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DELIRIUM
Whitney A. Gray, CRNP, MSN 
Katrina A. Booth, MD
BASICS
DESCRIPTION
Atemporary neurologic complication of illness and/or medication(s), especially common in older patients, manifested by new confusion and impaired attention
Amedical emergency requiring immediate evaluation to decrease morbidity and mortality
System(s) affected: neurologic
Synonym(s): acute confusional state, altered mental status, organic brain syndrome, acute mental status change, encephalopathy
EPIDEMIOLOGY
Predominant age: older persons
Predominant sex: male = female
Incidence
>50% in older ICU patients
11–51% in postoperative patients
10–40% in hospitalized older patients
Prevalence
8–17% in older ED patients
14% in older postacute care patients
ETIOLOGYAND PATHOPHYSIOLOGY
Multifactorial: believed to result from a decline in physiologic reserves with aging, resulting in a vulnerability to new stressors
Neuropathophysiology is not clearly defined; cholinergic deficiency, dopamine excess, and neuroinflammation are leading hypotheses.
Often interaction between predisposing and precipitating risk factors
With more predisposing factors (i.e., frail patients), fewer precipitating factors needed to cause delirium.
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If few predisposing factors (e.g., very robust patients), more precipitating factors needed to cause delirium.
Multicomponent approach addressing contributing factors can reduce incidence and complications.
RISK FACTORS
Predisposing risk factors
–Advanced age, >70 years
–Preexisting cognitive impairment
–Functional impairment
–Dehydration; high BUN:creatinine ratio
–History of alcohol abuse
–Malnutrition
–Hearing or vision impairment
Precipitating risk factors
–Severe illness in any organ system(s)
–Medical devices (urinary catheter, restraints)
–Polypharmacy (≥5 medications)
–Specific medications, especially benzodiazepines, opioids (meperidine), and anticholinergics (diphenhydramine), high-dose neuroleptics
–Pain
–Any iatrogenic event
–Surgery
–Sleep deprivation
GENERALPREVENTION
Follow treatment approach.
COMMONLYASSOCIATED CONDITIONS
Multiple but most common are the following:
New medicine or medicine changes
Infections (especially lung, urine, and blood stream, but consider meningitis as well)
Toxic-metabolic (especially low sodium, elevated calcium, renal failure, and hepatic failure)
Heart attack or stroke
Alcohol or drug withdrawal
Preexisting cognitive impairment increases risk
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DIAGNOSIS
Diagnosis is made using a careful history, behavioral observation, and cognitive assessment.
DSM-5 diagnostic criteria include (1):
–Disturbance in attention and awareness
–Change in cognition not due to dementia
–Onset over short (hours to days) period and fluctuates during course of day
–Evidence from history, exam, or lab that disturbance is caused by physiologic consequence of medical condition, intoxicating substance,
medication use, or more than one cause.
The Confusion Assessment Method (CAM) is the most well validated and tested clinical tool and has been adapted for ICU setting in adults (CAM-ICU) and children (pediatric CAM-ICU [pCAM-ICU]) (2)[B].
ALERT
Key diagnostic features of the CAM
–Acute change in mental status that fluctuates
–Abnormal attention and either disorganized thinking or altered level of
consciousness
Several nondiagnostic symptoms may be present:
–Shortand long-term memory problems
–Sleep–wake cycle disturbances
–Hallucinations and/or delusions
–Emotional lability
–Tremors and asterixis
Subtypes based on level of consciousness
–Hyperactive delirium (15%): Patients are loud, agitated, restless, and disruptive.
–Hypoactive delirium (20%): quietly confused; sleepy; may sit and not eat, drink, or move
–Mixed delirium (50%): features of both hyperactive and hypoactive delirium
–Normal consciousness delirium (15%): still displays disorganized thinking, along with acute onset, inattention, and fluctuating mental status
HISTORY
Time course of mental status changes
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Recent medication changes
Symptoms of infection
New neurologic signs
Abrupt change in functional ability
PHYSICALEXAM
Comprehensive cardiorespiratory exam is essential.
Focal neurologic signs are usually absent.
Mini-Mental State Examination (MMSE) is the most well-known and studied cognitive screen, but it may not be the most appropriate in an acute care setting; shorter cognitive screens have been studied in delirious patients (i.e., short blessed test [SBT], Brief Alzheimer Screen [BAS], and Ottawa 3DY) and may be helpful if performed serially over time. Most patients will perform poorly if delirium is present; dementia cannot be diagnosed when delirium is present.
GI/GU exam for constipation/urinary retention
DIFFERENTIALDIAGNOSIS
Depression (disturbance of mood, normal level of consciousness, fluctuates weeks to months)
Dementia (insidious onset, memory problems, normal level of consciousness, fluctuates days to weeks)
Psychosis (rarely sudden onset in older adults)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
Guided by history and physical exam
–CBC with differential
–Comprehensive metabolic panel (CMP)
–Urinalysis, urine culture, blood culture
–Medication levels (digoxin, theophylline, antiepileptics where applicable)
Chest radiograph for most
ECG as necessary
Others, if indicated by history and exam
Follow-Up Tests & Special Considerations
If lab tests listed above do not indicate a precipitator of delirium, consider
– Arterial blood gases
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–Troponin
–Toxicology screen
–Ammonia
–Thyroid-stimulating hormone
–Thiamine
Noncontrast-enhanced head CT scan if
–Unclear diagnosis
–Recent fall
–Receiving anticoagulants
–New focal neurologic signs
–Ruling out mass before lumbar puncture
Diagnostic Procedures/Other
Lumbar puncture (rarely necessary)
– Perform if clinical suspicion of a CNS bleed, malignancy-related syndrome, or infection is high.
EEG (rarely necessary)
–Consider after above evaluation if cause remains unclear or suspicion of seizure activity.
TREATMENT
The best treatment is prevention (3)[A].
Addressing six risk factors (i.e., cognitive impairment, sleep deprivation, dehydration, immobility, vision impairment, and hearing impairment) in atrisk hospitalized patients can reduce the incidence of delirium by 33%.
Principles: Maintain safety, identify causes, and manage symptoms.
Stabilize vital signs and ensure immediate evaluation.
GENERALMEASURES
Postoperative patients should be monitored and treated for
–Myocardial infarction/ischemia
–Infection (i.e., pneumonia, UTI)
–Pulmonary embolism
–Urinary or stool retention (attempt catheter removal by postoperative day 2)
Anesthesia route (general vs. epidural) does not affect the risk of delirium.
ICU sedation-avoidance of benzodiazepines may reduce risk (4)[B]. 
Multifactorial treatment: Identify contributing factors and provide preemptive
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care to avoid iatrogenic problems, with special attention to
–CNS oxygen delivery (attempt to attain): 
SaO2 >90% with goal of SaO2 >95%
Systolic BP<2/3 of baseline or >90 mm Hg
Hematocrit >30%
Fluid/electrolyte balance
–Sodium, potassium, and glucose normal (glucose <300 mg/dLin diabetics)
–Treat fluid overload or dehydration.
Treat pain
–Schedule acetaminophen (650 mg TID–QID) if constant pain; avoid if LFT elevation noted.
–Opioids (morphine, oxycodone) may be used for breakthrough pain.
ALERT
Avoid meperidine (Demerol).
Eliminate unnecessary medications.
– Investigate new symptoms as potential medication side effects (i.e., Beers medications).
Regulate bowel/bladder function.
–Bowel movement at least every 48 hours
–Screen for urinary retention.
Prevent major hospital-acquired problems.
–6-inch-thick foam mattress overlay or a pressure-reducing mattress
–Avoid urinary catheter.
–Incentive spirometry
–Venous thromboembolism (VTE) prophylaxis if bedfast
–Early mobilization
–Environmental stimulation 
Glasses and hearing aids 
Clock and calendar
Soft lighting
Music and television, if desired
–Sleep
Quiet environment
Soft music
Therapeutic massage
Restraints increase risk of delirium and falls/injury.
–Use as a last resort for patients at risk for self-injury or risk for injuring caregivers. Remove as soon as possible.
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MEDICATION
Nonpharmacologic approaches are preferred for initial treatment, but medication may be needed for agitation management, especially in the ICU setting (5)[C].
Medications treat only the symptoms and do not address the underlying cause.
No medication is FDAapproved for delirium.
Medications should not be used prophylactically.
First Line
Antipsychotics
Monitor QTc periodically if antipsychotics are used.
–Haloperidol (Haldol): initially, 0.25 to 0.5 mg PO/IM; reevaluate and potentially redose hourly until symptoms controlled and then use effective dose up to QID PRN. Critical care guidelines do not support use of antipsychotics for prevention of ICU delirium (4)[B].
–Quetiapine (Seroquel) 12.5 to 25.0 mg PO BID–TID
–Risperidone (Risperdal) 0.25 to 0.5 mg PO daily
Benzodiazepines should generally be avoided except in alcohol withdrawal, if patient taking a benzodiazepine regularly at baseline, or antipsychotic is contraindicated. Benzodiazepines can cause delirium.
Lorazepam (Ativan): initially, 0.25 to 0.5 mg PO/IM/IV TID–QID PRN; may need to adjust to effect (caution in impaired liver and renal function)
Contraindications: Avoid typical antipsychotics in patients with parkinsonism or Parkinson disease.
Precautions: Typical antipsychotics may cause extrapyramidal effects; benzodiazepines may cause delirium. Both increase fall risk. Antipsychotics may prolong the QT interval. Aripiprazole (Abilify) has minimal or no QT prolonging effect.
Dexmedetomidine, when compared to haloperidol, has been used in the ICU setting and proven to reduce agitation in delirious ICU adults. The primary adverse effects of this medication include hypotension and bradycardia (6)[C].
Second Line
Olanzapine (Zyprexa) 2.5 to 5.0 mg PO daily to BID
Cholinesterase inhibitors should be avoided. Multiple trials demonstrate adverse events with cholinesterase inhibitors in the management of delirium; evidence does not support their use.
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ISSUES FOR REFERRAL
Geriatric, psychiatric, or neurologic consultation is helpful if delirium is not easily explainable or resolving after full evaluation. Interprofessional team approach is best.
ADDITIONALTHERAPIES
Early mobilization critical
Out of bed several hours daily starting on hospital day 2 (or postoperative day 1) if no contraindications
ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS
Cognitive engagement is key.
New delirium is a medical emergency and requires admission, except in the setting of hospice care (i.e., terminal delirium).
IV fluids as needed for dehydration
Monitor for the development of delirium.
Assessment of precipitants/contributing factors (pain, constipation, urinary retention)
Reorient; maintain day/night orientation.
Skin care and turning regimen for immobile patients
Maintain and encourage mobility.
Encourage family presence and participation. 
Discharge criteria
–Resolution of precipitating factor(s)
–Safe discharge site if delirium is slow to resolve
ONGOING CARE
FOLLOW-UPRECOMMENDATIONS
If delirium at discharge, often needs postacute facility and ongoing assessment for resolution
If no delirium at discharge, follow up with primary care physician in 1 to 2 weeks.
Patient Monitoring
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Evaluate and assess mental status daily.
Continued evaluation for precipitating cause(s)
DIET
Liberalize diet to increase oral intake.
Nutritional supplements if intake poor
Consider temporary nasogastric tube if unable to eat and bowels working.
PROGNOSIS
May take weeks/months to fully resolve
Usually improves with treatment of underlying condition(s); can lead to chronic cognitive impairment
Delirium significantly increases a person’s 1 year mortality risk.
COMPLICATIONS
Falls and functional decline
Pressure ulcers and malnutrition
Future cognitive dysfunction
Higher risk for institutionalization
Death
REFERENCES
1.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
2.Van Eijk MM, van Marum RJ, Klijn IA, et al. Comparison of delirium assessment tools in a mixed intensive care unit. Crit Care Med. 2009;37(6):1881–1885.
3.Reston JT, Schoelles KM. In-facility delirium prevention programs as a patient safety strategy: a systematic review. Ann Intern Med. 2013:158(5, Pt 2):375–380.
4.Kalabalik J, Brunetti L, El-Srougy R. Intensive care unit delirium: a review of the literature. J Pharm Pract. 2014;27(2):195–207.
5.Barr J, Fraser GL, Puntillo K, et al; for American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263–306.
6.Schwartz AC, Fisher TJ, Greenspan HN, et al. Pharmacologic and
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nonpharmacologic approaches to the prevention and management of delirium.
Int J Psychiatry Med. 2016;51(2):160–170.
ADDITIONALREADING
Inouye SK, Robinson T, Blaum C, et al. American Geriatrics Society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc. 2015;63(1):142–150.
National Clinical Guideline Centre. Delirium: Diagnosis, Prevention, and Management. London, United Kingdom: National Clinical Guideline Centre; 2010.
Quinlan N, Marcantonio ER, Inouye SK, et al. Vulnerability: the crossroads of frailty and delirium. J Am Geriatr Soc. 2011;59(Suppl 2):S262–S268.
SEE ALSO
Dementia; Depression; Substance Use Disorders
Algorithm: Delirium
CODES
ICD10
R41.0 Disorientation, unspecified
F19.931 Oth psychoactive substance use, unsp w withdrawal delirium 
F10.231 Alcohol dependence with withdrawal delirium
CLINICALPEARLS
The CAM criteria for delirium are acute onset of fluctuating mental status, inattention, and either disorganized thinking or altered level of consciousness.
Hypoactive subtype of delirium can easily be missed.
Addressing six risk factors (i.e., cognitive impairment, sleep deprivation, dehydration, immobility, vision impairment, and hearing impairment) in hospitalized patients can reduce the incidence of delirium by 33%.
Delirium may not resolve as soon as the treatable contributors resolve; may take weeks or months
Avoid diphenhydramine and benzodiazepines in older patients.
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