Skip to main content

Advertisement

SpringerLink
Log in

Propofol and propofol glucuronide concentrations in hair following medical propofol administration and in forensic death cases

  • Original Article
  • Published:
Forensic Toxicology Aims and scope Submit manuscript

Abstract

Purpose

Propofol is the most preferred drug for general anesthesia as well as for analgosedation. However, the rate of abuse cases has increased in the past decade. Hair analysis is considered as the method of choice to determine chronic drug use, and propofol and propofol glucuronide have already been used to confirm previous propofol administration. However, given its frequent medical use, it is important that nonmedical propofol abuse can be distinguished from medical propofol application.

Methods

Nineteen hair samples collected from living subjects who received different doses of propofol in the setting of medical treatment and 31 hair samples from forensic death cases with indications of previous propofol administration were examined using our previously described method enabling the simultaneous extraction of propofol and propofol glucuronide from hair followed by validated liquid chromatography–tandem mass spectrometry analyses.

Results

Recent propofol administration was verified for eight of 19 living cases and 29 of 31 deceased cases. Of the living cases, propofol glucuronide could be detected in all eight cases, whereas propofol could only be detected in three of these cases. Propofol glucuronide could be detected more frequently and in higher concentrations than propofol following medical propofol administration and observed concentrations varied more widely.

Conclusions

Although further research is still required to clarify the mechanisms involved in propofol incorporation into hair and to establish reliable cutoff concentrations for the differentiation of medical from nonmedical propofol use, it seems likely that relatively high concentrations of propofol found across multiple hair segments strongly suggest a nonmedical propofol abuse.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kotani Y, Shimazawa M, Yoshimura S, Iwama T, Hara H (2008) The experimental and clinical pharmacology of propofol, an anesthetic agent with neuroprotective properties. CNS Neurosci Ther 14:95–106. https://doi.org/10.1111/j.1527-3458.2008.00043.x

    Article  PubMed  CAS  Google Scholar 

  2. Heuss LT, Schnieper P, Drewe J, Pflimlin E, Beglinger C (2003) Safety of propofol for conscious sedation during endoscopic procedures in high-risk patients-a prospective, controlled study. Am J Gastroenterol 98:1751–1757. https://doi.org/10.1111/j.1572-0241.2003.07596.x

    Article  PubMed  CAS  Google Scholar 

  3. Lamond DW (2010) Review article: safety profile of propofol for paediatric procedural sedation in the emergency department. Emerg Med Australas 22:265–286. https://doi.org/10.1111/j.1742-6723.2010.01298.x

    Article  PubMed  Google Scholar 

  4. Luginbühl M, Vuilleumier P, Schumacher P, Stüber F (2009) Anesthesia or sedation for gastroenterologic endoscopies. Curr Opin Anaesthesiol 22:524–531. https://doi.org/10.1097/ACO.0b013e32832dbb7c

    Article  PubMed  Google Scholar 

  5. Riphaus A, Bitter H (2012) Short version S3 guideline sedation for gastrointestinal endoscopy und medicolegal implications (in German with English abstract). Z Gastroenterol 50:407–410. https://doi.org/10.1055/s-0031-1299290

    Article  PubMed  CAS  Google Scholar 

  6. Maier C, Iwunna J, Tsokos M, Mußhoff F (2017) Deaths from propofol abuse. Survey of institutes of forensic medicine in Germany, Austria and Switzerland (in German with English abstract). Anaesthesist 66:109–114. https://doi.org/10.1007/s00101-016-0260-6

    Article  PubMed  CAS  Google Scholar 

  7. Classen M, Tytgat G, Lightdale C (2004) Gastroenterologische Endoskopie: das Referenzwerk zur endoskopischen Diagnostik und Therapie. Thieme, New York

    Book  Google Scholar 

  8. Simons PJ, Cockshott ID, Douglas EJ, Gordon EA, Hopkins K, Rowland M (1988) Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol. Xenobiotica 18:429–440. https://doi.org/10.3109/00498258809041679

    Article  PubMed  CAS  Google Scholar 

  9. Sneyd JR, Simons PJ, Wright B (1994) Use of proton nmr spectroscopy to measure propofol metabolites in the urine of the female Caucasian patient. Xenobiotica 24:1021–1028. https://doi.org/10.3109/00498259409043299

    Article  PubMed  CAS  Google Scholar 

  10. Follette JW, Farley WJ (1992) Anesthesiologist addicted to propofol. Anesthesiology 77:817–818 (PMID: 1416179)

    Article  PubMed  CAS  Google Scholar 

  11. Kranioti EF, Mavroforou A, Mylonakis P, Michalodimitrakis M (2007) Lethal self administration of propofol (Diprivan). A case report and review of the literature. Forensic Sci Int 167:56–58. https://doi.org/10.1016/j.forsciint.2005.12.027

    Article  PubMed  Google Scholar 

  12. Roussin A, Montastruc JL, Lapeyre-Mestre M (2007) Pharmacological and clinical evidences on the potential for abuse and dependence of propofol: a review of the literature. Fundam Clin Pharmacol 21:459–465. https://doi.org/10.1111/j.1472-8206.2007.00497.x

    Article  PubMed  CAS  Google Scholar 

  13. Wischmeyer PE, Johnson BR, Wilson JE, Dingmann C, Bachman HM, Roller E, Tran ZV, Henthorn TK (2007) A survey of propofol abuse in academic anesthesia programs. Anesth Analg 105:1066–1071. https://doi.org/10.1213/01.ane.0000270215.86253.30

    Article  PubMed  CAS  Google Scholar 

  14. Levy RJ (2011) Clinical effects and lethal and forensic aspects of propofol. J Forensic Sci 56:S142–S147. https://doi.org/10.1111/j.1556-4029.2010.01583.x

    Article  PubMed  CAS  Google Scholar 

  15. Fry RA, Fry LE, Castanelli DJ (2015) A retrospective survey of substance abuse in anaesthetists in Australia and New Zealand from 2004 to 2013. Anaesth Intensive Care 43:111–117 (PMID: 25579298)

    PubMed  CAS  Google Scholar 

  16. Menk EJ, Baumgarten RK, Kingsley CP, Culling RD, Middaugh R (1990) Success of reentry into anesthesiology training programs by residents with a history of substance abuse. J Am Med Assoc 263:3060–3062. https://doi.org/10.1001/jama.1990.03440220084035

    Article  CAS  Google Scholar 

  17. Weetman DB, Mascardo LA, Ross MB, Abramowitz PW (2004) Propofol as a drug of diversion. Am J Health Syst Pharm 61:1185–1186 (PMID: 15237574)

    PubMed  Google Scholar 

  18. Brechmann T, Maier C, Kaisler M, Vollert J, Schmiegel W, Pak S, Scherbaum N, Rist F, Riphaus A (2017) Propofol sedation during gastrointestinal endoscopy arouses euphoria in a large subset of patients. United Eur Gastroenterol J 1–11.  https://doi.org/10.1177/2050640617736231

  19. Roh S, Park JM, Kim DJ (2011) A case of propofol dependence after repeated use for endoscopy. Endoscopy 43:E362. https://doi.org/10.1055/s-0030-1256602

    Article  PubMed  Google Scholar 

  20. Koopmann A, von der Goltz C (2011) Propofol addiction initiated by anesthetic use. Am J Psychiatry 168:211–212. https://doi.org/10.1176/appi.ajp.2010.10091293

    Article  PubMed  Google Scholar 

  21. Iwersen-Bergmann S, Rösner P, Kühnau HC, Junge M, Schmoldt A (2001) Death after excessive propofol abuse. Int J Legal Med 114:248–251. https://doi.org/10.1007/s004149900129

    Article  PubMed  CAS  Google Scholar 

  22. Earley PH, Finver T (2013) Addiction to propofol: a study of 22 treatment cases. J Addict Med 7:169–176. https://doi.org/10.1097/ADM.0b013e3182872901

    Article  PubMed  CAS  Google Scholar 

  23. Bonnet U, Scherbaum N (2012) Craving dominates propofol addiction of an affected physician. J Psychoactive Drugs 44:186–190. https://doi.org/10.1080/02791072.2012.684635

    Article  PubMed  Google Scholar 

  24. Maier C, Leclerc-Springer J (2012) Life-threatening fentanyl and propofol addiction. Interview with a survivor (in German with English abstract). Anaesthesist 61:601–607. https://doi.org/10.1007/s00101-012-2036-y

    Article  PubMed  CAS  Google Scholar 

  25. Cirimele V, Kintz P, Doray S, Ludes B (2002) Determination of chronic abuse of the anaesthetic agents midazolam and propofol as demonstrated by hair analysis. Int J Legal Med 116:54–57. https://doi.org/10.1007/s004140100240

    Article  PubMed  Google Scholar 

  26. Pragst F, Rothe M, Spiegel K, Sporkert F (1998) Illegal and therapeutic drug concentrations in hair segments - a timetable of drug exposure? Forensic Sci Rev 10:81–111 (PMID: 26255716)

    PubMed  CAS  Google Scholar 

  27. Hayashi S, Miyamoto I, Takeda K (1991) Measurement of human hair growth by optical microscopy and image analysis. Br J Dermatol 125:123–129. https://doi.org/10.1111/j.1365-2133.1991.tb06058.x

    Article  PubMed  CAS  Google Scholar 

  28. Pecoraro V, Astore IPL (1990) Measurements of hair growth under physiological conditions. In: Orfanos CE, Happle R (eds) Hair and hair diseases. Springer, Berlin, pp 237–254

    Chapter  Google Scholar 

  29. Pragst F, Balikova MA (2006) State of the art in hair analysis for detection of drug and alcohol abuse. Clin Chim Acta 370:17–49. https://doi.org/10.1016/j.cca.2006.02.019

    Article  PubMed  CAS  Google Scholar 

  30. Maas A, Maier C, Iwersen-Bergmann S, Madea B, Hess C (2017) Simultaneous extraction of propofol and propofol glucuronide from hair followed by validated LC–MS/MS analyses. J Pharm Biomed Anal 146:236–243. https://doi.org/10.1016/j.jpba.2017.08.035

    Article  PubMed  CAS  Google Scholar 

  31. Jurado C, Kintz P, Menéndez M, Repetto M (1997) Influence of the cosmetic treatment of hair on drug testing. Int J Legal Med 110:159–163. https://doi.org/10.1007/s004140050056

    Article  PubMed  CAS  Google Scholar 

  32. Cirimele V, Kintz P, Mangin P (1995) Drug concentrations in human hair after bleaching. J Anal Toxicol 19:331–332. https://doi.org/10.1093/jat/19.5.331

    Article  PubMed  CAS  Google Scholar 

  33. Kintz P, Salomone A, Vincenti M (2015) Hair analysis in clinical and forensic toxicology, 1st edn. Elsevier, Amsterdam

    Google Scholar 

  34. Kintz P (2013) Issues about axial diffusion during segmental hair analysis. Ther Drug Monit 35:408–410. https://doi.org/10.1097/FTD.0b013e318285d5fa

    Article  PubMed  CAS  Google Scholar 

  35. Vaiano F, Busardò FP, Pascali J, Fioravanti A, Mortali C, Mari F, Bertol E (2017) Hair testing of propofol by liquid chromatography tandem mass spectrometry and azo-coupling derivatization. Drug Test Anal 9:1080–1084. https://doi.org/10.1002/dta.2190

    Article  PubMed  CAS  Google Scholar 

  36. Khedr A, El-Hay SSA, Kammoun AK (2017) Liquid chromatography-tandem mass spectrometric determination of propofol in rat serum and hair at attogram level after derivatization with 3-bromomethyl-propyphenazone. J Pharm Biomed Anal 134:195–202. https://doi.org/10.1016/j.jpba.2016.11.051

    Article  PubMed  CAS  Google Scholar 

  37. Soyka M, Schotz C (1997) Propofol dependency. Addiction 92:1369–1370. https://doi.org/10.1080/09652149736882

    Article  PubMed  CAS  Google Scholar 

  38. Gündel H, Kuhs H (1992) Propofol abuse for nine days experiences (in German with English abstract). Anasthesiol Intensivmed Notfallmed Schmerzther 27:181–182. https://doi.org/10.1055/s-2007-10000275

    Article  PubMed  Google Scholar 

  39. Bonnet U, Harkener J, Scherbaum N (2008) A case report of propofol dependence in a physician. J Psychoactive Drugs 40:215–217. https://doi.org/10.1080/0279/072.2008.10400634

    Article  PubMed  Google Scholar 

  40. Köroğlu G, Tezcan A (2015) A case report of the first propofol addiction in Turkey. Turk J Anaesthesiol Reanim 43:434–436. https://doi.org/10.5152/TJAR.2015.54872

    Article  PubMed  PubMed Central  Google Scholar 

  41. Welliver M, Bertrand A, Garza J (2012) Two new case reports of propofol abuse and a pattern analysis of the literature. Int J Adv Nurs Stud 1:22–42. https://doi.org/10.14419/ijans.v1i1.27

    Article  Google Scholar 

  42. Fritz GA, Niemczyk WE (2002) Propofol dependency in a lay person. Anesthesiology 96:505–506

    Article  PubMed  Google Scholar 

  43. Albermann ME, Musshoff F, Madea B (2011) Comparison of ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) concentrations in hair for testing abstinence. Anal Bioanal Chem 400:175–181. https://doi.org/10.1007/s00216-010-4443-8

    Article  PubMed  CAS  Google Scholar 

  44. Bendroth P, Kronstrand R, Helander A, Greby J, Stephanson N, Krantz P (2008) Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse. Forensic Sci Int 176:76–81. https://doi.org/10.1016/j.forsciint.2007.09.012

    Article  PubMed  CAS  Google Scholar 

  45. Yegles M, Labarthe A, Auwärter V, Hartwig S, Vater H, Wennig R, Pragst F (2004) Comparison of ethyl glucuronide and fatty acid ethyl ester concentrations in hair of alcoholics, social drinkers and teetotallers. Forensic Sci Int 145:167–173. https://doi.org/10.1016/j.forsciint.2004.04.032

    Article  PubMed  CAS  Google Scholar 

  46. Vesper I, Schmiegel W, Brechmann T (2015) Equal detection rate of cervical heterotopic gastric mucosa in standard white light, high definition and narrow band imaging endoscopy (in German with English abstract). Z Gastroenterol 53:1247–1254. https://doi.org/10.1055/s-0041-104226

    Article  PubMed  CAS  Google Scholar 

  47. Larsen R (2013) Anästhesie, 10th edn. Elsevier, München

    Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Beate Michel-Lauter, Dr. Martin Kramer, Ms. Birgit Tersteegen and Ms. Ilona Raith (Department for Pain Medicine, BG University Hospital Bergmannsheil, Bochum, Germany) as well as Ms. Melissa Peka (Victorian Institute of Forensic Medicine, Southbank, Australia) for their valuable support during sampling and data acquisition.

Author information

Authors and Affiliations

  1. Department of Forensic Toxicology, Institute of Forensic Medicine, University Bonn, Stiftsplatz 12, 53111, Bonn, Germany

    Alexandra Maas, Burkhard Madea & Cornelius Hess

  2. Department for Pain Medicine, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany

    Christoph Maier

  3. Department of Forensic Toxicology, Institute of Forensic Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Stefanie Iwersen-Bergmann

  4. Drug Harm Prevention Unit, Monash University, Southbank, Australia

    Jennifer L. Pilgrim & Matthew Di Rago

Authors
  1. Alexandra Maas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christoph Maier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefanie Iwersen-Bergmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jennifer L. Pilgrim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew Di Rago
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Burkhard Madea
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cornelius Hess
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexandra Maas.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee of the Ruhr University (Bochum, Germany) as well as by the Ethics Committee of the Victorian Institute of Forensic Medicine (Southbank, Australia) and was performed in accordance with ethical standards. Informed consent was obtained from all participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maas, A., Maier, C., Iwersen-Bergmann, S. et al. Propofol and propofol glucuronide concentrations in hair following medical propofol administration and in forensic death cases. Forensic Toxicol 36, 270–279 (2018). https://doi.org/10.1007/s11419-017-0399-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11419-017-0399-0

Keywords

Search

Navigation