May, Judith A. MD*,; White, Herbert C. DO§,; Leonard-White, Ardis MA§,; Warltier, David C. MD, PhD*†‡,; Pagel, Paul S. MD, PhD*‡
The perioperative implications of patients acutely intoxicated with or chronically abusing alcohol or drugs are well known to the anesthesiologist (1,2). However, little data have been collected, and few opinions stated, about the special issues of recovering patients. A single case report (3) describing the management of a recovering alcoholic undergoing cosmetic surgery is the only article in the peer-review medical literature to address recovery and elective surgery. The interactions between recovery and pain management are also incompletely described (4–7). Importantly, no prospective clinical trials have been conducted to guide the perioperative management of the recovering patient. The lifetime prevalence of alcohol and drug addiction is estimated to be approximately 14% and 7%, respectively, of the United States population (8). Long-term abstinence rates are >50% for recovering alcoholics and range between 30% and 50% for opioid and cocaine addicts with appropriate treatment (9), suggesting that there are at least several million individuals presently in recovery (10). An understanding of the pathophysiology of addiction, the process of recovery, and the possible interventions that may be instituted to minimize the risk of relapse contribute to the successful management of these patients.
Addiction: A Chronic Relapsing Disease
Addiction is defined by loss of control over an abusable substance, including an inability to voluntarily self-regulate drug use, compulsive preoccupation with obtaining or using a drug, and continued use despite adverse consequences (11). Addiction develops as a result of interactions between genetic predisposition, environmental and psychosocial factors, and drug exposure (4), and has a highly variable clinical course. Initial drug use is voluntary behavior, and most users do not develop drug dependence (12). However, repeated drug use in a susceptible individual produces pathological alterations in brain function that lead to addiction. Genetic predisposition to addiction may be related to fundamental alterations in neurocircuitry that enhance sensitivity to the reinforcing effects of drugs of abuse (13) and overwhelm cognitive control of behavior (14). A patient may enter recovery with abstinence and treatment, but once present, addictive disease is regarded as permanent. Nevertheless, addictive disease may be managed successfully, and many patients respond positively to treatment with long periods of abstinence (15).
The neurobiology of addiction is summarized in several reviews (12,16,17). Three concepts of relevance to anesthesiologists may be gleaned from this extensive experimental literature: uniform drug reward and reinforcement, cross-addiction, and disease permanence. The mesocorticolimbic dopamine system (Fig. 1) is central to the pathophysiology of addiction and relapse (16). This neurocircuitry involves the ventral tegmental area of the midbrain where dopaminergic neurons originate, and the basal forebrain, the nucleus accumbens, and the amygdala to which these neurons project (18). All drugs abused by humans have been shown in animals to interact with this system to produce reinforcement (12). Different pharmacological classes of drugs of abuse, including many of those routinely used by anesthesiologists, may initially activate different locations within the reinforcement cascade by several mechanisms, but all lead to reward stimulation (16). As a result, exposure to one drug may mimic the reinforcing effects of another; this phenomenon is termed “cross-addiction.” Permanent alterations in reinforcement neurocircuitry also appear to persist despite long-term abstinence, and support the clinical notion of addiction as a chronic, incurable disease (15,17). These data further suggest that the administration of drugs of abuse commonly used during and after anesthesia may reactivate addiction regardless of the relative length of abstinence.
What is Recovery?
Recovery is a complex process requiring intense, continuous personal effort that not only involves abstinence but also requires a series of changes to maintain sobriety (Table 1). Successful recovery requires acquisition of knowledge about substance-abuse disorders, renewal of self-esteem and personal responsibility, development of sober living abilities and social interactions, identification with sources of inspiration, and a unified approach to guide these changes (19). The terms “cured,” “former,” “recovered,” and “ex-” addict are not appropriate to describe the recovering patient. The incidence of relapse appears to be inversely related to the duration of recovery (9), but return to use has been observed in patients with decades of recovery. Abstinence alone does not constitute recovery because effective skills for coping with stress independent of drug ideation (e.g., craving) or use may not have been developed (4). Whether an abstinent individual has more difficulty coping with the operative experience than a patient in a well-established recovery program is unknown, however.
Mutual-help organizations, including Alcoholics Anonymous (AA) and other Twelve-Step programs, individual psychotherapy, behavioral modification, and pharmacological therapy, may all be effective in the management of addictive disease (20,21). The standard of care (22) in addiction treatment in the United States is based on the Minnesota Model (23), a multidisciplinary approach that includes involvement in a Twelve-Step program, individual and group psychotherapy, patient and family education, vocational rehabilitation, and spiritual renewal. Treatment within the Minnesota Model relies primarily on the experience of other recovering patients. AA and related groups are fellowships of recovering patients who help each other maintain sobriety (24). The Twelve Steps are the central tenet of the AA program that serve as guidelines for recovery (Table 2). Other components of recovery within AA include regular meeting attendance and sponsorship that increase the probability of maintaining sobriety (25).
Adjuvant Drug Therapy for Relapse Prevention
Several medications are presently used in sobriety maintenance therapy that may have important implications for the anesthesiologist (Table 3). Strategies include alteration of a drug’s metabolic consequences (e.g., disulfiram in alcoholism), reduction of drug reward (e.g., acamprosate in alcoholism), receptor antagonism (e.g., naltrexone in opioid addiction), and drug-substitution therapy (e.g., methadone in refractory opioid addiction) (26). Several drugs have documented efficacy in the treatment of patients with alcohol or opioid addiction, but effective pharmacological therapy for addiction to other drugs of abuse has yet to be demonstrated (27). A more frequent incidence of anxiety, psychotic, and affective disorders is also observed in recovering patients (28). Psychoactive drugs used to treat these concurrent disorders reduce the incidence of relapse by decreasing self-medication of psychiatric symptoms (29) and may also have anesthetic consequences that are reviewed elsewhere (30).
Disulfiram is an alcohol-sensitizing drug that is still occasionally used in the treatment of alcoholism (31). Disulfiram inhibits aldehyde dehydrogenase (32), leading to acetaldehyde accumulation and a severe aversive reaction when alcohol is ingested. Disulfiram also irreversibly inhibits other sulfhydryl-based enzyme systems responsible for drug metabolism (33). Inhibition of dopamine β-hydroxylase by disulfiram reduces presynaptic neuronal synthesis of norepinephrine and may produce an attenuated cardiovascular response to indirect-acting sympathomimetic amines. Disulfiram also reduces the clearance of diazepam, midazolam, and chlordiazepoxide and interferes with the metabolism of barbiturates, tricyclic antidepressants, phenytoin, and warfarin by inhibiting hepatic microsomal enzymes (34). Calcium carbimide is another alcohol-sensitizing drug used clinically in Europe and Canada that reversibly inhibits alcohol dehydrogenase and may cause less-pronounced drug interactions (35).
The μ opioid receptor antagonists, naltrexone and nalmefene, reduce alcohol ideation and decrease the incidence of relapse in recovering alcoholics (36–38). Clinical experience with naltrexone and nalmefene has been less successful in opioid addiction, but may be used as “insurance” in abstinence-based recovery (39). Naltrexone and nalmefene increase the threshold dose of opioid required to produce euphoria (40). The recovering patient who continues to receive an opioid antagonist during the perioperative period will have an increased requirement for opioid analgesics. Conversely, the μ receptor is up-regulated during chronic opioid antagonist treatment, and withdrawal of naltrexone or nalmefene is associated with increased sensitivity to opioid agonists (40).
Acamprosate is an amino acid derivative that substantially reduces ideation (41) and improves treatment retention (42) in recovering alcoholics. Acamprosate may decrease neuronal hyperexcitability caused by chronic alcohol abuse (43), a phenomenon known as “limbic kindling”(44), by altering γ-aminobutyric acid- and glutamate-mediated neurotransmission (45). The anesthetic implications of acamprosate are unknown. Antiepileptics, including carbamazepine (46), valproate (47), and gabapentin (48) are also thought to attenuate alcohol- or opioid-mediated limbic kindling. Carbamazepine and other antiepileptics hasten recovery from intermediate- and long-acting nondepolarizing muscle relaxants (49) by enhancing the clearance of these drugs, increasing plasma concentrations of α1-acid glycoprotein, and producing proliferation of postsynaptic acetylcholine receptors (50). Selective serotonin reuptake inhibitors appear to reduce drinking in alcoholics with depression (51) and may also prevent relapse (52) in recovering patients with anxiety or affective disorders (53). Profound bradycardia and severe hypotension during anesthesia have been rarely reported in patients treated with these drugs (54).
Methadone (55), the long-acting μ agonist levo-α acetyl methadyl (LAAM) (56), and the partial agonist buprenorphine (57), have been used effectively in the treatment of patients with opioid addiction as substitution pharmacotherapy in combination with behavioral interventions. Methadone, LAAM, and buprenorphine decrease withdrawal symptoms, inhibit drug ideation, and attenuate the positive reward associated with subsequent opioid use (58,59). Clearly, patients chronically treated with methadone, LAAM, or buprenorphine remain physically dependent on opioids despite attenuation of addictive behavior. Thus, verification of the dose of methadone, LAAM, or buprenorphine with the patient’s addiction specialist before surgery, and unconditional administration of the drug throughout the perioperative period to prevent withdrawal, are required. Patients receiving opioid substitution therapy experience normal pain responses to nociceptive stimuli (60) and require supplemental analgesia for control of surgical pain. Substituting a new opioid for methadone, LAAM, or buprenorphine for maintenance therapy during the perioperative period is probably inappropriate. Increasing the dose or frequency of administration of these drugs to manage acute pain is also not recommended because the boundaries between treatment of addiction and pain may be obscured (4).
Potential Challenges to Recovery Posed by the Perioperative Experience
Anesthesia and surgery may expose the recovering patient to several potential obstacles that increase the possibility of relapse. Numerous anecdotal descriptions of profound drug craving or frank relapse have been reported after brief perioperative exposure to sedatives or opioids in recovering patients with years of sobriety (5,61) (JAM, HCW, and ALW; personal observations), but the precise incidence of such phenomena has not been formally defined. Anxiety about the perioperative experience may be heightened in the recovering patient because of concerns about the possibility for relapse and the fear that pain will not be adequately treated because of the history of addiction (62). Anxiety and pain have been identified as important precipitants of relapse (63), and inadequate treatment of pain can facilitate drug ideation (5). Recovering patients may also display abnormal behavioral responses to stress that increase the risk of relapse (64).
The recovering patient may encounter new physicians during the surgical experience whose attitudes about, and treatment of, patients with addictive disease are prejudicial (65). Negative attitudes, including discrimination, cynicism about recovery, and lack of compassion, may further compound low patient self esteem. Educational deficiencies (66) and identification of addiction within a moral model (67) or as a consequence of underlying psychopathology (68) are frequent causes of negative attitudes about addiction. Surgeons unfortunately have the weakest educational background and the least desire to learn about treatment resources compared with psychiatrists and internists (69). Conversely, other well intentioned physicians may withhold or restrict pain medication from the recovering patient fearing that a relapse will be inadvertently provoked. The reluctance to provide analgesia because of fears about “causing” addiction (70) is a major reason for the undertreatment of pain, even in patients with widely metastatic cancer (71). The recovering patient may be left inadequately treated, a situation that may be further complicated if justified requests for additional analgesics are misinterpreted as addictive behavior.
The preoperative evaluation allows the anesthesiologist to obtain a detailed history of addiction and recovery and provides an opportunity to reduce anxiety about the operative experience (Table 4). Many patients will openly disclose their addictive disease and recovery, but others may be reticent to acknowledge this history because they are apprehensive about possible discrimination. Under these circumstances, the history of addiction and recovery may be elicited by tactfully asking direct questions in response to negative answers to routine inquiries about alcohol or drug use. The history of alcohol or drug abuse, type and quality of, and compliance with, a recovery program, and participation in mutual-help groups, are important components of the medical history. Involvement of an addictionologist, rehabilitation counselor, or sponsor in the patient’s recovery should be noted, the duration and relative success of recovery explored, and the history of and apparent factors responsible for triggering relapse episodes identified. Encouraging the patient to intensify the practices of their recovery program has been recommended because the patient’s support system is a powerful defense against relapse during periods of stress (5).
Much of the end-organ damage that occurs as a result of chronic substance abuse is reversible with long-term abstinence, but some permanent pathology may remain that requires further evaluation or stabilization before surgery. A urine drug screen may be indicated to exclude drug use and identify the need for further referral. Most recovering patients are aware that many drugs used for premedication have abuse potential and may refuse premedicants on these grounds. Patients familiar with biofeedback, guided imagery, or meditation may want to use these relaxation techniques instead of drug therapy. Some addictionologists have argued that premedication should be avoided because euphoria associated with drug administration may stimulate ideation (61). Conversely, use of pharmacological therapy to control anxiety is appropriate because increased apprehension (63) and exaggerated stress responses (64) may be present in the recovering patient. Twelve-Step meetings and increased sponsor contact may also be useful anxiolytics for the recovering patient.
Regional anesthetic techniques have been strongly advocated based on anecdotal reports (3,61). Whether regional anesthesia actually reduces the incidence of drug ideation or relapse compared with general anesthesia has yet to be evaluated in prospective clinical trials. Regional anesthesia using local anesthetics provides a theoretical advantage for the recovering patient by reducing or eliminating exposure to other drugs. A continuous regional anesthetic technique may also be used for analgesia in the postoperative period. Despite these potential advantages, regional anesthesia is not uniformly successful, is inadequate for many surgical procedures, and has well established contraindications that may preclude its use. It appears likely that all types of general anesthesia, including opioid-based and balanced techniques, may be safely performed because drug exposure alone represents only one of several factors that contributes to the risk of relapse.
A clear strategy for pain management should be established before surgery. Reassurance that the history of addiction will not be an obstacle to adequate treatment of postoperative pain, and the anesthesiologist’s broad expertise in pain management, deserve strong emphasis. Analgesics without abuse potential may be initially used for the relief of postoperative pain (61). These drugs may be used with or without continuous regional local anesthesia or selective nerve blocks in some recovering patients to provide adequate pain control and may also serve to reduce opioid analgesic requirements. Alternative pain modalities may also be considered. Importantly, the potential benefits of these methods must be weighed against the risk of inadequate analgesia, a significant factor in precipitating relapse (4). Opioids are the most effective clinically available analgesics for treatment of surgical pain. Use of opioids should be guided by specific clinical indications. The selection of the specific type of opioid and the route of administration may be less important than the scheduling of administration (4,6). Mixed opioid agonist-antagonists theoretically offer a reduced risk of abuse than pure μ agonists (72,73), but these drugs are not completely devoid of abuse potential and do not provide clear benefits over μ agonists for postoperative analgesia (74). Neuraxial administration of opioids has been advocated (61) because of theoretical reductions in the incidence of euphoria and the potential for associated drug craving, but this hypothesis has not been rigorously investigated. Scheduled administration of opioids or patient controlled analgesia (by IV or epidural routes) may provide benefits over pro re nata (PRN) dosing in the recovering patient by simplifying the pain management plan for nursing staff, reducing delays in drug administration that contribute to inadequate analgesia, and eliminating patient requests for opioids that may be misinterpreted as addictive behavior (4,6). However, the use of patient controlled analgesia in recovering patients is controversial because of the dynamics of self-administration (61). Prescription of opioids solely on a PRN basis is not recommended in order to reduce associations between pain symptoms and the administration of a reinforcing drug (6) that may increase overall pain perception and inappropriately justify greater drug use (75).
The recovering patient’s behavioral responses to pain management require regular evaluation by physicians and nursing staff. Abnormal attitudes or conduct that signify drug ideation or loss of control over pain medications need to be identified as early as possible. However, unusual behavior specifically related to pain therapy may instead indicate the presence of pseudoaddiction (76), a phenomenon that refers to drug-seeking behavior related to inadequate analgesia. In contrast to true addiction, pseudoaddiction is characterized by extinction of aberrant behavior when adequate analgesia is achieved (76).
Under ideal circumstances, the recovering patient will no longer require opioid analgesics and be completely free of all drugs of abuse before discharge (3), but this goal may be unrealistic during ambulatory surgery or brief hospitalization. Prescription and dispensation of opioids for outpatient analgesia pose a significant risk. Reassuring the patient that opioids may be safely administered after discharge while minimizing the risk of relapse is important. A single, limited-quantity prescription in a scheduled dose that provides adequate analgesia without euphoria or sedation is recommended (4). Unsupervised self-administration or unrestricted access to opioids by the patient is clearly not recommended. Instead, an impartial individual, such as a family member, close friend, or sponsor, familiar with the patient’s recovery, may be better suited to dispense the prescribed opioid, keep an accurate record of use, and dispose of unused medication. Frequent contact between the patient, the dispensing individual, and the prescribing physician, facilitates evaluation about the quality of analgesia, the progress of postoperative recovery, and the potential appearance of drug ideation (3,4).
The recovering patient presents the anesthesiologist with many challenges, but information presently available to guide perioperative management is limited. Future research will need to address a series of questions and hypotheses from a purely observational level to clinical trials (Table 5). Collaboration between addictionologists and anesthesiologists based on common interests, such as neurophysiology, the pharmacology of drugs of abuse, and the pathophysiological consequences of addiction, will facilitate these research objectives.
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