譫妄症 (Delirium) 台大醫院老年醫學部陳人豪 2016/8/28 Objectives Delirium Epidemiology Etiology Diagnosis Evaluation and Management Postoperative delirium Delirium (and acute problematic behavior) in the longterm care setting Delirium A syndrome of acute brain failure, manifesting as an acute change in attention and cognition Acute confusional state Typically multifactorial (like other geriatric syndromes) Under-recognition by nurses and physicians Epidemiology Delirium in older patients Overall prevalence in community: 1-2% Prevalence at hospital admission: 14-24% Incidence during hospitalization: 6-56% Postoperative incidence: 15-53% Nursing home/post-acute care: up to 60% Patients at the end of life: up to 83% Inouye SK. N Engl J Med 2006;354(11):1157-1165. Prognosis Time course Prevalence of delirium at admission: 23% Complete resolution of delirium: 14% Health outcomes need of nursing home placement among delirious hospitalized patients Poor recovery of basic and instrumental ADLs in postacute facilities complications or rehospitalization in postacute facilities mortality Levkoff SE. Arch Intern Med 1992;152(2):334-340. Moran JA. Aust J Hosp Pharm 2001;31(1):35-40. DSM-5 Diagnostic Criteria A. A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment) B. The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception) 1
Confusion Assessment Method (CAM) D. The disturbances in Criteria A and C are not explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma E. There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e., due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple etiologies Derived from DSM-III-R Requires features 1 and 2 and either 3 or 4: 1. Acute change in mental status and fluctuating course 2. Inattention 3. Disorganized thinking 4. Altered level of consciousness Sensitivity: 94-100%; Specificity: 90-95% Inouye SK. Ann Intern Med 1990:113(12):941-948. Delirium Severity CAM-Severity (CAM-S) short form Derived using factors from CAM diagnostic assessment tool Acute onset or symptom fluctuation (1 point if present) Inattention (1 point if mild or 2 points if marked) Disorganized thinking (1 point if mild or 2 points if marked) Altered level of consciousness (1 point if mild or 2 points if marked) Total score: 0-7 points Inouye SK. Ann Intern Med 2014;160(8):526-533. Categorize patients into 4 different risk groups None: 0 points Low (mild): 1 point Moderate: 2 points High (severe): 3-7 points Psychomotor Subtypes Hyperactive or agitated Marked by agitation and vigilance Easily recognized with best prognosis Hypoactive Marked by lethargy Less recognized or appropriated treated Mixed features (most common) Shift between hyperactive and hypoactive states Normal O Keeffe ST. Age Ageing 1999;28(2):115-119. Pathophysiology Poorly understood; no final common pathway Interconnection of several pathological mechanisms Neurotransmission Cholinergic deficiency Dopaminergic excess Inflammation Cytokines (IL-1, IL-2, IL-6, TNF-α) and interferon Chronic stress Stress related hypothalamic-pituitary-adrenal axis overactivity Young J. BMJ 2007;334(7598):842-846. 2
Causes of Delirium Predisposing Factors Drug use (esp. when the drug is introduced or the dosage is adjusted) Electrolytes and physiologic abnormalities (hyponatremia, hypoxemia) Lack of drugs (withdrawal) Infections (urinary tract or respiratory infection) Reduced sensory input (blindness, deafness, darkness, change in surroundings) Intracranial (stroke, bleeding, meningitis, postictal state) Urinary retention/fecal impaction Myocardial problems (MI, arrhythmia, heart failure) Cognitive impairment Large number and severity of comorbid illnesses Functional impairment Advanced age Chronic renal insufficiency Dehydration Malnutrition Depression Vision/hearing impairment Immobilization History of substance use Precipitating Factors Multifactorial Model Medications/medication change (including withdrawal) Intercurrent medical illnesses Electrolyte or metabolic derangements Procedures or surgery Inadequate pain relief Stroke Infections Indwelling urinary catheters Restraints Alcohol or recreational drug use Major psychosocial stressor Inouye SK. Clin Geriatr Med 1998;14(4):745-764. Drugs Commonly Causing Delirium Almost any medication if time course is appropriate Alcohol Antibiotics Anticholinergics Anticonvulsants Antidepressants Antihistamines Antiparkinsonian agents Antipsychotics Barbiturates Benzodiazepines Chloral hydrate H 2 blockers Lithium Opioids (esp. meperidine) Evaluation and Management Establish the diagnosis of delirium Differential diagnosis: 3 Ds (delirium, dementia, depression) Determine the potential cause(s) and manage lifethreatening contributors promptly Manage the symptoms 3
Evaluation Medical history Physical and neurologic examinations Laboratory tests Medical History Baseline level of function Changes in mental status History for identifying acute organic illnesses Drug reviews, including alcohol, benzodiazepine Social habits Review of systems Physical Examination Vital signs and oxygen saturation General medical evaluation Signs of infections Signs of organ failure Suprapubic and rectal examination Neurological examination Mental status examination Cognitive test: Mini mental status examination (MMSE) is not sensitive in identifying delirium; however, repeated MMSEs can reveal waxing and waning course Test for attention: Serial 7 s and digit span Laboratory Tests For most patients: CBC, blood sugar, renal and liver function tests, electrolytes (Na, Ca), urinalysis, chest x-ray Consider ECG, cardiac enzymes, thyroid function, ABG, serum drug levels, vitamin B 12 For selected patients: Brain CT scan or MRI: head trauma or new focal neurologic findings EEG and CSF study: seizure or signs of meningitis Situations Requiring Urgent Evaluation Medical issues Markedly abnormal vital signs (systolic BP < 90 mmhg, PR < 50 or > 120 bpm, RR > 30 bpm, Temp < 35.5 or > 38.3 ) New-onset respiratory distress, with increasing hypoxia and dyspnea Signs of serious underlying condition possibly causing delirium (e.g., symptoms of stroke) Psychiatric symptoms Escalating physically aggressive behavior or threats of violence Intermittent or persistent change to self or others 4
Principles of Management Management of delirium Interdisciplinary effort by doctors, nurses, family Multifactorial approach because delirium usually results from concurrent multiple factors Correction of all reversible contribution factors Avoidance of new precipitants Identify and treat predisposing and precipitating factors promptly Avoid complications of delirium Remove unnecessary indwelling devices Monitor bowel and urinary output Achieve proper sleep hygiene and avoid sedatives Monitor for nosocomial complications, including aspiration, pressure ulcer, UTI Optimize medication regimen Nonpharmacologic Strategies Environment Provide quiet, well-fit surroundings Provide orienting stimuli (e.g., clocks, calendar, familiar objects) Encourage family involvement Provide regular reorienting communication Limit room and staff changes Activities during daytime Cognitive activities Early mobilization and rehabilitation Correct sensory deficits: eyeglasses, lighting, hearing aids or cerumen removal Sleep Provide uninterrupted sleep time at night Normalize sleep-wake cycle Prevent dehydration Adequate intake of nutrition and fluids Feeding by hand if necessary Pharmacologic Strategies Use sitters Avoid physical and pharmacologic restraints Avoid urinary catheters Avoid psychoactive drugs; If absolutely necessary, use haloperidol Newer atypical antipsychotics have similar efficacy to haloperidol Use lorazepam in sedative and alcohol withdrawal, and history of neuroleptic malignant syndrome Remove offending and unnecessary drugs Reserve for patients at risk for interruption of essential medical care or patients who pose safety hazard to themselves or staff Antipsychotics Not FDA-approved for treating delirium Start low doses and adjust until effect achieved Maintain effective dose for 2 3 day 5
Typical Antipsychotics For acute agitation or aggression Haloperidol 0.25-0.5 mg po (peak effect: 4-6 hr) twice daily with additional doses every 4 hours as needed 0.25-0.5 mg im (peak effect: 20-40 min), observe after 30 min and repeat the same or twice the origin doses Titrate upward as needed (up to 3-5 mg/day) The drug of choice Goal: a manageable patient Observe for akathisia, extrapyramidal effects and prolonged QTc Atypical Antipsychotics Recommended dosing Risperidone 0.5-6 mg per day Quetiapine 25-800 mg per day (starting at 12.5 mg is recommended) Olanzapine 2.5-20 mg per day Increased risk of Stroke Death among older patients with dementia Observe for extrapyramidal effects and prolonged QTc Benzodiazepines Reserve for alcohol/benzodiazepine withdrawal Adjuncts to antipsychotics (agitation/insomnia) Lorazepam 0.5-1.0 mg po, with additional doses every 4 hr as needed Physical Restraint The highest relative risk of the precipitating factors for delirium Significant association with the severity of delirium Misconceived reason for physical restraint use among delirious patients to prevent injury Restraint reduction: not associated with falls Restraint free care: the standard of care Inouye SK. JAMA 1996;275(11):852-857. McCusker J. J Am Geriatr Soc 2001;49(10):1327-1334. Prevention of Delirium Primary prevention of delirium: the most effective strategy to reduce delirium Avoid medications known to precipitate delirium Multicomponent approaches 40% risk reduction for delirium in hospitalized older patients Yale Delirium Prevention Trial To evaluate effectiveness of intervention protocols targeted toward six risk factors Cognitive impairment Sleep deprivation Immobility Visual impairment Hearing impairment Dehydration Inouye SK. N Engl J Med 1999;340(9):669-676. 6
Who Needs Evaluation? P = 0.03 by log-rank test Clinical encounters with sick older people should routinely include assessment of cognition Young J. BMJ 2007;334(7598);842-846. Postoperative Delirium Peak onset is on second postoperative day Associated with postoperative pain, anemia, use of benzodiazepines and opioids Keys to prevent delirium Limit sedation Provide adequate analgesia Transfuse high-risk patients Delirium and Acute Problematic Behavior in Long-term Care American Medical Directors Association (AMDA) Practice Recommendations in 2008 Recognition Assessment Treatment Monitoring Young J. BMJ 2007;334(7598);842-846. Am Med Dir Assoc. Delirium and Acute Problematic Behavior in the Long-Term Care Setting. 2008. 36p. Recognition Step 1: Identify the patient s current behavior, mood, cognition and function Step 2: Identify and clarify problematic behavior and altered mental function Step 3: Assess the patient for individual risk factors for problematic behavior and delirium Assessment Step 4: Determine the urgency of the situation and the need for additional evaluation and testing Step 5: Identify the cause(s) of problematic behavior and altered mental function Step 6: Assess the patient for medical illnesses with or without delirium Step 7: Consider possible psychiatric illnesses Step 8: Consider dementia-related causes 7
Treatment Step 9: Establish a working diagnosis and validate conclusions Step 10: Initiate a care plan for treatment Step 11: Provide symptomatic and cause-specific management Step 12: Use medications appropriately to address problematic behavior Monitoring Step 13: Monitor and adjust interventions as indicated Step 14: Review the effectiveness and continued appropriateness of all medications Step 15: Prevent, identify and address any complications of the conditions and treatments Take Home Message Delirium A geriatric syndrome, with atypical presentation of illnesses in elders Common among older persons Associated with substantial morbidity/mortality Detected by using CAM most of the time Resulting in functional decline Multi-factorial, with underlying causes usually found by a comprehensive history, physical examination, and focused laboratory studies Successful prevention and management interventions include a multi-component intervention The best management is prevention Physical restraints should not be used in patients with delirium, and rarely should pharmacological restraints be used 8