Family Medicine Final Ppt

Depression

Patient HistoryThe patient is a 29 year old female who presents with a 3 month history of “feeling

tired.” She reports feeling “run down” all the time but also notes that she doesn’t sleep well. She is able to fall asleep when she goes to bed at approximately 10 pm, but wakes up routinely at 3 am and is unable to get back to sleep. She also admits to trouble concentrating at work and says this has started to affect her job performance. Her supervisor has told her that she has been making more mistakes lately and recently had a negative performance review. She is recently married and feels guilty that she hasn’t been able to fulfill her household responsibilities. She used to attend church every Sunday but hasn’t gone in months.

PMH/PSH – noneFamily/Social History - married; drinks sociallyAllergies – NKDAMedications – none

Genogram

Sphere of influence

ME

Case Background• Family Background

– Born & raised in California – Very religious family– Graduate of USC, works as a CPA– Recently married

Current Characteristics Lives in a rental apartment in Los Angeles Trying to save money to buy a house Likes to play tennis and competes in a weekly tournament Works long hours, little time to relax Likes to make healthy meals though usually doesn’t have much time to cook Doesn’t smoke and drinks alcohol socially

Future Wants to start having children

Patient physical exam, labs etc.

• Her vital signs are stable• Physical exam unremarkable• Labs reveal normal metabolic panel, CBC and

Thyroid function tests

Objectives

1. Recognize the common presenting symptoms of depression

2. Understand the multifactorial pathogenesis of depression

3. Learn about the treatment of depression and the sequelae of this condition

4. Recognize the importance of screening for suicidal risk

Depressive Disorders

• Depressive disorders are characterized by persistent low mood, loss of interest and enjoyment, and reduced energy. They often impair day-to-day functioning.

• DSM-IV divides depression into major depressive disorder or dysthymic disorder.

DSM-IV-TR Criteria for Major Depressive Episode

>5 of the 9 symptoms for at least 2 weeks (everyday, all day)

Mood: Depressed mood

Sleep: Insomnia or hypersomnia

Interest: Markedly diminished interest or pleasure in nearly all activities

Guilt: Excessive feelings of guilt or worthlessness

Energy: Loss of energy or fatigue

Concentration: Diminished ability to think or concentrate; indecisiveness

Appetite: Increase or decrease in appetite

Psychomotor: Psychomotor agitation/retardation

Suicide: Recurrent thoughts of death/suicidal ideation

Dysthymia

• Depressed mood for most of the day, for more days than not, for at least two years.–No episodes of major depression

during the last 2 years–Symptoms have not gone away for

more than 2 months at a time–Depressed plus 2 symptoms

Epidemiology

• Prevalence: male 5-12%, female 10-25% (M:F = 1:2)

• Mean age of onset: ~30 years• Lifetime prevalence of 15-25%• Greater incidence in women and elderly• Consider in scenarios where pt presents with

multiple unrelated physical symptoms• Most common mental disorder in primary care

EtiologyBiological – genetic: 65-75% MZ twins; 14-19% DZ twins – neurotransmitter dysfunction at level of synapse (decreased

activity of serotonin, norepinephrine, dopamine) – secondary to general medical condition

Psychosocial – psychodynamic (e.g. low self-esteem) – cognitive (e.g. negative thinking) – environmental factors (e.g. job loss, diet, bereavement,

history of abuse) – co-morbid psychiatric diagnoses (e.g. anxiety, substance

abuse, mental retardation, dementia, eating disorder)

Pathophysiology

• Multifactorial with complex interaction of genetic, psychosocial and neurobiologic factors

• Dysregulation of 5HT and NE in the brain are strongly associated with depression

• Dysregulation of 5HT and NE in the spinal cord may explain an increased pain perception among depressed patients

• Imbalances of 5HT and NE may explain the presence of both emotional and physical symptoms of depression.

There are at least two sides to the neurotransmitter story

Sex

Appetite

Aggression

Concentration

Interest

Motivation

Depressed Mood

Anxiety

Irritability

Thought process

References:1. Adapted from: Stahl SM. In: Essential Psychopharmacology: Neuroscientific

Basis and Practical Applications: 2nd ed. Cambridge University Press 2000.2. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.3. Doraiswamy PM. J Clin Psychiatry. 2001;62(suppl 12):30-35.4. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114.

Norepinephrine (NE)

• Both serotonin and norepinephrine mediate a broad spectrum of depressive symptoms

Serotonin (5-HT)

Vague Aches and pain

Functional domains of Serotonin and Norepinephrine1-4

Risk Factors for depression

• Prior episodes (recurrence rate 50%)• Family history• Prior suicide attempt• Female gender • Postpartum period• age: onset in 25-50 year age group

• Medical co-morbidity• Stress• Substance abuse• Lack of social support

Common Presentations

• Fatigue• Chronic pain• Substance abuse• Sleep disorder• “Check up”• Anxiety• Poor school/work performance

Physical findings• In primary care, physical symptoms are often the chief

complaint in depressed patients – But most have no significant physical abnormalities of exam– In a New England Journal of Medicine study, 69% of

diagnosed depressed patients reported unexplained physical symptoms as their chief compliant

• Those with more severe symptoms may reveal decline in grooming or hygiene along with weight changes

• Speech may be normal, slow, monotonic or lacking in content• Thought content includes feelings of inadequacy, helplessness

or hopelessness

Psychiatric comorbidities• Anxiety disorders (particularly panic disorder,

obsessive-compulsive disorder, and posttraumatic stress disorder)

• Cognitive disorders (specifically dementia) • Eating disorders • Somatoform disorders • Personality disorders • Sleep disorders (eg, obstructive sleep apnea) • Substance use disorders

Differential diagnosis

• MDD• Dysthymia• Bipolar disorder• Bereavement• Substance abuse• Metabolic/Endocrine• Dementia• Neoplastic• Medications

ScreeningThe most widely used and best-validated instruments in the primary care

setting are the PHQ-9 and its two-item version, the PHQ-2

PHQ-2 Questionnaire for Major Depressive Disorder During the past month:

1. Have you often been bothered by feeling down, depressed, or hopeless?2. Have you often been bothered by little interest or pleasure in doing things?

– An affirmative answer to either question is a positive test result; a negative answer to both questions is a negative test result.

– In patients with a positive screen result, the PHQ-9 or HAM-D should be performed to confirm the diagnosis and assess severity.

Morbidity and mortality• Greater chance of developing or dying from cardiovascular disease• Contributes to disruption of interpersonal relationships, development

of substance abuse and absenteeism from work and school• All depressed pts should be screened for suicidal and

homicidal/violent ideations - hx of suicide attempts or violence is risk factor for future attempts

• Women, esp younger than 30, attempt suicide more freq than man, but men more likely to complete

• one year after diagnosis of a MDE without treatment, 40% of individuals still have symptoms that are sufficiently severe to meet criteria for a full MDE, 20% continue to have some symptoms that no longer meet criteria for a MDE, 40% have no mood disorder

Depression and Suicide

– Primary care physicians assess for suicide in pts with depression in only about 1/3 of visits• 50% of persons who commit suicide had sought

professional help in prior month– Assess suicide risk• Ideation, intent, plan, availability, lethality• Ask: “this past week, have you had any thoughts that life is

not worth living or that you’d be better off dead?”– Consider “no suicide contract”• Promising the doctor that they won’t do anything until the

pt is seen the next day, or seen in a hospital

23

Depression Treatment• Psychotherapy

– Alone or as adjunctive therapy• Pharmacotherapy

– Effective for major depression and dysthymia• Psychotherapy and medication• Primary care supportive counseling

– Important part of treatment• Inpatient management

– indicated when pt presents risk to self or others or symptoms need to be managed in controlled setting

• Involvement of psychiatrist – warranted in pts whom more severe symptoms require more intensive care

Recommended Guidelines for Treatment of Depression

• If decision to use medication - usually start with SSRI• Titrate agent to achieve therapeutic dose or remission• Full effect may take 4-6 weeks• EPISODE PHARMACOLOGIC TREATMENT

DURATION– First 6-12 months– Second 3 years– Third Lifetime

Agents• Tricyclics

– Nortriptyline, Desipramine, Amitriptyline, Doxepin, others• MAOIs

– Phenylzine, Tranylcypromine, Isocarboxaxid• SSRIs

– Fluoxetine, Sertraline, Paroxetine, Citalopram, Fluvoxamine• SNRIs

– Venlafaxine, Duloxetine• Miscellaneous

– Bupropion, Nefazodone, Mirtazapine, Trazodone

Patient A/P

Patient had a positive PHQ-2 screen• Assessment: 29 y/o female with signs and

symptoms of a major depressive episode. Pt has >5 of the 9 symptoms necessary for diagnosis.

• Plan– Start patient on an SSRI– Discuss the benefits of combining medication with

psychotherapy– Educate the patient on what to do if symptoms worsen

Review ArticleCognitive Therapy vs Medications in the Treatment of

Moderate to Severe DepressionRobert J. DeRubeis, PhD; Steven D. Hollon, PhD; Jay D. Amsterdam, MD; Richard C. Shelton, MD;Paula R. Young, PhD; Ronald M. Salomon, MD; John P. O’Reardon, MD; Margaret L. Lovett, MEd;Madeline M. Gladis, PhD; Laurel L. Brown, PhD; Robert Gallop, PhD

• Cognitive therapy can be as effective as medications for the initial treatment of moderate to severe major depression, but this degree of effectiveness may depend on a high level of therapist experience or expertise.

ReferencesSimon GE, et al. N Engl J Med. 1999;341(18):1329-1335DeRubeis et al. Cognitive Therapy vs Medications in the Treatment of

Moderate to Severe Depression. Arch Gen Psychiatry. 2005;62:409-416Case Files: Family Medicine 2007American Psychiatric Association, Diagnostic and Statistical Manual of Mental

Disorders, 4th Edition, Text Revision.Butler R, Carney S, Cipriani A, Geddes J, Hatcher S, Price J, et al. Depressive disorders.

Clin Evid 2005;15:316–68.

Dementia

=progressive decline in memory accompanied by a loss of intellectual

capabilities severe enough to interfere with social or occupational function

IdaHPI –Ida is a 78 year old female with a past medical history significant for fibroids

and hysterectomy, who presented with weight loss, worsening memory trouble, and inability to perform her daily activities. She lost 11 lbs since her last visit last year. She has had progressive worsening of her short term memory over the last three years. At first she forgot only names and missed appointments. But lately things have gotten worse. She used to garden all the time and her daughter now finds her “watering the flowers to death” because she does not remember already watering them that day. She has been found wandering in the neighborhood twice in the last few months, saying she was headed home or for temple, when she was not headed in the direction of either. She also occasionally argues with her daughter or bursts out crying, which is quite unusual for her.

PMH – fibroidsPSH - hysterectomy

Social HistoryFamily Backgroundo Ida was born in Belgium, from which her family fled during WW2. She is of Jewish descent. o She worked for parks and recreation department in New York before moving to Miami to

live with her daughter.o Her daughter is a postal worker who supports and cares for her, but she is estranged from

her son and grandchildren.

Current characteristicso She lives with her daughter and son-in-law in their houseo She loves to garden flowers and vegetableso She is an active member of her temple, where she has many friends.o She is unable to perform her IADLs such as driving and paying her bills and recently has lost

the desire to eat, making her more and more dependent on her daughter and unwilling son-in-law

Upon Examination..

• Ida was oriented to person and place but not time• 24/30 on MMSE - she was unable to recall any of

the three words and did not spell world correctly backward

Labs

• Hg 11, Hct 32, MCV 92• All other results WNL

Dementia differential• Depression• Loss of hearing, vision• Space occupying lesions (subdural hematoma)• Infections (syphillis, HIV)• Neurodegenerative disorders (MS, PD, HD)• Normal pressure hydrocephalus

– Ataxia, incontinence and dementia• Metabolic (hypercalcemia, B12, folate deficiencies, intoxication)• Hypothyroidism• Medication (sedatives, antihypertensives, neuroleptics)

Ida: Imaging

• MRI results demonstrated cortical atrophy greater than expected for age, hippocampal atrophy, diffuse enlargement of sulci, ventricular enlargement

• No focal changes, no evidence of mass effect, no evidence of stroke

Diagnosis

1. Suspect if patient has trouble remembering medications, recent events, medical history.2. Ask family member/friend/caregiver about forgetfulness, ADLs, getting lost, hygeine, emotional outbursts3. Review medications4. Determine history of trauma, etc.

2. Differentiate from delirium and depressiondelirium – acute onset, waxes and wanesdepression (pseudodementia) – self reporting of problems

LABS Rule out metabolic, infectious causes - B12, folate, TSH, FTA-ABS, HIV,CBC, ESR, electrolytes, CA, albumin, BUN, CR, LFTs, UA

IMAGINGRule out structural etiologiesCT, MRI

5. Hearing and vision testing6. Rule out infectious causes (syphillis), vasculitis, MS

Epidemiology

1. Alzheimers Dementia- Most common, accounts for more than half all cases

2. Vascular Dementia (includes multi-infarct dementia) ~15%, second most common, due to ischemia/hypoxia, a/w HTN, DM, arterial disease, smoking

3. Lewy Body Dementia ~10-15%4. Mixed Type Dementia(AD and vascular)5. Frontotemporal Dementia ~5-10%

ADClinical• Slow, progressive decline in function• Short term memory affected first• Other domains follow later such as language,• executive function, visuospatial skills• Social withdrawl, frustration,• emotional outbursts, difficulty driving

DiagnosisNIH: “slowly progressive memory loss of insidious onset in a fully conscious patient”Rule out other etiologies - MRI/CT, infectious, metabolic, etcLP – elevated tau, decreased amyloid are highly sensitive and specific, but only used for

research(tau)

AD

Risk FactorsLifetime risk 1:4-1:2Age (40-45% patients >80 yo), Female, Race, educationFamily history (<10%)

PathologyDiffuse cerebral atrophy, especially cortical and medialtemporal Plaques (B-amyloid) and neurofibrillary tangles

VascularClinicalSymptoms may be similar to ADStepwise progression

DiagnosisImaging, difficult to determine clinicallyOften coexists with AD (Mixed type demetia)

RiskHTN, DM, smoking, arterial disease, apoE4, male

PathVaried - Cortical or subcortical from large or small vessels, blobal ischemic injury,

CADASIL,vasculitis etcMost commonly multi infarct dementia resulting from multiple lacunar infarcts

Dementia with Lewy Bodies

ClinicalRapid decline in function, visual hallucinations, extrapyramidal motor signs early

in disease, , episodic delirium (eg- staring into space, excessive daytime sleepiness)

DLB vs. AD: Executive function and visuospatial deficits more common than in AD, less

anterograde memory loss, can differentiate with SPECT

PathLewy bodies = intracytoplasmic inclusions throughout cortex, Ach and DA

disturbances, decreased neuronal density in hippocampus, amygdala, cortex

Frontotemporal

Clinical• Focal progressive changes – may present as progressive

aphasia,prosopagnosia, or extreme behavioral changes that may be interpreted as psychosis, w/ preserved memory and visuospatial function

• Generalized dementia follows between 1-10 yrs later • Not highly a/w motor symptoms, mortality not as high

RiskHighest in 50-60yo40-50% familial involvement

PathTau pathology or ubiquitin immunoreactive inclusions

Treatment

• Maintenance of activity – physical and mental• Quality of life preservation – caregiver, safe and comfortable

environment • Support for the caregiver• Treat any associated conditions – depression, hearing loss,

metabolic conditions, psychosis etc• Antidepressants, Atypical antipsychotics or anticonvulsants may

be used to manage uncontrollable behavior • Be careful! Anti-cholinergics (Benadryl, TCAs), anxiolytics, sleeping

pills may exacerbate cognitive impairment, falls, sedation• End of life preparation, advanced directives

Treatment 2

NMDA-R antagonist – Memantine (Nemenda)

ChE inhibitors can slow progression slightly– Tacrine (Cognex)– Donepezil (aricept)– Rivastigmine (exelon)– Galantamine (Razadyne)

• Questionable evidence for Vitamin E , NSAIDs

Ida: Assessment and PlanA : Ida is a 78 yo female suffering from dementia, probable Alzheimer’s type. We are

unable to confirm this diagnosis as it is only confirmable at autopsy or with PIB staining which is unavailable. However, other probably diagnoses have been ruled out and the type of dementia does not affect treatment. She is also suffering from anemia due to dietary deficiency and undesired weight loss. She is having trouble with her ADLs and her support system is fragile.

P :1. Counsel caregiver on maintaining a safe and comfortable environment.2. Determine status of advanced directives and counsel accordingly.3. Treat anemia and weight loss with caloric and iron supplementation.4. Discuss beginning an AChE inhibitor, and then adding Nemenda as tolerated.5. Monitor mood changes and look out for signs of depression at follow up after

environmental and diet changes are instituted.

NSAIDS and dementia?Breitner JC, Haneuse SJ, Walker R, Dublin S, Crane PK, Gray SL, Larson EB.

Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology. 2009 Jun 2;72(22):1899-905

Old studies showed a decreased incidence of dementia among people using long term NSAIDs.

This study investigated that relationship among older patients (>65yo) and found the inverse relationship.

This suggests NSAIDs may delay onset, but are not preventative.

Case Study Delerium• Mrs. M. is a 77 y/o AAF with hx. of ESRD presents to

ER with lower extremity weakness x 1-2 days and elevated blood pressure.– Feeling generally weak, now unable to ambulate– Off BP meds for about a week

• “BP controlled with Dialysis”– Headaches– Poor vision– Some SOB and coughing– Per social worker and daughter, mental status changed

from baseline

Case Background• Family Background

– Born & raised in Miami– Supportive family– Works as a houskeeper/retired– Recently widowed

Current Characteristics Lives with her daughter Is in a book club Plays cards with her daughter and friends Likes to cook

Future Wants to start a business from home

Learning Objectives

• Recognize that delirium is a common presentation of disease in the elderly

• Recognize that delirium is associated with adverse outcomes

• Know how to distinguish between delirium and other diagnoses (dementia, depression)

• Identify risk factors for delirium and strategies for risk reduction

• Discuss management strategies, recognizing the limitations of current data

PMHx– HTN– Glaucoma– Cataract– Anemia– Recent AV graft infection

Social Hx

• Lives at home with daughter• Quit smoking in 50’s• Widow

Cont.

• Allergies – none• Meds– Lisinopril– Aranesp– Xalatin eye drops– Phoslo– Nephrocaps– Zocor– Aspirin

Cont.VitalsT 97.1 HR 79 R 14 BP 175/69 Pox 98% 2L

Physical ExamGen – Alert, oriented? Female, HEENT – PERRLA, EOMI, MMMNeck – JVD, nl thyroidChest – bilateral rhonciCV – RRR, nl S1 and S2, no edema, no bruitsAbd – soft, NT/ND, no HSMExt – no E/C/CNeuro – equal/symetric +1 reflexes., CN intact, nl cerebellar signs, +5 strength in UE, -5 in LE Neg Rhomberg

Labs

138 96 7

3.7 33 2.5 90

5.3 13.6

41.5

Ca 9.7

CKMB 1.8

Trop I 0.05

EKG NSR, No ST changes

CXR NAD

UA: 1.006, 8.5, prot 100, occ bact, LE large, 27 WBC

Diff: N65 L20 M10

218

Imaging• Head CT– Small vessel disease with age indeterminate infarcts in

internal capsule. Possible subacute on old?

• MRI Head– moderate deep and sub-cortical ischemic white

matter changes – non acute– Bilateral patchy ischemic foci in the lentiform

nucleus and pons. No intracranial mass lesion– remote micro hemorrhage in the right posterior

inferior aspect of the thalamus

Problem List

Geriatric

Weakness, ambulatory only with assistance - new

Recent decline in mental status

HTN, uncontrolled

ESRD

UTI

Impaired vision

SOB, hypoxic

Small vessel disease, lacunar infarcts

Hospital Course

• Mental Status quickly deteriorated– Visual Hallucinations- Pt. began seeing frightening

creatures in the corner of her room.– Fluctuating mental status• Alert but not oriented at times• Unable to concentrate• Tangential thought

– “sundowning” – Patient placed in restraints

Delerium

Disturbance of consciousness i.e., reduced clarity of awareness of the

environment with reduced ability to focus, sustain, or shift attention

Change in cognition (memory, orientation, language, perception)

Development over a short period (hours to days), tends to fluctuate

Evidence of medical etiology

Causes: “I WATCH DEATH”

• I nfections• W ithdrawal• A cute metabolic• T rauma• C NS pathology• H ypoxia

• D eficiencies• E ndocrinopathies• A cute vascular• T oxins or drugs• H eavy metals

“I WATCH DEATH”

• Infections: encephalitis, meningitis, sepsis• Withdrawal: ETOH, sedative-hypnotics,

barbiturates• Acute metabolic: acid-base, electrolytes, liver

or renal failure• Trauma: brain injury, burns

“I WATCH DEATH”

• CNS pathology: hemorrhage, seizures, stroke, tumor (don’t forget metastases)

• Hypoxia: CO poisoning, hypoxia, pulmonary or cardiac failure, anemia

• Deficiencies: thiamine, niacin, B12• Endocrinopathies: hyper- or hypo-

adrenocortisolism, hyper- or hypoglycemia

“I WATCH DEATH”

• Acute vascular: hypertensive encephalopthy and shock

• Toxins or drugs: pesticides, solvents, medications, (many!) drugs of abuse– anticholinergics, narcotic analgesics, sedatives

• Heavy metals: lead, manganese, mercury

Medications and Delirium• Sedative-hypnotics, especially benzos• Narcotics, especially meperidine• Anticholinergics• Miscellaneous– Lidocaine -Propranolol– Amiodorone-Digoxin– H2 Blockers -Lithium– Steroids -Metoclopromide– NSAIAs -Levodopa

• Consider any drug a possible cause

Searching for the cause• History and PE (consider possible urinary retention &

PVR, impaction)• Discontinue or substitute high risk meds• Labs: CBC, lytes, BUN, Cr, glucose, calcium, LFTs, UA,

EKG• And if those don’t tell you, consider:• Neuroimaging • CSF• Tox screen, thyroid, B12, drug levels, ammonia, cultures,

ABG• EEG - in difficult cases to r/o occult seizures or psych

disorders - 17% false neg, 22% false pos

Presentation

• Acute + relatively sudden onset (over hours to days)

• Decline in attention-focus, perception and cognition

• Change in cognition must not be one better accounted for by dementia

• Fluctuating time course of delirium helps to differentiate

Characterised by:• Disorientation in time, place +/- person• Impaired concentration + attention• Altered cognitive state• Impaired ability to communicate• Wakefulness – insomnia + nocturnal agitation• Reduced cooperation• Overactive psychomotor activity – irritability + agression

Diagnosis

• Cannot be made without knowledge of baseline cognitive function

• Can be confused with – 1. dementia – irreversible, not assd with change in

consciousness– 2. depression– 3. psychosis – may be overlap but usually

consciousness + cognition not impaired

Differentiating features of delirium and dementia

Features Delirium DementiaOnset Acute InsidiousCourse Fluctuating ProgressiveDuration Days – weeks Months - yearsConsciousness Altered ClearAttention Impaired Normal (unless

severe)Psychomotor changes

Increased or decreased

Often normal

Reversibility Usually Rarely

Epidemiology

• At admission prevalence 14-24% • Hospitalization incidence 6 to 56%• 15-53% geriatric patients post-op• 70-80% older patients in ICU• 60% nursing home will have at some time• 83% of geriatric patients prior to death

Complications

• Mortality rate in hospitalized patients 22-76% • One year mortality rate is 35-40%• Prolongs hospital course• Increased cost of care in hospital• Increases likelihood of disposition to nursing

home, functional decline and loss of independence

Why does it matter?

• Strong association with underlying dementia

• Frequently, patient may never return to baseline or take months to over a year to do so

• Delirium is often the sole manifestation of serious underlying disease

Pathophysiology

• Not fully understood• Main theory = reversible impairment of cerebral oxidative

metabolism + neurotransmitter abnormalities• Ach – anticholinergics = cause of acute confusional states +

Pts with impaired cholinergic transmission (eg Alzheimers) are more susceptible

• Dopamine – excess dopamine in delirium• Serotonin – increased in delirium• Inflammatory mechanism – cytokines eg interleukin-1 release

from cells• Stress reaction + sleep deprivation• Disrupted BBB may cause delirium

Pathophys

• EEG shows diffuse cortical slowing• Neuropsyc and imaging– Disruption of higher cortical function

• Prefrontal cortex• Subcortical structures• Thalamus• Basal ganglia• Frontal and temporoparietal cortex fusiform cortex• Lingual gyri• Effect greatest on non-dominant side.

• Involves

1) Neurotransmission2) Inflammation3) Chronic stress

Pathogenesis

• Neurotransmission– Cholinergic deficiency

• Anticholinergics can precipitate delirium• Serum anticholinergic activity increased in those with delirium• Cholinesterase inhibitors can reverse this effect

– Dopaminergic excess– Neuropeptides, endorphins, serotonin, NE, GABA may play

a role.

Pathogenesis

Pathogensis

• Cytokines– Interleukins and interferons– Often elevated in Delirium– Have known strong CNS effects– Primary role – sepsis, bypass surgeries, dialysis,

cancers

Pathogensis

• Chronic stress– Untreated pain /

analgesia are strong risk factors

– Elevated cortisol assoc with delirium

Delirium Risk Factors

• Age• Cognitive impairment

– 25% delirious are demented– 40% demented in hospital

delirious• Male gender• Severe illness• Hip fracture • Fever or hypothermia• Hypotension • Malnutrition

• High number of meds • Sensory impairment• Psychoactive medications• Use of lines and restraints• Metabolic disorders:

– Azotemia– Hypo- or hyperglycemia– Hypo- or hypernatrmiea

• Depression• Alcoholism• Pain

Differential Diagnosis• CNS pathology• Dementia, particularly frontal lobe• Other Psychiatric disorders– Psychosis

• Depression: 41% misdiagnosed as depression Farrell Arch Intern Med 1995 – Bipolar disorder

• Aconvulsive status epilepticus• Akathisia• Overall, 32-67% missed or misdiagnosed

Management

• 1. Identify + treat underlying cause (return to pre-morbid state can take up to 3 weeks)

• 2. Complete lab tests + investigations eg. FBC, CRP, U+Es, BM, LFTs, TFTs, B12, MSU, CXR

• 3. Rule out EtOH withdrawl• 4. Assume an underlying organic cause

Management

• 5. Ensure adequate hydration + nutrition• 6. Use clear, straightforward communication• 7. Orientate the patient to environment +

frequent reassurance• 8. Identify if environmental factors are

contributing to confused state

Management

• Disturbed, agitated or uncooperative patients often require additional nursing input

• Medication should not be regarded as first line treatment

• Consider medication if all other strategies fail but remember all psychotropic meds can increase delirium + confusion

Medication Management

• Pharmacologic management of agitation- Low doses of high potency neuroleptics (i.e. haloperidol) – po, im or iv- Atypical antipsychotics (risperidone)- Inapsine (more sedating with more rapid onset than haloperidol – im or iv only – monitor for hypotension)

Use of Haloperidol• Lowest possible dose, e.g., .5-1.0 BID

tapering down as delirium clears• 0.5mg, repeat every 30 minutes until

agitation is controlled• Some advocate doubling of dose every 30

minutes until agitation is controlled (probably not wise in elderly!)

• Droperidol can be used IV - more rapid onset– Caution: sedation, hypotension, less anti-

psychotic than haloperidol

Benzodiazepines

- May worsen confusion in delirium- Behavioral disinhibition, amnesia, ataxia, respiratory depression- Contraindicated in delirium due to hepatic encephalopathy

• Summary• Delirium is common in older inpatients,

associated with poor outcomes, and commonly missed or misdiagnosed

• Prevention is the best approach• Management involves treating underlying

causes, minimizing medications, supportive care, and avoidance of restraints when possible

• ICU delirium poses particular challenges• Further research and RCTs are needed

A Mrs. M. is a 77 y/o AAF with hx. of ESRD presents to ER with lower extremityweakness x 1-2 days and elevated blood pressure. She has been feelinggenerally weak and now is unable to ambulate. She is most likely suffering from delirium, made evident by her recent deterioration in mental status, visual hallucinations, sundowing and waxing and waning of consciousness.

P• Identify and treat the underlying etiology• Increase observation and monitoring – vital signs, fluid intake and output, oxygenation, safety• Discontinue or minimize dosing of nonessential medications• Coordinate with other physicians and providers• Monitor and assure safety of patient and staff• suicidality and violence potential• fall & wandering risk• need for a sitter• remove potentially dangerous items from the environment• restrain when other means not effective

Article

• Non-pharmacological Interventions in the Prevention of Delirium

• Naji Tabet; Robert Howard• Age and Ageing. 2009;38(4):374-379. © 2009

Pharmacological therapy is widely used in established cases of delirium, but its efficacy and influence on the outcome is not clearly proven. The single best approach to the management of delirium remains the identification of underlying causes.