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Let’s be clear about Delirium Dallas Area Gerontological Society October 18, 2012 Vivyenne Roche MD Delirium Aurelianus First described the syndrome Hippocrates Disease denoting a mental 5 BC disorder & serious illness Differentiation from conventional madness “phrenitis, lethargus” Celsus de lira -off the path 1 AD Delirium Van Swieten Last used the term phrenitis, 1700-72 descriptive term, no causal relationship, inflammation of the diaphragm, combination of mental disorder with fever Morgagni Delirium replaced phrenitis 1769 1980 DSM III criteria by the APA Delirium - ? Prevalence • Point prevalence 1.1% for adults > 55 yrs. • 2.3 million elderly hospitalized patients/yr • Probably the most frequent complication of hospitalization in the elderly • Incidence on admission 10-25% (40%) • 5-35% (50%) may develop it in hospital • 14-56% of pts. on general medical wards Delirium - ? Prevalence High occurrence in postoperative patients General sx 10-15% Orthopedic sx 28-61% Cataract sx 1-3% Fem. neck fx./bil. knee replace. 65% Nursing home patients > 75 yrs. 60% Terminal delirium 25-85% Delirium - Importance • Predictor of poor prognosis • In hospitalized patients 2 to 20 times higher mortality rates in patients with delirium than those without it • Case fatality rates 25% to 35% • Closer nursing surveillance • Higher hospital costs per day Delirium - Importance • Longer hospital length of stay (LOS); Hospital LOS increased by 60% • Reduce delirium LOS by one day: save $1-2 billion dollars/year • Lasts hours, weeks, or months; 18% of patients had delirium at 6 months • 5 times higher nursing home placement, increased home care and rehabilitation use Delirium -Pathophysiology Physiology of Normal Aging: • Cerebral blood flow declines by 28% • Neuronal Loss • Lower amounts of acetylcholine, dopamine, GABA and norepinephrine • Loss of release of neurotransmitters and reduction in receptor function Less physiologic reserve Delirium -Pathophysiology Neuroanatomical location: Prefrontal cortex (TBI, cirrhotics) Thalamus (CVAs) Posterior parietal cortex (CVAs) Fusiform cortex (CVAs) Basal ganglia (ECT-induced delirium) Delirium -Pathophysiology Multiple neurotransmitters systems include serotonergic, GABA-ergic, noradrenergic, glutaminergic and histaminergic involved Neurotransmitters mediate delirium and are potential targets for treatment Acetylcholine deficiency/dopamine excess Delirium -Pathophysiology • Cholinergic function is critical for normal cognition • Administration of anticholinergics produce clinical delirium with typical EEG changes • Acetylcholine synthesis is decreased in cerebral hypoxia and hypoglycemia • Increased cerebral dopamine levels can cause delirium and dopamine inhibitors such as haloperidol can reduce anticholinergic and dopaminergic mediated delirium Delirium -Pathophysiology • Opiates known to cause delirium: they increase the activity of dopamine and decrease acetylcholine activity • Several commonly prescribed drugs for older people possess anticholinergic properties: Furosemide (0.22), Digoxin (0.25), Cimetidine (0.86), Prednisolone (0.55), Warfarin (0.12), Theophylline (0.44). Delirium -Pathophysiology • Serotonin is the most abundant neurotransmitter in the brainstem; its synthesis and release depends on its precursor tryptophan • Cerebral serotonin is increased in hepatic encephalopathy, septic delirium, and in the serotonin syndrome. Alcohol withdrawal, L DOPA-induced delirium and postoperative delirium have been associated with decreases in tryptophan • Serotonin syndrome related to combination of SSRIs and MAOIs or TCAs. Restlessness, tremor, hyperpyrexia, myoclonus, nausea, flushing and one of its main symptoms is delirium Delirium -Pathophysiology • Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the CNS • In hepatic encephalopathy there is increased ammonia levels, precursor of GABA. Benzodiazepine and alcohol withdrawal are associated with reduced GABA activity • Cytokines, TNF alpha, interleukin-1, interleukin-2 normally found in low levels in the CNS but increase after stress, infection, inflammation, and trauma. This leads to HPA axis activation, increased permeability of the blood brain barrier and interference with neurotransmitter synthesis and transmission. Proposed Mechanisms of Delirium and Possible Associated Clinical Conditions Medications Medications/Medical Illness Alcohol withdrawal Surgical Illness Benzodiazepine and Medications Alcohol Withdrawal Stroke Cholinergic Cholinergic activation Inhibition Dopamine Reduced Activation GABA Activity Cytokine GABA Benzodiazepines Excess Activation Hepatic Failure Serotonin Activation Glutamate Activation Medications Serotonin Cortisol Hepatic failure Substance withdrawal Deficiency Excess Alcohol withdrawal Tryptophan depletion Glucocorticoids Phenylalanine elevation Cushings Syndrome Surgery Stroke Surgical Illness /Medical Illness Delirium Ancient Greeks: syndrome that accompanied fever or other serious illness: phrenitis (frenzy); lethargus (lethargy) • Hyperactive presentation (hallucinations, agitation, inappropriate behavior) • Hypoactive presentation (hypersomnolence, lethargy-may present like depression) • Mixed-features of both Delirium Subtypes of delirium • Hyperactive (22%-30%) hypoactive (24%-26%) and mixed (42%-46%) • Comparable deficits in cognition with both • Hyperactive delirium occurs in benzodiazepine withdrawal, renal or hepatic encephalopathy often present with hypoactive delirium • There is no exclusive relationship between subtypes of delirium and different etiologies • Hypoactive pts: sicker on admission, longest lengths of stay, inc. pressure sores whereas the hyperactive pts. are more likely to fall Delirium - Diagnosis DSM IV Criteria Disturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain or shift attention Change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual disturbance Delirium - Diagnosis DSM IV Criteria Disturbance that develops over a short period of time (usually hours to days) and tends to fluctuate over the course of the day Evidence from history, physical examination, or laboratory findings that the disturbance is caused by a specific medical condition medication side effect, substance withdrawal /intoxication, or multiple causes Delirium - Diagnosis DSM IV Eliminated • Reduced level of consciousness • Sleep disturbance • Disorganized thinking • Changing psychomotor activity Delirium - Diagnosis The diagnosis is missed 33-67% of the time by physicians directly involved by patient care • Individual presentation • Presentation of illness in older cohort • Differential diagnosis Delirium - Diagnosis Individual Presentation • Patient dozes off when you’re trying to talk to her, you wake her up and 2 minutes later she goes off to sleep again Delirium - Diagnosis Individual Presentation • Mr. P. keeps picking at the bedclothes while you’re trying to talk to him • Patient can’t repeat 3 words after you Delirium - Diagnosis Individual Presentation • 82 yr. old lady comes to clinic. Brought by her daughter. Patient has history of dementia and goes to Adult Day Center. Daughter brings her today because Mom wouldn’t eat, needed help to walk, sat in the chair all day at the Center and kept falling asleep for the whole day. Delirium - Diagnosis Individual Presentation • Mini-Mental State Examination • Digit Span Test • Days of the week backwards Delirium - Diagnosis Presentation Differences in Older Patients • Delirium may be the only presentation of severe illness in older patients • “Silent” myocardial infarction (up to 40%) • 25% of older people have no fever associated with pneumonia, tuberculosis endocarditis or sepsis • 13% older bacteremic patients are afebrile Dementia Delirium Depression Delirium - ? Risk factors Advanced age Infections Electrolyte abnormalities CP disorders Hypoalbuminemia CNS disease Gastro/GU disorders Polypharmacy Sensory deprivation Trauma (falls, fractures, pain) Delirium - ? Risk factors CAM assessment Delirium Model Interaction between Vulnerability factors (predisposing factors) and Precipitating factors (insults) Delirium - ? Risk factors 13 Vulnerability factors (predisposing factors) sex, age, severe illness, MMSE <24, history of confusion, 2 measures of social support, vision impairment, depressive symptoms, hearing impairment, assistance with ADLs and IADLs Visual impairment Severe illness on admission Cognitive impairment BUN:Creatinine>18 Delirium - ? Risk factors Precipitating factors (insults) Use of physical restraints Malnutrition (albumin <3g/dL) > 3 Medications added within 24 hour period Use of a bladder catheter Iatrogenic events Delirium - Intervention Clinical trial-3 units (intervention/control) 852 pts -70 yrs. and older, no evidence of delirium on admission visual impairment severe illness cognitive impairment BUN/Cr >18 • Intermediate risk 1 or 2 factors present • High risk 3 or 4 factors present Delirium - Intervention Intervention group • Cognition-orientation, activities • Sleep protocol • Immobility-early mobilization protocol • Visual impairment-visual aides, adaptors • Hearing impairment-protocol • Dehydration-recognition, repletion Delirium - Intervention 100% follow-up Outcome-delirium • Exposing 19 at-risk pts. prevented one from developing delirium; 15% to 9.9% • No. of days of delirium (105 vs 161) and no. of episodes (62 vs 90) were lower in the intervention group Delirium - Intervention 100% follow-up, Outcomes • It was most effective in patients with intermediate risk at baseline (one to two risk factors) rather than the high risk group (3 or 4 risk factors) • No difference in severity or recurrence rates • Cost:$327 per pt. in the intervention group Delirium - Treatment 3 Simultaneous Approaches • Identification and treatment of the etiology of delirium • Environmental modification • Control of symptoms Delirium - Etiology • Extensive, multifactorial • 87% of delirium had a clear etiology • 56% patients had one etiology 44% had 2.8 etiologies/patient • 62% of hip fracture patients had multifactorial etiology • 3 commonest etiologies are infection, metabolic disturbance and medications Delirium - Etiologies D drugs E endocrine/endogenous depression M metabolic E ears/eyes N nutrition T tumor, trauma, toxins I infections A atherosclerotic CD, alcohol Delirium - Treatment Step 1 • Suspect it • Baseline cognitive status on admission • Nursing staff Delirium - Diagnosis Step 2 • History and Physical • Medication review • Labs: CBC, lytes, BUN/Creatinine, glucose, calcium, phosphate, liver enzymes, ABG; blood alcohol & ammonia level if indicated • Look for occult infection • EKG Delirium - Diagnosis Step 3 -No diagnosis • More labs: Mg, TSH, drug levels, tox. screen • CSF examination • MRI with diffusion weighted imaging if new focal neurological finding, or suspected new CVA • EEG especially useful to exclude non-controlled seizure activity-Diffuse slowing in both delirium (marked) and dementia. (EEG findings in alcohol or sedative-hypnotic withdrawal is fast) Delirium - Diagnosis Step 3 -No identifiable etiology • Vigilance • Daily physical examinations • Daily laboratory tests Delirium - Treatment Environmental modification • Improve orientation, clocks, calendars • Windows, appropriate lighting • Hearing aids and glasses • Family members involved • Mobility, no restraints, remove catheters • Patient placed at nurses station Delirium - Treatment Symptom control Should never replace diagnostic workup and management of underlying illness Only use if behavior interferes with diagnostic workup or prevents delivery of necessary medical care Delirium - Treatment Pharmacologic treatment No blinded randomized controlled trials HALDOL MOST STUDIED Haldol 5mg po/im for episode of delirium True/ False Delirium - Treatment Pharmacology Dopamine • Inc. cerebral dopamine levels can cause delirium • Dopamine inhibition can eliminate symptoms of delirium • Made in 4 major CNS pathways Antagonize dopamine by Decreasing synthesis Decreasing release Blocking dopamine receptors Delirium - Treatment Pharmacology Dopamine Decrease synthesis Alpha-methyl para-tyrosine inhibits dopamine formation by blocking tyrosine hydroxylase but this enzyme is also used to synthesize norepinephrine which results in widespread autonomic nervous system effects Delirium - Treatment Pharmacology Dopamine Decrease release Reserpine and tetrabenzine are very potent dopamine antagonists but they also inhibit vesicular storage of norepinephrine and serotonin Delirium - Treatment Pharmacology Dopamine receptor blockade 4 dopaminergic pathways: nigrostriatal, mesolimbic, mesocortical, hypothalamus Phenothiazines and haloperidol are dopaminergic specific 5 dopamine receptors D1, D2, D3, D4, D5, • Assoc. with adenyl cyclase D1 group D1,5 Independ. of adenyl cyclase D2 group D2,3,4 • Antipsychotics block the D2 group Delirium - Treatment Symptom treatment Haldol • Haloperidol sedates, treats hallucinations, paranoia and delusions, less anticholinergic and less hypotensive than other antipsychotics • Rapid onset, relatively wide therapeutic window, reasonable safety profile, no active metabolites, antipsychotic effects can last 3-6 days, various administration routes Delirium - Treatment Haldol • 2mg/day of haloperidol results in 53% to 74% of D2 receptor occupancy. Thresholds of 60% occupancy exert antipsychotic activity. A higher occupancy rate of 80% may increase side effects with no appreciable improvement clinically. • Schizophrenia: daily doses of 10mg/day • Extrapyr. effects, akathisia, tardive dyskinesia • Neuroleptic malignant syndrome: fever, delirium, tremulous rigidity, & autonomic hyperactivity Delirium - Treatment Pharmacologic treatment Haldol • Starting dose 0.5mg • Maximum dose 3-5mg/24 hours • Repeat every 30 minutes until desired effect • Taper the dose given in the first 24 hours over 3-5 days (largest amount before bed) • Abrupt withdrawal can ppt. recurrence Delirium - Treatment Pharmacologic treatment • Benzodiazepines if sedation is key • Benzodiazepines potentiate the action of antipsychotics • Lorazepam 0.25mg to 0.5mg can be used • Can make delirium worse, can precipitate paradoxical agitation: Discontinue it Delirium - Terminal Delirium • More than two thirds of Americans die in acute care settings • Term confined to delirium within last one to two days of life • Prevalence rates as high as 85% • Recognizing delirium in this cohort prevents common delirious symptoms such as agitation from being interpreted as pain • Multiple etiologies most likely • Hallucinations may be present; treat promptly www.gerisage.com Delirium 1. Delirium instead of Altered Mental Status 2. It is common and important 3. Target patients and suspect it early 4. Inattention, Digit Span Test, Days of the week backwards 5. Treat the underlying etiology, check meds 6. Haldol; Start LOW, GO SLOW 7. May take days, weeks, months to clear
"Altered Mental Status - Dallas Area Gerontological Society"