Confusion and Consciousness at the End of Life Sandy Macleod Nurse Maude Hospice Christchurch

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Confusion and Consciousnessat the End of
LifeSandy MacleodNurse Maude
HospiceChristchurch
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Disorders of Consciousness

• Naturally Occurring
• Sleep suspended consciousness
• Dreaming REM sleep
• Epilepsy
• Near Death Experiences
• Lightening up before Death
• Iatrogenic
• Hypnosis focused attention
• Palliative / terminal sedation
• - iatrogenic deep sleep
• General Anaesthesia
• - deep sleep with life support

• Disease Induced
• Terminal Restlessness - ?
• Torpor / Obtundation drowsiness
• Stupor unresponsiveness, aroused by vigorous
  stimulation
• Delirium a disorder of alertness
• Coma unresponsive
• Minimal Conscious State
• aware with minimal ability to respond
• Locked-in-Syndrome (akinetic mutism)
• aware but unresponsive
• Persistent Vegetative State
• awake but not aware
• Brain Death

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Ivan M. Sechenov, 1829-1905
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J. Hughlings Jackson (1835-1911)

• Doctrine of Dissolution
• 
  - CNS evolved on evolutionary principles
• 
  - organic injury results in re-adaptation
  at
• 
  lower and less evolved level of
  functioning
• 
  - more primitive functioning released
• 
  (positive or compensatory
  symptoms)
• 
  

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Consciousness(medical not philosophical
definition) the state of awareness ofthe self
and environment (James, 1890)that state of
an organism that enables cognition to
occur(Lipowski, 1985)
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To be conscious (aware of self and environment)
one needs to beawake, alert, and a little
aroused
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Awakeness the ability to be roused to
awareness of the external worldAlertness a
state of enhanced readiness to receive and
process information and to respond(Arousal
physiological readiness)Awareness the
content of consciousness
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Awakeness the on-off switchAlertness
the volumeAwareness the tuning
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Clinical Assessment of Consciousness

• Descriptive (subjective) levels of
  consciousness,
• 
  - Glasgow Coma Scale (GCS)
• Attention the ability to select, sustain and
  shift focus (indirect indicator of alertness and
  awakeness).
• Inattention, distractability and
  perseveration are objectively measurable at the
  bedside.
• EEG
• Eye Tracking Technology (ETT)

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Levels of Consciousness

• Full consciousness (awake, alert, attentive)
• Torpor
• Delirium - prodromal
• - hyperactive
• - mixed motoric
• - hypoactive
• Stupor
• Coma

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Bedside Tests of Attention

• Orientation in time
• Multiples of 2 (up to 256) / 100-7 / Count 20-1
• Spelling and reversal
• Short-term memory recall
• (examiners name, 3 paired objectives)
• Dysgraphia

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Delirium(Brain Failure)
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Delirium is a disorder of alertnessthe volume
or level of consciousness
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Definition of Delirium (DSM IV)

• Disturbance of consciousness or impaired
  attention
• Change in cognition (such as memory deficit,
  disorientation, language disturbance, perception)
• Rapid onset, fluctuating symptoms
• A general medical condition judged to be
  aetiologically related

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Clinical Features of Delirium

• Rapid onset, fluctuating (sundowning, lucid
  periods)
• Impairment of
• - attention recent memory,
• - orientation (time, misidentification of
  others),
• - thinking (muddled, fleeting delusions),
• - motoric function (hypoactive, hyperactive),
  
• - sleep-wake cycle (reversal),
• - affect (frightening and fearful (for all),
• - perceptions (hallucinations (visual))
• Danger to self and others (a Medical Emergency)

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Sundowner slide
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Clinical Assessment of the confused / muddled

• History rapid nocturnal onset, fluctuating
  symptoms
• Level of consciousness fluctuating, motoric
  activity, torpor, stupor
• Tests of attention inattentive, distractable
• Physical status febrile, cyanosed, anaemic .
• Confusion Assessment Method (CAM)
• Macleod,
  Pall Supp Care 2006

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Prevalence of Delirium

• Commonest mental disorder Manos 1997
• Under-recognised particularly hypoactive
• 
  Perez 1984,
  Meagher 2001
• Under-diagnosed non detection rates 33-66
  Inouye 1994
• Under-treated Rockwood 1994
• Mis-treated

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Delirium in Terminal Illness

• 25-88 of dying
• 42 on admission to PCU,
• 43 developed delirium,
• 88 died delirious
• 
  Lawler, Gagnon 2000

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Why do the symptoms of delirium fluctuate?
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Deliriant Thresholdafter Sherrington 1906,
after Goldscheider 1898

• A clinical point at which symptoms are
  expressed
• Determined by
• - the strength of toxin v. resistance of
  host
• - environmental modulating influence
  (Lipowski 1980, Arie 1981)
• - biological flux (gamma rhythms)
• - Dissolution Theory of Hughlings Jackson

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Deliriant Threshold

• Low if
• noxious insult
• aged, damaged or immature
  brain
• noisy, nocturnal environment
• High if
• weak insult
• healthy adult brain
• quiet, familiar environment
• 
  Inouye,Charpentier 1996

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Aetiology of Delirium

• Organic
• Multi-factorial and Cumulative
• (in palliative care settings)
• ? reversible in 50 (opioids, dehydration)
  (Lawler, 2000)

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Opioid- Related Delirium

• prevalence ? 10
• protective against post-operative delirium
  (Morrison, 2003) - 13 (Riley, 2006)
• ? renal function (morphine)
• ? the disease or/and the drug
• opioids are (mildly) anticholinergic (Agar,
  2009)
• pethidine gt morphine gt oxycodone gt methadone,
  fentanyl
• associated with rapid escalating and high doses
• intrathecal gt parenteral gt oral

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Opioid Switching

• Nocioceptive cancer pain (neuropathic excluded)
• Morphine responsive 138 of 186 pts (74)
• For 47 (25) morphine ineffective or intolerable
  (delirium 13, drowsiness 14.5, nightmares 5,
  nausea 5)
• 37 of the 47 (79) responded to oxycodone
• Another switch effective for a further 4 (9)
• In total 96 responded to opioid
• Riley,
  Supp Care Cancer 2006

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Dehydration at End of Life and Delirium

• Does dehydration cause delirium?
• Decreased fluid intake and increased loss,
  dehydration v. volume depletion, renal
  functioning, thirst.
• Hydration improved delirium symptoms in 30-70
  (Gagnon, 2000), no effect (Cerchietti, 2000,
  Morita, 2003)
• Is there a role for hydration at the end of
  life? Dalal, Bruera Curr Opin Supp Pall
  2009

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Visual Hallucinations in Palliative Care

• Prevalence 47 hospice in-patients
• Diff. Diagnosis
• bereavement pseudo-hallucinations
  (50-60 widowed)
• - Charles Bonnet S. (10-30 visually
  impaired)
• - delirium (occur in 40-70)
• - medications (opioids, tricyclics)
  hence morphines name
• - .
• blaming opioids is too simplistic
• 
  Fountain, CME Cancer Med 2002

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Delirium- clinical course

• Prodromal symptoms
• Duration median 8 days,
• less if hyperactive subtype (6 days) Manos
  1997
• Delay to clinical recovery
• Recovery preceded by deep sleep Hippocrates
• ? full cognitive recovery
• Amnesia (patchy) of illness
• Distressing recall (50) Brietbart 2002, PTSD

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Delirium - Complications

• Accidental injury (to self and others)
• Residual cognitive decline
• Distressing recollections /ASD / PTSD
• ( for patient and relatives)
• Death due to the cause of delirium
• - exhaustion
• - suicide 7 Curran 1937

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Management of Delirium

• The general principles of the management of
  delirium have prevailed since antiquity and are
  still applicable today Lipowski, 1980
• Bloodletting has been (mostly) abandoned
• Pharmacology has been refined

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Aims of Management of Delirium

• Extinguish / minimise noxious influences
• Raise the deliriant threshold and lenghten the
  lucid periods
• Symptomatic relief

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Principles of Management

• 1 Prevention
• 2 Safety
• 3 Treat causes
• 4 Symptom relief
• 5 Environmental stategies
• 6 Psychological strategies
• 7 Pharmacological strategies

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Prevention of Delirium

• Maintain highest possible deliriant threshold
• - minimise causative organic insults
• - strenghten host
• - bland / simple sensory environment
• - ? prophylactic neuroleptics (eg. quetiapine,
  anti-emetics)

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Safety and Delirium

• Single room
• Remove weapons
• Adequate(night)staff
• Mattress on floor
• Physical restraint
• Medico-legal
• Defusing/calming
• Collusion- wandering
• Emergency sedation

• - not for psych. transfer
• - staff assaults
• - utilise relatives
• - dangers of bed-rails
• - 4 1,MI,DVT,arrhythmia
• - common law v.MHA
• - no catharsis
• - patience, skill
• -

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Medical Treatment of Delirium

• Delirium is secondary to and symptomatic of
  systemic disease affecting the brain thus
  treatment should logically be directed at the
  underlying condition
• 
  Galen (AD 129 c.200/210)
• Need to treat underlying medical condition but to
  also provide symptomatic treatment regardless of
  the cause.
• Hirsch 1899

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Symptom Relief - Delirium

• antipyretic
• oxygen
• blood transfusion
• analgesia
• corticosteroids
• bisphosphonates
• glucose
• glasses, hearing aids
• ? hydration
• laxative

• - fever
• - hypoxia
• - anaemia
• - pain
• - raised ICP
• - hypercalcaemia
• - hypoglycaemia
• - sensory deprivation
• - 1-2 litres SC overnight
• - constipation

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The Environment and Delirium

• home v. institution
• sensory restriction / deprivation v.
  overstimulation
• limited interpersonal interactions
• constancy and familiarity (location, people)
• orientating aids (clocks, calenders, personal
  objects)
• moderate sensory balance
• - noise
  levels (lt45db during day,lt 20db at night)
• - well
  lit
• -
  temperature (21-23.8C)
  Meagher 2001

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The Environment and Delirium

• My wallpaper and I are facing a duel to the
  death. One or other of us has got to go
• 
  Oscar Wilde,
• 
  dying of meningitis,
• 
  Paris, 1900

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Psychology and Delirium

• One must not speak in his presence as if he
  could not understand what is being said.
• Persons and objects that the patient dislikes
  should be kept away. A person whom he likes
  should stay with him, speak to him gently, and
  thus help to calm and orient him.
• 
  Greiner 1817

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Psychological Interventions in Delirium

• Simple and effective
• Utilise lucid periods
• (Some) relatives help
• Supportive not exploratory
• Cognitive testing aggravates Stedeford 1978

• Reassure
• Orientate (use names Arie 1981)
• Explain
• Clarify
• Repeat
• Slow,clear speech
• Foster competency and autonomy
• Counter-projective dialogue unnecessary

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Relatives as Attendants for Delirious Patients

• Barrough (1596) advised it.
• Dependant upon the intuitive skills of the
  relative and their own mental state in terminal
  care some are too distressed.

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Pharmacology of Delirium

• Rest and sleep in the delirious patient should
  be aided by the administration of poppy boiled in
  oil
• Aretaeus of
  Cappadocia (AD c.81 c.138)

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Pharmacology in Delirium

• Only if other measures are ineffective
• Combine with other measures
• More likely utilised in hyperactive deliria
• Effective in both hypoactive and hyperactive
  subtypes

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Definitions

• Tranquillisation (L. tranquillus)
• - to make calm, quiet,
  serene, placid
• Sedation (L. sedare to sit, settle)
• - to immobilise, compose,
  sober, soothe
• Hypnosis (Gk. hupnos sleep)
• - to induce sleep, to
  hypnotise
• Anaesthesia (Gk. aisthesis sensation)
• - to render insensible

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Pharmacological Management of Delirium

• Antidotes
• Tranquillisation
• Sedation
• Anaesthesia

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Management of DeliriumPharmacological
Evidence-Base

• Anecdotal clinical experience vast
• Placebo controlled trials nil
• Comparator trial haloperidol and chlorpromazine
  more efficacious than lorazepam in 30
  hospitalised delirious AIDS patients
  Brietbart et al 1996
• Cochrane Review insufficient data
• 
  
  Britton,Russell 2000

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Anticholinergic Deliria and Antidotes

• Medications, often anticholinergics, causative in
  20-40 cases of delirium
• 
  
  Meagher 2001, Agar 2009
• Medications in atropine equivalents
• codeine 0.11, warfarin 0.12, prednisolone
  0.55 Tune 1992
• 
  
  
  Antidotes
• physostigmine 0.5-2.0mg IV,
• cholinesterase inhibitors eg. rivastigmine

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Tranquillisation of Delirium Antipsychotic
Medications(major tranquillisers, neuroleptics)

• Phenothiazines
• (chlorpromazine, levomepromazine
  methotrimeprazine)
• Butyrophenones
• (haloperidol) (one of 20 essential drugs in
  pall.care Dickerson 1999)
• Atypical Neuroleptics
• (risperidone, olanzapine, quetiapine,
  clozapine)

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Major Tranquillisers and DeliriumRelative
Contraindications

• DTs benzodiazepines, alcohol
• Post-ictal - benzodiazepines
• Hepatic Encephalopathy
• - flumazenil Bostwick 1998
• Lewy Body Dementia
• - cholinesterase inhibitors
  donepezil, Kaufer 1998

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Haloperidol in Delirium

• Medication of first choice
• Unusual pharmacokinetics
• Mechanism of action - ?
• - not dopamine blockade
• - anaesthetises the Ascending Reticular
  Activating System

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Dr Paul Janssen 1924-2003

• diphenoxylate -1956
• haloperidol -1957
• levamisole
• miconazole
• ketoconazole
• fentanyl
• risperidone

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Haloperidol pharmacokinetics
Settle, Ayd 1983

• Oral bioavailability - 60, parenteral 100
• Oral - subjected to first pass metabolism
• Oral Parenteral 2-3 1
• Serum peak levels
• oral 4-6 hours,
• IM 20-40 minutes,
• IV (SC) 2-20 minutes
• Half-life - 16 hours (regardless of route of
  administration)
• Steady state -1week haloperidol,1 month
  reduced haloperidol

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Haloperidol Adverse Effects

• Neurological (extra-pyramidal)
• - acute dystonia
• - akathisia
• - parkinsonism
• - tardive dyskinesia
• Cardiological
• - hypotension
• - QT prolongation
• ? Sedation ( the stimulant tranquilliser)

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Reduced Haloperidol

• The major active metabolite
• 10-20 clinical effect of haloperidol
• Concentrations correlate with incidence and
  seriousness of EPS side-effects
• 
  Brockmoller 2002
• 
  

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Haloperidol Neurological Adverse Effects

• Peak at oral dose range 5 20 mg
• Correlation with reduced haloperidol
• Oral undergoes first pass metabolism resulting in
  increased reduced haloperidol
• Rare with parenteral haloperidol

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Oral haloperidolcommonakathisiaparkinsonism in
the elderlyrareacute dystonias in
adolescentsParenteral haloperidolneurological
ADRs very rare(except AIDS, LBD,
?schizophrenia)In delirium 0 (Adams), 4
(Lawson), 7 (Menza), plus BDZ 0 (Menza)
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HaloperidolNeurological adverse effects-risk
factors

• Dosage 5-20mg/day Ayd 1975
• Extremes of Age
• Oral c.f. parenteral administration
• 
  Menza 1987, Maldonado 2000
• Lengthy duration of administration
• Pre-existing brain impairment
• (dementia, AIDS, schizophrenia)

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QT Prolongation(torsades de pointes arrythmia)

• Genetically long QTc (gt430msecM,450F)
• Electrolyte imbalance (hypokalaemia)
• Cardiac disease(AV block,MI)
• Female gender
• Older age
• Medication AOR (adjusted odds ratio)
• haloperidol 3.6, thioridazine 5.3,
  risperidone 1.8, droperidol 6.7, TCAs 4.4, SSRIs
  1.7, BDZs 1.0
• 
  Reilly 2000

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Haloperidol in Delirium

• Medication of first choice
• Parenteral route preferable
• Doses gt 20mg / 24hours unusual
• Maximum dose 250mg / 24hours IV
• Prophylactic anticholinergics not indicated
• Benzodiazepine augmentation sedative, minimises
  EPS side-effects

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Haloperidol Dosing Regime in Deliriumadapted
from Mass.Gen.Hosp.

• Starting dose (PO, SC, IV, IM, PR)
• - mild 0.5mg, moderately severe 1.5mg,
• very severe 5.0mg
• Titrating dose
• - double starting dose and repeat 30-45min
  until clinical control achieved
  
• Maintenance dose
• - 50 of dose required in first 24 hours
• Withdraw dose - as causes corrected

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Atypical Neuroleptics in Delirium

• risperidone
• olanzapine
• quetiapine
• clozapine
• ziprasidone
• ? efficacy
• ? availability of parenteral preparations

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Sedation in Delirium

• If behavioural control not achieved with
  environmental, psychological interventions and
  haloperidol
• Enhances depth of consciousness impairment
• - aggravates delirium
• - deep sleep must be achieved

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Anaesthesia and Delirium

• Very rarely indicated
• Proprofol

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Pharmacological Management of Delirium - other

• Opioids analgesia, sedative in naive
• Psychostimulants
• Alcohol (DTs)
• Benzodiazepines (hepatic encephalopathy)
• ECT
• Mianserin, trazodone
• Nicotine
• Paraldehyde
• Barbiturates

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Dying Crazy May Be Preventable
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Twilight States of Consciousness

• Lightening up before Death
• Near Death Experiences
• Near to death enhanced perception to light
  and cognitive powers are reported in the lay
  press and following survival mystical and
  religious interpretations may be proferred.

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We have all observed the mind clear in an
extraordinary manner in the last hours of
life.we have seen it become capable of
exercising a subtle judgement.the clearing up
of his mind was a mortal sign, a lightening up
before death Sir Henry
Halford, 1842
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Instances occur, and not very rarely, where the
delirium ceases, and the mind again for a time
becomes clear and sensations key,to be
followed, however, ere long by a return of
delirium, or may be of coma, or rapid sinking
of all bodily powers and speedy death
William Munk, 1887
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Lightening Before Death

• 100 consecutive inpatient deaths
• (Nurse Maude Hospice)
• 4 definite lightening ups in 48 hours before
  death

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THE GREEN FLASH
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Immediately before deaththe need for analgesic
medication decreasedand many patients exhibited
a short increase of vitality,appreciated food
again,and appeared to be generally improved
Witzel, BMJ 1975
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Palliative Sedation

• Terminal Sedation
• Sedation of Intractable Distress of the Dying
• Slow euthanasia
• Backdoor euthanasia
• Designer euthanasia
• ? Physician Assisted Euthanasia (PAE)
• ? Physician - Assisted Suicide (PAS)

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Quality of Death

• euthanasia (eù?ávaros)
  dying easily or happily
• dysthanasia (d?s?ávaros)
  a hard, bad, unlucky death
• 
  (Eugenios Voulgaris, 1804)

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Quality of Death

• Death invariably peaceful
• 
  Brodie 1854, Osler 1904
• 36 of patients dying of malignancy experience
  difficulties in last 48 hours and 8.5 had
  non-peaceful deaths
• 
  Lichter, Hunt 1990
• ? quality of death from cancer in 2009

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Palliative Sedation

• the intentional suppression of consciousness to
  control refractory symptoms
• the intent is to relieve an unendurable symptom,
  suffering to kill the symptom
• the intent is not to kill (murder) the patient

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Principle of Double Effect Thomas Aquinas

• An action with two or more possible effects,
  including at least one possible good effect and
  others that are bad, is morally permissible if
• the action must not be immoral in itself
• bad effect may be foreseen but must not be
  intended
• the action must not achieve the good effect by
  means of the bad effect
• the action must be undertaken for a
  proportionately grave reason

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Palliative Sedation-Prevalence

• 25 of dying patients in palliative care settings

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Palliative Sedation Clinical Indications

• Irreversible delirium
• Profound dyspnoea
• Intractable pain
• Refractory nausea / vomiting
• Acute haemorrhage
• ? Emotional anguish

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Palliative Sedation and Hastened Death

• There is no association between the doses of
  opioids and sedatives on the last day of life and
  survival (from hospice admission to death).
• Good, Ravenscroft, Cavenagh.
  Intern Med 2005
• There is no evidence that the initiation, or
  increases in doses of opioids or sedatives, is
  associated with precipitation of death
• Sykes,
  Thorns. Lancet Onc 2003

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Palliative Sedation Pharmacological Options

• morphine
• haloperidol
• levomepromazine (Nozinam)
• midazolam
• clonazepam
• flunitrazepam
• barbiturates

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Palliative Sedation Pharmacological Preference

• clonazepam
• levomepromazine
• barbiturate

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Palliative Sedation Method

• Benzodiazepine
• midazolam (60mg/24hrs/SC) v. clonazepam
  (4mg/24hrs/SC)
• Titrate to clinical effect deep sedation
• Risk of behavioural disinhibition
• Risk of respiratory depression
• Risk of falls, DVTs, decubitus ulcers
• Loss of efficacy
• (midazolam gt 240mg, clonazepam gt8mg
  parenteral / 24hrs)

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Palliative Sedation

• A humane, consented, high-risk management option
  of last resort for profoundly distressing and
  intractable symptoms at the end of life
• It is not PAE / PAS or the hastening of the end
  of life

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The End