Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

CHAPTER 15 – Behavioral and Psychiatric Disorders

Alan D. Kaye, MD, PhD, DABPM,
Jason M. Hoover, MD,
Robert A. Ertner, MD,
Patricia B. Sutker, PhD

  

 

Epidemiology of Mental Disorders

  

 

Characterization of Mental Disorders

  

 

General Approaches to Preoperative Evaluation of Patients with Mental Disorders

  

 

Mood Disorders

  

 

Major Depression

  

 

Dysthymic Disorder

  

 

Bipolar Disorders

  

 

Anxiety Disorders

  

 

Generalized Anxiety Disorder

  

 

Social Phobia

  

 

Obsessive-Compulsive Disorder

  

 

Post-traumatic Stress Disorder

  

 

Panic Attacks

  

 

Nonaffective Psychoses

  

 

Schizophrenia

  

 

Delusion Disorder

  

 

Substance-Related Disorders

  

 

Delirium, Dementia, and Other Cognitive Disorders

  

 

Delirium

  

 

Dementia

  

 

Other Cognitive Disorders

  

 

Disorders Identified in Developmental Stages

  

 

Mental Retardation

  

 

Attention-Deficit/Hyperactivity Disorder

  

 

Problem Behaviors in Late Life

  

 

Conclusion

Mental illnesses, or mental, personality, and cognitive disorders that interfere seriously with life activities and abilities to function, constitute a pervasive and prevalent health problem among varied American population subsets, including the young and the elderly. The presence of mental disorders, associated symptoms, possible concomitant pathology, and prescribed medications are of significance to all health care providers and not simply those in the field of mental health. Against the backdrop of rates and patterns of ill health and disability, the burden of mental disorders on health care utilization and effectiveness has become a topic of worldwide interest.[1] Beyond concerns about treatment adequacy for mental illnesses globally and in the United States there are considerations regarding management of the seriously mentally ill in emergency care and inpatient treatment situations, general medicine, family practice and pain clinics, and the surgical theater.[2] Important to anesthesiologists managing patient care is knowledge about patient mental and physical illnesses; histories of alcohol, drug, and tobacco use; the abuse and use of prescription medications, over-the-counter drugs, and herbal products; previous physical and mental traumas; and potential areas of cognitive impairment or compromise before, during, and after surgical procedures and in other treatment circumstances. It is important that anesthesiologists recognize the factors involved in determining the presence of the true mental disorder, because certain medical conditions can mimic psychiatric disturbances ( Table 15-1 ).[3]

The presence of mental disorders and the associated use of psychotropic medications, including antidepressants, anxiolytic drugs, major tranquilizers, and anticonvulsants and mood stabilizers introduce neurochemical, behavioral, cognitive, and emotional factors that increase the complexity of medical or surgical tasks. For example, patients with mental disorders may not communicate well about their diseases, symptoms, medications, and history; may present with difficult behaviors; and often bring a background of polypharmacy that requires unraveling.[4] The use of psychotropic medications has increased over each decade, with psychiatrists and family practice physicians prescribing tranquilizers, neuroleptics, and antidepressants, even among youth. [5] [6] [7] In the case of depression alone complexities have been described in prescribing medications and understanding side effect and adverse effect profiles, as well as drug interactions with other medications prescribed for mental and physical problems. In this chapter we review the major types of mental disorders, describe disorder epidemiology and characteristics, and outline issues and concerns that face anesthesia care providers in planning case management. Specifically, information is provided concerning appropriate perioperative management of patients with mental disorders undergoing surgical procedures requiring anesthetic intervention.


TABLE 15-1   -- Medical Conditions That Can Mimic Psychiatric Disorders

  

 

Endocrine Abnormalities

  

 

Hypothyroidism

  

 

Cushing's syndrome

  

 

Alcohol and Drug Abuse

  

 

Neurologic Disorders

  

 

Seizure

  

 

Head trauma

  

 

Demyelinating disease

  

 

Central nervous system tumors

  

 

Encephalitis

  

 

Toxic and Metabolic Disorders

  

 

Vitamin B12 or folate deficiency

  

 

Anticholinergic toxicity

  

 

Drug-induced toxicity

  

 

Collagen Vascular Diseases

Adapted from Derrer SA, Helfaer MA: Evaluation of the psychiatric patient. In Rogers MC, Tinker JH, Covino BG, Longnecker DE (eds): Principles and Practice of Anesthesiology. St. Louis, Mosby, 1993, pp 567-574.

 

 

EPIDEMIOLOGY OF MENTAL DISORDERS

For more than two decades, scientists have applied detailed, structured lay interviews to diagnose mental disorders in community surveys and to determine the incidence and prevalence of serious mental illnesses. A landmark project collecting data from 1980 to 1985, called the Epidemiologic Catchment Area (ECA) study, interviewed more than 20,000 adults aged 18 years or older in five surveys, yielding data from 18,571 households and 2,290 institutionalized residents. The maximum combined sample size was 20,291 adults who were interviewed directly at wave 1, and 12 months later in wave 2, using the Diagnostic Interview Schedule and 1-month recall to determine psychiatric diagnoses. [8] [9] [10] Findings revealed that 15.7% of those surveyed suffered a mental or addictive disorder during the past month and 6.6% developed one or more new disorders after being assessed as having no previous lifetime diagnosis at wave 2, with an estimated annual mental or addictive disorder prevalence rate of 28.1%. Using application to the 1980 U.S. adult population, the researchers estimated that 44.7 million persons were affected by one or more mental or addictive disorders and 35.1 million by a nonaddictive mental disorder in the 1-year interval. Looking at the data differently, Bourdon and colleagues determined that in any 6-month period, 19.5% of the adult population, or one in five individuals, suffer a diagnosable mental disorder.[11]

Mandated by the U.S. Congress, the National Comorbidity Study (NCS) included administration of a structured psychiatric interview to a representative sample of noninstitutionalized persons aged 15 to 54 years in the 48 contiguous states and a survey of campus-housing students. Data were collected between 1990 and 1992 in 8,089 respondents. The study purpose was to assess comorbidity of substance use disorders and non-substance psychiatric disorders using a modified version of the Composite International Diagnostic Interview.[12] Morbidity rates were found to be higher than ECA estimates, possibly owing to methodologic and illness-defining differences in study implementation. Nevertheless, results were impressive toward developing an understanding of mental disorder prevalence and comorbidity. Nearly 50% of respondents reported at least one lifetime disorder, and almost 30% at least one 12-month disorder, the most common being a major depressive episode, alcohol dependence, social phobia, and simple phobia. Morbidity was concentrated in approximately one sixth of the population who evidenced history of three or more comorbid disorders.[13] Factors of age, race, socioeconomic status, gender, and geographic region influenced prevalence trends. For example, women were found to have elevated rates of affective and anxiety disorders compared with men, who showed higher rates of substance use disorders and antisocial personality. The majority of individuals with psychiatric disorders failed to obtain professional treatment, suggesting that patients with mental disorders may not be identified readily by medical health care providers.

Calling attention to the strong association between reduced health-related quality of life, diminished productivity, and high health care utilization, Hoge and colleagues studied hospitalizations among active-duty military personnel from 1990 to 1999 and ambulatory visits from 1996 to 1999.[14] Rates of hospitalization and ambulatory visits were examined over these 10- and 4-year periods across the entire military. As many as 4,815,864 active-duty personnel were studied, with women accounting for 12%. Considering that the military represents approximately 1% of the adult working U.S. population between the ages of 18 and 45, these data have particular interest. Mental disorder diagnoses were involved in 13% of hospitalizations, accounting for nearly a fourth of inpatient bed days. In a 1-year cohort of personnel, 47% of those hospitalized for the first time for a mental disorder left military service within 6 months, a rate different from that of 12% after hospitalization for any of 15 other disease categories. More than 6% of the entire active-duty population were reported to have received outpatient treatment for a mental disorder annually in 1998 and 1999. Data showed that the most common primary diagnoses were alcohol- and substance-related, adjustment, mood, and personality disorders. Researchers concluded that mental disorders represent the most important source of military medical and occupational morbidity, underscoring that mental disorders are common, disabling, and costly to individuals and society.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

CHARACTERIZATION OF MENTAL DISORDERS

Definition of mental disorders is taken from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), in which each of the disorders is conceptualized as a clinically significant behavioral or psychological syndrome associated with present distress or disability, or perhaps with significantly increased risk of suffering death, pain, disability, or loss of freedom.[15] As such, a disorder is a manifestation of a behavioral, psychological, or biologic dysfunction. Mental disorders in individuals constitute an enormous public health problem, interfering with life activities and functions and afflicting 5.4% of the U.S. adult population each year.[2] As stated by Wang and associates, Public Law 102-321 defines serious mental illness as the presence of any DSM mental disorder, substance use disorder, or developmental disorder that leads to “substantial interference” with “one or more major life activities.” In this framework, mood and anxiety disorders and nonaffective psychoses are characterized, in addition to substance abuse disorders, difficult-to-define personality disorders, and disorders affecting development and life course phenomena, such as those identified in infancy or childhood (e.g., mental retardation) and/or associated with physical trauma leading to organic brain syndrome, and cognitive disorders, such as dementia of mid to late life stages.

Other disorders of interest to the practicing clinician are mental disorders resulting from a general medical condition, somatoform disorders, and disorders of eating, sleep, impulse control, and adjustment. Attention has also been directed toward clarifying the clinical status of primary care patients with symptoms of mental distress that fall below the threshold criteria for a mental disorder. Olfson and coworkers found that in primary care patients, the morbidity of subthreshold symptoms was often explained by confounding mental, physical, or demographic factors.[16] Yet depressive symptoms and panic symptoms tended to be disabling, and patients with these symptoms were suggested to be at increased risk for development of major depression, even though they were a heterogeneous group.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

GENERAL APPROACHES TO PREOPERATIVE EVALUATION OF PATIENTS WITH MENTAL DISORDERS

Regardless of the pathologic process or processes with which patients present, assessment of patients with mental disorders presents unique challenges to clinical anesthesiologists. Many of these patients will not communicate well with anesthesiologists either because they choose not to (e.g., embarrassment, hostility) or because they are unable to do so (e.g., profound psychosis, delirium, memory disturbances). It may be difficult to establish rapport with such patients even if they seem otherwise cooperative. There are also issues involving patients' abilities to consent or refuse certain medical interventions.[3] Most often, when anesthesiologists are confronted with patients, they find it easy to obtain data from medical records concerning the patients' medical history, medications being taken, and previous medical interventions. In the case of patients with mental disorders, for the just-stated reasons, it is often more difficult to obtain this information. However, only in a minority of cases will patients with mental disorders present without clinicians having access to their medical records. When patient medical records are available, clinicians must review these records carefully and be prepared to measure the information obtained from them against patient-reported history. Often, patients' records provide more accurate information than can be obtained otherwise. Likewise, physicians may trust the objective data obtained from a careful physical examination more than the history obtained.[3]

In some cases, it is possible to obtain direct consultation with primary care physicians or psychiatrists in charge of care for patients with mental disorders. If this is possible, concerns that anesthesiologists may have concerning the care of patients in the perioperative period can be addressed directly. However, despite possible interactions that may exist between caretakers, an earnest attempt to establish rapport with patients must be sought, because the potential exists to minimize emotional trauma that might present itself within the operating theater.[3] In this regard, the role of anesthesiologists as consultants cannot be overstated. In some instances, patients may present for surgery with a disease entity that mimics psychopathology but has not been diagnosed. Appropriate history-taking skills, physical examination, and laboratory tests may reveal one of these disorders. Furthermore, many substances, including both illicit drugs and legal pharmaceuticals, may produce signs and symptoms that mimic psychiatric disease. Any organic cause for symptoms must be eliminated fastidiously before subjecting patients to anesthesia, because there is potential for adverse outcomes arising from inappropriate management of such disorders.[3]

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

MOOD DISORDERS

Major Depression

In the DSM-IV, disorders of mood are classified in terms of episodes, such as depressive and manic episodes, depressive disorders including major depression and dysthymia, bipolar disorders, and mood disorders associated with general medical conditions and/or substance abuse.[15] Specifiers can be added to describe severity, other features such as postpartum onset, and course of recurrent episodes. Among the mood disorders, major depression has been studied most often and found to be a frequent and disabling psychiatric disorder in the United States. The prevalence of major depression has been shown to be 14.9% for lifetime and 8.6% for 12 months, and a predominance of women to men has been demonstrated in both lifetime and 12-month cases.[17] As many as 74% of NCS respondents with lifetime depression showed one or more disorders, with anxiety (58%) and substance abuse (38%) disorders found to be most common. The prevalence of depression in cancer patients has been found to be two to three times the rate documented in the general population, and as many as 25% of extended care facility patients may suffer from major depression. [5] [18] [19] Major depression appears to have increased, reaching younger age persons, yet often going undetected and undiagnosed in all age groups.

In the 2001-2002 National Comorbidity Survey Replication (NCS-R), Kessler and colleagues reported the prevalence and correlates of major depression using DSM-IV criteria in 9,090 household residents aged 18 years and older.[20] They calculated a prevalence of lifetime major depression of 16.2% and of 6.6% for a 12-month period, estimated to affect 32 to 35 million and 13 to 14 million adults, respectively. Among other results, risk seemed to be low until the early teens, but depressive disorders occur throughout the life cycle. Factors associated with risk were female gender, homemaker status, unemployed or disabled, never having married, lower education, and living in or near poverty levels; and major depression was highly comorbid with other mental disorders. As many as 72% of respondents with lifetime major depression met criteria for at least one other disorder, such as anxiety disorder at 59%, substance abuse disorder at 24%, and impulse-control disorder at 30%. Approximately 90% of 12-month major depression cases were classified as moderate, severe, or very severe. Depression has also been associated with physical illnesses, affecting multiple domains of functioning and well-being; and patients with depressive conditions have been shown to have poorer mental, emotional, and social functioning than even those with chronic medical conditions. [21] [22] For example, depressed patients may report higher levels of fatigue and fatigue-related interferences than cancer patients.[23]

Characteristics of depressive mood disorders include feelings of sadness, hopelessness, and discouragement, but sadness may be bypassed with complaints of somatic problems, persistent anger or increased irritability, disinterest or lack of pleasure in activities, changes in appetite and sleep patterns, and altered psychomotor behaviors, such as agitation. Decreased energy, tiredness, and fatigue are common, as are feelings of worthlessness and guilt. There may be concentration problems, difficulties in decision making, thoughts of death and suicide, and varied degrees of social and work impairment. In many cases, depressed persons present with tearfulness, irritability, ruminations, anxiety, phobias, concern over physical health, pain complaints, and brooding. Major depression is usually differentiated from mood disorder due to a general medical condition, substance abuse–induced mood disorder, dementia, and adjustment disorder with depressed mood and simple bereavement. Turning to the opposite end of the spectrum, manic episodes are characterized by inflated self-esteem or grandiosity, decreased need for sleep, pressured speech, flight of ideas, distractibility, increased involvement in goal-directed activities, and psychomotor agitation. Expansiveness and unwarranted optimism coupled with poor judgment may lead to imprudent excesses, as discussed later.

Selective Serotonin Reuptake Inhibitors

Depressed patients prescribed psychotropic medications rose from 44.6% in 1987 to 79.4% in 1997, an increase attributed primarily to a class of medications unavailable in 1987, the selective serotonin reuptake inhibitors (SSRIs) ( Table 15-2 ). [24] [25] [26] [27] [28] [29] [30] Psychopharmacologic research and discovery have altered depression treatment protocols, particularly over the past 20 years, and use of antidepressants has increased from 1988 to 1994 threefold to fivefold among youth younger than 20 years of age.[31] Noting that primary care physicians initiate more antidepressant pharmacotherapy than psychiatrists, the literature addresses issues involved in recognition and management of depression in primary care settings, clearly outlining that the pharmacology of depression treatment and its effects constitute a multifactorial challenge for physicians who must take into account medication side effects, adverse drug effects, and drug-drug interactions, as well as patient specific factors such as gender, age, and other illnesses.[5]

TABLE 15-2   -- Depressive Disorder Medications

Class

Generic Name (Trade Name)

Tricyclic antidepressants (TCAs)

  

 

Amitriptyline (Elavil, Endep, Entrofen, Loroxyl, Tryptizol)

  

 

Amoxapine (Asendin)

  

 

Clomipramine (Anafranil)

  

 

Desipramine (Norpramin, Pertofran)

  

 

Doxepin (Adapin, Sinequan)

  

 

Imipramine (Norfranil, Tofranil, Tipramine)

  

 

Maprotiline (Ludiomil)

  

 

Nortriptyline (Aventyl, Noratren, Pamelor)

  

 

Protriptyline (Vivactil)

  

 

Trimipramine (Surmontil)

Selective serotonin reuptake inhibitors (SSRIs)

  

 

Citalopram (Celexa, Cipram, Cipramil, Serostat)

  

 

Escitalopram (Lexapro)

  

 

Fluoxetine (Prozac, Sarafem)

  

 

Fluvoxamine (Dumirox, Feverin, Floxyfral, Luvox)

  

 

Paroxetine (Paxil)

  

 

Sertraline (Zoloft)

Monoamine oxidase inhibitors (MAOIs)

  

 

Deprenyl (Eldepryl, Selegiline)

  

 

Isocarboxazid (Marplan)

  

 

Moclobemide (Aurorix)

  

 

Phenelzine (Nardil)

  

 

Tranylcypromine (Parnate)

Atypical medications

  

 

Amisulpride (Deniban, Solian, Sulamid)

  

 

Bupropion (Wellbutrin, Zyban)

  

 

Duloxetine (Cymbalta)

  

 

Milnacipran (Ixel)

  

 

Mirtazapine (Remeron)

  

 

Nefazodone (Dutonin, Serzone)

  

 

Reboxetine (Edronax, Vestra)

  

 

Trazodone (Desyrel, Trazon, Trialodine)

  

 

Venlafaxine (Effexor)

  

 

Viloxazine (Vivalan, Vivarint)

Herbal and natural remedies

  

 

Ginkgo biloba

  

 

Ginseng

  

 

Hypericum perforatum (St. John's Wort)

  

 

S-adenosyl-L-methionine (SAMe)

  

 

Valeria officinalis (Valerian)

PERTINENT SIDE EFFECTS OF THESE MEDICATIONS: antiadrenergic effects, anticholinergic effects, blurred vision, constipation, decreased cardiac conduction, drowsiness, dry mouth, dysuria, hepatotoxicity, hyponatremia, orthostatic hypotension, sedation, seizures, tremors, urinary retention.

 

 

 

Antidepressants have a multitude of receptor and neurochemical modulating effects ( Table 15-3 ).[32] The SSRIs, as previously stated, are the most frequently prescribed antidepressants encountered by practicing anesthesiologists. As their name implies, they selectively potentiate the transmission of central nervous impulses along serotonergic pathways while having little effect on other neuroendocrine pathways, such as those involving norepinephrine or acetylcholine. As such, they tend to cause nausea, diarrhea, headache, sexual dysfunction, agitation, and despite some mild sedative effects, insomnia. They lack many of the side effects associated with other classes of antidepressants. However, side effects are noted and SSRIs such as escitalopram, possibly associated with hyponatremia, and sertraline, possibly linked to dry mouth, are reactions that should be recognized when present.


TABLE 15-3   -- Pharmacology of Antidepressants[*]

 

Antimuscarinic Activity[†]

Antihistamine Activity (H1)[†]

Anti-α1-Adrenergic Activity

Reuptake Inhibition

Elimination Half-Life (hr)

 

 

 

 

NE

5-HT

 

Amitriptyline

3

3

3

2

4

32–40

Doxepin

2

4

3

1

2

8–25

Imipramine

2

1

1

2

4

6–20

Trimipramine

2

4

3

1

1

9

Desipramine

1

0

1

4

3

12–54

Nortriptyline

1

1

2

2

3

15–90

Protriptyline

3

½

1

3

3

54–92

Amoxapine

1

1

2

2

2

8–30

Maprotiline

1

2

1

2

1

27–58

Trazodone

0

½

2

0

3

3–9

Fluoxetine

½

0

0

1

4

168–210

Bupropion

0

0

0

0

0

8–24

From Haddox JD, Chapko wski SL: Neuropsychiatric drug use in pain management. In Raj PP (ed): Practical Management of Pain, 3rd ed. St. Louis, Mosby, 2000, pp 489-512.

NE, norepinephrine; 5-HT, 5-hydroxytryptamine (serotonin).

 

*

*Relative scale of 1 to 4 with 1 = least effect.

Relative agents: atropine = 4 (antimuscarinic activity), diphenhydramine = 2 (antihistamine activity, phentolamine = 4 (anti-⟨1-adrenergic activity).

 

Notable among the SSRIs is fluoxetine, because it is a potent inhibitor of the cytochrome p450 2D6 isoenzyme.[33] The implication of this inhibition is a rise in the plasma concentration of drugs that depend on hepatic metabolism for clearance. Generally, other drugs used to treat coexisting diseases such as b blockers, benzodiazepines, and some cardiac antidysrhythmic drugs are affected. The most obvious results of this inhibition derive from treatment of the patients' depression itself, because patients may be treated with several antidepressants from different classes. Concomitant treatment of depressed patients with both fluoxetine and a tricyclic drug may result in substantial rises in plasma concentrations of the latter. Combination with monamine oxidase inhibitors (MAOIs), with the pharmacology discussed later, may precipitate serotonin syndrome, which is similar to neuroleptic malignant syndrome both in its presentation and its mortality and is marked by flushing, restlessness, anxiety, chills, ataxia, insomnia, and hemodynamic instability. Combining fluoxetine with the mood stabilizers carbamazepine or lithium may also precipitate this syndrome. There has been an ongoing debate as to whether SSRIs may increase the risk of suicide in a small subgroup of depressed patients. On this last point, however, evidence is lacking.

From the perspective of anesthesia, the SSRIs represent little additional challenge to administration of general anesthesia. Some care must be taken to limit drugs that depend on the cytochrome system for metabolism such as barbiturates, benzodiazepines, and certain neuromuscular blocking drugs. It is also of note that there is no effect of SSRIs on seizure threshold. This is an important point to remember during administration of general anesthesia to patients with coexisting seizure disorder or for patients undergoing electroconvulsive therapy (ECT) for the treatment of depression or other psychiatric disorders.

Tricyclic Antidepressants

Prior to the introduction of the SSRIs to clinical practice, the tricyclic antidepressants (TCAs) were the most widely used drugs used to treat clinical depression. They are so named because their chemical structure is composed of three conjoined rings. If the nitrogen atom on the center ring is a tertiary amine, the drug belongs to the first-generation TCAs; if it is a secondary amine, the drug is a second-generation tricyclic. Most of the side effects discussed below are more pronounced with the first-generation TCAs. It is generally believed that the TCAs are equally potent with regard to treatment of depression. On the other hand, all of the TCAs cause some anticholinergic symptoms, orthostatic hypotension, cardiac dysrhythmia, and sedation. However, they do so in varying degrees when compared with their efficacy as antidepressants. This differing side effect profile serves as the basis for much of the strategy employed by practitioners prescribing these drugs. For example, a drug that causes a greater degree of sedation might be chosen preferentially for patients experiencing insomnia as part of their symptomatology. Similarly, practitioners might avoid drugs that have greater anticholinergic activity in patients who have glaucoma or reflux disease, for example.

The degree of cardiac dysrhythmia potential is essentially the same for TCAs, and they should be avoided in patients with known cardiac conduction abnormalities such as second-degree atrioventricular block. It has been shown that despite their potential for causing cardiac dysrhythmias, they may paradoxically show some antidysrhythmic activity.[34] Also of note is the fact that despite the electrocardiographic (ECG) changes that occur with these drugs, the changes tend to dissipate with ongoing treatment, implying some sort of tolerance on the part of the cardiac conduction system to these effects.[35] However, these changes are of particular concern during the early phase of treatment of depressed patients with suicidal ideations. This concern arises from the fact that a frequently chosen method of suicide is overdose, and the medications chosen are those in possession of patients, in this case, possibly their antidepressants. Overdose with TCAs may be achieved by ingesting as little as 5 to 10 times the daily dosage, resulting in fatal arrhythmia or resistant myocardial depression. Despite these facts, overdose with TCAs typically presents as central nervous system (CNS) depression, including seizures, hypoventilation, and coma. Anticholinergic symptoms are also present and may confuse diagnosis. Normally, when patients present to the operating theater, these problems are not present. However, in the setting of trauma, there may be need for concern if acute drug ingestion is present as part of a suicide attempt or abuse of these drugs.

Considerations regarding the administration of general anesthesia to patients undergoing treatment of depression with TCAs revolve around the side effects of these medications and their interactions with other drugs. The mechanism of action of TCAs involves enhancement of serotonergic and noradrenergic activity. They also cause inhibition of histaminergic, cholinergic, and α1-adrenergic activity as well. This inhibition is responsible for many of the side effects of the drugs. Most of the anesthetic considerations affected by patients being treated with a TCA involve the cardiovascular system and are brought about by the interaction of the drug with a specific neurotransmitter, such as norepinephrine. Administration of TCAs causes an increase of this neurotransmitter to be stored in noradrenergic nerve terminals. Thus, administration of indirect-acting vasopressors such as ephedrine may cause an exaggerated response. This effect is most pronounced with acute treatment and gradually dissipates after the first 2 to 3 weeks. Caution is therefore advised with regard to using drugs with sympathomimetic effects on patients receiving TCAs.

Another neurotransmitter system that is of particular concern to the anesthesiologist is the cholinergic system. Many of the drugs used by anesthesiologists are anticholinergics or have anticholinergic effects. Preoperatively, some anesthesiologists employ scopolamine for its sedative, anxiolytic, and antisialogogic properties. Intraoperatively, glycopyrrolate and atropine are both used for their anticholinergic properties. Pancuronium, which has significant anticholinergic effects, is still used for procedures requiring a long period of muscle relaxation, especially cardiac surgery. Atropine and glycopyrrolate have been noted to have increased muscarinic activity in the presence of TCAs, and administration of pancuronium has been documented to precipitate tachydysrhythmias in a sample of patients studied.[36] Furthermore, there is the possibility that preoperative treatment with scopolamine may increase the incidence of emergence delirium, although there are no studies to support this suspicion.

Overall, the increased amount of neurotransmitters available in the CNS due to treatment with SSRIs is responsible for increasing the minimal alveolar concentration (MAC) of inhalational agents.[37] Also, in general, owing to the sensitization of the sympathetic nervous system by TCAs, there is the possibility that ketamine might have a similar effect to pancuronium, although evidence is lacking. Finally, halothane and the epinephrine used to extend the length of action of centrally or peripherally administered nerve blockade also have the theoretical potential to cause dysrhythmias, although evidence to support this concern is lacking.

Monoamine Oxidase Inhibitors

The monoamine oxidase inhibitors (MAOIs) represent a third class of antidepressants. As their name implies, they inhibit the enzyme monamine oxidase, which is responsible for the oxidative deamination of several biogenic amines, among them norepinephrine. As a consequence, they act to extend the effect of norepinephrine at the nerve terminals. Whereas their use has declined over the past several decades, largely owing to the advent of more specific drug therapies, these drugs are still available. MAOIs are reserved primarily for the treatment of patients who have failed treatment with other antidepressants. The MAOIs are devoid of many of the side effects of the earlier-mentioned drugs. The principal side effect is the ability to precipitate profound hypertension when foods are consumed that contain the substance tyramine, most commonly wines or cheeses, or when combined with drugs with intrinsic sympathomimetic effects such as certain b blockers. Tyramine and sympathomimetic drugs stimulate the release of norepinephrine from noradrenergic nerve terminals, and owing to the mechanism of the drug, the α-adrenergic effects of the neurotransmitter become pronounced. Other side effects of the drug include orthostatic hypotension, sedation, blurry vision, and peripheral neuropathy.

In addition to the just-mentioned side-effects, perhaps the greatest reason that MAOIs have fallen out of favor as first-line therapy for the treatment of depression is their tendency to interact with an extensive list of other drugs, including both prescription and over-the-counter medications, such as meperidine and the herbal medicine St. John's Wort. The manifestations of these reactions include but are not limited to the previously mentioned hypertensive crisis, serotonin syndrome, and, in many cases, exaggerated effects of many of the medications with which the MAOI interacts. This interaction profile severely limits the utility of this class of drugs. When patients who are being treated with MAOIs present for surgery there are several things for anesthesiologists to consider. In the past, it was suggested that MAOIs be discontinued 2 to 3 weeks before any elective procedure involving general anesthesia. This precaution is no longer encouraged or practical for many procedures, because discontinuation of the drug may acutely place patients at greater risk for suicide.[38]

As with the TCAs, the MAC is conceivably elevated in patients undergoing treatment with MAOIs, although this elevation has never been delineated. Furthermore, serum cholinesterase activity may be impaired, requiring the dose of succinylcholine to be reduced.[39] Liver function indices may become elevated during treatment with MAOIs; and, as such, halothane should probably be avoided owing to its potential to cause hepatic dysfunction. As with TCAs, indirect-acting vasopressors as well as epinephrine-containing local anesthetics should be avoided because of their potential to cause severe hypertension. Finally, because MAOIs are known to interact with opioids, their use should be limited by necessity. Meperidine is the most commonly implicated of the narcotics, but, with the exception of fentanyl, they all have the possibility of precipitating a hyperpyrexic response that can be confused with malignant hyperthermia and carries a similar potential for mortality.[40] Postoperative pain control can be achieved with minimal use of opioids and employment of alternatives such as NSAIDs and regional anesthesia, when possible.

Second-Generation Drugs

A final pharmacologic option for the treatment of depression is the use of alternative second-generation drugs such as venlafaxine, trazodone, bupropion, and mirtazapine. The methods of action of many of these drugs are currently being elucidated but remain poorly understood. Like the MAOIs, these drugs are most likely chosen by practitioners for the treatment of patients who have failed pharmacologic management of their depression with other drugs such as the SSRIs. Most often, the drug's side effect profile acts as guide for which drug is chosen. For example, venlafaxine may be linked to seizures and constipation as two side effects. Another drug in this class, trazodone, is the most sedating of the second-generation antidepressants and might be chosen to treat patients who suffer from insomnia. Unlike the TCAs, these alternative agents possess almost no anticholinergic effects and do not cause potential for cardiac dysrhythmias. For patients receiving more than one drug as part of their therapy, avoidance of MAOIs in patients undergoing therapy with a second-generation antidepressant is recommended.

Caution is warranted regarding St. John's Wort (Hypericum perforatum), used by many people in an attempt to treat themselves for what they feel is depression. Many of these individuals have never been diagnosed by a psychologist or psychiatrist as having depression but may still treat themselves nonetheless. Recent studies indicate St. John's Wort is no more effective than placebo in the treatment of major depressive disorder.[41] Its efficacy for less severe cases is disputed. However, there are still patients encountered in the scope of clinical practice who take this nutraceutical agent. The side effect profile is extensive, but the only major concern for anesthesiologists is the similarity that this drug bears to the MAOIs in their potential for precipitation of hypertension and hyperpyrexia by the aforementioned mechanisms.

Scher and Anwar reported that the proportion of surgery patients taking antidepressants is 35%.[42] Furthermore, the investigators found that a large percentage of such patients did not reveal the use of these drugs on routine preanesthetic assessment. In this regard, a similar percentage of patients, roughly one third, admitted to taking one or more nutraceuticals (herbal agents). However, 70% did not disclose this information on preanesthetic assessment, and many of these agents possess neurobehavioral effects and can interact with anesthetics. [43] [44] In addition to the potential effects of depressive psychopathology on patient reporting of illness, behaviors before and after surgery, and recovery outcomes, antidepressant medications may interact with anesthetics and influence behavior or cognitive functioning postoperatively. One such complication is the risk of developing acute confusional states, which is thought to be elevated in depressed patients taking antidepressants.

One group of researchers compared 80 depressed patients with 50 control patients undergoing orthopedic surgery and found that cortisol response to surgery is associated with postoperative confusion and that the use of fentanyl during anesthesia decreases the incidence of postoperative confusion, related to the inhibition of cortisol secretion by fentanyl.[45] Another study evaluated 80 patients ages 35 to 63 years with major depression who underwent anesthesia during orthopedic surgery, divided into those who continued or discontinued antidepressants 72 hours before surgery.[46] Depressed patients were taking imipramine, clomipramine, maprotiline, and mianserin. Results revealed a low incidence of intraoperative hypotension and arrhythmias in depressed patients whether antidepressant treatment was ceased preoperatively or not, but that discontinued use of antidepressants was associated with increased incidence of delirium, confusion, and depressive symptoms. In another investigation, Kudoh and colleagues observed temperature regulation during anesthesia and postoperative shivering in chronically depressed patients undergoing orthopedic surgery who were taking imipramine, clomipramine, maprotiline, or mianserin for more than 1 year compared to a control sample. The intraoperative core temperature and incidence of shivering in the depressed group were significantly higher.[47]

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Dysthymic Disorder

TheDSM-IV defines dysthymia as a chronically depressed mood that occurs for most of the day, more days than not, for at least 2 years.[15] The disorder can be found in children who may exhibit irritability rather than depression, or in addition to sadness. When depressed mood prevails, at least two additional symptoms may be present, such as poor appetite or overeating, insomnia or hypersomnia, low energy or fatigue, low self-esteem, difficulties concentrating or making decisions, and feelings of hopelessness. Often, patients with dysthymia see their symptoms as characterizing their personality over time. The lifetime prevalence is approximately 6% according to the DSM-IV, and it is noted that dysthymia is often marked by early, insidious onset and a chronic course.[15] Dysthymia may be superimposed on major depression; and in many cases, patients are prescribed medications similar to those used for major depression. Loss of interest, feelings of guilt or brooding about the past, excessive anger, and decreased activity, effectiveness, and productivity may be common; and with time the disorder may be associated with multiple physical illnesses or coexist with such illnesses.

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Bipolar Disorders

When individuals exhibit bouts or episodes characterized as manic, often in sequence with depressive episodes, they are characterized within this category. A manic episode is seen as a distinct period marked by abnormally, persistently elevated, expansive, or irritable mood accompanied by such additional symptoms as inflated self-esteem or grandiosity, decreased need for sleep, pressured speech, flight of ideas, distractibility, and increased involvement in goal-directed activities with high potential for painful consequences. The disturbance is sufficiently severe to cause marked impairments in social or occupational functioning and may include psychotic features. Mood in manic episodes may be seen as euphoric, unusually cheerful, or high; and the expansive quality is described as unceasing and indiscriminate, particularly in interpersonal, sexual, or occupational interactions. Uncritical self-acceptance may hold firm, and individuals may not recognize that they are ill and resist efforts to be treated. Mood may shift rapidly to anger or depression. Depending on the length, severity, and course of symptom complexes over time, individuals may be diagnosed as bipolar I or bipolar II disorder. Bipolar I disorder is characterized by one or more manic or mixed episodes, usually with major depressive episodes. The diagnosis of bipolar II disorder suggests recurrent depressive episodes and at least one hypomanic episode. Among the specifiers to designate subtypes within the bipolar spectrum are those reflecting severity, psychosis, remission, catatonic features, and postpartum onset. Seasonal patterns and the nature of cycling (rapid or not) are also considered, and thus the history of current and past episodes determines diagnosis of actual mood disorder.

The phenomenology of bipolar symptoms is multifaceted across and within individuals over time, taking into account both symptom severity and variability.[48] Studying the prevalence and disability of bipolar spectrum disorders in the United States and adding investigation of subthreshold cases, Judd and Akiskal found a combined community prevalence of 6.4%.[49] Subthreshold cases were at least five times more prevalent than DSM-defined core syndromal diagnoses, cited at about 1%. These researchers emphasized that bipolar disorders are associated with significant service utilization and psychosocial impairment. Among the pharmacologic treatments for bipolar disorders are drugs used to treat mood disorders generally, including antidepressants, lithium salts, and other medications. Lithium carbonate was the first and is still the most important antimanic agent ( Table 15-4 ). [25] [26] [27] [28] [29] [30] For cases refractory to treatment with pharmacologic agents, ECT may be used as an intervention of last resort.

TABLE 15-4   -- Bipolar/Cyclothymic Disorder Medications

  

 

Carbamazepine (Tegretol)

  

 

Valproic acid (Depakote)

  

 

Gabapentin (Neurontin)

  

 

Lamotrigine (Lamictal)

  

 

Topiramate (Topamax)

  

 

Lithium carbonate (Eskalith, Lithium, Lithobid)

PERTINENT SIDE EFFECTS OF THESE MEDICATIONS: ataxia, confusion, convulsions, lithium toxicity, nephrogenic diabetes insipidus, sedation, tremors.

 

 

 

The use of lithium carbonate to treat mania began after an Australian psychiatrist, John Cade, noticed the calming effect that the salt had on laboratory animals. For many years the soft drink 7Up contained lithium and was marketed as having a calming effect. While the mechanism of action of lithium is still not precisely known, it is widely distributed throughout the CNS, where it is believed to have a variety of effects. It is known that lithium interacts with many neurotransmitter systems, increasing the synthesis of serotonin while decreasing norepinephrine release, and these effects are thought to be responsible for its clinical effect.

Despite its efficacy in the treatment of mania, lithium has a very narrow therapeutic index and plasma levels of the drug must be monitored routinely. A serum concentration of 0.6 to 0.8 mEq/L is considered therapeutic for the treatment of stable mania. Slightly higher levels up to 1.2 mEq/L are accepted for treatment of acute episodes. Levels of 2.0 mEq/L are considered toxic and require withdrawal of the drug and aggressive hydration with sodium-containing solutions or administration of osmotic diuretics such as mannitol.[50] Lithium toxicity is evidenced by weakness, sedation, ataxia, and widening of the QRS complexes on the electrocardiogram. These symptoms in patients receiving lithium demand drug withdrawal and testing of serum lithium levels, because with greater toxicity, atrioventricular blockade, cardiovascular instability, seizures, and death may result.

Besides the possibility of toxicity, lithium also has long-term effects that require periodic monitoring. Lithium is known to inhibit the release of thyroid hormones, resulting in hypothyroidism in as many as 5% of patients receiving the drug. It may also cause nephrogenic diabetes insipidus that does not respond to treatment with vasopressin. In a small number of patients, leukocytosis may develop, noted as a white blood cell count between 10,000 and 14,000 cells/mm3. All of these effects resolve with withdrawal of the drug but mandate periodic testing of patients' thyroid levels, urine osmolality, and white blood cell count. In patients with known sinus nodal dysfunction, it may be prudent first to place a permanent pacemaker secondary to possible disturbances of the cardiac conduction system by lithium treatment.

Lithium ions are freely filtered in the glomerulus and then reabsorbed in the proximal convoluted tubule. The amount of reabsorption is inversely proportional to the concentration of sodium ions present in the ultrafiltrate. In patients receiving loop or thiazide diuretics, the increase in the concentration of sodium ions in the ultrafiltrate causes a subsequent increase in lithium reabsorption. Coupled with the relative decrease in extracellular fluid, lithium ion concentration may rise by as much as 50% and toxicity may ensue. Therefore, a reduced lithium dose along with more careful monitoring of lithium levels is recommended in patients receiving diuretic therapy with either of these agents. Besides the just-mentioned considerations, lithium interacts with several classes of anesthetic agents. Specifically, the length of action of several nondepolarizing neuromuscular blocking drugs is prolonged because of lithium's ability to replace sodium in propagation of action potentials.[51] In addition, the MAC is reduced in patients receiving lithium because of lithium's blockage of brain stem epinephrine and norepinephrine release; thus, emergence may be prolonged.[52] Nutraceuticals and herbal agents have also been used to treat mood disorders, and evaluation for these agents is necessary for anesthesiologists. In this regard, fish oils have had positive results in bipolar disorder and can affect the coagulation cascade.[53]

Electroconvulsive Therapy

An often-questioned treatment procedure for depression and other mental disorders, ECT remains within the arsenal of weapons to impact the symptoms of major depression and bipolar disorder.[54] It may also be applied in cases of schizophrenia, particularly when patients do not respond to other therapeutic efforts.[55] It is thought that the therapeutic mechanism of ECT is related to the generalized seizures it induces, and there are potentially important interactions between psychotropics, anesthetics, and ECT, necessitating effective cooperation between the medical disciplines involved in its administration. Several clinician researchers have explored combinations of anesthetics to facilitate favorable outcomes.[56] In general, ECT is thought of as a treatment of last resort, applied when either other treatments have failed or if patients develop suicidal ideations acutely.[57] At present, the mechanism of ECT is unknown. Until recently, most practitioners have touted the theory that seizure duration is the most important factor relating to treatment efficacy.[58] However, newer studies cast doubt on this theory.[59] The only absolute contraindications to ECT are elevated intracranial pressure and pheochromocytoma. Relative contraindications include recent cerebrovascular accident, aortic disease, cerebral aneurysms, cardiac conduction disturbances, and certain high-risk pregnancies.

Usually, once an electrical stimulus has been applied to the brain, a grand-mal seizure is induced. A brief initial tonic phase is followed by a more prolonged clonic phase that lasts on the order of 30 seconds to several minutes. Another technique is to induce three seizures at one sitting and use intubation with hyperventilation to decrease carbon dioxide. By hyperventilating and decreasing carbon dioxide levels, the seizure threshold can be lowered. On the average, approximately eight treatments are necessary to treat most patients with a response rate of close to 75%. Over the course of the treatments, the only significant side effect that develops is memory loss. To minimize this complication, the stimulus can be applied to the nondominant hemisphere only. However, efficacy is reduced by this maneuver.

During ECT treatments there are several physiologic consequences that mandate close monitoring of patients. Initially, a substantial vagal discharge is noted with consequent bradycardia and hypotension. This is immediately followed by a much longer period of time during which sympathetic activity predominates, resulting in hypertension and tachycardia. During this time, cardiac ischemia or significant tachydysrhythmias may develop. In fact, the most frequent cause of mortality in patients receiving ECT is myocardial infarction.[60] Several treatments have been suggested to address these side effects, including short-acting b blockers, narcotics, and nitrates. Careful consideration must be given to such agents, because profound bradycardia and asystole have been reported after their administration.[61]

Clinicians who administer anesthesia for ECT need to be aware of untoward physiologic responses and be prepared to treat them. In addition, they need to be aware of the effects that different agents used for anesthesia have on the administration of the therapy. In the past, traditional wisdom has suggested that methohexital was superior to other agents because of its ability to decrease seizure threshold. More recent research has indicated, however, that etomidate provides a longer window of seizure activity than does either methohexital or propofol.[62] Until agreement is reached concerning the exact mechanism of action of ECT, which agent is superior remains unknown. Ketamine, with its ability to lower seizure threshold, may seem to provide some benefit, but studies have not shown this to be the case.[63]

Given the tonic-clonic nature of seizure, muscle relaxation is essential, and because of the ultra-short duration of action, succinylcholine is an almost perfect agent for this purpose, because it may be administered as a single bolus or via infusion. However, there is potential to cause mild vagal blockade, and careful attention must be paid to its potential to amplify the initial vagal phase of the induced seizure. The administration of glycopyrrolate preprocedurally may help circumvent this complication. Mivacurium has also been used for this purpose but has the disadvantage of causing prolonged relaxation and increasing the total anesthetic requirements.

In addition to the standard monitors used for general anesthesia, electromyography (EMG) and electroencephalography (EEG) are also employed by most practitioners to monitor the length of induced seizure activity both peripherally and centrally. The inflation of a tourniquet on the limb used to monitor EMG before administration of the muscle relaxant helps to augment the efficacy of this monitoring modality. Intubation of the trachea is usually not required unless there is a history of gastroesophageal reflux or hiatal hernia, but ventilation must be supported during the procedure owing to the need for muscle relaxation. Thus, the antisialogogic effect of glycopyrrolate is an additional benefit of pretreatment with this medication.

Patients undergoing ECT are often receiving treatment with other psychotropic medications. These medications may have an impact on the physiologic implications of ECT, as well as possible interactions with medications used to anesthetize patients during ECT. For example, the aforementioned effects of TCAs on the sympathetic nervous system and on the cardiac conduction system may predispose patients receiving ECT to a more significant risk of profound hypertension and dysrhythmias. Patients taking MAOIs may find themselves at a similarly increased risk of hypertension. Lithium treatment may prolong the effect of benzodiazepines or barbiturates used for induction of general anesthesia while increasing the likelihood of treatment-induced cognitive side effects. Also, preprocedural treatment with centrally acting anticholinergic medications may increase the likelihood of postprocedural delirium. Clearly, the anesthetic record must be complete. This includes descriptions of which drugs are administered and in what quantities, especially drugs used to treat hemodynamic fluctuations. The induction stimulus, length of the induced seizure, and length of time to recovery must be assiduously documented. This is particularly important because ECT is administered repeatedly over a course of several weeks and the events of the previous treatment can serve to guide modifications of future treatments.

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ANXIETY DISORDERS

Generalized Anxiety Disorder

Studies over the past two decades have shown anxiety disorders as a whole to be the most prevalent of mental disorders, affecting as many as one in four individuals in American society at some time in their lives.[13] Although differing by subtype and among the most diverse, anxiety disorders are more often found among women, the more poorly educated, the unmarried, and the childless.[64] Leon and colleagues estimated that 30 million Americans may have suffered from an anxiety disorder, and Lépine called attention to the prevalence of the anxiety disorders and their cost to society. [65] [66] Among these disorders are generalized anxiety disorder, thought to hold current prevalence rates from 1.2% to 2.8%, and 4.0% to 6.6% for lifetime estimates.[66] Generalized anxiety disorder is a persistent and troublesome condition with high degrees of comorbidity, making it a consequence of and risk factor for other disorders. According to the DSM-IV, the essential features are excessive anxiety and uncontrolled worry about varied activities and events occurring over a period of 6 months.[15] Anxiety and worry are accompanied by additional symptoms, including restlessness, fatigue, concentration problems, irritability, muscle tension, and disturbed sleep. The intensity, duration, and amount of anxiety are disproportionate to the actual likelihood or impact of the feared event, and persons affected have difficulty changing their thought patterns from incessant worry. Many patients suffering generalized anxiety disorder seek treatment from their primary care providers.

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Social Phobia

Another of the anxiety disorders is social phobia, a relatively common disorder, although prevalence estimates differ depending on measurement instruments, time period under consideration, and other methodologic features. Nevertheless, estimates of lifetime prevalence range from 0.5% to 16% in one report and 3% to 13% in the DSM-IV. [15] [67] The essential feature is marked and persistent fear of social or performance situations leading to possible embarrassment, and exposure to the threatening situation provokes an immediate anxiety response such as panic attack. In most cases, individuals avoid the feared situations and the disorder interferes significantly with normal routines, academic or occupational functioning, and social activities, and relationships. Social phobia is common, associated with significant impairment in a number of life areas, and has been identified in 2.9% to 7.0% of primary care patients.[68] In this arena, patients are often women with a mean age at onset of 15.1 years, tend to be younger and less educated than others with anxiety disorders, and may hold poorer views of their health and physical function, with common suicidal ideation. The disorder may be unrecognized by medical providers across settings, particularly when patients present for surgery.

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Obsessive-Compulsive Disorder

Other anxiety disorders are panic disorder, agoraphobia, specific phobia, and obsessive-compulsive disorder. Disorders involving great fearfulness, behavioral agitation, somatic involvement, and avoidance of important life activities or situations are perhaps more obvious, such as panic disorder, agoraphobia, and specific phobia. Obsessive-compulsive disorder, however, may be difficult to identify, particularly among high-functioning, intelligent adults. The disorder is one of the most severe and chronic of the anxiety disorders, with essential features of recurrent obsessions or compulsions that are time consuming and distressing. Obsessions are commonly about themes of contamination, dirt, or illness; needs for orderliness; and somatic and religious ideation. Compulsions may include washing, checking, and repeating rituals, either behavioral or cognitive.[69] Although previously thought to be relatively rare in the general population, recent community studies have estimated a lifetime prevalence of 2.5% and 1-year prevalence of 1.5% to 2.1%.[15] In many instances, obsessive-compulsive disorder afflicts persons of higher intelligence and functioning capacity; therefore, the symptomatology may be masked by the appearance of productivity. Some degree of success in treatment has been achieved with use of the SSRIs.

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Post-traumatic Stress Disorder

Receiving considerable attention with the rise of domestic violence and civil unrest, the occurrence of natural disasters such as hurricane, acts of terrorism, and exposure to war and other traumatic events, post-traumatic stress disorder (PTSD) was first described in 1980.[15] Mental health professionals recognized officially what psychoanalysts postulated in the past century, that traumatic events may have long-lasting effects on the human psyche, with implications for mental and physical functioning, particularly as stressful events are prolonged, severe, life-threatening, and gruesome. Trauma exposure is a necessary condition for diagnosis in the DSM-IV, and the critical determinant is individual cognitive and affective reactivity to the trauma, with the event eliciting severe and incapacitating psychological distress, such as feelings of “intense fear, helplessness, or horror.”[15] Symptoms include high levels of anxiety; distressing thoughts, feelings, and images that recapitulate the trauma; avoidance of stimuli associated with the event; emotional numbing of responsiveness; restricted range of affect; sense of foreshortened future; interpersonal anomalies; and stress-related symptoms of distress, arousal, fear, and irritability. Data from a variety of studies suggest that traumatic events are not unusual and that the average American is likely to suffer one or multiple exposures.[70] PTSD may occur following a wide range of stressful events, including participating in war, torture, rape, and other criminal victimization; air and motor vehicle accidents; industrial accidents; and devastating acts of nature, such as hurricane and earthquake.

Given the epidemiology of traumatic events, it is not surprising that lifetime prevalence for PTSD in the community may vary from 1% to 14%, depending on the population sampled and study methodology.[15] Research focusing on special groups at high risk, such as survivors of natural disaster, combat veterans, former prisoners of war (POWs), and soldiers assigned graves registration duties in the war zone reveal highly variable rates, depending on the severity and nature of the stressful experience and, to a lesser degree, individual difference factors. Three examples are illustrative. Results of the National Vietnam Readjustment Study showed that among men, 15% and 30% met criteria for current and lifetime PTSD.[71] The figures for women were 9% and 27%, respectively. Sutker and colleagues found current rates of PTSD as high as 48% in a small sample of Gulf War veterans who performed graves registration duties in the war zone and as high as 70% and 86% for current PTSD in former POWs held by the Japanese during World War II and by the Koreans and Chinese in the Korean War. [72] [73] [74]

Treatment for PTSD has often incorporated a variety of medications, including antidepressants such as the SSRIs, TCAs, and MAOIs. Inhibitors of adrenergic activity such as clonidine, propranolol, and the diazepines have been used. Thus, patients suffering PTSD, and possibly other comorbid disorders, such as dysthymia, other anxiety disorders, and substance abuse disorders, may present for medical treatment and surgery with a complex array of prescription medications for anesthesiologists to understand. Behavioral complications of the disorder may pose barriers to effective communication and cooperation with physicians, and patients suffering PTSD may become irritable, anxious, confused, and belligerent under conditions where they experience misunderstandings, lack of control, and potential exposure to life-threatening stress. Medical intervention outcomes may be diminished by the direct effects of PTSD psychopathology.

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Panic Attacks

Common to the anxiety disorders overall, panic attacks represent a feature of psychopathology that bears consideration in evaluating patients for surgery and anesthesia. According to the DSM-IV, panic attacks involve a period of fear or anxiety distinguished by physiologic and cognitive symptoms.[15] These attacks seem to present unexpectedly and are often associated with phobic avoidance of situations in which they have occurred. Therefore, individuals who associate medical treatments and illnesses with panic attacks may be particularly vulnerable to suffer such attacks in a medical situation or in anticipation of such. Barlow found that panic disorder is less prevalent than some other anxiety disorders but is one of the most common found in outpatient treatment programs.[75] Patients with a history of panic attacks may describe use of TCAs, MAOIs, SSRIs, and benzodiazepines. Table 15-5 lists the medications commonly used to treat anxiety disorders. [76] [77] [78]

TABLE 15-5   -- Anxiety Disorder Medications

Class

Generic Name (Trade Name)

Benzodiazepines and other anxiolytic medications

  

 

Alprazolam (Xanax)

  

 

Barbiturates

  

 

β Blockers

  

 

Brotizolam (PIM 919)

  

 

Buspirone (BuSpar)

  

 

Chlordiazepoxide (Librium)

  

 

Clobazam (Frisium, Mystan)

  

 

Clonazepam (Klonopin)

  

 

Clonidine (Catapress)

  

 

Clorazepate (Tranxene)

  

 

Diazepam (Valium)

  

 

Estazolam (ProSom)

  

 

Flunitrazepam (Rohypnol)

  

 

Flurazepam (Dalmane)

  

 

Loprazolam (Triazulenone)

  

 

Lorazepam (Ativan)

  

 

Lormetazepam (Loramet, Lormetazepam, Noctamid)

  

 

Meprobamate (Miltown)

  

 

Midazolam (Versed)

  

 

Monamine Oxidase Inhibitors (MAOIs)

  

 

Nitrazepam (Nitrazepam, Mogadon)

  

 

Oxazepam (Serax)

  

 

Prazepam (Centrex)

  

 

Quazepam (Doral)

  

 

Selective serotonin reuptake inhibitors (SSRIs)

  

 

Temazepam (Restoril)

  

 

Triazolam (Halcion)

Tricyclic antidepressants (TCAs)

Sedative-hypnotic medications

  

 

Chloral hydrate (Noctec)

  

 

Diphenhydramine (Benadryl)

  

 

Doxylamine (Unisom Nighttime Sleep-Aid)

  

 

Estazolam (ProSom)

  

 

Flurazepam (Dalmane)

  

 

Hydroxyzine (Atarax, Vistaril)

  

 

Mirtazapine (Remeron)

  

 

Nefazodone (Dutonin, Serzone)

  

 

Quazepam (Doral)

  

 

Temazepam (Restoril)

  

 

Trazodone (Desyrel, Trazon, Trialodine)

  

 

Triazolam (Halcion)

  

 

Zaleplon (Sonata)

  

 

Zopiclone (Imovane)

  

 

Zolpidem (Ambien)

Herbal and natural remedies

  

 

Kava Kava

  

 

Melatonin

  

 

Valeria officinalis (Valerian)

PERTINENT SIDE EFFECTS OF THESE MEDICATIONS: abuse potential, aggression, amnestic syndromes, cognitive impairment, drowsiness, intoxication, respiratory problems, withdrawal symptoms such as diaphoresis, rebound insomnia, and tremor.

 

 

 

It is not surprising that patients suffering from anxiety as the fundamental symptom of their mental disorder may experience heightened fear, worry, and anxiety before anesthesia and surgery, associated with high levels of circulating catecholamines, behavioral and autonomic agitation, and fearful behaviors. Heart palpitations and peripheral vasoconstriction may be evidenced. Sedgwick and coworkers wrote that the treatment of choice is with benzodiazepines and β blockers continued throughout the operative period.[4] They pointed to the need for careful preoperative consultation and appropriate premedications using benzodiazepines or opiates and suggested that anesthetic requirements may be increased owing to increased level of circulating catecholamines with the risk of cardiac dysrhythmias. Benzodiazepines and barbiturates may be used in treatment of anxiety as premedicants, with the caution that patients taking barbiturates may suffer withdrawal phenomena and may have increased tolerance to some of the intravenous induction agents, such as thiopentone.

With over 29,000 herbal products, many have been tried for various anxiety states. [43] [44] For example, kava extracts are likely effective for short-term treatment of anxiety disorders. Multiple clinical trials have demonstrated positive results compared with placebo and low-dose benzodiazepines. However, dozens of case reports linking kava to hepatic failure have been reported worldwide, thus requiring anesthesiologists to obtain a detailed history and high index of suspicion. The mechanism for kava-induced hepatic dysfunction appears to be linked to the kava alkaloid pipermethystin, which has a strong negative effect on liver cell cultures. Furthermore, four alkaloids with similar structures to pipermethystin are known cytotoxic agents. It is thought that epoxidation of pipermethystin may lead to hepatotoxic products. Herb-drug interactions may also be linked to kava toxicity, because it is rarely administered alone and is typically taken with other supplements or drugs. There are case reports and theoretical considerations that warrant concern regarding kava intake with alcohol, certain herbal agents, alprazolam, fluoxetine, paroxetine, acetylsalicylic acid, oral contraceptives, celecoxib, omeprazole, paracetamol, and others with either reported or associated side effects, examples of such being potential hepatotoxicity and CNS depression. Finally, genetic polymorphism of the CYP2D6 enzyme may play a role in kava-induced liver toxicity. Different ethnicities have varying frequency of deficiency of this metabolizer of kavalactones. Roughly 10% or more of whites have a deficiency in this enzyme, whereas the Polynesian population (which has not reported kava-induced liver failure) does not demonstrate this enzyme deficiency. [79] [80] [81] [82] Clinical anesthesiologists should link signs of liver failure with a history of kava intake and request additional laboratory investigation.

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NONAFFECTIVE PSYCHOSES

Schizophrenia

A clinically complex and heterogeneous disorder, schizophrenia is defined by disturbances in emotional, behavioral, and cognitive arenas manifested in almost every aspect of life functioning, including sense of well being, social adaptation, health, and self-sufficiency.[83] With a community prevalence rate at about 1%, schizophrenia takes its toll on thinking, attention, language, communication, behavioral monitoring, affect, hedonic capacity, motivation, and general productivity in thought, speech, emotion, and behavior.[15] Symptoms have been classified into three broad categories: positive, negative, and cognitive. Positive symptoms reflect an excess or distortion of normal functions, particularly referring to sensory and perceptual experiences, thoughts, and behaviors that include hallucinations, delusions, and bizarre, strange, or grossly disorganized behaviors. Negative symptoms reflect diminution or loss of normal functions, or absence of emotions and behaviors ordinarily present, such as anhedonia, apathy, social withdrawal, and blunted affect. Negative symptoms also include restrictions in thought productivity and speech and in initiation of goal-directed activities. A third category of symptoms is impairment in attention, information processing, and memory. A thoughtful review of the biopsychologic aspects of schizophrenia reveals the heterogeneity of schizophrenia and the complexities in unraveling its components.[84] Although disturbances of language and, by inference, perception and thought are probably the most salient clinical phenomena, research summaries reveal comorbid problems with depression, anxiety, and PTSD.[83] Treatment advances have resulted from increased understanding of the multifactorial nature of the disease and its various presentations and subtypes, bolstered by a voluminous body of research in psychopharmacology, neuropsychiatry, neuropsychology, and neurobiology.

Kane described the gains resulting from research and development that yielded a new generation of antipsychotics that have been associated with less negative side-effect profiles.[85] He observed that the first three decades of widespread antipsychotic use, dating from the 1950s, were marked by major deficiencies, such as elevated incidence of acute and chronic neurologic effects, frequently poor or only partial outcome responses, and high rates of noncompliance. He emphasized that the introduction of clozapine helped to set the stage for new perspectives on antipsychotic drug treatment and development as well as outcome assessment ( Table 15-6 ). [86] [87] [88] [89] The success of clozapine in some refractory patients led to renewed interest in developing better treatment strategies, particularly for patients thought to be “poor responders.” Some treatment options have included adjunctive lithium, benzodiazepines, anticonvulsants, and ECT; however, the second-generation antipsychotics such as risperidone and olanzapine, marketed initially in 1994 and 1996, respectively, and quetiapine offer new hope for patients with schizophrenia.

TABLE 15-6   -- Nonaffective Psychoses Medications

Class

Generic Name (Trade Name)

Antipsychotic medications

  

 

Acetophenazine (Tindal)

  

 

Carphenazine (Proketazine)

  

 

Chlorpromazine (Thorazine)

  

 

Chlorprothixene (Taractan)

  

 

Clozapine (Clozaril)

  

 

Droperidol (Inapsine)

  

 

Fluphenazine (Permitil, Prolixin)

  

 

Haloperidol (Haldol)

  

 

Loxapine (Loxitane)

  

 

Mesoridazine (Serentil)

  

 

Molindone (Lidone, Moban)

  

 

Olanzapine (Zyprexa)

  

 

Perphenazine (Trilafon)

  

 

Pimozide (Orap)

  

 

Piperacetazine (Quide)

  

 

Prochlorperazine (Compazine)

  

 

Quetiapine (Seroquel)

  

 

Risperidone (Risperdal)

  

 

Sertindole (Serdolect)

  

 

Thioridazine (Mellaril)

  

 

Thiothixene (Navane)

  

 

Trifluoperazine (Stelazine)

  

 

Triflupromazine (Vesprin)

  

 

Ziprasidone (Geodon)

  

 

Zotepine (Nipolept)

PERTINENT SIDE EFFECTS OF THESE MEDICATIONS: acute and late-onset (tardive) extrapyramidal side effects, agranulocytosis, anticholinergic effects, disturbances of cardiac rhythm, dry mouth, dysregulation of temperature, hypersalivation, orthostatic hypotension, sedation, seizures, thromboembolism, tremors, withdrawal symptoms.

 

 

 

Patients with a history of schizophrenia, or schizophrenic-like disorders, such as schizoaffective disorder, require careful workup for medications taken over time as well as tactful and thoughtful management in the medical situation. Stressful events of all types may exacerbate symptoms of distrust, disorganization, and fears among these patients, and diagnosis of medical illnesses and prospects of surgery may trigger symptom exacerbation. This point is underscored by Pollard, Brook, and Shafer in a case report of a 40-year-old man treated for schizophrenia who underwent podiatric surgery with an ankle block regional technique.[90] In this event, the patient threatened violence to his wife and father when sedative effects were decreasing and necessitated appropriate management and psychiatric consultation. In an investigation of the relationship between postoperative confusion and plasma norepinephrine and cortisol response to surgery in patients with schizophrenia compared with a control sample, higher rates of postoperative confusion 72 hours after surgery in schizophrenic (28%) compared to control (6%) patients have been reported.[45] The researchers concluded that the occurrence of confusion in patients with schizophrenia was associated with an increase in plasma norepinephrine and cortisol levels during and after surgery.

Raised incidence of potential abnormal behaviors, including threats of violence and confusion postoperatively, have been observed to be of concern to anesthesiologists and surgeons.[6] Studies have pointed to the chronic administration of antipsychotic agents as being associated with other anomalies, such as alterations in autonomic functioning and pituitary-adrenal activity after surgery, as well as abnormal secretion of vasopressin, aldosterone, and atrial natriuretic peptide during anesthesia. [91] [92] These and other difficulties result from the multiple potential adverse effects of the antipsychotic agents in and of themselves, such as behavioral toxicity, motor aberrations, cardiovascular and autonomic nervous systems effects, and hepatotoxicity, as examples. There are also disturbances in autonomic nervous system functions, ECG abnormalities, and onset of diseases such as diabetes arising in association with long-term use of antipsychotics. Beyond the effects of the antipsychotic medications themselves, there are problems with drug-drug interactions between certain psychotropic drugs and anesthetic agents ( Table 15-7 ).[3] Additionally, it is notable that there is a dose-response relationship between number of physical problems and the risk of self-harm, necessitating physicians to consider the possibility of suicidal ideation in patients with physical illnesses complicated by schizophrenia, depression, and other mental disorders.[93]


TABLE 15-7   -- Interactions Between Psychotropic Medications and Anesthetic Agents

Psychotropic Medication

Anesthetic Agent

Interaction

Tricyclic antidepressants (TCAs)

Halothane and pancuronium

Tachydysrhythmias

 

Anticholinergics

Exaggerated anticholinergic responses

 

Sympathomimetics

Hypertension

Monoamine oxidase inhibitors (MAOIs)

Meperidine

Hypertension, seizures, hyperpyrexia

 

Sympathomimetics

Hypertension

Phenothiazines

Enflurane and isoflurane

Hypotension

Lithium

Barbiturates

Prolonged somnolence

 

Nondepolarizing relaxants

Prolonged blockade

 

Depolarizing relaxants

Prolonged blockade

Donepezil

Depolarizing relaxants

Prolonged blockade

Adapted from: Derrer SA, Helfaer MA: Evaluation of the psychiatric patient. In Rogers MC, Tinker JH, Covino BG, Longnecker DE (eds): Principles and Practice of Anesthesiology. St. Louis, Mosby, 1993, pp 567-574.

 

 

The method of action of all antipsychotics is direct interference with the centrally located dopaminergic neurotransmitter system. Furthermore, they have been shown to stimulate the parasympathetic nervous system and to block the effects of α-adrenergic stimulation of the sympathetic nervous system. This implies the possibility for cardiovascular side effects, including hypotension, tachycardia, prolongation of the QT interval on the ECG, and, although very rare, ventricular fibrillation and torsades de pointes. Owing to the functional hypovolemia induced during general or regional anesthesia, or to blood loss and fluid shifts for acutely injured and septic patients, respectively, these concerns become heightened intraoperatively. It should be noted as well that most antipsychotics are metabolized by the cytochrome P450 enzyme system, most notably the 2D6 isoenzyme. Several of the newer drugs are metabolized by several of the cytochrome isoenzymes concurrently, including the 1A2 and 3A4 subsystems.

The incidence of extrapyramidal side effects is higher with older, more potent agents such as haloperidol. With the advent of clozapine, the incidence of these side effects has decreased markedly. However, they still occur and can be life threatening. One such reaction that is seen rarely is laryngospasm, requiring treatment with an anticholinergic medication or diphenhydramine. More frequently seen are acute dystonic reactions such as oculogyric crisis, torticollis, or tremor. One of the more tragic dystonic reactions is tardive dyskinesia, which is characterized by involuntary choreoathetoid movements of the neck and face. Once these movements have begun, they may never resolve, even with withdrawal of the medication responsible. Nearly every neuroleptic medication may cause tardive dyskinesia, with clozapine posing the least risk.

Perhaps the most feared complication of treatment with antipsychotics is neuroleptic malignant syndrome (NMS).[94] NMS is very similar to malignant hypothermia (MH) and may share a similar etiologic mechanism. This syndrome most often occurs within the first several weeks of treatment with or a significant dosage increase of antipsychotic medications. It manifests as increased body temperature, skeletal muscle rigidity, and sympathetic nervous system instability (blood pressure fluctuations, diaphoresis, and tachydysrhythmias). Often liver function tests are abnormal, although the mechanism for this abnormality is uncertain. Because of the severe muscle rigidity, creatinine kinase levels may be elevated and the kidneys may become damaged from myoglobinuria. If these concerns become significant, muscle relaxation with a nondepolarizing neuromuscular blocking drug and subsequent mechanical ventilation of the lungs may become necessary. Treatment of this disorder requires withdrawal of the offending agent and initiation of bromocriptine or dantrolene therapy. Of these two therapies, dantrolene is preferred by some practitioners because of bromocriptine potentially precipitating hypotension. ECT may also have a therapeutic effect on these patients as well. Additional treatments are supportive and include antipyretics, intravenous hydration, and dialysis, in addition to those measures just described. Mortality in untreated cases can be as high as 20%. If the patient survives, further treatment with antipsychotics is usually not suggested secondary to the possibility of recurrence. In these patients, alternative therapies like lithium or ECT are advocated.

Anesthesia personnel must be aware of the similarity of NMS and MH and especially vigilant when providing care to persons with a documented history of the former because of the possibility, although unproven, that these patients may be predisposed to the development of the latter. Despite this possibility, it has been shown that administration of succinylcholine to patients receiving ECT as treatment for NMS is safe.[95] Intuitively, it would seem that because of the similarity of the two syndromes, they may, as previously stated, share a similar molecular mechanism. Although evidence to support this supposition is lacking, caution is advised when administering general anesthesia to patients with a history of NMS and more broadly to anyone receiving treatment with neuroleptics.

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Delusional Disorder

Among other psychotic disorders are schizophreniform and schizoaffective disorders, both sharing features in common with schizophrenia and depression, psychotic disorders judged to be a direct physiologic consequence of a general medical condition, and the unusual but interesting delusional disorder. The notion of delusion is plagued by conceptual confusion, but the DSM-IV calls attention to a condition characterized by the presence of one or more non-bizarre delusions that persist for at least 1 month but not in the context of an history of schizophrenia.[15] Apart from the direct impact of the delusions, psychosocial functioning is not markedly impaired and behavior may not be seen as odd or bizarre. In this disorder, the following themes are often found: erotomanic, grandiose, jealous, persecutory, and somatic.[95] Thus, patients may maintain unusual beliefs about romantic love or idealized spiritual union or hold a view of themselves as having great but unrecognized talents or insights. Persecutory delusions may be found, with the central delusional theme involving beliefs that one is being cheated, spied upon, or conspired against. Although such disorders are uncommon in clinical settings, they may appear unexpectedly to anesthesiologists or surgeons, particularly in adult patients in mid to late life. Evaluation of delusions is difficult, especially in the absence of obvious, marked psychopathology, and relationships with affective disorders, schizophrenia, and organic brain disorders, such as epilepsy, and a range of other disorders must be considered. In the case of somatic delusions, reported cases include patients suffering from temporal lobe epilepsy, narcolepsy, Huntington's chorea, cerebral malaria, multiple sclerosis, encephalitis, chronic liver disease, pellagra, disorders of the thyroid, and others.[95]

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SUBSTANCE-RELATED DISORDERS

Included in the DSM-IV are a variety of substance-related disorders having to do with side effects of medications, toxin exposure, and use and abuse of prescription and illicit drugs, as well as alcohol.[15]The substances are classified in 11 categories: alcohol, amphetamine or similarly acting sympathomimetics, caffeine, cannabis, cocaine, hallucinogens, inhalants, nicotine, opioids, phencyclidine or similarly acting arylcyclohexylamines, and sedatives, hypnotics, or anxiolytics. Use of substances may be seen as “abuse” or “dependence” depending on behavioral and psychologic characteristic use patterns, and assessment of features of both tolerance and dependence are critical in defining abuse and dependence. Problems resulting from substance intoxication, or recent ingestion of or exposure to a substance, may arise in evaluation of patients for anesthesia. Indicating the seriousness of such problems, Smothers and colleagues reported the first national prevalence estimates of DSM-IV alcohol use disorders among 2,040 inpatient admissions to 90 acute care, nonfederal U.S. general hospitals. [15] [96] These researchers found an estimated 1.8 million annual admissions met criteria for current alcohol use disorder, with an overall prevalence of 7.4%. Moreover, among current-drinking admissions, estimated prevalence was 24%.[96]

Although alcohol is one of the substances that might have been ingested by patients over time, possibly concomitant with hospital admission or preoperative evaluations, the potential complications to health and medical treatment associated with alcohol effects are enormous. Primary health care providers are often faced with patients who abuse substances of extreme variety, and when patients present for anesthesia and surgery there is a mandate to detect manifest mental problems, as well as covert substance use patterns that may impact response to anesthetic agents and the surgical procedure. Although beyond the scope of this chapter, it is necessary to call attention to the need for comprehensive anesthesia screening procedures to uncover patterns of alcohol use and abuse, as well as use of other drugs, many of which represent illegalities and thus may be glossed over by patients. Wu and associates reported that 2% of adults responding to the 1997 National Household Survey on Drug Abuse reported using services for alcohol or drug problems in the previous year.[97] One approach is application of the Alcohol Use Disorders Identification Test (AUDIT) for anesthesia screening. This 10-item measure was developed from a six-country collaborative project as a screening instrument for hazardous and harmful alcohol consumption and provides a simple method of detection for anesthesia screening.[98]

Clearly, there is a need for comprehensive but efficient screening for all possible drugs of use and abuse that may impact response to anesthesia and surgery. Identification of addiction and issues in pain management are critical to the safe and effective clinical management of anesthesia in surgical situations, as well as in the management of pain problems more generally. However, detailed consideration of those issues is beyond the scope of this chapter.

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DELIRIUM, DEMENTIA, AND OTHER COGNITIVE DISORDERS

Delirium

Delirium is a disturbance of consciousness accompanied by changes in cognition of multiple causes. The disturbance develops over the course of the day and may fluctuate during the day and over time. Awareness of the environment, ability to reason, and clarity of expression and thought are compromised. Disorientation, memory impairments, rambling speech, and perceptual distortions can occur. The range and type of disorders leading to delirium states are broad and beyond the scope of this chapter, yet delirium is considered because postoperative delirium is a major problem in many patients undergoing surgery, particularly among the elderly or patients with multiple illnesses or debilitation. An acute disorder of attention and cognition, delirium after surgery may be found in 28% to 50% of patients undergoing hip fracture repair.[99] Zahriya and coworkers reported that an inability to mount a stress response or lack of increase in white blood cell count and abnormal serum sodium levels were risk factors for occurrence of postoperative delirium in elderly patients undergoing hip fracture repair. Other conditions thought to be associated with acute confusional states and altered mental states include dementia, alcoholism, severe medical illness, vision or hearing impairments, advanced age, institutionalization, and depression, to name a few ( Fig. 15-1 ). [99] [100]

 
 

FIGURE 15-1  Approach to the patient with delayed emergence.  (From Bready LL: Delayed emergence. In Bready LL, Smith RB [eds]: Decision Making in Anesthesiology, 2nd ed. St. Louis, Mosby, 1992, pp 364-365.)

 



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Dementia

The DSM-IV defines dementia as characterized by multiple cognitive deficits that include memory impairment.[15] Classification is often determined by presumed etiology, such as dementia of the Alzheimer's type, vascular dementia, and dementia due to other general medical conditions, head trauma, Parkinson's disease, and Huntington's disease, to name some examples. In addition to memory impairment, symptoms of dementia may include aphasia, apraxia, agnosia, or executive function disturbances or deficit. Problems with judgment and insight are common, and patients with dementia may exhibit little or no awareness of memory loss or cognitive abnormalities. Motor disturbances leading to falls, neglect of personal hygiene, misplaced possessions, disinhibited behavior, and disregard of societal conventions may be observed. Because physical and mental stressors may exacerbate symptomatology, diagnosis of medical illness and receiving medical, surgical, and anesthesia treatments can be particularly stressful and disorganizing. Community studies reveal a 1-year prospective prevalence of almost 3% with severe cognitive impairment, and it is estimated that 2% to 4% of the population older than 65 are afflicted with Alzheimer's disease, a disorder that increases with age.[15]

Medical care of patients with limited and declining cognitive resources and adaptability as a result of an ongoing dementia is impacted adversely by patient difficulties in expression, language, and memory. Problems may result from individuals being unable to describe past and present illnesses to complete inability to communicate, or mutism. Physicians must rely on reports of significant others and family members to provide information pertinent to physical status or the basic data of the history and physical examination. Patients with dementia may become irritable, behaviorally agitated, and difficult to manage before surgical procedures and may be afflicted with delirium, postoperative confusion, and other impediments to recovery after procedures. Patients in the early stages of dementia may be taking anti-dementia medications such as donepezil. Clinical anesthesiologists should be aware that this agent is a cholinesterase inhibitor and can potentially exacerbate succinylcholine-induced muscle relaxation. Cholinesterase inhibitors may have vagotonic effects and cholinomimetic effects ( Table 15-8 ). [101] [102] The complete picture of presentation therefore is complicated and requires additional time and effort to work toward safe and effective delivery of anesthetic agents.

TABLE 15-8   -- Delirium, Dementia, and Other Cognitive Disorder Medications

Class

Generic Name (Trade Name)

Attention deficit disorder medications

D-Amphetamine (Dexedrine, Dexedrine Spansule, DextroStat)

 

Methylphenidate (Ritalin)

Central nervous system (CNS) stimulants

D-Amphetamine (Dexedrine, Dexedrine Spansule, DextroStat)

 

Methylxanthines (Caffeine, Theobromine, Theophylline)

Memory enhancers

Donepezil (Aricept)

 

Galanthamine (Reminyl)

 

Physostigmine (Antilirium)

 

Rivastigmine (Exelon)

 

Tacrine (Cognex)

Herbal and natural remedies

Ginkgo biloba

PERTINENT SIDE EFFECTS OF THESE MEDICATIONS: addiction potential, bradycardia, cardiac arrhythmias, circulatory collapse, diaphoresis, hypertension, reflex hyperactivity, skeletal muscle paralysis, vertigo.

 

 

 

Regarding new medications for the treatment of Alzheimer's disease, recent investigations on the safety and efficacy of memantine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, have shown promising results.[103] A randomized, double-blind, placebo-controlled clinical trial of 404 patients, already receiving donepezil, and with moderate to severe Alzheimer's disease, revealed significant improvement in cognition, activities of daily living, global outcome, and behavior after memantine administration. Thus, the use of memantine to treat patients with moderate to severe Alzheimer's disease may represent a novel pharmacologic approach to this dreaded disease.[103] Drugs on the horizon, such as alzamed, currently in phase 3 trials, may also show promise in providing yet another defense for patients against Alzheimer's disease.

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Other Cognitive Disorders

Mild to moderate cognitive impairments can occur as a result of head injury, specific medical conditions, and CNS dysfunction, but these deficits may not be sufficiently severe to meet criteria for dementia. For example, neuropsychological assessment may reveal evidence of weaknesses in executive functions, working memory, and semantic processing associated with head trauma or other CNS insult. Patients with cognitive disorders require identification and special attention in preoperative and postoperative conditions, because cognitive deficits place them at risk for confusion, behavioral agitation, depression, and other problems before and after surgery or after administration of anesthetics. There is also the possibility of increased vulnerability to anesthetic damage or drug interaction with anesthetic agents.

Clinicians and researchers have observed that anesthesia may provoke persistent alterations in cognitive performances in individuals at risk, including those with multiple illnesses, the elderly, and patients with dementia who have neuronal changes that may exacerbate pharmacotoxic effects. It is important that anesthesiologists recognize that acute and intermediate psychiatric problems may be associated with surgery or hospitalization.[104] For example, patients may experience delirium with psychotic elements as a result of the surgical or medical condition and may experience anxiety as a result of the imminent operation. Another source of stress for patients and anesthesiologists in the perioperative period is “intensive care unit (ICU) psychosis.”[104] The ICU setting may be linked to delirium in perioperative or very ill patients as a result of decreased sleep, increased arousal, social isolation, and mechanical ventilation.[104]

Regarding the postoperative period, in an assessment of 140 patients older than age 64 who completed a battery of cognitive tests before and at 9 days and 3 months after surgery, Ancelin and associates found a decline in performance 9 days postoperatively in 5.8% to 70.3% of patients, depending on the cognitive domain explored.[105] Twenty-nine percent of patients showed no significant alteration on any test score after 9 days, and 44% showed no deficit after 3 months. The greatest degree of impairment tended to be among the most elderly, least educated, and those having a history of cognitive deterioration. Type of anesthesia was found to be the most significant determinant of decline in verbal fluency, semantic prompt, visuospatial analysis, and implicit memory scores. Researchers concluded that anesthesia and orthopedic surgery are related to long-term (3-month) postoperative decline in the elderly, with secondary and implicit memory and visuospatial and linguistic tasks most frequently impacted. Among high risk factors were age older than 75, less education, high levels of depressive symptoms, and recent history of cognitive impairment. The influence of the stress of surgery and the effects of pain could not be evaluated, although they may play a role in cognitive decline. Other research has showed cognitive decline after major noncardiac operations, with impairment most notable immediately after surgery but sometimes persisting. Grichnik and colleagues studied 29 patients who had thoracic and vascular procedures preoperatively and 6 to 12 weeks postoperatively.[106] They found the incidence of cognitive deficit to be 44.8%, with severity of decline being an average of 15%.

The incidence of cognitive decline seems to be most notable in patients subsequent to cardiac surgeries, where it is well recognized and often studied. One investigation evaluated 127 patients undergoing coronary artery bypass grafting preoperatively and at 1 month and 1 year across several cognitive domains.[107] At 1 year, less than one third of patients showed significant cognitive change compared with baseline performance, and change was associated with both medical and surgical variables, pointing to multiple causes such as the nonspecific effects of anesthesia and prolonged surgery interacting with the specific effects of the surgical procedure itself. Among the medical history variables, diabetes was associated with short- and long-term change in executive functions and psychomotor speed. Interest in pharmacologic cerebral protection for cardiac patients has been high, with some evidence that lidocaine infused at induction of anesthesia and continued for 48 hours may have protective effects. One group found cerebral protection by lidocaine unrelated to any effect on depression or anxiety and at a level noticed by patients.[108] Similarly, Wang and colleagues showed a reduction in cognitive dysfunction in patients treated with lidocaine in the early postoperative period.[109] Exploration of possible protective agents to work against cognitive decline or impairments associated with the stress of surgery or anesthetic agents and their delivery is of high priority, particularly for patients who are at risk by reason of various vulnerabilities. Butterworth and Hammon concluded that although controversy persists among those who study cardiac surgery outcomes, there are data that lidocaine may have neuroprotectant effects in focal neurologic injury and in reducing adverse neurobehavioral outcomes.[110]

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DISORDERS IDENTIFIED IN DEVELOPMENTAL STAGES

Mental Retardation

Mental retardation is characterized by significantly subaverage general intellectual functioning with limitations in adaptive functioning, such as in communication, self-care, home living, interpersonal skills, and self-direction. Many causes and different levels of severity can be found, but patients are markedly limited in their abilities to manage the exigencies of life. In all cases, patients require custodial care at some level of supervision and generally are managed by a guardian or family member. Although many patients with mental retardation do not pose extreme behavioral problems, preparing them for surgery and anesthesia demands special precautions. For example, Chan and Chilvers described inducing anesthesia in a combative, intellectually impaired adult whose needs suggested that anesthesia induction in the home was helpful to facilitate essential surgery.[111] This adult, with a history of escalating violence toward hospital personnel, was administered an anesthetic in his home before hospital transfer for surgery, illustrating an innovative approach to improving response to treatment. This is but one example of the problems possibly encountered in treating medical illnesses and symptoms in individuals with mental retardation or other intellectually impairing conditions. Although rarer, autistic disorder may also be identified, a disorder marked by abnormal and impaired development in social interaction and communication and often associated with moderate mental retardation.

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Attention-Deficit/Hyperactivity Disorder

Often diagnosed when children are young, and now frequently in adults, attention-deficit/hyperactivity disorder (ADHD) is characterized by persistent patterns of inattention and/or hyperactivity and impulsivity greater than might be expected, typically appearing before age 7. The DSM-IV estimated disorder prevalence at 3% to 5% in school-aged children, and diagnosis requires evidence of problems in social, academic, or occupational functioning.[15] Inattention may be exhibited as failing to notice details, sustain attention, or persist with tasks to completion, and affected children may not follow through on requests, may be disorganized, and may avoid activities that require sustained self-application and mental effort. Frequent shifts in conversation, not listening, and failures to listen and follow rules may be seen. Impulsivity and hyperactivity may present as impatience, difficulty delaying responses, interrupting others, being constantly on the go, fidgeting and squirming, and avoiding sedentary activities. Found in a variety of contexts and thought to be familial, these behaviors are usually seen in two settings, such as home and school. In many instances, primary care physicians identify ADHD using reports of parents and teachers; and over time there has been increased treatment of symptoms with antidepressants and/or stimulants (see Table 15-8 ). [101] [102]

Although ADHD is a significant health complication, mental health disorders more generally constitute a common cause of disability and distress among both children and adolescents. One group reported that 20% of outpatients age 18 and younger met criteria for psychiatric diagnosis in a given year and that psychotropic medications accounted for a substantial, increasing fraction of outpatient costs.[112] In light of multiple psychotropic pharmacotherapy among children and adolescents in various settings, the need for careful screening of minors for medications as part of anesthesia evaluation is obvious. In such instances, discussions with parents and children may be necessary to develop a full picture of medication and perhaps even other drug use. In this regard, numerous nutraceuticals, or herbal agents, have been utilized and have had some positive results with ADHD. [113] [114]

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Problem Behaviors in Late Life

Aggressive and inappropriate behaviors in older people have been linked to varied physical and psychological conditions and associated with added risks in the event of medical treatments and surgeries. Behavior problems pose complex challenges for caregivers in the home and in medical settings. Although these behaviors are often reported in clinical or nursing home settings, or when patients are afflicted with dementia, a growing literature describes problem behaviors as common in the last year of life in older people.[115] Studying 6,748 decedents, Bedford and colleagues discovered that 20% exhibited problem behaviors in the last year of life, with risks being higher for those with dementia, mental illness, alcohol abuse, and bronchitis or emphysema. Such problems as violent threats and destroyed property were identified as relatively common, with implications for health care providers in general and anesthesiologists and surgeons more particularly.

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CONCLUSION

Patients of all ages and with diverse mental and physical conditions may present for anesthesia under many, and unexpected, circumstances. Mental and cognitive disorders may disrupt normal communication between physicians and patients and contribute to difficulties in deciding on the best medications and strategies for anesthesia. The information presented on mental disorders provides convincing evidence that thorough screening is required for all patients and that special care is demanded when there are mental or physical handicaps, complex histories of drug use, mental disorder symptoms, and other risk factors for anesthesia delivery and recovery from surgery. Of great concern are the potential interactions between drugs used during anesthesia and those prescribed for treatment of mental disorders, and anesthesiologists need also be aware of the behaviors that signify and characterize mental illness. Studies have shown that a high number of patients scheduled for surgical procedures take psychiatric medications or agents that possess potential neurobehavioral effects. Inasmuch as these studies indicate poor self-disclosure to health care providers, anesthesiologists are required to assess each patient carefully and thoroughly. In this regard, many psychiatric drugs can alter MAC requirements, affect sedation levels, and influence anesthetic techniques, such as successful delivery of regional anesthesia.

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