FIFTEEN years after the original article, “Opioid Addiction in Anesthesiology,” was published, addiction still remains a major issue in the anesthesia workplace. Between 1991 and 2001, 80% of US anesthesiology residency programs reported experience with impaired residents, and 19% reported at least one pretreatment fatality. Substantial advances have occurred in our understanding of addiction as well as both the technology and therapeutic approaches used to fight this disease, although outcomes have not appreciably changed. Starting with a brief review of the basic concepts of addiction, this article highlights the current thoughts regarding the pathophysiologic basis of addiction, as well as clinical manifestations, legal issues, and treatment strategies. Anesthesiologists (as well as any physician) may suffer from addiction to any number of substances, though addiction to opioids remains the most common. As recently as 2005, the drug of choice for anesthesiologists entering treatment was an opioid, with fentanyl and sufentanil topping the list. Other agents, such as propofol, ketamine, sodium thiopental, lidocaine, nitrous oxide, and the potent volatile anesthetics, are less frequently abused but have documented abuse potential. Alcoholism and other forms of impairment impact anesthesiologists at rates similar to those in other professions. Factors that have been proposed to explain the high incidence of drug abuse among anesthesiologists include the proximity to large quantities of highly addictive drugs, the relative ease of diverting particularly small quantities of these agents for personal use, the high-stress environment in which anesthesiologists work, and exposure in the workplace that sensitizes the reward pathways in the brain and thus promotes substance abuse. It is not the purpose of this article to present a manual for the treatment of addiction. Treatment should be administered by qualified personnel. All anesthesia personnel, however, should be aware of the basic nature of the problem and possess the necessary information to recognize and assist an impaired colleague. Prevalence There are limited data available to determine the current prevalence of drug use by anesthesia personnel. Records of disciplinary actions, mortality statistics, and registries for known addicts provide some information, but it is difficult to interpret these types of data in that there is no guarantee that all cases are reported and the total population out of which the reports emanate is rarely available. In the past, it had been concluded that the true prevalence of addiction in physicians is unknown, though it had been suggested that drug abuse is at least as prevalent as among the general population. A review of 1,000 treated physicians conducted by Talbott et al in 1987 suggested that addiction is common among anesthesiologists. Anesthesia residents represented 33.7% of all residents presenting for treatment but composed only 4.6% of all US resident physicians at the time of the study, thus presenting an apparent 4-fold increased prevalence of anesthesia residents in the study population. Subsequent studies have consistently differed from the results of Talbott et al . Five years later, a study by Hughes et al found the rate of substance abuse in the anesthesia resident population to be no higher than that of other specialties. Interestingly, this same study showed higher rates of substance abuse among emergency medicine and psychiatry residents. In 2000, Alexander et al . published a study examining the cause-specific mortality risks of anesthesiologists that suggested that the risk of drug-related death among anesthesiologists is highest in the first 5 yr after medical school graduation, and remains increased over that of other physicians. Most recently, a survey conducted in 2002 by Booth et al . found the incidence of known drug abuse among anesthesia personnel to be 1.0% among faculty members and 1.6% among residents. Etiology In 1956, the American Medical Association declared alcoholism to be an illness, and in 1987, it extended the declaration to include dependence on all drugs. There have been many theories regarding the etiology of chemical dependence, including biochemical, genetic, psychiatric, and, more recently, exposure-related theories.6 None alone has been able to identify specific causes, only to suggest what may increase the risk of developing addiction among anesthesia personnel. Genetic and Biochemical Theories Considerable research done in mice suggests a genetic basis for addiction. Tapper et al . engineered mutant mice with α4nicotinic subunits that contained a single point mutation, Leu9′→ Ala9′, in the pore-forming M2 domain. The resulting nicotinic acetylcholine receptors were hypersensitive to nicotine, with the mutant mice exhibiting reinforcement in response to acute low-dose nicotine administration. It is this exaggerated response to lower levels of stimuli that is thought to be important in the development of dependence in susceptible individuals. Tolerance and sensitization elicited by chronic nicotine administration were also observed, suggesting the possibility that behaviors associated with the use of drugs of abuse may be reinforced by much smaller doses in some persons who are genetically susceptible but not in others who do not share this genetic predisposition. There is strong evidence to suggest that drugs of abuse that activate the reward structures in the brain induce lasting changes in behavior that reflect changes in neuron physiology and biochemistry. Although the majority of individuals who experiment with psychoactive substances do not become dependent, there exists a subset of individuals who do. These individuals typically exhibit preexisting comorbid traits such as novelty-seeking and antisocial behavior, and there seems to be a genetic basis for both the susceptibility to dependence and these comorbid traits. According to one recent study, this genetic susceptibility plays a role in the transition from substance use to dependence and from chronic use to addiction. Many genes have been identified as possibly playing a role in the susceptibility to drug addiction, but as of this publication, investigators have been able to identify a functional mechanism related to the specific effects of abused drugs in only a few. Release of the neurotransmitter dopamine in the mesolimbic system of the brain is involved with the reinforcement of drug-seeking behaviors associated with several drugs of abuse, including nicotine. Picciotto et al . reported on mice lacking the β2subunit of the high-affinity neuronal nicotinic acetylcholine receptor. They found that mesencephalic dopaminergic neurons from mice without the β2subunit did not respond to nicotine, as did neurons from wild-type mice. The self-administration of nicotine was observed to be attenuated in these mutant mice. In humans, the cholinergic muscarinic 2 receptor has been associated with the function of memory and cognition. Wang et al . reported that variation in the gene responsible for the production of this receptor predisposed to both alcohol dependence and major depressive syndrome. Luo et al . looked at the relations between the variations in the cholinergic muscarinic 2 receptor gene and alcohol dependence, drug dependence, and affective disorders in a population of 871 subjects and identified specific alleles, genotypes, haplotypes, and diplotypes significantly associated with risk for either dependence or affective disorders. Because there is empirical evidence that the disorders of substance abuse are prevalent within multiple generations of some families, it makes sense that there should be some associated genetic component. How much of a role this component plays in the development of the disease is not yet known, because there are many factors that contribute to the development of a substance use disorder in a predisposed individual. Psychiatric Comorbid Conditions There is considerable association between chemical dependence and other psychopathology. A 1991 review of the data found personality disorders in 57 of 100 substance abusers. Of physicians admitted to one inpatient drug/alcohol treatment facility in 1984, 5.9% had a primary psychiatric diagnosis as well as chemical dependence. Therefore, it has been suggested that one source of motivation for the self-administration of drugs of abuse is the self-medication of symptoms associated with comorbid psychiatric disorders. The observation that individuals with the same personality traits tend to self-administer drugs from the same class, i.e ., opioids for anxiety and depression and amphetamines for attention deficit and hyperactivity states, lends credence to this theory. Individuals under evaluation for or treatment for substance abuse should have an evaluation with subsequent management of comorbid psychiatric conditions. Exposure-related Theories It has been suggested that emotional stress and access to agents may play much less of a role in the development of addiction than was previously thought. Gold et al .presented the hypothesis that the increased risk of addiction in certain occupational settings, such as within the practice of anesthesiology, is related to exposures that sensitize the reward pathways in the brain to promote substance use. It is known that drugs of abuse physically alter the chemistry of the addicted brain, changing the relative levels of the neurotransmitters γ-aminobutyric acid, dopamine, and serotonin associated with reward pathways such that drug-seeking behavior is favored over the rational evaluation of the risks of such actions. Gold et al . suggest that anesthesiologists who become addicted through such sensitization in the workplace may continue to use the agents to alleviate the withdrawal they feel when away from the exposure. The evidence to suggest this mechanism of addiction is based on the observation that low doses of opiate drugs can induce sensitization, and these agents are present and measurable in the exhaled breath of patients receiving them. However, these chemical changes result from levels of exposure typically associated with active use of drugs of abuse and not from the trace levels found in the work environment, and it is not made clear how the transition to active use of these agents occurs. This is certainly a novel and relatively new idea, and considerable research needs to be conducted in this area before any conclusions can be made regarding its validity. Clinical Manifestations Although not one of the specific criteria for diagnosis of drug-related disorders, denial can present a major obstacle to treatment of the addicted physician. The addict does not recognize that he or she has a problem, and treatment is seldom spontaneously sought. Denial is not lessened by education and training, and some have even suggested that physicians and other highly educated and highly functioning addicts may have a well-developed denial mechanism in place. Physician–patients are often described as having grandiose ideas of invulnerability and self-sufficiency, and as unable to accept that abuse leads to addiction and that addiction is loss of autonomy. Denial is not limited to the addict. Coworkers, friends, relatives, and associates will often make excuses for or prefer not to deal with the impaired physician. It can be difficult to accept that a problem in a colleague is a result of addiction, but failure to initiate an investigation because of “uncertainty” masked as concern for the individual is denial. Behavior Patterns Because of the unique proximity of the chemically dependent anesthesiologist to his or her drug of choice while at work, behaviors that would arouse suspicion in another setting may make the addicted physician seem quite functional. The addicted anesthesiologist becomes extraordinarily attentive at work as maintaining a job in close proximity to the source of drugs becomes more important than aspects of the individual’s personal life. Changes in behavior are frequently noted, with periods of irritability, anger, euphoria, and depression common. Often it is the individual with this disorder who is the last to recognize that a problem exists. It is therefore imperative that those people most likely to observe the signs and symptoms of addiction, i.e ., the relatives, friends, and coworkers, gain a clear understanding of the disease and understand what to do if they suspect someone may have a problem. Early identification of the affected individual can often prevent harm, both to the impaired physician and to his or her patients. Early detection is often difficult because of the compartmentalized relationships the individual may have with different members of their social structure. The spouse of an addict may observe behavioral changes that may pass unnoticed by colleagues at work, and the entire picture is seldom appreciated by any one person. Some of the changes typically observed in the affected anesthesiologist include but are not limited to the following : Withdrawal from family, friends, and leisure activities Mood swings, with periods of depression alternating with periods of euphoria Increased episodes of anger, irritability, and hostility Spending more time at the hospital, even when off duty Volunteering for extra call Refusing relief for lunch or coffee breaks Requesting frequent bathroom breaks Signing out increasing amounts of narcotics or quantities inappropriate for the given case Weight loss and pale skin The period of time over which these changes are manifested depends on the drug to which the individual has become addicted. Alcohol addiction typically takes years to become apparent, whereas addiction to the short-acting opioids, fentanyl and especially sufentanil, becomes apparent over the course of a few months of use. So powerful is the disease of addiction and the need for the drug that otherwise reasonable and intelligent people will resort to seemingly incredulous behavior to obtain their drug of choice. Addicts may chart the use of an agent when in fact either an alternate agent or none at all was administered. Entire cases may be done with inhalational agents and β-blockers and charted as opioid based. Addicts may substitute a syringe containing their drug of choice for one containing saline or a mixture of lidocaine and esmolol during a relief break. Some have admitted to rummaging through sharps containers looking for residual drug in discarded syringes. Addicts quickly become proficient at removing controlled substances from secure places. The security features of automated dispensing machines are easily defeated, and drugs may be removed from glass ampules and replaced with another liquid without evidence of tampering. Depending on the half-life of the abused agent, tolerance can develop rapidly. It is not uncommon for the addict in recovery to report self-administration of 1,000 μg fentanyl in a single injection, often simply to relieve the symptoms of withdrawal. When looking over the records of an addicted anesthesiologist, an increase in the quantity of opioids requested, particularly on Fridays, can often be noted.