HYDRATION & NUTRITION

And

NAUSEA & VOMITING

IN

PALLIATIVE CARE OF CHILDREN

Mike Harlos MD, CCFP

Medical Director, WRHA Palliative Care and St. Boniface General Hospital Palliative Care

Section Head, Palliative Care, University of Manitoba Dept. of Family Medicine

TREATMENT / INTERVENTION CONSIDERATIONS

• What are the goals of the treatment?

• Whose goals are they, and are they consistent with those of the patient?

• Is it possible to achieve the goals?

• What are the:

– Positive effects vs. Side effects (clinical assessment by health care team)

– Benefits vs. Burdens (experiential interpretation of positive and side effects by patient / family)

• Is there enough reserve to tolerate the treatment?

The “Path of Least Regret”

• How will families look back on the decisions for care?

• When family uncertain or ambivalent about “doing something” vs. “not doing something”, consider leaning toward “doing” if it is reasonable (eg. hydration)

• Power imbalance between health care professionals and patient / family… be perceptive about when this might be influencing the dynamic of decision-making

• Controversial topic; there is no consensus among the palliative care community

Hydration in the Terminal Phase

1. Morita T, Tei Y, Tsunoda J, Inoue S, Chihara S.Determinants of the sensation of thirst in terminally ill cancer patients.Support.Care Cancer 2001;9:177-86

2. Burge FI. Dehydration symptoms of palliative care cancer patients. J.Pain Symptom.Manage. 1993;8:454-64.

• Conflicting literature regarding whether there is1 or is not2 a correlation between dehydration and thirst in the dying

• There are specific circumstances where rehydration can be very helpful:

Opioid-induced neurotoxicity Hypercalcemia Reversible bowel obstruction

• In severe hypoalbuminemia, may aggravate peripheral edema

• No evidence for hydration causing ↑ terminal secretions

•Each circumstance is approached individually with regards to goals

Hydration ctd

Hypodermoclysis• Effective, simple route for hydration when venous access

compromised

• In adults usually give 30 - 50 ml/hr NS; there are reports of adding KCL

• Adverse reactions include local edema, cellulitis, discomfort at insertion site

• Use indwelling small gauge cathalon rather than butterfly needle

• Very little literature regarding pediatrics:

1. Steffey JM Hypodermoclysis in infants and children.J Iowa State Med Soc. 1963 Jul;53:393-6

2. Vyskocil JJ, Kruse JA, Wilson RF. Techniques for vascular access when venous entry is impossible. Route depends on urgency and the agent to be administered. J Crit Illn. 1993 Apr;8(4):539-45

NUTRITION

IN THE

DYING CHILD

Proposed NomenclatureBechard L.J., et al Nutritional Supportive CarePrinciples & Practice of Pediatric Oncology 4th Ed; Edited by Pizzo & Poplack

Wasting: • Involuntary weight loss

• Seen in anorexia nervosa, cancer, HIV, and others

• First see decline in body fat, then in body protein stores (fat-free mass; lean body mass)

• Energy repletion usually successful in restoring nutritional status

Cachexia: • Involuntary loss of fat-free mass in the setting of minimal or no overall weight loss

• Seen in cancer, critical illness, HIV, other metabolic stress

• Patients may be of normal weight yet malnourished

• Loss of lean body mass is associated with decreases in strength, immune function, pulmonary function, as well as increased disability and death

• Nutritional support may not reverse catabolic effects of underlying condition

“The cancer anorexia-cachexia syndrome is extremely

common in children with advanced cancer and is

frequently associated with a patient’s decline and death.

Its cause is multifactorial, and it is most often

irreversible, even in the face of hyperalimentation or

vigorous nutritional support”

Wolfe J., Grier H.E., Care of the Dying Childin Principles and Practice of Pediatric Oncology4th Edition; Philip A. Pizzo and David G. Poplack, Editors

Feeding Options

Oral • May require soft diet if mucositis present

• Caloric supplementation if required

• “Normal”

Enteral (Tube)

• Nasogastric or percutaneous gastrostomy

• Demonstrated improved weight gain in newly Dx pediatric cancer patients and in BMT settings

• Cost savings over TPN

Parenteral (TPN)

• Of demonstrated benefit in BMT patients

• Uncertain / unproven benefit in other cancer settings

• Risks include infection, hepatic toxicity, metabolic abnormalities;

• Careful patient selection and close monitoring required

Loss of AppetiteLook for Reversible Causes

• Pain

• Anxiety

• Nausea / Vomiting

• Thrush in the mouth or esophagus

• Constipation

• Drugs

• Depression

Goals of Nutrition and Fluid Management in the Dying Child

• Alleviate any hunger and thirst

• Reduce anxiety about intake

• Preserve the social aspects of mealtimes

Strategies Around Feeding

• Frequent small meals

• Favourite foods, cravings

• If not hungry, don’t force intake

• Help find other ways than feeding for family to nurture

Management Of Nausea And

Vomiting In

Palliative Care Of Children

0

10

20

30

40

50

60

70

80

90

100

% P

reva

len

ce

Hongo T. et al, Pediatrics International Feb 2003 p.60

Symptoms At The End of Life in Children With Cancer

Managing Nausea & Vomiting in Palliative CareSome Differences in Children vs. Adults

• Assessment, communication challenges

• Higher risk of extrapyramidal reactions, akathisia, and somnolence with dopamine antagonists in children

– Metoclopramide (Maxeran®)

– Prochlorperazine (Stemetil®)

– Haloperidol (Haldol®)

– Chlorpromazine

• If using dopamine antagonists, consider slow administration (45-60 min.), as well as concomitant use of diphenhydramine (Benadryl®) 0.5 – 1 mg/kg q4-6h po/IV continued for additional 24hrs after dopamine antagonist stopped.

N & V Management – Differences in Children vs. Adults ctd

• Route of administration

– Oral may be compromised by developmental, psychological, or practical reasons (eg. too nauseated)

– IV may be upsetting if no pre-existing line

– Very limited data on SQ dosing

– Tolerating SQ dosing?

• Ongoing chemotherapy and feeding even in terminal phase

• Available oral or transdermal doses may be inappropriately high

MECHANISM OF NAUSEA AND VOMITING

• vomiting centre in reticular formation of medulla

• activated by stimuli from:– Chemoreceptor Trigger Zone (CTZ)

• area postrema, floor of the fourth ventricle• outside blood-brain barrier (fenestrated venules)

– Upper GI tract & pharynx– Vestibular apparatus– Higher cortical centres

CortexCortex

CTZCTZ

VestibularVestibular

GIGI

VOMITING VOMITING CENTRECENTRE

Chemoreceptor Trigger Zone

Vestibular Cortical Peripheral

drugs• opioids• chemoTx• etc...

biochemical• Ca++

• renal failure• liver failure

sepsis

radiotherapy

tumor

opioids

anxiety

association

ICP

radiotherapy

chemotherapy

GI irritation• inflammation• obstruction• paresis• compression

CAUSES OF NAUSEA & VOMITING

PRINCIPLES OF TREATING NAUSEA & VOMITING

• Treat the cause, if possible and appropriate

• Environmental measures

• Antiemetic use:

– anticipate need if possible

(NB: Children do not usually require prophylactic antiemetics

when opioids started Ref: Beardsmore et al 2002 Palliative Care

in Paediatric Oncology; European J Cancer 38 p1900-1907)

– use adequate, regular doses

– aim at presumed receptor involved

– combinations if necessary

– anticipate need for alternate routes

Stimulus Area Receptors

Drugs,

MetabolicChemoreceptor

trigger zone

Motion,

PositionVestibular

VisceralAbdominal

organs

↑ ICP Cerebral cortex

DD22 5HT

MM HH11

DD22 5HT

HH11

VOMITING VOMITING CENTRECENTRE

5HTMM

HH11

5HT MMHH11DD22

EffectorEffectorOrgansOrgans

DopamineDopamine SerotoninSerotonin HistamineHistamine MuscarinicMuscarinic

Safety and Tolerability of 5HT3 Antagonists

Goodin S., Cunningham R. The Oncologist 2002 p424-436

• High specificity for 5HT3 receptors; extrapyramidal

reactions unlikely

• It has been suggested that the combination of a 5HT3

antagonist with dexamethasone should be the standard

antiemetic prophylaxis in all pediatric patients

• Granisetron well tolerated; fever and headache most

common adverse events

Safety and Tolerability of 5HT3 Antagonists ctd

Goodin S., Cunningham R. The Oncologist 2002 p424-436

• May prolong QT interval

– 19% of patients given ondansetron in one study

– Seems less with granisetron

– risk of torsades de pointes

– use with caution when high dose methadone used, or

in patients with arrhythmias or on other meds that

might prolong QT

0

10

20

30

40

50

60

70

80

Any AdverseHeadache

Asthenia

ConstipationDiarrhea

Dizziness

Insomnia

DyspepsiaAnorexia

Visual

Granisetron

Ondansetron

Comparative Incidence of Adverse Effects: Granisetron (n=542) vs. Ondansetron (n=543)

Perez et al; J Clin Oncol 1998;16:754-760

0 50 100 150 200 250 300 350

Scopolamine

Haloperidol

Prochlorperazine

CPZ

Promethazine

Metoclopramide

Dopamine

Muscarinic

Histamine

1250

RELATIVE ANTIEMETIC RECEPTOR AFFINITIES

DrugClass

Examples for Breakthrough Nausea (Not necessarily the same as for Chemotherapy Protocols)

SerotoninAntag.

• Granisetron1 : ≥ 4 yo: 20-40 mcg/kg/day divided once or twice daily single dose po/IV

• Ondansetron2: 0.15 mg/kg /dose given tid

H1 Antag.• Dimenhydrinate (Gravol®): 5 mg/kg/day divided q6-8h,

max 300 mg/dayChildren > 12 yo: 50 – 100 mg q 4-6h; max 400 mg/day

Anti-musc.: Transderm-V® (scopolamine patch) 3

2 – 3 yo ¼ Patch

3 – 9 yo ½ Patch

10+ 1 Patch

Antinauseants / Antiemetics

1 Komada Y et al. A randomised dose-comparison trial of granisetron in preventing emesis in children with leukaemia receiving emetogenic chemotherapy. Eur J Cancer 1999; 35(7):1095-1101.2 Principles and Practice of Pediatric Oncology 4th Ed.; Edited by Pizzo & Poplack 3 The Rainbows Children’s Hospice Guidelines 2002

DrugClass

Examples for Breakthrough Nausea (Not necessarily the same as for Chemotherapy Protocols)

DopamineAntagonists *

• Prochlorperazine1 (Stemetil®) for children >10kg – po/pr: 0.4 mg/kg/day in 3-4 divided doses– IM: 0.13 mg/kg/dose– IV: not recommended

• Metoclopramide1 0.1 – 0.2 mg/kg/dose q6h prn **

Prokinetics *• Metoclopramide1 0.1 – 0.2 mg/kg/dose q6h prn **• Domperidone2 0.2 – 0.4 mg/kg/dose up to qid; max. 1.6

mg/kg/day

* Consider using prophylactic Benadryl® concomitantly** Much lower than for established chemotherapy protocols

Antinauseants / Antiemetics ctd.

1 Pediatric Lexi-Drugs Sept. 20032 The Rainbows Children’s Hospice Guidelines 2002

DrugClass

Examples for Breakthrough Nausea (Not necessarily the same as for Chemotherapy Protocols)

Cannabinoids• Dronabinol: has been effective in children with doses

of 2.5 – 7.5 mg/m2 q2-4h prn up to 6 doses/day

• Not first line; dysphoria common

Dexamethasone

• limited data on dosing

• One reference*: 10 mg/m2 to a maximum of 10 mg, given once/day

Misc.• Lorazepam**: 0.02 - 0.04 mg/kg/dose, (max.1 or 2

mg/dose, depending on reference) po/IV q4-8h

Antinauseants / Antiemetics ctd.

* Principles and Practice of Pediatric Oncology 4th Ed.; Edited by Pizzo & Poplack

** Cancer Pain Relief and Palliative Care in Children, W.H.O. 1998