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    Народът срещу Д- р Конрад Мъри - 20. 10. 2011 - Ден 14

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    andeli
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    Народът срещу Д- р Конрад Мъри - 20. 10. 2011 - Ден 14

    Писане by andeli on Пет Окт 21, 2011 2:30 pm

    Morning Session

    Dr. Shafer Testimony continued

    Walgren direct continued


    Walgren starts talking about Propofol. Walgren asked Dr. Shafer if he would provide his opinion in this case around March 2011 and gave Shafer LAPD and toxicology reports. Walgren also gave Dr. Shafer a report from Dr. White. Dr. White had written that MJ could have orally digested Propofol. Dr. Shafer says that he was disappointed because oral Propofol cannot get pass liver. Shafer says by the first pass effect liver would almost remove all of the Propofol.


    (Dr. White is shown in the picture)

    Dr. Shafer has prepared a presentation called "Propofol not orally bio-available"

    Slide 1 is the title.

    Slide 2 shows the digestive track of human body. Dr. Shafer identifies the organs. Shafer says oral Propofol would come to the stomach, it would pass into the blood and all of that blood would go into the liver and only after it passes the liver it would go back to the blood vessels.



    Slide 3 is a close up of the digestive track. It shows all the veins from the digestive track goes into the liver. Shafer explains first pass effect of Propofol. 99% of the drug would have been removed and there's no reason to expect that oral propofol would have any effect. Dr. Shafer wrote in his report there is 0 possibility that MJ died because of oral Propofol.

    Slide 4 is a 1985 article by Dr.Glen (doctor to developed Propofol - Dr. Shafer says that he deserves to be called Father of Propofol)about Propofol. In this study propofol was given to mice, they found that IV doses was effective but even 20 times the IV dose is given to animals orally would not produce general anesthesia.

    Slide 5 1991 Study on piglets. This research shows that less than 1% of Propofol would be bio available in the piglets. This shows that Propofol would be cleaned out the system by the liver.

    Slide 6 1996 research done on rats. In this study they found out that 10% of the Propofol was available in rats. Dr. Shafer says it's because rats are a different species. It still shows that a majority of Propofol (90%) is cleaned out of the system.

    Slide 7 - US Patent dated June 23,2009. The research findings in this study was done in rats and the bio availability of Propofol was less than 1%.

    Slide 8 - US Patent dated Nov 17, 2009. Another research done on dogs and monkeys and the bio availability was less than 1%. All of these information was available when Dr. White and Dr. Shafer wrote their reports.

    Rest of the slides - Dr.Shafer then did a research about the oral bio availability in humans. Dr. Shafer says there was nothing published as humans as subjects. Dr. Shafer participated in a study done on human volunteers in Chile. 6 students volunterred. First 3 volunteers drank 20 ml/200mg of Propofol and other 3 drank twice that dose (400mg). they mesasured pulse, blood pressure and sedation was measured. They regularly took blood from the arm and measured for Propofol. None of the volunteers was sedated after orally digesting Propofol. Level of the oxygen never dropped, blood pressure never dropped. The study was presented last week in Chicago in a conference. Dr. Shafer also got a lifetime achievement award in that conference.



    Last slide is the conclusion of the human study, there was no effect of oral Propofol on humans.

    Shafer says he did the research because of this case and DEA wanting Propofol to be a controlled substance. Shafer thinks DEA is trying to do this because they believe MJ could have drank it. Shafer says that he wants to show that the drug cannot be abused orally.

    Shafer says that he told Walgren on the first phone call oral effect of Propofol was not possible and he later seek out these additional surveys and even conducted a study on humans to show that there was zero possibility.

    Walgren brings another presentation. This one is about Lorazepam. (long sidebar due to objection by chernoff)

    Slide 1 title.

    Slide 2 A study that was done by Shafer. He looked to Lorazepam or Midazolam. They gave it to patients by a computer. Blood was gathered at regular interval from the patients artery to study the concentration. The study was done at Stanford, and they colected a huge amount of data.

    Dr. Shafer reviewed toxicology levels in MJ and he's aware that CM said 2 doses of 2mg of Lorazepam. Dr. Shafer ran models to see if this dose would cause the Lorazepam levels in MJ's blood. 2 doses of 2mg of Lorazepam is not supported by the blood levels. The model shows that the concentration of 2doses of 2 mg at 2 am and 5 am is about 10% of what was found. Shafer says MJ was administered more Lorazepam.



    mid morning break

    If the 2 doses of 2 mg was given at 2:00 and 5:00 AM was the only amount given to MJ, the concentration the coroner should have found is 0.025, not 0.169.

    Dr. Shafer shows another model to reach 0.169 level at 12:00 noon. It shows 10 doses of 4 mg between midinght and 5 am. This number is consisted with the vials found at MJ's house (10 ml bottles with 4mg per ml concentration which equals to 40mg).

    Dr. Shafer explains metabolite of Lorazepam called lorazepam glucoronide. The liver attaches sugar to the lorazepam molecule so the kidneys can process the lorazepam. This process makes the drug inactive. Lorazepam glucoronide has no effect. The lorazepam will have an effect, but not its metabolite. The coroner looks for the levels of lorazepam and not its metabolite.

    Walgren shows the defense test done for Lorazepam. Pacific Toxicology converted the metabolite back to the drug itself and after this analyzed for Lorazepam. So their results was inflated as it included both the drug and it's metabolite. Their results for Lorazepam and its metabolite was 0.634 concentration. Pacific Toxicology didn't seperate between Lorazepam and it's metabolite.

    Walgren asks how can Lorazepam be found in the stomach. Dr. Shafer showing the digestive track explains the process. After IV injection the active drug goes to the blood. Later it goes to the liver and liver converts it to its metabolite. 25% of the metabolite goes to the bile and then the bile drains it into the intestine. At the junction between the stomach and small intestine, some of the metabolite sloshes back into the stomach. Dr.Shafer says MJ had 1/43 of a pill of Lorazepam and most of it was the metabolite and the true amount of Lorazepam was much smaller.

    Dr. Shafer says that this proves that MJ did not swallow Lorazepam for at least 4 hours prior to his death (between 8 AM and 12PM). So Flanagan's hypothetical scenario of MJ taking Lorazepam pills around 10AM is not possible.

    Walgren and Shafer switched to discussing Propofol. Walgren goes over several studies that Dr. Shafer has done about propofol.Dr. Shafer used the models that include age, weight and gender from those studies to run models about Propofol found in MJ.

    Shafer says that Propofol acts in the brain and it's the brain makes you fall asleep or stop breathing. So it's the brain concentration that matters.

    Defense witness Dr. White was a participant in one of the studies to show at what concentration of Propofol a person would stop breathing. At 2.3 mg/ml half of the patients would be expected to stop breathing. The range of apnea is 1.3mg to 3.3mg/ml . At 1.3mg, 5% of patients stop breathing, at 3.3mg 95 % stop breathing.

    Another study was done on pigs to determine the the delay between apnea and the time when blood circulation stops. The result showed that there is 9 minutes between respiratory arrest and cardiac arrest.

    Dr Shafer did simulations for this case. He assumed the time between respiratory arrest and cardiac arrest to be 10 minutes as a human being has more oxygen than a pig and MJ was on supplemental oxygen. Propofol concentration found by the coroner in Mj's in femoral blood was 2.6 , that's the concentration when blood circulation stopped. Shafer is trying different scenarios to reach to that number. Concentrations of Propofol rises quickly and also falls very quickly. This is because of the liver and propofol goes to other tissues.

    Scenario 1 : Only 25 mg Propofol bolus injection

    MJ would have been below the point where half of the patients would stop breathing (2.3) but above the 5% limit (1.3). He would have stopped breathing from 1minutes to 2 and half minutes after the injection. After 3 minutes everyone would be expected to breathe again. So even with a small dose there's a risk for short period of time. As MJ was given other drugs he would have a higher risk.

    Shafer doesn't think this is what happened to MJ. MJ would be apneic for 2minutes and his blood circulation would have lasted at least 10minutes and propofol would have been metabolised. So the femerol amount would have been much smaller than the coroner had found. Shafer rules out this scenario.



    Scenario 2 : 50mg Propofol bolus (half of the needle is filled with Propofol and other half with Lidocaine)

    MJ would likely have stopped breathing 1 minutes to 3 / 4minutes after he was given the dosethe dose. (not breathing for 3 minutes wouldn't cause brain damage) The heart would continue beating for 10 minutes. Again 50 mg Propofol wouldn't give the amount measured in the femoral blood. Shafer rules out this scenario as well.

    Scenario 3 : 100 mg Propofol bolus (All the syringe is filled with Propofol)

    Patient would stop within 1 minutes and heart would have stopped after 10minutes. Femoral blood level would have been under what coroner found. Shafer rules out this scenario.

    Multiple Self Injection Scenarios

    Scenario 4 : 6 self injections 50mg each over 90mn

    Self injection would involve drawing propofol and injection through the port . It takes time and requires coordination. Based on CM's intervew MJ had poor veins so self injection is unlikely and would be extremely painful without lidocaine. 50mg would put MJ sleep and make him sleep about 10 minutes and it would get a little longer with each injectionas there would be a little propofol left in the blood. Circulation would stop after 10 minutes. Femoral blood level would be well under the numbers found by coroner. Shafer rules out this scenario.

    Scenario 5 : 6 injections 100 mg each over 3 hours.

    This is an anesthetic dose. MJ would stop breathing and the circulation would stop after 10 minutes. Again the blood level of Propofol would be well below than what was measured in femoral blood. Shafer says MJ would have probably died after first or second injection ,but coroner would have found a lower femoral level of Propofol.

    Lunch break

    Afternoon Session

    Dr. Shafer Testimony continued

    Walgren Direct continued


    Multiple Injections by Murray Scenarios

    Scenario 6: 6 injections 50mg each

    In this scenario MJ would have stopped breathing multiple times and under this scenario MJ wouldn't be alive and the femoral blood level would be achieved. Dr. Shafer says this doesn't make sense as CM had to reinject repeatedly and the injections needed to continue after the breathing and the heart stopped. So Shafer rules out this scenario.



    Scenario 7 : 100ml infusion, 1000 mg



    In this model an infusion is started at 9:00AM and there was a bolus before the drip. When you give a drip , there is not much difference between blood and brain concentration. Levels first raise quickly. Later the liver would start to metabolize the propofol and the levels would slowly rise. When the patient approached to the apneic threshold breathing would have slowed down at a slow pace and carbon dioxide would have gone up. If there had been capnometry you would have seen the carbon dioxide go up.

    At 10:00 am MJ continues breathing but without capnometry CM doesn't see that there is a problem. Around 11:30 to 11 :45 breathing would have stopped as there is no oxygen in the lungs. MJ died at about noon with the infusion still running. This is the only scenario Dr Shafer could generate that produces the femoral level found at MJ consistent with CM 's explanations of how he gave propofol. This scenario fits all the data in this case. This what Dr Shafer thinks happened .

    CM could have detected there was a problem with capnometry, pulse oximetry. If CM was with MJ he would have seen slow breathing and could have turned off Propofol. CM might have thought everything was okay and walked out of the room. Shafer again mentions that CM bought 130 100ml vials which Shafer thinks measn 1 vial per night.

    mid afternoon break

    Walgren and Shafer starts working on a IV setup demonstration. Dr. Shafer brought same/similar equipment of what CM used or bought.
    Shafer hangs a bag od saline on the IV pole. He attaches the infusion set tubing to the saline bag. In the infusion set there's an injection port with a rubber stopper where you can stick a needle to give mediciation.

    Shafer shows a 22 gauge catheter (same size as what's used on MJ). Catheter remains in the vein (needle doesnt). Dr. Shafer attached the catheter to the saline tubing and shows that the fluid goes through very quickly. Saline bag has a non-vented tubing as there's no need for a vented tubing with the saline (the saline bag will shrink).

    For Propofol you'll need a vented tubing. CM bought vented infusion sets from Sea Coast. Dr. Shafer shows the vented infusion set that CM bought. It has a apparatus on top that allow the air to come in. This tubing is designed to be used with an infusion pump but there was no pump.

    Spike from Propofol tubing woul have been stuck into the bottle and this would be consistent with the tear found at the 100ml Propofol bottle from MJ's house. Shafer sticks the spike into the Propofol bottle and hangs it on the pole with the plastic handle on the bottle.



    Walgren shows that the 100ml bottle found in MJ's home also had the same handle. Objection by the defense.

    After the sidebar the following stipulation is entered to the record : the handle of the bottle was lifted for demonstration by Walgren. When the bottle was found, it was still attached to the bottle and unused.

    CM in his statement to the police said that he turned of the saline before giving Propofol with a syringe. Shafer shows the rubber clamp and how you can stop the flow with the clamp. Shafer demonstrates infusing 25mg of Propofol with syringe as CM mentioned in his interview. Propofol doesn't come out of the tube as the saline is turned off and not coming to push Propofol out. So CM's description of infusing it over 3 to 5 minutes is impossible if the turned off the saline. You need to unclamp the saline for Propofol to come out.

    Dr. Shafer demonstrates the vent on the propofol tubing. If he closes the vent Propofol stops, if he opens the vent Propofol runs through. Shafer then hook the vented tubing with a needle to the y connector. Dr. Shafer says that this is an extremely unsafe setup that is all based on gravity. If one bag is lifted there will be more force in that bag and it would slow the other one. If saline stops, propofol speeds up. If the rate of the saline is changed, it would change the rate of the Propofol. This is why this system is very dangerous. The only way to control the speed is the clamps.

    Walgren asks about the IV bag with a slit. Shafer says perhaps murray didn't know there was a hanging handle or didn't want to use it. Shafer puts the Propofol bottle with the spike into the cut IV bag to demonstrate it's possible.



    Shafer says this system explains why the long tubing found at the house didn't test positive for propofol, but the short tubing did. There was another long tube which was connected to the popofol bottle.

    Shafer empties the Propofol bottle quickly and removes the long vented tubing that had Propofol in it. It fits in his hand. Walgren asks if that tubing would fit into a pocket. Dr. Shafer says yes.

    Walgren does a recap of Dr. Shafer's testimony: 17 egregious deviations of care, 4 of them are also unetical, has shown a video about the way propofol is safely given, has explained that oral consumption propofol was impossible, that MJ received more than 4mg lorazepam, that at 10 am it was impossible that MJ swalllowed lorazepam,scenarios suggested an IV drip, demonstrated the IV set up and that the infusion line could be compacted in one hand and fit into a pocket.

    Walgren asks if CM was the direct cause of MJ's death if MJ self injected/ digested Propofol/Lorazepam. Shafer says yes as CM was the one that brought the propofol, left patient with access to the drugs and started the IV line. Shafer says CM is responsible for every drop of propofol or lorazepam.

    Walgren finishes his direct examination of Dr. Shafer.

    Due to scheduling issues testimony would start at 12:45PM PST on Friday October 21, 2011.


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    Re: Народът срещу Д- р Конрад Мъри - 20. 10. 2011 - Ден 14

    Писане by andeli on Пет Окт 21, 2011 2:55 pm



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