Propofol molecule model

Here are the reasons why:

(1) Propofol is easily available. It has become one of the most widely used anesthetic agents today. Because it is not a federally controlled drug, every clinic, hospital and pharmacy has ample supply of the drug, without checks and controls.

(2) Propofol is easily accessible. Again because of its status as an uncontrolled drug, there are no special precautions taken on the dispension, prescription and storage of the drug. Any medical professional can have access to it. A survey of academic anaesthesiology programs revealed that "there was no established system to control or monitor propofol as is done with opioids at 71% of programs. There was an association between lack of control of propofol (e.g., pharmacy accounting) at the time of abuse and incidence of abuse at the program."

Propofol

(4) Propofol has become a popular recreation drug among medical professionals. Subanesthetic levels of propofol have been described to induce a “high” that is characterized by euphoria and sensitization.  Studies have revealed that drug abuse is rampant among those people who are supposed to administer them, e.g. the medical professionals themselves. Among these, anaesthesiologists account for the majority. A study revealed that anesthesiologists are constantly exposed to sedatives and anesthetics while performing their jobs during surgery. This exposure can easily lead to substance dependence and abuse. According to Dr. Robert Hines of Department of Anesthesiology, Yale University School of Medicine, several factors contribute to the high incidence of abuse among anesthesiologists, namely:

• Easy access
• Constant contact with drugs at the workplace
• Easy diversion

(5) Sleep disorders are very common especially among those who live a fast-paced, stressful lifestyle lifestyle, e.g. celebrities and medical personnel. It is common knowledge that many Hollywood stars are hooked on prescription drugs and most of these drugs are sedatives and anti-depressants. Propofol seems to be one of the preferred drugs even though it is not indicated for insomnia as such. Michael Jackson was supposedly dependent on propofol for sedation.

Video: How Propofol Killed Michael Jackson (CNN)

So what is propofol?

(1) Propofol is a short-acting sedative-hypnotic agent. Its brand name is Diprivan, marketed by Astra Zeneca; however, generic versions are also available. It is primarily used in initiating or maintaining regional and general anesthesia during surgical procedures but is also used to induce sedation in patients on ventilators typically in intensive care units.

(2) Propofol has become a popular anesthetic because its relatively 'short action' allows for a quick recovery, and is considered safe with minimal side effects. The most common side effects described are mood swings, dizziness, drowsiness; and lack of coordination.

(3) Propofol is a prescription drug and is not available over-the-counter. According to its package insert however, as approved by the US FDA, propofol is only supposed to be administered by healthcare professionals trained in the administration of general anesthesia, such as anesthesiologists and certified registered nurse anesthetists (CRNA).

(4) Propofol is not a controlled or 'schedule' drug, unlike many sedatives.  Under the US Controlled Substances Act, certain drugs are controlled and classified into five different "schedules" depending on their medical use, safety and potential for abuse and addiction. Drugs which are highly addictive are classified as Schedule I (example: heroin) and then the schedule number increases with decreasing potency and dependence liability. Codeine found in cough syrups is a schedule V substance. Controlled drugs, as the name suggests, are strictly regulated. In the US, they are regulated at the federal level by the Drug Enforcement Administraion (DEA) and the US Food and Drug Administration (US FDA). Regulations are in place regarding their supply, distribution, storage and inventory in hospitals and pharmacies. Also regulated are the health professionals who are allowed to prescribe and administer these drugs.

A prefilled ampoule of Propofol

Compared to other medications such as opioids and fentanyl/sufentanyl, the potential for propofol addiction seems to be pretty low. However the clinical use of propofol has significantly increased that incidence of dependence several fold and studies have shown that subanesthetic doses of the drug may have an abuse potential.  In fact, recent surveys indicate that propofol abuse is on the rise. Researchers at the University of Colorado surveyed 126 academic anesthesiology training programs in the US and found the following:

• 18% of those surveyed admitted to have at least one case of propofol abuse or stealing during the past 10 years.
• Incidence of abuse was reported as 10 per 10,000 anesthesia providers per decade.
• Incidence of death among propofol users was 28%, many of whom were residents.

Furthermore even before its recent bad publicity, there have been hints that propofol is not as safe and harmless as it seems.

As early as 2004, the American Association of Nurse Anesthetics (AANA) issued a position statement regarding the access to and administration of propofol. Whenever propofol is used for sedation/anesthesia, it should be administered only by persons trained in the administration of general anesthesia, who are not simultaneously involved in these surgical or diagnostic procedures. This restriction is concordant with specific language in the propofol package insert, and failure to follow these recommendations could put patients at increased risk of significant injury or death. It has also issued a joint statement, together with the American Society of Anesthesiologists (ASA) on the same note. AANA also expressed concerns that even medical professionals not trained in anaesthesiology get to administer the drug. “...regulatory agencies, insurance companies, and various non-anesthesia professionals have downplayed the dangers of propofol, virtually treating its use as ‘so easy, anyone can do it!`”

In a less publicized 2005 case, a 24-year old woman was killed by an overdose of propofol, administered by somebody trained in giving IV injections. A male nurse acquaintance of the victim was convicted of first degree murder and sentenced to life in prison without the possibility of parole in May 2008.

According to this MSNBC report, the US FDA has received “an increasing number of reports about fatalities linked to propofol in recent years: 43 in 2008 and 35 in 2007, up from an average of 22 per year over the decade before that, according to FDA data. “Self-administration of propofol is very common among medical practitioners. Because it is a short-acting drug, several doses may be needed each day and can easily lead to overdose which can be life-threatening. There have been several reports of fatal propofol overdose. It is suspected that Michael Jackson had an overdose of propofol that led to his cardiac arrest.

So what comes next?

Michael Jackson

The AANA and the ASA have been very vocal about the abuse and dangers of propofol. Other scientists feel the same way: There have been criticisms of the system of drug regulation. According to Prof. David Nutt and colleagues, “harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages.” They proposed a modified system of classification. Two years ago, the Drug Enforcement Administration (DEA) was petitioned to regulate propofol.

It took a high profile case such as the death of Michael Jackson to bring worldwide attention to the misuse and dangers of Propofol. The DEA is reportedly considering adding it to the list of controlled drugs. If this happens, the access and availability of Propofol will be strongly restricted, a move than can save lives.

References

1. AANA. Position Statement Number 2.14. Securing Propofol. June 2009.
2. AANA. Turning a Harsh Spotlight on Propofol Misuse. American Association of Nurse Anesthetics. July 9 2009.
3. AANA-ASA Joint Statement Regarding Propofol Administration, April 14, 2004
4. Belluck P et al.. With High-Profile Death, Focus on High-Risk Drug. The New York Times August 6, 2009.
5. Fullerton-Batten J. The Junkie in the O.R. Men's Health. Men's Health 2008.
6. Hines R. Substance Abuse in Anesthesia Providers: An Update. Refresher Course. Yale University School of Medicine.
7. Kirby RR et al. Death from Propofol: Accident, Suicide, or Murder? Anesth Analg 2009; 108:1182-1184.
8. McAuliffe PF. Second-hand exposure to aerosolized intravenous anesthetics propofol and fentanyl may cause sensitization and subsequent opiate addiction among anesthesiologists and surgeons Med Hypotheses. 2006;66(5):874-82.
9. McKenzie J. More Medical Professionals Abusing Propofol. ABC News Aug 21, 2009.
10. MSNBC. DEA may limit drug eyed in Jackson case. July 15, 2009.
11. National Health Services. What is a controlled drug (medicine)?
12. Nutt D et al. Development of a rational scale to assess the harm of drugs of potential misuse.The Lancet, Volume 369, Issue 9566, Pages 1047 - 1053, 24 March 2007.
13. Roussin A et al. Pharmacological and clinical evidences on the potential for abuse and dependence of propofol: a review of the literature. Fundam Clin Pharmacol. 2007 Oct;21(5):459-66.
14. US DEA. Drug abuse prevention and control.
15. US DEA. Drug Scheduling.
16. US DEA. The Controlled Substances Act.
17. US FDA. Controlled Substances. Statement by Robert J. Meyer.
18. US FDA. Scheduling of Drugs Under the Controlled Substances Act, testimony of Nicholas Reuter March 11, 1999.
19. Wischmeyer PE et al. A Survey of Propofol Abuse in Academic Anesthesia Programs. Anesth Analg 2007; 105:1066-1071