Delirium

Delirium (Acute Brain Failure)

• Acute onset of fluctuating cognitive impairment (global) and a disturbance in attention and awareness.
• Delirium is a syndrome, not a disease, and it has many causes, all of which result in a similar pattern of S & S.
• The brain could fail like the heart, liver, or kidney.
• Classically, delirium has a sudden onset (hours or days).
• A brief and fluctuating course.
• Rapid improvement when the causative factor is identified and eliminated.
• Abnormalities of mood, perception, and behavior are common psychiatric symptoms.
• Reversal of sleep-wake pattern.

Incidence of Delirium Among Medically Ill Patients

• Community overall: 1%-2% BUT increases with age: 14% > 85 years
• Hospitalized elderly: 15-40%
• Postoperative patients: up to 50%
• Near-death terminal patients: up to 80%

Medical Populations Under Study	Prevalence of Delirium (%)
General Medicine Wards	9-24% (Ritchie et al., 1996; Valdes et al., 2000; Maldonado, Dhami, & Wise, 2003; Gonzalez, de Pablo, et al., 2004; Speed et al., 2007)
HIV/AIDS	30%-40% (Fernandez, Levy, & Mansell, 1983; Uldall et al., 2000)
Medical-ICU	60%-80% (Ely et al., 2001)
Post-Stroke	13%-48% (McManus et al., 2007)
Surgery
Postoperative Delirium	10%-74% (Vaurio et al., 2006; Wiesel, Klausner, et al., 2011)
General Surgical Wards	7%-52% (Dyer & Teasdale, 1995; Buch, Gustafson, & Sandberg, 1999)
Spine Surgery	12.5% (Kawaguchi et al., 2006)
Post-CABG	25%-32% (Nevin, Colchester, et al., 2001; Ebert & Hermann 2001)
Post-Cardiotomy	50%-67% (Smith & Dimsdale, 1989; van Mast & Roest, 1996; Maldonado et al., 2009)
Abdominal Aneurysm Repair	33% (Benoit et al., 2005)

• Outpatient Minor (Cataract) Surgery: 4.4% (Milstein et al., 2002)
• At Time of Hospitalization: 10%-15%
• In Nursing Homes: 15%-60%
• Frail Elderly Patient: 60% (Francis et al., 1990)
• Elective Hip or Knee Replacement: 25% (Gustafson, Berggren, et al., 1988; Marcantonio, Flacker, et al., 2000)
• Bilateral Knee Replacement: 41% (Williams-Russo et al., 1992)
• Femoral Neck Fracture Repair: 65% (Gustafson, Bucht, et al., 1988; Marcantonio et al., 2000)
• Oncology: |
• General Prevalence: 25%-40% (Weinrich & Sarna, 1994; Olofsson et al., 1996; Tuma & DeAngelis, 2000) |
• Palliative Care Units: 26%-42% (Lawlor, Pereira, et al., 2000; Mortta, Tei, et al., 2001; Lawlor, 2002; Centeno, Sanz, & Bruera, 2004) |
• Bone Marrow Transplantation: 73% (Fann et al., 2007) |
• Advanced Cancer: Up to 85% (Lawlor et al., 2000) |
• Psychiatry: |
• Among Psychiatric Patients: 14.6% (Ritchie et al., 1996) |

(Maldonado, 2015)

Delirium Risk Factors (Maldonado, 2015)

Modifiable Factors

• Various pharmacological agents, especially GABAergic (Benzodiazepines) and opioid agents, and medications with anticholinergic effects
• Prolonged and/or uninterrupted sedation
• Immobility
• Acute substance intoxication/withdrawal
• Use of physical restraints
• Water and electrolyte imbalances
• Nutritional deficiencies
• Metabolic disturbances and endocrinopathies (primarily deficiency or excess of cortisol)
• Poor oxygenation states (e.g., hypoperfusion, hypoxemia, anemia)
• Disruption of the sleep-wake cycle
• Uncontrolled pain
• Emergence delirium

Non-Modifiable Factors

• Older age
• Baseline cognitive impairment
• Severity of underlying medical illness
• Preexisting mental disorders

Neuropathogenesis of Delirium

• Precipitants of Delirium
  (e.g., infection, trauma, anesthetics, surgery, hypoxia, hypoglycemia, metabolic derangements)

  • Neuroinflammation
  • Oxidative Stress
  • Diurnal Sleep/ Melatonin Dysregulation

• Aging

• Network Disconnection

• Neurotransmitter Dysregulation

• Neuroendocrine Abnormalities

Pathophysiology of Delirium, Neurotransmitter Changes (E Marcantonio, 2006)

• Medications
• Alcohol withdrawal
• Stroke
• Cytokine Excess
• Dopamine Activation
• Serotonin Activation
• Medications
• Substance withdrawal

Delirium

• Cholinergic Activation
• Cholinergic Inhibition
• Reduced GABA Activity
• GABA Activation
• Glutamate Activation
• Serotonin Deficiency
  • Tryptophan depletion
  • Phenylalanine elevation
• Surgical Illness
• Medical Illness
• Cortisol Excess
  • Glucocorticoids
  • Cushing’s Syndrome
  • Surgery
  • Stroke

Causes: “I WATCH DEATH”

• I nfec tions
• W ithdrawal
• A cute metabolic
• T rauma
• C NS pathology
• H ypoxia
• D eficiencies
• E ndocrinopathies
• A cute vascular
• T oxins or drugs
• H eavy metals

Life Threatening Causes of Delirium (WHHHIMP)

• Wernicke’s encephalopathy
• Hypoxia
• Hypoglycemia
• Hypertensive encephalopathy
• Intracerebral hemorrhage
• Meningitis/encephalitis
• Poisoning

DSM-5 Diagnostic Criteria for Delirium

A) A disturbance in attention (reduced ability to 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 days) and tends to fluctuate in severity during the course of the day.

C) An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability) or perception.

D) The changes in criteria A & C are not better explained for by a preexisting, established or evolving neurocognitive disorder or not in the context of coma.

E) There is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by the direct physiological consequences of another medical condition or substance.

DSM-5 Diagnostic Criteria for Delirium (Continued)

• Specify whether:

  • Substance intoxication delirium
  • Substance withdrawal delirium
  • Medication-induced delirium
  • Delirium due to another medical condition
  • Delirium due to multiple etiologies

• Specify if:

  1. Acute: Lasting a few hours or days.
  2. Persistent: Lasting weeks or months.

• Specify if:

  • Hyperactive: mood lability, agitation, not cooperative with care
  • Hypoactive: sluggishness and lethargy that approaches stupor.
  • Mixed level of activity

Differential Diagnosis

• Major Neurocognitive Disorder (Dementia)
• Mild Neurocognitive Disorder
• Depression/mania
• Schizophrenia/Other psychotic disorders

Delirium Vs Dementia

• Features
  • Delirium
    • Onset: Acute
    • Course: Fluctuating
    • Duration: Days to weeks
    • Consciousness: Altered
    • Attention: Impaired
    • Psychomotor changes: Increased or decreased
    • Reversibility: Usually
  • Dementia
    • Onset: Insidious
    • Course: Progressive
    • Duration: Months to years
    • Consciousness: Clear
    • Attention: Normal, except in severe dementia
    • Psychomotor changes: Often normal
    • Reversibility: Rarely

Workup

• History
• Interview - also with family, if available
• Physical, cognitive, and neurological exam
• Vital signs, fluid status
• Review of medical record
  • Anesthesia and medication record review
    • temporal correlation?

Exam

• P/E, Neurological exam (tremor, primitive reflexes, Asterixis).
• MSE: Tests orientation, short-term memory, attention, concentration, constructional ability.
• Quick emergency screening for delirium: day of the week, months backward.
• Specific neuropsychological tests:
  • MMSE/MOCA: < 20 out of total 30 points; suggestive of Delirium. But, Not helpful without knowing baseline.
  • MMSE is a little shorter and easier for pts but MOCA is better to detect mild NCD and early dementia.
  • MINI-cog (clock drawing test & 3-item recall test): quick screening for dementia.

Workup (Continued)

• Electrolytes
• CBC
• EKG
• CXR
• EEG - not usually necessary
• Arterial blood gas or Oxygen saturation
• Urinalysis +/- Culture and sensitivity
• Urine drug screen
• Blood alcohol
• Serum drug levels (digoxin, theophylline, phenobarbital, cyclosporin, lithium, etc)

Consider:

• Heavy metals
• Lupus workup
• Urinary porphyrins

Algorithm for the Management of Delirium (Maldonado, 2015)

• Recognition of patients at risk
• Implementation of prevention techniques
• Enhanced surveillance and screening
• Treatment or correction of underlying medical problems and potentially reversible factors (e.g., correction of electrolyte imbalances, infection, end organ failure, sleep deprivation, pain, metabolic and endocrinological disturbances, substance or medication intoxication or withdrawal)
• Treatment of all forms of delirium (with pharmacological and nonpharmacological approaches).

Factors Contributing to the Poor Detection Rate of Delirium (Maldonado, 2015)

Systems Factors

• Lack of consensus over the optimal assessment of delirium
• Location of care (worse in surgical rather than medical settings)
• Busy clinical settings (especially low nurse-to-patient ratio)
• Inadequate application of sedation holidays in sedated-ventilated patients
• The rapid transfer of patients from one unit to another, which may decrease the proper documentation and diagnosis

Clinician Factors

• Lack of knowledge and training
• Lack of confidence
• Lack of suspicion
• Lack of time of the clinical staff
• Expectation that altered mental status or delirium are a “normal occurrence” in certain medical settings, such as the ICU

Patient Factors

• Older subjects
• Patients experiencing Comorbid dementia
• Fluctuating course of presentation
• Presence of hypoactive features

Is Psychiatric Diagnosis Made by Non-Psychiatrists in Medical Setting Accurate?

• Prospective study of 157 pts, done by (Aljarad, Alhuthail and Alosaimi, KKUH, Riyadh, 2007)
• The most common psychiatric disorder in medically ill inpatients in this cohort was depressive disorders, with an accurate diagnosis in almost half of the patients.
• Diagnoses of cognitive disorders or substance abuse by physicians other than psychiatrists were 100% accurate.
• Misdiagnosis of cognitive disorders was common and they are easily mistaking them as depression.

Objective Measures for the Diagnosis of Delirium

• DSM-5 (Gold Standard)
• Delirium Rating Scale
• Confusion Rating Scale
• Confusion Assessment Method
• Delirium Symptom Interview
• Delirium Assessment Scale
• Cognitive Test for Delirium
• NEECHAM Confusion Scale
• Confusional State Evaluation
• Memorial Delirium Assessment Scale
• Delirium Severity Scale Delirium Index
• Delirium Rating Scale–Revised-98
• Intensive Care Delirium Screening Checklist
• Confusion Assessment Method for the Intensive Care unit
• Delirium Detection Score
• Nursing Delirium Screening scale
• Delirium Detection Tool–Provisional
• Stanford Proxy Test for Delirium (validation study in SA)

Validation of the Stanford Proxy Test for Delirium (S-PTD) Among Critical and Noncritical Patients

1. Department of Psychiatry, King Saud University, Riyadh, Saudi Arabia
2. Department of Critical Care Medicine, King Saud University, Riyadh, Saudi Arabia
3. Psychosomatic Medicine Service, Departments of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA

• Background: The Stanford Proxy Test for Delirium (S-PTD) is a tool developed to be completed by nurses at the end of their shift. It was designed to use the knowledge acquired during a full shift of nurse-patient interaction. The objective of our study was to validate the S-PTD among a mixed sample of patients in both the intensive care unit (ICU) and non-ICU settings.

• Methods: A cross-sectional study was conducted in an ICU and three general medical wards in a tertiary care hospital. Patients were independently and blindly assessed for delirium (by the patients’ primary nurses using the S-PTD at the end of their shift, and 2) a Consultation liaison psychiatrist who conducted a neuropsychiatric evaluation based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

• Results: A total 288 patients were included in current analysis. Using the S-PTD, delirium was identified in 72 (25.0%), while an expert neuropsychiatric examination, based on DSM-5 identified delirium in 75 (26.0%) patients. This study demonstrated that the S-PTD has very strong discriminating ability (area under the curve = 0.946, p < 0.001). An S-PTD cut-off score ≥ 3 was associated with an 82.7% sensitivity, an 95.3% specificity, an 86.1% positive predictive value, a 94.0% negative predictive value, and a 92.0% overall diagnostic accuracy. These results were similar in both ICU and general ward patients.

• Conclusion: The S-PTD has excellent sensitivity and specificity in detecting delirium in both ICU and ward patients, even when compared to the gold-standard, a DSM-based neuropsychiatric examination.

Multicomponent Management of Delirium Symptoms

• Prevent complications

• Ensure hydration is adequate

• Family/carer involved in care

• Ensure good communication – use interpreters/liaison officers/communication aids

• Use vision and hearing aids

• Ensure pain relief is adequate

• Normalize sleep patterns

• Reorientation and reassurance strategies

• Relaxation techniques

• Educate client and family/carers

• Encourage activity – mobility and ADLs

• Antipsychotic medications

Person with Delirium

Treatment of All Forms of Delirium (Maldonado, 2015)

• A. Identify and treat underlying medical causes.
• B. Treat or correct underlying medical problems and potential reversible factors.
• C. Conduct an inventory of all pharmacological agents that have been administered to the patient.
  • i. Discontinue any medication or agent known to cause delirium (benzodiazepines, opioid) or to have high anticholinergic potential, if possible, or institute a suitable alternative.

Management

• Monitor and assure safety of patient and staff:
  • suicidality and violence potential
  • fall & wandering risk
  • need for a sitter
  • remove potentially dangerous items from the environment
  • restrain ONLY when other means not effective (it may worsen delirium).

D. Implement Early Mobilization Techniques:

4. Daily awakening protocols (sedation holiday).
5. Remove IV lines, bladder catheters, physical restraints, and any other immobilizing apparatuses as early as possible.
6. Initiate aggressive PT and OT ASAP.
7. Provide required sensory aids.
8. Promote as normal a circadian light rhythm as possible:
   • a. Better if this can be achieved by environmental manipulations, such as light control (i.e., lights on and curtains open during the day; lights off at night) and noise control (i.e., provide ear plugs, turn off TVs, minimize night staff chatter).
   • b. Provide as much natural light as possible during the daytime.
9. Provide adequate intellectual and environmental stimulation as early as possible.

Guidelines for Managing Agitation

E. Avoid using GABA-ergic agents to control agitation, if possible.

• Exception: cases of CNS-depressant withdrawal (i.e., alcohol, benzodiazepines, barbiturates); or when more appropriate agents have failed and sedations are needed to prevent patient’s harm.

F. Adequately assess and treat pain. i. Avoid the use of opioid agents for behavioral control of agitation.
ii. Rotate opioid agents from morphine to hydromorphone or fentanyl.

G. In Case of Hyperactive Delirium, Consider the Use of the Following Agents:

10. Dopamine antagonist agents (e.g., haloperidol, risperidone, quetiapine, aripiprazole) as mainly symptomatic treatment for agitation, psychosis, etc.

• b. Before using them esp. haloperidol:
  • Obtain 12-lead ECG; measure QTc.
  • Check electrolytes; correct K+ and Mg+, if needed.
  • If possible, avoid other medications known to increase QTc and/or inhibitors of CPY3A4.
  • Discontinue dopamine antagonist agents’ use if QTc increases to >25% of baseline or >500 msec.

11. Other options:

• -Alpha-2 agonist agents (e.g., dexmedetomidine, clonidine, guanfacine)
• -Anticonvulsant and other agents with glutamate antagonism or Ca+ Ch modulation (e.g., VPA, gabapentin, amantadine, memantine)

H. In Case of Hypoactive Delirium:

• i. Some evidence suggests that DA antagonists may still have a place, given the excess DA theory.

  • a. If haloperidol is used, recommended small night dose.

• b. If an atypical is preferred, consider an agent with low sedation (i.e., risperidone, aripiprazole).

• ii. In cases of extreme psychomotor retardation or catatonic features, in the absence of agitation or psychosis, consider the use of psychostimulant agents (e.g., methylphenidate, dextroamphetamine, modafinil) or conventional dopamine agonists (e.g., bromocriptine, amantadine, memantine).

• Melatonin/ Ramelteon help to prevent delirium.

Delirium Has Bad Prognosis

• May progress to stupor, coma, seizures or death, particularly if untreated.
• Increased risk for postoperative complications, longer postoperative recuperation, longer hospital stays, long-term disability.
• Elderly patients 22-76% chance of dying during that hospitalization.
• Several studies suggest that up to 25% of all patients with delirium die within 6 months.

Outcomes of Delirium

• 40% permanent cognitive impairment
• 35% die
• 25% recover
  • (30% of them develop dementia within 3 years)

10 Delirium Myths Debunked

1. My patient is paranoid, therefore he is schizophrenic
2. Delirium is rare
3. Delirium is not serious
4. Sleep deprivation causes delirium
5. Delirium goes away rapidly
6. Delirium usually lasts for days or weeks
7. The patient’s medical problem has been treated, so the delirium should resolve
8. My delirious patient cannot make medical decisions
9. My patient cannot be delirious because he is oriented to time and place
10. My patient has depression, not delirium, because he is not getting out of bed
11. Delirium cannot be treated

Conclusion

• Delirium is common and is often a harbinger of death- especially in vulnerable populations
• It is a sudden change in mental status, with a fluctuating course, marked by decreased attention
• It is caused by underlying CNS pathology, flare up of systematic medical problems, drug intoxication/withdrawal, or a combination
• Recognizing and treating delirium and searching for the cause can save the patient’s life