Disturbance in consciousness with reduced ability to focus, sustain, or shift attentionA change in cognition or the development of a perceptual disturbance that is not better accounted for by a preexisting, established or evolving dementiaDevelops over a short period of time (usually hours to days) and tends to fluctuate over the course of the dayThere is evidence from the history, physical exam, or laboratory findings that the disturbance is caused by the direct physiological consequences of a general medical condition
Greater than > 70 % of seriously ill patients rate mental awareness as important JAMA 2000; 284: 2476 - 248289% of seriously ill patients would not choose a treatment if the outcome is cognitive impairment; the more risk the less inclined to treatment NEJM 2002; 346: 1061 - 1090
76% witnessed delirium or confusion38% witnessed these symptoms dailySense of fear and helplessnessMay contribute to caregiver risk for Major Depressive Disorder and quality of life impairments (in aggregate with prevalence and frequency of other distressing events) Am J Geriatr Psychiatry 2003; 11: 309 - 319Most caregiver measures center on the consequence of care provision for the caregiver’s well being and function. This study measured the impact of caregiver exposure to distress of their loved ones. Delirium the second most prevalent symptom after severe pain (80%)Sense of helplessness (between 1 = somewhat and 2 = very) 1.22 on scaleFear 0.79 (0= none 1 = somewhat)
Causes of Delirium Acronym (adapted from Capital Health)D Drugs, drugs, drugs, dehydration, depression E Electrolyte, endocrine dysfunction (thyroid, adrenal), ETOH (alcohol) and/or drug use, abuse or withdrawal L Liver failure I Infection (urinary tract infection, pneumonia, sepsis) R Respiratory problems (hypoxia), retention of urine or stool (constipation) I Increased intracranial pressure; U Uremia (renal failure), under treated pain M Metabolic disease, metastasis to brain, medication errors/omissions, malnutrition (thiamine, folate or B12 deficiency)
What are the benefits and burdens of:Labs, tests to search for reversible causes of delirium?CBC, lytes, BUN/creat, calcium, glucose, UA, O2 satTreatments of underlying cause(s)?Antibiotics, oxygen, bladder catheter, otherTreatments of agitated behavior?Antipsychotics, sedative hypnoticsChange in setting of care
TARGETED RISK FACTOR AND ELIGIBLE PATIENTS STANDARDIZED INTERVENTION PROTOCOLSTARGETED OUTCOMEFOR REASSESSMENTCognitive impairment*All patients, protocol once daily; patients with base-line MMSE score of <20 or orientation score of <8, protocol three times dailyOrientation protocol: board with names of care-team members and day’s schedule; communication to reorient to surroundings Therapeutic-activities protocol: cognitively stimulating activities three times daily (e.g., discussion of current events, structured reminiscence, or word games)Change in orientation scoreSleep deprivationAll patients; need for protocol assessedonce dailyNon-pharmacologic sleep protocol: at bedtime, warm drink (milk or herbal tea), relaxation tapes or music, and back massageSleep-enhancement protocol: unit-wide noise-reduction strategies (e.g., silent pill crushers, vibrating beepers, and quiet hallways) and schedule adjustments to allow sleep (e.g., rescheduling of medications and procedures)Change in rate of use ofsedative drug for sleep†ImmobilityAll patients; ambulation whenever possible, and range-of-motion exercises when patients chronically non-ambulatory, bed or wheelchair bound, immobilized (e.g., because of an extremity fracture or deep venous thrombosis), or when prescribed bed restEarly-mobilization protocol: ambulation or active range-of-motion exercises three times daily; minimal use of immobilizing equipment (e.g., bladder catheters or physical restraints)Change in Activities of Daily Living scoreVisual impairmentPatients with <20/70 visual acuity on binocular near-vision testingVision protocol: visual aids (e.g., glasses or magnifying lenses) and adaptive equipment (e.g., large illuminated telephone keypads, large-print books, and fluorescent tape on call bell), with daily reinforcement of their useEarly correction of vision, «48 hr after admissionHearing impairmentPatients hearing «6 of 12 whispers onWhisper TestHearing protocol: portable amplifying devices, earwax disimpaction, and special communication techniques, with daily reinforcement of these adaptationsChange in Whisper Test scoreDehydrationPatients with ratio of blood urea nitrogen to creatinine»18, screened for protocol by geriatric nurse-specialistDehydration protocol: early recognition of dehydration and volume repletion (i.e., encouragement of oral intake of fluids)Change in ratio of blood urea nitrogen to creatinine
If patient does not fully respond to treatmentReevaluatediagnosis/presumed causeInquire about adherence to medicationConsider dosage adjustment Titrate before rotate - just like with pain!Consider a different medicationRefer to a specialist
BMJ 2011;343:d4065 doi: 10.1136/bmj.d4065Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trialBettina S Husebo postdoctoral fellow, Clive Ballard professor, Reidun Sandvik registered nurse, Odd Bjarte Nilsen statistician, Dag Aarsland professor AbstractObjective To determine whether a systematic approach to the treatmentof pain can reduce agitation in people with moderate to severe dementialiving in nursing homes.Design Cluster randomised controlled trial.Setting 60 clusters (single independent nursing home units) in 18 nursinghomes within five municipalities of western Norway.Participants 352 residents with moderate to severe dementia andclinically significant behavioural disturbances randomised to a stepwiseprotocol for the treatment of pain for eight weeks with additional follow-upfour weeks after the end of treatment (33 clusters; n=175) or to usualtreatment (control, 27 clusters; n=177).Intervention Participants in the intervention group received individualdaily treatment of pain for eight weeks according to the stepwise protocol,with paracetamol (acetaminophen), morphine, buprenorphine transdermalpatch, or pregabaline. The control group received usual treatment andcare.Main outcome measures Primary outcome measure was agitation(scores on Cohen-Mansfield agitation inventory). Secondary outcomemeasures were aggression (scores on neuropsychiatric inventory-nursinghome version), pain (scores onmobilisation-observation-behaviour-intensity-dementia-2), activities ofdaily living, and cognition (mini-mental state examination).Results Agitation was significantly reduced in the intervention groupcompared with control group after eight weeks (repeated measuresanalysis of covariance adjusting for baseline score, P<0.001): theaverage reduction in scores for agitation was 17% (treatment effectestimate −7.0, 95% confidence interval −3.7 to −10.3). Treatment of painwas also significantly beneficial for the overall severity of neuropsychiatricsymptoms (−9.0, −5.5 to −12.6) and pain (−1.3, −0.8 to −1.7), but thegroups did not differ significantly for activities of daily living or cognition.
Aromatherapy massage RCT showed short-term benefit in anxiety in patients with cancer related anxiety.Lavandula augustifolia (Lavender) aromatherapy - agitation in elderly patients with dementia. Cross-over randomized study. N=70Improvement in Agitation (p<0.0005), irritability (p<0.001), physical aggression, physical behavior non-aggressive, and verbally agitated behavior (p<0.001).Other studies showed cutaneous application of oil for effect, given decrease in olfactory function in elderly.
Delirium in Palliative Care & Hospice
Delirium:Recognizing, Assessing and Managing Terminal Restlessness Suzana Makowski, MD MMM Associate Director of Palliative Care in the Cancer Center UMass Memorial Healthcare, Worcester, MA JoAnne Nowak, MD Medical Director, Merrimack Valley Hospice, Lawrence, MA Special thanks to Jennifer Reidy, MD who helped prepare the content
DeliriumDelirare: to be crazyDe lira: to leave thefurrows
Early Descriptions“they move the face, hunt in “Sick people…lose their judgment empty air, pluck nap from the and talk incoherently…when bedclothes…all these signs are the violence of the fit is abated, bad, in fact deadly” the judgment presently returns…”Hippocrates:400 BCE Celsus: 1st Century BCE
Delirium • Synonyms: acute confusional state, organic brain syndrome, encephalopathy, terminal agitation, terminal restlessness • Often mistaken for depression, anxiety, or dementiaTerminal Agitation:A symptom or sign: thrashing, agitation that may occur in the last daysor hours of life.May be caused by: • pain • anxiety • dyspnea • delirium
DSM-IV Criteria: Delirium• Disturbance of consciousness affecting attention• Change in cognition• Develops over a short period of time, and may fluctuate• Caused by physiologic consequence of a general medical condition
Clinical Subtypes: Delirium Less likely to be diagnosed Mixed• Confusion • Confusion• Agitation • Fluctuates • Somnolence• Hallucinations between both • Withdrawn• Myoclonus Hyperactive Hypoactive
Delirium vs. Dementia vs. DepressionFeatures Delirium Dementia DepressionOnset Acute (hours to Insidious (months to Acute or Insidious days) years) (wks to months)Course Fluctuating Progressive May be chronicDuration Hours to weeks Months to years Months to yearsConsciousness Altered Usually clear ClearAttention Impaired Normal except in May be decreased severe dementiaPsychomotor Increased or Often normal May be slowed inchanges decreased severe casesReversibility Usually Irreversible Usually
Dying with Dementia Agitation • 87% Confusion • 83% J. Geriatric Psychiatry 1997
Which of the following medications cancause delirium?a) Lorazepamb) Hyoscyaminec) Dexamethasoned) All of the abovee) None of the above
Opioids Corticosteroids Benzodiazepines Anticholinergics Diuretics Tricyclics Lithium H2 Blockers NSAIDs Metoclopramide Alcohol/drug use or withdrawalWHAT CAUSES IT?
Diagnosis of exclusionDelirium during the dying process Signs of the dying processMultiple causes, often irreversibleTERMINAL DELIRIUMCAN IMPENDING DEATH CAUSE IT?
Case: Paul – is he at risk for delirium?Predisposing factors Possible precipitating factorsDementiaAge Drug side effects?Metastatic lung cancer Hypoxemia?Immobility Infection?Poor oral intake Constipation?Poly-pharmacy Urinary retention? Metabolic disorder? Brain metastases? Emotional distress?
General Assessment: Delirium• Hospice diagnosis, co-morbidities• Onset of mental status change• Oral intake, urine output, bowel movements• Recent medication history• Review of systems: fever, N/V, pain, dyspnea, cough, edema, dec ubiti• Alcohol or illicit drug use• Falls, safety• Emotional, spiritual distress
Assessment: Paul• Metastatic non-small cell lung cancer• Severe Alzheimer’s disease• More restless, combative in last 3 days• Hand-fed small, pureed meals & thickened liquids but minimal in 3 days• Small amount dark urine, no BM in 1 week
Assessment Tools: Delirium• Confusion Assessment Method (CAM) – 94-100% sensitive, 90-95% specific – 10-15 minutes by trained interviewer• SQiD (single question in delirium) – “Do you think Paul has been more confused lately?” – 80% sensitive and 71% specific in oncology patient
Confusion Assessment MethodFeature 1: Acute Onset Obtained from a family member or nurse:and Fluctuating Course • Is there evidence of an acute change in mental status from the patient’s baseline? • Did the (abnormal) behavior fluctuate during the day, that is, tend to come and go, or increase and decrease in severity?Feature 2: Inattention • Did the patient have difficulty focusing attention, for example, being easily distractible, or having difficulty keeping track of what was being said?Feature 3: • Was the patient’s thinking disorganized or incoherent, suchDisorganized thinking as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?Feature 4: Altered • Overall, how would you rate this patient’s level ofLevel of consciousness consciousness? alert [normal]), vigilant [hyperalert], lethargic [drowsy, easily aroused], stupor [difficult to arouse], or coma [unarousable])The diagnosis of delirium by CAM requires the presence of features 1 and 2 and either 3 or 4.
Diagnostic Approach to Delirium• Delirium is a clinical, bedside diagnosis• Careful, gentle approach to patient• Appearance, vital signs• Focused exam based on history• Consider rectal exam, catheter
Paul’s assessment: Delirium• Lethargic, frail, elderly man lying in hospital bed; fidgeting of arms, legs; slow but persistent attempts to sit up or slide between side rails; quiet but anxious expression• CAM: all features present• Afebrile, BP 105/62, HR 95, RR 24• Positive findings: – MM dry; – Foley catheter w/cloudy, dark urine; – abd distended but soft, – quiet BS; rectal +stool; – decubitus stable w/o infection
Paul’s follow up Goals of care: Peaceful death at home • DNH • no needlesticks Treated the treatable Treated the delirium • Disimpaction, daily bowel • Haloperidol 0.5-1mg SL qHS regimen and q8hrs prn • Treated UTI w/ liquid • Calmer environment antibiotics • Improved communication • Weaned lorazepam • Encouraged safe movementIn 2-3 days, Paul was back to baseline
Step 1: Treat underlying causesStep 2: Non-pharmacologicalStep 3: PharmacologicalMonitor: GIP or continuous careAddress family, caregivers and otherpsychosocial impacts of deliriumDeliriumMANAGEMENT
Which of the following are appropriateinterventions for delirium?a) Music during turns/personal careb) Minimize ambient sound (alarms, bells, voice)c) Aromatherapy such as Lavender or Melissa with bed bathd) Spiritual interventions such as prayer, ritual, meditatione) Cognitive behavioral therapy for PTSDf) Engaging family or familiar people in careg) All of the above
Assessing severity of agitation Aggressive, hostile Irritability, intimidation Mood lability, loud speech Motor restlessness Uncooperative, intense stare Adapted from Scott Irwin, San Diego Hospice
Hierarchy of interventions for agitated delirium Seclusion Emergency and/or medicine restraint Voluntary medication Verbal intervention Check for needs, Step 1: Treat underlying causes non-pharmacologic Step 2: Non-pharmacological Step 3: Pharmacological Address family, caregivers and other psychosocial impacts of delirium Adapted from Scott Irwin, San Diego Hospice
Delirium ManagementSTEP 1: TREAT UNDERLYING CAUSE
Case 2: Rosie’s distress• 88 yo great-grandmother with end-stage pulmonary fibrosis, renal insufficiency.• “CMO” and morphine drip was started to treat her dyspnea – then sent home with hospice. Please help! She is moaning, agitated, in pain even when we touch her lightly. Other times, we can’t wake her up.
rugs, drugs, drugs, dehydration motion, encephalopathy, environmental change ow oxygen, low hearing/seeing nfection, intracerebral event or metastasis etention (urine or stool) ntake changes (malnutrition, dehydration), Immobility remia, under treated pain etabolic diseaseSTEP1: TREAT CAUSE Management
Opioid neurotoxicity: important cause • Morphine metabolized in the liver to – Morphine 6-glucoronide – Morphine 3-glucoronide • Builds up disproportionately in renal failure • Neuro-agitation: – Increased RR, agitation, myoclonus, and sometimes seizuresAnti-psychotics may worsen opioid neurotoxicity:benzodiazepines and phenobarbitol are treatments of choice
Rosie’s distress: treat underlying cause Attempt to reverse morphine neurotoxicity • Stop morphine • Start lorazepam or phenobarbitol • Consider IV/SQ fluids depending on goals of care PRN SL oxycodone or IV fentanyl if needed for pain or dyspnea or schedule methadone Oxygen for hypoxemia-induced deliriumSTEP1: TREAT CAUSE Management
Treat the painAddress sleep-wake cycleCreate familiar environmentFacilitate range of motion & exerciseAGITATION WITH DEMENTIA
Sleep-wake cycle: normalizeMelatonin 3-7mg in the evening, with sunset.
NON-PHARMACOLOGIC APPROACH• Engage social work • Engage chaplaincy & psychology • Acknowledge• Consider past faith, legacy, regret trauma, Ψ history Emotional Existential Environment Physical• Engage • Nurses, aides, and aides, housekeeping doctors , family. • Exquisite care of the• Consider the 5 body senses
Physical environment & body Sight • Light/dark cycles, visual cues, familiar faces Sound • Reduce ambient noise, music therapy, familiar voices Smell • Cleanliness, aromatherapy, home cooking Touch • Massage, physical therapy, movement Taste • Drink if thirsty – but hydrating drinks. Eat if hungry – and assure good bowels.STEP2: NON-PHARM Management
Case 3: Mr. U65 year old retired engineer with metastatic lungcancer to bone.HPI: Severe pain, principally in area of leg requiringcomplex pain management. Now he is experiencingincreased confusion, agitation, restlessness at night.Past Medical History: Generally healthy until diagnosis.Social History: Married to a non-Catholic woman. Has 2grown daughters. Raised Catholic but has not been tochurch much since his marriage.
Case 3: Mr. U’s agitation• Physical: under treated pain• Emotional: sadness at losing his family• Existential: – Fear of afterlife – Unresolved conflicts – Never married in the Church Created non-judgmental ritual, presence Witnessing by hospice team and family
Hypoactive delirium • Day-night cycle can be critical • Methylphenidate 5mg qam and qnoon – Watch for anxiety, symptomatic palpitationsSTEP3: PHARMACOLOGIC Management
If all else fails, use antipsychoticsMANAGING DELIRIUM
Antipsychotics are the mainstay of pharmacologic treatment Black Box Warning! But they increase death! Increased risk by 1.6 – 1.7 RR absolute increase from 2.3% to 3.5% during intervention Risk / benefit and goals of care TimeSTEP3: PHARMACOLOGIC Management
Treat like other breakthrough symptoms: Schedule medicine based on t ½ Breakthrough medicines based on Cmax Consider selection of antipsychotic based on profileSTEP3: PHARMACOLOGIC Management
Pharmacology of Anti-psychoticsDrug Cmax T½Chlorpromazine 1-4 hours 16-30 hours25mg SQ/IV/PR q3 hours prnup to 2g/dayQuetiapine 1-2 hours 6-7 hours25-100mg PO q1 hour prnup to 1200 mg/dayRisperidone 1-1.5 hours 3-24 hours0.25-1mg PO q1 hourup to 6mg/dOlanzapine 4-6 hours 20-70 hours5-10mg PO q4 hours prnup to 30mg/dayHaloperidol 30 min – 1 hour 4-6 hours0.5 – 2 mg q1 hr prn
Profiles of antipsychotics MuscarinicAdapted from www.PalliativeDrugs.com
Chlorpromazine vs. HaloperidolAntipsychotic Agent Chlorpromazine HaloperidolSedation +++ +EPS ++ ++++Anticholinergic ++ +OrthostaticHypotension +++ +++++ = very high incidence, +++ = high incidence, ++ = moderate incidence, + = low incidenceDrug Facts and Comparisons (Oct 2003)
More on Anti-psychoticsLength of Sed Sed - EPSuse Haloperidol Chlorpromazine 3-7 Days 0.5-2 mg q1 hour prn 12.5-25 mg q 3 IM, IV, SC hours prn up to 3 PO (tab/sol) grams/day SCI IM, IV, PR SCI? PO - erratic Risperidone Olanzapine Quetiapine >7 Days (Risperdal) (Zyprexa) (Seroquel) PO: tab,sol,odt PO: tab,odt PO: tab IM: long acting IM: intermittent Ziprasidone (Geodon) PO: cap IM: intermittent
Choose based on level of behavior If more hyperactive, consider atypical antipsychotics If more hypoactive, consider haloperidolTitrate medication if initial dose is not effective.Consider switching medication if: Lengthy treatment anticipated Lack of response despite increase dose.
Inadequate or no response:Reassess cause again, depending on goals of care.Consider sedation if needed. benzodiazepines, barbiturates or propofol This is palliative sedation!
Agitated delirium - severeFor imminent risk of harm to self or others due to agitation,mix in following order: Haloperidol 2- DiphenhydramineLorazepam 1-2mg 5mg 50-100mg
Agitated delirium – severe (alternatives)• Chlorpromazine 50-100mg SQ/PR up to 2g/day – Increase dose by 25-50mg q1-4 hours until controlled – Likely to not need diphenhydramine – Consider lorazepam along side• Olanzapine 5-10mg IM q4 hours up to 30mg/day• Phenobarbitol 20-40mg starting dose q3 hours prn – especially useful for brain mets.
Hierarchy of interventions for agitated delirium Seclusion Emergency and/or medicine restraint Voluntary medication Verbal intervention Check for Step 1: Treat underlying causes needs, non- Step 2: Non-pharmacological pharmacologic Step 3: Pharmacological Address family, caregivers and other psychosocial impacts of delirium Adapted from Scott Irwin, San Diego Hospice
Case 4: Philip’s struggle63 yo retired photographer with end-stage CHF, inthe context of drug abuse history. He was anactive duty veteran.He was estranged from his family and no longeractive in his Jewish faith.Severe dyspnea. Now over 2 weeks becomingincreasingly confused multiple times each day.Sometimes confusion is agitated, sometimessomnolent.
Philip’s struggle “Philip has terminal agitation, and I think he needs more …?” – Is it terminal agitation, or something else? – How can you find out?Based on what we’ve talked about this far:What would your next step be?
Philip’s medicationsMSContin and Roxinol for dyspneaOxygenLorazepam q4 hours prn for anxietyFurosemide qDay for edemaMetoprolol bid for CHFLisinopril for CHF
Addressing Philip’s DELIRIUMStep 1: reverse the reversibleOpioids rotated Step 2: Non-pharmacologicBenzos weaned Social worker addressed Step 3: PsychopharmAssessment for UTI – PTSDnegative Chaplain was involved Hyperactive periods lessPoor intense BUThydration/nutrition –not reversed due to Mental status continuedgoals of care to wax and waneOxygen increased Haloperidol was started
Philip’s struggleWith these interventions, he awokewith more alertness for a brief afew days.Later he showed signs of activedying: Mottling of hands and feet Irregular breathing patternsHe died peacefully 7 days later. http://upload.wikimedia.org/wikipedia/commons/a/ab/USAF_photographer.jpg
Tending to delirium takes a community volunteers family & friends hospicechaplain caregivers nursing home caregivers
Which are you most likely to use today?a) Recognize the difference between agitation and deliriumb) Use specific tools for assessment (CAM, SQiD)c) Engage all members of the IDT earlierd) Remember the non-pharmacologic interventionse) Know my pharmacology