Preventing delirium in geroforensic population

1. Adonis Sfera, MD and Luzmin Inderias, MD
Preventing Delirium in Geroforensic
Population

2. Q&A
 Polydipsia or hypodipsia (drinking too much or not
enough fluids) may lead to acute delirium
True/False
 Urinary tract infections may precipitate an
exacerbation of schizophrenia
True/False
 Hypoactive delirium is easily differentiated from
major depressive disorder
True/False

3. Memo
 Delirium is a medical emergency which causes
permanent brain damage if not managed quickly and
correctly.
 Most clinicians currently under-recognize delirium,
potentially harming our patients.
 Prevention and treatment of delirium requires a true
interdisciplinary approach, and is worth the effort as it
saves lives!

4. The goal of this lecture
 Consider delirium in your differential.

5. Outline
 Vignettes
 Definition
 Delirium in psychiatric inpatients
 Uncharted territory: delirium in geroforensics
 Why does delirium happen
 Recognising it
 Risks and precipitants
 Prevention is better than cure
 Hydration and delirium

6. CASE 1
 LF is a 63 years old patient with history of
schizophrenia and several medical problems
including chronic kidney disease with sodium
imbalance, HTN and cardiac pacemaker.
 In January LF was transferred to the acute hospital
due to impaired awareness and cognition which
developed over a short period of time, resulting in
patient’s getting agitated and pulling his catheter
out.
 LF’s history and clinical presentation meet the DSM
V criteria for acute delirium.

7. CASE 2
 67 years old female with history of schizoaffective
disorder and mild cognitive impairment. Medical
problems: hypertension, hyperlipidemia and
obesity.
 Became combative, agitated and confused with
both visual and auditory hallucinations.
 PRN medication given consisting of haloperidol,
lorazepam, followed by increase in agitation.
 Diagnosed with UTI.

8. Definition
 Delirium is an age-related neurobehavioral syndrome
also called acute confusional state or acute brain failure.
 Its manifestations consist of fluctuating cognition,
deficits of attention, disorganized or violent behavior,
altered sleep-wake cycle, hallucinations and delusions.
ENGEL GL, ROMANO J. Delirium, a syndrome of cerebral insufficiency. J Chronic Dis. 1959 Mar;9(3):260-77).

9. The history
Hippocrates (5 BC)
Hippocrates referred to delirium as “phrenitis” from
which we derive the word frenzy.
“As the motion of the arms I observe the
following facts: in acute fevers, pneumonia,
phrenitis and headache, if they move before the
face, hunt in empty air, pluck nap from the
bedclothes, pick up bits and snatch chaff from
the walls - all these signs are bad, in fact deadly.”
Hippocrates (Prognostic, XXII)
Phrenitis was replaced with the word delirium in
1769

10. Delirium in literature
After being rejected by his daughters and exposed to the storm, king Lear
becomes delirious, perhaps by cerebral vascular disease.
He recovers slightly before his death and is reconciled with his youngest
daughter, Cordelia.

11. The frenzy (delirium)of Orlando Furioso
 Renaissance Italian poet Lodovico Ariosto (1516)
describes the frenzy (delirium) of Orlando Furioso
after not sleeping or eating for three days probably
resulting in dehydration and electrolyte imbalance:
“He neither sleeps nor eats; though three days pass,
Three times the dark descends, he has not stirred.
His grief so swells, his sorrow so amass
The madness clouds him, in which long he erred.
……………………………………
O miracle,
His intellect returned to its pristine
Lucidity as brilliant as before,
As his fair discourse latter witness bore.”
(Canto XXXIX)

12. Delirium: DSM-5 Diagnostic Criteria
 A. A disturbance in attention (i.e., reduced ability to direct, 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 a
few days), represents a change from baseline attention and awareness, and
tends to fluctuate in severity during the course of a day.
 C. An additional disturbance in cognition (e.g., memory deficit, disorientation,
language, visuospatial ability, or perception).
 D. The disturbances in Criteria A and C are not explained by another
preexisting, established, or evolving neurocognitive disorder and do not
occur in the context of a severely reduced level of arousal, such as coma.
 E. There is evidence from the history, physical examination, or laboratory
findings that the disturbance is a direct physiological consequence of
another medical condition, substance intoxication or withdrawal (i.e., due to a
drug of abuse or to a medication), or exposure to a toxin, or is due to multiple
etiologies.

13. ICD-10 types of delirium
 F00-F09 Organic, including symptomatic, mental disorders
 F05 Delirium, not induced by alcohol or other psychoactive
substances
 F05.0 Delirium, not superimposed on dementia
 F05.1 Delirium superimposed on dementia
 F05.8 Other delirium
 F05.9 Delirium unspecified
 F10-19 Mental and behavioral disorders due to psychoactive
substance use
 F1x.03 Acute intoxication, with delirium
 F1x.4 Withrowal state with delirium
 F1x.40 Without convulsions
 F1x.41 With convulsions

14. Delirium matters, but why?
 More than 7 million hospitalized Americans suffer from
delirium each year.
 More than 60% of delirium cases are not recognized by
the health care system.
 Predictor of poor prognosis
 In hospitalized patients case fatality rates 25% to 35%
 Higher hospital costs per day
Source: American Delirium Society https://www.americandeliriumsociety.org/

15. More reasons
 60% longer hospital length of stay (LOS)
 Reducing delirium LOS by one day: saves $1-2 billion
dollars/year
 5 times higher nursing home placement
Source: American Delirium Society https://www.americandeliriumsociety.org/

16. Why is delirium under-recognized?
 The diagnosis of delirium is missed 33-67% of the time.
 Delirium may be the only presentation of severe illness in
older patients, for example:
“Silent” myocardial infarction presents with delirium in up
to 40% of cases.
25% of older people have no fever associated with
pneumonia, tuberculosis, endocarditis or sepsis, delirium
being the only manifestation.
13% of older bacteremic patients are afebrile, but may
present with delirium.

17. Epidemiology
 In the US, the overall prevalence of delirium in the
community is 1–2%.
 The incidence of delirium arising during a hospital
stay ranges from 6% to as high as 56%.
 In geriatric neuropsychiatric patients the
incidence is 40-60%.
Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and
treatment. Nature reviews Neurology. 2009;5(4):210-220. doi:10.1038/nrneurol.2009.24.

18. Etiology - multifactorial
 Infection
 Polydipsia, hypodipsia with electrolyte imbalance
 Medications adverse effects
 Hypoperfusion
 Malignancy
 Pain
 Fecal impaction
 Urinary retention
 Sleep deprivation
 Physical restraints
 Endocrine problems

19. Delirium: an entity in-between psychiatry
and medicine

20. Delirium in primary psychiatric disorders
 The literature regarding delirium in severe psychiatric
disorders in is extremely scarce: a total of 8 studies
between 1996 and 2014.
 The literature regarding delirium in geroforensic
population is nonexistent.

21. This is what we know
 In the past individuals with schizophrenia and
schizophrenia-like disorders (SLD) did not live long
enough to develop age-related diseases (both
medical neuropsychiatric).
 Medical complications and suicide contributed to a
20-30% shorter lifespan in this population.
 Schizophrenia “survivors” are a new category of
individuals specific for our generation.

22. Delirium in psychiatric inpatients
 Patients with severe psychiatric illness have many risk
factors for delirium, such as cognitive impairment (Gill
and Mayou, 2000).
 Delirium is under-recognized in mental health setting
because its symptoms overlap with those of the primary
psychiatric illness.
 The highest prevalence of delirium was found in
individuals diagnosed with bipolar disorder (35.5%),
schizoaffective disorder (15.8%), schizophrenia
(12.1%)(Ritchie et all. 1996).

23. Delirium in psychiatric inpatients
A recent nationwide retrospective study from Denmark
concluded that:
 in psychiatric inpatients delirium is associated with
elevated mortality.
 anticholinergic and sedative-hypnotic agents are the
most commonly associated with delirium.
 the best predictors of delirium are cognitive impairment
and a previous history of delirium as 40% of patients with
delirium had more than one episode.

24. Delirium is frequently misdiagnosed
as a psychiatric condition
 Delirium is under-recognized in psychiatric patients because its symptoms
overlap with those of the primary psychiatric disorder.

25. A patients’ experience of delirium
 http://www.europeandeliriumassociation.com/patient-
video.html
 Think of delirium in elderly patients with chronic
psychosis.
 Delirium occurs in many hospitalized older patients and
has serious consequences including increased risk for
death and admission to long-term care facilities.
 Wong et al. JAMA. 2010.

26. Chronic delirium
Previously delirium been characterized
as an acute, severe and reversible
condition.
However, symptoms may endure
despite treatment or resolution of the
precipitating factors, resulting in
permanent cognitive impairment.
Novel studies found that 18% of
patients had delirium at 6 months.
American Delirium Society https://www.americandeliriumsociety.org/

27. Post-delirium cognitive impairment
 Most patients demonstrate persistent difficulties and only
rarely return to premorbid levels of functioning
 Even young patients experience post-delirium cognitive
impairment.
https://www.youtube.com/watch?v=x0QlOesVP9A&feature=
youtu.be

28. Differential diagnosis
 Delirium vs. Dementia
 Delirium vs. mania
 Delirium vs. acute paranoia
 Delirium vs. depression
 Delirium vs. psychosis

29. Delirium, dementia and exacerbation of psychosis
Clinical feature Delirium Dementia Exacerbation of
psychosis
Onset acute slow acute
Circadian course fluctuating stable stable
Level of consciousness affected spared spared
Attention impaired impaired may be impaired
Cognition impaired impaired may be impaired
Hallucinations usually visual often absent usually auditory
Delusions poorly systematized often absent sustained and
systematized
Psychomotor activity increased or reduced often normal variable
Involuntary movements Asterixis, myoclonus,
tremor
absent absent
EEG abnormal abnormal Usually normal

30. Clinical type of delirium Symptoms Resembles
Hyperactive Increased arousal
Restless,
Agitated
May be aggressive
Mania
Psychotic
decompensation
Hypoactive Decreased alertness
Slow speech
Apathetic
Depression
Mixed Combination of the
above
Rapid cycling

31. Delirium risk factors
Predisposing factors Precipitating factors
Dementia Restraints
Dehydration Dehydration
Co-morbidity More than 5 medications
Sensory impairment Bladder catheter

32. Delirium in the geroforensic population
 Forensic detainees represent a special population.

33. Schizophrenia predisposes to dementia
- Patients with schizophrenia and schizophrenia-like psychoses develop
late life dementia more often than the general population.
-Cognitive impairment is a feature of schizophrenia.
-Kraepelin used the term “dementia praecox” to describe schizophrenia.
-Over 25% of elderly with schizophrenia have moderate to severe
cognitive impairment.
Raghavakurup Radhakrishnan, Robert Butler, Laura Head. Dementia in schizophrenia. Advances in Psychiatric Treatment Mar
2012, 18 (2) 144-153; DOI: 10.1192/apt.bp.110.008268

34. The number of inmates over the age of 65 has more
than doubled between 2007 and 2013
0
5,000
10,000
15,000
20,000
25,000
30,000
35,000
2007 2013
15,500
31,854
Source: Bureau of Justice Statistics

35. Geroforensic population more predisposed to delirium
than nonforensic seniors
forensic detainees age more rapidly than the general population
maintained on higher doses of psychotropic drugs
lowering medication dosages often delayed to avoid relapse of aggression
more likely to have history of unhealthy life styles and of drugs or alcohol
addiction
obesity more likely: altered volume of distribution of antipsychotic drugs
more likely hepatitis c, altering albumin level and hepatic drug metabolism

36. Why care about delirium in geroforensic
population?
 Forensic institutions house individuals with severe
psychiatric disorders and significant history of
violence maintained on psychotropic drugs for
extended periods of time which predisposes this
population to adverse effects.
 Psychotropic drugs may impair both the hydration
status and thermoregulation, predisposing for
medication adverse effects.

38. Drug adverse effects
 Dementia and aging are the main risk factors for
delirium.
 Patients with dementia-delirium co-morbidity present
with a mortality risk of 65%.
 Dementia and aging are crucial for the development of
medication adverse effects which occur in over 15% of
older patients at an annual cost of 20 billion .
Pretorius RW, Gataric G, Swedlund SK, Miller JR. Reducing the risk of adverse drug events in older adults. Am Fam Physician. (2013)
87(5):331-6.

39. Medication adverse effects as risk factors of
delirium in psychiatric inpatients
 Anticholinergic medications
 ECT
 Lithium-antipsychotic combination
 High doses of low potency antipsychotic
drugs(Huang et al. 1998)
 Non-psychiatric medications including antibiotics
 Delirium may be a complication of treatment or
discontinuation of treatment with psychotropic
drugs (Kruszewski et al. 2009)(Lin and Ceo 2010).

40. Medications and aging
 The effects of medications in older adults is a new field
of study, even though more than one-half of all
prescription medications are dispensed to persons older
than 60.
Pretorius RW, Gataric G, Swedlund SK, Miller JR. Reducing the risk of adverse drug events in older adults. Am Fam Physician. (2013)
87(5):331-6

41. The Beers Criteria for Potentially
Inappropriate Medication Use in Older Adults
 A guideline for healthcare professionals to help improve the
safety of prescribing medications for older adults.
 It emphasizes risk-benefit ratio, polypharmacy, drug-drug
interactions and adverse drug reactions.
 The criteria are used in geriatrics clinical care to monitor and
improve the quality of healthcare.
 The "Beers Criteria" contains lists of medications that pose
potential risks outweighing potential benefits for people 65 and
older.
 By using Beers criteria practitioners may prevent harmful side
effects, including those that could be life-threatening.
Source: American Geriatric Society http://www.americangeriatrics.org

42. Antibiotics and delirium: a recent link
A recent study demonstrated that antibiotic toxicity can represent an unrecognized cause
of delirium in hospital patients, with manifestations observed in three distinct phenotypes:
 1. encephalopathy accompanied by seizures or myoclonus arising within days
after antibiotic administration (caused by cephalosporins and penicillin);
 2. encephalopathy characterized by psychosis arising within days of antibiotic
administration (caused by quinolones, macrolides, and procaine penicillin)
 3. encephalopathy accompanied by cerebellar signs and MRI abnormalities
emerging weeks after initiation of antibiotics (caused by metronidazole).
 Shamik Bhattacharyya, R. Ryan Darby, Pooja Raibagkar, L. Nicolas Gonzalez Castro, Aaron L. Berkowitz. Antibiotic-associated encephalopathy. Neurology
(2016) vol. 86 no. 10 963-971. doi: http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002455

43. UTI and schizophrenia
 Novel study: urinary tract infections 29 times more
likely in schizophrenia relapse.
 Most likely mechanism: delirium
Miller BJ, Graham KL, Bodenheimer CM, Culpepper NH, Waller JL, Buckley PF. A prevalence study of urinary tract infections in acute relapse of schizophrenia.
J Clin Psychiatry. 2013 Mar;74(3):271-7. doi: 10.4088/JCP.12m08050.

44. The UTI-delirium connection

45. The bottom line
 Under-recognition of delirium in geroforensic
institutions translates into poorer health care outcomes in
spite of higher medical spending.

46. Aging and hydration
 Homer: “old age is like a dried olive branch”.
 Aristotle: “one should know that living beings are
moist and warm . . . However old age is dry and cold.”
 Galen: “Aging is associated with a decline in innate
heat and body water.”
 Galen’s most pertinent observation was that
dehydration is difficult to diagnose, and this remains
true today.

47. Dehydration and morbidity
 Dehydration is a predisposing factor for delirium
 Dehydration has been associated with increased mortality
rates among hospitalized older adults.
 Dehydration is one of the ten most frequent diagnoses
responsible for hospitalization in the United-States.
 Dehydration has been associated with impaired cognition,
acute confusion, falls and constipation.
 The cost associated with dehydration in the US is estimated
at $1.14 billion a year.
Pretorius RW, Gataric G, Swedlund SK, Miller JR. Reducing the risk of adverse drug events in older adults. Am Fam
Physician. (2013) 87(5):331-6

48. Hydration, cognition and psychopathology
 Persistent subclinical dehydration is associated with
anxiety, panic attacks, and agitation.
 Fluctuation in tissue hydration results in inattention,
hallucinations, and delusions.
 Severe dehydration leads to somnolence, psychosis, and
unconsciousness (loss of awareness of the
surroundings).
 CNS symptoms are present when dehydration results in a
1% loss of body water and are very prominent at 5% loss.
 Breitbart W and Alici Y. Agitation and delirium at the end of life: “we couldn’t manage him”. JAMA. 2008;300(24):2898-2910.

49. Polydipsia or hypodipsia
 Polydipsia and hypodipsia (drinking to much or not
enough water) are encountered in individuals with
history of schizophrenia or schizophrenia-like
psychosis.
 Both predispose to electrolyte imbalance and
delirium.
 Both are regulated by the same brain area, the
subfornical organ (SFO).

50. The thirst center: subfornical organ (SFO)
Adonis Sfera, Michael Cummings, Carolina Osorio. Dehydration and cognition in geriatrics: a hydromolecular hypothesis. Front. Mol. Biosci., 12 May 2016
| http://dx.doi.org/10.3389/fmolb.2016.00018

51. Further research in geroforensic delirium
 It is necessary to answer the question: which
individuals require low dosage regimens of
psychotropic drugs in order to avoid age-related
adverse effects and which need and can tolerate
larger doses to avoid relapses into aggressive
behavior?