JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
of propofol for intravenous use were not released in the U.S. By 1986, AstraZeneca had reformulated propofol by solubilizing the drug in soybean oil and egg whites. This process led to propofol’s unique white color, its slang name as the “milk of amnesia,” and its contraindicated use in patients with egg allergies. By 1989, propofol was (FDA)-approved for use in the U.S., but it was not scheduled as a potentially abused drug. In 2009, pop singer Michael Jackson died from a mixture of intravenous propofol (25 mg) and two benzodiazepines, oral diazepam, and intravenous lorazepam, administered by his personal physician, Conrad Murray, M.D.; who was later convicted of manslaughter. 23 In 2010, AstraZeneca (UK) and Teva Pharmaceuticals (Israel) discontinued their manufacture of propofol related to an increasing number of lawsuits and public protests over the use of propofol to carry out lethal injection for US death penalty cases. After 2010, propofol was manufactured by Sandoz Pharmaceuticals (Australia); but its production was halted in 2013, when the state of Missouri approved propofol for lethal injection. 24 By 2013, propofol had replaced the short-acting barbiturates, thiopental, and methohexital, as the preferred induction agent for general anesthesia in over 80% of U.S. cases because: (1) recovery was more rapid and “clear” when compared to sodium thiopental inductions; and because (2) sodium thiopental manufacture had been significantly curtailed or halted worldwide due to its use in lethal drug injections in the U.S., including in Louisiana. 24 In 2013, theWorldHealthOrganization (WHO) added propofol to its Model List of Essential Medications needed in any healthcare system. 25 On October 11, 2013, the first execution by the lethal injection of propofol was halted by Missouri Governor Jay Nixon following threats from the European Union to discontinue propofol exports to the U.S. 24 Today, propofol is manufactured only by the German company, Fresenius-Kabi, and its price is skyrocketing. Diagnostic and surgical procedures are often delayed or cancelled related to shortages of propofol in U.S. hospitals. In conclusion, propofol is a necessary and essential anesthetic drug with a wide range of applications in general anesthesia for surgery, monitored anesthesia care for diagnostic procedures, and sedation during mechanical ventilation in the ICU. However, the abuse of propofol by young healthcare professionals, particularly OR workers, was significant in this study; and was most likely underreported. When administered improperly, even by highly trained personnel, propofol is a dangerous drug with an abuse potential that rivals opioids and often results in fatalities. Given the results of the present investigation and others worldwide, propofol should be regulated as a controlled substance. REFERENCES 1. Wilson C, Canning P, Caravati M. The abuse potential of propofol. Clin Toxicol 2010; 48: 165-70. 2. Iwersen-Bergmann S, Rösner P, Kühnau HC, Junge M, Schmoldt A. Death after excessive propofol abuse. Int J Legal Med 2001; 114: 248–51. 3. Strehier M, Preuss J, Wollersen H, Madea B. Lethal mixed intoxication with propofol in a medical layman. Arch Kriminol 2006; 217: 153-60.
Dr. Diaz is a professor of public health and preventive medicine, and program head of the environmental and occupational health sciences, School of Public Health, professor of anesthesiology, School of Medicine, at Louisiana State University Health Sciences Center in New Orleans and Dr. Kaye is a professor of anesthesiology andpharmacology, andChair of the department of anesthesiology at Louisiana State University Health Sciences Center in New Orleans. 22. Diaz JH, Prabhakar A, Urman RD, Kaye AD. Propofol infusion syndrome: a retrospective analysis at a level 1 trauma center. Crit Care Res Pract 2014; 2014:346968. Doi: 10.1155/2014/346968. Epub 2014 Dec 17. 23. Surdin, Ashley (25 August 2009). “Coroner Attributes Michael Jackson’s Death to Propofol”. The Washington Post. Retrieved 22 May 2010. 24. “After EU threats, Missouri halts execution by Propofol injection”. Al Jazeera America October 12th 2013. 25. “WHO Model List of Essential Medicines” (PDF). World Health Organization. October 2013. p. 6. Retrieved 22 April 2014. 17. Stelow EB, Johari VP, Smith SA, et al. Propofol associated rhabdomyolysis with cardiac involvement in adults: chemical and anatomic findings. Clin Chem 2000; 46:577-581. 18. Perrier ND, Baerga-Varela Y, Murray MJ. Death related to propofol use in an adult patient. Crit Care Med 2000; 28:3071-3074. 19. Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth 1998; 8:491-499. 20. MarinellaMA: Lactic acidosis associatedwith propofol. Chest 1996, 109:292. 21. Hanna JP, Ramundo ML: Rhabdomyolysis and hypoxia associated with prolonged propofol infusion in children. Neurology 1998, 50:301-303. 15. Parke TJ, Stevens JE, Rice ASC, et al. Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports. Brit Med J 1992; 305(6854):613–16. 16. Okamoto MP, Kawaguchi DL, Alephs NA. Evaluation of propofol infusion syndrome in pediatric intensive care. Am J Health-System Pharmacists 2003; 60:2007-14. 4. Kranioti EF, Mavroforou A, Mylonakis P, Michalodimitrakis M. Lethal self- administration of propofol ( Diprivan ): a case report and review of the literature. Forensic Sci Int 2007; 167: 56-8. 5. Klausz G, Rona K, Kristof I, Toro K. Evaluation of a fatal propofol intoxication due to self administration. J Forensic Legal Med 2009; 16: 287-9. 6. Roussin A, Montastruc JL, Lapeyre-Mestre M (21 October 2007). Pharmacological and clinical evidences on the potential for abuse and dependence of propofol: a review of the literature. Fundamental Clin Pharmacol 2007; 21: 459–66. 7. Crimele V, Kintz P, Doray S, Ludes B. Determination of chronic abuse of the anaesthetic agents midazolam and propofol as demonstrated by hair analysis. Int J Legal Med 2002; 116: 54-7. 8. Drummer OH. A fatality due to propofol poisoning. J Forensic Sci 1992; 37: 1186-9. 9. Chao TC, Lo DS, Chui PP, Koh TH. The first fatal 2, 6-di-isopropylphenol (propofol) poisoning in Singapore: a case report. Forensic Sci Int 1994; 66: 1-7. 10. Kirby RR, Colaw JM, Douglas MM. Death from propofol: accident, suicide, or murder? Anesth Analg 2009; 108: 1182-4. 11. Hirsch D, Fox C, Kaye AD. Anesthetic Induction Agents. In Essentials of Pharmacology with Black Box Warnings. AD Kaye, AM Kaye, and R Urman, Eds., Springer, 2014, pp 103-112. 12. Chui J, Mariappan R, Mehta J, Manninen P, Venkatraghavan L. Comparison of propofol and volatile agents for maintenance of anesthesia during elective craniotomy procedures: a systematic review and meta-analysis. Can J Anaesth 2014; 61(4):347-56. 13. Charatan F. Concerns mount over recreational use of propofol among US healthcare professionals. Brit Med J 2009; 339: b3673. 14. Wischmeyer PE, Johnson BR, Wilson JE, et al. A survey of propofol abuse in academic anesthesia programs. Anesth Analg 2007; 105: 1066-71.
Acknowledgements
Incompletely analyzed elements of this article were presented in poster format only at the 2015 Annual Meeting of the Society of Forensic Toxicologists in Atlanta, GA.
32 J La State Med Soc VOL 169 MARCH/APRIL 2017
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