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Intractable Pain &
Palliative Sedation in
Children
John J. Collins MB BS, PhD, FRACP
Head of Department
Pain Medicine and Palliative Care
The Children’s Hospital at Westmead, Sydney
Australia
[email protected]
INTRACTABLE PAIN and
PALLIATIVE SEDATION IN CHILDREN
Objectives: Definition
Epidemiology of Intractable Pain in Children
Review of practice
Review of literature
Ethical issues
INTRACTABLE PAIN IN CHILDREN AT THE
END OF LIFE: DEFINITIONS
Pain that cannot be alleviated using conventional treatment is
intractable
Intractable pain that does not respond to therapies beyond
conventional practice is refractory
The relief of refractory pain may require a therapy that reduces
conscious awareness
Intractable pain in childhood is unusual and is mostly seen in
the setting of cancer pain and at the end of life
Intractable childhood cancer pain is usually disease related
INTRACTABLE PAIN IN CHILDREN
AT THE END OF LIFE: 1995
A retrospective study published in 1995 examined the opioid
requirements of children with terminal malignancy*
Twelve (6%) of the patients required therapies beyond conventional
opioid dosing
Eleven patients had spinal cord compression, solid tumour
metastatic to the spinal nerve roots, nerve plexus, or large
peripheral nerve
Fifty per cent of the patients had adequate analgesia with either
regional anaesthesia or with high dose opioid infusion alone
Remaining patients required sedation to control refractory pain
*Collins JJ, Grier HE, Kinney HC, Berde CB. Control of severe pain in terminal pediatric
malignancy. Journal of Pediatrics 1995; 126(4):653-657
THE MANAGEMENT OF INTRACTABLE PAIN IN
CHILDREN AT THE END OF LIFE: 1995 →
Practice has become more sophisticated, greater understanding of:
1. Management of the paediatric pain crisis
2. Calculation of opioid “rescue” dosing and dose escalation
3. Opioid switching
4. Management of opioid side-effects
5. NMDA antagonists as new therapeutic options
6. Invasive approaches to pain management in children
Fewer children may need to be sedated to reduce conscious
awareness of intractable symptoms
NMDA RECEPTOR ANTAGONISTS
NMDA- receptor antagonists depress central sensitisation in animal experiment
and in humans*
Dextromethorphan, dextrorphan, ketamine, memantine and amantadine, among
others have been shown to have NMDA-receptor antagonist activities**
The clinical usefulness of some of these medications is compromised by an
adverse effect to side effect ratio
There are no data of their utility in paediatrics, other than procedural pain
management
Clinical usage is increasing, particularly in the setting of severe neuropathic pain
and rapid opioid dose escalation and perceived tolerance
*Eide PK, Jorum E, Stubhaug A, et a. Relief of post-herpetic neuralgia with the N-methyl-D-aspartic acid receptor antagonist ketamine:
a double-blind cross-over comparison with morphine and placebo. Pain 1994; 58:347-354
**Persson J, Axelsson G, Hallin RG, et a. Beneficial effects of ketamine in a chronic pain state with allodynia. Pain 1995; 60:217-222
**Nelson KA, Park KM, Robinovitz E, et al. High dose dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic
neuralgia. Neurology 1997; 48:1212-1218
**Eisenberg E, Pud D. Can patients with chronic neuropathic pain be cured by acute administration of the NMDA-receptor antagonist
amantadine? Pain 1994; 74:37-39
INVASIVE APPROACHES TO INTRACTABLE
PAEDIATRIC CANCER PAIN
Anaesthetic approaches
Experience of using regional anaesthesia for children with intractable
pain is limited.
A retrospective study of children with terminal cancer showed that
regional anaesthesia may be appropriate in a highly select subset of
children*
The indications for regional anaesthesia mostly related to either
dose-limiting side-effects of opioids or opioid unresponsiveness in
patients where pain was confined to one region of the body
Rapid intravenous opioid dose reduction was required in some cases
*Collins JJ, Grier HE, Sethna NF, Berde CB. Regional anesthesia for pain associated with
terminal malignancy. Pain 1996; 65:63-69
EAPC DEFINITION OF
PALLIATIVE SEDATION *
• ‘Therapeutic (or palliative) sedation... Is the
monitored use of medications intended to induce a
state of decreased or absent awareness
(unconsciousness) in order to relieve the burden of
otherwise intractable suffering in a manner that is
ethically acceptable to the patient, family and
health-care providers.’
*
Cherny N, Radbruch L. European Association for Palliative Care (EAPC) recommended
framework for the use of sedation in palliative care. Palliative Medicine.
2009;23(7);581-593.
PALLIATIVE SEDATION
A medical intervention utilised to control symptoms when all other
interventions have failed.
A medical therapy for imminently dying patients.
It involves administration of pharmacological agents with the express
intention of:
• relieving pain
• other symptoms other than pain
• other causes of intolerable suffering
Reduced level of consciousness is anticipated and accepted as an
effect of therapy
SYMPTOM MANAGEMENT
Symptom Intervention
Burden
Intervention
Intervention
REFRACTORY
Symptom
Progression towards end of life
QUESTIONS TO CONSIDER FOR PAIN
AS A SYMPTOM FOR PALLIATIVE
SEDATION
Are primary therapies (chemotherapy, radiation therapy
etc) feasible, and, if so, likely to improve patient
outcome?
Has the opioid dose been titrated up to maximum
tolerated doses?
Have side-effects been addressed with treatment of
alternative opioids?
Have anaesthetic options been considered?
PROPOSED GRADATIONS OF
PALLIATIVE SEDATION
1. Degree:
mild to deep
2. Duration:
intermittent to continuous
From: Morita, T. Proposed definitions for terminal sedation. Lancet, 358,
335-336, 2001
MILD SEDATION
To maintain consciousness so that patients can
communicate with care-givers
DEEP SEDATION
Almost or complete unconsciousness
From: Morita, T. Proposed definitions for terminal sedation. Lancet, 358,
335-336, 2001
INTERMITTENT SEDATION
Some periods when patients are alert
CONTINUOUS SEDATION
To alter a patient’s consciousness until they die
From: Morita, T. Proposed definitions for terminal sedation. Lancet, 358,
335-336, 2001
PALLIATIVE SEDATION IN CHILDREN
Few data
Mainly case reports
Clinical experience in paediatrics limited
Rarely required clinically: optimal palliative
care can effectively manage most symptoms
Ethical issues
CHW review of practice
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•
•
•
Retrospective chart review
January 2008- December 2013
Patients known to Palliative Care Team
Sedation for management of refractory
symptoms
• 1.4% of total cases (3 children)
• Ethical approval by CGU at CHW
RESULTS
Study number
1
2
3
Age
17mo
12yo
16yo
Gender
Male
Female
Male
Diagnosis
AML
Rhabdomyosarcoma
Osteosarcoma with
pulmonary metastases
Comorbidities
Nil
Nil
Nil
Time known to pall care
prior to death
2months
3months
8.5months
Location of care when
sedation commenced
Hospital
Hospital
Hospital
Location of death
Hospital
Hospital
Hospital
Indication for sedation
Pain and respiratory
distress
Pain, anxiety, respiratory
distress
Hallucinations,
respiratory distress
RESULTS
Study number
1
2
3
Type of sedation
(cont/intermittent)
Time between starting
sedation and death
Intermittent Deep
Sedation
Continuous
Continuous
23 days
48 hours
70 hours
Drugs used- opioid
Morphine
Methadone
Morphine
Drugs usedbenzodiazepine
Midazolam
Midazolam
Midazolam infusion
Drugs used- other
Levomepromazine
Ketamine
1x Haloperidol S/C
Route of administration
IV
IV
IV
Consent for sedation
Verbal consent. Multiple
discussions documented
Discussions that sedation
likely to occur with
increased medication
Discussions that sedation
likely to occur with
increased medication
Known goals of care at
time of sedation
Yes. Comfort.
Yes. Comfort
Yes. Comfort.
Adverse events
Nil
Nil
Nil
Clarification of important points:
• Sedation vs Sedative medication for EOL care
• Increased fatigue and sleepiness, and reduced
consciousness can be part of the natural dying
process
• Primary vs Secondary sedation*
* Morita T, Tsuneto S, Shia Y. Proposed definitions for terminal sedation. The Lancet. 2001 July 28; 358: 335-336.
AN ALGORITHM FOR THE IDENTIFICATION OF
SYMPTOM REFRACTORINESS
Any further interventions capable of providing adequate relief?
Yes
No
Is the anticipated acute or chronic morbidity of the intervention
tolerable to the patient?
Yes
No
Are the interventions likely to provide relief within a tolerable
time frame?
Yes
No
“Difficult” symptom amenable to further trials of standard
therapies
C
O
N
S
I
D
E
R
S
E
D
A
T
I
O
N
REQUIRED DOCUMENTATION
1. Goals of care clearly stated: the relief of suffering
must predominate over other considerations
2. Patient, family and treating clinicians are in
agreement
3. Are refractory symptoms identified?
4. Are parameters for sedative titration identified?
PALLIATIVE SEDATION
PHARMACOTHERAPY
Literature anecdotal, guidelines empirical
Opioids:
morphine
Benzodiazepines:
midazolam, diazepam
Phenothiazines:
chlorpromazine
Barbiturates:
pentobarbital
ETHICAL CONSIDERATIONS
Ethical validity is derived form the “Principle of
double effect”
Distinguishes primary intent on relieving
suffering to the potential unavoidable
consequence of a hastened death
CONDITIONS TO INVOKE THE
“PRINCIPLE OF DOUBLE EFFECT”
1.
The treatment is at least neutral (if not beneficial), but
may have untoward as well as beneficial
consequences
2.
The clinician intends the beneficial outcome but the
unforseen outcome may be unavoidable
3.
The untoward outcome is not necessary to achieve
the desired beneficial outcome
4.
Adequate relief of unendurable symptoms is a
compelling reason to place the patient at risk of the
untoward outcome
CONSIDERATION
PAEDIATRIC ISSUE
Discussion about symptom management & decision
making process for palliative sedation
Language must be clear, concise, & if the child is
included, developmentally appropriate.
Interpreters should be used for culturally and
linguistically diverse communities.
Indications for sedation
Refractory symptoms when all therapeutic options
have been implemented or explored
The child is in the terminal phase of the illness
Consent
May include the consent/assent of the child
Selection of sedation method
To accommodate the principle of proportionality. In
particular, consider short half-life medicines if
sedation if to be reversed
Dose titration, monitoring, care
Consider the use of paediatric sedation measures
Discussion about nutrition, hydration, and
concomitant medications
These considerations to be made in discussions with
the family and in the light of benefits versus burdens
Documentation
Documentation to placed in an easily located part of
the medical records
Care and information need of family
This should be on-going
Care of clinicians
This should be on-going
CONCLUSIONS
The relief of intolerable symptoms is a moral imperative
Must distinguish between “difficult” and “refractory”
symptoms
Guidelines for the identification of refractory symptoms
essential
Very small numbers of children need palliative sedation
Guidelines assist in the task of providing adequate relief
whilst maintaining ethical equilibrium
References
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Morita T, Tsuneto S, Shia Y. Proposed definitions for terminal sedation. The Lancet. 2001 July 28; 358:
335-336.
Anquinet L, Rietjens JAC, van der Heide A, Bruinsma S, Janssens R, Deliens L, Addington-Hall J,
Smithson WH, Seymour J. Physicians’ experiences and perspectives regarding the use of continuous
sedation until death for cancer patients in the context of psychological and existential suffering at the end
of life. Psycho-Oncology. 2013 May: 23: 539-546. doi: 10.1002/pon.3450
Levine D, Lam CG, Cunningham MJ, Remke S, Chrastek J, Klick J, Macauley R, Baker JN. Best practices
for paediatric palliative cancer care: a primer for clinical providers. The Journal of Supportive Oncology.
2013 September;11(3):114-125.
Morita T, Tsuneto S, Shima Y. Definition of sedation for symptom relief: A systematic literature review
and a proposal of operational criteria. Journal of pain and symptom management. 2002Oct: 24(4): 447453.
Inghelhrecht E, Bilsen J, Mortier F, Deliens L. Continuous deep sedation until death in Belgium: A survey
among nurses. Journal of Pain and Symptom Management. 2011May5;41(5):870-879.
Anquinet L, Rietjens JAC, Seal C, Seymour J, Deliens L, van der Heide A. The practice of contiuous deep
sedation until death in Flanders (Belgium), The Netherlands, and the U.K.: A comparative study. Journal
of Pain and Symptom Management. 2011July20; 44(1). doi: 10.1016/j.jpainsymman.2011.07.007.
Sinclair CT, Stephenson RC. Palliative Sedation: assessment, management, and ethics. Hospital Physician.
2006March; 42(3):43-46
Morrison W, Kang T. Judging the quality of mercy: drawing a line between palliation and euthanasia.
Pediatrics.2014;133:S31-S36. doi:10.1542/peds.2013-3608F.
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Cherny N, Portenoy R. Sedation in the management of refractory symptoms: guidelines for evaluation and
treatment. Journal of palliative care. 1994, 10:2, 31-38.
Claessens P, Menten J, Schotsmands P, Broeckaert B. Palliative sedation: a review of the research literature.
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Hinds PS, Oakes LL, Hicks J, Anghelescu D. End-of-life care for children and adolescents. Seminars in
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Pousset G, Bilsen J, Cohen J, Mortier F, Deliens L. Continuous deep sedation at the end of life of children in
Flanders, Belgium. Journal of pain and symptom management. 2011;41:449-455.
Deschepper R, Laureys S, Hachimi-Idrissi S, Poelaert J, Distelmans W, Bilsen J. Palliative sedation:why we
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use of sedation in palliative care. Palliative Medicine. 2009;23(7);581-593.
Heath JA, Clarke NE, Donath SM, McCarthy M, Anderson VA, Wolfe J. Symptoms and suffering at the end
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Waldman E and Wolfe J. Palliative care for children with cancer. Nature Review Clinical Oncology.
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management. Journal of palliative care. 1996; 12(3):40-45.
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Paediatric Pain and Palliative
Care Fellowships at CHW
PAIN x2
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PALLIATIVE CARE x2
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