Learning Objectives Delirium Defined in DSM‐5 • Key clinical features of delirium • Essential elements of the bedside assessment and work‐up • Causes of delirium • Pathoetiologic models • Treatment strategies Patient Case 1: Presentation to Urgent Care Clinic DELIRIUM KNOWN BY ANY OTHER NAME IS • 61 year‐old man with schizophrenia & epilepsy brought to urgent care by sister for “ 2 days of confusion & fever.” STILL DELIRIUM . • Takes quetiapine XR 600mg daily (x 24 months) & • carbamazepine XR 400mg BID (x 6 weeks). Altered Mental Status • Smokes 1.5 ppd; no illicit drugs or ETOH • Acute Brain Syndrome • Physical Exam: BP 95/52, HR 115, temp 101.7 F • Acute Confusional State • Agitated; diffuse rash on trunk, face, extremities. • “ICU Psychosis” • Reports small girl he sees in the room carrying a black • Toxic‐Metabolic Encephalopathy bag & oriented to “apartment” and “May 1917.” • Sundowning https://www.brainyquote.com/quotes/keywords/rose.html • Can barely repeat 3 words without getting sleepy • 0/3 recall at even one minute • No other psychiatric diagnosis can be made in the presence of delirium • Counts down from 20 by saying “20, 100, 17…” Patient Transported to Emergency Center via 911 Motor Subtypes of Delirium • WORK UP in EC & on admission Hyperactive • ABG: no hypercarbia or hypoxia • Agitated, pacing, fidgeting, wandering, restless, violent • Labs: WBC 18,000 mg/dL with hypereosinophilia, atypical lymphocytes & (don’t give benzodiazepines!!) platelet count of 97,000 • Comprehensive Metabolic Panel: Hypoactive • Creatinine 1.7 mg/dL & AST 278 U/L and ALT 298 U/L • Few spontaneous movements, slower movements, less awareness of • TSH, UA, urine toxicology, RPR, HIV, CK, folate, B12, ammonia– unremarkable surroundings, less speech, slower speech, listless • CSF: WBC 3; protein 40 mg/dL glucose 65 mg/dL • Often missed • Carbamazepine level: within therapeutic range • Common in metabolic disorder, organ failure delirium, ICU & palliative care & • CT head: “mild cortical atrophy with mild subcortical white matter ischemic associated with poorer prognosis changes” Mixed • EEG: “diffuse slowing; no epileptiform activity” • Combination of features ANTICHOLINERGIC MEDICATION BURDEN Some BIG Neuropsychiatric/Cognitive Features of Delirium OFFENDERS TCAs Incontinence “A complex neuropsychiatric syndrome that includes a wide range of cognitive Paroxetine Quetiapine and non‐cognitive disturbances.” Olanzapine H1 blockers DEFICITS in the following domains: Anti‐emetics Attention 97‐100% Visuospatial ability 87‐96% Orientation 76‐96% Motor control 24‐94% Short‐term memory 88‐92% Language 57‐67% Long‐term memory 89‐96% Perception 50‐63% Sleep‐wake cycle 92‐97% Delusions 21‐31% Thought process 54‐79% Mood/affect 43‐86% COMMON CAUSES OF DELIRIUM HOW COMMON IS DELIRIUM • 0.4% >18 in general population False Positives and Negatives on Urine Drug • 1.1% >55 in general population \ Screens Emerg Med Clin N Am 33 (2015) 753–764 • 10‐30% of medically ill in the hospital • 30% in surgical intensive care • 30‐40% hospitalized with AIDS • 28‐42% terminal cancer patients on admission • 40‐50% s/p surgery for hip fractures • 60% nursing home pts >75 have episodes • 80‐88% terminally ill in palliative care • 90% post‐cardiac surgery Emerg Med Clin N Am 33 (2015) 753–764 WHO GETS DELIRIOUS? Pathologies to Consider with Vital Sign Mental Status & Physical Signs of Toxic Abnormalities in DeliriumEmerg Med Clin N Am 33 (2015) 753– 764 Syndromes Emerg Med Clin N Am 33 (2015) 753–764 Am Fam Physician. 2014;90(3):150‐158. Delirium Work‐Up STARTS WITH. EEG in Delirium A GOOD H&P • Oxygen saturation, ABG • CT head (faster & better for agitated • EEG –not necessary but can help confirm dx • Serum glucose patient): good to r/o acute hemorrhage • CBC w/ differential • MRI brain more sensitive & specific for • shows diffuse slowing (most common) or triphasic waves (esp. in hepatic CNS lesion presence & type encephalopathy or uremia) • Serum chemistry • EKG • LFTs, ammonia • EEG • delirium tremens: may be normal or fast • Thyroid function tests • CXR • Urinalysis with micro & culture • LP & CSF analysis • Urine drug screen • may be useful for confirmation of diagnosis (no EEG changes in • Blood cultures primary psych disorders) • B12, RPR, HIV, hepatitis panel • Autoimmune & paraneoplastic work‐up in the right setting but not routine • useful if seizures – convulsive or non‐convulsive‐ are suspected as cause of delirium Examining the Patient In Order to Diagnose Delirium Pathophysiology of Delirium Bedside cognitive assessment is critical to diagnosis • Level of consciousness • Neurotransmitter Hypothesis • Can use Glasgow Coma Scale • ↓ACh and ↑DA, NE, Glutamate • • Orientation: person, place, time, situation GABA and 5HT dysregulated • Impaired oxidative metabolism • Attention/concentration • Inflammatory: ↑ cytokines • count down from 20 • Physiologic stress: • months of year backwards • faulty blood‐brain barrier • digit span (should be able to to do 2 less backwards than can be done • Sick euthyroid syndrome forward) • Hypothalamic/pituitary/adrenal axis hyperactivity • Immediate recall: repeat 3 words • Intraneuronal cellular signaling • Delayed recall: test 3 word recall after a few minutes dysfunction Specific Assessment Instruments for Delirium Risk factors for Delirium • Age‐related brain changes, i.e. “reduced cerebral reserve” • Prior CNS disorders: stroke, tumor, traumatic brain injury, cognitive impairment/dementia • Malnutrition: • Thiamine deficiency: not just alcoholics: hyperemesis gravidarum, s/p bariatric surgery, s/p chemotherapy • Low serum albumin –a risk factor at any age (may signify poor nutrition, chronic disease, liver or renal insufficiency, and results in greater bioavailability of many drugs) • Medication/toxin/alcohol exposure/intoxication/withdrawal – benzodiazepines, opioids, drugs with anticholinergic activity • Surgery & anesthesia – age, duration of anesthesia, lower education, second operation, post‐op infection, respiratory bCAM (~0.9 sens & spec) complications = predictors of post‐op delirium Consequences of Delirium • Increased Length of Stay • 100% in general medical patients; 300% in critical care • Why? Persistent cognitive & behavioral changes + more iatrogenic complications • Decreased independent living/increased institutionalization • Persistent cognitive deficits • 25% elderly delirious with symptoms lasting months • Rate of cognitive decline in patients with Alzheimer’s disease who develop delirium is accelerated 3 fold • Increased Mortality even when controlling for comorbidities, demographics, dementia • Index hospitalization for delirium = mortality range from 4‐65% • Longer the delirium ‐‐ the higher the mortality risk Am Fam Physician. 2014;90(3):150‐158. DISTINGUISHING DELIRIUM FROM OTHER CONDITIONS FIRST, PREVENT DELIRIUM FROM OCCURING Delirium vs. Schizophrenia vs. Depression SECOND, TREAT UNDERLYING CAUSE Delirium Schizophrenia Depression • Impaired awareness/attention Unimpaired; clear Unimpaired PREVENTION & MANAGEMENT OF DELIRIUM Am Fam Physician. 2014;90(3):150‐158. • Orient patient (pictures, consistent staff, • Poor attention Poor attention Diurnal attention variation windows, calendars, appropriate lighting) • Impaired memory Memory intact +/‐ memory complaints • Promote regular routines, day –night • VH most common AH most common AH most common cycle • Avoid complete sensory deprivation / • Fleeting delusions Complex, systematized Complex, mood overstimulation often paranoid delusions congruent delusions • Avoid restraints; use Posey vest (velcro, • Sleep‐wake disturbance No characteristic pattern Initial insomnia, early zippers) wakening or hypersomnia • Treat pain, constipation, dehydration • Avoid delirium inducing medications • Ensure glasses & hearing aids are working & in proper condition • Mobilize early • Avoid urinary catheterization AFTER DIAGNOSING & TREATING UNDERLYING CONDITION… PHARMACOLOGIC TREATMENT OF DELIRIUM DISTINGUISHING DELIRIUM FROM OTHER CONDITIONS • Benzodiazepines: Use ONLY for Delirium vs. Dementia delirium due to ETOH, benzodiazepine Delirium Dementia Do not use in Lewy Body Dementia withdrawal or • Impaired consciousness Unimpaired consciousness* or Parkinson disease patients catatonia • Even low doses, • Poor attention Attention varies by dementia** lorazepam= • VH most common VH more more common than AH independent delirium risk factor • Fleeting delusions Paranoid often fixed delusions • Older & sicker: • Sleep‐wake disturbance Nocturnal insomnia increased risk of lorazepam induced delirium • Delirium superimposed on dementia: delirium can accelerate the progression of dementia and may never fully resolve in this setting • * Exception: Lewy Body Dementia (LBD): fluctuation in levels of alertness is one of the cardinal features • ** Vascular dementia, LBD, Frontotemporal dementia, HIV dementia, NPH, etc. Am Fam Physician. 2014;90(3):150‐158. PATIENT 2: PRESENTATION TO URGENT CARE CLINIC MANIFESTATIONS OF SEROTONIN SYNDROME & RELATED SYNDROMES • 47 year‐old woman with hypertension, depression, DM type II, seasonal allergies & sciatica • Confusion, restlessness, and tremulousness beginning “a couple days ago.” • Patient is an accountant but couldn’t write a check this morning. • Medications: duloxetine, lisinopril, tramadol, HCTZ, glyburide, trazadone, prn diphenhydramine, and metformin. • No illicit drug or alcohol use per husband. • HR 105, BP 147/92, RR 20, Temp 100.8 F • Awake, agitated, diaphoretic, restless. • Oriented to “clinic and 2017.” • Exam: Tremor,