PALLIATIVE PALLIATIVE SEDATIONSEDATION

Myth, Mercy or Myth, Mercy or Euphemism?Euphemism?Dr Nigel Sykes

St Christopher's HospiceLondon

Nova Scotia Hospice Palliative Care Association Nova Scotia Hospice Palliative Care Association Annual Conference 2011Annual Conference 2011

A Confusion of TermsA Confusion of Terms

Terms:Palliative sedationTerminal sedationEarly terminal sedationPalliative sedation therapyPrimary sedationSecondary sedationProportionate sedationControlled sedation for intractable

distress in the dyingSudden sedationContinuous deep sedation

A Manifold Definition of A Manifold Definition of Palliative Sedation Palliative Sedation

(Adapted from Jones, 2011)(Adapted from Jones, 2011)

Palliative Sedation is the use of sedatives that is either continuous or intermittent; deep or mild; the primary or secondary pharmacological effect; proportionate or disproportionate to ‘refractory symptoms’ ; which include or do not include ‘existential distress’; in a patient who is or is not imminently dying; at the request or not of the patient; who intends or does not intend to be unconscious until death; with the doctor also intending this or not; withholding or not withholding nutrition and hydration; with or without an advance refusal; such that this protocol does or does not actually hasten death; and is intended or is not intended to do so by the patient; and is intended or is not intended to do so by the patient

This yields 4,782,969 possible definitions of Palliative Sedation…

Is the likely clinical effect of Is the likely clinical effect of thisthis Definition… Definition…

Palliative Sedation is the use of sedatives that is intermittent; mild; proportionate to ‘refractory symptoms’ ; in a patient who is imminently dying; not withholding nutrition and hydration

……the same as the likely the same as the likely clinical effect of clinical effect of thisthis

Definition?Definition?Palliative Sedation is the use of

sedatives that is continuous, deep, disproportionate to ‘refractory symptoms’ ; in a patient who is not imminently dying but is intended to be unconscious until death; withholding nutrition and hydration

A Euphemism for Euthanasia?

A Confusion of PurposesA Confusion of PurposesSedation can mean:The giving of sedatives for specific

symptom control, e.g.SeizuresDelirium in the absence of correctable

factorsA treatment for insomniaThe attempt to make a patient

unaware of a intractable symptom by reducing their conscious level

An expert survey achieved only 40% agreement with a single definition of

sedation (Chater, 1998)

What is an intractable What is an intractable symptom?symptom?

An "intractable" symptom is one:that does not respond to available

treatment orfor which the treatment is

unacceptable to the patient because of: insufficiently rapid action or

excessive side effects (Cherny and Portenoy, 1994)

Sedation is used significantly more often by doctors who predict that a symptom will

be intractable than by those who actually try all the treatments (Morita, 2004)

Reasons for sedationReasons for sedation

Multicentre study of 387 terminally ill patients

Haemorrhage 0.8%Distress 1.8%Pain 1.8%Nausea and vomiting 2.3%Breathlessness 6.5%Delirium 15.2%

(Fainsinger et al., 2000)

How often is sedation used How often is sedation used in Palliative Care?in Palliative Care?

Reports of the proportion of patients who require sedation in the closing

days of life vary widely:1% (Fainsinger, 1998) 88% (Turner et al., 1996)

This situation is not getting any better:Prospective study of the use of all depths and

lengths of sedation in eight palliative care units showed a rate of 7.5%

(Claessens et al, 2011)

Retrospective study from one palliative care unit of the use specifically of continuous deep sedation showed a rate of 43%

(Rietjens et al., 2008)

Sedation in Palliative Sedation in Palliative CareCare

The use of sedative drugs has always been a part of Palliative Care at the end of life:For mental distress (but only as an adjunct

to the giving of properly attentive time) (Saunders, 1960)

For anxiety or agitated confusion (Saunders, 1965)

Opiates should not be used as sedatives (Saunders, 1958)

“It should hardly ever be necessary to use the very heavy sedation that completely smothers the patient’s

personality, although many who see these patients only occasionally do not believe that it is possible to avoid this”

(Saunders, 1967)

““Very heavy sedation that Very heavy sedation that completely smothers the completely smothers the

patient’s personality”patient’s personality”The crux of ethical and clinical

concern seems to be whether sedative use: Obliterates the patient’s personality

and destroys the possibility of further emotional and spiritual development

Kills the patient

Sedatives can do both these things

Sedation for intractable Sedation for intractable symptomssymptoms

The paramount moral obligation is to relieve suffering

“A doctor who leaves a patient to suffer intolerably is morally more reprehensible than the doctor who performs euthanasia”

Twycross, 1996

Mercy

Principle of Double EffectPrinciple of Double Effect(The Get-out Clause)(The Get-out Clause)

A harmful effect of treatment, even resulting in death, is permissible providing that it: was not intended and arises as a side effect of a beneficial action and the harmful effect was not the means of achieving the beneficial

effect

But if we need to invoke the Principle of Double Effect does this suggest we are routinely shortening patients’ lives by sedation?

Truth or Myth?

Classification of end of life Classification of end of life care sedationcare sedation

(Broeckaert, 2000)(Broeckaert, 2000)

Mild Intermittent

Acute

Deep Continuous Non-acute

Classification of end of life care Classification of end of life care sedationsedation

(Morita, Tsuneto and Shima, 2001)(Morita, Tsuneto and Shima, 2001)

Mild Intermittent

Primary Pain No organ failure

Deep Continuous Secondary

Psychological distress

Organ failure

How is depth of sedation How is depth of sedation assessed?assessed?

Glasgow Coma Scale (Teasdale and Jennett, 1974)Communication Capacity Scale (Morita et al., 2001)

Consciousness Scale for Palliative Care (Goncalves et al.,2008)

Physicians’ unsubstantiated report

Assessment of the deepest sedation requires infliction of pain: Supra-orbital pressure (GCS) Pain (unspecified method) or change in position

(CCS) Trapezius pinch (CSPC)

How willing are palliative care staff to carry out these assessments routinely?

Depth of SedationDepth of SedationIt has been suggested that the depth of

sedation tends to increase as death approaches45% of patients originally given ‘mild’

sedation had ‘deep continuous’ sedation by two days before death (Claessens et al., 2011)But this is based on only 9 patients and it is not

clear how the sedative doses changed in the interim

How different is this from the natural trajectory of dying?50% of Palliative Care not receiving

sedatives are unable to manage complex communication five days before death

(Morita et al., 2003)

Comparison of percentage of patients spontaneously awake in sedated and non-sedated groups during the last week of life

(n=23) (from Fainsinger et al. 1998)

0

20

40

60

80

100

6 5 4 3 2 1 0

Days before death

% Sedated

Non-sedated

Comparison of percentage of patients spontaneously awake in sedated and non-sedated groups during the last week of life

(n=124)(from Kohara et al. 2005)

010

203040

50607080

90100

6 5 4 3 2 1 0Days before death

%

Sedated

Non-sedated

Comparison of percentage of unrousable patients in sedated and non-sedated

groups during the last week of life (n=23) (Fainsinger et al, 1998)

0

20

40

60

80

100

6 5 4 3 2 1 0

Days before death

%

SedatedNon-sedated

Comparison of percentage of unrousable patients in sedated and non-sedated groups

during the last week of life (n=124) (Kohara et al, 2005)

01020304050607080

6 5 4 3 2 1 0

Days before death

%

SedatedNon-sedated

What is in the Name?What is in the Name?

The root of the word sedation is the Latin sedatio meaning ‘soothing’ or ‘allaying’

The clinical purpose of sedative drugs in palliation is the reduction of irritability or agitation, i.e. the relief of distress

Sleep is not the intention but may occur either:if a high enough sedative dose is required

to relieve the distress or If a tired, ill patient is enabled to be

comfortable and relaxed

ContinuousnessContinuousness

Sedation is a response to a symptomContinuous symptoms need continuous

relief See use of regular morphine in chronic pain for

details30% of patients receiving sedatives do so

only on an ‘as required’ basis Median 2.5mg midazolam on a median of 2

occasions (Dunn et al., 2008)Liverpool Care Pathway Guidance suggests

use of a continuous subcutaneous infusion if two or more ‘as required’ doses of sedative have been given in 24h (NCPC, 2006) So ‘as required’ rapidly becomes ‘continuous’

Continuous sedative administration is neither rare nor necessarily sinister

ProportionalityProportionalityThere is a growing consensus that the

essence of sedative use in Palliative Care is proportionality

Morita, Tsuneto and Shima, 2002De Graeff and Dean, 2007Brockaert and Claessens, 2009Cherny and Radbruch, 2009Hasselaar, Verhagen and Vissers, 2009 Quill et al., 2009

But not everywhere. The Dutch National Guideline on Palliative Sedation speaks of proportionality but assumes: The aim is to reduce consciousness The patient should be within 2 weeks of dying Administration of fluids should be stopped A doctor should be present at initiation of

sedation(KNMG 2005/2009)

Proportionate Responses are Proportionate Responses are key to Palliative Care key to Palliative Care

PracticePracticeThe mode of use of sedatives is

analogous to that of other symptom control measures, such as opioids for pain:A low initial dose is titrated higher

against the response until distress is relieved, i.e. the dose used is proportional to severity of distress

Relief of distress is the end-point, not a particular level of consciousness

What is a Proportionate What is a Proportionate Dose of Sedative?Dose of Sedative?

Midazolam is the most commonly used sedative in Palliative Care (Sykes and Thorns, 2003a)

Mean midazolam doses reported range from 22 to 70mg/24h (Mercadante et al., 2009) But individually as high as 240mg/24h

In our study of 238 patients: Overall mean midazolam dose was 25.7 mg/24 h Mean midazolam dose for patients receiving

sedation throughout the last week of life was 54.5 mg/24 h (Sykes and Thorns, 2003b)

Effect of Sedation on Effect of Sedation on Palliative Care patients’ Palliative Care patients’

SurvivalSurvivalStudy With

sedationWithout sedation

Stone, 1997(UK)

18.6 days 19.1 days

Ventafridda, 1990 (Italy)

25 days 23 days

Chiu, 2001(Taiwan)

28.5 days 24.7 days

Sykes, 2003b (UK)

38.6 days 14.2 days

Kohara, 2005(Japan)

28.9 days 39.5 days

Duration of SedationDuration of Sedation

Mean duration of sedation estimated to be 2.5 days (range 1.3-3.9)Based on ten studies, totalling

1,900 patients (Porta Sales, 2001 updated)

Suggests that sedation is generally a response to symptoms

associated with the onset of dying

Midazolam use at St Midazolam use at St Christopher’sChristopher’s

In a random recent month:55 patients died51 (93%) had at least one dose 35 (64%) had a continuous s.c. infusion14 (40%) of infusions started within 48h of

death14 (40%) of infusions started 3 to 7 days

before death All had either already stopped eating or ate until 3 to

5 days before death7 (20%) infusions lasted between one week

and one month Of these patients five continued to eat until 3 to 5

days before death The other two had gastrostomy feeding

Was our sedation rate 93% or zero?

Case History 1Case History 1

58 year old man with astrocytomaGeneral condition noted to be

deterioratingDeveloped an acute onset of

violent agitation and paranoiaMidazolam 20mg given i.m. stat

followed by 55mg/24h by s.c. infusion

Died 55 hours later

Case History 2Case History 2

70 year old woman with lung cancer and a previous history of schizophrenia

Admitted because of general deteriorationDeveloped delusions and progressive

agitation unresponsive to haloperidol doses up to 12mg per day

Over 24h she received 125 mg levomepromazine and 60 mg midazolam by s.c. infusion, but also another 60 mg midazolam and 200 mg levomepromazine in s.c stat doses for continuing agitation

At the end of this period her breathing was noted to be noisy. 200 mg phenobarbital was given s.c. and the patient died 6 h later.

And yet some will ask:And yet some will ask:

Is sedation used to cover up potentially remediable delirium?73% of delirium in palliative care is

irreversibleLife expectancy of patients with irreversible

delirium is under 17 days (Leonard et al., 2008)

What about provision of hydration and nutrition?This is a separate decision, but the great

majority of patients who receive sedatives already have minimal oral intake

What about sedation for existential distress? Does not correlate with physical deterioration

Use of sedatives in existential or Use of sedatives in existential or psychological distresspsychological distress

Hard to tell if such distress is really intractable Level of distress can be variable and idiosyncratic Standard treatments have low morbidity Intractability can only be decided by a

multiprofessional clinical team skilled in psychological care who know both patient and family and have made repeated assessments

Team access to psychiatry, chaplaincy and ethics is required (Cherny and Radbruch, 2009)

Some sedative use may be helpful, as may respite sedation to provide periods of ‘time out’

But the induction of sleep for extended periods should be a truly exceptional occurrence

ConclusionsConclusions

‘Sedation’ continues to mean different things to different people

In specialist palliative care units use of sedatives in the last days of life is not associated with shortened survival overall

Most use of sedatives is for the management of restlessness and confusion occurring as part of the process of dying

Impaired consciousness is common at the end of life with or without sedatives

The aim of sedative use is to relieve distress, not to induce sleep

The key to ethical use of sedatives is proportionality, whatever the indication

If Palliative Sedation is If Palliative Sedation is approached properly…approached properly…

It will be an act of Mercy for our patients whose distress cannot be relieved by other means

It will be a Myth that it shortens patients’ lives

And soIt will not be a Euphemism for

Euthanasia