University of Southern California Dissertations and Theses

The reclassification of propofol as a controlled drug: a comprehensive literature review and recommendations for practice

(USC Thesis Other)

The reclassification of propofol as a controlled drug: a comprehensive literature review and recommendations for practice

PDF

Download a page range

Download transcript

Copy asset link

Request this asset

Transcript (if available)

Content THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG: A Comprehensive
Literature Review and Recommendations for Practice
By
Summer Flanders

A Doctoral Capstone Presented to the
FACULTY OF THE USC KECK SCHOOL OF MEDICINE
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the Requirements for the Degree
DOCTOR OF NURSE ANESTHESIA PRACTICE

May 2022

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

ii

The following manuscript was contributed to in equal parts by Summer Flanders, Jacqueline
Schuster, and Laura Dillon.

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

iii

Dedication
The authors dedicate this work to anesthesia providers who have been impacted by
substance use disorder. We hope that this paper will shed light on the prevalence and severity of
this issue in the anesthesia community. It is of utmost importance to protect and support our
fellow colleagues and enact safeguards and barriers to drug abuse in the profession.

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

iv

Acknowledgements
We would like to sincerely thank our advisor, Dr. Charles Griffis. This paper would not
have been possible without his relentless support, encouragement, and enthusiasm! His wealth of
knowledge and passion in this field of research were paramount to our success, and we consider
ourselves extremely lucky to have worked under his guidance.
We would also like to acknowledge Dr. Bamgbose for her direction and expertise during
this process. Finally, to our friends and families: thank you for your patience and love during the
pursuit of our doctoral degrees in nurse anesthesia.

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

v
Table of Contents

Dedication ……………………………………………………………………………………….. iii
Acknowledgements ……………………………………………………………………………............ iv
Abstract …………………………………………………………………………………………………. vi
Chapter 1 ......................................................................................................................................... 1
Introduction ..................................................................................................................................... 1
Research Question and Specific Aims ......................................................................................... 2
Background and Significance ...................................................................................................... 3
Pharmacology of Propofol ....................................................................................................... 3
Schedule IV Drug Regulations ................................................................................................. 4
Propofol and the Neurobiology of Substance Use Disorder .................................................... 5
Abuse of Propofol .................................................................................................................... 7
Chapter 2 ......................................................................................................................................... 9
Literature Review ............................................................................................................................ 9
Propofol Use and Misuse ............................................................................................................. 9
Reports on the Operationalization of Propofol Rescheduling ................................................... 12
Chapter 3 ....................................................................................................................................... 14
Methods ......................................................................................................................................... 14
Chapter 4 ....................................................................................................................................... 15
Results ........................................................................................................................................... 15
Recommendations ...................................................................................................................... 16
Conclusion and Recommendations for Practice ........................................................................ 17
Chapter 5 ....................................................................................................................................... 18
Discussion and Conclusion ............................................................................................................ 18
Discussion .................................................................................................................................. 18
Conclusion ................................................................................................................................. 19
References ..................................................................................................................................... 21
Figure XI: The Neurobiology of Addiction ................................................................................... 26
Appendix A: Literature Review Matrix ........................................................................................ 27
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

vi

Abstract
The misuse and abuse of propofol, a widely used anesthetic drug, is prevalent among
anesthesia providers. The unique pharmacologic properties of propofol make it particularly
dangerous when administered outside of a monitored environment. Research shows that the
pharmacology of propofol, the neurobiology of addiction, and ease of access are driving factors
behind its abuse in the anesthesia profession. Overdose and death have been associated with the
misuse of propofol by anesthesia providers. Currently, propofol is not classified as a controlled
substance by the US DEA. This paper makes a case to reclassify propofol as a Schedule IV
controlled substance and reviews how doing so will reduce ease of access and subsequent abuse.
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

1
Chapter 1

Introduction

Propofol is not classified as a controlled substance by the United States Drug
Enforcement Administration (DEA), yet has a high incidence of abuse by anesthesia providers
(Wilson et al., 2010). Propofol is a short-acting intravenous anesthetic often administered by
anesthesia providers for induction of anesthesia, maintenance, and sedation during surgery (Feng
et al., 2017). It is also commonly used in intensive care units nationwide as a long-term sedative.
Since propofol was approved for use in 1989, it has become the most commonly used
intravenous anesthetic agent. The popularity and preference of propofol among health care
providers is due to pharmacodynamic properties including rapid onset of action, brief duration,
and side effects that are manageable in a monitored environment with airway support
capabilities.
According to Schneider et al. (2017), propofol accounts for 41% of reported substance
abuse cases among anesthesia providers. Propofol abuse is likely underreported due to the stigma
associated with addiction. The first reported case of propofol abuse was in 1992 by a New York
anesthesiologist (Stocks, 2011), shortly after it was adopted into anesthesia practice. While the
abuse of propofol has spread worldwide, it is most prevalent in anesthesia providers (Kranioti et
al., 2007). Neither the Food and Drug Administration (FDA) nor the Environmental Protection
Agency (EPA) have published guidelines on the proper disposal protocol for propofol.
Unregulated methods for the disposal of propofol heightens the potential for abuse by anesthesia
providers. In fact, ease of access is the most commonly reported reason for its abuse (Schneider
et al., 2017).
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

2
The therapeutic index of propofol is very narrow. This is defined as the lethal dose in
50% of the population divided by the effective dose in 50% of the population (Nagelhout &
Plaus, 2014). Persons using the drug illicitly can easily administer an overdose, resulting in loss
of airway reflexes and subsequent cardiovascular collapse (Stocks, 2011). Reducing the
accessibility of this drug is of paramount importance in order to maintain wellness in the
anesthesia provider community.
Research Question and Specific Aims
The research question guiding this investigation is: What is the compelling rationale for
the reclassification of propofol as a Schedule IV controlled drug?
The specific aims of this project are as follows:
1. To provide justification for the reclassification of propofol as a Schedule IV drug
according to the Controlled Substance Act because of the nature, uses, and
potential for abuse of this drug.
2. To discuss the neurobiology of substance use disorder and relate these principles
to the pharmacology of propofol.
3. To discuss reported propofol misuse by anesthesia providers as evidence to
consider reclassifying propofol as a Schedule IV drug in order to prevent misuse.
For the purposes of this paper, “Schedule IV drug” refers to a drug classified by the Drug
Enforcement Administration which has medical uses, but also possesses a low to moderate
potential for addiction and misuse. The potential for misuse is lower than Schedule I, II, and III,
but greater than Schedule V drugs. Schedule IV drugs are described as medically-useful drugs
that possess a low potential for abuse and dependence (Crane, 2019). Schedule II-IV drugs are to
be administered only by prescription and by qualified licensed health professionals. The dose
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

3
administered and wasted excess of controlled drugs must be accounted for in appropriate
healthcare institutional records before and following each use (Commonwealth of Massachusetts,
n.d.).
Background and Significance
Pharmacology of Propofol
Propofol is an alkylphenol organic compound developed by James Baird Glen in the
1970s and was eventually implemented into anesthesia practice in the late 1980s (Walsh, 2018).
Propofol is often used for induction of general anesthesia and conscious sedation. It is a
favorable anesthetic agent because of its quick onset of action due to fast equilibration in the
plasma and brain. It works by acting as an agonist on gamma aminobutyric acid receptors
(GABA), leading to its sedative-hypnotic effects. Propofol also has a very short duration of
action, related to rapid redistribution and fast systemic clearance by the liver, allowing for quick
emergence from anesthesia (Walsh, 2018; Folino & Parks, 2019).
Propofol binds to GABA receptors in the central nervous system, which is a common
receptor site associated with other drugs that have high potential for abuse such as
benzodiazepines, alcohol, and barbiturates (Wilson et al., 2010). By prolonging dissociation of
GABA from receptor sites, the GABA-mediated chloride channels are kept activated, resulting in
increased chloride conductance and hyperpolarization of cell membranes, decreased neuronal
firing, and rapid, dose-related decreases in consciousness (Folino & Parks, 2019). Research
shows that propofol elicits the same neurobiological changes and pharmacologic characteristics
typically associated with drugs of abuse (Stocks, 2011). Animal studies investigating the
pharmacodynamic effects of propofol have shown it stimulates the reward circuitry of the
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

4
mesolimbic system, triggering the release of dopamine, which is similar to the effect of addictive
drugs like amphetamines and opiates (Wilson et al., 2010; Xiong et al., 2018).
Fospropofol, a water-soluble prodrug of propofol, was approved for marketing by the
Food and Drug Administration in 2008 (“Schedules of Controlled Substances,” 2009).
Fospropofol has the same clinical effects as propofol and thus, the same propensity for abuse,
once metabolized in the body to the active metabolite propofol. Interestingly, fospropofol was
classified as a Schedule IV drug in November 2009; however, propofol does not fall under this
same classification.
There is not enough evidence to support the development of physical dependence
(defined as the development of an unpleasant withdrawal syndrome following prolonged use of a
drug) related to misuse of propofol. However, it does produce feelings of euphoria, disinhibition,
and stress relief, leading to psychological dependence (defined as a drive to continue the use of a
drug to produce pleasant psychic feelings, or avoid unpleasant feelings) (Koob & Bloom, 1988;
Levy, 2011). These psychological effects lead to cravings and continued abuse of the drug
despite adverse consequences (Koob & Bloom, 1988). Animal studies have also shown the
sedative-hypnotic effect of propofol is potentiated due to increased levels and binding of the
cannabinoid anandamide to cannabinoid receptors in the central nervous system (Wilson et al.,
2010). Additionally, propofol plays a role in the inhibition of the excitatory N-methyl-D-aspartic
acid (NMDA) receptor and voltage-gated sodium channels (Levy, 2011). These combined effects
increase desirability for recreational use.
Schedule IV Drug Regulations
Drugs are classified into five schedules by the DEA based on their propensity for abuse
or dependency. Schedule I drugs have the highest potential for abuse while Schedule V drugs
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

5
have the lowest potential. Schedule IV drugs are typically sedative-hypnotics and can produce
euphoria, but possess a low to moderate potential for misuse (DEA, 2020). If propofol were to be
reclassified as a Schedule IV drug, the production, distribution, and storage of the drug would be
subject to regulation. To comply with Schedule IV regulations, anyone in possession of propofol
would be required to account for the quantity of drug either administered, stored, or wasted
(DEA, 2010). This reclassification would require medical personnel to account for and properly
dispose of propofol.
Different methods exist in the health care system to provide accountability for controlled
substances. For Schedule I-V drugs, these systems include a record of drug transactions and
computer analysis of drug usage and discrepancies. These processes help to identify drug
diversion in medical professionals by generating records and revealing potential patterns of
misuse. Specific protocols are unique to each facility, but these methods overwhelmingly
improve accountability for controlled substances (Schmidt & Schlesinger, 1993).
Propofol and the Neurobiology of Substance Use Disorder
In order to better understand the issues surrounding propofol misuse, it is useful to review
the complex neurobiology of substance use disorder (SUD) and relate these principles to the
previously-discussed pharmacology of propofol. Substance use disorder is a complex disease
process that requires contributions from multiple disciplines to understand, including
psychology, neurology, and biology (Baler & Volkow, 2006). The development of SUD involves
intricate interactions between the individual and environment, both of which are relevant
concerns in considering anesthesia providers and the clinical environment in which care is
delivered. Another factor of concern is the genetic background of an individual, since the risk of
SUD appears to run in families (Toriello, 2014).
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

6
Once ingested, drugs of abuse are believed to affect the reward circuitry of the brain in a
predictable fashion (Baler & Volkow, 2006). Normally, the reward mechanism of the brain is
triggered by activities that produce pleasure, such as eating or sex. These pleasurable activities
result in a surge in dopamine levels in the brain, specifically in the nucleus accumbens, an area
within the mesolimbic pathway and basal forebrain, rostral to the preoptic areas of the
hypothalamus (Ikemoto, 2010). Dopamine levels return to normal once these activities are
complete. However, unlike food and sex, drugs of abuse continue to stimulate the release of
dopamine, conditioning the brain to pursue activities that elicit this reward.
Over time, neuroplastic changes develop in the reward circuit, involving modifications in
neuronal synapses. Evidence shows that substance abuse disorder causes disruptions in the basal
ganglia, the amygdala, and the prefrontal cortex of the brain. These disruptions lead to an
increased drive to seek out the substance of abuse and reduced functioning of the brain’s
executive control systems (Surgeon General, 2016). Repeated drug use can cause both up- and
down-regulation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
receptor, which has increased permeability to calcium and enhances responsiveness to glutamate,
along with the NMDA receptor. Increased responsiveness to glutamate enhances the signal
transmission between neurons and strengthens synaptic connections that are associated with
learning, and serve to reinforce this behavior. Over time, the surge in dopamine associated with
the drug begins to decrease, making it difficult to experience the same level of pleasure that was
once achieved by the drug (Volkow et al., 2016). The drive to abuse the drug then changes from
pleasure-seeking to necessity in order to relieve the distress of not having the drug (Baler &
Volkow, 2006).
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

7
Drugs of abuse create chemical pathways in the brain that encourage and incentivize the
addicted person to continuously obtain and use that drug. This poses a particularly significant
problem for anesthesia providers who are abusing propofol and suffer from substance use
disorder. The conditioned changes in the addicted anesthesia provider’s brain encourages them to
engage in behaviors in order to acquire more propofol (Surgeon General, 2016). The
neurobiological changes that occur in the addicted anesthesia provider’s brain encourage them to
reprioritize acquiring and using their drug of choice above patient safety. Because of this
reprioritization, they are no longer capable of safely and effectively doing their job, regardless if
they are actively under the influence at work.
In addition, according to a report released by the US Surgeon General, substance abuse
results in changes to the brain that reduce executive control systems. These control systems are
central to a person’s ability to make decisions and regulate actions, emotions, and impulses
(Surgeon General, 2016). These impediments on a provider’s executive functioning could prove
disastrous to the patient; it is vitally important that the person administering anesthesia be able to
effectively make decisions regarding patient care (Figure XI).
Abuse of Propofol
Anesthesia providers have few barriers to accessing propofol in its current unclassified
status, which increases its appeal as a potential drug of abuse (Stocks, 2011). Ease of access to
deadly drugs is a critical factor in the elevated rate of substance use disorder (SUD) in CRNAs
and the rapid course of SUD to overdose and death (American Association of Nurse Anesthetists
[AANA], 2016). In a study examining SUD treatment cases, Early and Finver (2013) found that
90% of those who abused propofol were anesthesia providers with access to the drug. In
addition, a survey conducted by the University of Colorado showed an association between the
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

8
abuse of propofol and its status as a non-controlled substance in anesthesia students
(Wischmeyer et al., 2007). Lack of regulation of propofol eliminates accountability when
wasting the drug and makes it easier for providers to divert the remaining volume. Propofol’s
effects are fast acting and quickly dissipate, making it difficult to detect abuse (AANA, 2016).
Due to its short half-life and rapid redistribution, only blood sampling immediately after use can
detect the presence of propofol.
Propofol reduces respiratory drive, decreases tidal volume and respiratory rate, blunts
protective airway reflexes, and decreases upper airway muscle tone which may result in airway
obstruction (Levy, 2011). If propofol is not administered by a provider trained in airway
management, a single administration can lead to apnea, hypoxia, and death (Levy, 2011).
Mortality rates are as high as 38% for anesthesiologists who misuse propofol (Bonnet &
Scherbaum, 2012).
Another contributing factor to drug abuse is the job-related stress of anesthesia
providers, who face increasing production pressure, larger caseloads, and sicker patients to care
for (Luck & Hedrick, 2004). Anesthesia providers may grow complacent to the hazards of these
drugs due to the ease of access and daily administration to patients. Research has shown that up
to 15% of anesthesia providers deal with drug abuse during their careers (Luck & Hendrick,
2004). Anesthesia providers with SUD encounter major challenges to treatment due to the nature
of their career. While the stressors associated with the anesthesia profession are unlikely to
change, reclassification of the drug to a Schedule IV controlled substance can serve as a barrier
to easy access and abuse. This team of researchers supports the reclassification of propofol as a
Schedule IV drug, in alignment with recommendations put forth by the AANA to reduce the
accidental fatalities associated with its misuse (AANA, 2016).
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

9
Chapter 2
Literature Review
Propofol Use and Misuse
Schneider, Ponto, and Martin (2017) conducted an evidence-based practice project at a
large teaching institution to explore substance abuse related to barriers of disposal among
anesthesia providers. Initially, the authors conducted a focus group with 15 Certified Registered
Nurse Anesthetists (CRNAs) to determine how propofol was being disposed of, and then utilized
this information to compile and distribute a survey to 280 CRNAs. The survey revealed several
barriers to the disposal of propofol waste at this institution. This led to development of two
changes in practice within the department: the use of propofol bottle openers and activated
carbon pouches (the contents of the pouch render the propofol inactive as it is poured in).
CRNAs received education for both of the products and trialed them for six weeks. At the
conclusion of six weeks, the research team compared the number of unemptied or partially
emptied propofol vials left in the unsecured bins in the operating rooms with baseline data using
the same methods. Post-intervention data revealed propofol bottle openers and carbon pouches
reduced the number of unemptied or partially empty propofol bottles (Schneider et al., 2017).
The researchers concluded reducing barriers to disposal of propofol contributed to the safe use
and disposal of the drug. The authors went on to posit that effective and appropriate disposal of
propofol may lead to a decrease in potential for abuse among providers (Schneider et al., 2017).
Kranioti et al. (2007) measured the postmortem concentrations of propofol of a 38-year-
old female anesthesiologist who had succumbed to overdose. The measuring concentrations of
propofol in the deceased physician were consistent with therapeutic plasma levels, defined as a
blood concentration of 1.3-6.8 μg/mL, which is adequate for loss of consciousness and apnea.
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

10
The authors stress that patient safety at these therapeutic concentrations requires monitoring and
appropriate respiratory support in a clinical setting. The deceased physician had a femoral blood
propofol concentration of 2.4 μg/mL, which proved to be lethal in this case. The authors
concluded that unmonitored propofol use can be deadly (Kranioti et al., 2007).
Wischmeyer et al. (2007) conducted a survey which included 126 anesthesiology
residency programs nationwide. The survey investigated the incidence of propofol abuse over 10
years and had a 100% response rate. The results of this survey were based on the program’s self-
reporting and revealed 18% of anesthesia departments had one or more individuals abusing
propofol during the time period measured on the survey. Out of the 126 programs, 25 known
events of propofol abuse were reported. A majority of the programs did not exert any regulation
of propofol at the time of the event, with 22 of the 25 events of abuse occurring in facilities
where propofol was not a controlled substance. Twenty eight percent of those who abused
propofol in the reported population died from overdose. The survey reported that the observed
rates of propofol misuse in this population of anesthesia providers was 0.1% (Wischmeyer et al.,
2017). The authors voiced concern over propofol-related deaths in anesthesia providers and
suggested the utility of reclassifying it as a Schedule IV drug, which could potentially curb abuse
and death.
Bryson and Silverstein (2008) published a manuscript which discussed the basis of
addiction among anesthesia providers, prevalence of addiction, and the most commonly abused
drugs. Propofol, in addition to fentanyl and sufentanil, are frequently abused drugs among
anesthesia providers. A contributing factor in propofol abuse is the lack of documentation to
substantiate its abuse. Without reclassification as a controlled drug, there is no system which
accounts for propofol waste and it is quite simple for anesthesia providers to divert small
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

11
amounts of the drug – thus actual abuse numbers are thought to be higher than reported. The
authors state that ease of access is the main reason for drug abuse among anesthesia providers.
Among addiction experts, the consensus is that controlling a drug may allow for earlier detection
and documentation of abuse (AANA, 2016).
Bonnet and Scherbaum (2012) explored psychological addiction to propofol through a
case study of a 30-year-old male anesthesiologist. The anesthesiologist was injecting 100-200mg
of propofol up to 40 times a day and described the high as euphoric; he experienced intense
compulsions to abuse propofol. The authors examined records from the individual’s inpatient
detoxification stay, where details regarding withdrawal, cravings, and symptoms were outlined.
The patient displayed behaviors consistent with SUD, such as neglecting responsibilities in order
to abuse propofol. His most significant symptoms were psychological dependence, cravings, and
loss of control. Psychological cravings for propofol persisted even after physical withdrawal
symptoms subsided. After evaluation by psychologists during his 14-day hospital stay, he was
diagnosed with propofol dependence. The authors cite this case study as anecdotal evidence that
propofol has addictive properties and warn against the dangers of its non-regulated access
(Bonnet & Scherbaum, 2012).
Earley and Finver (2013) conducted a retrospective case study of the medical records of
health care professionals (HCPs) who were treated at a large addiction center for over 20 years.
The records of HCPs who abused propofol were identified and reviewed. Details regarding these
HCP’s demographics were noted, with a focus placed on the variables of gender, medical
education and specialty, drugs used, course of SUD, and comorbidities. The goal of the case
study was to identify characteristics of HCPs who abused propofol and search for trends. Their
results showed that individuals who abused propofol were more likely to work in the operating
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

12
room, identify as female, and provide anesthesia. All of these individuals had work-related
access to propofol. Most of the patients in this group identified propofol as their preferred drug
of choice. The majority of the group had a history of depression, physical injury, and had a
higher incidence of family and genetic history of SUD. The study discusses how the incidence of
propofol abuse in HCPs is increasing, with anesthesia providers being the most at-risk. The
authors recommended screening to identify HCPs predisposed to develop propofol abuse based
on the identified high-risk characteristics (Earley & Finver, 2013).
Reports on the Operationalization of Propofol Rescheduling
There are potential challenges associated with the classification of any drug as a
controlled substance. A strict federal policy on the proper use and disposal of a controlled drug
must be followed by the anesthesia provider. This potentially increases provider workload and
time between operating room (OR) cases. Clinicians who oppose the control of propofol argue
that the abuse of propofol is less than other substances. They state that additional steps required
to account for the drug will impede rapid turnover of patients in ORs by creating more steps for
anesthesia providers to follow in order to accurately account for the drug. In addition, there are
increased costs related to the need for space to securely store the drug, along with training
pharmacy staff to ensure compliance with new regulations for proper waste and disposal
(Schneider et al., 2017). It should also be noted that controlled drugs such as opioids and
benzodiazepines continue to be abused and diverted by healthcare personnel despite strict
regulations. Control of these drugs as scheduled substances may not be the most efficacious
option in preventing misuse (Berge et al., 2012).
In 2010, the DEA released a statement regarding propofol reclassification. The
document stated that the potential for abuse of propofol is high among anesthesia providers due
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

13
to its ease of access. Furthermore, a mortality rate greater than 33% is associated with the misuse
and abuse of propofol (DEA, 2010). This demonstrates the danger of uncontrolled access to
propofol and the need to place precautions (despite potential negative effects upon workflow) in
order to protect anesthesia providers by classifying propofol as a Schedule IV drug (DEA, 2010).

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

14
Chapter 3
Methods
A review of existing literature was performed in order to build a comprehensive
understanding of this topic and provide informed recommendations. This search employed
PubMed, CINAHL, and the USC Norris Medical Library online database to identify relevant
peer-reviewed literature that pertained to our topic. The search terms “propofol” and “misuse” or
“addiction” or “controlled” yielded 4,658 results via PubMed, of which 36 sources were initially
selected. Inclusion criteria was based on publication date (2007-2018), relevance (use and misuse
of propofol), source (acceptable quality in peer reviewed publication), and applicability to the
topic (discussion of abuse potential and consequences, and reclassification). These selections
were narrowed down further, and 3 articles were ultimately used. A PubMed search of the terms
“propofol” and “history” yielded 476 results. These results were reviewed by the authors and 1
article was selected based on the inclusion criteria. PubMed was also searched using “propofol”
and “pharmacology” or “chemical properties” resulting in 14,682 relevant articles of which 3
were retained based on inclusion criteria. The USC Libraries Website was explored using the
terms “propofol” and “anesthesia provider” or “health care provider” and “abuse” or “misuse.”
Peer-reviewed articles that matched this search included 439 results, of which were screened to
finally include 2 articles that were used by the authors. CINAHL provided 16 results using the
terms “propofol” and “controlled” or “addiction,” and 2 articles met the inclusion criteria. A
Google search of “propofol” and “Schedule IV drug” led to the American Association of Nurse
Anesthetist website along with the DEA website, both of which were used for multiple
recommendations and reviews. A total of twenty-nine publications and seven
policies/recommendations were incorporated in this review.
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

15
Chapter 4
Results
In examining the literature relevant to the specific aims of this study, this team of
investigators found interesting and consistent facts.
Regarding Specific Aim #1, the research team reviewed the pharmacology of propofol in
an effort to discern what makes this drug so attractive and dangerous to the anesthesia
practitioners who divert and abuse it. The literature reveals that propofol is a sedative-hypnotic
drug that enhances the effect of GABA, producing a rapid dose-related decrease in level of
consciousness (Wilson et al., 2010). The drug has a very narrow therapeutic index, meaning that
the difference between a dose that would cause sedation and a lethal dose is very small. All of
these pharmacological properties support propofol’s desirability and therefore potential for
abuse.
Regarding Specific Aim #2, the neurobiology of the addictive process involved in SUD
was reviewed in an effort to understand how practitioners, once addicted to propofol, posed a
constant threat to themselves and their patients. It was found that the complex interaction
between the anesthesia provider and their environment contributes to an increased risk of
substance abuse. Drugs of abuse create chemical pathways in the brain that encourage the
addicted person to continuously obtain and use that drug. The neurobiological changes that occur
in the addicted anesthesia provider’s brain encourage them to reprioritize acquiring and using
their drug of choice above patient safety. Because of this reprioritization, they are no longer
capable of safely and effectively doing their job.

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

16
Regarding Specific Aim #3, the literature documenting abuse of propofol by anesthesia
practitioners was reviewed to identify the scope of the problem and the outcomes of propofol
abuse both for practitioners and for patients as evidence to support reclassification of the drug.
Abuse of propofol is a widespread phenomenon, which appears primarily related to the ease of
access to the drug (AANA, 2016). Reclassifying propofol as a Schedule IV drug will prevent
misuse and abuse by anesthesia providers by implementing protocols which account for drug use
and disposal.
Recommendations
Based on literature review findings, the authors of this paper have provided an executive
summary of current evidence to illustrate the potential addictive properties of propofol and its
propensity for misuse by health care providers due to ease of access and the misuse of this drug.
In addition, propofol’s narrow therapeutic index lends itself to the potential for overdose and
death. The authors provided evidence demonstrating the mechanisms by which availability and
accessibility of propofol leads to increased diversion and rates of abuse in the anesthesia setting.
Consistent with the study by Stocks in 2011, the authors believe that the classification of
propofol as a Schedule IV drug will decrease the incidence of abuse and associated fatalities.
These findings help to establish evidence-based practice recommendations to reclassify propofol
as a Schedule IV controlled substance, which is in alignment with the American Association of
Nurse Anesthetists and American Society of Anesthesiologists position on the handling of
propofol. The implementation of propofol as a Schedule IV drug should follow each institution’s
established guidelines for the control of drugs in this specific category.

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

17
Conclusion and Recommendations for Practice
This paper examined the propensity of propofol abuse among anesthesia providers, the
pharmacology of propofol, the neurobiology of addiction, and the numerous case reports of
abuse among anesthesia providers.
The following practice recommendations are proposed, based on a systematic review of
the pharmacology of propofol and the potential for abuse:
1. Propofol should be reclassified by the FDA and DEA as a Schedule IV drug. This
reclassification will support safer use of this drug. Evidence shows that the ease of access of
propofol contributes to the abuse of the drug (Stocks, 2011; Wilson et al., 2010).
2. Anesthesiology settings should promulgate policies supporting the controlled use of
propofol. Propofol remains one of the most commonly abused drugs among anesthesia providers.
The implications of propofol abuse by an anesthesia provider is not only detrimental to the
clinician, but will also negatively impact their colleagues and endanger patients (AANA, 2017).
3. Nurse anesthesia education should expand the current Council on Accreditation
requirement for education on substance use to include in-depth exploration of the neurobiology
of addiction in an effort to arm graduates with a better understanding of the risks of working with
potentially deadly drugs (Council on Accreditation of Nurse Anesthesia Educational Programs,
2019).

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

18
Chapter 5
Discussion and Conclusion
Discussion
This paper sought to address three specific aims. First, to provide justification for the
reclassification of propofol as a Schedule IV drug according to the Controlled Substance Act
because of the nature, uses, and potential for abuse of this drug. Second, to discuss the
neurobiology of substance use disorder, and relate these principles to the pharmacology of
propofol. Third, to discuss propofol misuse by anesthesia providers and provide evidence that
reclassifying propofol as a Schedule IV drug will promote provider wellness and prevent misuse.
Review of the relevant literature reveals to this research team that the reclassification of propofol
as a Schedule IV drug is of utmost importance.
The first specific aim was addressed by examining the pharmacodynamics,
pharmacokinetics, and physicochemical qualities of propofol as commonly used in anesthetic
practice. Existing literature provided strong evidence that the inherent properties of propofol
support the potential for addiction and abuse. Propofol is a potent GABA agonist, producing
rapid decreases in consciousness, reduced protective airway reflex activity, and behaves
similarly to other drugs that are commonly abused (Wilson et al., 2010). Benzodiazepines, which
have similar pharmacological effects as propofol and also act on the GABA receptor, are
classified as Schedule IV controlled substances. Therefore, it is reasonable that propofol should
be reclassified as a controlled substance to better align with these standards for safe practices. A
review of the literature illustrates that propofol has a high potential for lethal consequences for
those who are abusing this drug due to the loss of respiratory drive and reduction of protective
airway reflexes (Levy, 2011). It is essential that propofol be administered only by a trained
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

19
professional in a monitored environment, or dire consequences may ensue. This potential for
lethal effect further drives the authors’ argument for the reclassification of propofol as a
Schedule IV drug. The authors believe that this is the most effective way to limit the number of
deaths associated with the unmonitored administration of propofol.
The second specific aim explored the neurobiology of drug abuse and identified parallels
between the illicit use of propofol, neuroplasticity, and changes in neurotransmitters and
receptors in the brain. Like other drugs of abuse, propofol affects dopamine levels in the brain
and the interaction of dopamine with its receptor. The pharmacologic profile of propofol along
with ease of access to the drug makes it a potentially addictive substance among anesthesia
providers (Stocks, 2011).
The third specific aim was addressed by a review of literature which demonstrated that
propofol is a drug of abuse among anesthesia providers due to its accessibility and unique
qualities (Stocks, 2011). The most significant factor leading to abuse of propofol is that it is not a
controlled substance and most facilities do not regulate its disposal. As previously discussed,
literature shows that this lack of regulation directly correlates with a higher incidence of abuse
(AANA, 2016). Reclassification of propofol as a Schedule IV drug will promote provider
wellness by helping to prevent misuse or abuse.
Conclusion
Propofol is a commonly abused drug by anesthesia providers mainly due to ease of
access. The unique pharmacology of propofol, along with the risk of provider addiction as
evidenced by SUD, highlights the necessity of reclassifying propofol as a Schedule IV drug in
order to improve patient safety. The consensus among addiction experts is that controlling a drug
may allow for earlier detection and documentation of abuse (AANA, 2016). This early detection
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

20
of abuse could potentially save lives and prevent prolonged drug abuse by anesthesia providers.
Unfortunately, whenever change is proposed, there are those who will be reluctant to adapt to a
new way of practice. Accounting for unused propofol at the end of every case and properly
wasting the drug per protocol of the institution are issues that contribute to reluctance to control
this drug. These extra steps could potentially impede fast turnover rates in the operating room
and decrease the number of surgeries that are able to be performed each day. However, as
anesthesia professionals, we are bound to protect other members of our profession. Our
obligation is to safeguard our colleagues by preventing substance abuse. Anesthesia providers
are at a much greater risk of substance abuse due to the nature of the profession and close contact
with highly addictive, readily available drugs on a daily basis (AANA, 2016).
Substance abuse disorder is a disease of the brain and not a choice, and each and every
anesthesia provider is at risk of becoming addicted to substances at some point during his or her
career. Because of this, it is essential that we take every precautionary measure possible to
prevent this from happening and protect anesthesia providers from the dangers of substance
abuse. The findings of this review support the reclassification of propofol as a controlled drug.
Ultimately, the most important and compelling reason to reclassify propofol is the probability
that doing so will not only decrease the abuse of propofol, but improve the safety of patients and
will save the lives of anesthesia providers involved in the misuse of this drug. Those who are
abusing propofol will be more easily identified, which will allow for the possibility of early
intervention and restoration of these professionals to a safe and healthy life.

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

21
References
American Association of Nurse Anesthetists. (2016). Addressing Substance Use Disorder for
Anesthesia Professionals: Position Statement and Policy Considerations.
https://www.aana.com/docs/default-source/practice-aana-com-web-documents-
(all)/professional-practice-manual/addressing-substance-use-disorder-for-anesthesia-
professionals.pdf?sfvrsn=ff0049b1_4
Baler, R. D., & Volkow, N. D. (2006). Drug addiction: The neurobiology of disrupted self-
control. Trends in Molecular Medicine, 12(12), 559-566.
Berge, K. H., Dillon, K. R., Sikkink, K. M., Taylor, T. K., & Lanier, W. L. (2012). Diversion of
drugs within health care facilities, a multiple-victim crime: Patterns of diversion, scope,
consequences, detection, and prevention. Mayo Clinic Proceedings, 87(7), 674–682.
https://doi.org/10.1016/j.mayocp.2012.03.013
Bonnet, U., & Scherbaum, N. (2012). Craving dominates propofol addiction of an affected
physician. Journal of psychoactive drugs, 44(2), 186–190.
https://doi.org/10.1080/02791072.2012.684635
Bryson, E. O., & Silverstein, J. H. (2008). Addiction and substance abuse in anesthesiology.
Anesthesiology, 109(5), 905–917. 10.1097/aln.0b013e3181895bc1
Chao, T. C., Lo, D. S., Chui, P. P., Koh, T. H. (1994). The first fatal 2,6-diisopropylphenol
(propofol) poisoning in Singapore: A case report. Forensic Science International, 66(1),
1-7.

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

22
Commonwealth of Massachusetts. (n.d.). General accountability guidelines for controlled
substances in hospitals and clinics with pharmacies. https://www.mass.gov/info-
details/general-accountability-guidelines-for-controlled-substances-in-hospitals-and-
clinics#nursing-units-
Council on Accreditation of Nurse Anesthesia Educational Programs. (2019, October).
Standards for Accreditation of Nurse Anesthesia Educational Programs.
https://www.coacrna.org/wp-content/uploads/2020/01/2004-Standards-for-Accreditation-
of-Nurse-Anesthesia-Educational-Programs-revised-October-2019.pdf
Crane, M. (2019, November 25). Classification of Drugs: Narcotics and Prescription Drug
Schedules. American Addiction Centers.
https://americanaddictioncenters.org/prescription-drugs/classifications
Drug Enforcement Agency. (2010, October 27). Schedules of Controlled Substances: Placement
of Propofol Into Schedule IV. Federal Register.
https://www.federalregister.gov/documents/2010/10/27/2010-27193/schedules-of-
controlled-substances-placement-of-propofol-into-schedule-iv
Drug Enforcement Agency. (2020). Drug Scheduling. https://www.dea.gov/drug-scheduling
Drummer, O. H. (1992). A fatality due to propofol poisoning. Journal of Forensic Science, 37,
1186-1189.
Earley, P. H., & Finver, T. (2013). Addiction to propofol: A study of 22 treatment cases. Journal
of Addiction Medicine, 7(3), 169–176. https://doi.org/10.1097/ADM.0b013e3182872901
Feng, A. Y., Kaye, A. D., Kaye, R. J., Belani, K., & Urman, R. D. (2017). Novel propofol
derivatives and implications for anesthesia practice. Journal of Anaesthesiology Clinical
pharmacology, 33(1), 9–15.
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

23
Folino, T. B., & Parks, L. J. (2019). Propofol. StatPearls Publishing.
https://www.ncbi.nlm.nih.gov/books/NBK430884/
Gouda, B., Gouda, G., Borle, A., Singh, A., Sinha, A., Singh, P. (2017). Safety of non-anesthesia
provider administered propofol sedation in non-advanced gastrointestinal procedures: A
meta-analysis. Saudi Journal of Gastroenterology, 23(3), 133-143. doi:
10.4103/sjg.SJG_501_16
Ikemoto, S. (2010). Brain reward circuitry beyond the mesolimbic dopamine system: A
neurobiological theory. Neuroscience and Biobehavioral Review (35)2, 129-150.
Iwersen-Bergmann, S., Rösner, P., Kühnau, H. C., Junge, M., & Schmoldt, A. (2001). Death
after excessive propofol abuse. International Journal of Legal Medicine, 114, 248-251.
Koob, G. F., & Bloom, F. E. (1988). Cellular and molecular mechanisms of drug dependence.
Science, 242(4879), 715-723.
Levy, R. J. (2010). Clinical effects and lethal and forensic aspects of propofol. Journal of
Forensic Sciences, 56(01), 142-147. doi: 10.1111/j.1556-4029.2010.01583.x
Luck, S., & Hendrick, J. (2004). The alarming trend of substance abuse in anesthesia providers.
Journal of PeriAnesthesia Nursing,19(5): 308-311.
https://doi.org/10.1016/j.jopan.2004.06.002
Nagelhout, J. J. & Plaus, K. L. (2014). Nurse Anesthesia (5th edition). Elsevier.
Kranioti, E. F., Mavroforou, A., Mylonakis, P., & Michalodimitrakis, M. (2007). Lethal self
administration of propofol (diprivan). A case report and review of the literature. Forensic
Science International, 167(1), 56-58. https://doi.org/10.1016/j.forsciint.2005.12.027
Maurer, W. G., & Philip, B. K. (2010). Propofol infusion platforms: Opportunities and
challenges. Journal of Digestion, 82(2), 127–129. doi: 10.1159/000285703
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

24
Schneider, D., Ponto, J., Martin, E. (2017). Propofol disposal in the anesthesia setting:
Overcoming barriers. AANA Journal, 85, 417-423.
Schedules of controlled substances; placement of fospropofol into schedule IV. (2009). The
Federal Register, 74(192). https://search-proquest-
com.libproxy1.usc.edu/docview/190176770?accountid=14749
Schmidt, K. A., & Schlesinger, M. D. (1993). A reliable accounting system for controlled
substances in the operating room. Anesthesiology, 78(1), 184–190.
https://doi.org/10.1097/00000542-199301000-00025
Stocks, G. (2011). Abuse of propofol by anesthesia providers: The case for re-classification as a
controlled substance. Journal of Addictions Nursing, 22(1-2), 57-62. doi:
10.3109/10884602.2010.545091
Toriello, H. V. (2014). Genetics and substance abuse disorders. International Public Health
Journal, 6(3), 235-243. https://search-proquest-com.libproxy1.usc.edu/docview/
1625577439?accountid=14749&rfr_id=info%3Axri%2Fsid%3Aprimo
U.S. Department of Health and Human Services (HHS), Office of the Surgeon General (2016).
Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and
Health. https://addiction.surgeongeneral.gov/
Volkow, N. D., Koob, G. F., & Mclellan, A. T. (2016). Neurobiologic advances from the brain
disease model of addiction. New England Journal of Medicine, 374(4), 363–371. doi:
10.1056/nejmra1511480
Walsh C. T. (2018). Propofol: Milk of Amnesia. Cell, 175(1), 10–13.
https://doi.org/10.1016/j.cell.2018.08.031
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

25
Wilson, C., Canning, P., & Caravati, E. (2010). The abuse potential of propofol.
Clinical Toxicology, 48(3), 165–170. https://doi.org/10.3109/15563651003757954
Wischmeyer, P., Johnson, B., Wilson, J., Dingmann, C., Bachman, H., Roller, E., Zung, T., &
Henthorn, T. (2007). A survey of propofol abuse in academic anesthesia programs.
Journal of Anesthesia and Analgesia. 105(4), 1066-1071. doi:
10.1213/01.ane.0000270215.86253.30
Xiong, M., Shiwalkar, N., Reddy, K., Shin, P., & Bekker, A. (2018). Neurobiology of propofol
addiction and supportive evidence: What is the new development? Brain Sciences, 8, 36.

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

26
Figure XI: The Neurobiology of Addiction

THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

27
Appendix A: Literature Review Matrix

APA Reference Summary of Main
Concept
Quantitative or
Qualitative
Research?
Methods (designs,
instruments,
questionnaires)
Main findings
of the study
Capstone application
Schneider, D.,
Ponto, J., Martin, E.
(2017). Propofol
Disposal in the
Anesthesia Setting:
Overcoming
Barriers. AANA
Journal, 85, 417-
423.
Propofol is an
uncontrolled
substance which
“accounts for 41%
of reported
substance abuse
cases among
anesthesia
providers” mainly
due to ease of
access. It is
important to
dispose of
propofol
appropriately in
order to reduce the
risk of abuse.
Quantitative This evidence-based
practice project was
conducted with 280
CRNAs practicing in
the clinical setting.
First, baseline data
on propofol disposal
was collected at a
large teaching
institution over a 6
week period. Based
on this data and
information collected
from an informal
focus group of 15
CRNAs, a survey
was administered to
the CRNAs at the
institution in order to
best identify the
barriers to disposal.
The results of this
survey led to the
development of two
interventions:
propofol bottle
openers and activated
carbon pouches.
Education about
these products was
given to CRNAs who
then trialed them for
6 weeks. Post-
intervention data
about propofol
disposal was then
collected.
Propofol bottle
openers and
carbon pouches
reduced the
number of
unemptied or
partially empty
propofol bottles
found in
unsecured bins
in the OR.
Controlling propofol will
decrease the rate of incorrect
disposal and therefore reduce the
potential for abuse by anesthesia
providers.
Kranioti, E. F.,
Mavroforou, A.,
Mylonakis, P., &
Michalodimitrakis,
M. (2007). Lethal
self administration
of propofol
(diprivan). A case
report and review of
the literature.
Forensic Science
International,
167(1), 56-58.
Retrieved from
http://libproxy.usc.e
Propofol (2,6-
disopropylphenol)
has a rapid onset,
short duration of
action, and low
toxicity which
makes it a
commonly abused
drug among
anesthesia
providers.
Propofol is
“abused for its
sedative and
relaxing
Qualitative A literature review
along with a case
report of a 38-year-
old female
anesthesiologist who
was found dead in a
hospital dormitory
were conducted.
The
postmortem
concentrations
of propofol
were at
therapeutic
levels in this
particular case
study along
with three
others that the
authors found
in the literature.
Therapeutic
concentrations
Propofol is dangerous due to it
being lethal even at therapeutic
doses for non-supported patients.
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

28
du/login?url=https://
search-proquest-
com.libproxy2.usc.e
du/docview/702784
89?accountid=1474
9

properties” which
can lead to
psychological
dependence.
of propofol are
based on
patients who
are supported
respiratory-
wise, and the
same
concentration
may be lethal
in a patient
who is non-
supported or
non-intubated.
Walsh, C. T. (2018).
Propofol: Milk of
Amnesia. Retrieved
October 25, 2019,
from https://www-
sciencedirect-
com.libproxy2.usc.e
du/science/article/pi
i/S00928674183104
7X
This article
provides a brief
summary of the
history of
anesthetics and
how the
development of
propofol in the late
20th century has
greatly improved
the safety of
anesthesia.
N/A N/A N/A History of anesthesia and the
development of propofol
Courtney Wilson,
Peter Canning & E.
Martin Caravati
(2010) The abuse
potential of
propofol, Clinical
Toxicology, 48:3,
165-170. doi:
10.3109/155636510
037579
54
This article
analyzes the
potential for
propofol abuse
based on
symptoms of
withdrawal and
tolerance. It also
explains the
pharmacokinetics
of the drug and
how it behaves
similarly to other
commonly abused
substances.
Qualitative Systematic review of
45 articles from peer-
reviewed journals
and includes cases
reports, cross-
sectional and
prospective trials,
and review articles.

This study
supports the
recommendatio
n for
controlling
propofol
because of its
high potential
for abuse based
on findings that
demonstrate
incidences of
withdrawal,
dependence,
tolerance, and
even death.
This study supports
recommending propofol as a
controlled substance.
Maurer, W. G., &
Philip, B. K. (2010).
Propofol Infusion
Platforms:
Opportunities and
Challenges. Journal
of Digestion, 82(2),
127–129. doi:
10.1159/000285703
A variety of
platforms have
been developed
for administering
propofol to
address safety
concerns, however
these methods do
not negate the
need for
appropriate
training in
pharmacodynamic
s,
pharmacokinetics,
and airway
management,
Qualitative Literature review Despite efforts
to develop safer
platforms for
administering
propofol, the
therapeutic
window
remains narrow
and presents a
significant
safety concern
for anyone
administering
the drug. The
American
Association of
Anesthesiologis
Propofol has a very narrow
therapeutic window and can only
be safely administered by
individuals with appropriate
training.
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

29
especially for non-
anesthesiologists
that administer the
drug.

ts in addition to
the American
Association of
Nurse
Anesthetists
both support
that it is
imperative for
any non-
anesthesiologist
s administering
propofol to
have additional
training that
support their
understanding
of the
pharmacodyna
mics and
pharmacokineti
cs of the drug,
along with
airway skills.
Gouda, B., Gouda,
G., Borle, A., Singh,
A., Sinha, A.,
Singh, P. (2017).
Safety of non-
anesthesia provider
administered
propofol sedation in
non-advanced
gastrointestinal
procedures: A meta-
analysis. Saudi
Journal of
Gastroenterology,
23(3), 133-143. doi:
10.4103/sjg.SJG_50
1_16
This meta-analysis
included trials in
which propofol
was administered
to patients
undergoing non-
advanced
gastrointestinal
endoscopy by a
registered nurse
under the
supervision of a
gastroenterologist.
It was found to be
safe with a pooled
hypoxia rate of
0.014.
Quantitative A meta-analysis was
conducted that
included 25 both
prospective and
retrospective studies.
Hypoxia rates,
airway related
interventions during
the procedure, and
airway related
complications were
included in the
pooled analysis.
Hypoxemia
was the most
common
adverse event
in the literature.
Out of 137,087
patients, 2931
hypoxia
episodes
occurred -
defined as an
oxygen
saturation
<90%.
This study shows that propofol is
not dangerous when given by
non-trained providers. However,
the meta-analysis only looked at
GI endoscopy procedures in
which propofol was administered
by an RN. We don’t know if the
RN received special training.
Levy, R. J. (2010).
Clinical Effects and
Lethal and Forensic
Aspects of
Propofol*. Journal
of Forensic
Sciences, 56(01).
doi: 10.1111/j.1556-
4029.2010.01583.x
Propofol is a
widely used
intravenous
anesthetic which
has recently been
recognized as
having the
potential for
“dependency,
recreational use,
and abuse.”
N/A Author manuscript When
administered
by experienced
and qualified
clinicians,
propofol is
relatively safe.
However, “it
reduces
respiratory
drive, blunts
protective
airway reflexes,
and can reduce
upper airway
muscular tone
resulting in
airway
obstruction.
This article supports control of
propofol due to its potential for
abuse and lethal consequences if
self-administered or administered
by an untrained provider.
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

30
Without proper
management by
an experienced
provider, a
single injection
of propofol can
result in apnea,
respiratory
arrest, hypoxia,
and death.”
Stocks, G. (2011).
Abuse of Propofol
by Anesthesia
Providers: The Case
for Re-
Classification as a
Controlled
Substance. Journal
of Addictions
Nursing. Volume
22(1-2), 22 March
2011, p 57-62. DOI:
10.3109/10884602.2
010.545091
High availability
and ease of access
to propofol with
little to no
regulations are
primary factors in
propofol abuse.
NA Literature review and
recommendation for
practice
When propofol
is treated as a
controlled
substance, rates
of propofol
abuse and
incidence of
fatal overdose
decreased.
Limiting access to propofol could
reduce the incidence of propofol
abuse and lethal overdose by
anesthesia providers.
Wischmeyer, P.,
Johnson, B.,
Wilson, J.,
Dingmann, C.,
Bachman, H.,
Roller, E., Zung, T.,
& Henthorn, T.
(2007). A Survey of
Propofol Abuse in
Academic
Anesthesia
Programs. Journal
of Anesthesia and
Analgesia. Volume
105(4). DOI:
10.1213/01.ane.000
0270215.86253.30
Rates of propofol
abuse and related
deaths have
increased in the
past 10 years. At
all departments
that experienced a
propofol related
death, propofol
was not treated as
a controlled
substance.
Qualitative and
Quantitative
A survey was sent
via email to 126
anesthesia residency
programs in the U.S.
Survey questions
focused on propofol
abuse and related
details in the past 10
years. Incidence data
was calculated using
survey responses.
The survey had
100% response rate.
Data received
showed that the
incidence of
propofol abuse
among
anesthesia
providers was
10 per 10,000.
18% of
departments
had at least one
incidence of
propofol abuse,
the mortality
rate for
propofol abuse
was 28%, and
lack of control
of propofol was
significantly
associated with
diversion and
abuse.
Implementing control of propofol
may lead to a decrease in
diversion, abuse, and overdose
deaths.

Earley, P. H., &
Finver, T. (2013).
Addiction to
propofol: a study of
22 treatment cases.
Journal of addiction
medicine, 7(3), 169–
176.
https://doi.org/10.10
97/ADM.0b013e318
Those who abuse
propofol are more
likely to have easy
and frequent
access to the drug,
such as
anesthesiologists
and CRNAs.
Qualitative and
Quantitative
The authors reviewed
a large database of
cases of health care
providers in
substance abuse
treatment at a large
addiction center.
Medical records of
those who abused
propofol were
Health care
providers in
SUD treatment
who abused
propofol were
most likely to
work in the
OR, with the
majority
trained as
Establishing that ease of access as
an important factor in abuse
incidence of propofol. The
profession of anesthesia is
significantly at risk for
developing propofol misuse as
compared to other occupations.
THE RECLASSIFICATION OF PROPOFOL AS A CONTROLLED DRUG

31
2872901 examined, compared,
and results were
drawn from the data.
anesthesia
providers.
Bonnet, U., &
Scherbaum, N.
(2012). Craving
dominates propofol
addiction of an
affected physician.
Journal of
psychoactive drugs,
44(2), 186–190.
https://doi.org/10.10
80/02791072.2012.6
84635
A case study of an
anesthesia resident
misusing propofol.
Qualitative and
Quantitative
The authors
examined the case of
a 30-year-old male
by reviewing
inpatient records and
comparing the results
with criteria for
criteria to
dependence on
hypnotics
Based on
evidence from
an addicted
anesthesia
resident,
propofol may
have a greater
propensity for
addiction than
previously
assumed. The
patient
experienced
intense
cravings for
propofol and
other
physiological
dependence
symptoms
consistent with
SUD
Establishes anecdotal evidence of
physiological dependence on
propofol in humans

Abstract (if available)

Abstract The misuse and abuse of propofol, a widely used anesthetic drug, is prevalent among anesthesia providers. The unique pharmacologic properties of propofol make it particularly dangerous when administered outside of a monitored environment. Research shows that the pharmacology of propofol, the neurobiology of addiction, and ease of access are driving factors behind its abuse in the anesthesia profession. Overdose and death have been associated with the misuse of propofol by anesthesia providers. Currently, propofol is not classified as a controlled substance by the US DEA. This paper makes a case to reclassify propofol as a Schedule IV controlled substance and reviews how doing so will reduce ease of access and subsequent abuse.

Linked assets

University of Southern California Dissertations and Theses

Conceptually similar

PDF

The reclassification of propofol as a controlled drug: a comprehensive literature review and recommendations for practice

PDF

The reclassification of propofol as a controlled drug: a comprehensive literature review and recommendations for practice

PDF

Development of an educational toolkit for environmentally sustainable propofol disposal among nurse anesthesia providers

PDF

Wellness programs for healthcare graduate students: a literature review with recommendations for nurse anesthesia programs

PDF

Effective methods for addressing psychological challenges among anesthesia providers returning from practice in austere environments: a literature review with professional recommendations

PDF

Airway fire: extensive literature review and practice recommendations

PDF

Capnography monitoring requirement increases patient safety in non-operating locations: an extensive literature review with practice recommendations

PDF

Development of an educational toolkit for environmentally sustainable propofol disposal among nurse anesthesia providers

PDF

Best practice recommendations for anesthesia providers managing surgical patients on buprenorphine medication assisted treatment

PDF

The emotional and psychological response of healthcare providers involved in organ procurement: a literature review with practice recommendations for certified registered nurse anesthetists

PDF

Recommendations and template for an active shooter protocol in the operating room: an integrative review

PDF

The emotional and psychological response of healthcare providers involved in organ procurement: a literature review with practice recommendations for certified registered nurse anesthetists

PDF

Ketamine for complex regional pain syndrome: an integrated literature review with practice recommendations

PDF

Ketamine for Complex Regional Pain Syndrome: an integrated literature review with practice recommendations

PDF

Airway fire: extensive literature review and practice recommendations

PDF

Emergence delirium prevention in American veterans diagnosed with post-traumatic stress disorder: a critical literature review with practice recommendations

PDF

Airway fire: extensive literature review and practice recommendations

PDF

The harmful environmental effects of anesthetic gases: a literature review with practice recommendations

PDF

The harmful environmental effect of anesthetic gases: a literature review with practice recommendations

PDF

Current state of perioperative medication management of methadone, buprenorphine and naltrexone

Asset Metadata

Creator Flanders, Summer (author)

Core Title The reclassification of propofol as a controlled drug: a comprehensive literature review and recommendations for practice

School Keck School of Medicine

Degree Doctor of Nurse Anesthesia Practice

Degree Program Nurse Anesthesiology

Publication Date 04/05/2021

Defense Date 04/03/2021

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag Abuse,Addiction,anesthesia,certified registered nurse anesthetist,controlled drug,controlled substance,CRNA,DEA,drug,drugs of abuse,misuse,nurse anesthesia,nurse anesthetist,OAI-PMH Harvest,propofol,reclassification,reclassify,Schedule IV,substance use,substance use disorder

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Bamgbose, Elizabeth (committee chair), Griffis, Charles (committee chair), Hogan, Jennifer (committee chair)

Creator Email sflander@usc.edu,summerflanders@gmail.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c89-435860

Unique identifier UC11666715

Identifier etd-FlandersSu-9399.pdf (filename),usctheses-c89-435860 (legacy record id)

Legacy Identifier etd-FlandersSu-9399.pdf

Dmrecord 435860

Document Type Capstone project

Rights Flanders, Summer

Type texts

Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the a...

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus MC 2810, 3434 South Grand Avenue, 2nd Floor, Los Angeles, California 90089-2810, USA