September 17, 2011


The death of Michael Jackson has made its expected transition from a celebration of his life and music to an uncomfortable public autopsy of
how he died. More than a month after his death, the official coroner’s autopsy had yet to be officially released but various media outlets have sniffed out
one particular drug to appear in the pop star’s toxicology report: propofol.

The widely-used but little-discussed drug provoked a number of “what is Propofol?” news segments.

Avery Tung, associate professor of anesthesia and critical care for the Medical Center. He conducted a research project examining relationships between sleep and anesthesia, and published several papers and scientific abstracts looking at how propofol mimicked the effects of actual sleep.

Q: First of all, what is propofol and how often is it used?

Tung: Propofol is given intravenously to induce anesthesia in surgical patients and to provide sedation for patients in the Intensive Care Unit. It’s the most common induction agent of anesthesia in current use.

Q: What side effects does propofol have?

Tung: It can cause a decrease in blood pressure, it can depress or even stop breathing and it can cause pain on injection.

Q: And because of those side effects, its use is restricted?

Tung: The package insert with the drug states that it should only be used by persons trained in the administration of general anesthesia, which in this hospital means an anesthesiologist.

Propofol Package Insert

Q: Tell me about the first propofol and sleep study you published
(Anesthesia and Analgesia. 2001 May;92(5):1232-6)

Tung: The first thing we did was to sedate rats with propofol for the entire period they would normally be asleep…and see how they would behave afterward relative to how they behaved beforehand, compared to rats that were allowed to sleep naturally. What we found is that rats were no more sleep deprived, as measured by EEG criteria, after a period of propofol sedation, than rats that underwent naturally-occurring sleep.

We concluded that the need to sleep was not accumulating inside rats that received propofol and therefore either propofol was preventing their “sleep debt” from building up or propofol was, like sleep, helping rats to discharge it.

Q: You tested this conclusion again using a different experiment (Anesthesiology. 2004 Jun;100(6):1419-26); how did that one work?

(Rats in this study were deprived of sleep for 24 hours by being placed on a platform above a pan of water. Whenever rats begin to sleep, the platform rotates, forcing them to wake up and walk to avoid falling in the water)

Tung: In the second experiment, we sleep deprived a rat and looked at the recovery from sleep deprivation. Normally when a rat is sleep deprived, it shows a rebound increase, a transient increase in sleep for a while as they sort of discharge their sleep need or sleep debt.

So we then allowed rats to sleep naturally or gave them a period of sedation with propofol and looked to see how they recover. What we found is that recovery in rats given propofol occurred as quickly as recovery in rats allowed to sleep normally. We concluded that, at least in rats, subjects can discharge their sleep debt under propofol sedation to the same degree as they are able to do it using naturally occurring sleep.

Q: But does that mean that propofol sedation is the same as sleep?

Tung: Propofol sedation is nothing at all like sleep. Sleep is reversible with external stimulation - if you shake somebody, they wake up. Propofol is obviously not like that. Sleep shows a characteristic pattern of EEG behavior, while propofol does not. Sleep, in general, preserves blood pressure and the ability to breathe and propofol
does not. They are very different states.

Q: All of your propofol research has been in rats, has there been any research done in humans along these lines?

Tung: No, there has not. It does appear that humans given propofol for prolonged periods do not appear to be sleep deprived when you turn off the drug. No data exist to support the specific use that has been alleged
in the Michael Jackson case (propofol as a treatment for insomnia). Use to facilitate regular sleep is NOT at all safe. The benefit is way outstripped by the risk…if there is any benefit.

Nobody is advocating its use outside a hospital for patients that are not critically ill. That is outside the boundaries of accepted care.

Related Links:
Propofol: A Dangerous Kind Of Sleep
FDA Letter lists reasons for REFUSING to remove warning on Propofol package insert, that it should only be administered by anesthesiologists


Post a Comment