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People vs. Dr. Conrad Murray

Murray's Former Patients:

He's the Best Doc Ever

10/26/2011 7:20 AM PDT BY TMZ STAFF

Dr. Murray's Former Patients Testify
Updated 10/26/11 at 9:00 AM
1026_mj_trial
The defense is trying to make the case ... Dr. Conrad Murray is a great doctor with a pristine reputation -- and to prove their point, they're calling several of Murray's former patients to the stand ... each with glowing reviews.

First up ... a heart attack patient named Gerry Causey -- who told the jury, Murray saved his life. Causey said Murray is "the best doctor" he's ever had.

Interestingly, Causey told jurors he didn't want to be sedated during the operation because he was too scared ... so Murray didn't put him under.

He also said Murray took great care in explaining everything he was doing.

Prosecutors made sure to point out -- Murray's treatment was done in a monitored environment with the help of a large staff.

0104_break_mj Patient # 2 -- Andrew Guest
Updated 10/26/11 at 9:15 AM

1025_Andrew_Guest_MJtrialPatient #2 Andrew Guest said Dr. Conrad Murray performed 2 different procedures on his heart in 2002 -- telling jurors, "That man sitting there is the best doctor I’ve ever seen."

Guest said Murray often called him on weekends to check up on him.

During cross-examination, lead prosecutor David Walgren asked Guest, "I don't mean to be flip ... but  he never give you Propofol in your bedroom did he?"

Guest shot back, "I am alive today because of that man."
0104_break_mj

Patient # 3 -- Lunette Sampson
Updated 10/26/11 at 9:35 AM

1025_Lunette_Sampson_MJtrialLunette Sampson -- who suffered 3 heart attacks in 2008 and 2009 -- told the jury Murray saved her life, fixing another doctor's botched operation.

During cross examination, Walgren suggested Murray was able to fix Sampson's heart because he had access to her medical records ... a privilege Murray never afforded the ER doctors, who scrambled to save Michael Jackson's life.


0104_break_mj
Patient # 4 -- Dennis Hix
Updated 10/26/11 at 9:50 AM

1025_Dennis_hicks_MJtrialDennis Hix testified Dr. Murray placed about 13 stints in his heart ...  for free.

Hix said Dr. Murray also operated on his brother's heart free of charge ... telling jurors, "I’m 66.  I've gone to a lot of doctors, A LOT of doctors, and I’ve never had one who gave me the care he did."







0104_break_mj
Patient # 5 -- Ruby Mosley
Updated 10/26/11 at 10:20 AM


1025_Ruby_Mosely_MJtrialRoby Mosley told jurors Dr. Murray couldn't have been greedy because he opened up a clinic in one of Houston's poorest neighborhoods in honor of his father.

Murray fought back tears as Mosley described how he selflessly treated patients who couldn't afford his care.

128 COMMENTS

No Avatar
31.

UPYOURS    

TOO FUNNY. These types of witnesses are usually reserved for after a person is found guilty. As usual, the defense is farking up

904 days ago
32.

blondie    

this case has nothing to do with how he treated his patients. this case is about the death of michael jackson and the misuse of propofol AND patient abandonment. that's it. he is guilty. amen.

904 days ago
33.

Bubba    

The next witness for the defense will be Randy Quaid. He will testify that he knows Murray didn't kill MJ it was the Hollywood Star Whackers who done it!

904 days ago
34.

Bea    

Notice that Murray cries when he feels sorry for himself, but he has never cried or shown emotions or empathy for Michael or anyone else during the trial. When they showed the pictures of Michael dead, when they told about the heartbreaking reaction of Michael's mother when she heard that her son was dead, during all the testimonies about how reckless he had treated Michael, he showed no emotions at all.

904 days ago
35.

t    

His dead patients can't testify.

904 days ago
36.

kmartin    

No matter how many previous patients come in to testify it still remains the same. Dr. Murrary should have never used such a drug in a 'home setting' with no assistant(s) & appropriate equipment. I don't care if Michael was addicted to drugs or not...no DOCTOR should have agreed to accomodate him!!!!

904 days ago
37.

Pegasus    

Lack of an ECG machine was a separate egregious violation.

This machine allows you to monitor the heart rate and see whether it s low, high, normal or abnormal. Dr. Shafer says that Murray cannot even tell us what Michael’s heart was doing at the time of the arrest.

Capnography is the monitoring of the concentration of carbon dioxide (CO2). Failure to measure this concentration is an egregious violation.


The lower line shows a complication - a temporary stop in exhaling carbon dioxide which is a warning of an airway obstruction
In the report Dr. Shafer listed it among serious violations first but later elevated it to the egregious one. He explained – in the hospital setting it wouldn’t be that crucial as there is a lot of other monitoring equipment which will set off the alarm in case of a problem. But in a home setting with no equipment available, capnography is one of the first things to have as is its absence is a set up for disaster.

A capnogram can show when the patient stopped exhaling carbon dioxide and it may serve as the very first warning of a respiratory arrest. And a respiratory arrest is all we are talking about here.

Another egregious violation is not having the emergency drugs at hand.

These include drugs to raise the blood pressure, stabilize the heart rhythm and accelerate the heart if it gets too slow. If we come to think of it Murray did not have any medication at all to help Michael’s heart and cardiovascular system though he is supposed to be a cardiologist.

The medication needed included ephedrine to raise the blood pressure (which acts as adrenalin) and a muscle relaxant in order to paralyze the very strong muscles in the mouth which won’t allow the tubing to be inserted into the airway for bringing in oxygen there.

This didn’t contribute to the death of Michael Jackson, but Dr. Shafer said but it shouldn’t have even got to the point when such medication was required.

Failure to make records is an egregious and unconscionable violation.

Dr. Shafer stressed it again and again that keeping the records was not optional. It is part of the care of the patient. The doctor should always be able to reference himself to what happened 10 minutes ago and find an answer to a question – What did you do why the patient is having this reaction now?

These questions should be asked and answered even after the procedure. And this is why Dr. Shafer listed this violation not only as egregious but as an unconscionable one too.

If the next day after the procedure Michael Jackson felt unwell he had the full right to ask his doctor what he had done to him. With no medical records kept he was denied the right to know it.

And since he didn’t survive, his family is denied to know what happened either. Dr. Shafer gave an example of his father – what was he supposed to think and how he would feel if his father had gone to a medical facility, stayed there for 80 days and died, and doctors would not have been able to provide a single record to explain what happened? And shrugged their shoulders saying that they didn’t know?

No matter how absurd it looks this is exactly the situation with Conrad Murray who didn’t keep a single record!

David Walgren asked Dr. Shafer, “What if the patient asked not to keep records?” Dr. Shafer said it didn’t matter. He was still to do it - there is no basis for claiming any confidentiality here. Any such claims would be completely false here.

At this point I recalled that Dr. Klein did record giving Demerol to Michael during those cosmetic procedures though it was probably an area where Klein would like to avoid questions.

I also recalled that Kenny Ortega shared his concerns about Michael’s health with this “doctor” and Murray replied to him to stop being an amateur doctor or psychologist and told him to leave Michael’s health to him. Let me remind you of the email Kenny Ortega sent to Randy Phillips of AEG on the night of June 20 2009 where he described how Michael felt on June 19:

Randy Sat, June 20, 2009 at 2.04 am

I will do whatever I can to help with this situation. If you need me to come to the house just give me a call in the morning. My concern is, now that we’ve brought the Doctor into the fold and have played the tough love, now or never card is that the Artist may be unable to rise to the occasion due to real, emotional stuff. He appeared quite weak and fatigued this evening. He had a visible case of the chills, was trembling, rambling and obsessing. Everything in me says that he should be psychologically evaluated. If we have any chance at all to get him back in the light, it’s going to take a strong Therapist to help him through this as well as immediate physical nurturing. I was told by our Choreographer that during the Artist’s costume fitting with his Designer tonight they noticed he’s lost more weight. As far as I can tell there is no one taking responsibility (caring for) him on a daily basis. Where was his assistant tonight? Tonight I was feeding him, wrapping him in blankets to warm his chills, massaging his feet to calm him and calling his doctor. There were four security guards outside his door, but no one offering him a cup of hot tea. Finally, it is important for everyone to know, I believe he really wants this. It would ****ter him, break his heart if we pulled the plug. He’s terribly frightened it’s all going to go away. He asked me repeatedly tonight if I was going to leave him. He was practically begging for my confidence. It broke my heart. He was like a lost boy. There still may be a chance he can rise to the occasion if we get him the help he needs.

Sincerely,

Kenny

Needless it to say that not only Murray fully neglected the first warnings of a tragedy but he didn’t record any of Michael’s complaints into his medical records for a simple reason that there were no medical records whatsoever.

Dr. Shafer said that the records were indispensable as in case another doctor were to treat the patient he should have the full medical history (his lab results, his reaction to this or that medication, duration of certain drugs administered, the effect they had, etc.). Medical records are indispensable for making a referral to another doctor. After all, the state which licences doctors is responsible for the care the doctor provides to patients and has the right to demand their records too.

Murray’s irresponsibility towards his patient had one more side to it. Dr. Shafer reviewed Murray’s statement to the detectives and noted that Murray complained about “not knowing what therapy was given to Michael by other doctors” (for example Dr. Klein).

Dr. Shafer says it was Murray’s obligation to follow upon it and find out, because providing a certain therapy and not knowing what others are doing is inconceivable. Walgren asked him – and what if the patient says it is none of your business? In that case Murray should have said that he could no longer be his doctor, replied Dr. Shafer.

From that interview with the police Dr. Shafer learned that the only reference to a physical examination of Michael Jackson had been done months prior to those nightly propofol infusions. However according to the standard of medical care a physician is to make assessment of his patient each time he intends to do a sedation procedure.

And if he saw that Michael was dehydrated as he was sweating a lot during exercise – why didn’t he measure his blood pressure and pulse? And he didn’t do as little as a simple recording of the vital signs! Any physician does that, while Murray did not. Lack of a regular physical assessment is another serious departure from the standard of care and coupled with the failure to keep records is so profound a violation that Dr. Shafer could hardly find a word to describe it.

He said it had no excuse.

Failure to have a proper doctor-patient relationship is an egregious violation

This relationship is built on the foundation that the doctor will always put the patient’s interests first. It doesn’t mean doing what he asks of – it means doing what is right for the patient and acting in his best interests. If the patient requests something foolish or dangerous, it is a doctor’s obligation to use medical judgment and say ”no”.

Dr. Shafer called it an employee-employer relationship where one stated what he wanted and the other said “yes”.

With due respect for Dr. Shafer I will correct him a bit here and say that it was not so much an employee-employer relationship between Murray and Michael Jackson – it was an employee-employer relationship between Murray and AEG Live.

On the instructions of AEG (who thought that Michael was “simulating” a problem) Murray totally disregarded Michael’s deteriorating state of health and cut short even feeble Ortega’s attempts to seek professional medical help.

Murray took orders from Randy Phillips of AEG who demanded that Michael should stop seeing Klein and should attend every rehearsal no matter in which condition he was – or they would “pull the plug”.

In the above email Kenny Ortega says it himself that they “have brought the doctor into the fold and have played the tough love”. They have brought, and not Michael Jackson and they have “played the tough love” towards him together with Murray.

So when Dr. Shafer speaks of Murray acting as an employee of Michael Jackson he assumes that there were only two parties in this relationship, when one asked for propofol and the other agreed. Even in his worst dream Dr. Shafer is unable to imagine that there could be a third party to this process which would dictate its will to Murray and ask him to fully disregard Michael Jackson’s complaints.

But as to the essence of the problem Dr. Shafer is right – Murray did fully abandon medical judgment and was not acting in his patient’s interests at all.

Dr. Shafer says that if Murray had acted as a doctor he would have referred Michael Jackson to sleep disorder specialists for evaluation and therapy.

In fact even Kenny Ortega saw the need for Michael to be evaluated by psychology experts and a qualified therapist – only no one paid attention to his words, including Conrad Murray. However it noteworthy that Kenny Ortega did not approach Murray with this request – no, he approached Randy Phillips with it!

This alone shows who the real master of the situation was. However a true doctor will never bend to anyone’s orders and will be guided by nothing else but medical judgment and the oath of Hippocrates he takes to observe a code of medical ethics.

Dr. Shafer says that Murray’s unwillingness to say “no” and his failure to refer Michael to a proper specialist directly resulted in Michael Jackson’s death.

And I would add to that package Murray’s full willingness to say “yes” to those in whose real employment he was.

904 days ago
38.

Pegasus    

Failure to obtain an informed consent is an egregious and unconscionable violation.

Dr. Shafer says an informed consent would have involved making clear to the patient that the risk of death from propofol (administered in that environment) was very real and there is no evidence whatsoever that Michael Jackson knew that his life was at risk. The informed consent requires discussion of an alternative therapy and there is nothing to show that this conversation ever occurred.

It was to be a written consent and was to have been signed every night .

“What is meant by a patient’s right to autonomy as it relates to informed consent?” asked Walgren. Dr. Shafer explained that a person has the right to dictate what happens to his body and his life. It is a fundamental human right and principle of ethics, and health-care providers recognize and respect the right of the patient to take these decisions – through the process of informed consent.

Dr. Shafer said that by not obtaining an informed consent Jackson was denied this autonomy.

Failure to continuously observe the mental status of the patient is another egregious violation.

When administering sedation the doctor converses with his patient assessing his mental status and how awake he is. Since it is no deep anesthesia (where the body is cut and there should be no pain) for sedation the doctor gives just enough drug and takes care not to give more. The doctors stays by a patient’s bedside and never abandons him. Dr. Shafer says that in his 25 years of practice he has never walked out of the operating room.

An anesthesiologist giving sedation is like a driver at the steering wheel who cannot walk away for 2 minutes to relieve himself because it is very likely that during that time a disaster will take place. And Dr. Murray did leave the steering wheel. If he needed to leave the room there should have been some back-up personnel to replace him.

“And will being on the phone even in the general vicinity of the patient be an independent egregious violation?” asked Wlagren.

Dr. Shafer said that it was a setup of disaster.

“The patient is receiving IV drugs and the doctor is not focused on the patient – instead he is talking on the cell phone, sending text messages, answering emails. You cannot multitask like this, even if you are a couple of feet away, particularly with no monitors in place and no alarms. A patient who is about to die does not look that different from a patient who is okay”.

“You don’t know that the oxygen saturation is dropping, you don’t know that breathing has stopped, because you are distracted” and all “this is when the patient is essentially dying”, Dr. Shafer said. You cannot be distracted by all those activities and the period of 45 minutes – while Murray was busy on the phone – speaks for itself.

From a distance it is not that easy to say whether the patient is breathing. All that happens is that the stomach rises and falls a little bit. There were no monitors, no blood pressure equipment and from a distance Conrad Murray could not see the readings on the pulse oxymetry device he had on the patient’s finger. Michael Jackson could have been not breathing for a considerable period of time and it would not have been obvious to a person standing at a distance if there were no monitors in place.

Michael Jackson could look okay to Conrad Murray while actually he was not – and this Dr. Shafer says is what he believes what happened.


You need to constantly check the infusion pump administering propofol. However this device for precise dosing was not there
The need to monitor the patient has to be done continuously. Even if the equipment had been present it had to be continuously checked, followed every few minutes for blood pressure, carbon dioxide and oxygen saturation in the blood – and it is every few seconds which matter.

So there is a need not only to set these monitors in place but to constantly observe them. It is violation not to have the equipment in the first place and it is a separate violation not to use it and not make continuous observation. The latter fact is evidenced by Murray leaving the room and by a long period of phone calls and distracting activities.

Michael Jackson’s death was an expected consequence of Murray’s failure to continuously monitor the patient.

If Murray had left the room for two minutes only it would have been relatively easy to resuscitate Michael Jackson. All it would require is to ventilate his lungs and turn off the infusion line so that no more propofol was administered.

A stop in breathing is no big deal for anesthesiologists. They give so big doses for anesthesia that every patient stops breathing. It is routine and normal, it happens every day and is completely expected when administering propofol. The anesthesiologist knows that it is going to happen and makes the necessary intervention so that there is a continuous flow of air to the patient.

If Conrad Murray had been at the head of the bed and seen Michael Jackson stop breathing he should have lifted his chin to open up the route for air or filled the lungs with oxygen through the mask – and nothing would have happened. There would have been no adverse outcome at all, said Dr. Shafer.

In short if Conrad Murray had paid a little attention to Michael Jackson it was no problem to save his life.

The lack of continuous do***entation is another fundamentally egregious and unconscionable violation.


You write down the main parameters every 5 minutes
As you make the observation you write it down – the blood pressure, the heart rate and how fast the person is breathing, said Dr. Shafer. If he had been doing it he would have seen in a few minutes that Michael Jackson was dying.

The family has the right to know what happened during the administration of propofol. That right has been denied to them by lack of continuous charting the process. It violates the rights of Michael Jackson and the Jackson family.

The failure to call 911 was another of those outrageous, egregious violations.

In that setting it was almost impossible for Michael Jackson to have been revived without an assistance. You have to get advanced support there instantly, immediately and there is nothing that has a higher priority than calling 911.

Conrad Murray was expected to immediately assess the situation and then call 911. The assessment would include checking the pulse and looking for signs of responsiveness (you literally shake the patient) – so it takes a matter of seconds to make an assessment. And the fact that the propofol was given (which shouldn’t have) is no impediment for calling 911 immediately.

David Walgren assumed that Murray became aware of Michael Jackson’s condition at around noon and the delay in calling 911 was something like 20 minutes. How would Dr. Shafer assess that Dr. Murray called Michael Amir Williams at 12.12, left a voicemail message to him and then had the bodyguard Alvarez make a 911 call at 12.20?

Dr. Shafer said: “That is so egregious that I actually find it difficult to comprehend. You have a patient who had a respiratory arrest and you call and leave a voice message? It is just inconceivable. A physician would not do that…. I almost don’t know what to say. It is completely and utterly inexcusable”.

Walgren assumed that Michael Jackson stopped breathing when Dr.Murray was away for 2 minutes – would he be alive if Murray promptly called 911?

Dr. Shafer said that he would but most probably have sustained a neurological brain injury due to the lack of proper resuscitation effort and lack of equipment. If there had been the resuscitation equipment [or it had been used, like the ambu bag, for example], he would have survived and would be uninjured.

Walgren asked, “And how effective is a one-handed compression on the bed?”

Dr. Shafer said, “Not at all”. When you do chest compressions on the bed the patient just sinks into the cushions. You have to push the force against the spine and squeeze the heart. It should go directly down and with one hand it is difficult to do it in the right direction. So it is always two hands, pushing straight down and a patient being on a hard surface.

Even if Murray says he had one hand under Michael’s body and compressed with the other hand, you cannot muster your force like that because you need your body behind this effort – in that kind of positioning there is no power. You need to throw your body into it because this is what it takes to move the breast bone and effectively pump blood for the patient.

However based on Murray’s own words that when he returned Michael had a thread pulse, the issue here was not that Michael’s heart had stopped – the issue was that he stopped breathing and because of that oxygen was running out of his lungs. His heart only stopped because it was starved of oxygen. In the presence of a pulse the heart doesn’t need to be compressed – what you need to do is get oxygen into the lungs.

904 days ago
39.

Pegasus    

A mouth-to-mouth resuscitation done by Murray to resuscitate his patient was a serious violation in these cir****tances.

Dr. Shafer says that if nothing else is available a mouth-to-mouth resuscitation is the only alternative. But for a health-care provider the need to resort to it means the admission of a failure to have the necessary resuscitation equipment available. The mask would have been much more efficient – because when you breathe into a patient it is your expired air. The usual level is no more than 20%. And if he had ventilated Michael’s lungs with oxygen he would be alive now.

In his interview with the police Murray described raising Michael’s legs. This was a minor violation as Dr. Shafer said it was just a waste of time. You raise a person’s legs if you believe you need more blood going into the heart, but since Michael’s heart was beating anyway Dr. Shafer said he didn’t know why Murray had done it – he needed oxygen and not raising his legs!

It shows that Dr. Murray was clueless as to what to do.

Walgren asked – and what is flumazenil used for? Dr. Shafer said that this is a drug which is used to reverse the effects of any of the Valium type of drugs which include Lorazepam and Midazolam. Intravenous Flumazenil is an antidote as it can quickly reverse an overdose of those drugs.

There was nothing wrong with giving Flumazenil but the small 4 mg dose of Lorazepam given hours before would not require a reversal, so Dr. Shafer found it curious that Conrad Murray would choose at this critical moment of Michael’s life to give a drug which would reverse Lorazepam. It does not fit.

Dr. Shafer’s interpretation of it is that Murray knew that he had given a lot more of Lorazepam than the 4mg he mentioned in his statement – which is why he quickly reached for an antidote for it!

The fact that Murray did not admit to the paramedics and the UCLA emergency room doctors that he had given propofol is another egregious deviation from the standard of care.

When a person’s life hangs in the balance as it did to withhold information is inexcusable. In addition to that he mischaracterized it as a witnessed arrest which is very different from what it was. A witnessed arrest is usually not the arrest for lack of breathing – it is something like a heart attack. You see the person and suddenly he is down and you realize that something catastrophic has happened.

You assume it is some sort of a cardiac disaster because in the presence of a physician a patient should not be allowed not to breathe, therefore a cessation in breathing is assumed not to have occurred. So the therapy that was directed at Michael Jackson was a therapy towards a cardiac event. The fact that it was a respiratory arrest caused by sedatives, specifically Propofol, was withheld – so neither the paramedics, nor the physicians knew what they were treating.

When a patient goes into an arrest you have only seconds to go one way or the other. They were not given the information to choose a treatment path that was appropriate for what had happened.

In a scenario when the patient is transferred from one physician to another one it is a professional, ethical and moral obligation to tell the truth. The doctor is obliged to tell the truth, the whole truth and nothing but the truth. Anything less than the truth is inexcusable. And this is another egregious and unconscionable violation of the standard of care.

Dr. Shafer stressed again that the doctor-patient relationship is built on trust and the patient’s interest always going ahead of the doctor’s interests. By withholding such information you violate this trust. “When it is withheld from the people who are trying to save the life of your patient you violated that trust in ways that are so foreign to me that I truly have trouble of conceiving it”. The patient has a right to expect the doctor to be honest.

Walgren asked – what is polypharmacy? Dr. Shafer said that it is administering many drugs at once.

Walgren enumerated the drugs Conrad Murray administered that night – Lorazepam, Diazepam (Valium), Midazolam as well as Propofol. “Is it polypharmacy?” “Absolutely”, said Dr. Shafer. “How would you characterize it?”

Dr. Shafer shook his head and said that it didn’t make any sense. Lorazepam and Midazolam are very similar drugs and from the perspective of the brain they are nearly identical. The molecules do exactly the same thing in the brain. The only difference is how long they hang around for.

Dr. Shafer does not see any rationale for switching between Lorazepam and Midazolam in a patient who is having trouble falling asleep. So the therapy that was used does not suggest any understanding of these drugs.

Additionally they’ve been given along with Propofol. That is common. “We commonly combine Medazolam with Propofol during anesthesia, but we do it with an understanding”, said Dr. Shafer. We don’t go willy-nilly – let’s give him more Lorazepam, let’s give him more Midazolam. The care of the polypharmacy in this case suggests that it was done without any real understanding of the drugs being used, how they worked and how they interacted. And this of itself was a serious violation of the standard of care.

Dr. Shafer looked very sad when he was saying all that because it clearly means to him that Conrad Murray is ignorant, incompetent and totally unprofessional.

Walgren asked, “And would you consider the 25ml dose of Propofol safe in this setting?” “Not at all”, said Dr. Shafer.

“In this setting there are so many variables than make it impossible to predict the response to a dose of Propofol. It is no safe dose.

“Midazolam has been given. Lorazepam has been given. It would take me a couple of days to try and figure out with the models that I have what the effect of that would be. Then you have a patient who may be withdrawing from benzodiazepines (Valium-like drugs). After all this patient has been given them for 80 days every night and he may have withdrawal from them. Or he may have tolerance to them. We don’t know”.

“Could the patient have tolerance to Propofol? It is not well-do***ented because nobody does this. But we do know that all the other drugs act at the same location (the same receptors). All the other drugs that act there are associated with dependence and symptoms of withdrawal. So maybe the patient is dependent on it? Or may be withdrawing?

Any dose of Propofol is potentially dangerous in these cir****tances.

“We are in the pharmacological Never-Neverland here – something that only has been done to Michael Jackson and no one else in history, to the best of my knowledge”, said Dr. Shafer.

904 days ago
40.

Barbarascy    

And the point is? This IS NOT about what he did with his former patients. This is about what he did concerning Michael Jackson. And what he did with Jackson was negligent, stupid, and played a part in Jackson's death. He could have done many great things before that night with Jackson. It does not excuse, or explain why he was in Jackson's home with a substance that was not supposed to be used in a person's home. It does not explain why he didn't do things that might have saved Jackson's life. Things any doctor should have known. Yes, Jackson might have been a drug addict, but who told Dr. Murray that he had to be his dealer?

904 days ago
41.

Pegasus    

The study of treating insomnia with propofol was an experimental study, was made a year after Michael Jackson’s death and there were no deviations from the standard of care during the experiment.

Dr. Shafer evaluated the article published in China after Michael Jackson’s death in November 2010. The article claims that treatment of refractory chronic primary insomnia by means of propofol showed successful results. (This paper is important as Dr. Shafer’s opponent, Dr. Paul White is expected to cite this article).

Dr. Shafer said that at the time propofol was given to Michael Jackson there was no literature about propofol being used for treatment of insomnia.

“There are over 13,000 publications in the medical literature about propofol. Out of that number over 2,500 papers are about propofol sedation. If you ask for literature on propofol and insomnia you get one article in the entire world and it is this one”, Dr. Shafer said.

As an editor of one of the leading Anesthesiology journals Dr. Shafer would not accept it for publication as there is a number of red flags – it does not tell how much propofol was used, it claims that after 5 days of 2 hour propofol infusions six months later the patients were still much improved in their sleep pattern, etc. The evidence is not adequate for such an extraordinary claim and Dr. Shafer did not find the conclusions of the paper convincing.

The paper says that propofol therapy is “an efficacious and safe choice for restoring normal sleep in patients with refractory chronic primary insomnia”.

“Efficacious and safe based on 64 patients is too bold a statement for such poor evidence”, said Dr. Shafer. This suggested that the paper was poor edited. To be fair to the authors they say that more studies should be made before conclusions can be drawn.

What is also important that before the study was conducted its protocol had been approved by the hospital’s ethics committee, and each of the participants had given his or her written consent. The experiment took place in a hospital setting in a sleep disorder center. Prior to the treatment each participant had fasted for 8 hours. Their blood pressure and oxygen saturation were constantly monitored during treatment. Propofol was infused intravenously for 2 hours using a micro-injection pump (an infusion pump). And there was no polypharmacy, but just propofol.

Though Dr. Shafer was concerned about the validity of the results in that paper he had no concerns over the standard of care in treatment of those patients. What is described, he said, is entirely appropriate. And it only highlighted the violations in the standard of care made by Murray in treating Michael Jackson’s insomnia.

(S0 that study was a decided difference from the criminal experiment Murray was conducting on Michael Jackson. However to me it shows that propofol as a means to treat insomnia may has some prospects. And also – what was okay to do in a proper setting, with a proper consent and proper monitoring for 64 Chinese people would also have been okay for Michael Jackson had it been done in the same way. If he had had at least 3 or 4 hours of sleep every night he would have been able to function and give his shows).

All in all Dr. Shafer described 17 egregious violations of the standard of care out of which 4 were also unethical and unconscionable.

The egregious ones were likely to end in a catastrophic outcome and death of Michael Jackson. David Walgren and Dr. Shafer stressed that each of those violations individually was likely or should have been expected to result in death. And all those risks were completely foreseeable too.

Walgren asked, ”ssuming that Murray gave a polypharmacy of drugs to a dehydrated, exhausted patient who may or may not have fasted and that Dr. Murray gave 25ml of propofol and walked out of the room and assuming purely for hypothetical reasons that Michael Jackson ingested either Lorazepam or Propofol – would it be Dr. Shafer’s opinion that Conrad Murray would be DIRECTLY responsible for Michael Jackson’s death? The answer was ABSOLUTELY.

Answering Walgren’s question the doctor stressed once again the fundamental principles of a doctor-patient relationship. He said that this relationship goes back down to the dawn of civilization. Doctors are permitted to know the most private details of a person’s body and of a person’s life. Doctors are permitted to give very powerful drugs that might harm or kill a patient, and are permitted to cut into a patient’s body to remove a cancer or repair an organ or replace a knee.

Doctors are allowed to do these things because they give a Hippocratic oath which dates back to 500 BC. It says: “In every house in which I come I will enter only for the good of my patients”, because at the core of a doctor-patient relationship is that the principle that you put the patient first. This is the cornerstone of this relationship. It is because you put the patient first that you are entrusted with surgery, drugs and intimate knowledge of the patient, said Dr. Shafer. The Geneva Declaration says: “The health and life of my patient will be my first consideration”. Columbia University says: “We put patients first”.

And when Dr. Murray agreed to treat Michael Jackson with propofol and disregarded his patient’s interests in so many ways Dr. Shafer said that Dr. Murray put himself first – not Michael Jackson.

904 days ago
42.

Pegasus    

Day 14. Thursday, October 20

This day is so important that I will try to transcribe it the best I can.

1. David Walgen talked about Propofol first.

He reminded Dr. Shafer that in March 2011 he had enquired whether Dr. Shafer would be able to give his expert opinion on this case and when Dr. Shafer agreed he provided him with all the materials concerning the case – medical records, statements and the like.


Dr. Paul White claimed in his review that propofol would be effective if taken orally
Dr. Shafer also received a review made by his colleague and friend Dr. Paul White made on March 8, 2011 where Dr. White suggested that Michael Jackson may have orally consumed the propofol.

Dr. Shafer said “I was disappointed because it is not possible” and explained, “On the first-passed principle alone oral propofol has no biological activity”.

The first-passed principle required explaination. It means that Propofol is so rapidly metabolized by the liver that very little propofol gets past it. Everything that enters the stomach and the intestines goes first to the liver.


Dr. Shafer said it was not possible due to rapid metabolism of propofol and the principles taught to first-year medical students
And “the liver has such powerful mechanisms for metabolizing propofol that only a very small percent can get past it. This is the principle that is taught to first-year medical students”

“It is called the first-passed effect.” Any stuff you take first passes the liver, the liver seizes it from the stomach and in the case of propofol you would expect nearly all the drug be removed by this first passed effect.”

Guys, with so much medical information studied here we can also regard ourselves as first-year medical students. After this first-passed principle was explained I see that when we take a pill it does not go into our blood immediately – first it may be (at least partially) broken into pieces in the liver and the body will receive very little. This is why if pharmacologists want the drug to be really effective they must work on the way it passes the liver barrier first.

And it is clear that propofol does not pass that barrier because it was designed to be taken straight into blood.

Walgren produced a paper called “Propofol is not bio available” (exhibit 216) made by Dr. Shafer specially for this testimony.

“Bio-available” was also explained. Dr. Shafer said, ”It refers to whether the drug is available to the body after it is taken orally. If you inject something intravenously by definition it is all in the blood stream. But if you eat something it may or may not get into the blood stream. And the amount which gets into the blood stream is the amount called “bio-available”.

What it essentially means is that you can take some drugs in kilos but they will still be cleaned out of the body before they enter the blood stream and start working there for the simple reason that they are not bio-available. And propofol is this kind of a non-bio-available drug.


Murray listens to a first-year medical school lecture
Dr. Shafer presented a series of slides which show a human digenstive system. Any drug is first processed in the stomach, then goes to the small intenstines, then to the large intenstines (if anything of the drug is still left after that) and eventually out through the rectum. Liver is a huge organ near the stomach into which all blood from the digestive tract organs flow.

When propofol enters the stomach absorption of propofol into blood starts almost immediately. The nature of the propofol molecule is that it can pass immediately through the tissue of the stomach into the blood stream.

All the organs in the digestive tract have blood vessels inside them (and will absorb propofol), but the matter is that all blood from these vessels will first go through the liver. And only when that blood passes through the liver, what remains of the drug is taken to the heart and the brain.


Even if the drug from the digestive tract gets into blood, this blood will first go through the liver and only then to the heart
This picture shows that all veins coming from various parts of the digestive tract first come together into a large vein which then takes all blood (with propofol in it) through the liver.

In the liver propofol is metabolized (or undergoes a reaction which break it down into other biochemical elements). This means that practically none of it is left in its original form and goes to the heart and brain to work there.

And this is exactly the first-passed effect named earlier.

“How would you characterize the degree that propofol is activated?”, asked Walgren. Dr. Shafer says that as a result of the first-passed effect 99% of the drug is removed and there is no reason to expect the propofol taken orally to have any biological activity in the body.

Dr. Shafer added that due to the most recent information the lining of the guts is very active against propofol, is resistant to it (and therefore is not absorved and does not go into the blood in these organs).

All of the above confirmed Dr. Shafer’s conclusion made in April 2011 that “there was ZERO possibility that Michael Jackson could have died of an oral consumption of propofol”.

Walgren stressed that this conclusion was based on the fundamental principles taught to first-year medical students? Yes, Dr. Shafer sadly agreed.

Neither of them is saying it but what is known to every first-year student should be known to Professor White too and this is why Dr. Shafer said he was disappointed by the statement Dr. White of March 8, 2011. He knows that Dr. White also knows that it is untrue, is sad about it and can only wonder why he claimed a non-scientific thing like that.

The theoretial part was confirmed by the studies where animals were given propofol orally but it did not take any effect on them (so all of them should be alive!).

Propofol was studied by various scientists (Dr. Gwen studied it for 15 years) before bringing it to the market. In 1985 propofol was given to mice via different routes. It was found that even a small dose of 5-15mg per kg given intravenously was effective, while even a massive dose of 300mg per kg given orally did not cause the animals to go into general anesthesia – and all this due to the first-passed effect taking place in the liver.

In 1991 the same result was confirmed on piglets – there less than 1% of propofol was bioavailable and the rest was cleaned out of the system. In rats there was some study to study difference as one study said 10% of propofol was bioavailable (1996) but the other study made 15 years later said that only 1% was.


In dogs and monkeys 99,75% of propofol taken orally was cleaned out of the system without having any effect on them
Dogs and monkeys also received propofol orally but the most they showed in blood was around 0, 25%.

Naturally all of them survived the process – and later we will learn that Dr. Shafer also drank propofol to test it on himself and he is still here to testify!

These findings absolutely rule out the possibility which Dr. White suggested in his report – that Michael Jackson could have taken propofol orally and this could have led to his death.

Walgren pointed it out and Dr. Shafer agreed that by the time Dr. White had made his statement in March 2011 all those studies had been published and available to the scientific community.

Translated from the highly polite and politically correct scientific language it means that Dr. White couldn’t have known about those studies (if he is a true scientist) and was therefore willfully misrepresenting the scientific data (or was lying if we put it in simpler terms).

While this unpleasant fact was touched upon in the court room Dr. White seemed to be very much engrossed by something in his computer.

With the help of Dr. Pablo Sepulveda, Professor of anesthediology in Chile, one of the leading scientists in the field and the host of an international conference in May, Dr. Shafer also made research on human volunteers who took the propofol orally.

There were 6 subjects in the study – the first three took 20ml (or 200mg) of propofol and the next 3 took twice as much dose - 40ml(or 400mg).

Naturally the pulse oxymetry was present and their blood pressure was constantly monitored – but neither the oxygen level nor the blood pressure ever dropped. Blood samples were taken from their arms and was measured for propofol. The level of their sedation/alertness was measured by a common validation scale used by anesthesiologists.


This paper was co-authored by Dr. Shafer and presented on October 14, 2011 in Chicago
However none of them showed any sedation levels at any time – propofol did not take any effect when taken orally.


Its conclusion is that propofol does not take effect if taken orally
The paper on those findings was presented to the annual International Society of Anesthetic Pharmacology by Dr. Shafer’s colleagues last Friday in Chicago which is a forum which brings together doctors and pharmacologists.

Dr. Shafer himself could not attend it due to his father’s death.

By the way Dr. Shafer was the recepient of a life-time award for his work in pharmacology at that conference.

Murray’s trial and Dr. White’s review were not the only reason why Dr. Shafer conducted that human study. The other reason is that there is an effort on the part of the Drug Enforcement Agency (DEA) to make propofol a restricted drug and handle it almost like morphine. It was Dr. Shafer’s view the publicity of Michael Jackson possibly drinking propofol might be one of the reasons that it is being pursued by the DEA.


Dr. Shafer conducted the study to show that there is no risk in patients abusing propofol orally
If the drug becomes controlled Dr. Shafer’s personal belief is that patients will be hurt. Anesthesiologists need to have easy access to propofol during the process of administering this drug. If you run out of it the patient will wake up – therefore it shoudl be always freely available to them. Any additional paperwork requirements as is usual for controlled drugs will place patients at risk.

Now Dr. Shafer’s study has shown that the drug cannot be abused orally – if the drug is to be abused it will be done only by IV which limits the range of abusers to health-care providers (the public does not generally have access to IV).

Dr. Shafer concluded that the human study only confirmed his initial opinion that there was ZERO possibility that Michael Jackson’s death was caused by a possibility of him orally consuming propofol.

Let me make a note here.

I was somewhat surprised when the defense approached the judge that they would no longer pursue the propofol-taken-orally-line of defense. It seemed to me that it was an unnecessary move - if they don’t claim it any more why not keep quiet over it and just not raise it during the trial?

But now I see that by approaching he judge they didn’t want the Prosecution not to touch upon this subject either and the only reason why they didn’t want it was saving the reputation of their main expert Dr. White.

They didn’t want the jury to know that Dr. White disregarded the fundamental principle of “first-passed effect” which is known to every first-year medical student and that he was clearly not telling the truth when he spoke about Michael taking propofol orally.

Well, now we know that Dr. White is capable of claiming something which will totally contradict the medical science. At least my trust for this expert has diminished greatly.

904 days ago
43.

Pegasus    

2. The theory of Lorazepam taken orally and Lorazepam in general came next.

When I was watching it for the first time it seemed that it was difficult even for the power of science to make an absolutely precise determination on what happened with Lorazepam that night (though it doesn’t change anything in respect of Murray’s guilt). Let us see what the second viewing will bring us.

The Lorazepam study and its pharmacokinetics was an even bigger set of slides, prepared by Dr. Shafer (exhibit 217).


Dr. Shafer does not lose time while the sides are conversing
Dr. Shafer is totally amazing – so much work done at the expense of his free time, with no fees charged, at a difficult time like his father’s death and all in pursuit of the truth and restoring the good name for his profession! Only true scientists are capable of that…

In one of his earlier papers Dr. Shafer was the principal investigator of Lorazepam and Midazolam administered IV to patients in intensive care units and for today’s study he relied on the findings related in that paper.

Dr. Shafer explained that the paper was looking into the difference between Lorazepam and Midazolam which were given in the intensive care unit (ICU) by a computer. The computer was used to target exactly the right amount of drug in the blood.

Also the computer recorded precisely how much drug it gave to the patients in the IC unit where patients stay for a long time. Depending on how deep a sedation was needed the computer increased or reduced the dose.


Dr. Shafer conducted a huge study on which dose of Lorazepam and Midazolam given IV produces which concentration in blood
It was a “double-blind” study where the scientists didn’t know which drug the computer was giving - the computer knew which drug went to which patient but the person using the computer did not. The idea was to see the difference between those two drugs.

The scientists regularly took blood samples from the arterty to get a precise link between the dose of each drug and its concentration in the blood.

The data for the article was so huge and its conclusions so reliable that Dr. Shafer’s article is widely cited by other researchers. The study was done at Stanford University – Dr. Geller, the Head of the Intensive Care Unit, was responsible for conducting the study and Dr. Shafer was responsible for the data analysis.

Walgren asked Dr. Shafer why he relied on this study in discussing the present case. Dr. Shafer said it was because of the huge amount of data gathered then – the number of patients was huge, each patient was studied very intensively and for a long period of time too. Therefore this study provides the best pharmacokinetic model to use in order to predict the level of Lorazepam concentration in the blood after a dose.


i*****lance could kill...
Aha, so the basis for that article was Dr. Shafer’s huge collection of data on the correlation between what dose of Lorazepam produced what concentration in the blood?And since we know what concentration of Lorazepam was in the blood in this case he will probably be able to tell us what dose was given?

Only will it be possible to find out whether it was given intravenously or taken orally? There is no doubt that it was given intravenously and by Murray – the only problem is how to prove it as not everything is in the power of science. Okay, let’s go on and see.

Dr. Shafer reviewed both Dr. Murray’s statement that he had given Michael Jackson 4mg of Lorazepam in two doses 2mg each and the toxicology report which stated a reading of 0,169 micrograms/ml of Lorazepam in the femoral (peripheral) blood.

Walgren asked him if he was able to find out whether the statement about the given dose matched up to the level found in the blood. Dr. Shafer said “yes” and provided a computer model called ”2 doses of 2 mg each” which shows what happens to such a dose of Lorazepam over time.


The doses Murray claims he has given would never produce the concentration of Lorazepam found in the blood after death (green line)
The red horizontal line of the diagram starts at midnight and goes all the way to 12 o’clock noon time. The vertical line shows the level of Lorazepam concentration in the blood (in micrograms per ml). The green horizonal line is the concentration of Lorazepam in the femoral blood measured on autopsy.

The diagram allows us to see what happens to the concentration of drug with time.

According to Murray’s statement the first IV injection was made at 2 in the morning. The model shows that initially the drug is all in the vein, but then due to its going to other tissues (called distribution process) and due to the process of metabolism the concentration of the drug in the blood falls rather quickly. If at the moment of the IV injection it was O,05 an hour later is it is already one third of it.

The second dose given at 5 am goes higher than the first (as the first dose is still working) – but again there is a very rapid washout of the drug and by 12 o’clock as the supposed time of Michael Jackson’s death we see that the predicted concentration of Lorazepam in the blood is much lower than what was found on autopsy.

It is only 10% of what was measured at the time of Michael’s death. And after death all processes in the body stop as the circulation of blood stops (and no further changes take place).

So speaking of the above scenario Dr. Shafer said “This did not happen”, because otherwise the coroner would have found Lorazepam at the low level shown in the picture. (And this means that Michael Jackson received much more than 4mg).

In order to explain what dose of Lorazepam could produce the level of 0,169 mcg/ml in the blood Dr. Shafer presented a different computer simulation called “10 doses of 4mg each”.

Under this model the dose of 4mg was to be given 10 times with an half an hour break between them. If the doses are stacked that way and after the amount given reaches 40mg it will then start to drop and by noontime will generate the level measured on autopsy.

Let me say one thing about this model.

According to this model the drug administration is supposed to start at midnight and finish by approx. 4.30 am after which the level of Lorazepman in the blood begins falling. At cross-examination of Dr. Shafer the next day Chernoff will ask him questions as to why his diagram starts at midnight when Michael was even away from home.

I don’t remember what Dr. Shafer replied but to me it does not change much - Dr. Shafer could have used a dose of not 4mg but 8 mg given 5 times and then the period of administering the drug would be reduced by half. It seems that this simulation was made in a hurry as the defense only recently declared their Lorazepam theory. With his father’s funeral Dr. Shafer had no time to take care of this point. If he had had more time he would have corrected midnight to 1 or 2 o’clock in the morning and would have doubled the dose which would roughly produce the same result.

Actually Dr. Shafer himself said that he didn’t know the dose. Usually the dose should be on the medical record but in Murray’s case there was no medical record – so the only number Dr. Shafer could work with is the final concentration of Lorazepam in Michael’s body while all the rest is open to assumption. And it is impossible to simulate the situation precisely in the absence of medical records.

Walgren showed Dr. Shafer a vial of Lorazepam and Dr. Shafer said that it was a 10ml vial, where each millilitre has 4 milligrams each. So 10ml x 4mg makes 40mg. Dr. Shafer said that the simulation he prepared was consistent with the level measured on autopsy and the dose in each vial (though in my opinon nothing could have stopped Murray from using two vials for one syringe, or making the infusions not every half hour but every quarter of an hour)

Then Prosecutor Walgren and Dr. Shafer determined the way some Lorazepam found its way into Michael Jackson’s stomach. What is important here is that if it was taken my mouth then it would be in the stomach in its original form, and if it was injected into the blood system it would get into the stomach as a metabolite.

Lorazepam may be found in the body in two forms – as lorazepam proper and as its metabolite, the chemical thing which is produced by the liver when the drug goes through it. It is called lorazepam-glucoronide. This “gluco” stands for a molecule of sugar which liver attaches to the drug so that it could be taken out by kidneys. Without attaching that molecule the body cannot clean it out of the system.

The lorazepam-glucoronide loses it biological activity, becomes inactive and will not put a person to sleep. Why it is necessary for the body is because it allows the drug to be taken away from the system by the urine.

What puts a person to sleep is the original molecule of Lorazepam and it was this original Lorazepam which was measured by the coroner in Michael’s blood as 0,169 micrograms/ml. Why it was in the blood is because it was injected by IV.

The same type of original Lorazepam was measured by Dr. Shafer in his study at Stanford University.

Let me note once again that the coroner measured Lorazepam in the blood and the defense’s lab test measured it in the stomach . So the amount of Lorazepam in the blood has to be compared with the amount of it in the stomach in order to see where it came first and via which route it found itself in the stomach.


Dr. Shafer said that the number of Lorazepam in the stomach provided by the private lab was substantially inflated
Walgren produced the lab report from the private company (exhibit 218) which analyzed the amount of Lorazepam in Michael’s stomach at the request of the defense.

The amount found by the private lab in the stomach was 634 micrograms/ml which is 0,634 mg (or approximately four times as much as the 0,169 mg amount found in the blood by the coroner, if my calculations of all these mg are correct).

Trying to find out by what procedure the private lab (Pacific Toxicology) calculated the Lorazepam in the stomach Dr. Shafer approached this company and asked for their procedure manual, however they didn’t provide any. It was only after David Walgren got their standard operations procedure do***ent that Dr. Shafer was able to see how the lab had come to that number.


It was inflated because the defense's test summarized the Lorazepam proper (on the left) and its metabolite (on the right)
What he found out was that they summarized both the drug itself and its metabolite produced by the liver (which as far as I understand is not done as it inflates the result). Due to their method the lab came to a substantially inflated number, said Dr. Shafer. Now it is difficult to say by how much it was inflated, but it clear that it was.

Walgren wondered, “Even though the number was substantially inflated, some Lorazepam was nevertheless found in the stomach, so how could Lorazepam administered intravenously find itself in the stomach?”

In answer to that Dr. Shafer showed a very complicated route Lorazepam goes and how it gets into the stomach even if injected into the blood by IV.

The blood takes the drug to the liver and from the liver it goes to the bile duct and the gall bladder, and from the gall bladder it sloshes back into the stomach. “Sloshes” means it is being spilled or splashed.


some Lorazepam sloshes from the gall bladder into the stomach
Unfortunately it does happen as many of us have a burning sensation in the stomach because of this bile juice thrown back there.

And if there is Lorazepam there it will go there together with it – however whatever amount of Lorazepam is found there it can be found only in the form of a metabolite (as it went through the liver and was processed there).

This splosh happens to approximately 25% of the drug processed by the liver, while the rest 75% is successfully washed out of the system and goes to the colon. Dr. Shafer says that 25% is that Lorazepam metabolite in the stomach is quite an expected result after its IV administration.


Even on the basis of the defense's inflated number the amount of Lorazepam in the stomach was 1/43d of a tablet
Then Dr. Shafer took the defense’s ac***ulative result of Lorazepame in the stomach (of Lorazepam proper and its metabolite wrongly calculated together) and multiplied it by how much fluid there was, and this is the way he came to a trivial or very small amount of Lorazepam of 0, 047 mg.


You can compare the amount of Lorezapam found in the stomach with the actual pill (follow the arrow to the dot on the right). The conclusion is that Lorazepam was NOT taken orally
So even in case we talk of the inflated number of 634 micrograms of Lorazepam from the Pacific Toxicology lab, it was still no more than 1/43d of the usual 2mg Lorazepam tablet in the stomach of Michael Jackson.

Dr. Shafer’s conclusion also included a very important fact that nearly all of that amount was a metabolite and not a drug in its original form (and this shows that it came from the blood via the liver and not from the mouth).

Dr. Shafer said that this way the defense’s own test results prove that Michael Jackson did not take Lorazepam orally anywhere near the time of his death.

The period of “near the time of death” means at least four hours before it – if the death took place sometime around noon. Dr. Shafer said it firmly that if it occurred at noon time the results obtained by the defense totally disproved that Michael Jackson could have taken Lorazepam orally during the four hours prior to his death (if he died at around 11.00 am I gather that the time span would be 7.00-11.00 am).

But since the conclusion covers only the period of four hours before death just as I was afraid the defense would be now arguing about the earlier time of taking Lorazepam. Frankly, to me it does not change a thing. Murray is so terribly guilty over everything else that even if science is unable to precisely determine what happened at a period of time prior to 8 or 7 o’clock it will be nothing but a small vague spot on the otherwise absolultely clear picture.

Especially since we cannot rule out that it was Murray himself who dissolved some pills in the juice and offered it to Michael Jackson for drinking. By the way can anyone who tried Lorazepam say whether it is bitter or neutral to the taste?

Why I am asking is because Chernoff verified with the coroner investigator Ms. Fleak whether the juice on the night stand had been tested for its contents. She answered “No”.

The question itself is a curious one. It is suggestive of the idea nurchured by the defense – that Michael could have dissolved something in there. However when a patient takes tablets he doesn’t dissolve them in liquid (unless they are huge) but swallows them and then drinks something afterwards. If the defense thinks that Michael could dissolve those pills in the juice, we can think the same about Murray. Indeed, who can guarantee that he didn’t give any liquid ****tails of Lorazepam to Michael for those three days when he was supposedly “weaning him off propofol”?

Murray offering Michael a ****tail of Lorazepam is just a speculation – but you will agree that it is a no less speculation than Michael swallowing Lorazepam himself.

Walgren asked Dr. Shafer about the possibility of taking Lorazepam orally earlier than 8 o’clock. Dr. Shafer said that he would need time to make more calculations but said that at midnight the night before it was entirely possible (only Michael would not take that crazy number of pills at the beginning of the night when he didn’t yet know that he would not be able to fall asleep).

Whatever is the case Dr. Shafer said that the amount of Lorazepam in Michael’s stomach was trivial (“trivial” means a drop in the bucket). Let me add to it that Michael Jackson died of acute propofol intoxication with the effect of bensodiazepines being only an additional one (and Murray himself said that he had given Michael a good deal of them that night).

904 days ago
44.

LadyD    

Prayers for Michael's children, the Jackson family and their extended family members. Stay strong with your bond of love. Much love to all.

904 days ago
45.

Pegasus    

3. So Walgren turned to Propofol again and moved into the area of simulating the response of the body to this drug.

Walgren wondered, “If a researcher were to seek out an expert to conduct this type of modeling would you be one of probably two people in the world they would seek out?”

Dr. Shafer modestly said, “Yes, it is a small community” (so he is probably a unique or even best expert in the world!)

In pharmacokinetics they look at drugs in motion in the body and specifically at how a certain dose of drug gives you a certain concentration and at how it rises and falls over time. This science gives you a chance to learn how much propofol will be found in the blood after a particular dose.

Pharmacodynamics is about the power of the drug and how powerful the drug in your body. It does not talk about the concentration of drug but about the effect of it in your body (the concentration may be low but the effect may be high).

For these sciences to be useful they need to be mathematical - equations show which concentration of a drug has which effect and bring scientists to a number they can work with.

Dr. Shafer shows a slide demonstrating the linkage between the two - the motion of a drug in the body and its power at any given time.

His comment on the picture:

You give a dose of a drug and pharmacokinetics shows which is the concentration of it in the blood. By a dose he means all doses. Maybe a little bit here, a little bit there, a little bit later – so whatever was given and at whatever time it was given is the dose.

The concentration you predict is not just one number – it is a curve over time, the concentration of drug over time following the dose (falling or rising).

The pharmacodynamics then says for will be the drug effect for each given concentration at any given point in time. Since the concentration changes over time, the drug effect will change over time too.

Dr. Shafer refers to his two papers which provided the corresponding data and computer models for infusing propofol in every operating room all over the world. His model is unique as it includes the patient’s weight, age and even gender – and this is why it could be precisely matched to Michael Jackson.

Besides the ability to measure the concentration of propofol in blood Dr. Shafer also developed a technique for measuring the concentration of propofol in the brain. One paper on that was written with Dr. White (who is now the defense’s expert). They were studying apnea (a stop in breathing) and Dr. Shafer took Dr. White’s numbers at which concentration of propofol apnea will occur.

Dr. White’s paper says that at the number of 2,3 mg/ml of propofol half of all patients will be expected to be apnic (not breathing). But as every patient is different Dr. White provided a range which is plus-minus 0,5mg which is called a standard deviation.

The lowest figure in the range will account for the most sensitive patients, while the higher one will refer to the most resistant ones. At the lower end of that dose 5% of patients will be at risk of apnea, while at the higher end 95% will be at such risk. And at the level of 3,3mg/ml everyone will be apnic.

After breathing stops the heart will go on beating. While it is beating, propofol will still be circulating in the blood. And while it is circulating, it will be metabolised and will be going away out of the system. The experiment on some unfortunate piglets showed that the heart stops beating 9 minutes after breathing stops (I gathered that the piglets were revived by CPR though).

For a human being the period until the heart stops was calculated as 10 minutes.

Having all that data Dr. Shafer was able to make simulations of several scenarios of administering Propofol to Michael Jackson and see whether any of them could be realistic.

The 1st simulation was based on Dr. Murray’s statement that he had given only 25 ml of Propofol.

Its bottom horizonal line shows time and is marked in minutes.

The vertical line shows the concentration of propofol in the blood.

The central green horizontal line shows the amount of propofol found in Michael Jackson’s femoral (peripheral) blood after his death (2,6 mcg measured on autopsy).

Below it is another horizontal line called “apnea threshold”. It shows Dr. White’s number of 2,3 as the concentration of propofol in the brain where half of patients will be apnic (not breathing).

The level of propofol in Michael Jackson’s femoral blood is very close to the level where apnea is expected (actually it is higher than that).

At the moment when propofol is injected its blood concentration is very high. This concentration descends incredibly fast. There are two reasons for that – first, as this large amount of drug hits the liver it is metabolized there, and second, it is quickly removed by the fat tissues in the body.

However it takes time for propofol to get into the brain. There is so much propofol outside the brain that it really pushes itself in, says Dr. Shafer. So the level there gradually rises and in two minutes reaches a peak. After the peak the brain level of propofol falls slowly, as it still needs to be removed from the brain in order to be metabolized.

However the brain concentration does not even remotely reaches the apnea threshold at which breathing stops of half of the patients (according to Dr. White’s figures).


If patient-to-patient deviations are added to this model a small number of patients will be at risk even with this small dose
Then Dr. Shafer adds two standard deviations in two directions (from Dr. White’s work). Below the edge of this range no one will be apnic. Above the upper edge of that range everyone will be apnic (nobody will be breathing).

And this new addition shows that even with this small dose a very small fraction of patients will be at risk . The risk arises when propofol reaches a peak concentration in the brain (the period of 0,5- 2,5 minutes). After 3 minutes there will be no more risk again and everyone will be expected to breathe.

Dr. Shafer said that the level of propofol found in Michael Jackson’s femoral blood and used for this model was the most conservative one (2,6). The level measured at the hospital was 4,1. One more was 3,2 from the heart and 2,6 was measured at the coroner’s office.

So even with this small amount of propofol a stop in breathing could occur in Michael’s case (and that is why Murray should have been careful even with this small dose).

And its effect was aggravated by the benzodiazepines he also gave to Michael – Lorazepam, Midazolam and Diazepam. All these drugs have a potential to decrease breathing, so giving Propofol on top of it was gravely increasing the risk of apnea and the standard of care for administering propofol was required even with this small dose too.

Dr. Shafer says, “This is why I say that there is no such thing as a small dose of anesthesia. Even with this small dose there is some risk”.

But then Dr. Shafer says that the scenario of only 25 ml given is not what really happened to Michael Jackson. Even if he stopped breathing at the peak brain level, his heart would go on beating due to oxygen in the lungs for some 10 minutes more. During this period the concentration of propofol would go on falling and at the time of death its level would be vanishingly small – many times as low as the level actually found in his femoral blood.

Dr. Shafer said:

“So this did not happen. Michael Jackson received more than 25 mg”.
The second simulation model was made on the assumption that Michael Jackson received 50 mg of propofol by IV.

The way Conrad Murray described giving propofol was taking the syringe and filling it with propofol and lidocaine. The description said that he was using equal mixtures (the words 1:1 showed up in the interview). A 10cc syringe would have 5cc of propofol or 50 ml.

Dr. Shafer suggested a simulation for 50 ml of propofol administered to Michael Jackson as a bolus (pushed all at once) by half a 10cc syringe (lidocaine was disregarded).

The propofol in the blood would be initially so high that it doesn’t even show in the diagram but then goes down quickly.

The brain level of propofol rises quickly and when it reaches its peak level most patients will be expected not to breathe. Within 5-6 minutes after that it goes low enough for you to expect patients to again be breathing.

It is quite likely that Michael Jackson would have stopped breathing with this dose because there were so many other drugs he had already received from Dr. Murray. This would have happened in the period of 1-4 minutes after receiving the dose.

If he had not breathed for 3-4 minutes and had regained his breathing (due to resuscitation effort) Dr. Shafer expects Michael would not have sustained any brain injury.

After breathing stops, as an absolute minimum the heart would continue beating for another ten minutes. Provided the heart is beating there is still circulation and propofol is being metabolized. So the level one would expect on autopsy would be around 0,4 mcg which is only a fraction of what the coroner measured in Michael Jackson’s femoral blood.

Therefore this model rules out that Michael Jackson was given a single dose of 50ml of propofol.

( to be continued)

904 days ago
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