Propofol: A dangerous kind of rest


The death of Michael Jackson 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 sniffed out one particular drug that appears in the pop star's toxicology report: the general anesthetic propofol.

Avery Tung, associate professor of anesthesia and critical care for the Medical Center, conducted an NIH-funded 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. After Tung sat down with ABC News following Jackson's death,  we spent a little more time with him discussing the anesthetic and his research.

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. It pretty much has replaced pentothal because it has fewer side effects and it makes people feel better when they wake up.

What side effects does propofol have?

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

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

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. In the ICU, it is restricted only for use in intubated, mechanically ventilated patients.

Why restrict it to use under an anesthesiologist's guidance?

Propofol can be deceptively easy to use. Because people recover so quickly, there's a temptation to use it in places which aren't safe. But it's stronger than other drugs, and can clearly destabilize blood pressure and breathing, Users can easily slip over the line from sedation to general anesthesia, develop blood pressure or breathing difficulties, and need specialized resuscitation measures.

Why is it used in non-surgical cases in the intensive care unit?

For a number of reasons. Mechanically ventilated patients can be uncomfortable, or experience pain and anxiety. They might also be a danger to themselves and others due to agitation, or need help to tolerate the ventilator. Not everybody in the ICU needs sedation, and some need to be sedated fairly deeply so that they are only partially responsive to stimulation.

You chose to study the effects of propofol on sleep deprivation. Is sleep deprivation an issue in the ICU?

Sleep deprivation is a huge issue in the ICU, and has been documented since the 1980's. Because of potential pain and anxiety, because the lights are always on, because there is noise always present and nurses are checking on patients on an hourly basis, there is really no quiet time. The circadian rhythms and light cycles that people are normally exposed to aren't as present in an ICU setting either. No one knows whether sleep deprivation adversely affects outcomes in the ICU because there's no way to set up a control for sleep, but many of the effects of sleep deprivation can clearly make care in the ICU more difficult.

Tell me about the first propofol and sleep study you published

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.

You tested this conclusion again using a different experiment. How did that one work?

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.

(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 splashing down in the water)

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.

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

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. (For instance, Tung explains, cyclical patterns of REM and nonREM sleep are not observed during propofol sedation, in rats or humans) Sleep, in general, preserves blood pressure and the ability to breathe and propofol does not. They are very different states.

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

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 (using 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 currently accepted care.