Post on 18-Dec-2015
Sundowning & DeliriumSundowning & Delirium
Francisco Fernandez, M.D., USF Health, Francisco Fernandez, M.D., USF Health, Department of Psychiatry, Tampa, FLDepartment of Psychiatry, Tampa, FL
www.thecjc.orgwww.thecjc.org
Sundowning: DefinitionSundowning: Definition
• Sundowning Sundowning a group of behaviors occurring in a group of behaviors occurring in some older patients with or without dementia at the some older patients with or without dementia at the time of nightfall or sunset. time of nightfall or sunset.
• BEHAVIORS:BEHAVIORS:• ConfusionConfusion• Anxiety, agitation, or aggressiveness Anxiety, agitation, or aggressiveness • Psychomotor agitation (pacing, wandering)Psychomotor agitation (pacing, wandering)• Disruptive, resistance to redirectionDisruptive, resistance to redirection• Increased verbal activity Increased verbal activity
• Overlap with dementia, delirium, and sleep Overlap with dementia, delirium, and sleep disturbance. disturbance.
Epidemiology of Sundowning Epidemiology of Sundowning SyndromeSyndrome
• Not uncommon phenomenonNot uncommon phenomenon• Exact prevalence unknown Exact prevalence unknown • Reports have ranged between Reports have ranged between
2.4% and 25%2.4% and 25%• In patients with Alzheimer’s disease In patients with Alzheimer’s disease
or dementia, the range is widened up or dementia, the range is widened up to 66%to 66%
Risk Factors for Sundowning: Risk Factors for Sundowning: Physiologic FactorsPhysiologic Factors• Circadian abnormalities in elderly and in Circadian abnormalities in elderly and in
patients with Alzheimer’s disease progress patients with Alzheimer’s disease progress concomitantly with their behavioral and concomitantly with their behavioral and cognitive dysfunction. cognitive dysfunction. • Sundowning is more common in AzD. Sundowning is more common in AzD.
• Neurofibrillary tangles found in the hypothalamus of Neurofibrillary tangles found in the hypothalamus of patients with Alzheimer’s may lead to the behavioral patients with Alzheimer’s may lead to the behavioral changes of sundowning through mechanical disruption of changes of sundowning through mechanical disruption of brain tissue.brain tissue.
• Pathologic damage to the suprachiasmatic nucleus Pathologic damage to the suprachiasmatic nucleus (SCN) is believed to result in disruptive behaviors (SCN) is believed to result in disruptive behaviors associated with sundowning.associated with sundowning.
Risk Factors for Sundowning: Risk Factors for Sundowning: Environmental FactorsEnvironmental Factors• Amount of daily light Amount of daily light
exposureexposure• Activities during the Activities during the
dayday• Noise levelNoise level• Disruptions at nightDisruptions at night• MedicationsMedications• Medical Medical
comorbiditiescomorbidities
• Nursing home residents Nursing home residents with sundowning were with sundowning were more likely tomore likely to• Recent admissionRecent admission• Moved to a new roomMoved to a new room• Staff shift changesStaff shift changes• Low levels of lighting Low levels of lighting
during the day and bright during the day and bright hallway lighting during hallway lighting during the nightthe night
• Increased naptime during Increased naptime during daytime hours and daytime hours and reduced nighttime sleepreduced nighttime sleep
Etiology of SundowningEtiology of Sundowning
• Dysfunction of the circadian rhythm result in Dysfunction of the circadian rhythm result in disturbed sleep and agitationdisturbed sleep and agitation• Deterioration of the SCN seen in patients with Deterioration of the SCN seen in patients with
Alzheimer’s disease is actively investigated to be an Alzheimer’s disease is actively investigated to be an important factor in the disruption of the circadian important factor in the disruption of the circadian rhythms.rhythms.
• Suprachiasmatic nucleus volume and cell number are Suprachiasmatic nucleus volume and cell number are found to be decreased in those between the ages of 80 found to be decreased in those between the ages of 80 and 100 years. and 100 years.
• Melatonin is found to be decreased in the cerebrospinal Melatonin is found to be decreased in the cerebrospinal fluid levels of patients with Alzheimer’s disease.fluid levels of patients with Alzheimer’s disease.
Mrs. FlabeetzMrs. Flabeetz• 84 yo female, living at 84 yo female, living at
the NH for the last 8 the NH for the last 8 years after a stroke; was years after a stroke; was having problems having problems managing at homemanaging at home
• Axis III: Type II Diabetes Axis III: Type II Diabetes and hypertensionand hypertension
• Active in her NH, using Active in her NH, using her walker; also a little her walker; also a little more forgetful and more forgetful and repetitive, and this has repetitive, and this has been getting slowly been getting slowly worse over the last year worse over the last year
In the ER…In the ER…• Came into ER after being Came into ER after being
found on the floor of the NHfound on the floor of the NH • Unable to get up and Unable to get up and
complaining of L hip and complaining of L hip and abdominal painabdominal pain
• In the ER, very muddled up In the ER, very muddled up & disoriented& disoriented
• incontinent of foul smelling incontinent of foul smelling urineurine
• Picking at imaginary things, Picking at imaginary things, scared, and very frightened scared, and very frightened
Initial work up…Initial work up…• No fracture on X-rayNo fracture on X-ray
• Normal CBC, lytes and Normal CBC, lytes and troponinstroponins
• CT head shows mild atrophy CT head shows mild atrophy & bilateral lacunar infarcts& bilateral lacunar infarcts
• Urine collected from foley Urine collected from foley inserted shows inserted shows E. coliE. coli; ; started ABXstarted ABX
• Admitted to Medicine for Admitted to Medicine for further assessment and further assessment and work up of confusionwork up of confusion
Alas! It’s been 5 days later, and she’s still not better …
TRANSFER TO PSYCHIATRY!!!!!!!
What would you do?What would you do?
Is this Delirium? Dementia?? Is this Delirium? Dementia??
Or something else???Or something else???
Would you transfer to Would you transfer to Psychiatry Service? Psychiatry Service?
Delirium Delirium
• Most common psychiatric disorder in the medically illMost common psychiatric disorder in the medically ill• Point prevalence - 20% of all admissionsPoint prevalence - 20% of all admissions
• 30% new onset among medical inpatients30% new onset among medical inpatients• 50% medical and surgical patients > 60 yo50% medical and surgical patients > 60 yo• 89% of patients with known dementia89% of patients with known dementia
• Higher prevalence with increasing age, CNS disease, Higher prevalence with increasing age, CNS disease, CABG, and THRCABG, and THR
• NOT a benign condition - sign of impending death in NOT a benign condition - sign of impending death in 25% cases25% cases
• Etiology - multifactorialEtiology - multifactorial
Rothschild et al, Arch Int Med 2000; Burns et al, JNNP 2004
Diagnostic Criteria: DSM-IVDiagnostic Criteria: DSM-IV
• Disturbance of consciousness (reduced Disturbance of consciousness (reduced clarity of awareness of environment) clarity of awareness of environment) • Reduced ability to focus, sustain or shift Reduced ability to focus, sustain or shift
attentionattention• A change in cognition (memory, A change in cognition (memory,
disorientation, language disturbance) or disorientation, language disturbance) or the development of a perceptual the development of a perceptual disturbance that is not better accounted disturbance that is not better accounted by dementiaby dementia
Diagnostic Criteria: DSM-IVDiagnostic Criteria: DSM-IV
• The disturbance develops over a short The disturbance develops over a short period of time (usually hours to days) period of time (usually hours to days)
• All abnormalities tend to fluctuate during All abnormalities tend to fluctuate during the course of the daythe course of the day
Diagnostic Criteria: DSM-IVDiagnostic Criteria: DSM-IV
• There is evidence from the medical history, There is evidence from the medical history, physical examination, or laboratory findings physical examination, or laboratory findings of: of:
1.1. A general medical condition etiologically relatedA general medical condition etiologically related• Sepsis, seizures, tumor, hypercalcemia, hypoglycemiaSepsis, seizures, tumor, hypercalcemia, hypoglycemia
2.2. Substance induced intoxication or withdrawalSubstance induced intoxication or withdrawal
3.3. More than one etiology More than one etiology
4.4. NOSNOS
““Motoric” SubtypesMotoric” Subtypes
Various levels of psychomotor activity Various levels of psychomotor activity
are associated with delirium:are associated with delirium:1.1. HypoactiveHypoactive
2.2. HyperactiveHyperactive
3.3. MixedMixed
CharacteristicsCharacteristics HypoactiveHypoactive HyperactiveHyperactive
AgeAge 54.3 (18.7)54.3 (18.7) 59.4 (17.8)59.4 (17.8)
MMSEMMSE 13.6 (7.4) 13.6 (7.4) 13.2 (7.3)13.2 (7.3)
Digit spanDigit span 4.1 (2.4)4.1 (2.4) 4.6 (2.2)4.6 (2.2)Clouding of Clouding of ConsciousnessConsciousness
5.7 (2.4)5.7 (2.4) 5.6 (2.3)5.6 (2.3)
SomnolenceSomnolence 5.4 (2.3)5.4 (2.3) 2.4 (2.0) ***2.4 (2.0) ***
HallucinationsHallucinations 3%3% 67% ***67% ***
IllusionsIllusions 0%0% 26% ***26% ***
DelusionsDelusions 3%3% 50% ***50% ***
ParanoiaParanoia 0% 0% 20%***20%***
AgitationAgitation 21%21% 72% ***72% ***
Adapted from Ross et al., Int Psychoger 1991
““Motoric” SubtypesMotoric” Subtypes
• Subtyping not fully accepted by all Subtyping not fully accepted by all disciplinesdisciplines
• Subtyping may have implications for Subtyping may have implications for treatmenttreatment
Epidemiology & Risk FactorsEpidemiology & Risk Factors• Depending on the cohort, the prevalence of Depending on the cohort, the prevalence of
delirium ranges from 8% to 80%delirium ranges from 8% to 80%• Post-surgical rates > general medical patientsPost-surgical rates > general medical patients
• Advancing age increases the risk (> 60 yoa)Advancing age increases the risk (> 60 yoa)
• 15-20% of patients on a medical surgical 15-20% of patients on a medical surgical ward have an undetected delirious processward have an undetected delirious process
Burns et al, JNNP 2004; Kales et al, JNNP 2002; vanZyl & Davidson, Can J Psych 2003
Epidemiology and Risk Epidemiology and Risk FactorsFactors• The Commonwealth-Harvard Study The Commonwealth-Harvard Study
(Levekoff et al., (Levekoff et al., Int Psychoger, Int Psychoger, 1991)1991)• Patients 65 yoa or olderPatients 65 yoa or older• Admissions to Beth Israel Hospital from Admissions to Beth Israel Hospital from
Hebrew Rehabilitation Center (n=114) and Hebrew Rehabilitation Center (n=114) and East Boston CHC (n=211)East Boston CHC (n=211)• CHC CHC 24.2% were delirious 24.2% were delirious• HRC HRC 64.9% were delirious 64.9% were delirious
Epidemiology and Risk Epidemiology and Risk FactorsFactors
• CNS abnormality CNS abnormality • Dementia, coexisting structural brain disease, Dementia, coexisting structural brain disease,
and HIV-1 infection increase the riskand HIV-1 infection increase the risk
• Drug dependencyDrug dependency• Alcohol, sedative hypnotics, stimulants, steroid Alcohol, sedative hypnotics, stimulants, steroid
(rapid taper) increase the risk(rapid taper) increase the risk
• Low serum albumin Low serum albumin • Malnutrition, chronic disease, aging, nephrotic Malnutrition, chronic disease, aging, nephrotic
syndrome, hepatic insufficiency syndrome, hepatic insufficiency
Why is Delirium important?Why is Delirium important?
Delirium has a poor prognosisDelirium has a poor prognosis
• LOS (>7d more)LOS (>7d more)• risk dementia dx (55%/2y)risk dementia dx (55%/2y)• ADL declineADL decline• institutionalizationinstitutionalization• mortality (2.1x/12 mos)mortality (2.1x/12 mos)
McCusker et al, JAGS 2003; McCusker et al, Arch Int Med 2002;
Rahkonen et al, JNNP; Inouye et al, JGIM 1998
Delirium Risk : A Predictive Delirium Risk : A Predictive modelmodel• Independent risk factors on Independent risk factors on
admission in a prospective admission in a prospective cohort of elderly medical inptscohort of elderly medical inpts 1. 1. Vision < 20/70Vision < 20/70
2. Severe illness (APACHE > 16)2. Severe illness (APACHE > 16)3. MMSE <243. MMSE <24
Inouye et al, Ann Int Med 1993
DiagnosisDiagnosis
• Rapid recognition of either prodromal or Rapid recognition of either prodromal or fully developed clinical featuresfully developed clinical features• ““A,B,C’s” of Neuropsychiatry (Affect, Behavior A,B,C’s” of Neuropsychiatry (Affect, Behavior
and Cognition)and Cognition)• Prodromal featuresProdromal features
• Restlessness, anxiety, irritability, sleeplessness, Restlessness, anxiety, irritability, sleeplessness, hypervigilance, distractibility, fatigue, disinterest, hypervigilance, distractibility, fatigue, disinterest, hypersomnolence, inattentiveness, depressed, hypersomnolence, inattentiveness, depressed, disillusionmentdisillusionment
Diagnosing DeliriumDiagnosing DeliriumDelirium Sx InterviewDelirium Sx Interview
1. Orientation1. Orientation
2. Sleep disturbance2. Sleep disturbance
3. Perceptual disturbance3. Perceptual disturbance
4. Speech disturbance 4. Speech disturbance
5. Disturbance of consciousness5. Disturbance of consciousness
6. Psychomotor activity6. Psychomotor activity
7. Affect & behavior7. Affect & behavior
Albert et al, J Ger Psych Neurol 1992
Diagnosis: MSEDiagnosis: MSE
• Mental status examination Mental status examination • Cognitive history Cognitive history chart review chart review
• What changes (consciousness, restlessness, What changes (consciousness, restlessness, anxiety, moodiness)anxiety, moodiness)
• When did changes occur (starting/stopping When did changes occur (starting/stopping drug, fever, hypotension, deteriorating renal drug, fever, hypotension, deteriorating renal function, rhythm changes)function, rhythm changes)
• MMSE, focused NBEMMSE, focused NBE
Diagnosis Testing - StandardDiagnosis Testing - Standard
MMSE & CDT-Not designed for delirium-Useful at separating “normal” from “abnormal”-Not specific for distinguishing delirium from dementia-May be useful as change from baseline-Overkill add TMT-A, TMT-B
Diagnostic Testing: ToolsDiagnostic Testing: Tools
SensitivitySensitivity Specificity Specificity
• CAM*CAM* .46-.92 .46-.92 .90.92 .90.92• Delirium Rating Scale Delirium Rating Scale .82-.94.82-.94 .82-.94 .82-.94• Clock draw+Clock draw+ .87 .87 .93 .93• MMSE (24 cutoff) .52-.87MMSE (24 cutoff) .52-.87 .76-.82 .76-.82• Digit span test .34Digit span test .34 .90 .90
*validated for delirium & capable of distinguishing delirium *validated for delirium & capable of distinguishing delirium from dementiafrom dementia
+validated for delirium, correlated with deterioration of +validated for delirium, correlated with deterioration of dominant frequencies on EEGdominant frequencies on EEG
1. 1. [Acute Onset][Acute Onset] Is there evidence of an acute change in mental status from the patient's baseline? Is there evidence of an acute change in mental status from the patient's baseline?2A. 2A. [Inattention][Inattention] Did the patient have difficulty focusing attention, for example, being easily Did the patient have difficulty focusing attention, for example, being easily
distractible, or having difficulty keeping track of what was being said?distractible, or having difficulty keeping track of what was being said?2B. 2B. (If present or abnormal)(If present or abnormal) Did this behavior fluctuate during the interview, that is, tend to come Did this behavior fluctuate during the interview, that is, tend to come
and go or increase and decrease in severity?and go or increase and decrease in severity?3. 3. [Disorganized thinking][Disorganized thinking] Was the patient's thinking disorganized or incoherent, such as rambling Was the patient's thinking disorganized or incoherent, such as rambling
or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?subject to subject?
4. 4. [Altered level of consciousness][Altered level of consciousness] Overall, how would you rate this patient's level of Overall, how would you rate this patient's level of consciousness? (Alert [normal]; Vigilant [hyperalert, overly sensitive to environmental stimuli, consciousness? (Alert [normal]; Vigilant [hyperalert, overly sensitive to environmental stimuli, startled very easily], Lethargic [drowsy, easily aroused]; Stupor [difficult to arouse]; Coma; startled very easily], Lethargic [drowsy, easily aroused]; Stupor [difficult to arouse]; Coma; [unarousable]; Uncertain)[unarousable]; Uncertain)
5. 5. [Disorientation][Disorientation] Was the patient disoriented at any time during the interview, such as thinking Was the patient disoriented at any time during the interview, such as thinking that he or she was somewhere other than the hospital, using the wrong bed, or misjudging the that he or she was somewhere other than the hospital, using the wrong bed, or misjudging the time of day?time of day?
6. 6. [Memory impairment][Memory impairment] Did the patient demonstrate any memory problems during the interview, Did the patient demonstrate any memory problems during the interview, such as inability to remember events in the hospital or difficulty remembering instructions?such as inability to remember events in the hospital or difficulty remembering instructions?
7. 7. [Perceptual disturbances][Perceptual disturbances] Did the patient have any evidence of perceptual disturbances, for Did the patient have any evidence of perceptual disturbances, for example, hallucinations, illusions or misinterpretations (such as thinking something was moving example, hallucinations, illusions or misinterpretations (such as thinking something was moving when it was not)?when it was not)?
8A. 8A. [Psychomotor agitation][Psychomotor agitation] At any time during the interview did the patient have an unusually At any time during the interview did the patient have an unusually increased level of motor activity such as restlessness, picking at bedclothes, tapping fingers or increased level of motor activity such as restlessness, picking at bedclothes, tapping fingers or making frequent sudden changes of position?making frequent sudden changes of position?
8B. 8B. [Psychomotor retardation].[Psychomotor retardation]. At any time during the interview did the patient have an unusually At any time during the interview did the patient have an unusually decreased level of motor activity such as sluggishness, staring into space, staying in one decreased level of motor activity such as sluggishness, staring into space, staying in one position for a long time or moving very slowly?position for a long time or moving very slowly?
9. 9. [Altered sleep-wake cycle].[Altered sleep-wake cycle]. Did the patient have evidence of disturbance of the sleep-wake Did the patient have evidence of disturbance of the sleep-wake cycle, such as excessive daytime sleepiness with insomnia at night?cycle, such as excessive daytime sleepiness with insomnia at night?
Dx Delirium with CAM Dx Delirium with CAM http://www.hartfordign.org/publications/trythis/issue13.pdfhttp://www.hartfordign.org/publications/trythis/issue13.pdf
1. Acute onset, fluctuating course1. Acute onset, fluctuating courseANDAND
2. Inattention2. InattentionAND EITHERAND EITHER
3. Disorganized thinking3. Disorganized thinkingOROR
4. Altered level of consciousness4. Altered level of consciousness
*sensitivity 94 - 100%; specificity 90 - 95%*sensitivity 94 - 100%; specificity 90 - 95%
Inouye et al, Ann Int Med 1990
Diagnostic Testing: EEGDiagnostic Testing: EEG
• Diffuse slowingDiffuse slowing• Most helpful to get a baselineMost helpful to get a baseline
• Patients with AzD may have abnormally slowed Patients with AzD may have abnormally slowed EEGEEG
• Worsens from baseline with deliriumWorsens from baseline with delirium
• Patients with minimal slowing may have test Patients with minimal slowing may have test read as “normal”read as “normal”
• Alpha (13 cps) may slow down (9 cps) and still be in Alpha (13 cps) may slow down (9 cps) and still be in normal rangenormal range
• Comparison with baselineComparison with baseline• Comparison with repeat EEG post deliriumComparison with repeat EEG post delirium
What Causes Delirium?What Causes Delirium?
The Importance of DDxThe Importance of DDx
Differential Diagnosis: UrgentDifferential Diagnosis: Urgent
• When in doubt, throw out the When in doubt, throw out the • WWernicke’sernicke’s• WWithdrawalithdrawal• HHypoxiaypoxia• HHypoglycemiaypoglycemia• HHyper- hypotensionyper- hypotension• IInfectionnfection• IIntracranial bleedntracranial bleed• MMeningitiseningitis• PPoisoningoisoning
• Failure to make these diagnoses may lead to permanent CNS Failure to make these diagnoses may lead to permanent CNS damagedamage
I WATCH DEATHI WATCH DEATH
• II InfectionInfection: : Most Most common are common are pneumonias & UTI in pneumonias & UTI in elderly, but sepsis, elderly, but sepsis, cellulitis, SBE and cellulitis, SBE and meningitis can also meningitis can also occuroccur
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal:Withdrawal: benzodiazapines, benzodiazapines,
ETOH, opiatesETOH, opiates
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal Withdrawal• AA Acute metabolicAcute metabolic: :
electrolytes, renal electrolytes, renal failure, acid-base failure, acid-base disorders, abnormal disorders, abnormal glycemic control, glycemic control, pancreatitispancreatitis
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal Withdrawal• AA Acute metabolic Acute metabolic• TT TraumaTrauma: : head injury head injury
(SDH, SAH), pain, (SDH, SAH), pain, vertebral or hip fracture, vertebral or hip fracture, concealed bleed, urinary concealed bleed, urinary retention, fecal retention, fecal impactionimpaction
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal Withdrawal• AA Acute metabolic Acute metabolic• TT Trauma Trauma• CC CNS pathologyCNS pathology: :
tumor, dementia, tumor, dementia, encephalitis, meningitis, encephalitis, meningitis, abscessabscess
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal Withdrawal• AA Acute metabolic Acute metabolic• TT Trauma Trauma• CC CNS pathology CNS pathology• HH Hypoxia Hypoxia from from
COPD exacerbation, COPD exacerbation, CHFCHF
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal Withdrawal• AA Acute metabolic Acute metabolic• TT Trauma Trauma• CC CNS pathology CNS pathology• HH Hypoxia Hypoxia
• DD DeficienciesDeficiencies: : B-B-12, folate, protein, 12, folate, protein,
calories, watercalories, water
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal Withdrawal• AA Acute metabolic Acute metabolic• TT Trauma Trauma• CC CNS pathology CNS pathology• HH Hypoxia Hypoxia
• DD Deficiencies Deficiencies• EE EndocrineEndocrine
thyroid, cortisol, cancer thyroid, cortisol, cancer
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal Withdrawal• AA Acute metabolic Acute metabolic• TT Trauma Trauma• CC CNS pathology CNS pathology• HH Hypoxia Hypoxia
• DD Deficiencies Deficiencies• EE Endocrine Endocrine• AA Acute Acute
vascular/MIvascular/MI : : stroke, stroke, myocardial infarctionmyocardial infarction
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal Withdrawal• AA Acute metabolic Acute metabolic• TT Trauma Trauma• CC CNS pathology CNS pathology• HH Hypoxia Hypoxia
• DD Deficiencies Deficiencies• EE Endocrine Endocrine• AA Acute vascular/MI Acute vascular/MI• TT Toxins-drugs Toxins-drugs
Really anything, but anti-Really anything, but anti-cholinergics, long acting cholinergics, long acting benzodiazepines, narcotics benzodiazepines, narcotics (meperidine) and other (meperidine) and other psychotropics are common psychotropics are common bad actors, OTC, OPMbad actors, OTC, OPM
I WATCH DEATHI WATCH DEATH
• II Infection Infection
• WW Withdrawal Withdrawal• AA Acute metabolic Acute metabolic• TT Trauma Trauma• CC CNS pathology CNS pathology• HH Hypoxia Hypoxia
• DD Deficiencies Deficiencies• EE Endocrine Endocrine• AA Acute vascular/MI Acute vascular/MI• TT Toxins-drugs: Toxins-drugs:• HH Heavy Heavy
metalsmetals (lead, (lead, mercury, platinum)mercury, platinum)
Dementia and DeliriumDementia and Delirium
• Dementia is a risk factor for deliriumDementia is a risk factor for delirium• Diagnosis of delirium in context of Diagnosis of delirium in context of
dementia is often misseddementia is often missed• Of 2000 consecutive admissions:Of 2000 consecutive admissions:
• 9.1% of patients had diagnosis of dementia9.1% of patients had diagnosis of dementia• 41.4% of these demented patients had delirious 41.4% of these demented patients had delirious
process on admissionprocess on admission
Erkinjuntii et al., Erkinjuntii et al., Arch Int Med, Arch Int Med, 19861986
Delirium versus Dementia?Delirium versus Dementia?
DELIRIUMDELIRIUM• Acute Acute • InattentionInattention• AbN LOCAbN LOC• Fluctuations/minutesFluctuations/minutes• ReversibleReversible• HallucinationsHallucinations
commoncommon
DEMENTIADEMENTIA• GradualGradual• Memory disturbanceMemory disturbance• N LOCN LOC• None/daysNone/days• IrreversibleIrreversible• Hallucinations Hallucinations
common only in common only in advanced diseaseadvanced disease
It is common for Delirium to be superimposed on Dementia!
So What? Who Cares?So What? Who Cares?Delirium is unimportantDelirium is unimportant!!
3 criteria:3 criteria:
CommonCommon, , MorbidityMorbidity & & CostlyCostly!!•On admit? 15-20%
•In hospital? 7-31%
•Ortho - 25-65%
•ICU: 90%
•Death ~20-35%
•Cognitive drop in 40%
•Premature institutionalization
•LOS doubles
• ++ hospital $
•Caregiver burden
What can trigger Delirium?What can trigger Delirium?
ANYTHING!!!ANYTHING!!!
Patient Predisposing FactorsPatient Predisposing Factors• AgeAge
• Dementia Dementia
• Male Male
• Dehydration Dehydration
• MalnutritionMalnutrition
• ↓ ↓ Physical fn/ immobilityPhysical fn/ immobility
• ↓ ↓ HearingHearing
• ↓ ↓ Vision Vision
• Severity of illness Severity of illness
• Comorbid psych dxComorbid psych dx
(Depression;(Depression;
EtOH abuse)EtOH abuse)
Elie et al, JGIM 1998; Burns et al, JNNP 2004
Environmental Predisposing Environmental Predisposing FactorsFactors
• # of room changes# of room changes
• Absent clock/watchAbsent clock/watch
• Absent reading glassesAbsent reading glasses
• Absence of familyAbsence of family
• Bladder catheterBladder catheter
• ICU or LTCICU or LTC
• RestraintsRestraints
McCusker et al, JAGS 2001
Delirium PrecipitantsDelirium PrecipitantsProspective study incidence of deliriumProspective study incidence of delirium
229 elderly medical inpatients 229 elderly medical inpatients • Fluid/ electrolyte dysfunction (40%)Fluid/ electrolyte dysfunction (40%)• Infection (40%)Infection (40%)• Drugs (30%)Drugs (30%)• Metabolic/Endo (26%)Metabolic/Endo (26%)• Sensory/ Environmental (24%)Sensory/ Environmental (24%)• perfusion/perfusion/ (14%) (14%)• NeurologicalNeurological• EtOH/Drug WithdrawalEtOH/Drug Withdrawal
**No clear precipitant in 15 – 25%**No clear precipitant in 15 – 25%
Francis et al, JAMA 1990
Delirium WorkupDelirium Workup
History: History: time course of mental status changestime course of mental status changes
association with other events (i.e.. meds, association with other events (i.e.. meds, illness)illness)
Pre-existing impairments of cognition or Pre-existing impairments of cognition or sensory modalitiessensory modalities
Physical ExamPhysical Exam
• VitalsVitals:: normal range of BP, HR, pO2, Temp normal range of BP, HR, pO2, Temp • Good physical exam:Good physical exam: particular emphasis on particular emphasis on
Cardiac, pulmonary and neurological systems Cardiac, pulmonary and neurological systems
• Hydration statusHydration status (dry axilla = dehyd!) (dry axilla = dehyd!)
• Also rule out Also rule out • fecal impaction fecal impaction • urinary retention (bladder U/S, in-and-out catheter)urinary retention (bladder U/S, in-and-out catheter)• Infected decubitis ulcerInfected decubitis ulcer
Treatment and ManagementTreatment and Management
• Identify and “correct Identify and “correct the correctibles”the correctibles”• Multiple causes in Multiple causes in
elderlyelderly• Careful monitoringCareful monitoring
• Place patient near Place patient near nursing station (1:1)nursing station (1:1)
• VS, I & O, OVS, I & O, O22
• Reduce psychiatric Reduce psychiatric symptomatologysymptomatology• AgitationAgitation• PsychosisPsychosis
• Discontinue non-Discontinue non-essential medicationessential medication• Drug toxicity and Drug toxicity and
drug induced drug induced delirium is most delirium is most common common
• See Medical Letter - See Medical Letter - Drugs that cause Drugs that cause psychiatric symptomspsychiatric symptoms
•(Larsen et al., (Larsen et al., J Gerontol, J Gerontol, 1985)1985)
Treatment and ManagementTreatment and Management
• ENVIRONMENTALENVIRONMENTAL• Restraints often indicated: posies, vests, Restraints often indicated: posies, vests,
mitts, helmets, geri-chairs, locked leathersmitts, helmets, geri-chairs, locked leathers• Provide cognitive structure, emotional Provide cognitive structure, emotional
support to patient and loved onessupport to patient and loved ones• Make sure behavioral monitoring is Make sure behavioral monitoring is
adequate and if empathy existsadequate and if empathy exists• Soft light, clock, familiar objects from homeSoft light, clock, familiar objects from home
Nonspecific Treatment of Delirium, Nonspecific Treatment of Delirium, Mild Agitation, Lability, and PsychosisMild Agitation, Lability, and Psychosis
A Case for PsychopharmacologyA Case for Psychopharmacology
Zorn SH et al. Interactive Monoaminergic Brain Disorders. 1999:377-393. Schmidt AW et al. Eur J Pharmacol.2001;425:197-201.
Quetiapine
M1
5-HT2AD2
5-HT2C
5-HT1A
1
H1
Risperidone
D2
1
5-HT2A
5-HT2C
H1
Olanzapine
M1
H1 5-HT2C
5-HT2A
D2
1
Ziprasidone
D2
5-HT1D
5-HT2C
5-HT1A
5-HT2A
1
H1
Clozapine
5-HT2C
M1
5-HT2A
H1 1
D2
Pharmacology Of Atypical AntipsychoticsPharmacology Of Atypical Antipsychotics
100100
00 200200 400400 600600 800800
Quetiapine (mg/d)Quetiapine (mg/d)
1010
2020
3030
4040
5050
6060
7070
8080
9090
Rece
pto
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up
an
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%)
Rece
pto
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up
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%)
D2 occupancyD2 occupancy
5-HT2 occupancy5-HT2 occupancy
00
Quetiapine 5HTQuetiapine 5HT22 & D2 & D2
OccupancyOccupancy
IM Ziprasidone vs IM Haloperidol: QTIM Ziprasidone vs IM Haloperidol: QTc c
Interval at CInterval at Cmaxmax
4.66
0
5
10
15
20
Adapted from Miceli et al. APA poster. 2002.*IM ziprasidone 30 mg is 50% above recommended dose. Preliminary data may not reflect final findings and results from the respective studies.
12.8
14.7
0
5
10
15
20
IM ziprasidone 20 mg
(n=25)
IM haloperidol7.5 mg(n=24)
IM ziprasidone30 mg*(n=25)
IM haloperidol10 mg(n=24)
Injection 2 (4 hours after 1st injection) Injection 1
Mea
n (
95%
CI)
QT
c i
nte
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ch
ang
e fr
om
bas
elin
e (m
s)
Mea
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95%
CI)
QT
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s)
Risks of Using v Not Using Risks of Using v Not Using Atypical AntipsychoticsAtypical Antipsychotics• Increased mortality in elderly patients Increased mortality in elderly patients
with dementia-related psychosis with dementia-related psychosis • 17 placebo controlled trials17 placebo controlled trials• Modal duration of 10 weeksModal duration of 10 weeks• Risk of death in treated patients 1.7 times Risk of death in treated patients 1.7 times
that seen in placebo treated patientsthat seen in placebo treated patients• Varied causeVaried cause
• CV (HF, sudden death)CV (HF, sudden death)• Infectious Infectious
Final VerdictFinal Verdict
• Atypical antipsychotics are not approved for Atypical antipsychotics are not approved for the treatment of patients with dementia-the treatment of patients with dementia-related psychosisrelated psychosis
• FDA stated “The agency is not advising FDA stated “The agency is not advising against all off-label use of atypicals, but is against all off-label use of atypicals, but is reminding the public that these drugs are not reminding the public that these drugs are not approved fro treating dementia and is approved fro treating dementia and is advising patients treated with these drugs to advising patients treated with these drugs to have their treatment plans reviewed”.have their treatment plans reviewed”.
If In Its Infinite Wisdom … If In Its Infinite Wisdom …
• The FDA were treating a patient, what The FDA were treating a patient, what would they do with would they do with • HallucinationsHallucinations• DelusionsDelusions• Pressured motor activityPressured motor activity• Overt aggressionOvert aggression• Disruptive behaviorsDisruptive behaviors• Behaviors endangering others Behaviors endangering others • AssaultsAssaults
What is Best Practice?What is Best Practice?
• AssessmentAssessment• Medical risks Medical risks • Psychiatric risksPsychiatric risks
• Treatment optionsTreatment options• Risk v benefits for eachRisk v benefits for each
• Coordinate care with PCP/geriatricianCoordinate care with PCP/geriatrician• Communicate with PCP and familyCommunicate with PCP and family• Establish monitoring systemEstablish monitoring system• Review literature in support of off-label useReview literature in support of off-label use
Dosing Atypical Antipsychotics in Dosing Atypical Antipsychotics in DementiaDementia• Start low and go slowStart low and go slow• Titrate quickly in Titrate quickly in
patients who are patients who are moderately stressed or moderately stressed or agitatedagitated
• Switch agents if patient Switch agents if patient unable to tolerateunable to tolerate
• Avoid using if patient Avoid using if patient recently had a heart recently had a heart attack or stroke unless attack or stroke unless behavior is life behavior is life threateningthreatening
• Reassess needReassess need• Every week x 4Every week x 4• Every month x 4Every month x 4• Every 4 months Every 4 months
thereafter (if stable)thereafter (if stable)• Reduce dose and Reduce dose and
monitor monitor • Use lowest effective Use lowest effective
dosedose• Eliminate medication if Eliminate medication if
patient is stable patient is stable • Use prn meds to avoid Use prn meds to avoid
decompensationdecompensation
AgentAgent IM Dose (mg)IM Dose (mg) CommentsComments
HaloperidolHaloperidol 0.5 – 20 mg0.5 – 20 mg Akathisia, Akathisia, dystoniadystonia
DroperidolDroperidol 1.0 – 40 mg1.0 – 40 mg Prolongation of Prolongation of QTQT
Lorazepam*Lorazepam* 0.5 – 4 mg0.5 – 4 mg Respiratory Respiratory depression, depression, cognitive changescognitive changes
OlanzepineOlanzepine 2.5 – 10 mg 2.5 – 10 mg Weight gain over Weight gain over time, anticholtime, antichol
ZiprasidoneZiprasidone 10 – 20 mg 10 – 20 mg Prolongation of Prolongation of QTQT
Nonspecific Treatment of Moderate to Nonspecific Treatment of Moderate to Severe Delirium, Agitation, Lability, Severe Delirium, Agitation, Lability, and Psychosisand Psychosis
A Case for PsychopharmacologyA Case for Psychopharmacology
IV-Haloperidol IV-Haloperidol drug of choice drug of choice
• Virtually no anticholinergic or Virtually no anticholinergic or hypotensive propertieshypotensive properties
• Generally does not suppress Generally does not suppress respirationsrespirations
• Minimal cardiotoxicityMinimal cardiotoxicity• Can be given parenterally without Can be given parenterally without
added toxicityadded toxicity
Treatment of Agitation: Treatment of Agitation: ProtocolProtocolIV-HALOPERIDOL PROTOCOLIV-HALOPERIDOL PROTOCOL• Mild: Mild: 1-2 mg haloperidol iv 1-2 mg haloperidol iv • Moderate: Moderate: 5 mg haloperidol iv5 mg haloperidol iv• Severe: Severe: 10 mg haloperidol iv10 mg haloperidol iv
Treatment of Agitation: ProtocolTreatment of Agitation: Protocol
MGH ProtocolMGH Protocol• Keep doubling the dose Keep doubling the dose
of iv haloperidol until of iv haloperidol until calmcalm
• May require “mega” May require “mega” doses (2 grams/day)doses (2 grams/day)
• When calm, administer When calm, administer 2/3 total in divided 2/3 total in divided dosesdoses
• Taper by 10-20% dayTaper by 10-20% day
MDAH ProtocolMDAH Protocol• Fix IV-H dose at 10mg & add Fix IV-H dose at 10mg & add
lorazepamlorazepam• Fix lorazepam dose at 10mgFix lorazepam dose at 10mg
THI VariantTHI Variant• Add opiateAdd opiate
• Buprenorphine (0.1-0.3 mg) Buprenorphine (0.1-0.3 mg) to haloperidol-lorazepamto haloperidol-lorazepam
• Hydropmorphone (0.5-2 mg) Hydropmorphone (0.5-2 mg) to haloperidol-lorazepamto haloperidol-lorazepam
Treatment of Severe Agitation: Treatment of Severe Agitation: ProtocolProtocol• If previous IV-H protocols failIf previous IV-H protocols fail
• Trial of continous intravenous infusion of IV-HTrial of continous intravenous infusion of IV-H• 10-50 mg/hour10-50 mg/hour• 1 - 2 gms/day1 - 2 gms/day
• Trial of droperidol but greater propensity for Trial of droperidol but greater propensity for hypotension limits its use in cardiovascular hypotension limits its use in cardiovascular patientspatients
• Add opiateAdd opiate• Propofol (FDA approved)Propofol (FDA approved)• ParalysisParalysis
Non-pharmacological Non-pharmacological InterventionsInterventions
A Case For Risk Factor ReductionA Case For Risk Factor Reduction
Interventions To Prevent Interventions To Prevent DeliriumDelirium
• 852 patients aged 70+852 patients aged 70+• Prospective matching of patients on Prospective matching of patients on
intervention unit with patients on 2 usual care intervention unit with patients on 2 usual care unitsunits
• Risk factor reduction strategy targetting:Risk factor reduction strategy targetting:• cognitive impairmentcognitive impairment• sleep deprivationsleep deprivation• immobilityimmobility• visual impairmentvisual impairment• dehydrationdehydration
Treatment and ManagementTreatment and Management
• Unambiguous communicationUnambiguous communication• Glasses, hearing aids etc...Glasses, hearing aids etc...• Avoid medical jargonAvoid medical jargon• Communicate succinctly & clearlyCommunicate succinctly & clearly• Make contact while communicating Make contact while communicating • Translators if necessaryTranslators if necessary
Cole et al, CMAJ 2002; Conn & Lieff, Can Fam Phys 2001; Inouye et al, JAGS 2000
Treatment and ManagementTreatment and Management• Provide cognitive structure, emotional support to Provide cognitive structure, emotional support to
patient and loved onespatient and loved ones• Same staffSame staff• Quiet; avoid excess noise/stimulationQuiet; avoid excess noise/stimulation• Simplify spaceSimplify space• Maximize uninterrupted sleepMaximize uninterrupted sleep• Restraints as last resort for patient safetyRestraints as last resort for patient safety• Make sure behavioral monitoring is adequate and if Make sure behavioral monitoring is adequate and if
empathy existsempathy exists
Cole et al, CMAJ 2002; Conn & Lieff, Can Fam Phys 2001; Inouye et al, JAGS 2000
Treatment and ManagementTreatment and Management
• Maintain functionMaintain function• Fluid balance and hydrationFluid balance and hydration• Adequate nutritionAdequate nutrition• Encourage self-careEncourage self-care• Walk with assistance or range of motionWalk with assistance or range of motion
• Minimum – 3 times/dayMinimum – 3 times/day
Cole et al, CMAJ 2002; Conn & Lieff, Can Fam Phys 2001; Inouye et al, JAGS 2000
ResultsResults
Study Control
Any episode 9.9% 15% p=0.02
# episodes 62 90 p=0.03
Delirium days 105 161 p=0.02
Inouye NEJM 1999
If it is not delirium, and it is not If it is not delirium, and it is not dementia, and there is no dementia, and there is no significant agitation …significant agitation …
SundowningSundowning
To Reduce SundowningTo Reduce Sundowning• Provide orientation cluesProvide orientation clues• Give adequate daytime stimulationGive adequate daytime stimulation• Evaluate for deliriumEvaluate for delirium• Maintain adequate levels of light in daytimeMaintain adequate levels of light in daytime• Establish bedtime routine and ritualEstablish bedtime routine and ritual• Provide consistent caregiversProvide consistent caregivers• Remove environmental factors that might keep patient Remove environmental factors that might keep patient
awakeawake• Discourage drinking stimulants or smoking near bedtimeDiscourage drinking stimulants or smoking near bedtime
To Reduce SundowningTo Reduce Sundowning• Give diuretics, laxatives early in dayGive diuretics, laxatives early in day
• Provide personal care at same time each dayProvide personal care at same time each day
• Ensure patient has glasses, working hearing aidEnsure patient has glasses, working hearing aid
• Place familiar objects at bedsidePlace familiar objects at bedside
• Monitor amount of sensory stimulationMonitor amount of sensory stimulation
• Consider late afternoon bright light exposureConsider late afternoon bright light exposure
• Avoid prn sedative hypnoticsAvoid prn sedative hypnotics
• Establish regular dose of drug for disturbing behavior (if needed)Establish regular dose of drug for disturbing behavior (if needed)
• Assist caregiver in obtaining respite helpAssist caregiver in obtaining respite help
If You Want to Run With the Texas Wild If You Want to Run With the Texas Wild Dogs …. You Can’t Pee Like a Puppy!Dogs …. You Can’t Pee Like a Puppy!