1. Cynthia M.A. Geppert, MD, DPS, FAPM,
Delirium
Cynthia M.A. Geppert, MD, DPS, FAPM,
Chief Consultation Psychiatry & Ethics New Mexico Veterans Affairs Health Care System

2. Objectives By the end of the presentation the learner will be able to:
Recognize the core signs and symptoms of delirium according to DSM-5
Give examples of risk factors for development of delirium
Propose treatment plans for delirium

3. What is Delirium???
A Video Game?
A Heavy Metal Band?

4. Or A Neuropsychiatric Disorder
“Delirium is defined as a transient, usually reversible, cause of cerebral dysfunction and manifests clinically with a wide range of neuropsychiatric abnormalities. It can occur at any age, but it occurs more commonly in patients who are elderly and have compromised mental status.”
Medscape

5. DSM-5 Criteria for Delirium
Disturbance in attention
Reduced ability to direct, focus, sustain or shift attention) or awareness.

6. Rapid and Fluctuating
Disturbance develops over a short period (usually hours to days)
Fluctuate over the course of a day.

7. Evidence of
That the disturbance is caused by direct physiological consequence of:
General medical condition
Intoxicating substance
Medication use
More than one cause (multifactorial)

8. Epidemiology Prevalence at hospital admission is 14-24%
15-53% of older post-operative
6-56% of general hospital
Mortality 10-26%
70-87% in intensive care
83% at end of life
10-30% of elderly patients in ER
(Inouye, NEJM2006;341: )

9. Burden of Delirium in Hospital
In hospital, delirium associated with:
10-fold increase in death
3-5 fold increase in complications,
Prolonged length of stay
Need for nursing home at discharge
TAKE Home point: minimize length to delirium
(Inouye SK. NEJM.2006;)

10. Delirium, Death, and Dementia
Meta-analysis of 3000 patients with hospital delirium over 2 years:
2.0 OR for death, 2.0 for institutionalization,2.4 for development of dementia.
Independent of baseline dementia, comorbid medical illness, illness severity, age, sex.
(Witlow J. JAMA. 2010)

11. Delirium Causes: “I Watch Death”
Infection
Withdrawal
Acute-metabolic
Trauma
CNS pathology
Hypoxia
Deficiencies
HIV, sepsis, Pneumonia
Alcohol, barbituate, sedative-hypnotic
Acidosis, alkalosis, electrolyte disturbances, hepatic & renal failure
CHI, post-operative, burns, abscess, hemorrhage, hydrocephalus, subdural
Seizures, stroke, tumors, metastases, vasculitis, encephalitis, syphilis
Anemia, carbon monoxide, hypotension, pulmonary or cardiac failure
B12, thiamine, folate, niacin

12. More Death Endocrinopathies Acute Vascular Toxins Heavy metals
Hyper/hypoadrenocorticism, hyper/hypoglycemia, myxedema, hyperparathyroidism
Stroke, shock, arrhythymia, hypertensive emergency
RX & OTC drugs, illicit drugs, pesticides, solvents
Lead, manganese,mercury

13. Deliriogenic Medications
Anesthetics
Anticholinergic
Antihistaminergic
Antimicrobials
Anticonvulsants
Lithium
Asthma
Antihypertensive/cardiac medications
Corticosterioids
Immunosuppressive
GI drugs
Muscle relaxants
Parkinson’s drugs
Analgesics: NSAIDs/Opioids
Sedatives/hypnotics
APA Guideline

14. Clinical Signs and Symptoms
The characteristic picture is rapidly developing disorientation, confusion and global cognitive impairment.
Reduced awareness
Difficulty focusing
Distracted attention
Impaired cognition
Illusions or hallucinations

15. More Symptoms Sundowning (worse in evening, better in morning)
Other sleep-wake cycle disturbances
Agitation or somnolence
Delusions-hallucinations, paranoia
Disorientation to place, date, and even person.
Incoherence
Restlessness
Mood lability, irritability

16. Subtypes of Delirium
Hyperactive, hypoactive, mixed subtypes: mixed most common.
Hypoactive more likely in older (65) patients than younger.
Hypoactive most likely to be missed and worse prognosis, hyperactive best.
Psychotic features most distressing to caregivers and family.

17. Is There ICU Psychosis?
No there is no such thing. While environmental events can influence delirium, they cannot cause it.
The science fiction environment of the ICU does not make patients psychotic, but also does not help them recover.

18. Delirium Versus Dementia
Symptom
Consciousness
Orientation
Course
Onset
Attention
Psychomotor
Hallucinations
Sleep-wake cycle
Speech
Delirium
Decrease or hyper
“Clouded”
Disorganized
Fluctuating
Acute or subacute
Impaired
Agitated or lethargic
Perceptual disturbances
Visual Hallucinations
Abnormal
Slow/incoherent
Dementia
Alert
Disoriented
Steady slow decline
Chronic
Usually normal
Delusions more common
Fragmented./normal
Aphasic/anomic difficulty finding words

19. Clinical Management
First Aggressively Treat the Underlying Medical Condition!
Maintain patient’s overall health and safety: minimize catheters, IV,leads
Restraints worsen delirium, increase fall risk do not use unless absolutely necessary to protect patient and staff and ALL other interventions fail.

20. Yale Delirium Prevention Trial
Demonstrated effectiveness of interventions aimed at 6 factors:
30-40% of delirium preventable
Orientation and therapeutic activity for cognitive impairment
Early mobilization
Minimize psychoactive drugs

21. Factors Continued Prevent sleep deprivation
Use adaptive equipment such as shearing aids and glasses for sensory impairment.
Address volume depletion early
Attention to nutrition and elimination
(Inouye SK. NEJM 1999;340:669-76)

22. More Environmental Avoid staff and room or ward changes
Involve family members in care
Use of orienting and familiar objects: family pictures, calendars
Regular schedule for administering medications and procedures
Normalize sleep cycle

23. Environmental Measures
Close monitoring by nursing staff
Reassurance and simple explanations
Minimize external stimulation
Quiet well-lighted rooms
Sitters may be necessary to keep the patient from injuring herself.

24. Role of Pharmacology Use when environmental measures fail:
Symptoms of delirium threaten the safety of patient or staff or other patients.
Or result in interruption of necessary treatment: removal of lines and monitors, inability to cooperate with care.

25. Cochrane Review of Benzodiazepines for Delirium
Objective was to determine the efficacy and adverse events associated with using benzodiazepines for delirium not due to alcohol withdrawal.
Only 1 trial met selection criteria and showed superiority of dexmedetomidine to lorazepam in increasing number of delirium free days in ventilated ICU patients.

26. Cochrane Conclusion
No adequately controlled trials could be found to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients, and at this time benzodiazepines cannot be recommended for the control of this condition.
Lonergan E, Luxenberg J, Areosa Sastre A. Benzodiazepines for delirium. Cochrane Database of Systematic Reviews 2009, Issue 4.

27. Haloperidol Versus Atypical Antipsychotics for Delirium
Four studies have compared the two:
DB RCT (risperidone)
SB RCT (olanzapine)
2 retrospectives (olanzapine, quetiapine)
Analysis of the studies found atypicals as efficacious as haldol
With fewer EPS side effects likely and thus safer.
Rea RS. Pharmacotherapy Apr;27(4):

28. Which Atypical?
Review of 13 studies using risperidone, quetiapine, olanzapine and ziprasidone. (no aripiprazole cases)
Retrospective prospectiive, open-label and double blind design
Risperidone, olanzapine and quetiapine all appear similarly effective.
Treatment safe and few side effects.
Boettger S. Palliat Support Care Sep;3(3):

29. Clinical Pearls for Atypicals
Risperidone: oral and m-tab dissolvable, no IM except depot.
Dosing 0.5 mg q 6 hrs NTE 2 mg in 24 hours.
Mildly sedating with highest risk of EPS.
Olanzapine: IM, oral, and disintegrating tablet.
Dosing 2.5 mg IM/oral q 6 hrs, NTE 10 mg in 24 hrs.
Watch hypotension DO NOT GIVE WITH IV BENZOS
Very sedating good for agitation with combativeness.
Quetiapine: oral only. BLACK BOX FDA QTc
First choice for palliative care.
Watch hypotension
mg q 6 hrs.
Good sedation and especially anxiolysis, mood disturbance.
Aripiprazole: oral and IM
Dosing oral 2.5 mg q 6 hrs and IM 9.75 mg q 12 hrs. NTE
Not sedating, but calming, safest in cardiac or very ill medical patients.

30. Quick and Dirty on the QTc
Highest Risk
Mild to Moderate Risk
Little Risk
Haldol IV
Quetiapine with new FDA QTc prolongation warning
Vieweg WV. J Clin Psychiatry 2003;5:
Ziprasidone
Oral Haldol
Olanzapine
Risperidone
Clozapine
Aripiprazole

31. Dexmedetomidine:
Recently advantages of alpha (2) agonists in ICU have been studied.
Landmark JAMA study compared dex and midazolam for efficacy and safety in patients ventilated for more than 24 hours.
RCT with 375 med/surg ICU patients sedation/delirium assessed with the RAS/CAM.

32. Dexmedetomidine
Dex ( mcg/kg/hr vs. midazolam mg/kg/hr.
Prevalence of delirium was 54% in dex group and 76% in midazolam; 1.9 fewer days to extubation for dex.
Dex more likely to have bradycardia but less HTN and tachycardia
Riker JAMA; 301:

33. Melatonin Makes the Morning
Review of 2 RTC
Some evidence may have benefit in preventing/managing delirium
No evidence reduces severity or improves behaviors.
1 study Ramelteon effective preventing delirium vs. placebo.
Both agents well tolerated.
Am J Alzheimers Dis Other Demen Mar;30(2):

34. Unappreciated Valproic Acid
Indications: rapid control of agitation, not good hypoactive delirium.
QTc prolongation or other contraindications to antipsychotics such as recent MI or CVA, Parkinson’s.
Stroke, TBI, dementia
Available as pill, sprinkles, IV start 125 mg for very old or 250 mg q 6hrs.

35. Contraindications
LFTs: over 3 x elevation in transaminases do not use.
CBC: causes thrombocytopenia and more rarely pancytopenia
Lipase and amylase can cause hemorrhagic pancreatitis
Ammonia needs monitoring as can cause hyperamonnemia.
(Sher et.al. Psychosomatics

36. Summary Delirium is a medical not psychiatric disorder
Poor outcomes and high morbidity
Identify and reverse or reduce factors causing/contributing to delirium
Minimize duration of delirium
Provide supportive care: keep patient safe