Key points
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An estimated 26.2% of Americans age 18 and older have a diagnosable mental disorder in a given year (58 million people).
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Mental disorders and their associated use of psychotropic medications, including antidepressants, anxiolytics, major tranquilizers, anticonvulsants, and mood stabilizers, introduce neurochemical, behavioral, cognitive, and emotional factors that complicate medical or surgical tasks.
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Anesthesiologists face unique challenges assessing patients with psychiatric disease, in all steps of patient treatment, regardless of the pathology.
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Pharmacologic therapy for major depression includes selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin and norepinephrine reuptake inhibitors. Each class has potentially lethal interactions with other medications, including nutraceuticals.
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Patients with bipolar disease, psychotic disorders (schizophreniform, schizoaffective), dementia, and substance abuse may be taking medications that affect anesthetics or may present in states with altered anesthesia requirements, posing problems perioperatively.
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Medications for anxiety, posttraumatic stress disorder, panic attacks, and social phobias can cause tolerance and have similar effects as some anesthesia agents.
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Patients undergoing electroconvulsive therapy must have careful medication evaluation to prevent drug interactions and possible inability to seize from anticonvulsant properties of routine medicines.
Mental illnesses, cognitive disorders, and mental health problems affect persons in all walks of life; few families in America are untouched by mental illness. An estimated 26.2% of Americans age 18 years and older suffer from a diagnosable mental disorder in a given year. When applied to the 2009 U.S. Census residential population estimate for ages 18 and older, this figure translates to approximately 58.1 million people. Mental disease interferes with life activity and ability to function and constitutes a pervasive and prevalent health problem among varied American population subsets, including young and elderly groups. The presence of mental disorders, associated symptoms, possible concomitant pathology, and prescribed medications are of significance to all health care providers, not only mental health care professionals. The burden of mental disease on health care utilization and effectiveness has become a topic of worldwide interest and concern.
Beyond concerns about the adequacy of treatment for mental illnesses, both in the United States and globally, special considerations involve management of patients with serious mental illness in emergency care and inpatient treatment situations, general medicine, family practice and pain clinics, and the operating room (OR). Important to anesthesiologists managing patient care is knowledge about the patient’s mental and physical illnesses; history of alcohol, drug, and tobacco use; use and abuse 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; medical conditions that can mimic psychiatric disturbances include endocrine diseases (hypothyroidism, Cushing’s syndrome); neurologic diseases (seizure, demyelinating disease, encephalitis, CNS tumor/mass, head trauma); alcohol and drug abuse; metabolic disorders; and chemical or drug intoxication.
This chapter reviews the major types of mental disorders and outlines issues and concerns that face anesthesia care providers in planning case management. Specifically, the focus is on appropriate perioperative management of patients with mental disorders undergoing surgical procedures requiring anesthetic intervention.
Mental disorders
The use of psychotropic medications (e.g., antidepressants, anxiolytics, major tranquilizers, anticonvulsants, mood stabilizers) introduces 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. The use of psychotropic medications has increased significantly over the last several decades, with psychiatrists and family practice physicians prescribing tranquilizers, neuroleptics, and antidepressants, even to young persons. With depression alone, numerous complexities exist 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.
Epidemiology
The National Comorbidity Survey Replication (NCS-R) estimates the incidence of mental illness for Americans aged 18 and older is 26.2%. The President’s Commission on Mental Health concluded in 1978 that the annual prevalence of specific mental disorders in the United States was about 15%. Bourdon et al. assessed that in any 6-month period, 19.5% of the adult population, or one in five individuals, suffers from a diagnosable mental disease. Epidemiologic estimates have shifted over time because of changes in the definitions and diagnosis of mental health and mental illness. For more than two decades, scientists have used well-structured lay interviews as part of community-wide surveys to diagnose mental disorders and determine the incidence and prevalence of serious mental illnesses.
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 age 15 to 54 years in the 48 contiguous states, along with a survey of campus-housing students. Data were collected between 1990 and 1992 for 8089 respondents. The study’s purpose was to assess comorbidity of substance use disorders and non-substance-based psychiatric disorders using a modified version of the Composite International Diagnostic Interview. Morbidity rates were higher than the 1980–1985 Epidemiologic Catchment Area (ECA) project estimates, possibly because of methodologic and illness-defining differences in study implementation. Nevertheless, results were impressive toward developing an understanding of mental disorder prevalence and comorbidity. Almost 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. Factors of age, gender, race, socioeconomic status, and geographic region influenced prevalence trends. Women had 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.
Characterization
A mental disorder is a clinically significant psychological or behavioral pattern generally associated with subjective distress or disability, likely with significantly increased risk of suffering death, pain, disability, or loss of freedom, and not a part of normal development or culture. The recognition and understanding of mental health conditions has changed over time and across cultures, and the definition, assessment, and classification of mental disorders still vary, although standard guideline criteria are widely accepted. A few mental disorders are diagnosed based on the harm to others, regardless of the patient’s perception of distress. More than one third of people in most countries report meeting criteria for the major mental disorder categories at some point in their life.
Mental disorders constitute an enormous public health problem, interfering with life activities and functions. U.S. Public Law 102-321 defines “serious mental illness” as the presence of any DSM mental disorder (see later), substance use disorder, or developmental disorder that leads to “substantial interference” with “one or more major life activities.” This framework is used to characterize mood and anxiety disorders, nonaffective psychoses, 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 associated with physical trauma leading to organic brain syndrome, as well as cognitive disorders, such as dementia of midlife to late-life stages. Clinicians may also need to attend to other forms of mental disorder resulting from a general medical condition, somatoform disorders, and disorders of eating, sleep, impulse control, and adjustment.
This discussion also clarifies the clinical status of primary care patients with symptoms of mental distress that fall below the threshold criteria for a mental disorder. Olfson et al. found that in primary care patients, the morbidity of subthreshold symptoms was often explained by confounding mental, physical, or demographic factors. However, depressive symptoms and panic symptoms tended to be disabling, and these patients may have been at increased risk for development of major depression, even though they were a heterogeneous group.
Preoperative Evaluation
Practicing clinical anesthesiologists face unique challenges when they assess patients with psychiatric diseases, regardless of the pathologic nature of the disease. Such issues may arise during all steps of patient treatment, including history taking, obtaining informed consent, and physical examination.
Patient history
Many of these patients will not communicate well with the anesthesiologist either because they are unable to do so (e.g., if they suffer from profound psychosis, delirium, memory disturbances, and so on), or because they choose not to talk (e.g., out of embarrassment or hostility). It may be difficult to establish rapport with such patients even if they seem otherwise cooperative. Often, anesthesiologists find that it is easier to obtain data from medical records (history, medications, previous interventions). A few patients with mental disorders, however, will present without clinicians having access to their medical records. When medical records are available, clinicians must review these records carefully and be prepared to measure this information against patient-reported history. Often, patient 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.
In some cases the anesthesiologist evaluating the psychiatric patient may consult directly with the primary care physician or psychiatrist in charge of care and address preoperative concerns. In addition, the anesthesiologist should establish rapport with the patient to minimize emotional trauma in the OR. In this regard the anesthesiologist’s role as consultant cannot be overstated. Some patients may present for surgery with an undiagnosed disease that mimics psychopathology. Appropriate history-taking skills, physical examination, and laboratory tests may reveal a mental disorder. 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 of the potential for adverse outcomes from inappropriate management of such disorders.
Informed consent
Another issue is obtaining informed consent from patients with psychiatric diseases. Informed consent is ethically and legally required before surgery, and surgery without consent may be considered civil or possibly criminal assault and battery. Criteria for informed consent dictate that (1) the patient must possess sufficient decision-making capacity, (2) it must be a voluntary decision (free from coercion), and (3) sufficient information must have been provided to the patient prior to the final decision. Competent patients have a right to decide whether to accept or reject proposed surgery, even if aware that it could be lifesaving.
When the patient is incapable of informed consent and does not refuse surgery, surgeons seek permission from next of kin or a legally designated surrogate. Only the court can legally declare a patient incompetent, but psychiatric consultants can evaluate a patient’s decision-making capacity. Frequently, when psychiatric consultation is requested to determine the capacity of a patient refusing surgery, the reason for refusal is unrelated to the patient’s decision-making capacity (e.g., it is deemed that insufficient information has been provided to the patient, or that the patient displays fear or emotional unreadiness).
Underrecognized perioperative psychiatric problems
Considering the high prevalence of mental disorders in the American population, it is not surprising that many surgical patients are taking antipsychiatric medications at the time of surgery. However, many patients’ psychiatric history is not obtained or even considered until problems arise postoperatively. One reason for this retrospective evaluation is underrecognition of psychological distress by the surgical team preoperatively. A psychiatric history should be routinely obtained during the general preoperative evaluation and as an outpatient before admission when the surgery is elective. Disorders may flare during the postoperative period, and abrupt discontinuation of psychiatric medication, as a result of oversight or the patient’s inability to take oral medication for a sustained period, adds to the risk of relapse of psychiatric disorders as well as symptoms of medication discontinuation.
Mood disorders
Mood disorder is the term designated to a set of diagnoses in the American Psychiatric Association (APA) Diagnostic and Statistical Manual of Mental Disorders , fourth edition (DSM-IV) classification system in which disturbance in a person’s mood is hypothesized to be the main underlying feature. Mood disorders were formerly called “affective disorders,” a name initially proposed by British psychiatrist Henry Maudsley. Mood disorders are further categorized into major depression and bipolar disorders based on depressive or manic episodes.
A mood disorder is characterized by a depressed mood, a lack of interest in activities normally enjoyed, changes in weight and sleep, fatigue, feelings of worthlessness and guilt, difficulty concentrating, and thoughts of death and suicide. If a person has experienced most of these symptoms for longer than 2 weeks, they may be diagnosed as having had a “major depressive episode.” In the DSM-IV a person having one or more major depressive episodes is considered to have major depression. After one episode, “major depressive disorder (single episode)” would be diagnosed. After more than one episode, the diagnosis becomes “major depressive disorder (recurrent).” Depression without periods of mania is also called unipolar depression because the mood remains at one emotional state, or “pole.” Specifiers can be added to describe severity, other features (e.g., postpartum onset), and course of recurrent episodes.
Major Depression
Among the mood disorders, the most studied is major depression, a common and disabling psychiatric disorder in the United States. The prevalence of major depression is estimated to be as high as 5.3% in adults (17 million patients) and 4% in adolescents. Major depression has a 17% lifetime prevalence in the general U.S. population. Lifetime risk of an episode for women is 20%. In the 2001–2002 NCS-R, Kessler et al. reported the prevalence and correlates of major depression using DSM-IV criteria in 9090 household residents age 18 years and older. 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.
As many as 74% of NCS respondents with lifetime depression showed one or more coexisting disorders, with anxiety (58%) and substance abuse (38%) most common. The prevalence of depression in cancer patients is twofold to threefold the rate documented in the general population, and as many as 25% of patients in extended care facilities may have major depression. , , The incidence of major depression appears to have increased, reaching younger persons, yet often going undetected and undiagnosed in all age groups.
Characteristics
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 disorders due to general medical condition,” substance abuse–induced mood disorders, dementia, and adjustment disorders with depressed mood and simple bereavement.
At the opposite end of the spectrum, manic episodes are characterized by inflated self-esteem or grandiosity, decreased need for sleep, pressured speech, flights 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.
Risk factors
Factors associated with increased risk for major depression are female gender, genetic inheritance, history of trauma, homemaker status, sexual abuse, physical abuse, physical disability, bereavement at a young age, alcoholism, insufficient family structure, unemployment or disability, lack of marriage history, lower education, and living in or near poverty levels. Risk seems to be low until the early teenage years, but depressive disorders can occur throughout the life cycle. Major depression is 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 (59%), substance abuse disorder (24%), and impulse-control disorder (30%). Approximately 90% of 12-month major depression cases were classified as moderate, severe, or very severe.
Depression is also associated with physical illness, affecting multiple domains of functioning and well-being. Patients with depressive conditions have poorer mental, emotional, and social functioning than even those with chronic medical conditions. , For example, depressed patients may report higher levels of fatigue and fatigue-related interferences than cancer patients.
Pharmacologic therapy
Selective Serotonin Reuptake Inhibitors
Selective serotonin reuptake inhibitors (SSRIs) are undoubtedly the most commonly prescribed antidepression medications. The U.S. Centers for Disease Control and Prevention (CDC) found that of 2.4 billion drug prescriptions in 2005, 118 million were for antidepressants. Antihypertensive prescriptions came in second with 113 million. Depressed patients prescribed psychotropic medications rose from 44.6% in 1987 to 79.4% in 1997, with the increase attributed primarily to SSRIs, which were unavailable in 1987 ( Table 15-1 ). ,
| Class | Generic (Trade) Names | Common Side Effects; Comments |
|---|---|---|
| Selective serotonin reuptake inhibitors (SSRIs) | Citalopram (Celexa, Cipram, Cipramil, Serostat) Escitalopram (Lexapro) Fluvoxamine (Dumirox, Feverin, Floxyfral, Luvox) Fluoxetine (Prozac, Sarafem) Paroxetine (Paxil) Sertraline (Zoloft) | SSRIs are safer when overdosed. Nausea, diarrhea, headache Loss of libido, erectile dysfunction, failure to reach orgasm Increase in suicidal ideation Serotonergic syndrome |
| Tricyclic antidepressants (TCAs) | Amitriptyline (Elavil, Endep, Entrofen) Amoxapine (Asendin) Clomipramine (Anafranil) Desipramine (Norpramin, Pertofran) Doxepin (Adapin, Sinequan) Imipramine (Norfranil, Tofranil, Tipramine) Maprotiline (Ludiomil) Nortriptyline (Aventyl, Noratren, Pamelor) Protriptyline (Vivactil) Trimipramine (Surmontil) | Cardiac: increased heart rate and blood pressure Dry mouth, blurred vision, drowsiness, dizziness, skin rash Weight gain or loss Sexual problems |
| Monoamine oxidase inhibitors (MAOIs) | Deprenyl (Eldepryl) Phenelzine (Nardil) Selegiline (Emsam) Tranylcypromine (Parnate) | Heart attack, liver inflammation, stroke, seizure Severe hypertension if taking together with tyramine-rich foods or beverages Weight gain, constipation, dry mouth, dizziness, headache, drowsiness, insomnia, sexual side effects |
| Reversible inhibitors of MAO-type (RIMAs) | Moclobemide (Aurorix) | Urticaria, angioedema, asthma; insomnia, anxiety, agitation; vertigo, headache, seizure; nausea, diarrhea; hypertension |
| Noradrenaline reuptake inhibitor (NARI) | Reboxetine (Edronax, Vestra) | Dry mouth, constipation, headache, drowsiness, dizziness, sweating, insomnia, hypertension |
| Norepinephrine and dopamine reuptake inhibitor (NDRI) | Bupropion (Wellbutrin, Wellbutrin SR) | Restlessness, insomnia, headache, worsening of migraine conditions, tremor, dry mouth, agitation, confusion, rapid heartbeat, dizziness, nausea, constipation, menstrual complaints, rash |
| Serotonin and noradrenaline reuptake inhibitors (SNRIs) | Venlafaxine (Effexor) Duloxetine (Cymbalta) Milnacipran (Ixel, Savella, Dalcipran,Toledomin) | Nervousness, agitation, headache, insomnia, seizure Nausea, diarrhea, rash Sexual side effects: problems with arousal or satisfaction ↓Sexual function; headache, ↑heart rate, hyperhidrosis, mood swing to mania |
| Combined reuptake inhibitors and receptor blockers (CRIRBs) | Nefazodone (Dutonin, Serzone) Trazodone (Desyrel, Trazon, Trialodine) | Drowsiness, nausea/vomiting, headache and dry mouth |
| Noradrenergic and specific serotonergic antidepressant NSSA (NaSSA) | Mirtazapine (Remeron) | Dizziness, blurred vision, sedation, somnolence, malaise/lassitude, ↑appetite and weight gain, dry mouth, constipation, ↑libido/sexual function; vivid, bizarre, lucid dreams or nightmares |
| Herbal | Gingko biloba remedies Ginseng Hypericum perforatum (St. John’s wort) | Nausea, diarrhea, dizziness, headache, bleeding, weakness, seizure, headache Nervousness, excitability, headache, euphoria, bleeding GI symptoms, dizziness, confusion, tiredness, sedation |
| Atypical | Amisulpride (Deniban, Solian, Sulamid) Viloxazine (Vivalan, Vivarint) | Amenorrhea, galactorrhea, nausea, weight gain, akathisia, sexual dysfunction GI symptoms; dysarthria, tremor, agitation, SIADH, ↑libido |
Discoveries from psychopharmacologic research have altered depression treatment protocols, particularly over the past 20 years, and use of antidepressants increased threefold to fivefold from 1988 to 1994 among those under age 20. In recent decades, primary care physicians have initiated more antidepressant pharmacotherapy than psychiatrists. The pharmacology of depression treatment is well detailed, including side effects, adverse drug effects, and drug-drug interactions, as well as patient-specific factors such as gender, age, and other illnesses.
Antidepressants act on multiple receptors and induce various neurochemical modulating effects ( Table 15-2 ). The SSRIs are the most frequently encountered antidepressants by practicing anesthesiologists. SSRIs selectively potentiate the transmission of central nervous system (CNS) impulses along serotonergic pathways while having little effect on other neuroendocrine pathways, such as those involving norepinephrine or acetylcholine. Thus, SSRIs lack many of the side effects associated with other classes of antidepressants. However, SSRIs may cause nausea, diarrhea, headache, sexual dysfunction, agitation, and besides some mild sedative effects, insomnia. Specifically, escitalopram may be associated with hyponatremia. Fluoxetine is a potent inhibitor of the cytochrome P450 2D6 (CYP2D6) isoenzyme. The inhibition of this enzyme leads to a rise in the plasma concentration of drugs that depend on hepatic metabolism for clearance, such as β-blockers, benzodiazepines, and some antidysrhythmic drugs. 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 tricyclic plasma concentrations. Combining SSRIs with monamine oxidase inhibitors may precipitate serotonin syndrome, which is similar to neuroleptic malignant syndrome both in presentation and mortality and is marked by flushing, restlessness, anxiety, chills, ataxia, insomnia, and hemodynamic instability. Combination of fluoxetine with the mood stabilizer carbamazepine or lithium may also precipitate serotonin syndrome. Whether SSRIs potentially increase the risk of suicide in a small subgroup of depressed patients is an ongoing debate. ,
| Drug | Anti-histamine Activity (H 1 ) † | Anti-muscarinic Activity † | Anti–α 1 -adrenergic Activity | REUPTAKE INHIBITION | Elimination Half-Life (hr) | |
|---|---|---|---|---|---|---|
| NE | 5-HT | |||||
| Amitriptyline | 3 | 3 | 3 | 2 | 4 | 32-40 |
| Doxepin | 4 | 2 | 3 | 1 | 2 | 8-25 |
| Imipramine | 1 | 2 | 1 | 2 | 4 | 6-20 |
| Trimipramine | 4 | 2 | 3 | 1 | 1 | 9 |
| Desipramine | 0 | 1 | 1 | 4 | 3 | 12-54 |
| Nortriptyline | 1 | 1 | 2 | 2 | 3 | 15-90 |
| Protriptyline | 0.5 | 3 | 1 | 3 | 3 | 54-92 |
| Amoxapine | 1 | 1 | 2 | 2 | 2 | 8-30 |
| Maprotiline | 2 | 1 | 1 | 2 | 1 | 27-58 |
| Trazodone | 0.5 | 0 | 2 | 0 | 3 | 3-9 |
| Fluoxetine | 0 | 0.5 | 0 | 1 | 4 | 168-210 |
| Bupropion | 0 | 0 | 0 | 0 | 0 | 8-24 |
* Relative scale of 1 to 4 with 1 = least effect.
† Relative agents: atropine = 4 (antimuscarinic activity), diphenhydramine = 2 (antihistamine activity, phentolamine = 4 (anti–α 1 -adrenergic activity).
For anesthetic management, SSRIs do not pose too much challenge. SSRIs have no effect on seizure threshold. Some attentions should be paid to drug combinations and the effects of drugs taken by patients on the CYP450 system if patient has been taking barbiturates, benzodiazepines, and certain neuromuscular blocking drugs.
Tricyclic Antidepressants
The tricyclic antidepressants (TCAs) were the most widely used drugs to treat clinical depression prior to the SSRIs, after imipramine (Tofranil) was shown to be effective for treating depression in the 1950s. TCAs primarily work by increasing the level of norepinephrine in the brain and, to a lesser extent, serotonin levels. Some TCAs also are antihistamines (which block the action of histamine) or anticholinergic (which blocks the action of acetylcholine, a neurotransmitter). These additional actions allow for uses of TCAs other than for treating depression, as well as introducing additional side effects. A TCA’s 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; most side effects associated with TCAs are more pronounced with first-generation TCAs. If it is a secondary amine, the drug is a second-generation TCA.
Tricyclics may inhibit the antihypertensive effect of clonidine (Catapres). Therefore, combining TCAs with clonidine may lead to dangerous elevations in blood pressure (BP). TCAs may affect the heart’s electrical conduction system. Combining TCAs with drugs that also affect the heart’s conduction system (disopyramide, pimozide, procainamide) may increase the frequency and severity of an abnormal heart rate and rhythm. Combining TCAs with carbamazepine (Tegretol) may result in lower TCA blood levels because carbamazepine increases the breakdown of TCAs, potentially reducing their effect. TCAs may increase the BP-elevating effect of epinephrine, norepinephrine, dopamine, phenylephrine, and dobutamine.
It is generally believed that the TCAs are equally potent in treatment of depression. On the other hand, all 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. The degree of cardiac dysrhythmia potential is essentially the same for TCAs, which should be avoided in patients with known cardiac conduction abnormalities, such as second-degree or higher atrioventricular block. Despite their potential for causing cardiac dysrhythmias, TCAs may paradoxically show some antidysrhythmic activity. Also, the electrocardiographic (ECG) changes that occur with these drugs tend to dissipate with ongoing treatment, implying some form of tolerance by the cardiac conduction system to these effects.
These changes are a concern, however, during the early phase of treatment of depressed patients with suicidal ideation. A frequently chosen method of suicide is overdose, and the medications chosen are those in patients’ possession, in this case, possibly their antidepressants. Overdose with TCAs may be achieved by ingesting 5 to 10 times the daily dosage, resulting in fatal arrhythmia or resistant myocardial depression. Despite these facts, overdose with TCAs typically presents as CNS depression, including seizures, hypoventilation, and coma. Anticholinergic symptoms are also present and may confuse the diagnosis. Normally, when patients present to the OR, these problems are not present. In the trauma patient, however, there may be need for concern if acute drug ingestion is present as part of a suicide attempt or abuse of these drugs.
Anesthetic management of patients taking TCAs focuses on side effects and drug-drug interactions. The mechanism of the antidepressant effects of TCAs involves enhancement of serotonergic and noradrenergic activity. TCAs’ inhibition of histaminergic, cholinergic, and α 1 -adrenergic activity is responsible for many of their side effects. The main concerns for these patients being treated with a TCA involve the cardiovascular system and the interaction of the drug with a specific neurotransmitter, such as norepinephrine. Administration of TCAs increases storage of this neurotransmitter in noradrenergic nerve terminals, and thus administration of indirect-acting vasopressors such as ephedrine may cause an exaggerated release of epinephrine. This effect is most pronounced with acute treatment and gradually dissipates after the first 2 to 3 weeks. Caution is therefore advised when administering drugs with sympathomimetic effects to patients receiving TCAs.
The anticholinergic effects of TCAs can cause problems because many 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. Furthermore, there is the possibility that preoperative treatment with scopolamine may increase the incidence of emergence delirium, although there are no formal studies that support this suspicion.
Monoamine Oxidase Inhibitors
The monoamine oxidase inhibitors (MAOIs) were the first class of antidepressants to be developed. MAOIs elevate the levels of norepinephrine, serotonin, and dopamine by inhibiting the enzyme monoamine oxidase. MAO breaks down norepinephrine, serotonin, and dopamine. When MAO is inhibited, norepinephrine, serotonin, and dopamine are metabolized significantly less, increasing the concentration of all three neurotransmitters in the brain. As a consequence, they act to extend the effect of norepinephrine at the nerve terminals. MAOIs fell from favor because of concerns about interactions with certain foods and numerous drugs, as well as the introduction of newer and safer antidepressants. MAOIs are reserved primarily for patients who have failed treatment with other antidepressants.
The MAOIs are devoid of many side effects of other classes of antidepressants. Their principal side effect is profound hypertensive crisis, as well as serotonin syndrome when the patient consumes tyramine-containing foods (most often wines or cheeses) or when combined with drugs having intrinsic sympathomimetic effects (e.g., meperidine, certain β-blockers). Tyramine and sympathomimetic drugs stimulate the release of norepinephrine from noradrenergic nerve terminals, enhancing the α-adrenergic effects. Other side effects include orthostatic hypotension, sedation, blurry vision, and peripheral neuropathy.
Anesthetic Considerations
Formerly, MAOIs were 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.
The MAOIs can also significantly increase the minimum alveolar concentration (MAC). Furthermore, serum cholinesterase activity may be impaired, requiring the dose of succinylcholine to be reduced. Liver function indices may become elevated during treatment with MAOIs. 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 narcotic most often involved, but with the exception of fentanyl, all opioids can precipitate a hyperpyrexic response that may be confused with malignant hyperthermia and has similar potential for mortality. Postoperative pain control can be achieved with minimal use of opioids and by employing alternatives (e.g., NSAIDs); regional anesthesia is preferred whenever possible.
Second-Generation Antidepressants
The second-generation antidepressants such as venlafaxine, trazodone, bupropion, and mirtazapine are reserved for the treatment of patients who have failed other pharmacologic management (e.g., SSRIs). Again, these drugs’ side effect profile can guide choice of drug. For example, venlafaxine may be linked to seizures and constipation as two side effects. Trazodone is the most sedating of the second-generation antidepressants and might be chosen to treat patients with insomnia. Unlike the TCAs, these alternative agents possess almost no anticholinergic effects or potential for cardiac dysrhythmias. For patients receiving more than one drug as part of therapy, avoidance of MAOIs in those undergoing therapy with a second-generation antidepressant is recommended.
Caution is warranted regarding St. John’s wort (Hypericum perforatum), used by many people to treat what they think is depression. Most of these individuals have never been diagnosed by a psychologist or psychiatrist as having depression. Recent studies indicate St. John’s wort is no more effective than a placebo in the treatment of major depressive disorder. Its efficacy for less severe cases is disputed. However, patients encountered in clinical practice still take this nutraceutical. The side effect profile is extensive, but the only major concern for anesthesiologists is the similarity of H. perforatum to the MAOIs in precipitating hypertension and hyperpyrexia.
Kudoh et al. compared 80 depressed patients with 50 controls 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. Another study evaluated 80 patients age 35 to 63 with major depression who underwent anesthesia during orthopedic surgery, divided into those who continued or discontinued antidepressants 72 hours before surgery. 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 postoperatively. Kudoh et al. 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.
Dysthymic Disorder
Dysthymic disorder tends to be a long-lasting illness and is considered a chronic depression, but with less severity than major depressive disorder. The term was first used by James Kocsis during the 1970s. Dysthymia , also known as neurotic depression, is a serious state of chronic depression; however it is less acute and severe than major depressive disorder. DSM-IV defines dysthymia as a chronically depressed mood that occurs for most of the day, more days than not, for at least 2 years. Dysthymic 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.
Lifetime prevalence is approximately 6% , and dysthymic disorder is often marked by early, insidious onset and a chronic course. Dysthymia may be superimposed on major depression; and many 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 are common; and with time, dysthymic disorder may be associated with multiple physical illnesses.
Bipolar Disorders
Bipolar disorder, or manic-depressive disorder, also referred to as “bipolar affective disorder” or “manic depression,” is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or more depressive episodes. 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 manifested 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, flights 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 present psychotic features. Mood in manic episodes may be seen as euphoric, unusually cheerful, or high; the expansive quality is described as seemingly 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 may 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. Designated subtypes within the bipolar spectrum reflect 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.
Risk factors
It is likely that genetic factors play an important role in bipolar disorder. About 80% to 90% of individuals with bipolar disorder have a blood relative with either depression or bipolar disorder. Bipolar disorder is not caused by a single gene change, however, but rather is probably the result of multiple gene abnormalities. Carney and Jones found that patients with bipolar disorder were also more likely to reside in an urban setting. Additionally, the younger population has a higher risk for bipolar disorder, which is encountered significantly more often between ages 15 and 30. Stressful major life changes (e.g., death of loved one) also increase the risk for bipolar disorder.
Some common medications may be related to bipolar disorder, such as corticosteroids and cancer medications. Certain medical conditions are also associated with a higher prevalence of bipolar disorder, such as thyroid disease, vitamin deficiency, end-stage renal disease, and some neurologic diseases (e.g., Parkinson’s, dementia).
Comorbidities
Substance abuse, cardiovascular diseases, obesity, and diabetes often coexist with bipolar disorder. Carney and Jones studied 3557 patients with bipolar disorder, 61% women (2162) and 39% men (1395). The control population of 726,262 was 53% female (381,116 subjects). The percentage of patients with bipolar disorder who had three or more chronic medical comorbidities was more than threefold higher than for controls (40.5% vs. 12.1%; p <.0001).
Many people with bipolar disorder also have alcohol or drug problems. Nicotine abuse/dependence was 192% more likely among patients with bipolar disorder than in subjects without mental health problems. The odds ratio (OR) were also much higher for alcohol abuse/dependence (19.63; 95% confidence interval [CI], 17.59-21.90) and polysubstance disorders (42.91; 95% CI, 37.83-48.66). Conditions related to alcohol use, such as peptic ulcer disease, liver disease, and pancreatitis, were also more common in patients with bipolar disorder. Liver disease and pancreatitis likely resulted from anticonvulsant use in this population. Street drugs or alcohol may seem to ease symptoms but can actually trigger, prolong, or worsen depression or mania.
Cardiovascular disease could be the expected result of weight gain, unhealthy diet, and increased nicotine use in patients with bipolar disorder. About 23% of these patients have hypertension, representing a 185% increase in stroke. Patients diagnosed with bipolar disorder also are more likely to have endocrine diseases such as diabetes, thyroid problems, and obesity
Comorbid anxiety disorders include posttraumatic stress disorder (PTSD), social phobia, and generalized anxiety disorder. Attention-deficit/hyperactivity disorder (ADHD) has symptoms that overlap with bipolar disorder, which therefore can be difficult to differentiate from ADHD. Sometimes one is mistaken for the other; other persons may be diagnosed with both conditions.
Prevalence
The lifetime community prevalence of bipolar disorder is 4% to 6.4%, which is significantly higher than for schizophrenia (0.5%-1.5%). Interestingly, race, ethnicity, and gender have no effect on the prevalence of bipolar disorder, but women are more likely to experience rapid cycling, mixed states, depressive episodes, and bipolar II disorder than men. Patients with bipolar disorder have high rates of disability and higher rates of mortality than individuals without bipolar disorder. Natural causes such as cardiovascular disease and diabetes, as well as suicide and other “unnatural” causes, are key contributors to the high mortality rate. Judd and Akiskal found subthreshold cases were at least five times more prevalent than DSM -defined core syndromal diagnoses. These researchers emphasized that bipolar disorders are associated with significant service utilization and psychosocial impairment.
Lithium
Bipolar disorder is usually treated with medication and counseling, and for refractory cases, electroconvulsive therapy is used. Pharmacologic management includes one set of drugs for mania symptoms, another set to treat depression, and some medications for maintenance. Medications typically used include lithium carbonate and antidepressants. Lithium carbonate was the first and is still the most important antimanic agent. ,
Although its mechanism of action is still imprecisely understood, lithium is widely distributed throughout the CNS, where it is believed to have a variety of effects. Lithium interacts with many neurotransmitter systems, increasing the synthesis of serotonin while decreasing norepinephrine release; these effects are likely responsible for its clinical effect. Despite its efficacy in the treatment of mania, lithium has a very narrow therapeutic index, and plasma levels 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 acceptable for treatment of acute episodes. Levels of 2 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.
Lithium toxicity is evidenced by weakness, sedation, ataxia, and widening of the QRS complex on the electrocardiogram (ECG). 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 unresponsive to vasopressin therapy. In a small percentage of patients, leukocytosis may develop, noted as a white blood cell (WBC) count of 10,000 to 14,000 cells/mm 3 . All these effects resolve with withdrawal of the drug but mandate periodic testing of thyroid level, urine osmolality, and WBC 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.
Electroconvulsive therapy
The mechanism of action for electroconvulsive therapy (ECT) is still unknown, and thus it is still a controversial treatment for depression and other mental disorders. Nevertheless, ECT remains one way to address the symptoms of major depression and bipolar disorder. ECT may also be applied in patients with schizophrenia, particularly when they do not respond to other therapeutic efforts. The therapeutic mechanism of ECT may be related to the generalized seizures it induces, and potentially important interactions occur among psychotropics, anesthetics, and ECT. Several studies have investigated combinations of anesthetics with ECT to facilitate favorable outcomes. In general, ECT is regarded as a treatment of last resort, applied when either other treatments have failed or if patients develop suicidal ideations acutely.
Although most practitioners believe that seizure duration is the most important factor relating to ECT efficacy, newer studies cast doubt on this theory. The only absolute contraindications to ECT are elevated intracranial pressure and pheochromocytoma. Relative contraindications include recent cerebrovascular accident (CVA, stroke), 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 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 CO 2 levels, the seizure threshold can be lowered. On average, eight treatments are necessary to treat most patients, with a response rate of almost 75%. Over the course of ECT, the only significant side effect is memory loss. To minimize this complication, the stimulus can be applied to the nondominant hemisphere only, although efficacy is reduced by this maneuver.
During ECT, several physiologic consequences 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 during which sympathetic activity predominates, resulting in hypertension and tachycardia; cardiac ischemia or significant tachydysrhythmias may develop. In fact, the most frequent cause of mortality in patients receiving ECT is myocardial infarction. Several treatments have been suggested to address these side effects, including short-acting β-blockers, narcotics, and nitrates. Careful consideration must be given to such agents (e.g., propranolol), because profound bradycardia and asystole have been reported after their administration.
Patients undergoing ECT are often receiving other psychotropics. These medications may influence the physiologic implications of ECT and interact with medications used to anesthetize patients during ECT. For example, the effects of TCAs on the sympathetic nervous system and 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 anticholinergics may increase the likelihood of postprocedural delirium. Clearly, the anesthetic record must be complete, including descriptions and quantities of drugs administered, especially those 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 several weeks, and the events of the previous treatment can serve to guide modifications of future treatment.
Anesthetic considerations
Lithium is the most commonly prescribed drug for bipolar disorder and interacts with several classes of anesthetic agents. First, lithium prolongs the duration of several nondepolarizing neuromuscular relaxants because of its ability to replace sodium in propagation of action potentials. Therefore, clinicians need to adjust the dosing and select the appropriate nondepolarizing muscle relaxants. Second, because of the blocking effects of lithium on the release of epinephrine and norepinephrine from the brainstem, the MAC of many volatile agents is reduced in patients receiving lithium. The patient’s emergence from general anesthesia thus may be affected. Third, nutraceuticals and herbal agents are also used to treat mood disorders, and again, anesthesiologists must evaluate for these agents. In this regard, fish oils have had positive results in bipolar disorder and can affect the coagulation cascade.
Concerns also surround the metabolic changes in the acute phase of bipolar disorder. Guan et al. studied the prevalence of metabolic abnormalities in acute-phase patients starting treatment and found abnormal levels of triglycerides (> 1.7 mmol/L) in 29.1% of patients versus 15.4% of controls, of high-density lipoprotein (HDL < 0.91 mmol/L) in 15.5% patients versus no controls, of fasting glucose (> 6.1 mmol/L) in 5.4% patients versus no controls, and for body mass index (BMI) in 34.5% patients versus 10.8% controls.
Clinicians who administer anesthesia for ECT need to be aware of untoward physiologic responses and must be prepared to treat them. They also need to know the effects of different anesthetic agents on administration of the therapy. Traditionally, methohexital was thought to be superior to other agents because of its ability to decrease seizure threshold. More recent research, however, indicates that etomidate provides a longer window of seizure activity than either methohexital or propofol. Until agreement is reached about 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 do not support this.
Given the tonic-clonic nature of seizures, muscle relaxation is essential, and because of the ultrashort duration of action, succinylcholine is an almost perfect agent for this purpose; it may be administered as a single bolus or by infusion. However, succinylcholine may cause mild vagal blockade, and its potential to amplify the initial vagal phase of the induced seizure must be carefully monitored. 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 for general anesthesia, most practitioners also use electromyography (EMG) and electroencephalography (EEG) 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 increases monitoring efficacy. Intubation of the trachea is usually not required unless the patient has a history of gastroesophageal reflux or hiatal hernia, but ventilation must be supported during the procedure because of the need for muscle relaxation. Thus, the antisialogogic effect of glycopyrrolate is an additional benefit of pretreatment with this medication.
Stress from surgery may psychologically and physiologically destabilize bipolar disorder, and acute relapse into mania in the postoperative period can be extremely disruptive to care, even life threatening. Patients unable to take oral medication for prolonged periods preoperatively or postoperatively (e.g., recurrent abdominal abscesses and fistulas) cannot receive lithium, antidepressants, some antipsychotics, or most anticonvulsant mood stabilizers. During this time, parenteral antipsychotics serve as the primary choice for mood stabilization (although valproic acid can be given intravenously as well). For patients taking medication orally, lithium poses a safety issue for those with rapid fluid shifts (e.g., acute burns).
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