Delirious … you or the patient? November 2004

Questions to ponder… What risk factors are associated with delirium? What tools are available to assess for delirium? What is the importance of diagnosing delirium? What is the appropriate workup? What medications are associated with confusion in the hospitalized older patient? Can delirium be prevented? Is delirium a marker for bad outcomes? Once delirium occurs, can multitargeted strategies change the outcome? Are medications useful for the management of patients with hyperactive or agitated delirium? Is preventing delirium cost effective?

Overview Background and definition Risk factors Screening tools Workup Preventing delirium Delirium as a marker of bad things to come Treating delirium – Multitargeted strategies – Medications

Definition and background DSM IV: reversible state of confusion with reduced level of consciousness manifest as inability to focus, sustain or shift attention Acute confusional state Acute onset, fluctuating course Attention impairment Up to 60% hospitalized elders Often iatrogenic, often misdiagnosed

Risk Factors Advanced age Underlying dementia/cognitive impairment Acute medical illness Alcohol abuse Male gender Depression Malnutrition Terminal illness ICU stay (up to 80%)

Iatrogenic Risk Factors The things we do… – Physical restraints – Polypharmacy – Malnutrition – Other restraints… Foley catheters IV lines Telemetry boxes Oxygen tubing

Screening or Assessment Tools DSM IV definition Serial MMSE Confusion Assessment Method (CAM) CAM-ICU

DSM –IV definition Acute confusional state associated with: – Disturbance of consciousness with reduced ability to focus, sustain, or shift attention – Change in cognition (memory impairment, disorientation, language deficits) or development of perceptual disturbance that is not due to underlying/established dementia – Development during hours/days with fluctuating course

MMSE Pro: familiarity Con: not specific (deficits may be due to underlying dementia, limitations due to low literacy level…) How to use: serial MMSE during hospital course; change in performance suggests delirium

Confusion Assessment Method Quick and easy Sensitivity %, specificity 90-95%

CAM 1. Acute onset and fluctuating course (history can be obtained from family/friends or staff) 2. Inattention (did the patient have difficulty keeping track of conversation?) 3. Disorganized thinking (was conversation rambling or incoherent, unclear, illogical or unpredictable?) 4. Altered level of consciousness (vigilant, lethargic, stupor, coma; anything other than “alert”)

Disorganized thinking Set A 1. Will a stone float on water 2. Are there fish in the sea? 3. Does 1 lb weigh more than 2 lbs 4. Can you use a hammer to pound a nail? Set B 1. will a leaf float on water? 2. Are there elephants in the sea? 3. Do 2 lbs weigh more than 1 lb? 4. Can you use a hammer to cut wood?

Workup: Delirium is a Marker! Medication review Labs: Na, glucose, ca, creat/BUN Infection (UTI, pneumonia) Hypoxemia Neuroimaging for subdural EEG Sleep apnea Pain (skin, urinary retention) Myocardial ischemia Alcohol or benzo withdrawal Consider LP (arboviral infections/encephalitis in elderly!) Review for underlying dementia

Medications associated with delirium: First Think Drugs! General: anticholinergics and benzodiazepines! Opioids (especially meperidine) Tricyclic antidepressants Antihistamines (NO BENADRYL FOR SLEEP!!!!) Antiparkinsonian meds: levodopa/carbidopa, amantadine, bromocriptine) H2 receptor blockers Antibiotics (ciprofloxacin) Anticonvulsants Prednisone Clonidine

Perioperative Delirium Orthopedic and vascular surgeries: 40-50% incidence Vascular surgeries: associated with underlying hyperlipidemia, amputation, age over 65, depression

Cardiac Surgery and Delirium Associated with delirium and persistent memory impairment Microembolism, hypoperfusion, inflammatory responses Highest risk: history of cerebrovascular disease, PVD, diabetes, cardiomyopathy, urgent operation, long surgery time, high transfusion requirement CABG with “beating heart/off pump” technique associated with less delirium …

Preventing delirium, can it be done? Inouye NEJM 1999 – Randomized trial of 852 patients – Multicomponent intervention plan – Delirium developed in 9.9% intervention group vs 15% usual care group – Total number days with delirium: 62 intervention group, 90 in control group – NO DIFFERENCE in severity or recurrence of delirium once it developed: KEY IS PREVENTION

Preventing Delirium Recognizing patients at risk (screening high risk patient) Avoiding risky medications Close observation for infection Family/friend involvement Decrease isolation: hearing aids, glasses Decrease sleep disturbances Environmental cues (opening blinds…) Avoiding restraints Avoiding “restraints” (foley catheters, oxygen, IV fluids, telemetry boxes) that are not needed Vigilance for withdrawal syndromes (benzo, ETOH, SSRI)

Delirium, Bad Things to Come? Observational data suggests that delirium associated with adverse outcomes including loss of independence, need for placement, cognitive decline, increased mortality Problem: confounding… (those at highest risk for delirium are also the oldest and the sickest…)

Prognostic Significance of Delirium… Prospective studies do demonstrate delirium and dementia being associated with decline in cognitive and functional status, even up to 12 months after hospital stay Highest decline in patients with both dementia and delirium

Can multitargeted strategies change outcomes of patients with delirium? Lack of data… Several studies have failed to demonstrate a difference in patients with delirium treated with various strategies compared to “usual care” – Problem: “Hawthorne Effect” – Studies randomized, but “usual care” group likely benefited from presence of study itself…

Antipsychotic use… Commonly used… Care to ensure not missing underlying pain, urinary retention, psychiatric disorder, withdrawal syndrome, infection! If used, use atypicals in very, very low dose! Remember, no great data to support this use… so use care… Avoid benzodiazepine use (unless for withdrawal)

Typical antipychotics… Haloperidol – Try to avoid – High risk of tardive diskinesia and EPS with long term use (over 50% in elderly) – If used, use low dose (0.5 mg), and limit to 1-3 days – Newer routes of atypical agents (IV, sublingual, IM) should make use of haloperidol in this setting obsolete…

General risks of antipyschotics… Much less risk of EPS and TD Orthostasis Sedation Cardiovascular effects (QT prolongation) Weight gain Edema

Risperidone (risperdal) Emerging (although small studies) to support use with agitated delirium Begin 0.25 mg – 0.5 mg, 1-2 times/day Effectiveness at low doses in elderly (max 1- 3 mg/day) Limited in past by only oral route – new routes soon to be available

Olanzepine (zyprexa) mg Sedation (usually started at night) with more anticholinergic side effects Routes: PO or rapidly dissolving tablet (Zydis) Link with weight gain and diabetes…

Quetiapine (seroquel) Start at 25 mg Can rapidly increase up Sedating, use at night More commonly used longer term for behavior problems with dementia (limited EPS and TD effects)

Ziprasidone (geodon) Restricted use at UNC IV form mg Contraindicated with acute CV disease (nondose dependent QT prolongation)

Clozapine Great with underlying parkinsonian symptoms due to little risk of increasing tremor Significant rate of agranulocytosis Restricted use

Anticholinesterase inhibitors?? Agents such as donepezil being studied Observational data suggest benefit with behavioral disturbances with dementia

Is preventing delirium cost effective? Probably cost neutral…

Take Home Points… Delirium is very common and often missed in hospitalized older patients (15% on a general medical unit, up to 50% undergoing surgeries…) Think drugs, lines, sleep deprivation, pain, infection… Think prevention!