Putting the Pharmacology of Michael Jackson’s Death into English

A vial of Versed, one of the medications used on Michael Jackson

What everyone has been speculating about for months did indeed end up being the truth—according to a search warrant released today, Michael Jackson died from an overdose of propofol, brand name Diprivan. However, the cocktail of drugs found in Jackson’s system and in his rented home were enough to bring down several people. Dr. Conrad Murray admits to giving Jackson lorazepam (Ativan) and midazolam (Versed) through an IV before finally giving Jackson the Diprivan.

Because this information is part of a search warrant, it gives incomplete and oversimplified information. I don’t believe the single dose of Diprivan is what killed Jackson; it was a cumulative overdose of many central nervous system-depressant drugs, each of which are usually safe when used properly, but grossly misused by Jackson and his physician.

According to the LA Times, a (partial) list of other drugs confiscated in the house, along with the Ativan, Versed and Diprivan, included diazepam (Valium), temazepam (Restoril, used to induce sleep), clonazepam (a muscle relaxant), trazodone (Desyrel, a tricyclic antidepressant used to induce sleep) and tizanidine (Zanaflex, another short-acting muscle relaxant). Another drug, tamsulosin, a drug used to treat an enlarged prostate, was found in the home. Time marches on for everyone—even aging-phobic Jackson, who was a plastic surgery addict, could not stop the normal enlargement of his prostate!

Bottom line, Jackson had an enormous tolerance for a group of drugs that are not quickly excreted from the body, a group that build up in a person’s fat (and everyone’s got fat, even skinny people like Jackson!) and take a long time to clear. That is called a drug’s half-life.

None of these drugs are terribly dangerous drugs if used correctly. I have personally given IV Versed and Ativan in an ER situation (reducing dislocated shoulders and patellas), but I was trained to do so, had intubation equipment ready, and of course most importantly—was in a hospital setting!

A CNN article includes Dr. Murray’s timeline and ultimately what he did when he “found” Jackson not breathing at 11 a.m. According to the doctor’s statement, he gave Jackson 10 mg. of Valium at 1:30 a.m. after rehearsal for the soon-to-start “This Is It” shows in London.

Valium is a tricky drug with a long half-life. It takes 20 to 100 hours (twenty to one hundred, not a typo) for a body to excrete half of a dose of Valium. Another consideration is there is no antidote medication available for the treatment of benzodiazepine accumulation (there is an IV medication available but not always readily at hand, for medication floating about in the circulation), consequently most medical people would agree that care is mostly supportive. In other words, if a person stops breathing, you give that medication if you have it, intubate the person and breathe for them until they can do so on their own.

Ten milligrams of Valium makes me unconscious for 24 hours and loopy for another day.

When the Valium failed to knock Jackson out, Murray gave him a 2 mg. IV dose of Ativan (not an unsafe dose, but don’t forget that 10 milligrams of Valium is on board and not yet being excreted) and then an hour later, 2 milligrams of Versed (again not an unusual dose, but remember that Valium and Ativan are on board.

Two milligrams of Ativan puts me to sleep for about 5 hours. Two milligrams of Versed makes me forget where I am for about 30 minutes; I have no memory of falling asleep but utterly forget what I did or what I said (all were given in medical situations, during diagnostic or surgical procedures by physicians or CRNAs—not recreational!). Versed doesn’t really knock a person out that well …

Ativan has a half-life of 10 to 20 hours, and Versed around two to six hours.

At 5 a.m. another two milligrams of Ativan was given, and at 7:30 a.m., yet another Versed dose.

We have a total of 10 milligrams in Jackson’s system, along with 4 milligrams of Ativan and Versed—that we know about according to the affidavit.

The statement said that Murray gave Jackson “several different drugs” before finally giving him a 25 milligram dose of Diprivan (again, not an abnormally high dosage), which put Jackson to sleep at 10:40 a.m. for the last time. The doctor claims he left the room for only two minutes, and returned to find Jackson not breathing.

The half-life of Diprivan is 30 to 60 minutes. In my opinion, Jackson needed respiratory support for at least one hour after that dose of Diprivan.

Dr. Murray’s “treatment” included CPR and a drug “to reverse the effects of the sedative,” something called Anexate, which reverses the effects of benzodiazepines. There are no antidotes for Deprivan. The treatment for this type of overdose is ventilation. I seriously doubt Jackson’s heart stopped beating in those two minutes that he was unattended. Small amounts of highly diluted lidocaine are added to IV Diprivan to reduce the pain upon injection, and Murray admits he did this. I doubt the lidocaine caused any problems.

There is nothing mentioned about narcotics (morphine, Demerol, Dilaudid, etc.) being found in Jackson’s system. I strongly suspect those meds could well have been on board, too, even if Dr. Murray didn’t “prescribe” them, it’s reasonable to assume that if they were in the household, they were being used. The affidavit released was in conjunction with the search warrant on Murray’s Houston practice, not a coroner’s report.

Descriptions of the treatment room include a pulse oximeter to monitor oxygen concentration in the blood and also the heart rate, along with oxygen tanks, so I presume Jackson had a nasal cannula in place to supplement oxygen. But to breathe, the diaphragm needs to contract, and it knows to do that when the brain tells it to do so. But a class of drugs that is a known central nervous system depressant can and does wipe out that message to breathe.

In a nutshell, just because Jackson didn’t received the desired therapeutic effects of the drugs (sleep) certainly did not mean the drugs did not have an effect on his system. Dr. Murray should have understood this if he had any understanding of pharmacology at all. It’s pretty apparent he didn’t understand this particular class of drugs at all, yet I, an RN with a crummy AS degree, get it.

So what’s the crime? Here’s where I can take some less-educated guesses, because I am not an attorney. However, I know what would happen to me if I’d been the one to give those medications, even if they’d been prescribed by a physician.

I would be fired, I would expect disciplinary action from the Board of Registered Nursing, I’d lose my license, I'd expect be charged with manslaughter (either type depending on the whims or the mercy of the prosecuting DA) and I’d certainly expect to be sued by the patient's survivors.

What should Dr. Murray expect? The same thing. Here’s the problem: where is the DA going to find a respected MD who will come forward and point the finger at Dr. Murray? Will Jackson’s celebrity actually help this time?

As for the other doctors being investigated, I certainly would expect some sort of disciplinary action be taken against them, but nothing huge. Perhaps their ability to write prescriptions for controlled substances may be taken away for a period of time. But if the dermatologist, Dr. Arnold Klein, did have intubation equipment and did have the knowledge to intubate in case of Diprivan overdose, there is no malpractice. Overprescribing perhaps, but he was at least aware of what can go wrong.

What is the Mickey Fine Pharmacy guilty of? That’s a bit tougher. Was there knowledge that pseudonyms were being used? It’s really not up to a pharmacist to question the validity of a prescription written by an MD unless there is a question of dosage. However, this pharmacy had a nice long history with Jackson, and in 2007 sued for a past-due pharmacy bill of $100,926! The pharmacy had an oral agreement to bill Jackson monthly for his prescriptions, and had not been paid in two years.

Obviously the pharmacy knew of Jackson’s aliases and should have questioned the amount and type of drugs being sent to Jackson.

(Note that the Mickey Fine Pharmacy is also where Anna Nicole Smith received her pharmacopeia of drugs that eventually killed her.)

And what of AEG’s “comprehensive” physical exam that found Jackson “healthy?” Anyone care to bet there was extensive drug testing as part of that physical and that AEG knew the extent of Jackson’s addictions?

Why did AEG find it necessary to hire a “personal physician,” and a cardiologist to boot? If Jackson’s love of Diprivan was as long-standing as it was said to be, and also a not-to-well-kept secret, Jackson should have had an anesthesiologist (which of course means that AEG would have found Jackson’s behavior acceptable) prepared to offer respiratory support. Why a cardiologist, and a marginal one at that? I know Jackson himself recommended Dr. Murray. Why was he accepted?

We have not heard the last of this one, my friends. The coroner’s toxicology report is going to be very interesting.

Coroner's preliminary finding: Jackson overdosed on propofol

'Lethal levels' of anesthetic propofol killed Michael Jackson

Houston search warrant