PALLIATIVE CARE OF CHILDREN 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? Burdens include travel, financial, family

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

Hydration in the Terminal Phase Controversial topic; there is no consensus among the palliative care community 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 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

Hydration ctd 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

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: Steffey JM Hypodermoclysis in infants and children. J Iowa State Med Soc. 1963 Jul;53:393-6 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 Nomenclature Bechard L.J., et al Nutritional Supportive Care Principles & 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 Child in Principles and Practice of Pediatric Oncology 4th 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 Appetite Look 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

Symptoms At The End of Life in Children With Cancer Hongo T. et al, Pediatrics International Feb 2003 p.60

Managing Nausea & Vomiting in Palliative Care Some 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.

Differences in Children vs. Adults ctd 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

Cortex CTZ GI VOMITING CENTRE Vestibular

Chemoreceptor Trigger Zone CAUSES OF NAUSEA & VOMITING Chemoreceptor Trigger Zone Vestibular Cortical Peripheral drugs opioids chemoTx etc... biochemical ­ Ca++ renal failure liver failure sepsis radiotherapy tumor anxiety association ­ ICP chemotherapy GI irritation inflammation obstruction paresis compression

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

Chemoreceptor trigger zone Stimulus Area Receptors Drugs, Metabolic Chemoreceptor trigger zone Motion, Position Vestibular Visceral Abdominal organs ↑ ICP Cerebral cortex D 2 5HT M H1 5HT M H1 VOMITING CENTRE D 2 5HT H1 Effector Organs M D 2 5HT H1 Dopamine Serotonin Histamine Muscarinic

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

Comparative Incidence of Adverse Effects: Granisetron (n=542) vs. Ondansetron (n=543) Perez et al; J Clin Oncol 1998;16:754-760

RELATIVE ANTIEMETIC RECEPTOR AFFINITIES 1250

Antinauseants / Antiemetics Drug Class Examples for Breakthrough Nausea (Not necessarily the same as for Chemotherapy Protocols) Serotonin Antag. 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/day Children > 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 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

Antinauseants / Antiemetics ctd. Drug Class Examples for Breakthrough Nausea (Not necessarily the same as for Chemotherapy Protocols) Dopamine Antagonists * 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 * 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 1 Pediatric Lexi-Drugs Sept. 2003 2 The Rainbows Children’s Hospice Guidelines 2002

Antinauseants / Antiemetics ctd. Drug Class 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 * Principles and Practice of Pediatric Oncology 4th Ed.; Edited by Pizzo & Poplack ** Cancer Pain Relief and Palliative Care in Children, W.H.O. 1998