“Doctor, why does my skin turn yellow?”

Dr Wong Yuet Lin ElaineDr. Wong Yuet Lin, ElaineDepartment of Medicine and Geriatrics

United Christian Hospital

F/75 Madam LSCP bid G d i Premorbid

o community dwelling elderlyo stick walker

Good evening, doctors……

o independent activity of daily living

Social historySocial historyo widow, living with son in public housing estateo attending day care center six times per weeko illiterateo illiterateo worked as amah, retired in 1991

Past medical history and MedicationsP t M di l Hi tPast Medical History

o hypertensiono diabetes mellutis o hyperlipidaemia yp po old ischemic stroke with good recovery 2005

- CT brain : right brainstem infarct - EMS 20, MFAC 6, BBS 35

o OA kneeo OA kneeo thyroid abscess (2000) o bereavement (2000)

- psychiatric assessment : MMSE 17, poor attention during test f l d t ti f hist f d ti - no formal documentation of history of dementia

o bilateral hearing loss refuse hearing aids

Medication before admissiono aspirin 80mg dailyo adalat retard 40mg bdo zocor 5mg nocteo metformin 750mg tdso metformin 750mg tdso amaryl 4mg om

Admission to surgical ward (20 Jan 2010)……

History o sudden onset of yellowing of skin for few days, noted by day care center nurse

lf t d t l i d l t lo self noted tea color urine and pale stoolo no right upper quadrant pain o no fever/chills/rigoro no recent weight losso no recent weight losso denied history of herbs, over-the-counter medication or health supplemento no travel history

Physical examinationo deep jaundice o hepatomegaly 4cm below right costal margino hepatomegaly 4cm below right costal margino no stigmata of chronic liver diseaseo orientated, no sign of hepatic encephalopathyo vital signs stable

Blood test results after admission……Before admission On admission to

surgical ward ( 20 Jan 2010 )

After admission ( 21 Jan 2010 )

Bil 8 190 243ALT/AST 11/-- 840/1079 1032/--

ALP/GGT 59/-- 220/155 207/--

INR -- 1.4 1.3Albumin 43 31 25Hb 11.7 9.8 10.7Platelet 340 209 317WCC 8 3 7 6 6 2WCC 8.3 7.6 6.2Ur/Cr 4.4/76 11/150 3.9/93

Na 145 135 137K 4 3 4 2 4 1K 4.3 4.2 4.1

One day after admission (21 Jan 10)……

Bedside ultrasound abdomen by surgical colleagueso gallbladder wall thickened, not distendedo pr minent intra hepatic ducts c mm n bile duct 1cmo prominent intra-hepatic ducts, common bile duct 1cmo no stone

LFT staticLFT static

Afebrile, Vital sign stable

OGD arranged : chronic duodenal ulcer at D1, acute gastritis

Hypoglycemia noted : metformin/amaryl offHypoglycemia noted : metformin/amaryl off

Take over to medical team two days after Take over to medical team two days after admission (22 Jan 2010)……

Constrast CT abdomen : no mass, no biliary obstruction

Medical team was consulted for management of acute hepatitisMedical team was consulted for management of acute hepatitisPatient was assessed at 4pm

o deep jaundice, hepatomegaly 4cm below right costal margino Hstix 19.8 after OHA off, subcutaneous actrapid was given o Vital signs stable, afebrileo orientated, cheerful, relevant speech, communicable with hearing aids

Patient : doctor, why does my skin turn yellow ?D t it’ b th i bl ith liDoctor : it’s because there is some problem with your liver, we will transfer you to our unit for further management. Patient : I understand, thanks doctor.

Patient was transferred to medical ward at 5pmNotes written by medical nursing staff

o transfer in from surgical ward, reason for transfer explained to song , po vital sign stable, afebrile, Hstix recheck 12o orientated, went to toilet with son’s accompany

Something happened at that nightnight……

Midnight of 23 Jan 10

Nursing notes 2am :

o patient tried t climb fr m bedo patient tried to climb from bedo GCS 14/15, disorientated to time and place, confused speech, safety vest applied o on call medical officer informed, patient assessed, vital sign stable, blood test ordered

4am :4am o patient used her knife to cut the safety vest, agitatedo security guard called, patient was put on physical restrainer

What happen? What’s the diagnosis? Hepatic encephalopathy? Undocumented history of dementia with BPSD? Acute stroke? Acute stroke? Delirium?

Morning round at 23 Jan 10 (three days Morning round at 23 Jan 10 (three days after admission )……

Patient on physical restraindisorientated, confused speech, inattention, not agitated, occassionally could follow one step command, four limbs power around 4Refuse breakfast, Hstix 6Fever up to 38 degree, urine stix positiveFound acute retention of urine (400ml)Bowel opening daily

Psychiatric notes in 2000 reviewed

- illiterate, work as amah, retired in 1991- personality : introverted, few friends, dependent on husband, anxiety prone- low mood after husband’s death - MMSE 17 ( 3,3,3,1,2,2,1,2,0,0,0 ), poor concentration during test- diagnosis : bereavement- plan : counseling given, follow up prn

Son contacted via phone and premorbid cognitive state reviewed

- poor memory for one year- orientation good

hi f d l i h ll i i- no history of delusion or hallucination- no depressive or irritable mood, no reverse sleep cycle- no history of fall, hygiene good

Underlying dementia?

MCI?

Investigation result after confusion……..

ammonia level normal

Before admission Admission ( 20 Jan 2010 )

After admission ( 21 Jan 2010 )

After confusion (23 Jan 10 )

25 Jan 10

Urgent CT brain : small vessels disease, bilateral lacunar infarct

Bil 8 190 243 244 250

ALT/AST 11/-- 840/1079

1032/-- 844/713 553/--

ALP/GGT 59/ 220/15 207/ 194/ 181/

MSU : wcc scanty, no growth

ALP/GGT 59/-- 220/155

207/-- 194/-- 181/--

INR -- 1.4 1.3 1.4 1.3

Albumin 43 31 25 27 28

Blood culture : negative Hb 11.7 9.8 10.7 10.0 10.1

Platelet 340 209 317 313 373

WCC 8.3 7.6 6.2 8.2 12.1

Ur/Cr 4.4/76 11/150 3.9/93 5.2/124 5.8/116

Na 145 135 137 135 138

K 4.3 4.2 4.1 4.2 4.2

MMSE MMSE 2000 After 2000 (poor attention) confusion

orientation 3 3 0 0orientation 3,3 0,0registration 3 2C l l i d 1 0Calculation and attention

1 0

Recall 2 2Recall 2 2Language 2,1 2,1Visual construction

2,0,0,0 1,0,1,0

T t l k 17 9Total marks 17 9

Diagnosis and PlanProvisional DiagnosisProvisional Diagnosis

o Deliriumo Acute hepatitiso ?Urinary tract infection ?fever due to acute hepatitiso ? r nary tract nf ct on ?f r u to acut h pat t so ?Underlying dementia ?MCIo

Plano put on zinacefo sit out, avoid physical restraino physiotherapy referred for early mobilizationo encourage oral intake, dietician referred

Why does this lady develop delirium?y y p Can this be prevented ? Should we start haloperidol? What will be her prognosis?

Wh t is th s f h t h titis? What is the cause of her acute hepatitis?

Progress in subsequent days……24 Jan 10 morning round (one days after acute confusion)24 Jan 10 morning round (one days after acute confusion)……

o fragmented sleep last nighto sit out while assessment, still disorientation, poor attention, confused speech o fever persist, vital sign stableo finish 1/3 breakfast o finish 1/3 breakfast o Physiotherapist/Occupational therapist : power 4/5 over four limbs, transfer barely independent,

walk with stick with mild assistance, EMS 7, MFAC 4, BI 64

25 Jan 10 morning round (two days after acute confusion)25 Jan 10 morning round (two days after acute confusion)……o sleep well last night o still disorientated but decreased confused speech, attention improvedo keep on PT/OT training

26 Jan 10 morning round (three days after acute confusion)……o orientated, cooperative, no more confused speecho finished whole bowel of congee 350ml during breakfasto stick walker under supervision, increased stability

Patient was transferred to convalescence hospital for further rehabilitation and monitoring of liver function at 28 Jan 10rehabilitation and monitoring of liver function at 28 Jan 10…….

B f i in p ti nt’s p ssBefore reviewing patient s progress

Let’s have a discussion of today’s topic………

Delirium - ReviewDelirium - Review

Wh d ti t d l Why do patients develop delirium?delirium?

C t f d li i• Concept of delirium• DSM-IV criteria• Pathophysiology of delirium

Ri k f d l f d l f d li i • Risk factor model for development of delirium

Concept of deliriumPhenomenon of delirium first recognized as early as first century CE by Celsus

Clear description of this term : Hippocrate’s writing 2500 ago

DSM-IV-TR criteria : most commonly used gold standard nowadayDSM IV TR criteria : most commonly used gold standard nowaday

Acute mental disorder : acute onset, daily fluctuating course, inattention and other cognitive impairment

Accompany by presence of acute medical illness

Diagnosis of delirium according to g gDSM-IV-TR criteria

All four criteria (A-D) are required to confirm a diagnosis of d li idelirium

General diagnostic criteria (A-C)g(A) Disturbance of consciousness (that is, reduced clarity of awareness of the environment) with

reduced ability to focus, sustain, or shift attention(B) A change in cognition (such as memory deficit, disorientation, language disturbance) or the

development of a perceptual disturbance that is not better accounted for by a pre-existing, t bli h d l i d tiestablished, or evolving dementia

(C) The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day

*Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR®) American Psychiatric Publishing, Inc., Arlington, VA)

DSM-IV classification of causes of delirium

Criteria D

o For delirium due to a general medical condition(D) Evidence from the history, physical examination, or laboratory findings indicates that the disturbance is caused by the direct physiological consequences of a general medical conditionF b i i i d li io For substance intoxication delirium(D) Evidence from the history, physical examination, or laboratory findings indicates that of either (1) the symptoms in Criteria A and B developed during substance intoxication, or (2) medication use is etiologically related to the disturbance

o For substance withdrawal deliriumo For substance withdrawal delirium(D) History, physical examination, or laboratory findings indicate that the symptoms in Criteria A and B developed during, or shortly after, a withdrawal syndrome

o For delirium due to multiple etiologies commonly seen in elderly (D) History physical examination or laboratory findings indicate that the delirium has more than one (D) History, physical examination, or laboratory findings indicate that the delirium has more than one etiology (for example, more than one etiological general medical condition, a general medical condition plus substance intoxication or medication side effect)

PathophysiologyN t f ll nd t d lik l t b mpl xNot fully understood, likely to be complex

Neurotransmitter imbalance o cholinergic deficiency g yo elevated brain dopaminergic fucntion o relative imbalance between the dopaminergic and cholinergic system o glutamate, beta-aminobutyric acid, serotonin, norepinephrine

Different mechanisms may occur in different acute illnesses

Metabolic or ischemic insult (hypoxemia,hypoglycemia) : impaired th i d l f t itt synthesis and release of neurotransmitters

Trauma/infection/surgery : release of proinflammatory cytokines -> activate microglia in brain -> affect neurotransmitter synthesis/release

High level of cortisol : elderly has impairment in feedback regulation of cortisol, predispose to delirium

Risk factor modelMultifactorial : complex interaction between predisposing and precipitating factors precipitating factors

Relation between vulnerability and degree of y ginsult

o patient with high vulnerability develop delirium even with mild degree of insultP ti t ith l l bilit i t t o Patient with low vulnerability resistant to delirium even with noxious insult

Elderly patient : high y p gvulnerability

Risk factors associated with delirium• Old age

• Possible underlying cognitive impairment • Hypoglycemia/Hyperglycemia

“Key” for successful management

Predisposing Precipitating

Age > 65 Infection

Male sex Electrolyte disturbance

• Hypoglycemia/Hyperglycemia• Anemia • Low albumin• Acute liver failure • Infection ( ?urinary tract infection )o addressing and manage all the risk

factors

“Individualized”

Dementia or other cognitiveimpairment

Metabolic disturbance : acid-base,- glucose disturbance, adrenal orthyroid functionHearing or Visual impairment Organ failure- acute renal or liver failure

i di f il

• Infection ( ?urinary tract infection )• Immobilization device : foley insertion, physical restrains• Environmental factors : change of ward/staff

Individualizedo different patients /clinical

setting -> different risk factorso search carefully with clinical

- respiratory or cardiac failureFunctional dependence Acute stroke

History of falls or fracture hip Anemia

Alcohol abuse Malnutrition or low albumin

P h ti d D ithd l i t i ti

Definitely our patient is at high risk………

o search carefully with clinical sensibility in each case

Psychoactive drugs Drug withdrawal or intoxication

Polypharmacy High number of hospital procedure

Multiple physical illness Immobilization device

What are the possible risk factors for our patient?

Chronic renal or liver failure

History of stroke or neurologicaldisease

Psyc

T i l ill P l l d i i

Environmental factors

Psychological factors

Terminal illness Prolong sleep deprivation

Development of delirium

- vulnerability ( predisposing factors)degree of insults (major causes and

Risk factor model - degree of insults (major causes and

precipitating factors of delirium )model

Pathophysiology ( diff r nt m ch nisms Pathophysiology ( different mechanisms in different acute illnesses )

Diagnosis accordingTo DSM-IV criteria

Why delirium is important?

C•Commonness•Under-recognition •Adverse outcomesP i d li i•Persistent delirium

•Delirium progress to dementia?

Commonness“Prevalent” delirium : on admission (14-24%)* no consensus on definition of time interval : definition of within 36/48/72 hours

“Incidence” delirium : develop during hospital stay (6-56%)* high incidence delirium due to poor screening of prevalence delirium on admission

Common in different clinical settingso Community 1-2%o Hospital elderly 14-56%o General medical 15-50%o Postoperative patient 15-53%o Hip fracture 43-61%o ICU 70-87%o ICU 70 87%o Palliative care 83%o Nursing Home or Post acute care setting 50%o Emergency department 30%

U d i iUnder-recognitionUnder detection rate 32-67%

Reasons for under recognitionReasons for under-recognitiono non-specific presentation, daily fluctuating -> lucid period pitfall for diagnosiso a low-status medical presentation, not require extra resourceso not a medical problem, consider it as psychiatry problemo not a medical problem, consider it as psychiatry problemo multiple etiology different from the classic “myth” of “one man one disease ” o hypoactive deliriumo Common in patients with previous cognitive impairment -> masking effect

Screening tools to improve detection rate? Still not commonly used in most health care setting…..

Adverse outcomes

Independent risk factors for poor outcomes* Occurrence and outcome of delirium in medical in-patients : a systematic literature review.

Age and ageing 2006, 35:350-364. Siddiqi N, House AO, Holmes JD.- Results of outcomes in 19 study cohorts- delirium associated with increase mortality at 12 months, increase length of hospital stay and institutionalizations

o Hospital complications (aspiration, pressure sore, incontinence, acute retention of urine, decrease oral intake pulmonary embolism)

o Functional and cognitive decline, loss of independenceo Prolong length of hospital stayo Psychological impact to familieso Increase post discharge health care support o Institutionalizationo One year mortality rate 35 40%o One year mortality rate 35-40%

Persistent deliriumTraditional belief : reversible and transient

Recent studies : delirium persist much longer than believed Recent studies : delirium persist much longer than believed * Persistent delirium in older hospital patients : a systematic review of frequency and prognosis. Age and Ageing 2009, 38:19-26. Cole MG, Ciampi A, Belzile E, et al.

o 18 studies reviewed o combined proportions with persistent delirium at discharge, 1,3 and 6 months were o combined proportions with persistent delirium at discharge, 1,3 and 6 months were

44.7%, 32.8%, 25.6% and 21%o outcomes ( mortality, nursing home placement, function, cognition ) are poorer in

patients with persistent delirium

Risk factors associated with persistent delirium identified* Risk factors for delirium at discharge : Development and Validation of a predicitive model.Arch Intern Med, 2007, Vol 167(No.13):1406-1413. Ionuye SK, Zhang Y, Jones RN, et al.

o Five independent risk factors identified : po dementia (OR 2.3)o vision impairment (OR2.1)o functional impairment (OR1.7)o high comorbidity (OR1 7)o high comorbidity (OR1.7)o use of physical restrain(OR3.2)

Delirium progress to dementia?Relationship remains unclear : a spectrum of cognitive disorder? ( both associated with cholinergic deficiency, inflammatiion )

Dementia : strongest risk factor associated with delirium

Permanent cognitive and functional decline after an episode of delirium reported in some cases delirium reported in some cases

Delirium commoner in patients with incipient dementia?* Delirium episode as a sign of undetected dementia among community dwelling elderly subjects : a 2 year follow up p g g y g y j y pstudy. J. Neurol. Neurosurg. Psychiatry, 2000, 69, 519-521. Rahkonen T, Paanila S, Sivenius J.

Poor outcome for patients with delirium superimposed on dementia : accelerate rate of progression of dementia and poorer outcome than dementia : accelerate rate of progression of dementia and poorer outcome than those without delirium* Consequences of not recognizing delirium superimposed on dementia in hospitalized elderly individuals. J. Gerontol. Nurs, 2000, 26, 30-40. Fick D, Foreman M

Wh t i th li i l f t What is the clinical feature of deliriumof delirium

C f t• Core features• Subtypes• Subsyndromal delirium

S i• Severity

Core featuresAcute onset with daily fluctuating courseAcute onset with daily fluctuating course

o Disturbance in attentiono Disorganized thinkingo Altered level of consciousness e g viligant lethargy o Altered level of consciousness e.g. viligant, lethargy o Disorientationo Memory impairment o Perceptual disturbance o Psychomotor agitation and retardationo Sleep-wake cycle disturbance

A h Approach : establish Baseline cognitive function, any recent change

Severity of delirium : relationships with outcome?o many tools for assess severity : M i l D li i A S l (MDAS) D li i I d (DI) D li i o many tools for assess severity : Memorial Delirium Assessment Scale (MDAS), Delirium Index(DI), Delirium

Assessment Scale (DAS), Delirium Rating Scales-revised version (DRS-R-98)

o largely used in clinic research, may have role in clinical practice

Subtypesfirst described by Lipowski (1990) : refer to psychomotor activity or level of arousal

Three subtypeso Hyperactive : hallucination, delusion, agitation, restlessness, hypervigilanceo Hypoactive : lethargy sedation respond slowly to questioning o Hypoactive : lethargy, sedation, respond slowly to questioning o Mixed : fluctuate between hyperactive and hypoactive form

Hypoactive delirium : significant higher rate at people age over 65yp

Lack of consensus on classification of subtype of delirium : barrier to research

Different pathophysiology, causes, prognosis and responses to treatment?

Subsyndromal deliriumNo consensus of definition

o not meet DSM-IV criteria but exhibit few core features of delirium hibit d l t tl i t i it bilit di t tibilit o some exhibit prodromal symptoms : restlessness, anxiety, irritability, distractibility,

sleep disturbance

may progress to full-blown delirium over 1-3 daysy p g y

Some report similar worse outcomes to those with mild delirium *The prognostic significance of subsyndromal delirium in elderly medical inpatients. J Am Geriatr Soc, 2003 June, 51(6) :754-60. Cole M, McCUsker J, Dendukuri N, Han L

Need close monitoring in this group of patient?

Confusion Assessment Method (CAM)Most commonly used Most commonly used perform with formal cognitive testingReliable when used by trained interviewer : sensitivity 94-100%, specificity 90-95%, high inter-rater reliabilityCAM Algorithm ( presence of 1+2 and either 4 )

1 Acute onset + fluctuating course 1. Acute onset + fluctuating course 2. Inattention3. Disorganized thinking 4. Altered level of consciousness * Clarifying confusion : the confusion assessment method : A new method for detection of delirium Annals of Internal Medicine. 1990 Dec 15;113(12):941-8. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI

Routine screening needed? Mode of screening? Which screening test? Who should be screened?

Table 2 Tools for the assessment of deliriumTable 2 Tools for the assessment of delirium

Fong TG et al. (2009) Delirium in elderly adults: diagnosis, prevention and treatmentNat Rev Neurol doi:10.1038/nrneurol.2009.24

Is there any effective ytreatment for delirium?

N h l i l • Non-pharmacological • Pharmacological treatment• Prevention

G l i i lGeneral principalsMulti-disciplinary approach

Identification and treatment of the etiological causesIdentification and treatment of the etiological causes

Addressing all the precipitating and modifiable risk factors

Treating the behavior symptoms

Preventing complications

Maintaining function and independence

Counseling to their care giver and relativeCounseling to their care-giver and relative

Non-pharmacological treatment

“ First-line” treatment, Nursing care based………

n imp i m nt ( l h d )sensory impairment (spectacles, hearing aids)

nutrition, hydration and electrolytes disturbanceavoid faecal impaction, watch out for acute retention of urine

i t ti orientation programme (reorientation, clear instructions, frequent eye contact, clock, calendars)

avoid Physical retrain (decrease mobility, increased agitation/injury, prolongation of delirium)

early mobilization d h quiet patient-care setting, avoid noise at night time

low-level lighting at night, bright light at daytime avoid sleep deprivationlimiting room and staff changes environment modification to minimize risk of injury

Evidence to support a multi-disciplinary approach?

Three systematic reviews performed and only two randomized control trial identified* S t ti d t ti d ltidi i li f d li i i ld di l i ti t d i d t i l C l * Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial. Cole MG, McCusker J, Bellavance F, Primeau FJ, Bailey RF, Bonnycastle MJ, and Laplante J. Canadian Medical Association Journal, 2002. 167(7): p. 753-759.ole et al (2002) [100]* Systematic intervention for elderly inpatients with delirium: a randomized trial. Cole MG, Primeau FJ, Bailey RF, Bonnycastle MJ, Masciarelli F, Engelsmann F, Pepin MJ, and Ducic D,. Canadian Medical Association Journal, 1994. 151(7): p 965-70 (1994) [53]p. 965 70 (1994) [53]

o received consultations by a geriatrician/geriatric psychiatrist and treatment recommendations

o daily visits by a liaison nurse to ensure adherence to interventiono daily visits by a liaison nurse to ensure adherence to interventiono unable to demonstrate a significant difference between the two groupo a cross contamination effect, general standard of care (control group) was high, study

was underpowered

Ph l i l Pharmacological treatmentIndications

o severe behavioral or emotional disturbance e.g. interfering with sleep-wake cycle, anxiety, fear and hallucinations anxiety, fear and hallucinations

o threatens own or others safety o interfere with essential medical or nursing careo ensure medical causes for agitation treated e.g. pain, constipation, urinary retension,

hypoxia hypoxia o other non-pharmacological measures failed to ease the symptoms

Aim : alert and manageable patients

When start treatmento commence at lowest dose, shortest duration, titrate against level of agitationo clear documentation : dose, frequency, route, side effects, q y, ,o close monitoring of vital signs, mental state by nursing staffo review regularly by physicians : drug use to treat delirium can increase confusion or

lead to over-sedation

Treatment Choice based on expert guidelineso few high-quality, randomized, controlled trials

A i P hi t i A i ti (APA) id li l t d t d 2004o American Psychiatric Association (APA) guidelines, last updated 2004o mainly for use in hyperactive delirium, role in hypoactive delirium : controversial

H l id l id l dHaloperidol : most widely usedo 0.25mg oral (tablet/drop), 0.5-1mg Intramuscular route : peak effect ~ 20-40mins o efficacy shown in randomized, controlled trials : reduce symptoms severity/duration

Ad R ti l ff l h h l o Adverse Reactions : extrapyramidal side effects, acute dystonias, lengthen the QT interval, anti-cholinergic effecs (AROU, dry mouth, constipation, increased confusion), sedation

o Avoid in patients with withdrawal syndrome, hepatic insufficiency, neuroleptic malignant syndrome

Atypical antipsychoticso risperidone 0.25mg daily -> 0.5mg bd, olanzapine 2.5mg daily -> 5mg daily, quetiapine 12.5mg daily

o comparable efficacy to haloperidol demonstrated in small randomized control trialo comparable efficacy to haloperidol demonstrated in small randomized control trialo more favorable motor side-effect profile than haloperidol : Prkinson’s disease, Lewy body

dementia, prefer in elderlyo risk of prolong QT interval, increased risk of stroke in older patients with dementia

Benzodiazepineo not recommended as first-line agents treatment due to effect limited by adverse

effect :paradoxical excitation, over-sedation, exacerbation of confusion, respiratory depression

o use in particular situations : alcohol or sedative-hypnotic drug withdrawal delirium related to seizures diffuse o use in particular situations : alcohol or sedative-hypnotic drug withdrawal, delirium related to seizures, diffuse Lewy body disease, parkinson’s disease, neuroleptic malignant syndrome

o second-line treatment following failure of antipsychotics o lorazepam : preferred agent in geriatric patients, shorter half-life, lack of active

metabolites, availability in parenteral form , y p

Cholinesterase inhibitors o donepezil 5mg daily o efficacy reported by case report o efficacy reported by case report

Is there any prevention for d li ium?delirium?

P i iblPrevention possible?30-40% preventable

Incidence delirium : i di t f f il f h it l ?Incidence delirium : an indicator of failure of hospital care?

Intervention program : HELP

Proactive Geriatric consultation : post fracture hip, decrease delirium 40%

Education program to staff Education program to staff

Pharmacological Prophylaxis

Preventive measuresPreventive measuresRisk factors associated with development of incidence delirium Risk factors associated with development of incidence delirium, five independent risk factors identified* Precipitating factors for delirium in hospitalized elderly persrons : prevdictive model and interrelationship with baselinevulnerability. JAMA 1996, 275(11):852-7. Inouye SK, Charpentier PA

o use of physical restraints ( RR4.4 )o use of physical restraints ( RR4.4 )o malnutrition ( RR4.0 )o more than three medications added ( RR2.9 )o use of bladder catheter ( RR2.4 )o any iatrogenic event ( RR1 9 )o any iatrogenic event ( RR1.9 ) factors targeted on to prevent incident delirium during hospitalization?

Hospital Elder Life Program (HELP) : innovative strategy of p E L f g m ( EL ) gy fhospital care for elderly patients* A Multicomponent intervention to prevent delirium in hospitalized older patients. NEJM, 1999 Mar 4;340(9):669-

76. Inouye SK, Bogardus ST Jr, Charpentier JA, Leo-Summers L, Acampora D, Holford TR, et al.o delirium incidence ( intervention group 9.9% vs usual care group 14%, matched OR 0.6, m ( g p 9.9 g p , m . ,

CI 0.39-0.92)o reduce days of deliriumo measures include : maintain orientation to surroundings, meeting needs for nutrition,

fluid, sleep hygiene, promote mobility, visual and hearing adaptationsf , p yg , p y, g p

Ph l i l h l iPharmacological prophylaxisHaldoperidol as prophylaxis?

o Need more study to confirm its roleU i i l d d li io Use in surgical case may reduce delirium* Prophylactic consecutive administration of haloperidol can reduce the occurrence of postoperative delirium in gastrointestinal surgery. Yonago Acta. Med 42, 1790184 (1999) Kaneko T et al. .

Cholinesterase inhibitors (Donepezil 5mg daily) as prophylaxis?o Prevention studies not demonstrate efficacy

* Donepezil in the prevention and treatment of post-surgical delirium. American Journal of Geriatric Psychiatry, 2005. 13(12): p 1100 1106 Liptzin B Laki A Garb JL Fingeroth R and Krushell R 13(12): p. 1100-1106. Liptzin B, Laki A, Garb JL, Fingeroth R, and Krushell R, * A randomized, double-blinded, placebo-controlled trial of donepezil hydrochloride for reducing the incidence of postoperative delirium after elective total hip replaccement. Int. J. Geriatr. Psychiatry. 22, 343-349 (2007). Sampson EL et al.

How about our patientHow about our patient……

Good rehab progress in convalesence hospital o walk with stick with supervision, exercise tolerance > 50 meters

ADL i i l lo ADL supervision levelo MMSE increase to 14o Discharge home

Follow in our GI clinico HBsAg –ve, anti-HBs –veo Anti HCV veo Anti-HCV –veo Anti-HAV –ve ( IgM )o IgM normal, anti-mitochondrial antibodies(AMA) –ve, Antinuclear antibodies(ANA) -ve,

Anti-smooth muscle antibodies(SMA) +ve

Before admission (27 Oct 09)

On admission to surgical ward ( 20 Jan 2010 )

After confusion (23 Jan 10 )

25 Jan 10 27 Jan 10 Convalesence hospital( 1 Feb 2010 )

Before discharge( 10 Feb 10 )

Follow up in GI clinic ( 25 Mar 10 )

Bil 8 190 244 250 196 131 59 14

ALT/AST 11/-- 840/1079 844/713 553/-- 197/-- 118/-- 60/-- 13/22

ALP/GGT 59 220/155 194/-- 181/-- 219/-- 239/-- 216/-- 78/--

INR 3 0 0INR -- 1.4 1.4 1.3 1.0 -- 1.04 --

Albumin 43 31 27 28 28 30 32 41

Hb 11.7 9.8 10.0 10.1 10.4 9.4 8.9 11.3

Platelet 340 209 313 373 420 380 254 316

WCC 8.3 7.6 8.2 12.1 10.5 5.8 5.3 6.3

Ur/Cr 4.4/76 11/150 5.2/124 5.8/116 -- 5.0/75 4.8/80 4.6/89

Na 145 135 135 138 -- 141 139 146

K 4.3 4.2 4.2 4.2 -- 3.7 3.9 4.3

S h t’ th f t So what’s the cause of acute hepatitis in our patient?hepatitis in our patient?

Why did our patient’s skin turn yellow……..

Anti-HEV IgM +ve…………

Acute hepatitis E !!Acute hepatitis E !!

H i i EHepatitis EFirst discovered in 1982, labeled as Hepatitis E in 1989

Four genotypes: 1 2 3 4 and a single serotypeFour genotypes: 1,2,3,4 and a single serotype

Small non-enveloped particle consists of a single-strand RNA

highly endemic in Central and South East Asia, North and West Africa as well as Mexico

Highest rate of symptomatic disease in young to middle-age adults

S l k i i t d i Seasonal peak in winter and spring

I f i iInfectivityFecal-oral route : acquired by ingestion of contaminated food or water

incubation period ranges from two weeks to two months before symptoms appeary p pp

Infectivity peaked at 2 weeks before the onset of symptoms

Virus excretion in stools o up to 14 days after onset of jaundiceo approximately 4 weeks after oral ingestion of contaminated food or watero approximately 4 weeks after oral ingestion of contaminated food or water

Cli i l fClinical featuresResemble other types of acute viral hepatitis

Initially presented with non-specific symptomsInitially presented with non specific symptomso anorexiao malaiseo fevero vomiting

Followed by o jaundicejo tea colour urineo hepatomegaly

Less common symptomsLess common symptomso arthralgiao diarrhoeao pruritus o urticarial rash

Di i d iDiagnosis and prognosisDiagnosis by serology test

o presence of anti-HEV IgM antibodies d t ti f HEV RNA b l h i ti (PCR)o detection of serum HEV RNA by polymerase chain reaction (PCR)

Prognosis o Recovered in 3-6 weekso Chronic infection not occuro Mortality rate report in young adult 0.5-3%, Mortality in third trimester can reach

20%20%

Change in epidemiology in recent years

Previously only recognized as a endemic disease in developing countries

In recent years, local acquired hepatitis E infection in developed country increasingly reported

o more common than previous recognizedo more common than prev ous recogn zedo may be more common than hepatitis A

Several new observationso mostly due to genotype 3 or 4o mostly due to genotype 3 or 4o many case affected elderly men with other coexisting illness o poor prognosis in patient with pre-existing chronic liver disease o frequently misdiagnosed as drug-induced liver injury o chronic infection with genotype 3 has been reported among immunosuppressed persons

* Hepatitis E : an emerging infection in developed countries. Lancet Infect Dis. 2008 Nov;8(11):698-709. Dalton HR, Bendall R, Ijaz S, Banks M

* Epidemiology of Hepatitis E : current status. J Gastroenterol Hepatol 2009 Sept;24(9):1484-93. Aggarwal R, Naik S.

L l d f CHPLocal data from CHPNotifiable disease in Hong Kong

Rising trend of hepatitis E in last 10 years ( on the contrary, hepatitis A showed d d )decreasing trend )

o 1997 : 4 caseo 2008 : 90 caseso 2009 : 74 caseso 2009 : 74 caseso till 2010 Feb : 22 caseso Hepatitis A : 595 cases (1997)

decrease to 64 cases (2009)

Seasonal peak at winter and spring seasons ( Jan to April )pr )

Characteristics of viral Hepatitis E ppatients from 1998 to 2007

More male than female

Higher age

Hepatitis A Hepatitis E

Total 2596 276Higher age

Majority patient required hospitalization : median duration f t 7 d

Total number of case

2596 276

Male : Female ratio 1.8 : 1 2.5 : 1

of stay 7 days

Higher mortalityo 3 female and 6 males, age 53-82

Female ratio

Median age in years ( range )

26 (2-94) 48.5 (2-85)

o Median duration of onset to death was 24 days ( 13 to 77 days )

Most case sporadic, no

( g )

Proportion of patients requiring

62% 77%p ,

outbreak

Fourteen imported case

hospital treatment

Number of 4 (0 15%) 9 (3 26%)deaths ( case fatality rate )

4 (0.15%) 9 (3.26%)

P iPreventionGood personal, food, environment hygiene

Virus heat-sensitive o food cooked thoroughly before consumptiono oyster cooked with shells removedo oyster cooked with shells removedo use separate chopstick for raw and cooked food during hotpot

Vaccination not available currently ( a subunit vaccine Vaccination not available currently ( a subunit vaccine shown to be effective in preventing clinical disease, not yet commercially available )