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What Is Propofol--and How Could It Have Killed Michael Jackson?

The King of Pop's doctor, Conrad Murray, is on trial for involuntary manslaughter, but could propofol alone have caused MJ's death? Harvard anesthesiologist Beverly Philip explains what gives this drug such lethal potential
Michael Jackson at Cannes



Wikimedia Commons/Georges Biard

In the first week of the trial of Conrad Murray, Michael Jackson's physician, Los Angeles jurors heard audio recordings of the late pop star's slurred speech, in addition to the litany of prescription drugs he had taken in the hours and weeks prior to his June 25, 2009, death.

It will be up to them to decide if they agree with the Los Angeles County coroner's office, which labeled Jackson's death a homicide.

According to the 2009 autopsy report (pdf), "the cause of death is acute propofol intoxication," which caused the singer to stop breathing. In addition to propofol (a hypnotic drug used for general anesthesia, sedation and in veterinary medicine) the examiner also found traces of lorazepam (a benzodiazepine drug used to treat anxiety and insomnia); midazolam (another benzodiazepine, indicated for insomnia and medical sedation); lidocaine (a local anesthetic often included with propofol to relieve injection pain); diazepam (a benzodiazepine to treat anxiety, insomnia and alcohol withdrawal); and nordiazepam (a benzodiazepine-derived sedative, often used to treat anxiety) in Jackson's bloodstream.

To support the weighty pronouncement of homicide, the medical examiner concluded that: "circumstances indicate that propofol and the benzodiazepines were administered by another. The propofol was administered in a nonhospital setting without any appropriate medical indication. The standard of care for administering porpofol was not met."

Prosecutors are following this line of evidence, arguing that Murray should be held responsible for Jackson's death because he lacked adequate justification, expertise and equipment for giving this powerful drug to his client (who was reportedly aiming to stay rested in preparation for a comeback tour). Although Murray was using a device to keep tabs on Jackson's vitals, as is recommended while using a general anesthetic, the fingertip pulse and blood-oxygen monitor he used is "specifically labeled against continuous monitoring," said an executive from Nonin Medical, Inc., which makes the $275 device, CNN reported Friday. And according to testimony from a paramedic that responded to the 911 call and found Jackson without a pulse, Murray did not mention giving Jackson anything other than the lorazepam.

Given Jackson's apparently substantial admixture of meds and oft-discussed medical conditions, why was propofol the most likely candidate for his death—and can it be used more safely? To find out, Scientific American spoke with Beverly Philip, a professor of anesthesia at Harvard Medical School.

[An edited transcript of the interview follows.]


Propofol is not your run-of-the-mill sleeping aid. How does it differ from more commonly used sedatives?
It's not a sleeping aid at all. What it is is a general anesthetic. This puts people into general anesthesia—a sleeping aid doesn't do that.

This is not meant to be used at home. This is meant to be used by anesthesiologists in a clinical setting. So the use as a sleep aid is way off the mark.

How does propofol work in the body?
We don't know exactly how general anesthesia works. This works as other general anesthetics work, acting on receptors in the brain—possibly the GABA [gamma-aminobutyric acid] receptors, because that is a mechanism for a lot of sleepiness in the brain.

Are there negative side effects that propofol can have—even when it is used as directed and in a proper setting?
Yes. Unlike other sedatives, this drug has an extraordinarily narrow safety margin. It changes the body's state very rapidly so that the patient will go unconscious and stop breathing. It can affect the breathing even before unconsciousness. So even in trained hands, it is very difficult to titrate just where you want. We can do it, but that's what we're trained and educated to do—it's not easy. If I'm inducing anesthesia, it will act inside of 60 seconds.

So as a cardiologist and personal physician to Michael Jackson, is it likely that Conrad Murray did not have the proper training to administer this type of drug safely?
I have heard nothing about how he had had training to use the drug. How it was used here, we call it recreational use. This had nothing to do with the medical care of a patient, which is a situation in which you have things to make it safe, so it's not even in the ballpark of normal use.

The drug also has some reportedly pleasant side effects, such as euphoria. Is that common among sedatives?
When it first came out it was very obvious that it causes euphoria. It's not that dissimilar to alcohol. It reduces inhibition, people get giddy, and whatever thoughts they have on their mind, they tell you. It can also cause hallucinations, because whatever is in a person's head is more likely to be seen. We see it as they go off to sleep and as they wake up.

Recreationally, a lot of people die from this. It's very difficult to administer safely even in the most controlled settings.

The FDA [U.S. Food and Drug Administration] is in the process of making this a restricted drug, recognizing its euphoric property.

Are there other anesthetics that are used off-label as sleep aids?
There are other things that are quite in a different class. For example, Valium and its cousins: In very, very high doses, someone could sleep, but you have to give lots of it, and it works very slowly to cause sleep.

Drugs in the Valium class and painkillers have a reversing agent that's commercially available. There's no reversing agent for propofol.

The coroner's reports from Michael Jackson's autopsy also found evidence that he was on other drugs at the time he died, including lidocaine, lorazepam and diazepam. Is it possible Jackson's death was due to a reaction from these drugs or do you think propofol alone could have killed him?
There's quite a sufficient answer just with this drug alone. But as with any other intoxicant, when you've taken any other drug, they all add up—and propofol is no different.

The fact that there's no reversing agent, and the ability to pull someone out of it—which we call rescuing—requires considerable professional training.

This is not a sleeping aid. This is a general anesthetic drug. Everyone has been saying, "Michael Jackson wanted to be asleep." No one talked about relaxing drugs. With this drug in unskilled hands, this sleep was permanent. It induces general anesthesia, which is not like a night's sleep.

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