The safety of propofol
BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b4024 (Published 06 October 2009) Cite this as: BMJ 2009;339:b4024All rapid responses
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The excellent editorial by Hartle and Malhotra[1] is both timely and
insightful, supporting the continued appropriate use of propofol by
trained healthcare professionals in suitable hospital environments.
Further to the single lay person case of propofol abuse suggested, another
case of a 21-year-old man in Germany who had purchased the drug from eBay
exists, where he self-administered several daily doses through a
cannula.[2]
Propofol abuse in healthcare workers other than the nurse and
anaesthetist examples presented[1] are also reported. Outside the hospital
setting a GP injected propofol on a daily basis for ten months, where mild
euphoria with almost no withdrawal effects were found.[3] A hospital
physician abusing propofol reported intense craving.[4] However, despite
these reports of addictive behaviour a prospective double-blind randomized
placebo-controlled crossover study in healthy volunteers using escalating
low dose propofol (0.08 mg/kg loading dose and 0.5 mg.kg-1.h-1 infusion;
0.16 mg/kg loading dose and 1.0 mg.kg-1.h-1 infusion; 0.32 mg/kg loading
dose and 2.0 mg.kg-1.h-1 infusion) did not demonstrate addictive
behaviour.[5] Therefore propofol availability outside hospital anaesthetic
and intensive care environments should be restricted and sale to
individuals over the internet should not be permitted in any country.
References
[1] Hartle A, Malhotra S. The safety of propofol. BMJ 2009;339:b4024
[2] Strehler M, Preuss J, Wollersen H, Madea B. Lethal mixed
intoxication with propofol in a medical layman. Arch Kriminol.
2006;217:153-60.
[3] Soyka M, Sch utz CG. Propofol dependency. Addiction. 1997;92:1369
-70.
[4] Bonnet U, Harkener J, Scherbaum N. A case report of propofol
dependence in a physician. J Psychoactive Drugs. 2008;40:215-7.
[5] Zacny JP, Lichtor JL, Coalson DW, Finn RS, Uitvlugt AM, Glosten
B, Flemming DC, Apfelbaum JL. Subjective and psychomotor effects of
subanesthetic doses of propofol in healthy volunteers. Anesthesiology.
1992;76:696-702.
Competing interests:
None declared
Competing interests: No competing interests
Sir,
The authors correctly point out the remarkable benefits of Propfol in
current anaesthetic practice and reassure us of its limited abuse
potential.
Unfortunaely, in doing so, they incorrectly state that the drug is
only safe when used "by the right people" - in the authors opinion this
equates to anaesthetists and intensivists.
They leave out the whole body of emergency
medicine specialists who use Propofol widely for procedural sedation with
equal success and safety profile. Its 4-hour compliant nature (short
duration) makes it popular even with managers!
They claim that its "use by non-anesthetists is contentious" while
the evidence base of its successful and safe use in emergency medicine is
extensive. Our own experience supports very good use of Propofol in
procedural sedation. However, this often attracts uninformed criticism by
many non EM colleagues who actually do not have comparable experience in
its use for procedural sedation in emergency medicine setting, as compared
to GA, and yet maintain their antiquated reservations.
Perhaps it would be timely to appreciate that the world of (non-
anaesthetic) emergency medicine is changing.
Competing interests:
None declared
Competing interests: No competing interests
More about the safety of propofol
Recently, Andrew Hartle and Surbhi Malhotra have addressed the
question of propofol safety.[1] We agree with their conclusion that
propofol is a safe drug when it is correctly administered in a medical
setting. However, it should not be occulted that both pharmacodynamic and
clinical data have established the potential for diversion, abuse and
dependence (addiction) on propofol.
Based on the very few number of case reports of abuse and addiction
to propofol published to date, they conclude that the potential of
propofol for being voluntarily used for other aims than its therapeutical
indications is low. However, even if this number is low, in most of these
published case reports, abuse and dependence on propofol were serious.
Death was reported in six of the twelve cases referenced in Medline
between 1992 and 2009. When the reason of the death has been investigated,
it was found not related to an overdose, but to the rapidity of injection
without ventilatory assistance, which induced apnoea and consecutive fatal
respiratory depression. In most of the published case reports, abuse or
addiction concerned healthcare professionals. This is not surprising since
healthcare professionals can both have access to information about the
pleasant subjective effects of propofol (which have been demonstrated in
clinical trials with healthy volunteers)[2-3]and obtain this drug more
easily than the general population.
In addition to clinical observations, the potential for abuse and
dependence on a drug can be determined on the basis of pharmacodynamic
preclinical data. Various pharmacological tests performed on animals are
suitable to predict a problematic use of psychoactive drugs in human. In
the case of propofol, these experimental studies performed on animals
strongly suggest a real potential for abuse, which could be expected in
human. Therefore, in addition to clinical observations, pharmacodynamic
data obtained both in animal and human highlight the potential for
diversion, abuse and dependence on propofol.[4]
Michael Jackson had a problematic use of propofol and of other
substances of abuse. As for other drugs of abuse, such as opioids, risks
of addiction to propofol should be mentioned. The potential for diversion,
abuse and dependence on propofol should be known by persons starting
propofol use for diversion purpose, since it is associated to an increased
risk of death when administration is not performed in a context of
ventilatory assistance.
References:
[1]Hartle A, Malhotra S. The safety of propofol. BMJ 2009;339:b4024.
[2]Zacny JP, Lichtor JL, Zaragoza JG, Coalson DW, Uitvlugt AM,
Flemming DC, Binstock WB, Cutter T, Apfelbaum JL. Assessing the
behavioral effects and abuse potential of propofol bolus injections in
healthy volunteers. Drug and Alcohol Depend 1993;32:45-57.
[3]Zacny JP, Lichtor JL, Thompson W, Apfelbaum JL. Propofol at
subanaesthetic doses may have abuse potential in healthy volunteers.
Anesth Analg 1993;77:544–52.
[4]Roussin A, Montastruc JL, Lapeyre-Mestre M. Pharmacological and
clinical evidences on the potential for abuse and dependence of propofol:
a review of the literature. Fundam Clin Pharmacol 2007;21:459-66.
Competing interests:
None declared
Competing interests: No competing interests