Dr Shafer
Walgren
If the 2X2 mg at 2 and 5 was the only amount given to MJ, the concentration the coroner should have found is 0.025, not 0.169
Shows another model , to reach 0.169 at 12 noon. Shows 10 doses of 4 mg between midinght and 5 am. (I'im not too sure of the time range, it was in the early part of the night)
There is no medical rocords, so Dr Shafer doesn't know what was given, has to work with what the coroner found.
Shows a vial 10ml, each ml has 4mg, so thats 40mg lorazepam in a 10ml vial. So 40mg is consitent with the concentration found by the coroner, and consistent with the vials found at Mjs house.
metabolite : produced by the liver, the lorazepam metabolite is calld is 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, not its metabolite
Showing the defense test for lorazepam made by Pacific Toicology. Dr Shafer has reviewed it. He had to go through D Walgren to receive pacific Toxicolgy's procedures, the lab didn't want to give them to Dr Shafer. Their method converted the metabolite back to the drug itself, and after this, analaysed for lorazepam. So their results included both the drug and its metabolite.
So their results was the drug + metabolite. 0.634 concentration.
You would expect the metabolite to show up in the liver, so the 0.634 is a substantially inflated number. There was no breakdown bewteen the drug an the metabolite in Pacific toxicolgy analysis.
Lorazepam was found in the stomach. How is it possible ?
Showing digestive track diagrams again, explains what would happen to an IV injection of lorazepam :
IV injection : active drug goes to the blood, and at some point goes to the liver, the liver converts the active drug to its metabolite, about 25 % of the metabolite goes to the bile, 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 (example : vomit, when some bile goes into the stomach) ; That's how you will find lorazepam metabolite in the stomach.
.047 mg lorazepam = 1/43 of pill was lorzaepam + its metabolite. Most of this is the metabolite, not lorazepam itself. The true amaount of active lorazepam is much smaller than this. This proves that MJ did not swallow lorazepam for at least 4 hours prior to his death. Assuming time of death is 12, MJ did not swallow lorazepam between 8am to 12 noon. So there is no chance that he did that at 10 Dr Shafer would need 5 minutes to calculate if oral consumption was possible prior to 8 am.
0.47 mg is a trivial amount.
Re explains what pharmacokinetics and pharmacodynamic is
kinetics : motion
dynmaic : power
Showing studies done about propofol pharmacokinetics and pharmacodynamics. Dr Shafer was principal investigator in this studies. The models in these studies are programmed into infusion pumps worldwide. They are the only models that include, age, weight and gender of the patient.
Propofol acts in the brain. The brain makes you fall asleep or stop breathing. So it's the brain concentration that matters. The actual term is effect site = drug concentration in the brain.
Shows a study using an EEG (electro encephalogram = brain waves) to study the brain during propofol, so he could relate propofol effects on the brain to blood concentration. Dr White participated in the study. The aim is to know at what concentration 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 : what is the delay between apnea and the time when blood circulation stops. The study was done on pigs :the result was 9 mn between respiratory arrest and cardiac arrest.
Dr Shafer did simulations for this case :
for this case , took 10mn between resiratory arrest and cardiac arrest (a human being has more oxygen than a pig ), MJ was on supplemental oxygen, so considers 10mn a safe number.
Propofol concentration found by the coroner in Mjs in femoral blood was 2.6 , that's the concentration when blood circulation stopped.
1st : propofol 25 mg : what would happen if one were given 25mg propofol bolus?
showing model : 2.6 concentration femoral blood. Apnea threshold 2.3 . Level of propofol in femoral blood is close to apnea threshold (femoral blood is slightlu abve)
Concentration rises quickly, and falls very quicly, because of the liver, and propofol goes to other tissues.
Brain concentration : MJ would have been below the point where half of patients would be apneic. But above the one 1.3 limit when 5% perons are apneic, with only propofol. He would have stopped breathing from 1mn to 2 and half minutes after the injection. After 3 mn, you wuold expect everybody to breathe again.
So with a small dose of 25mg , there is a risk, during a short period of time. The risk would be made higher with other benzos. All of the drugs MJ recieved potentially affect breathing, making the risk higher.
Doesn't think that's what happened to MJ : MJ would have benen apneic for 2mn, and his blood circulation wuld have lasted at leat 10Mn, propofol would have been metabolised, did not happen given the femoral concentration. After 10mn, the femoral concentration would have been much smaller than the one the coroner found. He rules out this scenario
2 - 50mg propofol bolus:
MJ would likely have stopped breathing , 1mn to 3or 4mn after the dose. If the period of apnea lasts around 3 mn, Dr Shafer wouldn't expect brain damage. The heart will continue beating for 10mn.
50mg bolus wouldn't give the level that the coroner measured in femoral blood (coroner level was much higher) : rules out a 50 mg single bolus injection.
3 100 mg , bolus injection :
patient will be apneic , Dr Shafer does that every day, it*'s an anesthetic dose. Mj would have stopped brething within 1 mn, heart wuld have stopped 10mn after , blood level would have been under what the coroner found. Rules out this scenario.
Multiple syringe injections scenarios :
- 6 self injections, 50mg each , over 90mn:
self injection would involve drawing propofol, injection through the port , takes time and coordination.
Based on CM, MJ had poor veins, self injection is not likely, and extremely painful without lidocaine. This scenario requires that MJ wakes up after each injection.
50mg would put him to sleep, each injection keeps him asleep for about 10n, each injection would keep him asleep a little longer, since there would still be e little propofol left in the blood.
10m until the circulation stops : the blood concentration level would be well under the femoral blood concentration found by the coroner. Rules out this scenario.
- Self injections, 100mg each, 6 injections, over 3 hours.
Anesthetic dose.
Mj would stop brathing , 10 mns after circulation stops, the blood level would be well below what was measured in femoral blood.
MJ would have probably died after the first or second injection, but coroner would have found a lower femoral level.
How can Murray even look in the mirror? Guess money made him foget what it means to be a doctor. To HELP people. To put the person FIRST!!!
