard to wean individuals who are dependent on drugs.
MJJC: After spending what must have been hours of going through Murray's police statement, then the evidence itself, did you feel shocked with the results you were coming up with - the amount of propofol that had to have been given by Murray to obtain the blood results found at autopsy, the botched attempt by Murray to create his own Tate Gallery of Modern Art drip, etc.?
Dr Steve Shafer: Since Conrad Murray ordered staggering quantities of propofol to give to Michael Jackson, and Michael Jackson had an anaesthetic concentration of propofol in his blood, I expected the simulations to confirm that he received anaesthetic quantities of propofol. They did.
MJJC: During your testimony, you have stated that MJ first had a respiratory arrest and then a cardiac arrest. Dr.Steinberg also testified similarly based on Murray’s own words (that there was heartbeat/ blood pressure when he found Michael). We have seen the defence argue that it might have been a cardiac arrest rather than respiratory arrest first. Even in the Murray documentary, they showed a scene between defence lawyers that they planned to ask you if a direct cardiac arrest was possible but later decided to not ask that question as they were afraid of your possible answer. Can you elaborate on this a little?
Dr Steve Shafer: I cannot find any evidence that the scenario outlined by the defence, instant cardiac arrest in 90 seconds, has ever occurred. I have spent hours looking for such evidence, including searching the medical literature and communicating with company officials who tracked propofol adverse events. To the best of my knowledge, this has never been reported. Not even once.
I also do not believe any anesthesiologist has ever seen this. There is no mechanism by which lorazepam and propofol would act together to cause instant death. If the Judge had permitted it, I believe the trial could have been extended for several years while every anesthesiologist in the United States took the witness stand to testify that this scenario was complete bunk.
Consider the absurdity of claiming that 25 milligrams injected over 4 minutes was so safe that almost no monitoring was required, while the same dose injected over 1 minute was so toxic as to cause magical instant death! It makes no sense.
Of all the misrepresentations by the defence, the assertion of magical instant death from a small dose of propofol is the most harmful to patients. It is false. Asserting instant cardiac death from a very small dose of propofol can only be expected to increase the anxiety of patients requiring sedation and anaesthesia.
MJJC: As far as we can understand from Defense line of questioning and Dr White testimony defence theory of what happened on June 25, 2009, is as follows: Murray gave MJ Valium and then 2 doses of Lorazepam and 2 doses of Midazolam. As MJ was unable to sleep Murray gave him a bolus of 25mg Propofol. During the night/day (unclear when) MJ swallowed 8 pills of Lorazepam unknown to Dr Murray. MJ was moving around the room even though he had an IV and a condom catheter on and with all these medications on board, he self-injected an already filed and left on the nightstand syringe that had 25mg of Propofol. What can you say about the Defense’s version of the events?
Dr Steve Shafer: The primary point is that it doesn’t matter. Michael Jackson would be alive if Conrad Murray had not committed multiple egregious and unconscionable violations of the standard of care. He was administering a general anaesthetic to Michael Jackson in his bedroom, with no training, monitoring, or backup. He abandoned his patient. When he returned, his patient was either dead or nearly so. It speaks for itself.
We know that Michael Jackson received a lot of lorazepam. Maybe he took pills. Maybe Conrad Murray gave him more intravenously than he admitted to. We do know is that there was not enough unmetabolized lorazepam in Michael Jackson’s stomach to suggest recent ingestion. We do know that there was evidence in the room of large doses of intravenous propofol administration. We do know that the amount of unchanged propofol in the urine suggests administration of well over 1000 mg (100 MLS) of propofol. Thus, the defence scenario is not consistent with the physical or autopsy data for either lorazepam or propofol.
MJJC: Dr Shafer, you said at the trial that probably at the time of death the drip was still on and that would explain why the propofol concentration on the femoral blood was so high. But Dr White said that he would doubt the propofol could still be infused once the blood circulation has stopped. Could you expand on this, please?
Dr Steve Shafer: I claimed that Michael Jackson died during the infusion, which is why the blood concentration was as high as it was. He didn’t have to die at the end of the infusion, and there is no reason to think that he did. He simply died during the infusion. The 100 ml propofol bottle was empty, I expect that he died before the bottle was empty, but that by the time Conrad Murray found him the bottle had run out as well.
I was surprised that the defence claimed that my simulations required that Michal Jackson die at the end of the infusion. There was no such requirement. I was disappointed that Paul White went along with this.
MJJC: In case there was cardiac arrest initially and not subsequently after respiratory arrest as Murray told the police, that cardiac arrest could have been caused by a sudden high/fast dose from the drip since there was no infusion pump to regulate the rate of the drip?
Dr Steve Shafer: No. The heart is quite a reliable organ. It can stop suddenly, but not from anything propofol does. What makes the heart stops abruptly is: 1) an arrhythmia, typically from an acute heart attack, 2) something that completely blocks circulation, such as injection of a large dose of air, or a blood clot from the legs that suddenly blocks flow into the lungs, 3) administration of a large dose of intravenous potassium, which interferes with the electrical activity of the heart. Propofol will stop breathing, and it will drop the blood pressure. Neither of those will cause the heart to abruptly stop. As far as I can tell, nobody has ever seen a patient’s heart suddenly stop from any dose of propofol.
MJJC: According to Walgren's words during closing arguments "we don't know whether Michael awoke, yelled for help and choke while Conrad Murray wasn't in his bedroom, and we'll never know" and to Alberto Alvarez testimony that Michael's eyes and mouth were wide open, I want to ask you: could Michael suffered before death and could he really yelled for help and choke while dying? And if no, why his eyes /mouth were open if he died sleeping?
Dr Steve Shafer: Michael Jackson did not suffer. He died because he stopped breathing. He was unconscious at the time. If he had been conscious, he would have been breathing.
It doesn’t mean anything if a patient’s eyes or mouth are open or closed after death. I witnessed my own father’s death during the time I was testifying. I was at his bedside. He was in and out of consciousness for about two hours before his death. My last communication from him, an “OK” sign with his hand, was about an hour before his death. After he died, I noted that his eyes and mouth were both open. I closed them.
Questions about propofol in general
MJJC: Do you feel that your testimony helped alleviate patient concerns about Propofol or are things more or less the same?
Dr Steve Shafer: It may have helped, but only a little. On Friday when Paul White testified I was working at the “Allen Pavilion,” a regional hospital run by Columbia University that serves a low-income area of Manhattan and the Bronx. I was caring for an elderly man who asked what drug he would get. I told him “propofol.” As usually happens, he asked if that was the drug that killed Michael Jackson. I told him that propofol didn’t kill Michael Jackson, Conrad Murray killed Michael Jackson. I also said that propofol was a very safe drug. He said, “I heard that doctor say that at on television, but I don’t believe him.”
I told him I was the doctor he saw on television. He thought that was hilarious: the doctor in blue scrubs, wearing a surgical hat, with a stethoscope around his neck working in this clinic for poor patients might be the “famous” doctor he saw on television. “Yea, right” was his answer. He didn’t believe me for a second. However, he was reassured by my “joke” about being the doctor he saw on television, and everything went well.
MJJC: Can a person become dependent or addicted to propofol? If yes what kind of dependency is it physical or psychological?
Dr Steve Shafer: There is not much data about this, because propofol must be given intravenously, and it really burns, which discourages abuse. However, there have been a number of deaths of anesthesiologists and other health care personnel from propofol abuse. Based on this, I am reasonably confident that it is addictive.
MJJC: Why would someone even have the idea to use Propofol as a sleep aid? If it is only to be used for surgery then why would anyone suggest giving it someone to get some sleep?
Dr Steve Shafer: The mechanism of action of propofol is the same as drugs like Ambien that are commonly used to induce sleep. This is a reasonable research question. However, it should never be put into practice until it has been studied in a proper research setting. After that work has been done, it should only be used with appropriate documentation and precautions.
MJJC: Are the drug companies who make Propofol looking into testing Propofol for sleep? Do you think there will be more research studies about Propofol being used for sleep?
Dr Steve Shafer: Yes to both questions.
MJJC: What are the known effects on the nervous system & the brain of long-term Propofol use?
Dr Steve Shafer: Not a lot, because it is rarely used for long-term use. I have been able to find one report of a patient who received propofol in the intensive care unit for 51 days. This is from the conclusion of the article: “To our knowledge, this report represents the first documentation of propofol use for long-term sedation in a mechanically ventilated pregnant patient and the longest duration of continuous infusion propofol published in the medical literature. Propofol was used for 51 days with no documented maternal adverse events.” (Tajchman SK, Bruno JJ. Prolonged propofol use in a critically ill pregnant patient. Ann Pharmacother. 2010;44:2018-22)
This patient was weaned from propofol over several days without adverse consequences. So administration for 2 months appears to not have long-term consequences, at least based on this example, and the fact that Michael Jackson continued to function at rehearsal. However, those are just two data points. More research needs to be done if one contemplates the development of propofol for long-term use.
MJJC: Does one get a "restful sleep" from Propofol? We have heard experts contradict each other on this.
Dr Steve Shafer: The contradiction reflects the state of the science. I received propofol for anaesthesia about a year ago, and I have given propofol to thousands of patients. There is often a feeling of having slept well after awakening from propofol.
However, studies suggest that propofol sleep it is quite different from normal sleep, and is not “restorative” the way that normal sleep is restorative. For example, dreams are important in brain function. Patients don’t dream on propofol, except at the time of awakening. My interpretation of the data is that propofol might be OK for getting a patient off to sleep, but that maintaining a patient on propofol for sleep (as we sometimes do in intensive care units) probably is denying patients restorative sleep.
MJJC: Do you agree that Propofol should be re-classified as a controlled substance?
Dr Steve Shafer: No. I think this will hurt patients. In emergencies, we need propofol immediately, and in large quantities. I am opposed to placing obstacles in the way of doctors caring for patients unless there is a clear benefit. Conrad Murray could have still obtained propofol for Michael Jackson because doctors can order controlled substances. Since most propofol abuse is by doctors, making it controlled won’t limit the ability of doctors to abuse it. It will just impair their ability to care for emergency patients.
This has been the subject of an issue of Anesthesia & Analgesia. Here is the cover of that issue:http://www.aaeditor.org/HWP/Covers/0710.cover.jpg.
MJJC: Do you think now the anesthesiology community will be more careful in how they promote and teach one to use Propofol?
Dr Steve Shafer: We already take this very seriously. We are very involved in teaching the safe use of sedatives to our medical colleagues. This will continue. Perhaps they will be more receptive to the importance of safe sedation. However, nothing we can do will reach a doctor who does not put patients first.
MJJC: Do you think the medical community has learned from Michael’s death in regards to prescribing to a powerful wealthy person and wrongdoing by a doctor?
Dr Steve Shafer: Absolutely. I mentioned this above. I am aware of this because I occasionally see this in my practice. Doctors serve patients by acting as doctors. That is a message for doctors and patients alike.
MJJC: Can you explain “Propofol lollipop” a little more?
Dr Steve Shafer: Propofol absorbed from the stomach never reaches the brain, because it is all removed by the liver. However, the blood supply to the mouth and oesophagus (above the diaphragm) does not return directly to the liver. Instead, it just goes to the heart, and from there goes everywhere including the brain. So a propofol lollipop would provide propofol to the venous blood, and from there to the brain. Paul White and I discussed this at one of the breaks prior to his testimony. It is a reasonable idea, provided the dose was adequately controlled.
Should this ever become available, then I would reconsider my position on classifying propofol as a controlled substance? My current view is highly influenced by the fact that it only works when given intravenously, and that really burns!
MJJC: What does Propofol taste like?
Dr Steve Shafer: It has the consistency of skim milk, and tastes like a very medicinal salad dressing.
MJJC: Beagle Propofol experiment done by the Defense has made PETA and MJ fans angry. We don’t expect that you have any direct information about the Beagle experiment but as the humans weren’t affected by drinking Propofol, is it safe to assume that the Beagles were unharmed as well?
Dr Steve Shafer: I think it is very unlikely that any harm came to the beagles. There should be no effect from drinking propofol. However, I am uncomfortable that neither the experimental protocol nor the results of the experiment were presented in court. I believe that when animals or humans participate in trials, there is an ethical obligation to write up and publish the research to add to the body of knowledge. It is the increased knowledge that morally justifies the research. I wrote our human study up for publication, asked Paul White to review it, and gave it to the defence. I believe they should have done the same with their beagle study.
MJJC: We heard the theory of some of the Benzos or/and Propofol that were given to MJ by Murray can be used for people with drug addiction to help them off their addiction to other drugs such as Demerol, Is this true? Can you comment on this?
Dr Steve Shafer: There is a technique of rapid detoxification that involves placing patients under general anaesthesia for a long period of time (hours to days) and pharmacologically reversing opioids with “opioid antagonists”, drugs that chemically block the effects of Demerol and similar drugs. This is controversial, but it probably works in some patients.
Questions about Demerol
MJJC: Was the amount of Demerol Dr Klein give to Michael normal or was it too large a dose?
Dr Steve Shafer: I can’t answer without knowing why Demerol was given. Dr Klein did not testify at the trial. I’m uncomfortable offering an opinion without more information.
MJJC: Does your answer change if you consider MJ’s history (burn victim) with the drug? Do you think it was excessive?
Dr Steve Shafer: Again, I apologize, but I don’t want to render an opinion without knowing why Dr. Klein was administering Demerol. This probably reflects my caution as an Editor-in-Chief of a medical journal. Medical editors are reluctant to render a public opinion unless they are confident they understand the facts.
MJJC: In your opinion, does Demerol aggravate insomnia as a side effect? Did it play any part in Michael's physical and mental health? What was the best treatment for Michael's insomnia?
Dr Steve Shafer: There are three questions here. I’ll answer them in order:
Demerol’s chemical name in the United States is “meperidine.” In many countries, it is known as “pethidine.” Meperidine has a metabolite, “normeperidine”, that is a nervous system stimulant. As a nervous stimulant, I would expect it to exacerbate insomnia.
The coroner examined both blood and urine for meperidine (Demerol) and normeperidine. Neither could be detected. Thus, meperidine did not play a direct role in Michael Jackson’s death on June 25th. However, you asked a more general question about “play any part in Michael’s physical and mental health.” It is a good question, and I will again need to apologize for not answering it. I have not read Dr Klein’s medical records or heard a detailed explanation of Michael Jackson’s care. I am uncomfortable speculating without that information.
Sleep disorders are complex, and treating them is a specialized branch of medicine. It is my understanding that any drug that affects the level of consciousness can exacerbate sleep disorders. There is a nice description of sleep disorders, and the treatment of common sleep disorders, at http://www.sleepfoundation.org/artic...s-and-insomnia.
Questions about lorazepam, flumazenil, and ephedrine
MJJC: Could the free lorazepam detected in the gastric liquid be explained by the stomach haemorrhage caused by CPR or even by accidental mixing of adjacent blood at the time of autopsy (as it was suggested by the Coroner, Dr Rogers in the preliminary, though not mentioned again during the trial)?
Dr Steve Shafer: Maybe. However, free lorazepam would be expected simply because molecules like lorazepam would be expected to cross from the blood into the stomach, just like they cross into all tissues. That is how the lidocaine and propofol got into the stomach. Lorazepam should behave just the same way.
Additionally, the enzyme beta-glucuronidase is secreted by the wall of the stomach into the stomach fluid. Beta-glucuronidase is the enzyme that would turn lorazepam glucuronide back into lorazepam. So blood could account for it, but most of it is likely the simple diffusion of lorazepam from the blood into the stomach.
MJJC: Is there any other reason for Flumazenil to be administered apart from reversing the effects of benzodiazepines (in this case Lorazepam)?
Dr Steve Shafer: No.
MJJC: Does it even make sense to give a person Flumazenil who according to Dr Murray only received 4 mg of Lorazepam to begin with?
Dr Steve Shafer: The most critical part of any resuscitation is to move air in and out of the patient’s lungs. The problem with giving flumazenil is that it distracted Conrad Murray from the critical task of moving air in and out of Michael Jackson’s lungs. If there were several people were involved in the resuscitation, then giving flumazenil would have made sense. However, since Conrad Murray was alone, any interruption longer than a few seconds was too long.
MJJC: Can you explain your consideration of the Lorazepam levels, in more detail?
Dr Steve Shafer: I’ll answer as well as I can, but I’m not sure exactly what you want to know. The lorazepam levels were high enough that you or I would have been very sleepy from them. However, patents become tolerant to lorazepam and related drugs (the “benzodiazepines”). Since Michael Jackson had a fairly high concentration, and according to Conrad Murray that was not enough drug to induce sleep, he must have been tolerant.
The defence wanted to attribute Michael Jackson’s death, in part, to oral lorazepam. The problem with this theory is that there was only a minute amount of lorazepam in Michael Jackson’s stomach. To explain this minute amount, the defence alleged that Michael Jackson swallowed lorazepam about 5 hours before the time of death. If that were true, then the lorazepam concentration would have peaked about the time Conrad Murray claims Michael Jackson was pleading for more drug to fall asleep. So that argument doesn’t make sense.
MJJC: According to the autopsy report there was ephedrine found in Michael's body. It's a drug that aggravates insomnia. How ephedrine goes with benzos and propofol, could it subdue effect of these drugs?
Dr Steve Shafer: There was a bottle of capsules composed of ephedrine, caffeine, and aspirin in the room. Ephedrine is sometimes used in resuscitation. Since there was ephedrine in Michael Jackson’s autopsy urine, as well as the urine that was found at the scene, I would assume that the ephedrine was from oral ingestion, and not from the administration as part of the resuscitation.
Ephedrine can reduce the effects of propofol and benzodiazepines on blood pressure and heart rate. Chronic ephedrine might aggravate insomnia.
Question about medical research in general
MJJC: Judge Pastor referred to Murray as making Michael Jackson part of a “scientific experiment”. This could, unfortunately, dissuade patients from feeling comfortable participating in clinical trials and other types of beneficial scientific and medical research. Can you discuss the important intersection between the research of scientists and the clinical practice of physicians?
Dr Steve Shafer: I’ve performed dozens of clinical trials. I don’t think this will adversely affect recruiting patients into clinical trials, because this “experiment” bears no resemblance to a scientific study. I think “experiment” is an accurate term because it correctly implies that Conrad Murray had no idea what he would find day after day of propofol administration. So this was an experiment that he was conducting every day to see how Michael Jackson would respond. However, I don’t think anybody would confuse this experiment with a proper scientific experiment.
The larger question you ask is about the intersection between research and practice. This is an important question, and (fortunately) one that has been given very careful consideration. The answer goes back to the Nuremberg Code, which followed the trial of Nazi doctors guilty of atrocities at the end of World War II. You can find an excellent account on Wikipedia. This was updated by the Belmont Report, published in 1978. Again, there is an excellent account in Wikipedia. As explained in the Belmont Report, “research” differs from clinical practice in that research is a systemic investigation intended to create generalizable knowledge. “Systematic” means that the investigator intentionally gathers data to answer a question. Generalizable knowledge means that the investigator believes the information gathered is useful to others and intends to “generalize” the knowledge, usually by publishing it. If you Google “Anesthesia & Analgesia policy in institutional review board approval and informed consent for research” you will find an editorial I wrote in March on the subject.
Questions about insomnia
MJJC: Decades of lies, slander, deceit, inhuman treatment from the media and public misconceptions had caused Michael immense hurt, pain and anguish resulting in insomnia. We know Propofol was not the answer, but what do you think he should have done (medically) to treat it?
Dr Steve Shafer: He should have been in the care of a sleep medicine doctor. He had a terrible affliction, one that requires expert care.
MJJC: Do you think meditation that Murray was talking about in his police interview could really help Michael to sleep?
Dr Steve Shafer: Maybe. Conrad Murray mentioned both propofol and lorazepam. These are both sedatives that act on the same receptor in the body, the “GABA” receptor. Most sleeping medications also act on GABA, the exceptions being antihistamines (e.g., Benadryl) and melatonin. So I would expect these drugs to induce sleep. However, they should not be used to maintain sleep, because the drugs interfere with some of the brain function that is required for sleep to be “restorative”, meaning that it refreshes the brain.
MJJC: Anything you want to say to the members of MJJCommunity and Michael Jackson fans in general.
Dr Steve Shafer: Once your questions about Michael Jackson’s tragic death have been answered, I encourage you to set it aside. Conrad Murray has been convicted. We have a reasonable understanding of what happened. It’s time to return to the bonds that brought the MJJCommunity together in the first place: your celebration of Michael Jackson’s life, his message, and his music.
I appreciate the opportunity to address your questions and hope that the answers are helpful to the MJJCommunity.