Pediatric Palliative Care Consultant
ABRIDGED POCKET EDITION
Melissa O’Neill Hunt, PharmD
Bridget McCrate Protus, PharmD, MLIS, BCGP, CDP
Janine Penfield Winters, MD
Diane C. Parker, RN, MSN, NE-BC, CHPN, CHPPN
DISCLAIMER: All clinical recommendations contained herein are intended to assist with determining the appropriate therapy for the patient. Responsibility for final decisions and actions related to care of specific patients shall remain the obligation of the institution, its staff, and the patients attending physicians. Nothing in this document shall be deemed to constitute the providing of medical care or the diagnosis of any medical condition. Use of product brand names are intended to assist the clinician in identifying products and does not connote endorsement or promotion of any kind. No financial support for the development of this book was provided by any product vendor or manufacturer. Optum Hospice Pharmacy Services
© 2017, Optum Hospice Pharmacy Services All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of Optum, except in the case of brief quotations embodied in critical reviews and certain other noncommercial uses permitted by copyright law.
Optum Hospice Pharmacy Services 4525 Executive Park Drive Montgomery, AL 36166 Tel: 866-970-7500 www.optum.com/hospicepharmacy
ISBN-13: 978-0-9889558-5-1 ISBN-10: 0-9889558-5-7 Editors Melissa O’Neill Hunt, PharmD Pediatric Clinical Pharmacist Optum Hospice Pharmacy Services Dublin, Ohio
Bridget McCrate Protus, PharmD, MLIS, BCGP, CDP Director of Drug Information Optum Hospice Pharmacy Services Dublin, Ohio
Janine Penfield Winters, MD Palliative Care Physician Otago Community Hospice Dunedin, New Zealand
Diane C. Parker, RN, MSN, NE-BC, CHPN, CHPPN Chief Nursing Officer Ark Hospice Columbia, South Carolina
Associate Editors Marliese Gibson, PharmD, BCPP Clinical Pharmacist Riverside Methodist Hospital Columbus, Ohio
Jason Kimbrel, PharmD, BCPS Vice President of Clinical Services Optum Hospice Pharmacy Services Dublin, Ohio
Contributors Dianne Gray, BS President Hospice and Healthcare Communications Scottsdale, Arizona
Lauren Sulcer Jenkins, PharmD Pediatric Consultant Huntsville, Alabama
“Palliative care seeks to enhance quality of life and the child’s ability to enjoy life in the face of an ultimately terminal condition. The goal is to add life to the child’s years, not simply years to the child’s life…”
American Academy of Pediatrics
Committee on Bioethics and Committee on Hospital Care. Palliative care for children. Pediatrics 2000;106(2):351-7. PREFACE PPCC Pediatric Palliative Care Consultant(PPCC) is intended to be a quick reference guide for palliative symptom management in pediatric patients. The authors and collaborators have systematically reviewed and collected the pertinent literature and resources related to pediatric palliative care and compiled the information into concise guidelines for effective management of symptoms. This abridged pocket guide includes chapters on some of the more common symptoms seen in pediatric palliative care. Each chapter focuses on pharmacological treatment options, comprehensive drug tables, and step-by- step algorithms that walk practitioners through patient specific symptom management. This pocket version is meant to provide easy access to information utilized on a regular basis while managing patients in the field. Additional information regarding these symptoms, as well as many other symptoms and disease states can be found in the full edition of the Pediatric Palliative Care Consultant.
This reference was designed to provide practical recommendations and improve symptom management in pediatric patients. It is the hope that this tool will aid all professionals who care for pediatric patients with chronic, life-limiting conditions, whether they have pediatric-specific training or rarely see a pediatric patient.
CONTENTS PPCC I. Introduction General Pediatric Considerations 1 Medication Administration in Pediatric Patients 4
II. Guidelines for Effective Management of Symptoms (PediGEMS) Constipation 17 Dyspnea 27 Nausea & Vomiting 34 Pain 43 Somatic Pain 54 Visceral Pain 63 Bone Pain 68 Neuropathic Pain 73 Methadone 81 Secretions 88 Seizures 94 Spasticity 117
III. Appendices Extrapyramidal Symptoms (EPS) from Medications 125 Medications Associated with Anticholinergic Side Effects 126 Drugs that Prolong the QT Interval or Induce Torsades de Pointes 127 Corticosteroid Equivalency Table 128 Benzodiazepine Equivalency Table 131
GENERAL PEDIATRIC CONSIDERATIONS PPCC Age Definitions1 Useful Conversions Neonate < 1 month old 2.2 lb…………………….. 1 kg Pre – term: < 36 weeks gestation 1 inch……………………. 2.54 cm Term: ш 36 weeks gestation 1 mL……………………… 20 drops Infant < 1 year old 1 teaspoon……………. 5 mL Child 1 – 11 years 1 tablespoon………… 15 mL Adolescent 12 – 16 years
Useful Equations ሺ ሻ ݐ ܿ݉ ൈܹݐሺ݇݃ሻܪ Body Surface Area ଶ 2 ܤܵܣ ሺ ሻ ൌ ξ (BSA) ͵ͲͲ
Ideal Body Weight Traub & Johnson Equation4 ݐ ሺܿ݉ሻ ൈͳǤͷܪ (IBW) ܫܤܹ ሺ݇݃ሻ ൌ ͳǡͲͲͲ
Créatinine Clearance Bedside Schwartz6
ݐܪ ͲǤͶͳ͵ ൈ Schwartz Equation (Table 2)5 ܥݎܥ݈ ൌ Height (Ht) in cm ܵܥݎ ݐܪ Serum Creatinine (SCr) in ܥݎܥ݈ ൌ ܭ ൈ 4 mg/dL ܵܥݎ Traub ݐܪ ͲǤͶͺ ൈ ܥݎܥ݈ ൌ ܵܥݎ
Table 1. Calculation of Fluid Requirements3 Body Weight Fluid Rate mL/kg/day mL/kg/hr First 10 kg (1-10 kg) 100 ~4 Second 10 kg (11-20 kg) 50 ~2 Each additional kg (>20 kg) 20 ~1 Normal Urine Output* Children 1-2 mL/kg/hr Adults 0.5-1 mL/kg/hr *Estimate urine output by weighing diapers if needed
Table 2. K Values for Schwartz CrCl Equation Age K Low birth weight <1 yoa 0.33 Full term <1 yoa 0.45 1-12 yoa 0.55 13-21 yoa female 0.55 13-21 yoa male 0.7
1 PPCC GENERAL PEDIATRIC CONSIDERATIONS
Table 3. Mean Expected Pediatric Values7 Age Range BP (mmHg) HR RR TBW SCr Systolic Diastolic (bpm) (breaths/min) (%) (mg/dL) Neonate 85 – 100 51 – 65 145 30-60 74 0.3 – 1 Infant 87 – 105 53 – 66 115 25-50 60 0.2 – 0.4 Toddler 95 – 105 53 – 66 104 20-30 59 0.3 – 0.7 School Age 97 – 112 57 – 71 83 16-24 - - Adolescent 112 – 128 66 – 80 70 15-20 - 0.4-1 Adult 120 80 - 12-18 55 0.5 – 1.2 BP = blood pressure; HR = heart rate; RR= respiratory rate; TBW = total body water; SCr = serum creatinine
Table 4. Developmental Alterations in Intestinal Drug Absorption9 Functional Alteration Neonates Infants Children Gastric acid secretion Reduced (pH >5) Adult (pH 2-4) Adult (pH 2-3) Gastric emptying time Variable Prolonged Prolonged slightly Intestinal motility Slower Increased Normal Intestinal surface area Reduced Near adult Adult pattern Biliary function Immature Near adult Adult pattern Microbial colonization Acquiring Near adult Adult pattern
Pharmacokinetics8 x Each patient’s diagnosis will affect their pharmacokinetic characteristics. Monitor for signs of toxicity as patient’s organ function declines. x Pharmacokinetic parameters are difficult to predict in premature infants. Dose cautiously and observe closely for response.
Absorption x Generally slower absorption in infants; Reaches adult values at 6 months of age. Neonates have less gastric acid production and less GI surface area R Reflux most common within 30-45 minutes of oral dose R Skin permeation for topical route may be variable
Distribution x Fat, water, and muscle distribution may not be proportional to body weight o Hydration can vary significantly throughout the day and with illness o Body fat increases during gestation and infancy o Blood-brain barrier underdeveloped in infants which may allow for easier penetration
2 GENERAL PEDIATRIC CONSIDERATIONS PPCC
Metabolism x May exceed adult values for some medications, especially early childhood o Dosing per body weight may seem high compared to adult dosing o Confirm maximum initial dosing in pediatric drug reference o Infants: Half-life increased, clearance decreased o Children: Half-life decreased, clearance increased
Elimination x Glomerular filtration rate (GFR) increases with gestational age o Near adult values at 12-24 months
References 1. Pediatric Exclusivity Study Age Group [Internet]. Silver Spring: U.S. Food and Drug Administration; 2009 April 30. [cited 2013 Sept 16] Available from: http://www.fda.gov/drugs/developmentapprovalprocess/formssubmissionrequirements /electronicsubmissions/datastandardsmanualmonographs/ucm071754.htm 2. Mosteller RD. Simplified calculation of body surface area. N Engl J Med 1987;317(17):1098. 3. Segar We. Parenteral fluid therapy. Curr Probl Pediatr 1972;3:23-40. 4. Traub SL, Johnson SE. Comparison of methods of estimating creatinine clearance in children. Am J Hosp Pharm 1980;37(2):195-201. 5. Schwartz GJ et al. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987;34:571. 6. Schwartz GJ, Munoz A, Schneider MF, et al. New equations to estimate gFR in children with CKD. J Am Soc Nephrol 2009;20(3):629-637. 7. Custer JW. Blood chemistries and body fluids. In: Custer JW, Rau RE. The Harriet Lane Handbook, eighteenth edition. Philadelphia: Mosby; c2009. p. 676-688. 8. Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology- drug disposition, action, and therapy in infants and children. N Engl J Med 2003;349:1157-67. 9. Kliegman RM, Stanton BF, St Geme JW, et al. Chapter 57, Principles of Drug Therapy. In: Nelson Textbook of Pediatrics, Nineteenth Edition. Philadelphia:Elsevier; c2011. p. 250. 10. Eldridge DL, Wells KC, Hoisteg CP. An evidence based review of single pills and swallows that can kill a child. Pediatric Emergency Medicine Practice 2010;7(3).
3 PPCC PEDIATRIC MEDICATION ADMINISTRATION Oral or Sublingual Administration4 x Consider concentration of liquid medications to ensure a measurable dose and appropriate volume for child’s age and swallowing ability. o 5 mL or less for children less than 5 years of age o 5-10 mL or less for children greater than 5 years of age o 1-2 mL or less for sublingual administration
Table 1. Oral Dosage Forms and Possible Manipulations Dosage Form Possible Manipulations* Simple compressed tablets (sugar or Can be crushed and mixed with soft film coated, immediate release) food or liquids Simple powder filled capsules Can be opened and mixed with soft (immediate release) food or liquids Enteric coated tablets Do not crush or chew Extended, sustained, or delayed Do not crush or chew release tablets Extended, sustained, or delayed Can be opened and mixed with specific release capsules containing food or liquids. Individual pellets individually coated pellets should not be crushed or chewed Gel capsules Pierce with a needle and mix with soft food or liquids Orally disintegrating tablets Can often be dissolved in water *Always consult a pharmacist prior to manipulating a medication formulation. Oral chemotherapy agents require special handling precautions. x Dosing cups – for older children who can drink from a cup o Multiple sizes available from 5-30 mL. Recommend using only if cup contains a graduation for the dose being measured, usually 2.5-5 mL increments. o Rinse with water prior to use to prevent medication from adhering to cup. o Pacifier caps can also be used with dosing cups to allow administration to infants. Small volumes should not be measured in a dosing cup. x Measuring spoons – for children able to sip or drink from a spoon o Use only calibrated measuring spoons. Never use household spoons. x Oral syringes – for infants and younger children or for bad tasting medication o Multiple sizes available ranging from 0.3 mL to 60 mL. Ensure that syringe has graduations appropriate for the volume being measured. For example, a 0.3 mL syringe can be used to measure 0.1 mL of medication. o Gently administer medication alongside the child’s cheek. o May split larger doses and administer half in each cheek. o May help bypass the taste-buds for medications with poor palatability. o Medicine droppers for infants: small volumes available in from 1 mL to 5 mL
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Table 2. Excipient Considerations6-8 Excipient Side Effects Considerations Benzyl alcohol Intraventricular hemorrhage, x Acceptable daily limit: 5 mg/kg/day metabolic acidosis, seizures, x Toxicity threshold: 99 mg/kg/day gasping, and increased x Present in oral solutions and elixirs of mortality dexamethasone Ethanol CNS depression, altered x Often found in elixirs and tinctures mental status, synergistic x May cause a disulfiram-like effect CNS depression depending (severe nausea/vomiting) in patients on active ingredient taking metroNIDAZOLE x Present in oral solutions of hyoscyamine Propylene glycol Lactic acidosis, seizures, x Adult acceptable limit: 25 mg/kg/day hemolysis, CNS /respiratory x Adult toxicity: 3,000 mg/kg/day depression, hyperosmolality, x Present in LORazepam oral solution and arrhythmias, hypotension, glycopyrrolate oral solution contact dermatitis Aspartame/ Headache, seizures, x Avoid in patients with phenylketonuria phenylalanine anecdotal reports of panic or pregnant women carry a fetus with attack, mood changes, phenylkenouria hallucinations, dizziness x Children safe threshold: 10 mg/kg/day Benzalkonium Bronchoconstriction, cough, x In albuterol nebulizer solutions chloride burning sensation, facial x Bronchoconstriction is inhibited by flushing, pruritus concurrent administration with a beta- 2-agonist Lactose Diarrhea, abdominal x Symptoms occur in infants, children, cramping, bloating, and adults with lactase deficiency and flatulence, bronchospasm infants with galactose intolerance x Commonly found in infant formulas, tablets, capsules, liquids and dry powder inhalers Sulfites Wheezing, dyspnea, chest x Reactions most common in patients tightness with asthma x Many anti-asthmatic medications containing sulfites have been reformulated Sorbitol Diarrhea, malabsorption x Found as a sweetener in many liquid formulations Saccharin Cross-sensitivity with x Not included in drug labeling sulfonamides x Avoid in children with sulfa allergy Coloring agents Abdominal pain, vomiting, x Possible side-effects depend on the indigestion, hives, dyes present photosensitivity, contact x Links to hyperactivity in children have dermatitis not been confirmed
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Recommended Sublingual Administration Technique1 1. Tablets can be wetted or crushed and mixed with 1-2 mL of water. o Avoid volumes >2 mL; liquid will likely leak out of the sublingual cavity. 2. Allow 5-10 minutes between SL doses or before eating or drinking to prolong drug exposure and promote absorption. 3. Do not crush enteric-coated or controlled-release tablets for SL administration. Only immediate release preparations should be utilized for SL administration. 4. Repeated instillations of alcoholic (elixirs) or glycol agents (parenteral drugs) can be irritating to the oral mucosa.
Table 3. Common Hospice Medications that can be given Sublingually1,3 Anticholinergics Antiemetics Antipsychotics Benzodiazepines Opioids atropine promethazine chlorproMAZINE ALPRAZolam HYDROmorphone (Isopto Atropine®) (Phenergan®) (Thorazine®) (Xanax®) (Dilaudid®) hyoscyamine haloperidol clonazePAM methadone (Levsin®) (Haldol®) (KlonoPIN®) (Dolophine®) diazepam morphine* (Valium®) (Roxanol®) LORazepam oxyCODONE (Ativan®) (Roxicodone®) fentaNYL *While morphine (Roxanol®) is administered sublingually, sublingual absorption is <20% with most of the drug in liquid form trickling down the esophagus for oral absorption. x Commercially-available liquids, compounded liquids, or solid dosage forms that are crushed can be flavored. Choose flavors that help mask bitterness and are most acceptable to the patient. Many pharmacies provide flavoring of liquid medications at no charge or minimal cost. o From birth to teenage years, children have a greater preference for salty, sour, and especially sweet tastes compared to adults. Infants may be more sensitive to bitter tastes.4 x Liquid medications or crushed solid medications can be added to a food or drink. o Always check with a pharmacist to ensure that mixing with food or drink will not decrease effectiveness. o Do not add medication to a substance that the child relies on for basic nutrition (milk, formula, etc.); the child may refuse as a result of altered taste. o Add medication to small amounts of liquid or food to ensure the child receives the entire dose. x Use a taste-masking spray. These are water-based lubricants flavored to mask medicine taste and sprayed in the mouth just prior to taking medications.11, 12
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x Give an ice cube or Popsicle® to numb taste buds prior. Give lollipop or Popsicle® to mask taste after. x Chill medications to mask flavor. Many liquid antibiotics require refrigeration after reconstitution for stability purposes; in addition to palatability.13 Consult a pharmacist to ensure that temperature changes or administration with food will not affect the effectiveness of the medication. x Mix medication in ice cream or cold pudding. x Pinch nose while taking medications to prevent odor influence on taste. x Administer medication to cheek with an oral syringe to bypass the taste buds. x Have older children drink medication through a straw.
Gastrostomy Tube Administration15 x Consider multiple factors prior to administering a medication through a gastrostomy tube including: o Length of the patient’s functional bowel: decreased length of functional bowel can decrease drug absorption. o Tube composition: silicone tubes clog more often than polyurethane tubes. o Tube internal diameter and distal tip diameter: tube diameters are measured in French units (1 French unit = 0.33 mm) and are designated as small-bore (5- 12 French) or large-bore (ш 14 French). Most feeding tubes are small-bore and likely to clog with drugs or thick formulas. o Location of the distal end of the feeding tube relative to site of drug absorption Stomach is the most tolerant of medications and enteral formulas. Duodenum or jejunum preferred in patients with pancreatitis, gastroparesis, severe reflux, high gastric residual volumes, or aspiration. o Drug formulation and excipients o Routine flushing regimen To prevent tube clogging and ensure medication delivery, flush tubes after starting and stopping enteral nutrition, and between each medication administration. Routine flushes every 4 hours are only recommended for nasojejunal tubes in children (1-3 mL for neonates and 3-5 mL for infants/children). o Drug interactions with enteral nutrition formula Consult a pharmacist to determine medications that should be separated from enteral nutrition to prevent decreased absorption or that may interact with enteral nutrition. o Size of the oral or enteric syringe needed for accurate dosing and safe intraluminal pressures Ensure the syringe used has an appropriate volume and graduations for accurate measurement of the prescribed dose. Excessive intraluminal pressure can cause the feeding tube to rupture and break. Use caution especially when attempting to unclog a clogged tube.16
7 PPCC PEDIATRIC MEDICATION ADMINISTRATION x Do not add medications directly to enteral nutrition products for administration. Hold enteral feedings before and after medication administration. x Crushing multiple solid medications or mixing multiple liquid medications increases risk of drug interactions and changes drug mixture compatibility and stability. x Medications that should not be administered through feeding tubes include:14 o Enteric-coated, film-coated tablets: may clump in water and clog tubes o Extended-release, delayed-release, or sustained-release: destroys the delivery mechanism and may cause overdose o Buccal or sublingual preparations: not designed for absorption in the GI tract o Carcinogenic, teratogenic, or cytotoxic medications: aerosolized particles may harm caregiver o Injectable medications: formulated for specific physiology of the blood x Liquid medication considerations: o Elixirs or suspensions are preferred over syrups which are more likely to cause clumping when exposed to enteral nutrition. o Dilute hyperosmolar or hypertonic liquids to prevent osmotic diarrhea, bloating, nausea, or cramping.
Recommended Gastrostomy Tube Administration Technique15 1. Stop continuous tube feedings 15 minutes prior to medication administration and restart feedings 15 minutes after administration. x Hold feedings for more than 30 minutes only if the medication requires longer separation to avoid drug-nutrition interactions (e.g., phenytoin). x If using bolus gastric feedings, then administer medications between feedings. 2. Flush the tube with an appropriate volume of sterile water after feedings are stopped, between each medication, and before feedings are restarted. x Flushing volume (1-15 mL) dependent on patient’s age, fluid status, and tube size. 3. Crush solid medications into a fine powder using a mortar and pestle and dilute in 15- 30 mL of sterile water before delivery into the tube. 4. Dilute liquid medications, especially highly concentrated or viscous liquids, with 10-30 mL of sterile water before delivery into the tube. x Dilution volume should be at least a 50:50 dilution.
Rectal Administration x Rectal medication administration should be avoided in premature infants, immunocompromised patients (e.g. oncology), patients with active rectal bleeding or thrombocytopenia, rectal trauma, acute exacerbations of inflammatory bowel disease, diarrhea, paralytic ileus, colonic obstruction, recent gastrointestinal or gynecological surgery, and in situations where abuse is suspected. x Cut suppositories in half length-wise if necessary.
8 PEDIATRIC MEDICATION ADMINISTRATION PPCC
Recommended Rectal Administration Technique2,17,18 1. Lubricate medications or devices with water-based lubricant prior to insertion. 2. Position child on his/her side with knees bent and drawn up toward the abdomen. 3. Insert medication as recommended per manufacturer directions, if known. o Insert ½-1 inch past the rectal sphincter for infants. o Insert 1 inch past the rectal sphincter for adults.17 Tablets/Capsules x Administer oral dosage forms rectally as whole tablets, or crush and mix in water. Do not crush enteric-coated or controlled-release tablets. x Ensure that the fluid volume is appropriate for the child’s age and size. o Younger children—Instill 1- 5 mL of warm water o Older children/adults—Instill 5 - 10 mL of warm water x Ensure that insertion depth is appropriate for child’s age and size. o Infants—Insert ½ - 1 inch past the rectal sphincter o Adults—Insert 1 inch past the rectal sphincter Liquids x Administer oral liquids rectally if dose can be given in an appropriate volume. x Limit liquid drug volumes based on patient size. Max volume 60-80 mL to prevent spontaneous expulsion; Enema volumes for children: 2 - 6 years: 180 mL (6 oz) 6 - 12 years: 360 mL (12 oz) Adolescents/adults: 480 mL (16 oz)
Table 4. Common Hospice Medications that can be given Rectally19-21 Analgesics Anticonvulsants Antiemetics Antipsychotics Benzodiazepines acetaminophen carBAMazepine metoclopramide chlorproMAZINE ALPRAZolam HYDROmorphone PHENobarbital prochlorperazine haloperidol clonazePAM ibuprofen valproic acid promethazine diazepam methadone LORazepam morphine midazolam naproxen oxyCODONE
Inhaled Medication Administration23 x Mouthpieces – Preferred interface for use with nebulizers or MDIs. Seal mouth around mouthpiece. x Masks – Preferred interface if a mouthpiece cannot be used. o Use child-sized mask to ensure minimal leakage and prevent aerosol from reaching the eyes. Avoid use with inhaled steroids due to face and contact. x Hoods – Preferred in infants who have significant distress with use of a mask or if an adequate mask-to-face seal cannot be achieved due to squirming or crying.24
9 PPCC PEDIATRIC MEDICATION ADMINISTRATION x Spacers – Decreases the velocity of medication droplets and creates droplets of a smaller size that travel more easily and deeper into the lungs. x Valved holding chamber – Interface for MDI or poor hand-breath coordination. o Use with masks for children who cannot form a seal around the mouthpiece. o Similar to a spacer, however a one-way valve prevents patient from breathing out into the chamber and disturbing the held medication. x Administer bronchodilators first to open airways, allowing better lung penetration.
Table 5. Age Guidelines for Use of Aerosol Delivery Device Types23 Aerosol Device and Interface Age Small-volume nebulizer with mask or hood 0-1 yoa Small-volume nebulizer with mask ч 3 yoa Small-volume nebulizer with mouthpiece ш 3 yoa Pressurized MDI with valved holding chamber/spacer and mask < 4 yoa Pressurized MDI with valved holding chamber/spacer ш 4 yoa Dry powder inhaler ш 4 yoa Pressurized MDI ш 5 yoa Breath-actuated MDI ш 5 yoa Breath-actuated nebulizer ш5 yoa
Nasal Medication Administration x The nasal cavity can only hold a small volume of approximately 0.1 mL per nare, therefore a concentrated solution may be needed to achieve an adequate dose.26 Divide dose and deliver half in each nare.27 x Atomizing medications provides a thin layer of medication to the nasal mucosa preventing medication drainage to the oropharynx and therefore allows for better absorption than nasal drops.27 x Irritation of the nasal mucosa may occur if the solution is more basic or acidic than typical nasal secretions, pH 5 to 7, or if the solution is not isotonic. x Prior to administering any medication nasally, clear mucus or blood from nostrils that may reduce medication contact with mucosal surface.28 x After nasal administration, avoid blowing nose to reduce medication loss.
Recommended Nasal Administration Technique: Bulb Syringe Use28 1. Position child on back; consider swaddling to assist with holding the child still. 2. Before inserting the bulb syringe into the nostril, depress the bulb to expel air. 3. Place the tip of the bulb syringe into the nostril until sealed. Occlude other nostril. 4. Slowly release bulb to provide suction of mucus from the nose. 5. Remove bulb syringe from nostril and squeeze mucus into a tissue. 6. Repeat suctioning of opposite nostril if necessary.
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Recommended Nasal Administration Technique: Spray bottles, Multi-Dose Counting Bottles, and Unit-Dose Devices13, 29 1. Prime or shake medication as directed. 2. Keep head and bottle in the upright position (some unit-dose devices may not need to remain upright and allow for alternative head positioning). 3. Insert applicator tip into the nostril and close off opposite nostril. 4. While breathing in through nose, activate medication spray. 5. Repeat in opposite nostril if necessary.
Recommended Nasal Administration Technique: Medicine Dropper and Standard Syringe with Nasal Atomizer29 1. Prepare appropriate dose of medication in the dropper or syringe. 2. Position patient in one of the following positions (if using an atomizer or drops for seizure, administer medication regardless of positioning) Lying head back – Lying in supine position with head just off the bed in hyperextension. Lateral head low – Lying on the side with side of the head resting on the bed. Administer medication in the lower nostril. Head down and forward – Kneeling down with top of the head on the ground with the forehead close to the knees and nostrils facing up. 3. Insert applicator tip into the nostril and administer medication. 4. Repeat in opposite nostril if necessary.
Topical Medication Administration2,30 x Absorption of topically applied medications depends on several factors including o Site of application: areas of thicker skin, decreased blood circulation, or decreased subcutaneous fat may decrease drug absorption. o Thickness and integrity of the skin: skin thickness varies with age, typically thinner in children, increasing absorption, as well as risk of toxicity. o Blood flow to the skin and body temperature: varies with age and is often increased in children which may increase absorption and risk of toxicity. At the end of life, blood flow may decrease. o Drug characteristics: low molecular weight or if lipophilic, increases absorption x Instruct caregivers to wear gloves when applying creams, ointments, or gels. x Do not apply creams, ointments, or gels to broken skin or cover with diapers. x Do not cut patches or manipulate in any way unless directed by physician. x Avoid contact with heat sources near area where patches are applied. x Ensure proper disposal of patches. Fold fentaNYL patches with adhesive together and flush in toilet.31
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References 1. WHO Expert Committee on Specifications for Pharmaceutical Preparations 46th report. Annex 5: Development of paediatric medicines: points to consider in formulation. WHO Technical Report Series No. 970, 2012. 2. Committee on Drugs. Alternative routes of drug administration – advantages and disadvantages (subject review). Pediatrics 1997. 3. Arvedson JC . Swallowing and feeding in infants and young children. GI Motility online 2006; doi:10.1038/gimo17. 4. Mennella JA, Beauchamp GK. Optimizing oral medications for children. Clin Ther 2008;30 (11):2120-2132. 5. WHO International Pharmacopoeia, 4th ed. 3rd supplement. Monographs: Dosage forms: General monographs: liquid preparations for oral use. 2013. 6. Fabiano V, Mameli C, Zuccotti GV. Paediatric pharmacology: remember the excipients. Pharmacological Research 2011;63:362-365. 7. Committee on Drugs. “Inactive” ingredients in pharmaceutical products: update (subject review). Paediatrics 1997;99(2):268-278. 8. Pawar S, Kumar A. Issues in the formulation of drugs for oral use in children: role of excipients. Pediatr Drugs 2002;4(6):371-379. 9. MedispenseTM. Alligator Medicine Spoon. http://www.classicmdm.com/newsite1/index.php [accessed September 12 2013]. 10. Ava the Elephant. Ava the Elephant Talking Medicine Dispenser. http://www.avatheelephant.com/ [accessed September 12 2013]. 11. Flavorx, Inc. Pill Glide. http://flavorx.com/products/pill-glide/ [accessed June 19 2013]. 12. Flavorx, Inc. Yo Gabba Gabba! Medication Time Flavoring Spray. http://flavorx.com/products/yo-gabba-gabba-spray/ [accessed June 19 2013]. 13. Lexicomp Online [Internet]. Hudson, OH: Lexi-Comp, Inc. [cited 2013 September 5]. 14. Williams NT. Medication administration through enteral feeding tubes. Am J Health Syst Pharm. 2008; 65(24):2347-2357. 15. Bankhead R, Boullata J, Brantley S, Corkins M, et al. A.S.P.E.N. Enteral Nutrition Practice Recommendations. J Parenter Enteral Nutr 2009;33(2):122-167. 16. Beyer PL. Complications of enteral nutrition. Chapter 17 in Matarese L and Gottschlich M. Contemporary Nutrition Support Practice. 2nd Ed. WB Saunders. Philadelphia, 2002. 17. American Society of Health-System Pharmacists. Safe Medication: How to use rectal suppositories properly. 2009. http://www.safemedication.com/safemed/MedicationTipsTools/HowtoAdminister/Howt oUseRectalSuppositoriesProperly [accessed September 5 2013]. 18. Children’s Physician Network, Pediatric Advisor 2012.2 Enemas: How to Give. http://www.cpnonline.org/CRS/CRS/pa_enemahom_hhg.htm [accessed May 10 2013]. 19. Tom WC. Alternative or off-label routes of administration. Pharmacists Letter 2006:222012. 20. Warren DE. Practical use of rectal medications in palliative care. J Pain and Symptom Mgmt. 1996;11(6)378-387. 21. Thomson D. non-enteral routes of administration for psychiatric medications. Psychosomatics. 1999;40(3):185-192. 22. Bisgaard H. Delivery of inhaled medication to children. J Asthma 1997;34(6):443-467. 23. Arzu A, Restrepo RD. AARC clinical practice guideline: aerosol delivery device selection for spontaneously breathing patients:2012. Resp Care 2012;57(4):613-626.
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24. Amirav I, Banaov I, Gerenberg M, Groshar D, et al. Nebulizer hood compared to mask in wheezy infants: aerosol therapy without tears! Arch Dis Child 2003;88:719-723. 25. Burchett DK, Darko W, Zahra J, Noviasky J, et al. Mixing and compatibility guide for commonly used aerosolized medications. Am J Health-Syst Pharm 2010;67:227-230. 26. Wermeling DP. Intranasal delivery of antiepileptic medication for the treatment of seizures. Neurotherapeutics 2009;6:352-358. 27. Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics online 2010; doi: 10.1542/peds.2010-0161. http://pediatrics.aappublications.org/content/126/3/532.full.html 28. Cincinnati Children’s Hospital Medical Center. Health topics: suctioning the nose with a bulb syringe. http://www.cincinnatichildrens.org/health/s/suction/ [accessed September 12 2013]. 29. Merkus P, Ebbens FA, Muller B, Fokkens WJ. Influence of anatomy and head position on intranasal drug deposition. Eur Arch Otorhinolaryngol 2006;63:827-832. 30. Margetts L, Sawyer R. Transdermal drug delivery: principles and opioid therapy. Cont Ed Anaesthesia Critical Care & Pain 2007;7(5):171-176. 31. Institute for Safe Medication Practices. Fentanyl Patches. ISMP 2012. http://www.ismp.org/docs/Fentanyl-Brochure.pdf [accessed June 19 2013].
13 PediGEMS Guidelines for Effective Management of Symptoms
x Constipation x Dyspnea x Nausea & Vomiting x Pain o Somatic Pain o Visceral Pain o Bone Pain o Neuropathic Pain o Methadone x Secretions x Seizures x Spasticity
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Non-Pharmacological Treatment2-6, 11 x The establishment of a regular bowel routine should be supported by providing access to a toilet with privacy, especially after meals. x Encourage increased activity when appropriate. This can be facilitated with physical therapy or a child life specialist. x Increase fluid intake of the child’s favorite drinks. (Children less than six months of age should not be given free water or fruit juices.) x Increase dietary fiber from sources such as: o Whole-grain cereals o Fruits: apples, dates, figs, peaches, pears, plums, prunes, or raisins o Vegetables: beans, broccoli, cabbage, carrots, cauliflower, celery o Fruit juices: apple, pear, or prune juice o Power pudding: blend 1 cup prune juice, 1 cup bran cereal, and 1 cup applesauce; administer 1-2 tablespoons daily and titrate as needed; 14 refrigerate up to one week. o Fruit paste: Boil 1 lb prunes, 1 lb raisins, 1 lb figs, and 16 oz brewed senna tea for 5 minutes, then add 1 cup brown sugar and 1 cup lemon juice and mix to form paste; freeze and serve 1-3 teaspoons 12 daily and titrate as needed. x Consider abdominal massage in a clockwise fashion. Warm hands placed on the stomach tend to increase abdominal relaxation. x Self-hypnosis, biofeedback, and cognitive-behavioral therapy may be effective in children with neurogenic bowel. x In infants, rectal stimulation may be successful. Dietary changes, such as a small amount of fruit juice, may be adequate.
Pharmacotherapy 4-5, 12 x The goal of pharmacotherapy should be focused on preventing constipation, where possible, and treating patients who have already become constipated to avoid impact on quality of life. x Stool softeners and/or stimulant laxatives should be initiated to prevent constipation when patients are started on opioids. x Daily maintenance therapy for pediatric patients should be initiated with an osmotic laxative, such as polyethylene glycol (PEG, Miralax). Ensure adequate fluid intake for maximum benefit and safety. PEG is considered the first-line osmotic therapy, as it has been reported superior to other osmotic agents in palatability and acceptance by children, but requires administration with 4-8 15-23 ounces of liquid. x Second-line osmotic agents, magnesium hydroxide, lactulose, and sorbitol, seem to be equally efficacious; therefore, choice is based on safety, cost, the
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child’s preference, ease of administration, and the practitioner’s experience. Although, if PEG is ineffective, a stimulant is often used, rather than trying another osmotic agent. x Osmotic laxatives may not be beneficial in patients with neuromuscular conditions or opioids-induced constipation. In these cases stimulant laxatives may be necessary. Senna would be considered first-line stimulant due to the risk of cramping with bisacodyl. x In the patient with chronic illness, stimulant laxatives may be necessary intermittently. However, prolonged use of these agents may lead to dependency, fluid and electrolyte imbalances, or vitamin and mineral deficiencies. In the hospice patient, senna (+/- docusate) is the preferred agent for opioid-induced constipation. x Stimulants and enemas should be avoided in infants. Glycerin suppositories and dietary changes should be first line in infants. x Suppositories and enemas should be used with caution in neutropenic or thrombocytopenic patients. x Certain enemas may be toxic to children. Phosphate enemas may lead to hyperphosphatemia. Soapsuds enemas can lead to perforation and bowel necrosis. Tap water enemas can cause hyponatremia. x Fecal disimpaction may be necessary before initiating maintenance therapy for constipation. o Rectal stimulation may be adequate to stimulate disimpaction, especially in infants or patients with neurologic deficit. o Glycerin suppositories in infants and bisacodyl suppositories in older children have shown efficacy for rectal disimpaction. o Suppositories help to soften and lubricate the fecal mass and allow for easier evacuation. o If suppositories are inadequate, rectal disimpaction may be performed with phosphate soda enemas, saline enemas, or mineral oil enemas followed by a phosphate enema. o PEG has been successful for oral disimpaction. Oral mineral oil should be avoided due to risk of aspiration. o High-dose magnesium hydroxide, magnesium citrate, lactulose, sorbitol, senna, and bisacodyl have also shown success in oral disimpaction.
Clinical Pearls x Patients receiving more than one opioid dose per day should have corresponding orders for medications to prevent opioid-induced constipation. o An osmotic laxative or stool softener should be scheduled and, if ineffective, a stimulant should be added. While osmotic laxatives
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may be adequate in healthy children, hospice patients often require a stimulant laxative initially. o Stool softeners provide the “mush,” but without the “push” of a stimulant the “mush” may not leave the colon. x For high impactions, give 2-3 “Vaseline Balls” orally instead of mineral oil. o “Vaseline Balls” – pea sized frozen balls of white petrolatum rolled in powder sugar or powered hot chocolate mix. x In infants, sweet syrup can be made using 2 tablespoons of brown sugar in 4 oz warm water. Dry brown sugar is less likely to contain organisms that might be found in a concentrated sugar liquid. x While PEG has a multitude of safety and efficacy data in children, it can be difficult to find the appropriate dose. Patients may complain of a “seesaw” effect, where the dose is either supratherapeutic or subtherapeutic and then the opposite after dosage adjustment. It’s availability over the counter may allow easy accessibility, but limit coverage by third party payers. x The gastrointestinal (GI) tract is a neurologic organ. Therefore, bowel motility issues are common in patients with neurologic disease. x Laxatives are contraindicated in patients with complete bowel obstruction (see Bowel Obstruction PediGEMS). Softening the stool may be acceptable in cases of partial obstruction.
Table 1. Pharmacological Management of Constipation24 Medication & Typical Starting Dose** Routes Pediatric Formulation Age Guide* Considerations Stool Softeners docusate PO: 5 mg/kg/day div q6h-QD PO Liquid: 50 mg/5 mL (Colace) <3 yoa: 10-40 mg/day div q6h-QD PR Caps: 50, 100, 240, 250 mg 3-6 yoa: 20-60 mg/day div q6h-QD Soln, enema: 283 mg/5 mL 6-12 yoa: 40-150 mg/day div q6-QD x Enemeez Plus contains >12 yoa: 50-400 mg/day div q6-QD benzocaine PR: >12 yoa: add 50-100 mg of x Administer liquid with docusate liquid to NS or water milk, fruit juice, or infant formula to mask taste x Option for patients who should avoid straining during defecation x Must be used with adequate fluid intake to maximize benefit and safety x Avoid using with mineral oil x SE: abdominal cramping, nausea, diarrhea, intestinal obstruction Continued
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Medication & Typical Starting Dose** Routes Pediatric Formulation Age Guide* Considerations glycerin <6 yoa: 1 infant suppository BID PR Supp: 1, 1.5, 2 g, 82.5% prn OR 2-5 mL of rectal solution as Soln, PR: 2.3 g/2.3 mL, 5.6 an enema g/5.5 mL >6 yoa: 1 adult suppository BID prn x Suppository tip or chip can OR 5-15 mL of rectal solution as an be used enema x Retain in rectum for 15 minutes x Penetrates and softens stools x Promotes bilirubin excretion by reducing enterohepatic circulation in newborns x Can stimulate passage of meconium x SE: abdominal pain, rectal irritation Stimulant Laxatives bisacodyl PO: PO Tab: 5, 10 mg (Dulcolax) 3-12 yoa: 5-10 mg PR Tab, EC, DR: 5 mg or 0.3 mg/kg q24h Supp: 10 mg >12 yoa: 5-15 mg/day; Max:30 mg Soln, enema: 10 mg/30 mL PR: x Do not crush or chew EC <2 yoa: 5 mg/day tablets 2-11 yoa: 5-10 mg/day >12 yoa: 10 mg/day x Do not use in infants x Oral dosing limited by severe cramping; Administer on an empty stomach x PR bisacodyl considered first line in NPO patient x Do not administer within 1 hour of ingesting antacids, alkaline material, or dairy products x SE: abdominal pain, nausea, cramping docusate and 2-6 yoa: ½ tab qHS, Max: 1 tab BID PO Tab: 50 mg docusate sodium senna (Senokot- 6-12 yoa: 1 tab qHS, Max: 2 tabs and 8.6 mg sennosides S) BID >12 yoa: 2 tabs qHS, Max: 4 tabs > 2 yoa BID x Administer with water, preferably in the evening x SE (usually mild): abdominal cramping, nausea, vomiting, diarrhea, urine discoloration (red/brown) Continued
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Medication & Typical Starting Dose** Routes Pediatric Formulation Age Guide* Considerations senna 1 mon-2 yoa: 2.2-4.4 mg PO Syrup: 8.8 mg/5 mL (Senokot) sennosides (1.25-2.5 mL) QHS, PR Liquid, conc: 33.3 mg/mL Max: 5 mL/day Drops: 8.8 mg/mL tablet > 2 yoa 2-6 yoa: 4.4-6.6 mg sennosides Strips, ODT: 8.6 mg (2.5-3.75 mL, ½ tab) QHS, Max: Tab, chewable: 10, 15 mg 3.75 mL or 1 tab BID Tab: 8.6, 15, 25 mg 6-11 yoa: 8.8-13.2 mg sennosides x Liquid products may (5-7.5 mL, 1 tab) QHS, Max: 7.5 mL contain propylene glycol or or 2 tabs BID sodium benzoate >12 yoa: 17.6-26.4 mg sennosides (10-15 mL, 2 tabs) QHS, Max: 15 mL or 4 tabs BID x Preferred for opioid-induced constipation x Drink plenty of fluids; Syrup can be taken with juice, milk, or mixed with ice cream to mask taste x SE (mild): abdominal pain, nausea, vomiting, diarrhea, may discolor urine (red/brown) or feces Osmotic Laxatives lactulose <18 yoa: 0.7-2 g/kg/day (1-3 PO Soln, PO, PR: 10 g/15 mL (Generlac) mL/kg/day) in divided doses Crystals for soln, PO: 10 Adult: 10-20 g (15-30 mL) QD g/packet, 20 g/packet Max: 40 g/day (60 mL/day) x As retention enema: mix
with H2O or NS & use a rectal balloon catheter – retain for 30-60 min x Contraindicated if on galactose-restricted diet x Infants may develop hyponatremia and dehydration x SE: abdominal pain, bloating, nausea, diarrhea magnesium <6 yoa: 2-4 mL/kg PO Solution: 290 mg/5 mL citrate 6-12 yoa: 100-150 mL x Mix solution with a full
(Citroma) >12 yoa: 150-300 mL glass of H2O and administer x Dosed daily or in divided doses on an empty stomach
x Monitor magnesium levels in patients with a CrCl <25 mL/min x SE: abdominal cramps, diarrhea, gas, hypermagnesemia, hypotension, or respiratory depression Continued
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Medication & Typical Starting Dose** Routes Pediatric Formulation Age Guide* Considerations magnesium <2 yoa: 0.5 mL/kg/dose PO Susp: 400 mg/5 mL hydroxide 2-5 yoa: 311-622 mg (5-15 mL) Susp, conc: 800 mg/5 mL (Milk of 6-11 yoa: 933-1244 mg (15-30 mL) Tab, chewable: 311, 400 mg Magnesia) >12 yoa: 1866-2488 mg (30-60 mL) x Mix solution with glass of
x Dosed QHS or in divided doses H2O and administer on an Tablet: > 2 yoa x Based on 400 mg/5 mL conc empty stomach x Administer tablet with a
glass of H2O x Repeated use may be appropriate x Monitor magnesium levels in patients with a CrCl <25 mL/min x Not used often in very ill children because of strong purgative action x SE: abdominal pain, diarrhea, nausea, vomiting, ј magnesium, hypotension, respiratory depression polyethylene >6 mon: 0.5-1.5 g/kg/day, NTE 17 PO Powder for soln: 17 g/dose, glycol 3350 g/day 17 g/packet (MiraLAX) Adult: 17 g (1 heaping tbsp) QD x Dose can be measured x Difficult to establish patient dose using bottle cap & added > 17 yoa to 4-8 ounces of liquid x For ease of measuring: 1 tspу5.5 g x SE (mild): abdominal bloating, cramping, nausea, diarrhea, flatulence sodium PO: 5-9 yoa: 7.5 mL QD PO Soln: sodium phosphate phosphates 10-11 yoa: 15 mL QD PR monohydrate 2.4 g, (Fleet Enema) >12 yoa: 15-45 mL QD heptahydrate 0.9 g/5 mL PR: 2-4 yoa: 1/2 of a 2.25 oz Soln, enema: sodium >2 yoa3 pediatric enema QD phosphate monohydrate 19 5-11 yoa: 2.25 oz enema QD g, heptahydrate 7 g/118 mL >12 yoa: 4.5 oz enema QD x Dilute oral solution in 8 ounces of cool water, follow with 8 more ounces of water x Avoid retention of enema solution x Short-term treatment of constipation x Maintain adequate fluid intake x Avoid oxalate (berry, nut, chocolate, bean, tomato) or phytate-containing foods (bran, wheat) x SE: abdominal discomfort, nausea, vomiting, diarrhea, mucosal bleeding, hypernatremia, hyperphosphatemia, dizziness, headache Continued
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Medication & Typical Starting Dose** Routes Pediatric Formulation Age Guide* Considerations sorbitol PO: 2-11 yoa: 2 mL/kg PO Soln, PO, PR: 70% >12 yoa: 30-150 mL PR Use 25%- 30% solution for > 2 yoa PR: 2-11 yoa: 30-60 mL (25-30%) PR: Dilute 1 part solution >12 yoa: 120 mL (25-30%) with 2.3 parts water x Single dose at infrequent intervals; Rarely used x Contraindication: anuria x SE: abdominal pain, nausea, vomiting, diarrhea, dry mouth (xerostomia) Prokinetic Agents Erythromycin (E- 2.5 mg/kg Q6H PO Susp: 200 mg/5 mL Mycin) Adult: 125-250 mg Caps, Tab: 250 mg x Administer before meals and x Chewable tablets should qhs not be swallowed whole x Do not break or chew delayed release and enteric coated tablets x Avoid IV administration, associated with fatal complications x Rarely used for constipation, unless underlying motility disorder x Consider if patient cannot tolerate metoclopramide (due to EPS) metoclopramide 0.1-0.2 mg/kg Q6H PO Soln: 5 mg/5 mL (Reglan) Adult: 10 mg PR Tab: 5, 10 mg x May dose up to 1 mg/kg for IM Tab, ODT: 5, 10 mg dopamine antagonism or IV Inj: 5 mg/mL chemotherapy induced x Some products contain nausea/vomiting sodium benzoate x Administer 30 min before meals and at bedtime x Rarely used for constipation, unless underlying motility disorder x Extrapyramidal symptoms (EPS) occur more frequently in children. May administer diphenhydrAMINE for EPS prevention. Concurrent administration with anticholinergic agents (e.g. diphenhydrAMINE) will decrease prokinetic effect, but not anti-emetic effect. x Black box warning: irreversible tardive dyskinesia x Contraindication: complete bowel obstruction x SE: sedation, confusion *Use cautiously in patients outside of FDA & manufacturer recommended age parameters. **Do not exceed usual maximum adult starting doses. Not intended for use in neonatal population.
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References 1. Hain RDW, Jassal SS. Paediatric Palliative Medicine. New York: Oxford; c2010. Chapter 10, Constipation; p. 106-109. 2. Culbert TP, Banez GA. Integrative Approaches to Childhood Constipation and Encopresis. Pediatr Clin N Am 2007;54:927-47. 3. PL Detail-Document, Treatment of Constipation in Children. Pharmacist’s Letter/Prescriber’s Letter. February 2012. 4. North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Evaluation and Treatment of Constipation in Children: Summary of Updated Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2006;43(3):405-7. 5. Baker SS, Liptak GS, Colletti RB, et al. Constipation in Infants and Children: Evaluation and Treatment. A Medical Position Statement of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr 1999;29(5):612-26. 6. Friedrichsdorf SJ, Drake R, Webster ML. Chapter 33, Gastrointestinal Symptoms. In: Wolfe J, Hinds PS, Sourkes BM, editors. Textbook of Interdisciplinary Pediatric Palliative Care. Philadelphia: Saunders; c2011. p. 311-34. 7. Santucci G, Mack JW. Common Gastrointestinal Symptoms in Pediatric Palliative Care: Nausea, Vomiting, Constipation, Anorexia, Cachexia. Pediatr Clin N Am 2007; 54: 673- 689. 8. Sreedharan R, Liacouras CA. Major Symptoms and Signs of Digestive Tract Disorders. In: Kliegman RM, Stanton BF, Gemelll JW, et al, editors. Nelson Textbook of Pediatrics, 19th ed. Philadelphia: Saunders, c2011. p.1242-3. 9. Feinberg AN, Feinberg LA, Atay OK. Gastrointestinal Care of Children and Adolescents with Developmental Disabilities. Pediatr Clin N Am 2008;55:1343-58. 10. Sandowski S, Jackson RM. Chapter 38, Abdominal Pain, Vomiting and Diarrhea. In: Hernandez CG, Singleton JK, Aronzon DZ. Primary Care Pediatrics. Philadelphia: Lippincott; c2001. p. 448-449. 11. Getto L, Zeserson E, Breyer M. Vomiting, Diarrhea, Constipation, and Gastroenteritis. Emerg Mede Clin N Am 2011;29:211-37. 12. Wrede-Seaman L. Pediatric Pain and Symptom Management Algorithms for Palliative Care. China: Intellicard, c2005. Constipation, p. 22-25. 13. Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol 1997;32(9):920-4. 14. Gibson C, Opalka P, Moore C, et al. Effectiveness of bran supplement on the bowel management of elderly rehabilitation patients. J Gerontological Nurs 1995;21(20):21-30. 15. Bell EA, Wall GC. Pediatric Constipation Therapy Using Guidelines and Polyethylene Glycol 3350. Ann Pharmacother 2004;38(4):686-93. 16. Gremse DA, Hixon J, Crutchfield A. Comparison of polyethylene glycol 3350 and lactulose for treatment of chronic constipation in children. Clin Pediatr (Phila) 2002; 41(4):225- 229. 17. Pashankar DS, Bishop WP, Loening-Baucke V. Long-term efficacy of polyethylene glycol 3350 for the treatment of chronic constipation in children with and without encopresis. Clin Pediatr (Phila) 2003; 42(9):815-819. 18. Nurko S, Youssef NN, Sabri M, et al. PEG3350 in the Treatment of Childhood Constipation: A Multicenter, Double-Blinded, Placebo-Controlled Trial. J Pediatr 2008;153(2):254-61.
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19. Youssef NN, Peters JM, Henderson W, et al. Dose Response of PEG 3350 for the Treatment of Childhood Fecal Impaction. J Pediatr. 2002;141(3):410-4. 20. Loening-Baucke V, Krishna R, Pashankar DS. Polyethylene Glycol 3350 Without Electrolytes for the Treatment of Functional Constipation in Infants and Toddlers. J Pediatr Gastroenterol Nutr 2004;39(5):536-9. 21. Michail S, Gendy E, Preud'Homme D, et al. Polyethylene Glycol for Constipation in Children Younger Than Eighteen Months Old. J Pediatr Gastroenterol Nutr 2004;39(2):197-9. 22. Pashankar DS, Loening-Baucke V, Bishop WP. Safety of Polyethylene Glycol 3350 for the Treatment of Chronic Constipation in Children. Arch Pediatr Adolesc Med 2003;157(7):661-4. 23. Voskuijl W, de Lorijn F, Verwijs W, et al. PEG 3350 (Transipeg) Versus Lactulose in the Treatment of Childhood Functional Constipation: A Double Blind, Randomised, Controlled, Multicentre Trial. Gut 2004;53(11):1590-4. 24. Lexi-Comp Online, Pediatric & Neonatal Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc; September 17, 2012. 25. Sondheimer JM, Gervaise EP. Lubricant versus laxative in the treatment of chronic functional constipation of children: a comparative study. J Pediatr Gastroenterol Nutr 1982; 1(2):223-226. 26. Zanetti G, Marchiori E, Gasparetto TD, et al. Lipoid pneumonia in children following aspiration of mineral oil used in the treatment of constipation: high-resolution CT findings in 17 patients. Pediatr Radiol 2007;37:1135-39. 27. Marchiori E, Zanetti G, Mano CM, et al. Lipoid pneumonia in 53 patients after aspiration of mineral oil: comparison of high-resolution computed tomography findings in adults and children. J Comput Assist Tomogr 2010;34(1):9-12. 28. Charney EB, Bodurtha JN. Intractable Diarrhea Associated With the Use of Sorbitol. J Pediatr 1981;98(1):157-8. 29. Hawley PH, Byeon JJ. A comparison of sennosides-based bowel protocols with and without docusate in hospitalized patients with cancer. J Palliat Med 2008; 11(4):575-581. 30. Bellomo-Brandao MA, Collares EF, da-Costa-Pinto EA. Use of erythromycin for the treatment of severe chronic constipation in children. Braz J Med Biol Res 2003; 36(10):1391-1396. 31. Akkawi F, Eksborg S, Andersson A, et al. Effect of oral naloxone hydrochloride on gastrointestinal transit in premature infants treated with morphine. Acta Paediatrica 2009;98:442-7. 32. Loening-Baucke V. Prevalence, Symptoms and Outcome of Constipation in Infants and Toddlers. J Pediatr 2005;146(3):359-63.
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