Ped Gi Handbook Naspghan

NASPGHAN
Pediatric Gastroenterology Hepatology and Nutrition Handbook
Introduction
This first Pediatric Gastroenterology, Hepatology and Nutrition Handbook a compendium from the NASPGHAN Fellows Committee, was conceived as a handy, problem-based, reference tool for the fellows intraining; but it grew from there into the handbook you now hold in your hands. It was designed to provide the most useful clinical information in a concise and convenient format. There are two versions of the handbook on the CD-ROM enclosed in this packet. One is organized in a problem-based outline format to be downloaded and used within a PDA platform. The second is designed for use on desktop or laptop computers (Windows or Mac-OS). It contains the entire text content, with tables and flow-charts in textbook quality print, for use as handouts or as teaching aids for rounds, talks, consults, etc. The authors were recruited from among the fellows training in North American programs and the information contained within the handbook was compiled from a variety of sources. Every effort has been made to verify the accuracy of the information here presented. This reference, however, is intended to be used as a handbook and therefore does not include a comprehensive review of these topics. Specific terms, such as medications, are cross-linked within the chapters as indicated and flowcharts and tables are arranged to be user-friendly and maximize viewable screen space. The chapters represent, what we felt, were the most common clinical concerns presented to the practicing pediatric gastroenterologist, but are by no means comprehensive. With each passing year it is our hope that the Handbook will be expanded and refined to enhance its value to the entire NASPGHAN membership. We would like to thank all the people who gave us their time and effort in crafting these fine chapters and without whom, this first handbook would not have been possible. Thank you for your faith in this enterprise. We would also like to thank the NASPGHAN leadership, specifically Dr. Richard Colletti and Dr. Harland Winter for their support and sage advice. To Margaret Stallings and the staff at NASPGHAN we give our thanks for their invaluable help. The efforts of Dr. William Berquist and the members of the Professional Education Committee in revising the final chapters are also greatly appreciated. Finally, this project would not have been possible without the generous support of SHS North America and we would like to thank them as well. We sincerely hope you find the material here covered to be truly helpful and easy to use. As always, we will welcome your comments and will keep on working to make each subsequent edition better. Sincerely, Robert E. Kramer, MD J. Antonio Quiros, MD Co-Editors
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NASPGHAN
Pediatric Gastroenterology, Hepatology and Nutrition Handbook Author List

Bradley Barth M.D. M.P.H. Clinical Fellow, Pediatric Gastroenterology Childrens Hospital Harvard University School of Medicine Boston, MA Upper GI Bleeding Mirna Chehade M.D. Instructor in Pediatrics Department of Pediatric Gastroenterology Mount Sinai School of Medicine New York, NY Cholestasis Denesh Chitkara M.D. Advanced Fellow, Enteric-Neurosciences Mayo Medical Center Rochester, MN Vomiting Dyspepsia Carolyn Daigneau RN CPNP Division of Pediatric Gastroenterology Texas Childrens Hospital Baylor University School of Medicine Houston, TX Constipation Jose J. Derdoy M.D. Assistant Professor of Clinical Pediatrics Childrens Hospital of Los Angeles University Southern California School of Medicine Los Angeles, CA Obesity Rima Fawaz M.D. Advanced Fellow, Pediatric Hepatology Mount Sinai School of Medicine New York, NY Lower GI Bleeding Ana Ma. Guilhon de Araujo SantAnna M.D. Clinical Fellow, Pediatric Gastroenterology St. Justine Hospital University of Montreal Montreal, CA Chronic Diarrhea Rula Harb M.D. Clinical Fellow, Pediatric Gastroenterology Childrens Hospital Los Angeles University Southern California School of Medicine Los Angeles, CA Abnormal Liver Tests Robert E. Kramer Assistant Professor of Pediatrics Division of Pediatric Gastroenterology University of Miami School of Medicine Miami, FL Obesity Mohamad Miqdady M.D. Department of Pediatric Gastroenterology King Hussein Childrens Hospital Amman, Jordan Constipation J. Antonio Quiros M.D. Assistant Professor of Clinical Pediatrics Division of Pediatric Gastroenterology UC Davis School of Medicine Sacramento, CA Dyspepsia Leonel Rodriguez M.D. Advanced Fellow in Gastrointestinal Motility Montefiore Medical Center Albert Einstein University School of Medicine Bronx, NY Vomiting James Rick M.D. (Capt. USAF) Department of Pediatric Gastroenterology Keesler Medical Center Biloxi, MS Ascites Maria-Stella Serrano M.D. Clinical Fellow, Pediatric Gastroenterology Louisiana State University School of Medicine New Orleans, LA Neonatal Cholestasis Steven Steiner M.D. Clinical Fellow, Pediatric Gastroenterology James Whitcomb Riley Hospital for Children University of Indiana Indianapolis, IN Acute Diarrhea Pushpa Sathya MD Fellow, Pediatric Gastroenterology Mc Master University Hamilton, ON Cholestasis in Children and Adolescents
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NASPGHAN
Index
I. II. III. IV. V. VI. VII. VIII. IX. X. XI. XII. XIII. XIV. XV. Vomiting.......................................................................................................................................... 4 Dysphagia........................................................................................................................................ 6 Functional Constipation & Encopresis ................................................................................................... 8 Dyspepsia ...................................................................................................................................... 11 Acute Diarrhea ............................................................................................................................... 13 Chronic Diarrhea............................................................................................................................. 17 Obesity.......................................................................................................................................... 20 Upper GI Bleeding........................................................................................................................... 23 Lower Gastrointestinal Bleeding ........................................................................................................ 26 Ascites .......................................................................................................................................... 28 Neonatal Cholestasis ....................................................................................................................... 32 Cholestasis in Children and Adolescents.............................................................................................. 37 Biochemical Tests of the Liver ........................................................................................................... 42 Parental Nutrition Guidelines............................................................................................................. 44 Drug Formulary .............................................................................................................................. 49
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NASPGHAN
I. Vomiting
A. Definition Vomiting is a physical act that results in the gastric contents forcefully brought up to and out of the mouth, aided by a sustained contraction of the abdominal muscles and the diaphragm at a time when the cardia of the stomach is raised and the pylorus is contracted. Pathophysiology 1. Vomiting Center (VC): is located in the dorsal portion of the medulla and that vomiting can be induced with electrical stimulation of this area. Afferent neural inputs to the VC are transmitted via the vagus and the sympathetic nerves. 2. Chemoreceptor trigger zone (CTZ): located in the area postrema of the medulla in the fourth ventricle. 3. Emetic stimuli can induce vomiting by two ways: Stimulating VC directly or indirectly by stimulating CTZ, which in turn activates the VC. VC can be stimulated directly by afferent stimuli from GI tract (chemical), pharynx, vestibular system, heart, peritoneum, thalamus, hypothalamus and cerebral cortex.. CTZ can be stimulated by drugs (opiates, digitalis, ergot derivatives, chemotherapy agents, ipecac, dopamine agonists), uremia, hypoxia, DKA, radiation and motion sickness. 4. Effector pathways: events leading to vomiting are the same. The emetic reflex begins with transient nausea and autonomic excitation, followed by nonperistaltic small bowel contractions and gallbladder contractions, then by intensive retrograde peristaltic wave that forces small bowel contents into the stomach suppressing gastric activity. The inspiratory muscles contract against a closed glottis (retching) resulting in esophageal dilation, then the abdominal muscles contract pushing gastric contents into the esophagus. Associated Phenomena 1. Hypersalivation 2. Cardiac Rhythm disturbances 3. Pupilary dilatation 4. Defecation Differential Diagnosis 1. Nonbilious a) Infectious: Most common cause of vomiting in children. (1) Viral: Most common viral agent is rotavirus (2) Bacterial: Salmonella, Shigella, Campylobacter, E. Coli, H. pylori (3) UTI, pyelonephritis, chronic sinusitis, otitis media, pharyngitis, pneumonia, peritonitis, hepatitis and meningitis (4) Parasites: Giardia b) Inflammatory: IBD, pancreatitis, appendicitis, cholecystitis, esophagitis, c) Gastritis, food allergy, cows milk protein allergy, celiac disease d) Metabolic (1) Inborn errors of metabolism: like MCAD deficiency, OTC deficiency, (2) Usually present in early infancy, associated with neurological symptoms, and metabolic acidosis, hyperammonemia, hypoglycemia and/or ketosis (3) Acute intermittent porphyrias (4) Uremia e) Endocrine (1) Diabetes mellitus (DKA), adrenal insufficiency (Addisons), (2) Carcinoid syndrome, ZE syndrome f) Neurologic: (1) Increased ICP: hydrocephalus, intracranial tumors, intracranial (2) Hemorrhage g) Cyclic Vomiting Syndrome: recurring attacks of severe vomiting, (1) sporadic and unpredictable in some and cyclic and predictable in others, usually in AM, with strong family history of migraine, diagnosed by clinical presentation and exclusion of other organic disorders (2) Abdominal migraine and migraine headaches h) Motion sickness i) Psychogenic: self-induced to seek attention, rumination, bulimia, anorexia nervosa, depression 2. Mechanical a) Newborn: Esophageal atresia, pyloric stenosis, gastric atresia, duodenal atresia, esophageal stenosis, duodenal web, intestinal duplication, annular pancreas, strictures due to NEC, Hirschprungs, midgut volvulus with malrotation, meconium ileus b) Children and adolescents: intussusception, malrotation, strictures due to inflammation, gastric volvulus, gastric outlet obstruction, inguinal hernia, SMA syndrome, UPJ obstruction, foreign body, bezoar, duodenal hematoma, surgical adhesions c) Functional: achalasia, GERD, gastroparesis, scleroderma, pseudo-obstruction, Ileus, familial dysautonomia d) Toxic: Drugs, poisonings (lead, staph toxin) e) Other: Overfeeding, Reye Syndrome, pregnancy f) Bilious (1) Mainly anatomic conditions causing obstruction distal to the lig of Treitz. 3. Consequences of Vomiting a) Metabolic: (1) Potassium deficiency (2) Alkalosis (3) Sodium depletion b) Nutritional c) Mechanical injuries to esophagus and stomach: (1) Mallory-Weiss (2) Boerhaaves syndrome (3) Tears of the short gastric arteries resulting in shock and hemopritoneum
B.
C.
D.
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NASPGHAN d) e) E. Treatment Name Mild Antiemetic Activity Antihistamines:diphenhydramine, hydroxyzine, promethazine, meclizine Anticholinergics: Hyoscyamine Benzodiazepines: Lorazepam, midazolam, diazepam Moderate Antiemetic Activity Phenotiazines: Prochlorperazine, perphenazine chlorpromazine, promethazine Buthyrophenone: Droperidol, haloperidole, domperidone Corticosteroids: Dexamethasone Cannabinoids: Dronabinol, nabilone Potent Antiemetic Activity Metoclopramide Indication Dental: erosions and caries Purpura
Mechanism
Motion sickness and mild chemotherapy induced vomiting Prophylaxis of motion sickness Chemotherapy induced vomiting
Probable Labyrinthine suppression and H1 block in CNS Antimuscarinic effect in labyrinth or CNS GABA inhibition
Chemotherapy and Cyclic Vomiting Syndrome Cyclic vomiting syndrome, postoperative, chemotherapy. Domperidone for motility disorders. Mild chemotherapy vomiting, emesis from increased ICP Chemotherapy
D2 receptor antagonist at CTZ D2 receptor antagonist at CTZ D2 receptor block at enteric nervous system Unknown Unknown
Chemotherapy, motility disorders, GERD
Normal dose: D2 receptor blockade at CTZ and enteric nervous system High dose: 5-HT3 activity enterically D2 receptor blockade Enteric acetylcholine release
Trimethobenzamide Cisapride
Often for acute gastroenteritis and to abort CVS Motility disorders, GERD. Discontinued because of cardiac effects Chemotherapy and postoperative vomiting
5-HT3 Receptor Antagonists: Ondansentron, granisetron
5-HT3 receptor blockade mainly in enteric nervous system
F. G.
Authors Leonel Rodriguez MD References Brown J, Li B. Recurrent Vomiting in Children. Clinical Perspectives in Gastroenterology. 2002; 5: 35-39 Fleisher DR. Functional vomiting disorders in infancy: innocent vomiting, nervous vomiting and infant rumination syndrome J Pediatr. 1994;125:S84-94 Forbes D. Differential diagnosis of cyclic vomiting syndrome. J Pediatr Gastroenterol Nutr. 1995;21:S11-14. Lee M. Vomiting. In: Sleisinger & Fordtrans Gastrointestinal and Liver Disease. WB Saunders Co. 7th edition. 2002. Li B, Sferra T. Vomiting. In: Wyllie R, Hyams J, eds. Pediatric Gastrointestinal Disease. WB Saunders Co. 2nd edition. 1999:14-31 Murray K, Christie D. Vomiting. Pediatrics in Review. 1998; 19:337-341 Sondheimer JM. Vomiting. In: Walker WA, Durie PR, Hamilton HR, Walker- Smith LA, Watkins JB, eds. Pediatric Gastrointestinal Disease, Pathophysiology, Diagnosis, Management. BC Decker. 3rd edition. 2000:97-102
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NASPGHAN
II. Dysphagia
A. Definition: From the Greek "difficult to swallow." In the pediatric patients, swallowing disorders are rarely isolated. In contrast to adults, growth and development of the swallowing apparatus, oromotor reflexes and maturation of feeding behavior should be considered in the pediatric population. B. Clinical manifestations and complications of impaired deglutition: 1. Cough 2. Pain on swallowing 3. Food impaction 4. Halitosis 5. Respiratory: apnea and bradycardia, choking episodes, chronic noisy breathing, reactive airway disease, chronic or recurrent pneumonia, bronchitis, otitis media and atelectasis. 6. Malnutrition 7. Sialorrhea 8. Chest Pain 9. Regurgitation 10. Weight loss 11. Globus pallidus-sensation of lump or tightness in throat Differential diagnosis: 1. Oral Phase: a) Nasopharyngeal: choanal atresia and stenosis, infections, tumors, trauma b) Oral cavity and oropharynx: cleft lip/palate, hypopharyngeal webs/stenosis, craniofacial syndromes, trauma, adenoid/tonsil hypertrophy, pharyngitis c) Larynx: stenosis, webs, paralysis, laryngomalacia, laryngotracheoesophageal cleft, trauma, post-intubation 2. Pharyngeal Phase: a) Anatomical defects: stenosis, webs, intubation, endoscopy, trauma b) Oropharyngeal incoordination and motility disorders: cricopharyngeal dysfunction-cricopharyngeal hypertension, hypotension, incoordination c) Neurologic defects (1) CNS: Head trauma, hypoxic brain damage, cortical atrophy, microcephaly, anencephaly, myelomeningocele, chiari malformation, dysautonomy, infections (2) Peripheral nervous system: trauma, congenital (3) Neuromuscular: myotonic muscular dystrophy, myasthenia gravis, guillian-barre syndrome, poliomyelitis d) Esophageal Phase: (1) Anatomic defects: strictures, stenosis, webs, diverticulae, tracheoesophageal fistula, trauma, aberrant cervical thymus (2) Vascular abnormalities: aberrant right subclavian artery, double aortic arch, right aortic arch with left ligamentum (3) Mucosal lesion: esophagitis (caused by GERD, infections like candida, CMV, HSV, TB and HIV, caustic ingestion, burns, radiation and also eosinophilic esophagitis, cows milk protein and food allergy, arretts esophagus, malignancy and food impaction, drugs that cause direct esophageal mucosal damage like tetracycline, potassium chloride, quinidine, aspirin and NSAIDs (4) Esophageal motility disorder: (a) Primary esophageal motility disorders: Idiopathic achalasia, diffuse esophageal spasm, nutcracker esophagus, nonspecific esophageal motility disorder, esophageal paralysis (atony). (b) Secondary esophageal motility disorders: GERD, eosinophilic esophagitis, chronic intestinal pseudoobstruction, dermatomyositis, systemic lupus erythematosus, scleroderma, diabetes, thyroid disorders, chagas disease, medications, depression, bulimia, anorexia, Graft-versus-host disease, mitochondrial disorders, neurologic, paraneoplastic syndrome. (5) Drug Effect: associated with reduced LES tone and reflux like theophylline, calcium channel blockers, nitrates, alcohol, fat and chocolate)
C.
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NASPGHAN D. Algorithm for evaluation and management of Dysphagia in Children
Algorithm for Evaluation and Management of Dysphagia in Children
Medical and Feeding History Physical examination Observational feeding trial
Oral Phase: drooling, choking, respiratory distress
Pharyngeal Phase: Dysphagia while swallowing
Esophageal Phase: Dysphagia after swallowing, +/- pain
Exclude nasopharyngeal, oral cavity, laryngeal and oropharyngeal defects
Exclude anatomical defects, motility disorders and oropharyngeal incoordination
Exclude neurological disorders
Dysphagia to solids only: Anatomic/ mucosal lesion
Dysphagia to solids liquids: exclude motility disorder
Consider ENT consultation
Videofluoroscopy (modified barium swallow and/or UGI series)
Consider Neurology consultation
UGI series Upper endoscopy Con. Eso. Manametry consider chest CT
Eso. Manometry UGI series upper endoscopy
(+) Aspiration
(-) Aspiration
Consider direct laryngoscopy and enteral tube feeds
Speech and swallow consultation to optimize safe feeds
E.
Management of Cricopharyngeal/ Esophageal Motility Disorders 1. CP Hypertension: consider CP Myotomy 2. CP Hypotension Incoordination: Aspiration control/Nutrition 3. Diffuse esophageal spasm, nutcracker esophagus, non-specific esophageal motility disorder-aggressive PPI treatment and prokinetics (GERD/esophagitis is the most common reason). Reports of TCA alleviating symptoms of globus pallidus, and chest pain. 4. Idiopathic Achalasia: Hellar myotomypartial fundoplication (Thal) vs. Botox of LES Authors Leonel Rodriguez M.D. Denesh K. Chitkara, M.D. References: Castell, D. Approach to the patient with dysphagia. In: Yamada, T. Textbook of Gastroenterology. 2nd edition. 1995. Castell, D. et al. Esophageal Manometry. In: Schuster, M. et al. Schuster Atlas of Gastrointestinal Motility. 2nd. Edition. 2002:69-85. Clouse RE, et al. Functional esophageal disorders. Gut 1999 (45) Supp II: II31-II36. Del Rosario, F. and Di Lorenzo, C. Achalasia and other motor disorders. In: Wyllie, R. and Hyams J. Pediatric Gastrointestinal Disease. 2nd. Edition. 1999:189-1197. Habib, F. et al. Oropharyngeal dysphagia in neurological patients. In: Corazziari, E. Chronic Gastrointestinal Disorders. 1999:387-398. Hirano, I. Achalasia. Clinical perspectives in Gastroenterology. 2002;(5): 165-172. Nurko S. Other Motility Disorders. In. Walker, W et al. Pediatric Gastrointestinal Disease. 3rd. edition. 2000. Ravich, W. Pharyngeal manometry. In: Schuster, M. et al. Schuster Atlas of Gastrointestinal Motility. 2nd. Edition. 2002: 59-68. Spiecker, M. Evaluating Dysphagia. American Family Physician 2000; 61(12): 3639-43. Tack, J. Chest Pain of oesophageal origin. In: Corazziari, E. Chronic Gastrointestinal Disorders. 1999:153-169. Tuchman, D. Disorders of Deglutition. In: Walker, W. et al. Pediatric Gastrointestinal Disease. 3rd. edition. 2000: 277-288.
F.
G.
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NASPGHAN
III. Functional Constipation & Encopresis

A. Definitions: 1. Constipation: delay or difficulty with defecation, present for two or more weeks. Note: To achieve a normal defecation a child should have a normal rectum and puborectalis muscle, normal internal and external anal sphincters, and normal innervation of these structures through both the autonomic and somatic nervous systems. 2. Encopresis: involuntary fecal soiling or incontinence secondary to chronic constipation. Physiologic encopresis is most common and is manifested as overflow incontinence that occurs as a result of severe constipation, fecal impaction and a dilated rectum. Related behavioral components including active stool withholding, fear, and embarrassment that may resolve with adequate treatment. 3. Normal defecation: frequency of defecation and the consistency of stool are related to age and diet. Some infants have a bowel movement after each feed due to an active gastrocolic reflex and others, particularly breast fed infants, can have normal stools every 2-3 days. Frequency declines to a mean average of 1.7 stools per day at 2 years of age and 1.2 stools per day at 4 years of age. After 4 years, the frequency remains unchanged. 4. Idiopathic constipation: (functional constipation or fecal retention) is commonly due to a painful defecation event such as an anal fissure, bad toilet-training experience, changes in routine or diet, stressful events, intercurrent illness, unavailability of toilets, or postponing defecation because the child is too busy. On the urge to defecate, he/she contracts his external anal sphincter to avoid pain or discomfort resulting in stool withholding. Chronic retention results in abdominal cramps, abdominal distension, irritability, and decreased oral intake. Chronic rectal dilatation results in decreased sensory capability, and weakened propulsive peristaltic activity. Eventually, the constipation becomes self-perpetuating.
B. Physiology of Defecation: Stool movement into the rectum stimulates the rectal wall, sends signals via the intrinsic nervous system resulting in the relaxation of the internal anal sphincter developing the sense of urgency associated with defecation. If defecation is convenient, the external sphincter will relax and stool is propelled by colonic peristalsis and a secondary reflex, via the somatic nervous system, is activated resulting in contraction of the abdominal musculature emptying the distal colon. If defecation is inconvenient, contraction of the external sphincter is initiated, first by reflex and then intentionally. Stool retention is assisted by contraction of the puborectalis muscle, which constrict and angulates the anal canal. If sustained, the reflex to the internal sphincter wanes and the urge to defecate disappears. C. Background: Chronic constipation is common, 3% of primary care physician office visits and 20-25% of the referrals to a pediatric gastroenterologist. It is important to distinguish functional constipation (i.e. without evidence of a pathological cause) from constipation with an organic cause. Beyond the neonatal period, the most common cause of constipation is functional or idiopathic constipation. D. History 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. Delay in passing first meconium? Hx of any period of normal stooling? Duration of constipation? Caliber (small in Hirschsprungs, large in functional) Frequency and consistency of stools? How long does it take to pass stool? Blood with stool? Fecal soiling? (Sometimes may be mistaken for diarrhea by some parents) Stool withholding behavior? Change in formula, diet, and travel? Problems with toilet training? Associated symptoms such as fever, vomiting, and bloody diarrhea? (Consider Hirschsprungs enterocolitis) What studies and/or medications have been used? What other things have the parents been doing to manage the problem? Are there other physical conditions/diagnoses e.g. UTI s, genetic syndromes, surgeries? Does the child take any other medications regularly? Is there any family history of constipation, colon problems?
E.
Red Flags 1. Fever, Vomiting, Bloody Diarrhea 2. Failure to thrive 3. Tight, empty rectum with presence of palpable abdominal fecal mass 4. Abnormal neurological exam Physical exam: 1. In addition to a thorough physical exam including vital signs and growth parameters, make sure you check the following: a) Abdomen: Distention, fecal masses, tenderness, and bowel sounds b) Back: signs of spinal abnormalities e.g. spinal dimpling, tuft of hair c) Rectal exam: during the first visit (1) Position of anus? (2) Anal wink? (3) Anal fissures, skin tags? (4) Soiling in the underwear or around the anus? (5) Anal stenosis? (6) Anal sphincter tone (nut-cracker sphincter)? (7) Rectal vault dilatation? (8) Stool in rectum consistency, fecal impaction explosive stool upon withdrawal of finger? (9) Hemoccult test d) Neurological exam: is essential (1) Lower extremity tone and strength (2) Cremasteric reflex (3) Deep tendon reflexes
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NASPGHAN G.
Pediatric Gastroenterology Hepatology and Nutrition Handbook Laboratory Studies: 1. These tests would be advisable for children who remain constipated in spite of medical therapy: 2. T4/TSH 3. Celiac Panel 4. Serum Calcium 5. Serum Lead level 6. Sweat test (if clinically indicated) Radiologic studies: 1. Abdominal X-ray (KUB): a) Helpful in the child who is obese with incomplete abdominal exam, refuses a rectal exam, or in whom there are other psychological factors (sexual abuse). b) Might be helpful if no stool in rectum to evaluate for obstruction. 2. Unprepped barium enema a) To evaluate for possible Hirschsprungs disease. b) Unprepped means no clean out (no enemas, no suppositories) and no rectal exam 48-72 hours prior to the study. Management: 1. Goals: a) b) c)
H.
I.
Pass 1-2 soft stools daily (painless stools help to overcome fear and withholding Allow the rectal vault to approach a normal size (on average this may take 6-12 months or longer Establish an adequate diet and fluid intake, a regular toilet routine and eliminate fear of defectaion. (1) Diet: It is important to encourage balanced diet that includes whole grains, fruits and vegetables as part of the treatment for constipation in children, elimination of certain foods e.g. milk, and cheese is not necessary and therefore not recommended. Fiber supplements are not recommended in children with dilated rectum since they are bulking agents. (2) Fecal Impaction If the impaction is significant, suppositories are not likely to be an effective way to evacuate the stool. Both oral and rectal therapy (enemas) might be needed. Mineral oil (rectal) may be used to soften hard stool in preparation for a stimulating enema or oral laxative. J. Treatment 1. Stool Softeners: act to soften stool but do not create the urge to defecate. Not a good choice for long-term use. Mineral oil: oral or reactal, not recommended in a child less than one year of age because of the risk of aspiration and a) lipoid pneumonia.May be mixed with orange juice or try a Popsicle/freezer pop crushed and pour oil over top and feed with spoon. b) Docusate sodium (Colace) not effective for long-term management but may be helpful for the child that continues to have hard stools after laxative therapy completed. 2. Stimulants: Act by stimulating the colon to contract. Bisacodyl: Oral or suppository a) b) Glycerine: suppositories are often prescribed but rarely helpful for removing hard impactions Senna (Senokot): Available in pills or liquid (chocolate flavored) and in Ex-Lax chocolate squares and granules. c) Needs to be used with a stool softener. Osmotic: The first three laxatives listed below are fermented in the colon to create the osmotic effect. a) Malt extract (Maltsupex) Safe and can be added to infant formula. b) Dark corn syrup: The glycoproteins that give the dark corn syrup its brown color are unabsorbed and pass into the colon. Works best in infants. Light corn syrup is ineffective. Lactulose (liquid or powder, Kristalose): Safe. Side effects: increased gas as a byproduct of its fermentation, and c) tolerance to lactulose may develop as a result of change in the fermentation capacity of the colon. d) Magnesium hydroxide (Milk of Magnesia) (also has some stimulant action). Given once a day, better at night. May be flavored with syrups e.g. chocolate, strawberry. Starts working in 6-10 hours. Comes in concentrated formulation that permits the child to take the volume of the regular dose (1) Overdose could result in hypermagnesimia, hypophosphatemia, and secondary hypocalcemia Polyethylene Glycol Electrolyte Solution & Powder: (Miralax) e) (1) A non-absorbable electrolyte solution that can be taken orally or by nasogastric tube if used for disimpaction or cleaning before colonoscopy (2) Powdered form that dissolves in 4-8 oz water or flavored beverage is also available. Also given once a day (3) Side effects include nausea, vomiting, bloating, and abdominal cramps. Aspiration pneumonia is a potential risk with nasogastric tube administration. Safety of long- term maintenance is not well established Enemas a) In cases of impaction it may be helpful to soften the stool in the rectal vault with mineral oil (oral or enema) or liquid glycerin (Baby Lax) before starting oral laxatives. b) Generally, no more than two enemas should be given in a single day. c) A large-volume enema (e.g. saline or soapsuds) usually is more effective than a small-volume enema (e.g. sodium phosphate) in significant constipation. d) There is a risk of mechanical trauma to rectal wall, abdominal distention, vomiting. e) Phosphate enemas: (Fleet Enema) it is an osmotic laxative, avoided in children less than 1 year of age because of renal immaturity f) Frequent use or large volume may cause severe and lethal episodes of hyperphosphatemia, hypocalcemia, with tetany. Use with caution in patients with renal impairment. (1) Soap suds enema: is prepared by adding 1 tsp of dish washing detergent (for hand use) to 1000 mls of water. Normal dose is 20 ml/kg (max 1 L), Soap suds enemas are not intended to be used for routine management of constipation. They are useful primarily for removing impacted stool. The routine use of soapsuds enemas can result in a detergent proctitis. (2) Saline enema: may be helpful if the child is not severely impacted. They can be prepared at home by mixing 1 tsp of table salt in 1000 mls of water; normal dose is 20 ml/kg (max 1 L). Saline enemas can be used in enema programs for children with anorectal malformations and spina bifida.
3.
4.
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NASPGHAN
Pediatric Gastroenterology Hepatology and Nutrition Handbook (3) Tween 80/Gastrografin: This enema consists of a detergent (Tween 80) and water-soluble contrast (Gastrografin) given under fluoroscopic control to assure filling of the colon and promote evacuation. Given in radiology department allowing imaging of colon. (4) Pulsated Intermittent Evacuation Enema (PIEE) (a) Is a newly developed device that works by mechanically destroying hard stool using pulsated water in varying volumes. It is generally given without sedation. The patient must weigh a minimum of 15 kg. 5. Stopping the Laxative: a) When the goals of treatment are met (the average treatment time is 6-12 months) taper the laxative slowly, usually by tsp increments with 2 weeks between decreases. The next decrease is not made unless the child has been doing well on the previous lowered dose. b) Keep a daily record of the stools passed during the taper and for a minimum of 3 months after stopping laxative treatment. Behavioral therapy: a) Remember children withhold to avoid pain. Stool withholding behaviors are often eliminated or at least decreased when the pain is eliminated by the laxative program that produces painless bowel movements. b) Be supportive and encourage children to relax with bowel movements. c) DO NOT PUNISH! d) Simple rewards like using a calendar or chart with stickers provide positive support to reinforce the childs progress. (e.g. Smiley Faces) e) Most children do not want to soil but frequently have developed tolerance to soiling and are not concerned about soiled clothing. It therefore may require more effort to get them to use the bathroom. Children with attention deficit and hyperactivity, tend to have more problems because they may be easily distracted. f) For some children, it may be helpful to enlist the help of a behavioral psychologist to support the medical treatment plan.|
6.
K.
Authors Carolyn Daigneau RN, CPNP Mohamad Miqdady MD References: Altemeier WA, Hemme, C. A pediatricians view: the importance of successful Passage. Pediatric Annals. 28 (5) 276-278, May 1999. Baker SS, Liptak GS, et. al. Constipation in infants and children: evaluation and Treatment. Journal of Pediatric Gastroenterology and Nutrition. 29: 612-626, November 1999. Bishop PR, Nowicki JM. Defecation disorders in the neurologically impaired Child. Pediatric Annals. 28 (5) 322-329, May 1999. Blum NJ, Taubman, B, Osborne ML. Behavioral characteristic of children with Toileting refusal. Pediatrics. 99 (5) 50-53, January 1997. Buttross S. Encopresis in the child a behavioral disorder: when the initial Treatment does not work. Pediatric Annals. 28 (5) 317-321, May 1999. Dautenhahn LW, Blumenthal BI. Functional constipation: a radiologists Perspective. Pediatric Annals. 28 (5) 304-306, May 1999. Guerrero RA, Cavender CP. Constipation: physical and psychological sequelae. Pediatric Annals. 28 (5) 312-316, May 1999. Klish W.J, Functional constipation & Encopresis, Oskis Pediatrics. Third edition, 1637-1639, 1999 Lewis LG, Rudolph CD Practical approach to defecation disorders in children. Pediatric Annals. 28 (5) 260-268, May 1999. Loening-Baucke, V. Functional constipation. Seminars in Pediatric Surgery.4 (1_ 26-34, February 1995. Lowe JR, Parks BR. Movers and shakers: a clinicians guide to laxatives. Pediatric Annals. 28 (5) 307-310, May 1999. Murphy MS, Clayden, G. Constipation. Walker WA and others, editors: Pediatric gastrointestinal disease: pathophysiology, diagnosis, Management, Ed 3rd ed., St. Louis, 2000 Mosby. North American Society for Pediatric Gastroenterology and Nutrition medical position statement Constipation in Infants and Children: Evaluation and Treatment. Nowicki MJ, Bishop PR. Organic causes of constipation in infants and children. Pediatric Annals. 28 (5) 293-300), May 1999. Parker PH. To do or not to do? that is the question. Pediatric Annals. 28 (5) 283-290, May 1999.
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NASPGHAN
IV. Dyspepsia
A. Definition: Elegant but inadequate term derived from the Greek bad to digest. chronic or recurrent pain or discomfort centered in the upper abdomen (epigastrium) most widely accepted definition1 B. C. Prevalence: 20% of adolescents in the community report upper abdominal pain, with 5-10% experiencing nausea2, 3. Clinical Manifestations1, 4: 1. Retching 2. Vomiting 3. Fullness 4. Belching 5. Queasiness 6. Nausea 7. Bloating 8. Early Satiety 9. Upper Abdominal Pain Differential Diagnosis: 1. Functional Disorders a) Functional Dyspepsia-Pediatric Rome II criteria-In children mature enough to provide an accurate pain history, at least 12 weeks, which need not be consecutive, within the preceding 12 months of: (1) Persistent or recurrent pain or discomfort centered in the upper abdomen; and (2) No evidence (including at upper endoscopy) that organic disease is likely to explain the symptoms; and (3) No evidence that dyspepsia is exclusively relieved by defection or associated with the onset of a change in stool frequency or stool form. b) GERD1-Predominant symptom is "heartburn"-see chapter on GERD c) Rumination Syndrome-6 weeks in the previous 12 months of recurrent regurgitation of recently ingested food which: (1) Begins within 30 minutes of meal ingestion (2) Is associated with either re-swallowing or expulsion of food (3) Is not associated with mechanical obstruction (4) Does not respond to treatment for GERD (5) Is not associated with nocturnal symptoms d) Post-viral Gastroparesis6- Symptoms following a viral illness e) Abdominal migraine: In 12 months time, 3 or more paroxysmal episodes of mid-line abdominal pain associated with headache, photophobia or an aura-warning period and a family history of migraines. In the absence of a documented metabolic, GI, CNS or biochemical abnormality 2. Inflammatory/ Mucosal Disease a) H. pylori infection b) NSAID use c) Inflammatory Bowel Disease d) Eosinophilic-Allergic Gastroenteritis e) Peptic disease f) Menetriers disease g) Parasites h) Varioloform gastritis i) Celiac Disease j) Schoenlein-Henoch Purpura k) Lactose/Carbohydrate mal-absorption or intolerance 3. Anatomic Disorder a) Malrotation b) Duodenal web 4. Other: a) Chronic Pancreatitis b) Chronic cholecystitis c) Uretero-pelvic Obstruction Abdominal Epilepsy: d) Psycogenic vomiting e) Anorexia Nervosa Diagnostic Evaluation: 1. General a) Physical Exam b) Basic laboratory tests: CBC, ESR, Albumin, Urinalysis, Liver tests, Amylase/Lipase, Stool for Occult blood, Giardia Ag (O+P). 2. Radiology a) Ultrasound-useful to screen biliary-hepatic-pancreatic system, diagnosis of UPJ obstruction b) UGI-useful to evaluate anatomic obstruction/malrotation of the upper gastrointestinal tract c) Scintigraphy-useful to evaluate rate of gastric emptying, and may guide prokinetic therapy. 3. Endoscopic Evaluation a) Indications: (1) Suspicion of reflux esophagitis (2) Removal of foreign object (3) Unexplained abdominal or chest pain (4) Unexplained vomiting (5) Stricture dilatation
D.
E.
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NASPGHAN 4. 5. F.
Pediatric Gastroenterology Hepatology and Nutrition Handbook Esophageal pH monitoring a) Indications-useful to detect extra-esophageal manifestations of GERD, and unrecognized GERD. Esophageal Manometry a) Indications-symptoms of dysphagia- with or without evidence of achalasia on UGI
Therapy 1. General Principles a) Anti-reflux measures b) Trigger avoidance 2. Diet a) Timing of meals b) Small-frequent feedings c) Liquid diet-may facilitate delayed gastric emptying 3. Alternative a) Hypnotherapy 4. Pharmacotherapy a) Anti-acid medication: (1) H2 Blockers: (a) Cimetidine (b) Famotidine (c) Ranitdine (2) Proton Pump Inhibitors: (a) Omeprazole (b) Esomeprazole (c) Lanzoprazole (d) Pantoprazole b) Pro-kinetic medications (1) Metoclopramide (2) Domperidone (3) Cisapride (4) Tegaserod11 c) Visceral Sensitivity (1) Tri-cyclic antidepressant d) Impaired Gastric Accomodation (1) Sumatriptin 5. Surgical Therapy a) Nutritional supplementation-Gastrostomy or Jejunostomy b) GERD-consider fundoplication-may exacerbate symptoms Authors Denesh K. Chitkara MD Antonio Quiros MD References Bytzer P. H(2) receptor antagonists and prokinetics in dyspepsia: a critical review. Gut 2002; 50 Suppl 4:iv58-62. Calvert EL, Houghton LA, Cooper P, Morris J, Whorwell PJ. Long-term mprovement in functional dyspepsia using hypnotherapy. Gastroenterology 2002; 123:1778-85. Chial H, Camilleri, M, Williams, DE, Litzinger, K, Perrault, J. Rumination syndrome in children and adolescents: diagnosis, treatment and prognosis. Pediatrics 2003; 111:158-162. Cucchiara S, Bortolotti M, Colombo C, et al. Abnormalities of gastrointestinal motility in children with nonulcer dyspepsia and in children with gastroesophageal reflux disease. Digestive Diseases & Sciences 1991; 36:1066-73. Hyams JS, Burke G, Davis PM, Rzepski B, Andrulonis PA. Abdominal pain and irritable bowel syndrome in adolescents: a communitybased study. J Pediatr 1996; 129:220-6. Hyams JS, Davis P, Sylvester FA, Zeiter DK, Justinich CJ, Lerer T. Dyspepsia in children and adolescents: a prospective study.[comment]. Journal of Pediatric Gastroenterology & Nutrition 2000; 30:413-8. Mertz H, Fass R, Kodner A, Yan-Go F, Fullerton S, Mayer EA. Effect of amitriptyline on symptoms, sleep, and visceral perception in patients with functional dyspepsia. American Journal of Gastroenterology 1998; 93:160-5. Muller-Lissner SA, Fumagalli I, Bardhan KD, et al. Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther 2001; 15:1655-66. Rasquin-Weber A, Hyman PE, Cucchiara S, et al. Childhood functional gastrointestinal disorders. Gut 1999; 45 Suppl 2:II60-8. Sigurdsson L, Flores A, Putnam PE, Hyman PE, Di Lorenzo C. Postviral gastroparesis: presentation, treatment, and outcome. Journal of Pediatrics 1997; 131:751-4. Tack J, Piessevaux H, Coulie B, Caenepeel P, Janssens J. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 1998; 115:1346-52. Talley NJ, Lauritsen K. The potential role of acid suppression in functional dyspepsia: the BOND, OPERA, PILOT, and ENCORE studies. Gut 2002; 50 Suppl 4:iv36-41. Talley NJ. Dyspepsia: management guidelines for the millennium. Gut 2002; 50 Suppl 4:iv72-8; discussion iv79.
G.
H.
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V. Acute Diarrhea
A. Definition 1. Abrupt onset of increased fluid content of the stools, usually with an augmentation in the frequency of the number of stools 2. Duration < 2 weeks 3. Excess water content of the stools from an alteration in the function of the small and large intestinal processes involved in the absorption of organic substrates and water Epidemiology 1. In developing countries, acute diarrhea is still one of the major causes of death in the children under 5 years of age. a) Children in these regions may have between 3 and 8 episodes of diarrhea per year. b) The World Health Organization (WHO) estimates that 3 million of children die per year due to diarrhea. 2. In developed countries it is still an extremely common problem. a) In the United States estimated that 1-2 episodes per child per year occur in children below 5 years of age b) Accounts for 10% of hospital admissions for children in this age range and about 400 deaths/year c) In England the hospitalization rate is approximately 7% below 5 years of age. Etiology 1. Infectious: most common cause of acute diarrhea in children a) Pathogens and relative frequencies (developed countries) (1) Viruses (a) Rotavirus: 25-40% (b) Calicivirus: 1-20% (c) Astrovirus: 4-9% (d) Enteric-type adenovirus: 2-4% (e) Norwalk-like virus:? (2) Bacteria (a) Campylobacter jejuni: 4-8% (b) Salmonella: 3-7% (c) Escherichia col: 2-5% (d) Shigella: 1-3% (e) Yersinia enterocolitica: 1-2% (f) Aeromonas hydrophilia: 0-2% (g) Clostridium difficile: 0-2% (3) Parasites (a) Giardia Lamblia: 1-3% (b) Cryptosporidium: 1-3% 2. Allergic/ Adverse Food Reaction a) Allergy b) Toxin Mediated (1) Staph aureus (2) Scombroid c) Adverse Reaction (1) Fruits/juices 3. Drug Induced a) Antibiotics b) Laxatives c) Motility agents (1) Metoclopramide (2) Erythromycin (3) Cisapride (4) Tegaserod d) Miscellaneous (1) Caffeine (2) Alcohol (3) Histamine 4. Travelers diarrhea a) At least 80% of diarrhea in travelers from developed countries to developing countries is caused by bacterial pathogens20 b) Most common illness acquired by visitors to developing countries, affecting 20-50% of the 35 million people who travel from industrialized countries each year21. c) No pathogen is identified in half of the cases (1) Most common pathogens found in the adult population are Escherichia coli, Shigella, Salmonella, Campylobacter, Vibrio parahaemolyticus (in Asia), rotavirus (in Latin America), and Giardia lamblia (2) If a bacterial infection suspected, empirical antibiotics are suggested, with nalidixic acid, TMP-SMX, furazolidone and erythromycin (if campylobacter infection is a possibility)21.
B.
C.
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NASPGHAN 5. Others a) b) c)
Systemic infection Urinary Tract Infection Acute appendicitis
D.
Pathogenesis: 1. Normal Physiology a) Normal small intestine absorbs large amounts of sodium, chloride and bicarbonate, and secretes H+ ions, bicarbonate and chloride. b) Water passively follows the transport of solutes. c) Absorption takes place in the mature epithelial cells lining the middle and upper part of the small intestinal villi d) Secretion occurs predominantly in the crypts (undifferentiated cells). e) Absorptive capacity normally exceeds the secretory activity, resulting in net absorption of water and electrolytes. 2. Sodium: Most important ion in this process has three main mechanisms of absorption a) Sodium absorption coupled to nutrients (1) Remains intact during most of the acute diarrheal disorders (a) Is considered the pathophysiological basis for the utilization of orally administered hydration solutions in children with diarrhea (b) Specific carrier (SGLT-1) which is involved in coupling the entry of glucose across the brush border to that of Na (c) Some carriers for different categories of amino acids also couple their entry into the enterocyte with the downhill transport of Na. b) Electrogenic, amiloride-sensitive sodium absorption (1) Sodium can enter the cell down its electrochemical gradient, through selective channels uncoupled to other substrates in the ileum and throughout the colon c) Neutral NaCl absorption (1) Predominates in the ileum (2) Mediated by two coupled antiports; one exchanges Na+/H+ (cation exchanger) and the other exchanges Cl/HCO3- (anion exchanger). (3) Transport process most responsible for intestinal Na and water absorption in the absence of intraluminal nutrients. 3. Chloride and bicarbonate a) The major anions being actively secreted into the crypts of the gut lumen b) Electrogenic, as a result, passive diffusion of Na (cation) and water follows. c) Regulatory agents responsible for the homeostasis of the absorption and secretion of water and electrolytes are hormone peptides, active amines, arachidonic acid metabolites, and nitric oxide. 4. Diarrhea: When the system is altered, diarrhea ensues and can be a result of an osmotic force in the lumen (ex: lactose in lactose malabsorbers) or an increased secretory state (enterotoxin-induced diarrhea). a) Osmotic diarrhea (1) Moderately increased stool output (2) Stops with fasting (3) Stool osmolality normal to increased (4) Stool sodium usually < 50 mEq/L (5) Large stool osmolality gap (Osmolality - (2[Na + K] ) 100 mOsm (a) Large gap due to increased amount of organic acids produced by fermentation of malabsorbed carbohydrates, less from secreted ions (6) Secretory diarrhea (a) Very large stool output (b) No change with fasting (c) Normal stool osmolarity (d) Stool Na usually > 70 mEq/L (e) Low stool osmolality gap (Osmolality - (2[Na + K] ) < 50 mOsm (f) The majority of the measured stool osmolality is accounted for by secreted ions, little or none due to organic acids b) Mixed Diarrhea (1) Combination of osmotic and secretory diarrhea (2) Stool osmolality gap (Osmolality - (2[Na + K] ) = 50-100 mOsm c) Viruses causing enteritis invade mature intestinal epithelial cells, multiply, cause cell lysis, and then re-invade cells further down the small intestine. d) Consequence is a malabsorptive or osmotic diarrhea. 5. Diarrhea caused by bacterial infection is most frequently secretory a) Due to changes in epithelial cell ion transport b) May adhere to or invade the epithelium, producing either enterotoxin or cytotoxins. Clinical Presentation 1. Benign self-limited condition, resolving in a few days in developed countries. a) Clinical presentation and course of illness are dependent on the host and on the infecting organism. (1) Usually, the younger the child, the higher is the risk of acute dehydration as a result of high body water turnover and limited renal compensatory capacity of very young children. b) Depending on the infecting organism, the clinical pattern of the acute episode of diarrhea differs : 2. Direct cytopathic effect a) Location: proximal small intestine b) Etiologies (1) Virus (a) Enteropathogenic Escherichia coli (EPEC) (2) Giardia
E.
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Pediatric Gastroenterology Hepatology and Nutrition Handbook c) Presentation: copious watery diarrhea, vomiting, dehydration (frequent); often with lactose intolerance; no blood in the stools. Enterotoxin a) Location: small intestine b) Etiologies (1) Enterotoxigenic E. coli (2) Vibrio cholerae c) Presentation: watery diarrhea, can be copious, no blood in the stools. Invasion a) Location: distal ileum and colon b) Etiologies (1) Salmonella (2) Shigella (3) Yersinia (4) Campylobacter (5) Enteroinvasive E.coli c) Presentation: dysentery, cramps, fever. Cytotoxicity a) Location: colon b) Etiologies (1) Clostridium difficile (2) Enterohemorrhagic E. coli (EHEC) (3) Shigella c) Presentation: Dysentery, cramps, fever (1) EHEC (O157: H7) or Shigella may be followed by hemolytic-uremic syndrome. (a) If EHEC (O157: H7) is detected in a stool sample, child is often hospitalized for surveillance of the renal function (2) C. difficile infection may range in severity from mild antibiotic associated diarrhea to pseudomembranous colitis with toxic megacolon Post-enteritis diarrhea (PED) a) Complicates 10% of the cases of acute diarrhea b) Defined by the WHO as an episode of acute diarrhea which lasts for at least 14 days (1) In developing countries, PED is inversely correlated with age. c) Risk factors are malnutrition and immunodeficiency. d) PED causes 30-40% of all diarrheal deaths in underdeveloped countries. (1) Can develop due to persistent bacterial colonization, lactose intolerance and protein sensitization (2) Protein sensitization is the most common among children from developed countries, in whom PED is very unusual
3.
4.
5.
6.
F.
Management 1. Rehydration a) Main goal of the initial therapy of acute diarrhea. b) Oral rehydration therapy (ORT) by the WHO (1) Developed 30 years ago. (2) Based on maintenance of glucose/Na absorption during acute diarrheal episodes, permitting the PO route for rehydration instead of IV (3) Effective even when the damage to the epithelium is diffuse and severe, with infections such as Rotavirus c) Debate about the ideal concentration of the components of the oral solution indicated for children from developed countries. (1) WHO solution, indicated mainly for the children from underdeveloped countries in whom diarrheal losses are higher, contains more sodium, glucose and is more osmolar (osmolarity= 90 mMol/L) than the solution indicated for developed countries (45-60 mMol/L). (a) Recent systematic review of the literature concerning lower osmolarity ORS showed reduced need for unscheduled intravenous infusions, lower stool volume, and less vomiting, compared with standard WHO rehydration solution. (2) In developing countries, some rice based preparations were shown to be effective, possibly reducing the number of days with diarrhea. d) The volume of ORS to be prescribed is between 50-100 ml/kg to be administered during 3-4 hours, per os (1) May be administered by NGT if vomiting e) Glucose-based ORS most safe, effective, physiologic and effective way to rehydrate, and maintain hydration in children with acute diarrhea worldwide, as recommended by WHO, American Academy of Pediatrics and ESPGHAN. 2. Refeeding a) Breast-fed infants should continue to take breast milk during an episode of acute diarrhea, even if the infant is dehydrated (1) Must receive the breast-milk and the ORS (2) Formula-fed infants more controversial (3) ESPGHAN & WHO, recommend ORS for mild or moderately dehydrated children over 3-4 hours and then with a rapid re-introduction of normal feeding. (4) Not necessary to change the quality of food after a period of acute diarrhea, although often still prescribed, with no benefit for the child. 3. Antibiotics a) Occasionally bacterial infections may be treated with antibiotics, but they are not useful in the majority of cases of acute diarrhea b) Consensus statement recommended antibiotic treatment for V. cholerae, Shigella, Giardia lamblia and Entamoeba histolytica (1) Cholera: tetracycline is indicated in children over 8 years of age and trimethoprim/ sulfamethoxazole (TMPSMX) in younger children. (2) Shigella: ampicillin is used in sensitive strains and TMP-SMX in resistant strains. (3) Giardiasis and amebiasis: metronidazole. (4) Special situations
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Pediatric Gastroenterology Hepatology and Nutrition Handbook (a) Enteropathogenic E. coli when the course is prolonged (b) Enteroinvasive E. coli & Yersinia in patients with sickle cell disease or other immun- suppressed states (c) Salmonella in very young infants, if febrile or with positive blood culture
4. 5.
6.
7. G. H.
Clostridium difficile a) Stop all other antibiotics if possible b) If serious infection the treat with Metronidazole PO or Vancomycin PO, ? if efficacy equal with IV Tx Micronutrients a) Zinc deficiency is common in malnourished children with diarrhea (1) Trial in Bangladesh showed that zinc supplementation (20mg/day) during the acute episode of diarrhea reduced the duration of diarrhea, diminished stool output and resulted in better weight gain, and normalized serum zinc concentrations. Probiotics a) Bacteria, derived from healthy, live microflora (1) Yeasts and even helminths have also been used b) Long been used to treat human diseases c) Lactobacillus GG is the most investigated and was proven effective for the prevention and/or treatment of acute diarrhea in children and adults, particularly in rotaviral gastroenteritis. Antidiarrheal : There is no place for antidiarrheal agents (ex: loperamide) in the treatment of acute diarrhea.
Authors Ana Maria Guilhon de Araujo SantAnna References Bhandari N, Bhan MK, Sazawal S. Mortality associated with acute watery diarrhea, dysentery and proctated diarrhea in rural north India. Acta Paediatr 1992; S381: 3-6. Davidson G, Barnes G, Bass D, Cohen M, et al. Infectious Diarrhea in Children: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Ped Gastroenterol Nutr 2002; 35 (suppl 2): S143-S150. DuPont H, Ericsson C. Drug therapy: Prevention and treatment of travelers diarrhea. N Engl J Med 1993; 328: 1821-1827. Geme JW 3rd, Hodes HL, Marcy SM, Pickering LK, et al. Consensus: management of Salmonella infection in the first year of life. Pediatr Infect Dis 1988; 7: 615-621. Glass RI, Lew JF, Gangarosa RE, LeBaron CW, Ho MS. Estimates of morbidity and mortality rates for diarrheal diseases in American children. J Pediatr 1991; 118:S27-S33. Goodgame RW. Viral causes of diarrhea. Gastroenterol Clin North Am 2001; 30: 779-795. Hahn S, Kim Y, Garner P. Reduced osmolarity oral rehydration solution for treating dehydration due to diarrhoea in children: systematic review. BMJ 2001; 323: 81-85. Lima AA. Tropical diarrhoea: new development in travelers diarrhoea. Curr Opin Infect Dis 2001; 14: 547-52. MacFaul R, Jones S, Werneke U. Clinical training experience in distric general hospitals. Arch Dis Child 2000; 83: 39-44. Mailliard ME, Stevens BR, Mann GE. Amino acid transport by small intestinal, hepatic, and pancreatic epithelia. Gastroenterol 1995; 108: 888-910. Pizarro DPG, Sandi L, Moran JR. Rice-based oral electrolyte solutions for the management of infantile diarrhea. N Engl J Med 1991; 224: 517-521. Provisional Committee on Quality Improvement Subcommittee on Acute Gastroenteritis: Practice parameter: the management of acute gastroenteritis in young children. Pediatrics 1996; 97: 423-436. Recommendations for composition of oral rehydration solutions for children of Europe. Report of an ESPGAN Working group. J Pediatr Gastroenterol Nutr 1992; 14: 113-115. Roy SK, Tomkins AM, Akramuzzaman SM, Behrens RH, et al. Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhea. Arch Dis Child 1997; 77: 196-200. Stefano G. Acute Diarrhea. In: Walker WA, Durie PR, JRHamilton, JAWalker-Smith, JBWatkins. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. 3rd edition. BC Decker, 2000. pp 28-38. Szajewska H, Mrulowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials. Victora CG, Huttly SR, Fuchs SC, Nobre LC, Barros FC. Death due to dysentery, acute and persistent diarrhea among Brazilian infants. Acta Paediatr 1992; S381: 7-11. Walker-Smith JA, Sandhu BK, Isolauri E, Banchini G, et al. Guidelines prepared by the ESPGAN Working Group on Acute Diarrhoea. Recommendations for feeding in childhood gastroenteritis. European Society of Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr 1997; 24: 619-620. Worl Health Organization: Persistent diarrhea in children, Geneva, 1985, WHO- Diarrheal Disease Control. World Health Organization: The state of the worlds children 1988-1997. Geneva: WHO, 1997. Wright E, Hirsch J, Loo D, Zampighi G. Regulation of Na+/glucose cotransporters. J Exp Bio 1997; 200: 287-293.
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VI. Chronic Diarrhea

A. Definition An increase in frequency, fluidity, or volume (>10 g/kg/day in children) of stool persisting for one month or longer, relative to the usual stool habits of an individual. B. Pathophysiology 1. Secretory a) Fluid secretion accompanies active ion secretion by the intestine b) The gap between the measured stool osmolality and two times the sum of the stool sodium and potassium is typically < 40, and stool sodium concentration is frequently greater than 90 meq/L c) Diarrhea persists despite fasting by the individual d) Causes (1) Enterotoxin-producing bacterial pathogens (Vibrio cholera or enterotoxigenic E. Coli) (2) Enterotropic-hormone-secreting tumors (carcinoid, VIPoma, gastrinoma, neural crest tumors, medullary carcinoma of thyroid) (3) Ingestion of laxatives (cascara, senna, phenolphthalein) (4) Congenital ultrastructural and metabolic abnormalities of enterocytes 2. Osmotic (Malabsorptive) a) Accumulation of nonabsorbable solutes in intestinal lumen results in an increase in intraluminal osmotic pressure, retarding water and electrolyte absorption b) The gap between the measured stool osmolality and two times the sum of the stool sodium and potassium concentrations is typically > 80 c) Diarrhea resolves with fasting d) Causes (1) Excessive ingestion of nonabsorbable solutes (i.e. sorbitol) (2) Consumption of laxatives containing poorly absorbed ions (magnesium) (3) Carbohydrate malabsorption (disaccharidase deficiency, celiac disease) (4) Pancreatic insufficiency (cystic fibrosis) (5) Overfeeding. 3. Abnormal intestinal motility a) Increased intestinal motility results in decreased mucosal contact time (1) Causes of increased motility (a) Extensive bowel resection (short gut syndrome) (b) Inflammation (inflammatory bowel disease) (c) Hyperthyroidism (d) Hypocalcemia (e) Toddlers Diarrhea (i) May represent a variant of irritable bowel syndrome, characterized by rapid transit through the colon (ii) May be associated with excess carbohydrate (i.e. fruit juice) consumption (iii) Growth usually normal unless diet overly restrictive b) Decreased intestinal motility may result in stasis and bacterial overgrowth (1) Bacterial overgrowth and ileal resection lead to disruption of the bile salt enterohepatic cycle (a) Bacterial deconjugation of bile salts to dihydroxy bile acids, and the resultant metabolism of unabsorbed fatty acids to hydroxy fatty acids, may lead to colonic secretory diarrhea (2) Causes of decreased motility (a) Malnutrition (b) Intestinal pseudo-obstruction (c) Scleroderma (d) Endocrinopathies (i) Hypothyroidism (ii) Hypercalcemia (iii) Diabetes mellitus 4. Mucosal damage a) Reduction of mucosal surface area and/or damage to the mucosal surface impairs water and electrolyte uptake b) Causes (1) Inflammatory bowel disease (2) Infectious enteritis (3) Allergic gastroenteropathy (4) Celiac disease (5) Radiation enteritis 5. Protracted Diarrhea of Infancy a) Defined as chronic diarrhea of more than two weeks duration beginning before 6 months of age and associated with malabsorption and malnutrition b) Causes (1) Cows milk/ soy protein intolerance (a) Most common cause (b) May present with vomiting, irritability, bloody stools, poor feeding and/or diarrhea (c) Stool pH may be low and test + for reducing substances, but with WBCs consistent with colitis (d) High rate of cross-reactivity between cows milk and soy protein allergy (up to 50%) (2) Protracted infectious enteritis (a) Enterocyte injury may induce or unmask milk or soy protein sensitivity by altering permeability of mucosal membrane (b) Villous injury may result in secondary lactase/ disaccharidase deficiency (3) Microvillus inclusion disease (a) Rare congenital abnormality in microvillus membrane resulting in characteristic inclusions of microvilli on electron microscopy of small bowel (b) Presents shortly after birth and usually fatal without small bowel transplant (4) Tufting Enteropathy
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Pediatric Gastroenterology Hepatology and Nutrition Handbook (a) Similar to microvillus inclusion disease but with abnormal attachment of microvilli to mucosal surface, resulting in alteration of normal enterocyte architecture (tufting) Autoimmune enteropathy (a) Presence of antibodies directed at small bowel epithelium (Anti-enterocyte antibodies) causing upper tract inflammation and malabsorption Congenital Chloridorrhea (a) Congenital transport defect in which chloride-bicarbonate exchange transporter in ileum and colon is reversed, resulting in chloride and water secretion (b) Stool chloride > sodium and potassium combined Hirschsprungs Disease (a) May present with chronic diarrhea and enterocolitis in small but significant minority of patients Congenital sucrose-isomaltase deficiency (a) Does not present until sucrose introduced into diet (b) Stools may be negative for reducing substances since sucrose non-reducing sugar, but pH low
(5) (6)
(7) (8)
C.
Evaluation 1. History a) Stool history should include frequency, consistency, appearance, presence of fecal incontinence, and the presence of mucus or blood b) Presence of nocturnal symptoms and the duration of symptoms should also be elucidated c) Accurate diet history, including ingestion of fruit juices and dairy products d) Age of onset, ethnicity, medications, and travel and family histories 2. Physical examination a) Growth parameters, including height, weight, OFC, and weight-height ratio (or BMI), should be plotted b) Vital signs may confirm a suspicion of dehydration or endocrinopathy c) Look for evidence of weight loss or muscle wasting d) Abdominal examination may reveal distention, organomegaly, thickened bowel loops, bowel sounds, bruits, or masses e) Anorectal examination is essential, allowing for instant inspection of stool, occult blood status, presence of impaction, and active perianal disease f) Extraabdominal examination may reveal skin, joint, lymph, eye or thyroid gland abnormalities. 3. Stool a) Qualitative or quantitative fecal fat analysis, fecal alpha-1 antitrypsin, and fecal pH and reducing substances are used to define fat, protein, and carbohydrate malabsorption, respectively b) Fecal gram stain may demonstrate leukocytes, suggesting inflammatory or infectious diarrhea c) Stool culture for enteric pathogens and Clostridium difficile, and stool analysis for ova and parasites and Giardia antigen are less likely to be positive in chronic diarrhea d) Fecal elastase measurement is a screening tool for pancreatic insufficiency e) Simultaneous stool osmolality and stool electrolytes allows for calculation of stool osmotic gap and differentiation between secretory and osmotic diarrhea f) An elevated stool magnesium level suggests laxative abuse. 4. Blood a) Complete blood count screens for anemia, and white blood cell count is often elevated in inflammatory bowel disease b) Inflammatory markers, such as sedimentation rate, C-reactive protein, and platelet count, are often elevated in inflammatory bowel disease c) Fat-soluble vitamin deficiency can be assessed by serum carotene, prothrombin time, and vitamin A, D, and E levels d) Decreased total protein and albumin levels in combination with elevated fecal alpha-1 antitrypsin suggest protein-losing enteropathy e) Measurement of gastrointestinal hormones, including gastrin and VIP, is used to screen for neuroendocrine tumors f) Consider screening for Celiac disease with anti-endomysial antibody and/or tissue transglutaminase IgA, coupled with quantitative IgA to rule out false negatives from IgA deficiency 5. Endoscopy a) Individuals with prolonged bloody diarrhea should undergo endoscopic examination with biopsies (1) Profuse diarrhea following antibiotic use dictates laboratory and/or endoscopic evaluation for Clostridium difficile (2) Melanosis coli (dark staining of colonic mucosa) may be present with laxative abuse b) Upper gastrointestinal endoscopy allows for the collection of duodenal fluid for culture in cases of suspected bacterial overgrowth, and for the collection of small intestinal biopsies for histologic and electron microscopic analyses. 6. Other a) Contrast radiographic studies allow for evaluation of inflammatory bowel disease and intestinal obstruction, blind loops, Hirschsprungs and fistulas b) Abdominal/endoscopic ultrasound or CT is used for suspicion of neurogenic tumors or gastrinoma c) Lactose-hydrogen breath test for suspected lactose intolerance Therapy: appropriate therapy rests on identifying and treating the underlying cause 1. Diet a) The resumption of a regular diet for age is necessary, especially when physical examination is normal b) Limitation of fruit juice or lactose-containing products may be indicated, depending on history c) High fat, low carbohydrate diet may be helpful in toddlers diarrhea d) Gluten-free diet indicated for Celiac disease e) Avoidance of suspected food allergens may be indicated by presentation, family history and results of medical evaluation (1) Protein hydrolysate formula for infants with suspected milk/soy protein allergy (i.e. Alimentum, Nutramigen, Pregestimil) however a small percentage may require elemental formula (i.e. Neocate, Elecare, Vivonex)
D.
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NASPGHAN 2. 3.
Pediatric Gastroenterology Hepatology and Nutrition Handbook Empiric therapy with anticholinergics, pancreatic enzymes, antibiotics, or bile salt sequestering agents is not recommended. Therapy follows proper diagnosis a) Octreotide may be used in chronic secretory diarrhea due to neuroendocrine tumors b) Antibiotics indicated for enteric infections, bacterial overgrowth c) Appropriate immunomodulator treatment for Inflammatory Bowel Disease and Autoimmune enteropathy d) Surgical evaluation for Hirschsprungs, transplant in microvillus inclusion disease and other congenital disorders
E. F.
Authors Steven J. Steiner, MD References Fitzgerald, JF and Clark, JH. Chronic Diarrhea (pp. 43-57). In: Manual of Pediatric Gastroenterology, New York, NY. Churchill Livingstone, 1988. Tealey, AR and Reichelderfer M: Chronic Diarrhea. Lippincotts Primary Care Practice 1998,2:410-6. Vanderhoof JA: Diarrhea (pp.32-42). In: Pediatric Gastrointestinal Disease, Second Edition, Philadelphia, PA. WB Saunders, 1999.
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VII.
Obesity
A. Definition: Obesity is defined as excess body fat. 1. Since BMI is an excellent estimate of excess adiposity, the body mass index (weight/height2) is widely used in adult populations as the sole criterion for classifying patients as either overweight (BMI, 25-29.9 kg/m2 ) or obese (BMI, > 30 kg/m2). a) Adult BMI >35 with identified comorbidity considered morbidly obese b) Adult BMI > 40 (even without identified comorbidity) considered morbidly obese 2. Body mass index in childhood changes substantially with age a) In the United States, the 85th and 95th centiles of body mass index for age and sex based on nationally representative survey data have been recommended as cut off points to identify overweight and obesity (1) Generally BMI > 85%ile but < 95%ile for age considered overweight (2) BMI > 95%ile for age considered obese (3) BMI > 97%ile for age considered morbidly obese (4) Cutoffs may overestimate adiposity in athletic youths with large muscle mass Epidemiology 1. Adults a) Overweight: In 1999 34% of Americans met the criteria for overweight, the highest percentage ever observed. b) Obese: In 1999, almost 27% of the American population had BMIs of greater than 30 kg/m2. 2. Children: The prevalence of child and adolescent obesity has increased dramatically over the last 30 years. a) For all race and ethnic groups combined, the prevalence of overweight and obesity was 22% and 10.9%, respectively b) The highest prevalence of overweight is found among 6 to 11 years old African-American girls (31%) and MexicanAmerican boys of similar age (33%).8 3. Risk Factors a) The two most important risk factors are parental obesity and ethnic background (1) Investigators noted that if both parents were obese, 80% of the children developed obesity (2) If one parent was obese, about 50% of the children developed obesity (3) If neither parent was obese, only 10% of the children became obese. b) Obese children are at risk for becoming obese adults. The risk of remaining obese increases with age and the degree of obesity. c) Children in the USA spend 75% of their waking hours being inactive, compared with remarkably little time in vigorous physical activity; estimated at only 12 min per day. d) The epidemic increase in childhood overweight is the most common health problem facing US children Causes 1. Obesity is a direct consequence of the first law of thermodynamics. Energy that is not consumed must be stored. Obese persons become obese because of cumulative excess in energy intake that exceeds their energy requirements. 2. Although the combination of increased energy intake and decreased physical activity is responsible for most child and adolescent obesity, a strong body of evidence suggests that genetic factors contribute greatly to the severity of symptoms resulting from this obesigenic environment. 3. Obese children tend to consume diets higher in fat which have higher caloric density. 4. Decreased resting metabolic rate may also be another factor involved in the development of obesity. Differential Diagnosis 1. Primary Obesity a) For most obese children, the cause is primary obesity and is not associated with a specific clinical, metabolic or genetic syndrome. (1) Primary obesity is associated with increased height, advanced bone age, and early puberty. b) Fewer than 5% of all cases are due to an underlying medical disorder. 2. Endocrine Disorders a) Cushing syndrome b) Hypothyroidism c) Pseudohypothyroidism type I d) Hyperinsulinemia e) Growth hormone deficiency f) Panhypopituitarism g) Stein-Leventhal syndrome (polycystic ovary syndrome) 3. Congenital Disorders a) Muscular dystrophy b) Myelodysplasia 4. Chromosomal Disorders a) Prader- Willi syndrome b) Down syndrome c) Turner syndrome d) Klinefelter syndrome e) Laurence-Moon-Biedl synd f) Alstrom-Hallgren syndrome g) Carpenters syndrome h) Cohens syndrome 5. Medications: certain drugs associated with increased weight gain a) Diabetes drugs: insulin, sulfonylurea, thiazolinediones b) Psychiatric/ Neurologic drugs: tricyclic antidepressants, SSRIs, MAOIs, lithium, clozapine, olanzapine, risperidone, valproic acid, carbamazepine, gabapentin c) Hormones: corticosteroids, hormonal contraceptives, progestational steroids d) Miscellaneous agents: antihistamines, -blockers, -blockers
B.
C.
D.
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Pediatric Gastroenterology Hepatology and Nutrition Handbook Medical Complications 1. Cardiovascular: Hypertension, hypertriglyceridemia, increased VLDL, hypercholesterolemia, increased LDL, decreased HDL, myocardial hypertrophy 2. Psychiatric: psychosocial dysfunction, low self-esteem, poor body image, depression, and learning disorders. 3. Endocrine: Early puberty, diabetes mellitus type II (adolescents)/ insulin resistance, sodium retention, polycystic ovary syndrome 4. Dermatologic: Acanthosis nigricans, varicose veins, striae/ stretch marks, skin irritation, maceration, hidradenitis suppurativa 5. Neurologic: Pseudotumor cerebri 6. Pulmonary: Obstructive sleep apnea, Pickwickian syndrome 7. Musculoskeletal: Blounts disease (tibia vara), slipped capital femoral epiphysis, osteoarthritis, forearm fracture, flat feet 8. Immunologic: Impaired cell-mediated immunity, reversed CD4-CD8 ratio 9. Gastrointestinal Complications: a) Reflux Esophagitis - Hiatal hernia, increased intra-abdominal pressure b) Esophageal Carcinoma c) Gallstones- Gallbladder cancer: More prevalent in women (increased cholesterol saturation index) d) Liver Disease Nonalcoholic steatohepatitis (NASH) or nonalcoholic fatty liver disease (NAFLD) which may progress to cirrhosis (15% to 20% patients after approximately one decade) or liver failure and increase risk for hepatocellular carcinoma e) Pancreatitis: Obese persons are at higher risk for pancreatitis due to gallstones, hypertriglyceridemia, and hypertriglyceridemia associated with diabetes. f) Colonic Polyps and Cancer of the colon Physical 1. 2. 3. 4. 5. 6. 7. 8. 9. Examination Anthropometric measurements: height, weight, BMI, skinfold thickness (triceps), mid-arm circumference and waist circumference. Fat distribution pattern (central or gynecoid). Tonsillar hypertrophy Thyromegally, thyroid nodules Hepatomegaly (fatty liver). Hyperpigmented skin in the axilla, neck and groin (acanthosis nigricans). Skin lesions in inguinal area and perineum (hydradenitis suppurativa) Tanner staging Blood pressure
F.
G.
Laboratory and Imaging 1. Thyroid status: TSH, T4 (specially if height is less than 50th percentile) 2. Lipoprotein profile, fasting (total cholesterol, HDL, LDL,Triglycerides) 3. Fasting glucose and insulin levels (for those with acanthosis nigricans). 4. ALT, AST, GGT (NAFLD, cholelithiasis) 5. Bone age 6. CRP- may reflect cardiovascular risk status Prognosis 1. Poor for long-term maintenance of weight loss (with current regimens) 2. Obesity cannot be cured but can be modified by consistent changes in eating behaviors and physical activity. Treatment 1. Conventional a) Most efforts to reduce obesity in children have used either family-based or school-based approaches. b) Although a few family-based studies produced significant long-term weight loss in motivated individuals, the overall success has been disappointing, leading some specialists to conclude that treatment of obese children is unrealistically optimistic. c) Treatment in childhood, however, has the advantage of having fewer years of obesigenic behavior to overcome and continued vertical growth. It therefore may offer the best window of opportunity for treatment of this chronic condition. d) The major components of all obesity programs are education, calorie restriction, increased physical activity, and behavioral changes (limitation of television watching). e) A common sense approach to prevention and treatment of childhood obesity should include family participation in the care plan, long-term follow-up as a chronic condition and a realistic weight goal for weight loss and maintenance. 2. Diets a) Although numerous fad diets are continuously proposed, there are few that are supported by rigorous clinical trials in adults, much less children b) Ketogenic diets, such as Atkins and Protein sparing modified fast diets are being studied (in both adults and adolescents) and have been shown in short term studies to result in greater weight loss and improvement in lipid profiles, compared to traditional low fat, low calorie diets (1) Most subjects seem to regain the weight after coming off the diet and long-term maintenance of ketosis is not usually recommended (2) Most successful studies were performed under strict dietary supervision, and would be quite difficult to maintain off protocol, especially for adolescents (3) Inadequate adherence to ketogenic diets may result in significant weight gain from increased caloric density of diet (4) Gallstones, arrhythmias, constipation, electrolyte disturbances have all been described on ketogenic diets 3. Medications: There are currently no weight-loss medications approved for use in children, although multicenter trials using sibutramine and orlistat have been performed in adolescents with short-term success a) Orlistat is a pancreatic lipase inhibitor which decreases dietary fat absorption to about 30% (1) In adults it decreases body weight by 5-10% and weight is generally regained with discontinuation of the drug (2) Side effects of steatorrhea and flatulence with dietary fat intake may limit compliance b) Sibutramine is a mixed serotonin, dopamine and norepinephrine reuptake inhibitor which acts in the CNS to decrease appetite (1) In adults it may reduce body-weight by 5-10%, and this is generally regained with discontinuation of the drug (2) Generally well-tolerated
H.
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Pediatric Gastroenterology Hepatology and Nutrition Handbook c) Metformin is a well-established medication for treatment of type 2 diabetes and polycystic ovary syndrome. It may be useful for treatment of insulin resistance in obese children and result in weight-loss as well. d) Bupropion is an antidepressant medication that has been found in placebo-controlled studies to result in improved weight-loss in both depressed and non-depressed adults participating in weight-loss programs. e) Other: More than 75 weight-loss drugs are in various stages of the FDA approval process before being approved for use in adults. 4. Surgery: Bariatric surgery creates an anatomic barrier preventing over-consumption and accumulation of excess calories either by restricting the gastric reservoir or by inducing malabsorption. a) Types (1) Gastric bypass (the most common performed today) (2) Gastric restriction (3) Jejunoileal bypass (4) Biliopancreatic bypass b) Although surgical treatment remains, by far, the most effective form of obesity therapy, there is a very high rate of morbidity (70% of patients who undergo gastric bypass experience dumping) and mortality in obese adults. c) The limited experience in children and adolescents seems to confirm a similar rate of complications. d) The use of bariatric surgery is only indicated in morbidly obese patients who have been properly screened and who have failed maximal medical management. Use in morbidly obese adolescents remains controversial.
J.
Prevention 1. Prevention and treatment of obesity ultimately involves eating less and being more physically active. 2. Appropriate screening measures should be in place to identify children at-risk for development of obesity and intervene as early as possible with simple dietary and behavioral changes a) Limit excess intake of high-calorie beverages such as whole milk, fruit juices and soft drinks. b) Educate families on the risks of fast food intake and teach children to make healthier choices when eating out. Conclusion 1. Given the profound consequences of childhood inactivity, poor nutrition, and obesity throughout the lifespan, urgency is warranted in responding to this epidemic. 2. Childhood obesity remains a very serious problem, with 25% to 50% of obese children ultimately becoming obese adults. 3. Fifty-year follow-up studies of obese adolescents have demonstrated increased morbidity and mortality, even independent of ultimate adult body weight status. Authors Jose J. Derdoy MD Robert E. Kramer, MD References Dietz W, Robison T: Assessment and Treatment of childhood obesity. Pediatr Rev 1993; 14:337-344. Epstein L: Family-based behavioral intervention for obese children. Int J Obes 1996; 20(suppl 1): 514-521. Rosenbaum M, Leibel R, Hirsh J. N Engl J Med 1997; 337:396-407. Dietz W. Health Consequences of Obesity in Youth: Childhood Predictors of Adult Disease. Pediatrics. 1998;101:518-525. Troiano R., Flegal K. Overweight Children and Adolescents: Description, Epidemiology, and Demographics. Pediatrics.1998;101:497504. Antonson D, Madison J. Eating Disorders and Obesity. In: Wyllie/Hyams. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. Philadelphia: W.B. Saunders Company, 1999:73-87. Graham K. Obesity. In: Schwartz M. The 5 minute Pediatric Consult. Philadelphia: Lippincott Williams & Wilkins, Second Edition, 2000:580-581. Strauss R, Pollack H. Epidemic increase in childhood overweight, 1986-1998. JAMA. 2001; 286:2845-48. Denke M. Anorexia Nervosa, Bulimia Nervosa, and Obesity. In: Sleisenger & Fordtrans. Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. Philadelphia: Saunders, 7th Edition, 2002: 321-336. Tershakovec A, Stallongs V, Hiralall A. Obesity. In: Lifschitz C. Pediatric Gastroenterology and Nutrition in Clinical Practice. New York: Marcel Dekker, Inc., 2002: 249-274. Ebbeling C, Pawlak D , Ludwing D. Childhood obesity: public-health crisis, common sense cure. Lancet. 2002; 360: 473-82 Strauss R, Rodzilsky D, Burack G. Psychosocial correlates of physical activity in healthy children. Arch Pediatr Adolesc Med 2001; 155:897-902. Cole T, Bellizzi M, Dietz W. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000;320:1240-3
K.
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VIII.
Upper GI Bleeding
A. Etiology 1. Birth to 1 month a) Gastritis (peptic or allergic) b) Gastric or duodenal ulcer c) Esophagitis d) Coagulopathy (DIC, hemorrhagic disease) e) Vascular anomaly f) Necrotizing enterocolitis g) Factitious (swallowed maternal blood, epistaxis, hemoptysis) 2. Childhood (1 month - 18 years) a) Gastric or duodenal ulcer 25-75 % b) Gastritis 15-25 % (1) Peptic (2) Allergic (3) H. pylori (4) Medication related (5) Mechanical trauma (foreign body, NG or G-tube) (6) Zollinger Ellison syndrome c) Esophagitis 10-25 % (1) Peptic (2) Allergic (3) Infectious etiologies (CMV, HSV, Fungal) in immunocompromised d) Varices secondary to liver disease or portal vein obstruction ( 0-15 %) e) Mallory-Weiss tear f) Gastrointestinal duplication g) Vascular anomaly h) Dieulafoy lesion (1) Rupture of small mucosal artery into gastric lumen, presenting with massive UGI bleeding (2) Usually in proximal third of stomach, associated with the lesser curve (3) Rare in children i) Coagulopathy j) Hemobilia k) G-tube or NG-tube trauma l) Factitious (epistaxis, hemoptysis, red food or drinks, red meat, iron supplementation. If melena, may be secondary to bismuth subsalicylate) Presentation 1. Hematemesis (or bloody NG output) (69%) 2. Melena (53%) 3. Hematochezia (if rapid transport through GI tract, h/o of bowel resection) (16%) 4. Anemia 5. Abdominal pain 6. Shock 7. Syncope Evaluation 1. History: Recent vomiting, feeding refusal, pain, stress, h/o liver disease, cystic fibrosis, coagulopathy, vitamin K given after delivery, possibility of foreign body, caustic ingestion or H. pylori infection, breast feeding, h/o recent dental work, oral surgery or GI procedures 2. Exam: HR, BP, orthostatics, pallor, jaundice, cutaneous evidence of chronic liver disease or cutaneous vascular malformations, evidence of nasal or oropharyngeal source, abdominal distention or rigidity, hepatosplenomegaly, capillary refill, perfusion 3. Laboratory: a) TYPE AND CROSS, b) HCT/Hg, Platelets c) PT/PTT d) Liver enzymes, Albumin 4. NG lavage a) Assists with location and determination of degree of active bleeding. b) Use room temperature normal saline, NOT ice cold water (risk of hypothermia, does not help with hemostasis) c) Can have false negative if bleeding site is distal to pylorus, or if volume of saline used is too small d) Tube poses small risk of exacerbating bleeding 5. Gastroccult emesis or NG aspirate, Hemoccult stool 6. Apt-Downey test to differentiate swallowed maternal blood a) Mix 1:5 bloody stool or emesis:water (should have at least 1-2 cc of sample) b) Centrifuge at 2000 rpm for 2 minutes c) Decant supernatant and use for remainder of evaluation, may discard cellular debris d) Mix 1 cc of 0.25N NaOH to 5 cc supernatant e) Observe for color change after 2 minutes (1) Fetal hemoglobin remains pink (2) Adult hemoglobin turns yellow-brown as it is denatured 7. Imaging (often low yield, but interventional radiology can be helpful in diagnosis and establishment of hemostasis) a) Abdominal plain film and upright for FB, perforation, NEC b) Ultrasound with doppler if liver disease suspected c) Tagged red cell scan (need 0.1 cc/ minute rate of bleeding,) (1) Tc-99m labeled RBCs re-injected into peripheral bloodstream to look for active bleeding (2) Can obtain delayed view at 24 hours if initially negative, and this may detect intraluminal pools of blood as small as 5 cc (Location of pool may not accurately correlate with site of bleeding).
B.
C.
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Pediatric Gastroenterology Hepatology and Nutrition Handbook Angiography (need > .5 cc/ minute rate of active bleeding) (1) Indicated for actively bleeding lesions or chronic bleeding not identified by other tests (2) Femoral artery approach, catheter guided through mesenteric arteries and contrast medium injected (3) Interventional techniques can be therapeutic e) Barium studies are insensitive and may delay therapy Endoscopy (sensitive, specific, can be therapeutic) a) If endoscopic therapy likely to be necessary, consider general endotracheal anesthesia Supportive Oxygen as needed Ensure good IV access at all times Volume resuscitation as needed Monitor vital signs frequently, follow serial Hgb/HCT as needed to assess persistence and severity of bleeding Type and screen for PRBCs, transfuse as indicated for rapidly decreasing HCT, vital sign instability Optimize coagulation (Vitamin K, FFP) as needed
8. D.
Therapy 1. General/ a) b) c) d) e) f) 2. Medical a)
3.
IV/PO H2 blocker (acid reduction) (1) Ranitidine (2) Famotidine (3) Nizatidine (4) Cimetidine b) IV/PO PPI (acid reduction) (1) Omeprazole (2) Lansoprazole (3) Rabeprazole (4) Pantoprazole c) IV Octreotide (vasoconstriction) for ongoing upper GI bleeding (1) Limited pediatric data (2) May decrease transfusion requirements by slowing variceal and non-variceal upper GI bleeding) d) PO/PG Sucralfate (cytoprotective) e) PO/PG Misoprostol (cytoprotective) f) Therapy for H. pylori infection (antimicrobial) if indicated Endoscopic (After medical therapy fails to control continued bleeding) a) Variceal bleeding (1) Band ligation (a) Advantages (i) Has been shown to be at least as effective as sclerotherapy in eradicating varices in adults and children (ii) Lower rate of all forms of complications (b) Disadvantages (i) Decreased visualization when variceal band ligator attached (ii) Requires at least two esophageal intubations (iii) May be more difficult than sclerotherapy in treatment of actively bleeding lesions (iv) Use limited in smaller children due to size of apparatus (currently minimum 9mm endoscope, adapter has outer diameter range of 12-13 mm) (c) Complications (i) Rebleeding (ii) Esophageal ulcers (iii) Esophageal perforation (iv) Food impaction at banded site (v) Predisposition to bacteremia (d) Technique (i) Identify varices using standard upper endoscopy (ii) Attach variceal band ligator to tip of endoscope (use of multi-band attachments decreases need for repetitive esophageal intubation) (iii) Advance endoscope until most distal target varix identified and deflect tip toward varix (iv) Apply suction until varix causes red-out, then trigger band placement (v) Repeat as needed, moving proximally (2) Sclerotherapy (a) Advantages (i) Only one esophageal intubation (ii) Smaller equipment may be used, thus smaller children may be treated (iii) Better visualization (iv) May be easier in treatment of actively bleeding lesions (b) Disadvantages: More frequent and severe complications than band ligation (c) Complications (i) Chest pain, acute dysphagia, fever are common (ii) Tissue necrosis and ulceration, possibly leading to fistulization into adjacent organs (iii) Stricturing (iv) Rebleeding (v) Esophageal perforation (vi) Predisposition to bacteremia (d) Technique (i) Identify varices using standard upper endoscopy (ii) Via endoscope channel, using 23 or 25 gauge, 4 or 6 mm needle, inject sclerosing agent into varix (iii) Recommended to only sclerose varices in the distal 5-6 cm of the esophagus to avoid complications
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Pediatric Gastroenterology Hepatology and Nutrition Handbook (iv) Sclerosing agents include Sodium Morrhuate, ethanolamine oleate, poliodocanol, sodium tetradecyl sulfate alone or mixed with ethanol. All have been used with comparable success. (3) Non-variceal Upper GI bleeding (most published pediatric experience limited to case reports) (a) Sclerotherapy for gastroduodenal ulcers as in adults (b) Laser therapy has been used to treat diffuse bleeding in adults, but rarely in children. Can be performed using 1.5 mm catheter via pediatric endoscope (c) Hemostatic clips may be applied endoscopically to halt focal arterial or venous bleeding, but can be cumbersome Sengstaken-Blakemore tube (1) Indicated in acute, uncontrollable esophageal hemorrhage, or for use as a temporizing measure until an appropriate therapeutic center can be reached. (2) Esophageal balloon is used to tamponade bleeding sites. Should be decompressed after 12-24 hours (incidence of mucosal damage increases with duration of use) (3) Serious complications in up to 20% of patients (upper airway obstruction due to balloon migration, esophageal ulceration or perforation due to excessive pressure TIPS (Transjugular Intrahepatic Portosystemic Shunt) (1) Indicated in recurrent variceal bleeding and refractory ascites, and provides effective therapy for the complications of portal hypertension (2) A temporizing measure to serve as bridge to transplantation (3) Technique (a) Via right internal jugular vein, needle advanced through liver parenchyma, bridging the hepatic vein and portal system (b) Tract is dilated and expandable stent placed Surgery: Important to involve surgical team early in case adverse or unexpected events occur
b)
c)
d) E. F.
Authors Brad Barth, MD, MPH Reference Fabion W, Perrault J. Gastrointestinal bleeding, W Walker, ed, B.C. Decker, Hamilton, Ontario, 2000; 164-178 Fox V. Pediatric endoscopy. Gastroenterological endoscopy, C Lightdale, ed, Thieme, New York, 2002; 720-752 Fox V. Gastrointestinal bleeding in infancy and childhood. Gastro Clinics North Am, 2000; 29(1):37-66 Heikenen J, Pohl J, Werlin S, Bucuvalas J. Octreotide in pediatric patients. J Ped Gastro Nut, 2002; 35:600-609 Helmy A, Hayes P. Review article: current endoscopic therapeutic options in the management of variceal bleeding. Aliment Pharmacol Ther, 2001; 15:575-594 Lewis B. Small intestinal bleeding. Gastro Clinics North Am, 2000; 29(1):67-95 McKiernan P, Beath S, Davison S. A prospective study of endoscopic esophageal variceal ligation using a multiband ligator. J Ped Gastro Nut, 2002; 34:207-211
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IX. Lower Gastrointestinal Bleeding

A. Definitions 1. Hematemesis is the passage of vomited blood that has a coffee ground or bright red color. This usually implies hemorrhage proximal to the ligament of Treitz. 2. Hematochezia is the passage of bright or dark red blood per rectum, usually indicating a lower GI source, although this may also be due to a fast intestinal transit time or a massive upper GI bleed. 3. Melena is the passage of black, tarry stools associated with bleeding proximal to the ileocecal valve or, less commonly, in the ascending colon if the colonic transit is sufficiently slow to allow bacteria to denature the hemoglobin. 4. Occult bleeding is the presence of blood in stool that is not grossly detectable. Physician Assessment 1. History taking should include the source, magnitude, duration of the bleeding, as well as any associated gastrointestinal and systemic symptoms. 2. Review of systems and family history should include GI disorders, liver disease, bleeding diatheses and medication use . 3. Physician should establish that blood is indeed present in the stool as food and medication can change the color of the stool. Table 1 4. Physical exam should initially be aimed at recognizing the signs and symptoms of shock. a) Later on, a careful examination of the skin, abdomen, perineum and rectum should be done looking for rashes, vascular malformations, stigmata of liver disease, presence of abdominal masses, tenderness, peritoneal irritation, skin tags, fistulas, anal fissures and hemorrhoids. A stool guaiac test is essential to confirm the presence of blood, however some substances can interfere with guaiac tests. Table 2 Differential Diagnosis Table 1.Substances that Commonly Color Stools Red Black Commercial Dyes #2 & #3 Bismuth Ampicillin Activated charcoal Beets Iron Laxatives Spinach Phenytoin Blueberries Licorice, Lead, Dirt, Rifampin Dark chocolate Table 2- Substances that interfere with Guaiac Tests for Fecal Occult Blood False-positive Results False-negative Results Meat Vitamin C Ferrous Sulfate (stool pH <6.0) Storage of specimen >4days Tomatoes, bean sprouts, cauliflower, broccoli, (Hemoglobin degradation) horseradish, turnips, fresh red cherries, Outdated reagent or card cantaloupes, grapes
B.
C.
C. Lower GI Bleeding Chart
C. Lower GI Bleeding (UGI bleeding ruled out)
Ill Appearing
Healthy Appearing
Signs of Systamic or liver
Signs of Systamic or liver
Inactive or intermittent
Massive and/or paroxysmal
CBC, stoll for O&P, culture and C. diff, air enema if intussusception suspected
CBC, ESR, PT, PTT, LFTs, GGT, blood typing and crossmatch, BUN and Cr, UA, stool for culture, O&P and C diff.
Infant: APT Downey test, consider change of formula
Child: CBC
CBC, blood typing and crossmatch Meckel scan bleeding scan
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Table 3-Causes of Lower Intestinal Bleeding Common Infants Anal Fissure Cows milk protein allergy NEC Swallowed maternal blood Children Anal fissure Intussussception Infectious enterocolitits (Salmonella, Shigella, Campylobacter, E. Coli 0157, Yersinia, C. Diff) Inflammatory Bowel Disease (>4 years old) Meckels diverticulum Perianal streptococcal cellulites Juvenile/inflammatory polyp
Uncommon Vascular lesions Hirschsprungs enterocolitis Meckel diverticulum Intestinal duplication Intussussception Inflammatory Bowel Disease (<4 years old) Vascular malformations Intestinal duplication Henoch-Schonlein Purpura Hemolytic-Uremic Syndrome Cecitis Infectious Diarrhea (CMV, amebiasis) Hemorrohids Hemorrhoids Colonic or rectal varices Ulcer at surgical anastomosis Solitary ulcer of the rectum Nodular lymphoid hyperplasia Sexual abuse Rectal Trauma Foreign Body Injury
Table 4-Conditions Associated with Intestinal Bleeding Condition Intestinal Lesion Turner Syndrome Epidermolysis Bullosa Down Syndrome Ehlers-Danlos Syndrome Hermansky-Pudlak Syndrome Blue rubber bleb nevus Syndrome Osler-Weber-Rendu Syndrome Klippel-Trenaunay Syndrome Pseudoxanthoma Elasticum Glycogen storage disease type 1b D. E. Authors Rima Fawaz M.D. References Faubion WA, Perrault J: Gastrointestinal Bleeding. In: Pediatric Gastrointestinal Disease. Walker WA et al. BC Decker. 3rd edition. 2000: 164-178. Squires RH: Gastrointestinal bleeding. Pediatr Rev.01-Mar-1999; 20(3):95-101. Heitlinger LA, McClung HJ. Gastrointestinal Hemorrhage. In: Pediatric Gastrointestinal Disease. Wyllie R, Hyams J. W.B. Saunders Co. 2nd edition. 1999:64-72 Fox, V. Gastrointestinal bleeding in infancy and childhood. Gastroenterology Clin North Am. 2000; 29(1): 37-66 Lawrence WW. Causes of Rectal Bleeding in Children. Pediatr Rev.01-Nov-2001; 22(11):394-395 Venous ectasia, Inflammatory Bowel Disease Esophageal lesion, Anal fissure, colonic stricture Hirschsprungs Disease, Meckels diverticulum, Pyloric Stenosis Fragile vascular walls Hermansky-Pudlak Syndrome Vascular malformations Vascular malformations, epistaxis Vascular malformations Fragile vascular walls Inflammatory Bowel aseDise
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X. Ascites
A. Background 1. Term ascites is derived from the Greek word askos meaning bag or sack 2. Defined as the pathological accumulation of fluid in the peritoneal cavity 3. May be congenital or acquired 4. Typically results from hepatic or urinary tract disease in children 5. Management depends on the causative factors Etiology: Most common etiologies vary by age of patient 1. Hepatobiliary a) Cirrhosis : ascites results from portal hypertension b) Portal dysplasia c) Congenital Hepatic Fibrosis d) Hepatitis: viral and alcoholic e) Budd-Chiari syndrome f) Liver metastasis g) Biliary atresia with cirrhosis h) Common bile duct perforation i) Gallbladder rupture j) Portal vein thrombosis 2. Cardiovascular a) Congestive heart failure/ arrhythmia b) Hydrops 3. Genitourinary a) Hydronephrosis b) Multi-cystic kidney c) Nephrotic syndrome d) Peritoneal dialysis e) Obstructive uropathy f) Bladder rupture/injury g) Kidney rupture h) Ovarian cyst 4. Gastrointestinal a) Malrotation with bowel compromise/ perforation b) Perforation c) Acute appendicitis d) Jejunal atresia e) Meconium peritonitis f) Pyloric duplication g) Protein-losing enteropathy/ intestinal lymphangiectasia 5. Infectious a) Cytomegalovirus b) Tularemia c) Spontaneous bacterial peritonitis d) Tuberculous peritonitis e) Parvovirus with hydrops f) Syphillus g) Chronic granulomatous disease 6. Metabolic with associated cirrhosis a) Niemann-Pick type C b) Neonatal hemochromatosis c) Lysosomal storage disease d) Wolmans disease e) Cystic Fibrosis f) Galactosemia g) -1 anti-trypsin disease 7. Other a) Pancreatic b) Chylous c) Trisomy d) Turners syndrome e) Ventriculo-peritoneal shunt f) Neoplasm g) Serositis h) Post-liver transplantation i) Peritoneal carcinomatosis j) Idiopathic k) Pseudo-ascites (1) Celiac disease (2) Cystic mesothelioma (3) Omental cyst
B.
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NASPGHAN l) m) n) o) C. Hemolytic anemia IVC Hyperalimentation Protein-calorie malnutrition Letterer-Siwe Disease
Pathophysiology 1. Cirrhotic ascites a) Distortion and obstruction of the sinusoidal vessels from hepatic venous outflow blockage caused by regenerative nodules and fibrosis b) Widespread changes in circulation also important c) Hypoalbuminemia in decompensated cirrhosis exacerbates the ascites by decreasing oncotic pressure d) Hypotheses (1) Underfill theory: contracted blood volume with secondary sodium and water retention (2) Overflow theory: unknown hepatorenal mechanism causes sodium and water retention (3) Vasodilation of the periphery 2. Non-cirrhotic ascites: a wide variety of mechanisms result in peritoneal fluid accumulation a) In low and high output heart failure as well as in nephrotic syndrome, decreased arterial blood volume leads to sodium and water retention b) Infectious and malignant peritoneal disorders cause peritoneal inflammation and exudation c) Chylous ascites results from congenital or acquired lymphatic obstruction or damage d) Leakage from a viscus in biliary, pancreatic and urinary ascites e) Underlying portal hypertension as well as another cause for ascites may coexist- mixed ascites accounts for about 5% f) Hepatic venous outflow obstruction in Budd Chiari leads to massive ascites Clinical Presentation 1. Increasingly diagnosed in the fetus by prenatal ultrasound a) Anatomic, metabolic, hemolytic and chylous etiologies must be evaluated in newborns with ascites of unclear etiology 2. May develop acutely or insidiously 3. Older children may present with weight gain, edema, increasing abdominal girth, and bulging flanks 4. Hernias (femoral, inguinal and umbilical) and an inverted umbilicus are seen in advanced ascites 5. Quantification of ascites maybe done on this simple scale a) Grade 1: detectable by careful exam b) Grade 2: small volume and easily detected c) Grade 3: obvious but not tense d) Grade 4: tense ascites 6. Physical Exam findings a) In those with cirrhotic ascites evidence of chronic liver disease like jaundice, spider angiomas, umbilical, abdominal wall or gastrostomy collateral veins, prominent clubbing, and palmar erythema may be present b) Splenomegaly and prominent abdominal wall veins often denotes portal hypertension c) Evaluation should also attempt to identify: (1) Cardiac disease (murmur, jugular vein distention, pericardial friction rub) (2) Renal disorder (3) Peritonitis (diffuse abdominal pain, rebound tenderness) (4) Pancreatitis (abdominal pain radiating to the back) (5) Lymphatic obstruction (lymphedema) (6) Hypoalbuminemia (edema) (7) Hemolysis (8) Nutritional disorders Diagnosis 1. Physical Exam a) Shifting dullness (1) The most sensitive clinical sign of ascites (2) Sensitivity of 60-88% and a specificity of 56-97% b) Fluid wave c) Bulging flanks d) Percussion: distinguishes ascites from obesity or an abdominal mass 2. Radiographic a) Abdominal radiographs (1) Centralization of bowel gas pattern (2) Flank strip sign (3) Diffuse haziness (4) Medial displacement of the liver edge b) Ultrasound (1) Most sensitive technique and can detect as little as 100 cc of free abdominal fluid in the adult (2) May detect intra-peritoneal fluid and debris in infants with abdominal distention (3) May identify potential intra-abdominal masses, vascular anomalies, and provide information about the size and echotexture of the liver and spleen. c) CT scan/ MRI 3. Paracentesis a) Procedure of choice for the evaluation of ascites with unclear etiology b) Also recommended to detect infectious peritonitis, when patients are hospitalized, and when there is clinical deterioration c) Few Contraindications and can be usually be performed despite prolonged prothrombin time, except in the setting of DIC or active fibrinolysis d) Complications (1) Bleeding (2) Abdominal wall hematoma (3) Infection (4) Bowel perforation
D.
E.
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Pediatric Gastroenterology Hepatology and Nutrition Handbook (5) Sudden labial or scrotal edema (6) Persistent leak at the puncture site (7) These can be limited by using a Z track, sterile technique, and avoiding scars Technique (1) Site (a) Traditional approach is a midline site caudad to the umbilicus (b) An alternative location is the flank, 2 cm superior and medial to the anterior superior iliac spine (2) Positioning: most procedures can be done with the patient supine, slight elevation of the head of bed to pull ascites to lower abdomen. (3) Ultrasound guidance maybe used in selected situations (obesity, multiple scars) (4) Percussion is used to pick the best flank if a midline approach is not utilized (5) Catheter: (a) A narrow bore catheter or metal needle (16 or 18 gauge angiocath or spinal needle) is sufficient to withdraw the necessary 10 to 20 cc of fluid needed for a diagnostic procedure (b) For larger volumes consider catheters specifically designed for paracentesis (ie 15 gauge Caldwell needle) Fluid Analysis (1) The fluid is inspected grossly and sent for analysis (a) Routine: cell count, gram stain, albumin, total protein and culture (in blood Cx bottle) (i) Bedside inoculation of culture bottles with adequate volume of fluid (10 cc) increases the yield of these cultures. (b) Optional: glucose, triglycerides, amylase, LDH, bilirubin (c) Unusual: TB culture/AFB stain, cytology/Cytospin, pH, lactate, peritoneal biopsy (2) Additional tests can be ordered based on clinical findings and gross appearance of the ascitic fluid (a) Turbid and cloudy: infectious (b) Hemorrhagic: pancreatic, malignant, or tuberculosis (c) Milky: chylous (d) Straw colored; cirrhosis, renal, cardiac, or nutritional. (3) Serum-ascites albumin gradient (SAAG) = serum albumin ascites albumin (a) High gradient ascites (SAAG > 1.1 gm/dl) (i) -Cirrhosis (a) Ascitic fluid from patients with liver disease and no secondary complications is generally straw colored, protein count is < 2.5 gm/dl, SAAG > 1.1 gm/dl, cell count is < 250 cells/mm3 with mostly lymphocytes, and the glucose and LDH are similar to serum values. (ii) Alcoholic hepatitis (iii) Cardiac ascites (iv) Liver metastases (v) Fulminant hepatic failure (vi) Budd-Chiari syndrome (vii) Portal Vein thrombosis (viii) Veno-occlusive disease (ix) Acute fatty liver of pregnancy (x) Mixed ascites (b) Low gradient ascites (SAAG < 1.1 gm/dl) (i) Peritoneal carcinomatosis (ii) Tuberculosis (iii) Pancreatic ascites (iv) Biliary ascites (v) Nephrotic syndrome (vi) Connective tissue disease (vii) Bowel obstruction (viii) Bowel infarction (c) If portal hypertension is present, the SAAG is greater than 1.1 gm/dl with 97% accuracy
e)
f)
F.
Management: Successful treatment of ascites depends on addressing the primary underlying cause 1. Cirrhosis a) Treatment has not been shown to improve survival or liver function b) Can improve quality of life and prevent complications of ascites c) Medical therapy for cirrhotic ascites includes dietary sodium restriction, fluid restriction, and diuretics d) Therapeutic large volume (LV) paracentesis with or without albumin infusion is effective for diuretic-refractory tense ascites e) Additional measures for those who remain refractory may involve transjugular intrahepatic portosystemic shunt (TIPS), peritoneovenous shunt (PN shunt), or orthotopic liver transplantation (OLTx) 2. Cardiac ascites: uncommon, but occurs in both high and low output failure a) Similar ascitic fluid analysis to cirrhosis b) Treatment with sodium restriction, diuretics c) Medical therapy to improve cardiac output and to reverse underlying etiology (arrhythmia, anemia, congestive heart failure) 3. Biliary ascites: uncommon, seen with common bile duct perforation in infants, trauma and gallbladder rupture a) Ascitic fluid is bilious and total bilirubin value is > serum value (this may also be seen in bowel perforation) b) Treatment is surgical 4. Pancreatic ascites: Rare, complication of acute pancreatitis, pancreatic duct leakage or rupture from a pseudocyst a) May have underlying infection b) Ascitic fluid may be hemorrhagic with elevated amylase 5. Chylous ascites: Uncommon, seen in congenital abnormalities and acquired obstruction of lymphatics, post-surgical, trauma (child abuse), and abdominal processes (Tb, malignancy, mesenteric adenitis) a) Ascitic fluid is milky and triglycerides are > serum value (usually >1000 mg/dl) b) Treatment involves long chain fatty acid restriction, MCT added to diet, TPN, and recently octreotide 6. Uroascites: Uncommon, occurs in newborns from urinary tract obstruction/disruption, anomalies, trauma or iatrogenic
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Pediatric Gastroenterology Hepatology and Nutrition Handbook a) Ascitic fluid is similar to that seen with cirrhosis although is the result of urine accumulation. b) Treatment is surgical 7. Spontaneous bacterial peritonitis (SBP): Infection of ascitic fluid without evidence of abdominal source a) Occurs mainly in pre-existing cirrhotic ascites and presents with abdominal distention, pain, fever, diffuse tenderness and worsening jaundice. Although, maybe asymptomatic b) Ascitic fluid has predominance of polymorphonuclear cells and leukocyte > 250 cells/mm3 c) Treatment is with a broad spectrum antibiotic with gram-negative coverage (cefotaxime) as well as adequate coverage for S. pneumoniae 8. Bacterial peritonitis: Must be differentiated from SBP. Occurs in setting of intestinal perforation, intra-abdominal abscess. a) Ascitic fluid shows >10,000 PMNs/mm3, low glucose (< 50mg/dl), elevated LDH (225 mU/ml), elevated total protein (> 1 gm/dl) and multiple organisms are cultured b) Treatment is surgical and antibiotics 9. Tuberculous peritonitis: Rare in children and if seen usually in setting of immunodeficiency or alcoholic cirrhosis a) Tubercles stud the peritoneum causing exudation of fluid b) Mononuclear cells predominate in the ascitic fluid c) AFB smears lack sensitivity and culture requires large volume to be positive, so peritonoscopy is critical if suspected d) Treatment is with anti-tuberculous drugs 10. General Treatment Modalities a) Sodium restriction (1) Technique: achieve negative Na balance (2) RESTRICTION: 2 meq/kg or 1-2 gm/day for adults (3) Disadvantages: works poorly alone, negative impact on appetite and nutrition b) Fluid restriction (1) Technique: Not until Na <125 (2) Disadvantage: Most pts are not hyponatremic Spironolactone c) (1) Dose: 2-3 mg/kg, up to 4-6 mg/kg, 400 mg maximum (2) Disadvantages: Hyperkalemic metabolic acidosis d) Furosemide (1) Dose: 1 mg/kg, up to 2-4 mg/kg, 160 mg maximum (2) Disadvantages: Hypokalemic alkalosis e) LV paracentesis (1) Technique: Up to 100 ml/Kg, max of 5 liters (2) Specifics: Safe, rapid, symptomatic relief. Most give albumin. Use needle designed for paracentesis if possible (15 g Caldwell) or 16 /18 g IV catheter (3) Disadvantages: Reaccumulation f) TIPS (1) Technique: Non-surgical, hepatic-portal fistula (2) Specifics: Lowers portal pressure, prevents rebleeding, alleviates cirrhotic ascites (3) Disadvantages: encephalopathy, high rate of shunt occlusion, long term efficacy? g) Peritoneovenous shunt (1) Technique: Surgical (2) Specifics: LeVeen, Denver shunts (3) Disadvantages: High morbidity/mortality
G. H.
Authors James Rick M.D. References Colletti RB, Krawitt EL. Ascites. Wyllie R, Hyams, JS eds. Pediatric Gastrointestinal Disease: Saunders, 1999: 104-115. Machin GA. Diseases causing fetal and neonatal ascites. Pediatric Pathology 4:195-211;1985 Reif S, Blendis L. Portal Hypertension and Ascites. Walker WA, Durie PR, Hamilton JR, Walker-Smith JA and Watkins JB eds. Pediatric Gastrointestinal Disease: B.C. Decker, 2000: 233-246. Reynolds, TB. Ascites. Clinics in Liver Disease 4(1);151-166.2000. Runyon BA. Approach to the Patient with Ascites. Yamada eds. Textbook of Gastroenterology, 1999:966-991. Wyllie R, Arasu TS. Ascites : Pathophysiology and Management. J of Pediatri 97(2): 167-176 Yu AS, Ke-Qin H. Management of Ascites. Clinics in Liver Disease 5(2);2001
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XI. Neonatal Cholestasis

A. Definitions 1. Cholestasis is defined physiologically as a reduction in bile flow a) Impaired bile flow is characterized by an accumulation in the liver and serum of substances that normally are secreted in the bile, such as bilirubin, bile acids and cholesterol. 2. Conjugated hyperbilirubinemia is the most recognizable laboratory manifestation of cholestasis, and its finding is always pathologic. 3. Clinical features of cholestasis include: a) Jaundice b) Pruritus c) Acholic stools d) Dark urine 4. These features result from: a) Functional defect in bile formation, mainly related to intrahepatic disorders (Hepatocellular cholestasis) b) Impairment in bile secretion and flow in relation to extrahepatic disorders (Ductular/Ductal cholestasis) 5. Lab findings include: a) Conjugated bilirubin 2 mg% or 20% of total bilirubin b) Increased ALP (more than 3-fold normal values) c) Increased GGT more than 5 fold d) AST/ALT increased no more than 5-8 fold. e) Increased bile acids (>50 umol/l) and cholesterol f) ALT:ALP ratio <2 6. Histopathology: Intralobular bilirubinostasis, hepatocellular necrosis and inflammatory infiltrates. Significance of cholestatic jaundice 1. Neonatal cholestasis is present in 1/2500-5000 infants 2. Many of the underlying pathologies related to it can be life-threatening at some point a) Must identify specific entities that are treatable medically or surgically b) Early appropriate therapy may minimize further liver damage and optimize the infants growth and development. Diagnosis 1. Clinical presentations of many of the disorders capable of producing cholestasis in infancy are similar (jaundice, dark urine, acholic stools, and varying degrees of hepatomegaly) a) Degree of impairment of hepatocellular synthetic function and hepatocellular necrosis among these conditions is quite variable b) In 70-80% of infants who have cholestasis, extensive evaluation leads to a diagnosis of either idiopathic neonatal hepatitis or extrahepatic biliary atresia 2. Careful history and physical examination are mandatory and examination of the stools is essential. 3. In the history consider: a) Timing and type of onset of clinical picture b) Consanguinity c) Ethnicity d) Family history of cystic fibrosis e) Infectious contacts including investigation on TORCHES f) Medications that may be hepatotoxic g) Prematurity 4. Physical exam a) General appearance (i.e. toxic appearance may suggest sepsis, galactosemia; well appearance may suggest biliary atresia) b) Facies (trisomies, Alagilles) c) Heart murmur (hypoperfusion, Alagilles) d) Cataracts (galactosemia) e) Rash/purpura (TORCH, sepsis) f) Hepato/splenomegaly 5. Labs a) Serum bilirubin, which should always be fractionated b) AST, ALT, GGT, ALP (1) Increased ALT/AST=Implies some hepatocellular damage (2) Increased ALK P/5 nucleotidase=Suggests hepatobiliary disease c) Positive bilirubin/urobilinogen in urine d) Hematologic (1) CBC, smear (2) Coombs (for unconjugated hyperbilirubinemia, or for rare cases of Coombs associated autoimmune hepatitis in infants) (a) Reticulocyte count (b) PT/PTT (Prolonged PT=May be due to impaired hepatic synthesis or fat malabsorption as well as malabsorption of vit. K)
B.
C.
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NASPGHAN e) f) g) h) i) j) k) l) m) n) o) p) Imaging a)
Pediatric Gastroenterology Hepatology and Nutrition Handbook Elevated serum bile acids, cholesterol and triglycerides Positive reducing substances in urine (Related to galactosemia) TORCH titers (Toxoplasma IgG, IgM/ Rubella IgG, IgM / Cytomegalovirus IgM / Herpes Simplex Virus culture, PCR, titer) Bacterial cultures (urine and blood, especially if toxic-appearing) Hepatitis screen (IgM in mother and neonate) Thyroid studies Galactose-1-PUT -fetoprotein (may be elevated in newborns, but is extremely elevated in tyrosinemia) Sweat test Serum AA screen and urine organic acids -1-antitrypsin levels; protease inhibitor phenotype (MM, ZZ) Urine succinylacetone (for tyrosinemia)
6.
7.
Ultrasound of liver, gallbladder and spleen (1) Provides useful information (2) No radiation exposure (3) May detect choledochal cysts, an abdominal mass that compresses the biliary tract, biliary stones, absent gallbladder (found in 90% of biliary atresia patients), triangular cord sign (sensitivity 83-100%) or ascites (a) Provides information regarding portal flow, if Doppler ultrasound is requested. b) Hepatobiliary scintigraphy (HIDA, DISIDA) (1) May differentiate extrahepatic from intrahepatic causes of obstruction (2) Helpful in excluding EHBA (3) Not very specific and patients with paucity of bile ducts may have false (+) results (4) Priming with phenobarbital (3-5 mg/kg/day for 48-72 hrs) may enhance biliary excretion and increases the specificity (a) Result is considered positive when there is good uptake of the radionuclide by the liver and but no excretion to the gut within 24 hrs. c) Skull, long bones, spine X rays looking for bony abnormalities (that could be related to syndromes). d) Intraoperative cholangiogram may need to be performed since none of the above are 100% sensitive or specific. Liver Biopsy a) The most reliable means for determining the diagnosis in a neonate who has cholestasis (1) Early in the course of some disorders, such as biliary atresia and -1-antitrypsin deficiency, characteristic histologic changes may not be evident b) Important histologic features to examine include: (1) Hepatocytes (giant cells, inclusions, PAS+/diastase material, necrosis) (2) Portal areas (degree of inflammation, number and character of bile ducts) (3) Central veins (presence of congestion) (4) Degree of fibrosis, presence of cirrhosis (5) Intralobular bilirubinostasis
D.
Factors predisposing neonates to cholestasis 1. The neonate experiences a period of relative cholestasis (physiologic cholestasis) in relation to the following: a) Decreased bile acid secretory rate which is affected by caloric and fluid intake b) Elevated basal serum bile acid levels which are qualitatively abnormal c) Decreased ileal reabsorption d) Inefficient hepatocyte uptake and transport of bile acids e) Decreased conjugation, sulfation and glucoronidation 2. Non-specific insults in this age group result in cholestatic effects including hepatocyte giant cell transformation, cholestasis, inflammation, hepatocellular necrosis, extramedullary erythropoiesis and fibrosis. Differential Diagnosis 1. Intrahepatic Disorders a) Idiopathic neonatal hepatitis(Also known as Giant Cell Hepatitis) (1) The extrahepatic biliary tracts are patent (2) Histologic findings include portal inflammation, giant cell transformation, increased extramedullary erythropoiesis, and bile stasis. (3) Acholic stools are infrequent (a) Jaundice develops during the 1st week of life in >50% of patients (b) Hepatosplenomegaly is a regular finding (c) These findings usually resolve, but approximately 20% of these patients could have a fulminant course or develop progressive fibrosis. b) Infectious (TORCHES and miscellaneous) (1) Infectious agents may damage the liver directly by invasion of hepatocytes or indirectly by production of hepatotoxins. (2) Sepsis (a) Can cause cholestasis through liver injury related to endotoxins and/or effector substances inflammatory cytokines- acting directly on the liver (i) There is evidence showing that pro-inflammatory cytokines are potent inhibitors of hepatobiliary transporter gene expression, explaining impaired transport function that leads to hyperbilirubinemia and cholestasis (b) Sepsis can also be related to cholestasis through the effects of ischemia/hypoperfusion septic shock-, medications/antibiotic side effects and parenteral nutrition. (3) TORCHES Infections (a) Often have low birth weight, and have associated hepatosplenomegaly, rashes, thrombocytopenia and ocular abnormalities (b) The appropriate use of viral cultures, serologic titers, imaging and ophthalmologic examinations lead to the diagnosis in the majority of these babies (c) These infections include: (i) Toxoplasmosis (ii) Other
E.
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Pediatric Gastroenterology Hepatology and Nutrition Handbook (iii) Rubella, Reovirus (controversial ) (iv) CMV, Coxsackie virus (v) Herpes, Hepatitis B/C, HIV (vi) Echovirus (vii) Syphilis c) Genetic/Metabolic: Disorders of carbohydrates, amino acid and lipid metabolism may result in cholestasis and frequently present with vomiting, lethargy, poor feeding, irritability and jaundice. (1) Disorders of carbohydrate metabolism (a) Galactosemia (i) An autosomal recessive disorder results from a deficiency of galactose-1-Puridyltransferase (ii) Accumulation of galatose-1-P results in jaundice, hepatomegaly, vomiting, failure to thrive, cataracts, hypoglycemia and aminoaciduria (iii) Non-glucose reducing substances may be found in the urine, but the definitive diagnosis relies on the finding of a decrease in the concentration of galactose-1-p-uridyltransferase within red blood cells. (b) Fructose intolerance: Clinical syndrome similar to galactosemia. (c) Glycogen storage disease type IV (rarely presents as neonatal cholestasis): Glycogen filled hepatocytes, enzyme analysis of liver tissue (2) Disorders of amino acid metabolism (a) Tyrosinemia: Elevated urine succinylacetone, increased AFP and coagulopathy disproportionate to other biochemical findings (3) Disorders of lipid metabolism (a) Nieman-Pick disease (b) Cholesterol ester storage disease (c) Wolmans disease (d) Gauchers disease (rarely presents with cholestasis) (4) Disorders of bile acid metabolism (a) 3-Hydroxy-C27-steroid dehydrogenase/isomerase deficiency (i) Second step in primary bile acid synthesis (ii) Identified in Saudi Arabian lineage (iii) Characterized by normal GGT and serum bile acid levels, despite level of cholestasis and elevated aminotransferases (iv) Diagnosis made by FAB-MS analysis of urine with absence of normal glyco and tauro conjugates of primary bile acids (b) 4-3-Oxosteroid 5-reductase deficiency (i) Fourth step in bile acid synthesis (ii) GGT generally elevated (iii) Diagnosis made by FAB-MS (5) Chromosomal disorders (a) Trisomies 17, 18, 21 (b) Donahues syndrome (6) Miscellaneous (a) -1- antitrypsin deficiency (i) Transmitted in an autosomal recessive fashion (ii) Variants of -1-Antitrypsin deficiency are classified according to protease inhibitory (Pi) phenotype system (iii) More than 80 variants have been reported (iv) The Z allele is the deficient variant most commonly associated with clinical disease (v) Children who have clinical liver disease often display the phenotype ZZ (vi) Affected infants typically develop jaundice in the first 2-4 mo of life (vii) In most cases, the jaundice resolves by 7 months, although fulminant hepatic failure and death occasionally occur. Cirrhosis may present later in life. Most individuals with ZZ manifest no liver disease. (viii) Dx is made by determining serum -1-antitrypsin concentration and Pi phenotyping (ix) Hepatic transplantation is currently the only effective management for end stage liver disease. (b) Cystic fibrosis (c) Neonatal iron storage disease (d) Zellwegers syndrome: Cerebrohepatorenal syndrome (i) Cholestatic jaundice, severe mental retardation, hypotonia, renal cortical cysts (ii) Abnormal facies characterized by epicanthal folds, hypertelorism and a prominent forehead. d) Endocrine (1) Hypothyroidism (2) Neonatal hypopituitarism (often with septo-optic dysplasia) (3) Congenital adrenal hypoplasia e) Cardiac (1) Any pathology that causes hypoperfusion could cause direct liver injury (a) Congestive heart failure (b) Hypoplastic left heart syndrome. This type of presentation is associated with striking increase in transaminases (2000s-3000s) and creatine phosphokinase levels followed in 1-2 days by jaundice that may persist for one month or more f) Other (1) Persistent intrahepatic cholestasis comprises a heterogeneous group of poorly delineated syndromes (2) Common features include constant/episodic cholestasis, manifested by pruritus, jaundice, malabsorption, hypercholesterolemia and FTT (3) In some of these conditions (paucity of bile ducts) pruritus often becomes the primary clinical feature in the first year of life, with subsequent development of widespread xanthomas (4) Conditions presenting with these features include:
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Pediatric Gastroenterology Hepatology and Nutrition Handbook (a) Alagilles syndrome: The liver disease in Alagille syndrome progresses quite slowly; survival into adulthood is common. (i) Hypoplasia of intrahepatic ducts (ii) Characteristic facies (small pointed chin, broad forehead, straight nose, and hypertelorism) (iii) Vertebral defects (hemi vertebrae, butterfly vertebrae) (iv) CV anomalies (peripheral pulmonary stenosis, coarctation of the aorta, tetralogy of Fallot) (v) Ocular abnormalities (posterior embryotoxon, exotropia, band keratopathy, and choloidal folds) (vi) Growth retardation (b) Progressive Familial Intrahepatic Cholestasis (PFIC) Syndromes (i) PFIC type 1 (Bylers syndrome) (a) Severe form of familial intrahepatic cholestasis that leads to the development of cirrhosis. (b) Notable for absence of hypercholesterolemia and low to normal GGT; transmitted in autosomal recessive fashion (c) Due to mutation in FIC1 transporter gene, speculated to play a role in enterohepatic circulation of bile salts (d) Treatment: biliary diversion, liver transplantation (ii) Benign recurrent intrahepatic cholestasis (BRIC) (a) Also due to mutation in FIC1 gene, but less severe than PFIC type 1, due to some residual FIC1 activity (b) Syndrome consisting of recurrent attacks of jaundice, pruritus, anorexia, and weight loss (c) Asymptomatic between attacks (iii) PFIC type 2 (a) Phenotypically similar to PFIC type 1 but more severe (b) Due to mutation in BSEP gene, thought to be the main bile salt transporter in the canalicular membrane (c) Also characterized by low GGT (d) Liver transplantation is the only therapy (iv) PFIC type 3 (a) The only form of PFIC with elevated GGT (b) Later onset and more severe course than PFIC 1 or 2 (c) Due to defect in MDR3 gene, responsible for translocation of phosphatidylcholine into bile, therefore more susceptible to bile duct epithelial injury from bile salt detergent effects (c) North American Indian cirrhosis (d) TPN related cholestasis (i) Has become the most the most common cause of conjugated hyperbilirubinemia in the NICU, with a variable range of severity. (ii) 30-50% of infants who receive TPN for more than 2 weeks develop cholestasis and the percentage increases to 80% in premature babies that have received it for more than 30 days (iii) The etiology is likely multifactorial, involving functional immaturity of neonatal bile secretion, lack of enteral feedings, sepsis, infection, glucose and lipid overload, quantity and quality of AA, lack of specific AA (such as Taurine) and toxic components of TPN infusates. (iv) Most of the patients liver function abnormalities resolve within 4-6 months after discontinuing TPN (v) TPN associated cholestasis is a diagnosis based on clinical findings and the absence of other known cholestatic disorders (vi) The main preventive measure is to start enteral feeds promptly, but cycling TPN may decrease cholestasis in these babies by decreasing insulin levels. This facilitates mobilization of fat and glycogen stores therefore decreasing the risk for fatty infiltration of the liver. (e) Drug toxicities (i) Drug-induced cholestasis has become an increasingly important problem caused by metabolic or immunological idiosyncrasy to a drug, making this effect unpredictable (ii) Some medications may be primarily cholestatic and others may result in hepatocellular necrosis (f) Histiocytosis X (g) Shock (associated with hypoperfusion) (h) Perinatal asphyxia (associated with hypoperfusion) (i) Inspissated bile syndrome (j) Intestinal obstruction (due to decreased ileal reabsorption) (k) NEC (l) Lupus (m) Neoplasms (Hepatoblastoma, etc)
2.
Extrahepatic Disorders a) Biliary atresia (1) Incidence ranges from 1/10000 to 1/20000 live births, more frequent in females (2) Most appear to be postnatal obliteration of the extrahepatic biliary tree, but up to 20% may be true congenital anomalies (these usually associated with other anomalies such as duodenal atresia, malrotation, vascular abnormalities and polysplenia) (3) In 80% of the patients the obstruction is present at the porta hepatis (4) Appear normal at birth, and remain healthy until 3-6 wks of age, when jaundice is more evident, and they have acholic stools and firm hepatomegaly (5) Typically, AST and ALT may be 2-5 times the upper limit, and conjugated bilirubin greater than 3 mg/dl; with GGT and cholesterol higher than in other causes of cholestasis (6) With progression biliary cirrhosis develops as well as failure to thrive (7) Liver Bx with variable degrees of bile stasis, prominent bile duct proliferation and periportal inflammation and fibrosis
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Pediatric Gastroenterology Hepatology and Nutrition Handbook (8) Definitive diagnosis is made with exploratory laparotomy with intraoperative cholangiography (9) If untreated, the life expectancy is 2 yrs, with death resulting from liver failure and/or portal hypertension Choledochal cysts (1) Dilatations of the biliary tree, most common is fusiform dilatation of the extrahepatic biliary tree (2) More frequent in females (3) Diagnosis is made by US and treatment is complete excision Cholelithiasis/ Choledocholithiasis Bile duct stenosis Choledocho-pancreatico-ductal junction anomaly Bile plug syndrome (1) Complication of neonatal hemolysis, TPN, diuretic therapy and bowel dysfunction (2) Treatment is supportive and prompt starting of enteral feedings Extrinsic bile duct compression
b)
c) d) e) f) g) F.
Therapy 1. No specific therapy is available to reverse cholestasis and its complications; therefore, these patients require medical management in an effort to maximize growth, prevent specific nutrient deficiencies and improve the overall quality of life. 2. Medical treatment of cause a) Sepsis/ UTI b) NEC c) Dietary regimens for galactosemia, fructosemia and tyrosinemia (improves renal function). d) NTBC (Nitro-trifluoromethylbenzoyl-cyclohexanedione) treatment for tyrosinemia, diet therapy not usually effective in progression of liver disease. e) Early introduction of enteral feedings and prompt discontinuation of TPN (1) Removing Manganese and cutting copper in half in TPN (no good trials but theoretically reduces oxidant injury). (2) Cycling TPN f) Removal of hepatotoxic medications g) Hormonal replacement 3. Nutritional Support A,D,E, and K vitamin supplementation and MCT predominant formula a) b) Calcium supplementation c) Other micronutrients that may be deficient include zinc and iron, sometimes requiring supplementation 4. Medical Support a) Pruritus/Xanthomas (1) Cholestyramine and cholestipol (2) Ursodeoxycholic acid (3) Rifampin, naloxone, hydroxyzine or diphenhydramine b) PORTAL HTN: Management of ascites includes salt restriction and diuretics 5. Surgical Options a) Kasai procedure for extrahepatic biliary atresia b) Partial external bile diversion for pruritus c) Porto-venous shunt for portal HTN/ascites d) Surgical resection of choledochal cyst or stone e) Correction of intestinal obstruction 6. Liver Transplantation a) Indicated for patients who develop end-stage liver disease b) Good survival rates c) A long-term, good quality of life is the rule rather than the exception. d) Life-long immune suppression may cause post-surgical complications (infection, nephrotoxicity and malignancy) Authors Maria-Stella Serrano, MD Reference: American Academy of Pediatrics Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia. Management of Hyperbilirubinemia in the Healthy Term Newborn. Pediatrics 1994;94(4):558-65. Balistreri WF. Neonatal cholestasis. J Pediatr 1985;106:171-84. Brough AJ, Bernstein J. Conjugated hyperbilirubinemia in early infancy: a reassessment of liver biopsy. Human Pathology 1974;5:507516. Choi SO, Park WH, Lee HJ. Ultrasonographic triangular cord: the most definitive finding for noninvasive diagnosis of extrahepatic biliary atresia. Eur J Pediatr Surg 1998;8:12-16. Hussein M, Howard ER, Mieli-Vergani G, Mowat AP. Jaundice at 14 days of age: exclude biliary atresia. Arch Dis Child 1991;66:1177-79. Liver Disease in Children (2nd edition) by Suchy, Sokol and Ballisteri. Mushtaq I, Logan S, Morris M, et al. Screening of newborn infants for cholestatic hepatobiliary disease with tandem mass spectroscopy. BMJ 1999;319:471-477.
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XII.
Cholestasis in Children and Adolescents

A. Definition: 1. The clinical, biochemical and histological manifestations of defective bile acid transport from the liver to the intestine. 2. Most result from inflammatory and destructive processes affecting the intrahepatic or extrahepatic biliary tree or developmental defects. 3. Can progress towards cirrhosis and hepatocellular insufficiency requiring liver transplantation. Etiology: 1. Cholangiopathies of the extrahepatic bile ducts: a) Biliary atresia (1) Necroinflammatory destructive cholangitis resulting in progressive destruction and obliterating fibrosis of the bile duct. (2) Intrahepatic bile ducts are also subjected to this dynamic, progressive, inflammatory, destructive process1. (3) Atresia is defined as absence of the lumen in part or the entire extrahepatic biliary tract, causing complete obstruction of bile flow1. (4) 15% have major abnormalities outside biliary system, such as polysplenia, malrotation, situs inversus and congenital heart disease. (5) Characterized by pale stools, jaundice, hepatosplenomegaly and FTT. (6) HIDA scan may be helpful in diagnosis, showing no excretion of bile into the small intestine. (7) Kasai portoenterostomy +/- OLT are treatment options. b) Anatomic anomalies of extrahepatic bile ducts (1) Agenesis of extrahepatic bile ducts (2) Aberrant and Accessory bile ducts (3) Bile duct duplication (4) Congenital bronchobiliary fistula (5) Spontaneous perforation of the CBD (6) Bile duct hypoplasia c) Congenital Bile duct cysts: (1) Choledochal cyst (a) Congenital anomaly of the biliary tract, characterized by varying degrees of cystic dilatation at varying segments of the biliary tract (extra or intrahepatic). (b) Five subtypes based on nature and location of the cystic dilatation. (c) The classic triad of intermittent abdominal pain, jaundice and right epigastric mass varies in incidence, uncommon in children and occurs in 20%. (d) Conjugated hyperbilirubinemia, hyperamylasemia or signs of mild chronic liver disease with obstructive symptoms are seen. (e) Children older than two years of age, present more commonly with pain. (f) Diagnosis is by ultrasound, CT or cholangiography. (g) Complete surgical excision of the cyst mucosa with jejunal Roux-en-Y loop is the treatment. (h) Cholangitis and pancreatitis secondary to stone formation are complications. (i) Adenocarcinoma of residual cyst tissue or gall bladder develops in 4-8% beyond age 20 yrs. (2) Congenital dilatation of the CBD 2. Cholangiopathies of intrahepatic bile ducts: a) Atretic cholangiopathies (1) Intrahepatic bile duct atresia: Atresia is not complete, but involves a reduced ratio of the number of interlobular ducts to the number of portal tracts. b) Paucity of Interlobular bile ducts : (1) Defined as ratio of the number of interlobular ducts to the number of portal tracts of less than 0.5 (Normal being 0.9-1.8). (2) The portal tracts devoid of bile ducts appear hypoplastic and the total number of portal tracts per unit of tissue section is reduced compared with normal control subjects. (3) Syndromic ( Alagilles syndrome) (a) Associated with other extrahepatic anomalies (i) Triangular facies (ii) Butterfly vertebra (iii) Peripheral pulmonic stenosis (iv) Posterior embryotoxon on ophthalmologic exam (b) Progressive intrahepatic bile duct destruction and hypoplastic extrahepatic bile ducts (c) Caused by the alteration of a single gene, JAG1 (involved in cell signaling) at chromosomal location 20p12. (d) Transmitted as an autosomal dominant gene with 94% penetrance and variable expressivity. (e) Prognosis is variable, with some requiring OLT and others characterized by resolution of jaundice, xanthomas and improvement in pruritis. (f) Hepatocellular carcinoma is a complication. (4) Non-Syndromic (a) May be an isolated defect. (b) Most frequent diagnosis in patients with conjugated hyperbilirubinemia in the first month of life (c) Heterogeneous group associated with (i) Infections (CMV, rubella, syphilis, and Hepatitis B) (ii) Alpha1 antitrypsin deficiency (iii) Endocrine disorders (hypopituitarism) (iv) Chromosomal anomalies (trisomy 21, Turners syndrome) (v) Altered bile acid metabolism (vi) Bylers disease (vii) Norwegian cholestasis (viii) Idiopathic causes (d) Progressive cholangiopathy with apparently faster bile duct destruction (e) Prognosis is variable because it is not a homogeneous group.
B.
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Pediatric Gastroenterology Hepatology and Nutrition Handbook c) Combined extrahepatic bile duct atresia and paucity of interlobular bile ducts 3. Fibrocystic Cholangiopathies: Dilatation of segments of the intrahepatic bile ducts associated with variable fibrosis. Most often associated with cystic diseases of the kidney. a) Autosomal recessive polycystic kidney disease (ARPKD) b) Congenital Hepatic Fibrosis (CHF) (1) AR disease characterized by hepatic fibrosis, portal hypertension and is usually associated with renal abnormalities of ARPKD4. (2) Histopathologic picture is variable (a) Characterized in some by fibrous enlargement of the portal tracts, which contains variable numbers of abnormally shaped bile ducts (b) Others show bands of connective tissue of variable width linking adjacent portal tracts (3) Typically seen in older children and adolescents with minimal renal involvement (4) Spectrum and severity of clinical features vary (5) Subtypes of CHF are recognized based on clinical symptoms (a) Portal hypertensive (most common, often presenting with esophageal variceal hemorrhage) (b) Cholangitic (characterized by cholestasis and recurrent cholangitis) (c) Mixed and latent forms (manifests later in life or is discovered incidentally) (6) Symptoms may appear early or late (7) Lab values in the absence of cholangitis and portal HTN are normal (AST, ALT, Bilirubin) although mild cholestasis may be seen (8) Liver is normal in size and firm in consistency (9) Diagnosis is by Ultrasound and CT of abdomen, with liver biopsy (10) Therapy depends on type of CHF (a) Antibiotics for cholangitis (b) Sclerotherapy, band ligation and portosystemic shunts for variceal bleeding (c) Transplantation is curative and indications for this would include recurrent cholangitis or progressive hepatic dysfunction. c) Carolis disease (Pure form) (1) Congenital ectasia or dilatation of the larger segmental intrahepatic bile ducts (2) Dilated portions are in continuity with the rest of the biliary system and hence contain bile (communicating type of cystic disease) (3) The saccular dilatations of the ducts lead to stagnation of bile, predisposing to biliary sludge formation and intraductal lithiasis, often complicated by superinfection (4) Not hereditary (5) May be associated with choledochal cysts (6) Presenting symptoms: abdominal pain and hepatomegaly with steatorrhea (7) Antibiotics +/- lobectomy of the affected lobe are treatment options. d) Carolis syndrome (Combined form) (1) Inherited as an AR trait (2) Same as Carolis disease but is associated with periportal fibrosis and the kidney lesions of ARPKD (corresponding to congenital hepatic fibrosis) (3) Variations in anatomic location and in the clinical presentation have been reported (4) Associated with periportal fibrosis (corresponds to CHF) (5) Presentation may be a combination of the classic symptoms of Carolis disease (cholangitis, septicemia) and CHF (cholangitis and portal hypertension) (6) Complications include amyloidosis and cholangiocarcinoma (Biliary Ca increased incidence of 100 times) (7) Lithiasis and bile stagnation with risk of infection exists (8) Diagnosis by Ultrasound, CT, isotope scans and cholangiograms. e) Autosomal dominant polycystic kidney disease (ADPKD) f) Isolated polycystic liver disease g) Mesenchymal Hamartoma h) Solitary (non-parasitic) cyst 4. Progressive familial intrahepatic cholestasis: a) Presents in infancy or anytime during first year of life b) It is an AR inherited disorder of childhood c) Leads to death from liver failure at ages ranging from infancy to adolescence d) Disorders of bile acid transporter proteins leads to PFIC e) Differs from BA synthesis defects in that bile acid levels in serum are elevated and pruritis is a prominent clinical manifestation f) Normal cholangiograms of intra and extra hepatic bile ducts g) Three types with three different mutations in the hepatocellular transport system genes involved in bile formation (1) PFIC 1 (Bylers Disease) (a) Labs: normal GGT, normal cholesterol, high concentrations of serum primary bile acids (b) Pruritus a prominent feature (c) Histology shows canalicular cholestasis, minimal giant cell transformation, and slight lobular and portal fibrosis with absence of a true ductular proliferation. (2) PFIC 2 (BSEP deficiency) (a) Also associated with severe pruritus (b) Labs: normal GGT and high serum primary bile acid concentration, low primary bile acid concentration (c) Defect is in the canalicular membrane with ATP dependant bile acid transport into bile being defective (d) More severe than PFIC1, jaundice is permanent and rapid appearance of liver failure. (3) PFIC 3(MDR3 deficiency) (a) Associated with mild to moderate pruritus (b) Labs: high GGT, moderate increase in serum primary bile acid concentration, low phospholipid concentration (c) Histology: ductular proliferation and inflammation and portal fibrosis, appearing like biliary cirrhosis (d) Defect is in the canalicular membrane with ATP dependent translocation of phosphatidylcholine into bile being defective
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Pediatric Gastroenterology Hepatology and Nutrition Handbook (e) Usually present later in life, increased risk of portal hypertension and GI bleeding and end up with liver failure later age.
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Treatment (1) UDCA: increases hepatocyte excretion of endogenous bile acids and limits their return to the liver by inhibiting their intestinal reabsorption (2) Partial external biliary diversion provides effective relief from pruritis and reversal of liver disease in PFIC 1 & 2 (3) OLT is an option if cirrhosis is present. Progressive obliterative: a) Primary Sclerosing cholangitis fibrosis of the biliary tree (1) Chronic hepatobiliary disorder that may affect patients of all ages (2) Characterized by inflammation of the intra and extra hepatic ducts (3) Leads to focal dilatation, narrowing or obliteration accompanied by local periductular fibrosis (4) Progression to biliary cirrhosis and portal hypertension may occur (5) Diagnosis (a) Cholangiography best defines the structural abnormalities of the larger bile ducts (b) Liver biopsy also helpful (6) Three presentations: (a) Neonatal onset (b) Postneonatal onset with an associated disease (IBD, AIH, histiocytosis, immunodeficiency, etc) (c) Postneonatal onset without any associated disease (7) Subtypes: (a) Isolated PSC (b) PSC IBD complex: (i) Liver disease may precede, coincide with or follow the diagnosis of IBD (ii) Severity/ activity of IBD may not correlate with activity of PSC (c) PSC - autoimmune hepatitis (AIH) complex/ overlap syndrome (8) Symptoms: prolonged jaundice, progressive fatigue, malaise, anorexia, hepatosplenomegaly, weight loss and pruritus. RUQ pain, fever and hyperbilirubinemia is often noted. May be completely asymptomatic. (a) Children may present with poor growth and delayed puberty (9) Labs: No specific lab findings for PSC. Mildly elevated ALT, bilirubin, PT, GGT and ALP, elevated ESR, IgG, ANA or ASMA, ANCA and decreased albumin (10) Complications: Cholangiocarcinoma, needs monitoring (11) Management: supportive. Symptomatic relief with Ursodeoxycholic acid and fat-soluble vitamin supplements in addition to monitoring for malnutrition and prevention of complications is indicated. Immunosuppressives such as Prednisone +/- azathioprine have been used. b) North American Indian cirrhosis Bile acid synthesis defects (BASD) a) Pathogenesis (1) Results from an insufficient production of normal primary bile acids, chenodeoxycholic acid and cholic acid combined with accumulation of potentially toxic intermediary metabolites as a result of a block in the synthesis (2) Cholestasis is exacerbated by a lack of primary bile acids that are essential for promoting bile flow (3) Two categories depending on whether the enzyme catalyzes reaction in the steroid nucleus or in the side chain (4) Deficiency of bile acids in bile, leads to defective absorption of lipids, which leads to deficiency of fat-soluble vitamins and poor growth (5) Bile acid transport elements may be secondarily affected in BASD. b) Diagnosis: specific BASD diagnosis based on mass spectrometry, which detects atypical bile acids in urine and serum on the basis of molecular weight c) Presentation: May present in neonatal period, early childhood or adolescence with jaundice, persistent cholestasis d) Labs: conjugated hyperbilirubinemia, elevated ALT, normal GGT, low or normal serum bile acid levels and the presence of atypical bile acids in serum and urine. e) Histology: progressive hepatocyte injury accompanied by periportal inflammation with progressive fibrosis, intralobular cholestasis and regressive canalicular changes f) Treatment: primary bile acids may be beneficial in supportive therapy Metabolic: a) 1- antitrypsin deficiency (1) Presentation (a) May present in infancy with persistant jaundice, late childhood or early adolescence with unexplained prolonged obstructive jaundice with or without pruritus. (b) Resembles biliary atresia but shows paucity of intrahepatic bile ducts (c) May include hepatosplenomegaly, abdominal distension, ascites or hemorrhage from esophageal varices. May also present as chronic hepatitis, cirrhosis, portal hypertension or hepatocellular carcinoma of unknown origin (2) Labs: elevated conjugated bilirubin, ALT, ALP, GGT, PT and cholesterol (3) Diagnosis: (a) Established by a serum 1-AT phenotype determination by isoelectric focusing or by agarose gel electrophoresis at acid pH. (b) Serum concentration of 1-AT may be helpful if used with phenotype to distinguish individuals who are homozygous for the Z allele from the SZ compound heterozygotes, both of whom may develop liver disease. Also important for genetic counseling (4) Histology: PAS positive, diastase resistant globules in the endoplasmic reticulum of hepatocytes (5) Treatment: avoidance of smoking and supportive treatment with prevention of complications, shunt surgery and OLT. (6) Prognosis: highly variable with some requiring liver transplantation and others being asymptomatic for years b) Cystic fibrosis (1) Approximately 25% will have hepatobiliary complications (2) 5-10% of patients developing multilobular biliary cirrhosis by late childhood (3) Cholestasis and retention of hepatotoxic bile salts occurs as a result of obstruction of bile ducts by inspissated secretions and viscid mucous. (4) Ursodeoxycholic acid is used to promote bile flow.
h)
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Pediatric Gastroenterology Hepatology and Nutrition Handbook c) Galactosemia Endocrine: a) Hypopituitarism b) Adrenal disorders 9. Obstructive: a) Cholelithiasis (1) Negligible incidence of cholelithiasis in males, but in adolescent females there is a remarkable increase in incidence between 11-13 yrs of age (2) In pediatric patients 72% are pigmented stones, 17% are cholesterol and 11% have stones whose composition is unknown (a) Up to 5 yrs of age, pigment stones are more common and from 6 yrs onwards, cholesterol stones are more common (3) Causes: Hemolytic disease (30%), TPN, lack of ileocecal valve, short bowel syndrome, Wilsons disease, Bylers syndrome, defects in bile acid synthesis, CF, pregnancy, BCP use (4) Presentation: May be asymptomatic or may present with abdominal pain, mild increase in serum bilirubin, aminotransferase and alkaline phosphatase (5) Diagnosis: ultrasound is the most sensitive and specific diagnostic tool, ERCP for evaluation/ removal of CBD stones (6) Treatment: Cholecystectomy is the treatment of choice, lithotripsy is an alternative b) Malignant neoplasms c) GVHD d) Lymphohistiocytic disorders 10. Other syndromes: a) Dubin Johnson syndrome (1) Epidemiology : Autosomal recessive, more common than rotors syndrome, especially in males (2) Presentation: (a) Although hepatic anion storage is normal, there is a decrease in bile secretion into canaliculi (b) Increase in conjugated and unconjugated bilirubin with normal LFTs and normal bile acids (c) Intercurrent illness, pregnancy, BCP may precipitate presentation, results in increase of direct bili to 20 mg/dL (d) May present with non-specific abdominal pain and hepatomegaly anytime from birth to adulthood (3) Histology: may show a distinctive brown-black pigmentation that is grossly visible (secondary to melanin or metabolism of epinephrine) in lysosomes (4) Diagnosis: (a) Oral cholecystography fails to visualize the gall bladder in Dubin Johnson syndrome (b) There is normal or slightly increased excretion of urinary corpoporphyrins. b) Rotors syndrome (1) Epidemiology (a) Autosomal recessive, less common than DJS (b) Seen in early childhood (no sex difference) (2) Pathogenesis: (a) Due to deficient glutathione transferase activity and decreased storage (b) Therefore both direct and indirect bilirubin refluxes back into circulation. (3) Diagnosis: (a) Hyperbilirubinemia (direct and indirect) with normal LFTs and bile acids (b) Liver histology and oral cholecystography are normal (c) Urinary corpoporphyrin III and I is 2.5-5 times higher than normal (4) Prognosis: Asymptomatic except for jaundice. No treatment required. 8.
c) Chromosomal disorders: (Trisomy 18, 21) 11. Drugs / Toxins: a) TPN cholestasis b) Other drugs Estrogens/OCP, cyclosporine, haloperidol, erythromycin, azathioprine C. Clinical Presentation 1. Jaundice 2. Pruritus 3. Malnutrition 4. Hepatosplenomegaly 5. +/- Ascites 6. +/- Abdominal pain/ distension. Pathogenesis 1. Altered bile duct morphogenesis 2. Infections, ischemia, or toxins in combination with genetic or immunologic susceptibility likely plays a role. 3. Bile acid is toxic to the biliary epithelium and results in the symptom complex at presentation Diagnosis 1. Serum a) b) c) d) e) f)
D.
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Bilirubin (conjugated, unconjugated and delta) ALT, AST, GGT, ALP, Alb INR, PTT TSH, Free T4 A1-AT phenotype Cholesterol
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NASPGHAN g) Serum bile acid levels h) Serum amino acids i) 1-antitrypsin level and phenotype Urine a) Urine reducing substances, Glucose b) Succinyl acetone c) Organic acids d) Bile acids Radiology a) Vertebral X ray for butterfly vertebrae b) Abdominal ultrasound vs CT scan c) Isotope scans/ HIDA d) Cholangiography Miscellaneous a) Sweat chloride or DNA testing for CF b) Ophthalmology exam c) Echocardiogram d) Liver biopsy
2.
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Management 1. Supportive a) Supportive treatment mostly for syndromic or non-syndromic causes until OLT is an option. b) Fat soluble vitamin supplements c) For TPN/drugs, discontinue agents or minimize effect d) For 1-AT deficiency, avoidance of smoking and supportive treatment with prevention of complications 2. Medical a) Treat the cause of cholestasis if possible b) For bile acid synthetic defects, replace cholic acid Ursodeoxycholic acid c) d) Phenobarb, Rifampin or Cholestyramine for pruritus e) Manage/ prevent upper GI bleeds and portal hypertension sclerotherapy, band ligation, -blockers, octreotide 3. Surgical a) Kasai procedure for biliary atresia b) In case of obstruction, relieve the obstruction (ERCP, lithotripsy, surgery, etc) c) For severe pruritus partial external biliary diversion d) Portosystemic shunt for intractable ascites/ portal HTN e) Liver transplant as indicated Authors Pushpa Sathya. MD. FRCP(C), FAAP References: Alvarez F, Bernard O, Brunelle F, et al. J. of Pediatrics 1981; 99: 370-375.
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XIII. Biochemical Tests of the Liver

A. Introduction: No one test can sufficiently evaluate liver disease. The tests that are commonly used have limited sensitivity and specificity and should be combined with a careful history and physical exam to evaluate for potential liver abnormality. B. Tests of Hepatic Cell Injury: 1. Aspartate Aminotransferase: (AST, formerly serum glutamic oxaloacetic transaminase, SGOT). a) Catalyzes the transfer of a amino group from aspartate to -ketoglutarate with the release of oxaloacetate and glutamate. b) Present as both cytosolic and mitochondrial isoenzymes. c) Present in liver, cardiac muscle, skeletal muscle, pancreas, kidney, and red cells. 2. Alanine Aminotransferase: (ALT, formerly serum glutamic pyruvic transaminase, SGPT). a) Catalyzes the transfer of a amino group from alanine to -ketoglutarate with the release of pyruvate and glutamate. b) It is present only in the cytosol. c) It is present in high concentrations in the liver, and lower concentrations in muscle. d) More specific for hepatocyte damage than AST. e) Can be markedly elevated in muscle disease. 3. The AST/ALT Ratio: a) Serum AST and ALT levels are elevated in cases of liver inflammation and hepatocyte injury. b) Modest elevations in levels (<500U/L) are found in many types of liver disease. c) Marked elevations are found in acute hepatocellular injury such as viral hepatitis, drug-induced hepatitis, and hepatic ischemia. d) The degree of enzyme elevation is not predictive of outcome in acute hepatitis e) The AST: ALT ratio is >2 in adults with alcoholic liver disease. This ratio rises in adults and children with chronic liver disease and cirrhosis. f) The AST: ALT ratio is < or = 1 in acute and chronic (nonalcoholic) liver disease. g) AST and ALT levels are useful in monitoring the progression of liver disease but are not specific for a particular diagnosis. 4. Lactic Dehydrogenase: (LDH) a) Enzyme is found in a wide variety of tissues including liver, red cells, cardiac muscle and kidney. b) There are 5 isoenzymes. c) Elevation is seen with skeletal and cardiac muscle injury, hemolysis, stroke, and renal infarction. Therefore, it is less sensitive and specific for the detection of liver disease than AST and ALT. d) Massive, but transient elevations are seen with ischemic hepatitis. Tests of Cholestasis: 1. Alkaline Phosphatase: (AP) a) Group of enzymes that catalyze the hydrolysis of phosphate esters at an alkaline pH. b) Found in liver (canalicular membrane), bone (osteoblasts), small intestine, kidney, placenta and tumors (Regan isoenzyme). c) Liver and bone are the major sources of AP in the serum (bone isoenzyme). d) Elevated hepatic isoenzyme results from increased enzyme synthesis and release rather than impaired biliary secretion. e) Does not distinguish intrahepatic from extrahepatic biliary obstruction. f) Serum activity of AP is decreased in Wilson Disease and in zinc deficiency, zinc is a cofactor for this enzyme 2. Gamma Glutamyl Transpeptidase: (GGT) a) Microsomal enzyme found in the epithelium of small bile ductules and hepatocytes. b) Catalyzes the transfer of -glutamyl groups between peptides or to an amino acid residue. c) Present in the kidney, pancreas, spleen, brain, heart, lung, and placenta. d) Not significantly present in bone, thus is useful in confirming the hepatic origin of elevated AP. e) Serum levels are highest in the newborn and the premature infant ( 5-8 times the adult normal level) and decline by 6-9 months of life. f) It is elevated in cases of biliary obstruction, as well as paucity of intrahepatic bile ducts in (Alagilles syndrome). g) Useful in differentiating the progressive familial intrahepatic cholestasis (PFIC) syndromes- normal in PFIC-1 (Bylers) and PFIC-2, and elevated in PFIC-3. 3. 5-Nucleotidase: (5-NT) a) Hydrolyzes the 5-adenosine monophosphate and similar nucleotides to inorganic phosphate. b) Located in sinusoidal and canalicular membranes in the liver. c) Elevation is specific for liver disease in the non-pregnant patient, and can be used to confirm the hepatic origin of and elevated AP. 4. Bilirubin: a) Bilirubin is a yellow tetrapyrrole pigment derived from the degradation of heme. b) Newly formed bilirubin (unconjugated) is bound to albumin and taken to the liver, where it is conjugated to one or two moieties of glucuronic acid (bilirubin monoglucuronide and diglucuronide). c) A fourth form occurs in the serum with elevated levels of conjugated bilirubin when it becomes bound to albumin ( bilirubin or bil-alb). d) Elevation of unconjugated bilirubin is indicative of hemolysis or Gilberts disease. e) Elevation of conjugated bilirubin (> 2.0 mg/dl or 15% of total) is indicative of hepatobiliary disease and is always pathologic (indicates inherited or acquired defects in hepatic excretion). f) The presence of bilirubin in the urine is an indication of conjugated hyperbilirubinemia because unconjugated bilirubin is not excreted in the urine. Tests of Hepatic Synthetic Function: 1. Prothrombin Time: (PT) a) Measures the rate of conversion of prothrombin to thrombin. b) Reflects the activity of the extrinsic coagulation pathway (factors I, II, V, VII, and X). c) Except factors VIII and Von Willerbrand, all factors are synthesized in hepatocytes. d) PT is a good indicator of liver synthetic function if vitamin K deficiency is excluded (factors II, VII, IX, and X are vitamin K dependant). e) A prolonged PT, especially > 4 seconds, in chronic liver disease suggests a poor prognosis. 2. Albumin and Other Serum Proteins:
C.
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Pediatric Gastroenterology Hepatology and Nutrition Handbook a) Albumin is synthesized in the rER of hepatocytes at the rate of 150mg/kg/day, and has a half-life of 20 days. b) Decreases in serum albumin can be caused by decrease in synthesis with significant parenchymal liver disease. c) Serum albumin level is also affected by many other extrahepatic factors including nutritional and volume status, catabolism, loss in urine or stool, vascular integrity and hormonal factors. d) Because of the long half-life of this protein, a low level is considered secondary to chronic, not acute, liver injury. e) Serum 1 and 2 globulins are synthesized in the liver, unlike serum -globulins which are synthesized in lymphocytes. f) Unlike albumin, globulin levels are elevated in severe or active liver disease and the cause for this is uncertain. Ammonia: a) Ammonia is produced mostly by the large intestine and cleared by the liver. b) The liver normally clears about 80% of portal vein ammonia in a single pass. c) In chronic liver disease, a disturbed urea cycle function as well as portal systemic shunting allows a large load of ammonia to bypass the liver and reach the central nervous system. d) Fasting serum levels should be measured, a protein meal will elevate post-prandial levels in patients with mild liver disease. e) Increasing levels of fasting serum ammonia may herald the development of hepatic encephalopathy.
3.
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Tests of Quantitative Liver Function: 1. These tests of dynamic liver function have been developed to reflect liver function accurately at a given point in time. a) For these tests a substrate is administered and its disappearance from the serum/saliva, and the appearance of its metabolites in plasma or breath is measured. b) Compounds with a high extraction ratio (70-80% of drug removed in one pass through the liver) are used to measure hepatic blood flow. These include: (1) Sulfobromophthalein (2) Indocyanine green (ICG) (3) radiolabeled bile acids. c) Compounds with a low extraction ratio (20-30%) are used to measure functional hepatic mass or hepatic metabolic capacity. These include: (1) Antipyrine clearance (2) Aminopyrine breath test (ABT) (3) Caffeine clearance (4) Galactose elimination capacity (5) Monoethylglycinexylidide (MEGX) Tests for Specific Liver Diseases: 1. Serum Ferritin: a) Ferritin is a major iron storage protein mostly distributed in human tissues, with a small amount in the serum. b) Not specific for liver disease and can be elevated secondary to inflammation or other iron overload conditions. c) Useful for the detection of idiopathic hemochromatosis where levels are elevated, higher in patients with liver failure (> 1000mcg/L) than those with pre-cirrhotic disease 2. Ceruloplasmin: a) Major copper binging protein synthesized by the liver. b) Its level is depressed markedly in patients who are homozygotes for Wilsons disease. c) Some patients with Wilsons disease may have normal to only slightly decreased levels, and in these cases a 24-hour urine collection for copper excretion can be helpful in making a diagnosis. 3. -Fetoprotein: a) This plasma protein is found during fetal life, and continues to be present is newborns, with levels declining to adult normals by one year of age. b) Elevation of serum levels of -fetoprotein are sensitive and specific for hepatocellular carcinoma and hepatoblastoma. c) It is a useful test to follow in high-risk groups such as patients with glycogen storage disease, chronic hepatitis B, alcoholic cirrhosis, and hemochromatosis. 4. 1- Antitrypsin: a) This protein is the major component of the 1 serum globulins. b) A1AT activity is determined genetically, and the different phenotypes can be detected by gel electrophoresis. This is called the protease inhibitor system (Pi), and the phenotype PiZZ is the only one clearly associated with the development of neonatal hepatitis and cirrhosis due to abnormal A1AT hepatocyte storage. Authors Rula Harb, MD References: Baker AL: Liver Chemistry Tests. In Kaplowitz N (ed): Liver and Biliary Diseases. Baltimore, Williams and Wilkins, 1992, pp 182-194. Batres LA, Maller ES: Laboratory Assessment of Liver Function and Injury in Children. In Suchey FJ, Sokol RJ, Balistreri WF (eds): Liver Disease in Children. Philadelphia, Lippincott Williams and Wilkins, 2001, pp 155-169. Davern TJ, Scharschmidt BF: Biochemical Liver Tests. In Feldman M, Friedman LS, Sleisenger MH (eds): Sleisenger and Fordtrans Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management, Vol 2. Philadelphia, Saunders, 2002, pp 1227-1239. Drouin E, Mitchell GA, Rasquin-Weber A: Other Inherited Cholestatic Disorders. In Walker WA, Durie PR, Hamilton JR, Walker-Smith JA, Watkins JB (eds): Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. BC Decker, Hamilton, 2000, p 1212. Setchell KD, OConnell NC: Disorders of Bile Acid Synthesis and Metabolism. In Walker WA, Durie PR, Hamilton JR, Walker-Smith JA, Watkins JB (eds): Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. BC Decker, Hamilton, 2000, p 1138.The Five-Minute Pediatric Consult, pp 932, 934-935.
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XIV.
Parental Nutrition Guidelines

A. Starting parenteral nutrition. 1. Start PN if you anticipate minimal to no enteral feeds after 5-7 days of illness or due to underlying pathology. 2. Patient must be hemodynamically and biochemically stable. PN cannot be used for fluid resuscitation. 3. Ordering forms vary between institutions but traditionally you will need to indicate the % of dextrose and amino acids, and the amount of intralipids. You will also need to specify a total volume to be provided daily, and the amount of electrolytes, trace elements and multivitamins. 4. A maximum osmolarity of 900 mOsm/L (10% Dextrose and 2% Aac with standard electrolytes) is allowed for peripheral PN, to prevent phlebitis and sclerosis. Higher osmolarities may be infused centrally. 5. Consider checking if your institution has a dietician or nutrition support team. They usually provide helpful suggestions when starting PN. 6. The minimal infusion rate for the prevention of hypoglycemia is 4 mg/kg/min. You may start at 5 mg/kg/min, and advance by 2 mg/kg/min every day, until levels of about 12 mg/kg/min are tolerated. 7. In situations of hyperglycemia preventing the administration of sufficient calories, insulin may be added to PN. 8. Amino acids are the major source of protein in PN. Some centers do not count them in calorie calculations. Use trophamine in neonates and infants, and Rravasol in older children. 9. The ratio of protein to non-protein calories is a useful measure of macronutrient balance. Metabolism is generally optimal when the ration of non-protein energy to nitrogen is between 150:1 and 250:1. Burn patients and other children with high protein requirements may be optimally fed with a ratio of 100:1. The ratio is calculated as follows: [Carbohydrate calories + fat calories]: [protein intake (g) / 6.25] 10. You may start lipids by giving 1 g/kg/d, and advance by 0.5-1 g/kg/d. Do not exceed 3 g/kg/d or 50% of caloric intake. Monitor triglyceride levels when advancing intralipids. PN fluid management: 1. PN fluid requirements may be calculated using the Holliday-Segar method (table 1). 2. Adjust fluid requirements according to fluid losses, such as from diarrhea, emesis, NG output losses, ostomy losses, fever, tachypnea. 3. Do not use PN for resuscitation purposes. Maintain the rate of PN infusion as constant as possible. 4. If you increase the volume of a PN solution, you must adjust all electrolytes, especially if they are expressed per liter of solution on the PN form. 5. Concentrated PN solutions are may result in high osmolarities and may exceed the limits of solubility of calcium and phosphorus salts causing precipitation. 6. Daily parenteral fluid requirements: Table 1: Daily parenteral fluid requirements: Body Daily maintenance fluid weight 0-10 kg 100ml/kg 10-20 kg 1000 ml + 50 ml/kg over 10 kg >20 kg 1500 ml + 20 ml/kg over 20 kg C. PN electrolytes management: 1. Adjust electrolyte concentrations based on estimated or measured electrolyte losses, such as in diarrhea, NG tube drainage, or ostomy losses. 2. Acute changes in serum electrolytes should not be corrected by changing PN rates. Use separate solutions for this, non-acute, less severe electrolyte disturbances can be corrected with changes in PN composition. (Check at what time of the day the previous PN solution was started in relation to the abnormal lab value, to make better judgements). 3. Calcium phosphate solubility is dependent on calcium and phosphorus salt concentrations, pH, temperature, amino acid concentration, infusion time, and magnesium availability. 4. For high calcium and phosphorus requirements, increase Aac concentration or PN volume if possible. You may use Trophamine TM or add L-cysteine (1000 mg/liter). Avoid solutions with borderline calcium phosphate compatibility, since variables such as temperature and time may cause delayed precipitation. 5. Daily parenteral electrolyte requirements: Table 2: Daily parenteral electrolyte requirements: Element Daily amount Sodium 2-4 mEq/kg Potassium 2-3 mEq/kg Calcium 0.5-2.5 mEq/kg Magnesium 0.25-0.5 mEq/kg Phosphorus 1-2 mM/kg Chloride 2-3 mEq/kg
B.
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6.
Suggested daily calories and macronutrient requirements: Table 3: Suggested daily calories and macronutrient requirements: Age Calories Carbohydrates Protein Fat (g/kg/d) (Cal/kg/d) (g/kg/d) (g/kg/d) Premature 80-120 4-18 2.0-3.0 0.5-3.0 infants Term infants 105 8-23 2.5-3.0 0.5-4.0 1-3 years 75-90 8-23 1.5-2.5 0.5-2.5 4-6 years 65-75 8-23 1.5-2.5 0.5-2.5 7-10 years 55-75 8-23 1.5-2.5 0.5-2.5 11-18 years 40-55 8-23 1.5-2.5 0.5-2.0
D.
PN micronutrient supplementation: 1. Suggested daily trace elements: Table 5: Suggested daily trace elements: Element Zinc Dose 100 g/kg/d (300 g/kg/d in premature infants to 3 month of age) 20 g/kg/d 2-10 g/kg/d 0.2 g/kg/d 1-3 g/kg/d (max 30-40 g/d) 5.0 30 Max 5000 g Comments Increase dose with intestinal losses and catabolic states Decrease dose with cholestasis Decrease dose with cholestasis Increase dose with intestinal losses, decrease dose with renal dysfunction Decrease dose with renal dysfunction, consider increasing dose with intestinal losses Increase dose in primary carnitine deficiency
Copper Manganese Chromium Selenium*
300 g
Carnitine*
1-2 mg/kg/d
a) * May be added after 1 month of NPO status and/or minimal enteral intake. b) Pediatric multivitamins are essential in PN. Check with your PN pharmacist as to which formulation is available. c) Trace elements commonly added to PN solutions include zinc, copper, manganese and chromium (check levels periodically). d) Consider checking 25-OH vitamin D especially when a patient is being weaned from chronic PN. E. Medications and PN: 1. Medications incompatible with parenteral nutrition solutions: a) Acetazolamide b) Acyclovir c) Amphotericin d) Amphotericin B lipid complex Ampicillin e) Ampicillin/sulbactam f) g) Calcium salts h) Cefazolin i) Ciprofloxacin j) Cisplatinum Cyclosporine k) l) Cytarabine m) Diazepam n) Doxorubicin o) Filgastim p) Foscarnet q) Furosemide r) Gancyclovir s) Imipenem t) Indomethacin u) Mannitol Methotrexate v) w) Metoclopramide Metronidazole x) Midazolam y) z) Nitoglycerin aa) Nitroprusside bb) Octreotide cc) Phenytoin dd) Promethazine ee) Trimethoprim/sulfamethoxazole ff) Tromethamine
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NASPGHAN 2. Medications incompatible with lipids: a) Acetazolamide b) Acyclovir c) Amikacin d) Aminophylline e) Amphotericin f) Amphotericin B lipid complex g) Ampicillin h) Ampicillin/sulbactam i) Calcium salts j) Ciprofloxacin Cyclosporine k) l) Diazepam m) Doxorubicin n) Filgastim o) Foscarnet p) Furosemide q) Gancyclovir r) Heparin s) Imipenem t) Indomethacin u) Iron dextran v) Magnesium salts w) Metronidazole Midazolam x) y) Morphine z) Nitroglycerin aa) Nitroprusside bb) Phenytoin cc) Trimethoprim/sulfamethoxazole dd) Tromethamine
F.
Metabolic complications of PN: 1. Hyperglycemia: a) Prevention: (1) Limit dextrose infusion to ~10-15% (2) Limit dextrose increments to 5% per day (3) Monitor serum and urine glucose b) Treatment: (1) Decrease dextrose intake (2) Add insulin to TPN or give IV insulin (if indicated). 2. Hypoglycemia: a) Prevention: (1) Avoid abrupt cessation of PN b) Treatment: (1) IV dextrose 3. Hypercapnia: a) Prevention: (1) Avoid excessive caloric or dextrose infusion b) Treatment: (1) Decrease total caloric intake and/or increase calories as fat 4. Azotemia: a) Prevention: (1) Adequate hydration prior to PN initiation (2) Avoid excessive amino acid infusion (3) Provide adequate nutrition to minimize lean tissue catabolism (4) Monitor BUN b) Treatment: (1) Free water administration in the PN bag or IV dextrose (2) Increase free water in subsequent PN bags (3) Decrease amino acid infusion 5. Hypertriglyceridemia: a) Prevention: (1) Avoid excessive lipid infusion (2) Monitor serum triglycerides weekly (3) Infuse lipids over 18-20 hours b) Treatment: (1) Decrease lipid infusion, may give lipids qod (a) If sustained, give only 0.5-1.0 g/kg/d of lipids 6. Hypokalemia: a) Prevention: (1) Adequate potassium in PN (2) Monitor serum potassium daily until stable, then biweekly b) Treatment: (1) If mild, increase potassium in PN (2) If severe, IV potassium 7. Hyperkalemia: a) Prevention: (1) Avoid excessive potassium administration (2) In patients with renal insufficiency, with appropriate restriction, monitor K daily.
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Pediatric Gastroenterology Hepatology and Nutrition Handbook Treatment: (1) Decrease potassium in PN Hyponatremia: a) Prevention: (1) Adequate sodium in PN (2) Avoid excessive fluid administration (3) Monitor serum sodium daily until stable, then biweekly b) Treatment: (1) Fluid restriction (2) If mild, increase sodium in PN (3) If severe, slow IV sodium in a crystalloid solution Hypernatremia: a) Prevention: (1) Provide adequate fluid (2) Avoid excessive sodium administration (3) Monitor intake/output, urine sodium, osmolarity b) Treatment: (1) If dehydrated, fluid replacement (2) If appropriate, decrease sodium in PN Metabolic acidosis: a) Prevention: (1) Measure and replace intestinal losses (2) Avoid excessive chloride in PN b) Treatment: (1) Treat underlying cause (2) Increase acetate and decrease chloride in PN Metabolic alkalosis: a) Prevention: (1) Measure and replace NG output b) Treatment: (1) Treat underlying cause (2) Increase chloride and decrease acetate in PN Hypocalcemia: a) Prevention: (1) Adequate calcium in PN (2) Monitor serum calcium biweekly (3) Monitor ionized calcium in hypoalbuminemic state (4) Monitor PTH and vitamin D levels b) Treatment: (1) Correct magnesium deficiency (2) Increase calcium in PN if ionized calcium is low Hypercalcemia: a) Prevention: (1) Monitor serum calcium until stable. (2) Restrict as appropriate b) Treatment: (1) Decrease calcium in PN (2) IV normal saline (3) May need to remove vitamin D from PN Hypomagnesemia: a) Prevention: (1) Adequate magnesium in PN (2) Monitor serum magnesium until stable. b) Treatment: (1) If mild, increase magnesium in PN (2) If severe, IV magnesium Hypermagnesemia: a) Prevention: (1) In patients with renal insufficiency, restrict as appropriate. (2) Avoid excessive magnesium administration b) Treatment: (1) Decrease magnesium in PN Hypophosphatemia: a) Prevention: (1) Monitor serum phosphorus daily until stable. b) Treatment: (1) If mild, increase phosphorus in PN (2) If severe, IV phosphorus Hyperphosphatemia: a) Prevention: (1) Monitor serum phosphorus daily until stable, then biweekly (2) Monitor serum phosphorus in patients with renal insufficiency, restrict as appropriate (3) Avoid excessive phosphorus administration b) Treatment: (1) Decrease phosphorus in PN
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
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NASPGHAN G. Useful conversion factors needed in PN ordering (table): Conversion of grams to moles: Na mg x 0.043 = mmol K mg x 0.025 = mmol Cl mg x 0.028 = mmol Fe mg x 0.018 = mmol Ca mg x 0.025 = mmol Mg mg x 0.041 = mmol Mn mg x 0.018 = mmol Cu mg x 0.015 = mmol Zn mg x 0.015 = mmol Cr mg x 0.019 = mmol Mo mg x 0.010 = mmol
H.
Caloric estimates of different PN solutions (Calories / cc) (table): Table 7. Caloric estimates of different PN solutions (Calories / cc): Dextrose 5% 10% 12.5% 15% 17.5% 20% %AAs 1 0.21 0.38 0.47 0.5 0.64 0.72 1.5 0.23 0.40 0.49 0.57 0.66 0.74 2 0.25 0.42 0.51 0.59 0.68 0.76 2.5 0.27 0.44 0.53 0.61 0.70 0.78 3 0.29 0.46 0.55 0.63 0.72 0.80 3.5 0.31 0.48 0.57 0.65 0.74 0.82 4 0.33 0.50 0.59 0.67 0.76 0.84 4.5 0.35 0.52 0.61 0.69 0.78 0.86 5 0.37 0.54 0.63 0.71 0.80 0.88
22.5% 0.81 0.83 0.85 0.87 0.89 0.91 0.93 0.95 0.97
25% 0.89 0.91 0.93 0.95 0.97 0.99 1.01 1.03 1.05
27.0% 0.98 1.00 1.02 1.04 1.06 1.08 1.10 1.12 1.14
30% 1.06 1.08 1.10 1.12 1.14 1.16 1.18 1.20 1.22
I. J.
Authors Mirna Chehade, MD References: Fisher JE. Total Parenteral Nutrition. Little, Brown and Company, 1992 Grant A, Todd E. Enteral and Parenteral Nutrition, a Clinical Handbook. Blackwell Scientific Publications, 1987 Grant JP. Handbook of Total Parenteral Nutrition. W.B. Saunders Company, 1992 Hendricks KM, Duggan C, Walker WA. Manual of Pediatric Nutrition. BC Decker Inc, 2000 Kerner JA, Jr. Manual of Pediatric Parenteral Nutrition. John Wiley & Sons, 1983 Rombeau JL, Rolandelli RH. Clinical Nutrition, Parenteral Nutrition. W.B. Saunders Company, 2001 The author would like to thank Kate Samela, MS, RD for useful comments.
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XV. Drug Formulary
Generic
Trade
Dosage
Forms
Adverse Effects
Drug Interactions
1. Bioavailability of alendronate is increased when administered with oral and IV ranitidine 2. Increases incidence of GI adverse effects from NSAIDs / salicylates 3. Reduced absorption with antacids, calcium, iron, multivalent cations and dairy products.
Information
Alendronate
Fosamax
Adults:10 mg PO QD Take with 8 ounces of plain water 30 minutes before first 5 mg, 10 mg, 35 mg, food, beverage, or 40 mg, 70 mg tabs other medication. Do not lie down for at least 30 minutes after taking alendronate
Use: bone demineralization caused by chronic steroid use and symptomatic Pagets bone disease. Contraindication: esophagitis and hypocalcemia Overdose: severe GI symptoms, hypocalcemia or hypophosphotemia. Treat with milk or antacids to bind alendronate. Not dialyzable. Ensure adequate calcium and vitamin D intake while receiving alendronate
Pill esophagitis Transient Hypocalcemia and hypophosphatemia
Alternagel, Amphogel, Aluminum Hydoxide Alu-Cap, (OTC) Alu-Tab, Dialume
Aluminum / Magnesium Hydroxide
Maalox, Mylanta
Amitriptyline
Elavil
Amoxicillin
Amoxil, Trimox
Peptic ulcer: Children: 320-960 mg/dose q 3-6 hrs or 1 and 3 hrs after meals and at bedtime Adults: 2-3 g/dose q 3-6 hrs or 1 and 3 hrs after meals and at bedtime GI bleeding prophylaxis: Infants: 120-320 mg/dose PO q 1-2 hrs Children: 320-960 mg/dose PO q 1-2 hrs Adults: 2-4 g/dose PO q hr Peptic ulcer disease: Children: 5-15 mL/dose every 3-6 hours Adults: 15-45 mL/dose every 3-6 hours GI bleeding prophylaxis: Infants: 2-5 mL/dose every 1-2 hours Children: 5-15 mL/dose every 1-2 hours Adults: 30-60 mL/dose every 1-2 hours Use caution with extra-strength preps in children. Depression (max take up to 4 weeks to notice effects): 6-12 years: 10-30 mg PO or 1-5 mg/kg/day divided TID (start at 1 mg/kg/day and titrate up to 5 mg/kg/day) Adolescents: Initial: 50 mg QD divided QID adjust PRN max 100 mg QD Adults: Initial: 50 mg daily divided QD-TID Maintenance: adjust dose to 50-150 mg daily divided QD-TID (max dose: 300 mg/day) Children: 40 mg/kg/day PO divided q8h (80-90 mg/kg/day PO divided q12 for penicillin resistant S.
Liquid: Alternagel120mg/mL Suspension: Amphogel 64 mg/mL 300 mg, 600 mg tabs Alu-Cap 400 mg caps Alu-Tab 500 mg tabs Dialume 500 mg caps
Constipation Hypophosphatemia, hypomagnesemia (high doses) Discoloration of feces (white speckles)
May result in decreased bioavailability of medications if administered concurrently. To minimize this interaction, administer the antacid dose 2 hrs before or 1 hour after the medication dose.
Use: hyperacidity; hyperphosphatemia Precaution: in setting of renal failure or prematurity aluminum toxicity may occur.
Maalox Aluminum= 45mg/mL Diarrhea Magnesium=40mg/mL Constipation Mylanta Discoloration of feces (white speckles) Aluminum=40mg/mL Magnesium=40mg/mL
May result in decreased bioavailability of medications if administered concurrently. To minimize this interaction, administer the antacid dose 2 hrs before or 1 hour after the medication dose.
Precaution: in setting of renal failure or prematurity, excess aluminum or magesium absorption may occur. Alternagel>Maalox>Mylanta>Amphojel in neutralizing capacity.
10, 25, 50, 75, 100, 150 mg tabs
Anticholinergic (blurred vision, confusion, constipation, urinary retention, hypotension, Parkinsonian syndrome) Drowsiness Headache Nausea / vomiting increased appetite Sexual dysfunction Increased QT interval More side effects than most other TCAs: consider Nortryptiline instead
1. Additive effects with CNS depressants 2. Increased risk of arrythmias in combination with cisapride 3. Increased risk of neurotoxicity, seizures, or serotonin syndrome in combination with MAO inhibitors. 4. May potentiate the effect of oral anticoagulants
Tricyclic Antidepressant For chronic pain, use lower doses, 2575 mg QD Contraindicated in patients with cardiac rhythm disorders. Consider using this or nortriptyline or paroxetine for IFN-alpha induced depression.
Rash 250 mg, 500 mq caps Nausea/Vomiting/Diarrhea 25 mg/mL, 50 mg/mL Seizures (high doses) Interstitial nephritis suspension Hypersensitivity reactions
1. Results in increased methotrexate levels Contraindication: penicillin allergy 2. Decreased effectiveness of oral contraceptives
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pneumoniae otitis media) Adults:250-500 mg/dose PO q8h Endocarditis prophylaxis (low risk): Children: 50mg/kg PO 1 hr before procedure (Max dose = 2 g) Adults: 2 gm PO 1hr before procedure Endocarditis prophylaxis(high risk): Children 50 mg/kg IV/IM Adults: 2 gm IV/IM 30 min before procedure with gentamicin (1.5 mg/kg); repeat ampicillin 6 hrs later with the dose (Max dose=2 g) Dose expressed as ampicillin Children:100-200 mg amp/kg/day IV divided q6h Adults: 1-2 g amp/kg IV q6-8h

3. probenecid may increase amoxicillin levels
Ampicillin
Omnipen, Principen
Rash 250 mg, 500 mg caps Nausea/Vomiting/Diarrhea Seizures 125 mg, 250 mg, 500 mg, 1 g, 2 g inj Interstitial nephritis Hypersensitivity reactions
1. Results in increased methotrexate levels 2. Decreased effectiveness of oral contraceptives. 3. Probenecid may increase ampicillin levels
Contraindication: penicillin allergy Use Vancomycin with gentamicin if penicillin allergic. Adjust for renal impairment. Sodium content: 3 mEq per gm of ampicillin
Ampicillin/sulbactam Unasyn
50 mg amp/mL inj
Nausea/Vomiting Seizures Interstitial nephritis Hypersensitivity reactions Pseudomembranous colitis Nausea Vomiting Diarrhea Bone marrow suppression Hypersensitivity reactions Hepatotoxicity Stomatitis Pancreatitis Nausea Vomiting Diarrhea Abdominal pain Diaphoresis Urinary frequency Bronchial constriction Lacrimation Miosis
1. Increases methotrexate levels 2. Decreases Contraindication- penicillin allergy effectiveness of oral contraceptives. 1. Metabolism blocked by allopurinol. Reduce Azathioprine is metabolized to azathioprine dose mercaptopurine. 25-33%. Can monitor metabolite levels 2. Decreases anticoagulant effect of warfarin
Azathioprine
Imuran
Children and Adults: 1-2 mg/kg PO/IV QD
50 mg tabs 5 mg/mL inj
Bethanechol
Urecholine
Prokinetic: Children: 0.1-0.2 mg/kg/dose PO TID- 5 mg, 10 mg, 25 mg, QID 50 mg tabs Adults:10-50 mg PO BID-QID
1. Increases effects Administer 30-60 minutes before meals of cholinergic agents Use with caution in patients with 2. Cholinergic effects hyperthyroidism, asthma, and peptic counteracted by ulcer disease atropine
Biotin (OTC)
Bisacodyl (OTC)
Holocarboxylase synthetase deficiency/HCD or Biotinidase deficiency: coenzyme R, Children and vitamin H adults: 5-10 mg PO QD RDA not established; requirement: 100200 ug/day Children: Oral administration: 3-12 yr: 5-10 mg PO QD or 0.3 mg/kg/day Rectal Ducolax administration: < 2 years: 5 mg PR QD 2-11 years: 5-10 mg PR QD > 12 yr and Adults: 5-15 mg PO/PR QD
5 mg capsules Tablets: 300 ug, 2.5 mg, 3 mg, 5 mg, 10 mg
None known
None known
Symptoms/signs of HCD: rash, alopecia, organic aciduria, metabolic acidosis, vomiting, seizures.
5 mg tabs (enteric coated) 5 mg, 10 mg supp
Nausea Vomiting Diarrhea Abdominal cramping
Antacids may prematurely dissolve enteric coating leading to gastric irritation.
Swallow tablet whole on empty stomach. Do not administer within 1 hour of milk and dairy products (causes gastric irritation) Onset: oral 6-10 hrs; rectal 15-60 min
RDA: Doses are expressed in terms of elemental calcium Children: 0-6 months: 210 mg Tums, Tums 6-12 months: 270 EX, Tums mg 1-3 yr: 500 mg 500, Oscal, Calcium Carbonate Caltrate, 4-8 yr: 800 mg Supplements (OTC) 9-18 yr: 1300 mg Rolaids, Calcium Carb Adults: 19-50 yr: 1000 mg Susp > 51 yr: 1200 mg Pregnant and Lactating: <19 yr: 1300 mg 19-50 yr: 1000 mg
Elemental calcium is in parentheses Tums: 500 mg (200 mg) Tums EX: 750 mg (300 mg) Tums 500: 1250 mg (500 mg) Oscal: 1250 mg (500 Constipation, hypercalcemia, nephrolithiasis, milk-alkali syndrome mg) Caltrate: 1500 mg (600 mg) Rolaids: 500 mg (200 mg) Rolaids 1000 mg (400 mg) Calcium Carb Susp 1250 mg/5mL (500
1. May potentiate digoxin toxicity 2. May antagonize effects of calcium channel blockers 3. Decreases bioavailability of iron salts, quinolones, tetracyclines, salicylates, zinc and alendronate
Absorption inhibited by high phosphate load. Administer with plenty of water to prevent constipation. Administer between meals to maximize calcium absorption and minimize phosphate binding
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mg/5mL) Carnitine Deficiency: Neonates: 10-20 mg/kg/day in TPN Children: 50-100 mg/kg/day PO divided BID-TID; max 3 g / day Carnitor, carnitine-deficient Vitacarn = L- dialysis patients: 10carnitine 20 mg/kg IV after each dialysis (maintenance dose ~5mg/kg/day after 3-4 weeks) Adults (CHF, hemodialysis): 0.5 g PO TID Infection: Neonates: 50-100 mg/kg/day IV/IM divided 12h Children: 50-100 mg/kg/day IV/IM divided q8h (max 2 gm/dose; 6 gm/day) Adults: 1-2 gm IV/IM q6-8h (max 2 gm/dose; 12 Ancef, Kefzol gm/day) Endocarditis Prophylaxis (penicillin allergic): Children: 25 mg/kg IV/IM 30 minutes prior to procedure ( max 1gm) Adults: 1gm IV/IM 30 minutes prior to procedure Children: 25- 100 mg/kg/day PO divided q6h (max 4 gm/day) Adults: 250-500 mg PO q6h (max 4 gm/day) Keflex, Endocarditis Keftab prophylaxis (low risk): Children: 50 mg/kg PO 1 hr prior to procedure Adults: 2 gm PO 1 hr prior to procedure
Carnitine
330 250 100 200
mg tabs mg capsule mg/ ml solution mg/ml inj
Body odor (dose related) diarrhea nausea/vomiting cramps seizures Depression Dizziness Paresthesia Fever Hypertension Hypercalcemia Muscle weakness
Valproic acid Sodium Benzoate D,L carnitine (sold in health food stores as vitamin BT) competitively inhibits L-carnitine
Little data supports the use of carnitine supplementation in malnourished or critically ill patients, although serum levels are often low. Reference range: Free carnitine: >20 micromoles/L Total carnitine: 30-60 micromoles/L Acylcarnitine: free carnitine ratio: =(total carnitine-free carnitine) /free carnitine Normal ratio: <0.4
Cefazolin
500 mg, 1000 mg inj
Leukopenia Thrombocytopenia Hypersensitivity reactions Seizures Rash Pseudomembranous colitis
1. Serum concentration may be prolonged by Probenecid 2. Increases nephrotoxicity of aminoglycosides
Precaution: Hypersensitivity reactions in 5-10% of penicillin allergic patients. Sodium content: 2mEq per gm of cefazolin. Dose adjust for renal impairment
Cephalexin
250 mg, 500 mg caps Nausea/Vomiting/Diarrhea 25 mg/mL, 50 mg/mL Pseudomembranous colitis susp Hypersensitivity reactions 250 mg, 500 mg and 1 Transient neutropenia gm tabs Anemia
1. Levels may be prolonged by Probenecid 2. Increases nephrotoxicity of aminoglycosides
Precaution: Hypersensitivity reactions in 5-10% of penicillin allergic patients. Administer on an empty stomach Adjust dose for renal impairment
Cholestyramine
Cimetidine
Cisapride
1. Decreases absorption of other medications. To minimize this 4 gm anhydrous resin interaction, per scoop or packet (9 Nausea, vomiting, electrolyte administer other Questran abnormalities, constipation, rash gm total weight per medications 2 hours scoop) before or 2-4 hours after cholestyramine. 2. Malabsorption of fat-soluble vitamins Inhibits the hepatic metabolism of drugs metabolized by the Neonates: 5-10 cytochrome P450 mg/kg/day PO/IV/IM Nausea pathway including divided q 8-12h Vomiting, phenytoin, Infants:10-20 Confusion, theophylline, mg/kg/day PO/IV/IM 200 mg, 300 mg, 400 Dizziness warfarin, tricyclic divided q 6 hrs mg, 800 mg tabs Gynecomastia antidepressants, Children:20-40 Tagamet, 60 mg/mL elixer Neutropenia carbamazepine, mg/kg/day PO/IV/IM Tagamet-HB 150 mg/mL inj cyclosporine, Agranulocytosis divided q 6h Alcohol content of Thrombocytopenia tacrolimus, Adults:300 mg elixer= 2.8% quinidine, and Elevated LFTs, PO/IV q 6h certain Hypotension May increase to 600 Bradycardia, cardiac arrhythmias with benzodiazepines. mg PO q6h for adults Decrease the rapid IV infusion with hypersecretory absorption of iron, conditions tetracycline, ketoconazole and fluconazole. Children: 0.1-0.3 QT prolongation QT prolongation has 10 mg, 20 mg tabs mg/kg/dose PO TIDTachycardia occurred when 1 mg/mL susp Propulsid QID (max 10 Nausea/Vomiting/Diarrhea/constipation cisapride is Available via limitedmg/dose) Abdominal cramping administered with access protocol only Adults: 10-20 mg Headache azole antifungals, Children (dose expressed as anhydrous resin): 240 mg/kg/day PO divided TID Adults: 3-4 gm PO TID-QID (max 32 gm/day)
May be mixed with water, juice, or applesauce. Do not administer dry powder
Administer with food. Adjust for renal and severe liver impairment
Drug interactions with cisapride have resulted in ventricular tachycardia and torsade de pointes. Take cisapride 15 minutes before meals.
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PO QID

Anxiety, nervousness, insomnia Photosensitivity Rash, Elevated LFTs hepatitis (+) ANA clarithromycin, erythromycin, indinivar, nelfinavir, ritonavir, and saquinavir due to inhibition of the cytochrome P450 system See package inserts black box for complete list of drug and disease interactions. Decrease dose by 50% in patients with liver impairment. Monitor baseline EKG prior to initiating therapy. Avoid grapefruit juice
Cromolyn sodium
Cyclosporine
Cyproheptadine
Children: < 2 years: 20 mg/kg/day PO divided QID (max 30 100 mg caps mg/kg/day) Gastrocrom 2-12 years: 100 mg 20 mg/mL oral concentrate PO QID (max 40 mg/kg/day) Adults: 200 mg PO QID (max 1.6 gm/day) Liver transplant; immunosuppression: Children and Adults: Initial: 10 mg/kg/day PO divided BID Maintenance: 5-40 mg/kg/day PO divided BID titrate to desired serum trough levels. IV dose= 2-4 mg/kg/day divided Neoral 25 mg, 100 mg BID caps IBD: 100 mg/mL Children and Neoral, Adults: 4 mg/kg/day microemulsion soln SangCya, SangCya 100 mg/mL has been studied. Sandimmune Doses should be microemulsion soln individualized based Sandimmune 25 mg, 50 mg, 100 mq caps on levels. Neoral 100 mg/mL soln cannot be used interchangeably with Sandimmune as the absorption is different. A one:one ratio has been recommended initially for conversion. However, lower doses of Neoral may be required after conversion to prevent toxicity Allergic conditions: Children: < 2 years: 0.25 mg/kg/day PO divided BID-TID 2-6 years: 2 mg PO q 8-12h (max 12 mg/day) 7-14 years: 4 mg PO 4 mg tabs Periactin 0.4 mg/mL syrup (5% q8-12h (max 16 mg/day) alcohol) Adults: 4 mg PO q8h Appetite stimulant: Children and adults: 2 mg PO QID increase every 2-3 weeks (max 8mg QID)
Nausea Diarrhea Headache Dizziness Arthralgia Rash Angioedema
No data reported
To prepare oral solution, open capsule and dissolve in hot water, then add equal amount of cold water. Do not give with juice or food.
Nephrotoxicity Hypertension Headache Hyperkalemia Nausea/Vomiting/Diarrhea Seizures Hypercholesterolemia Hirsutism Elevated transaminases Gingival hypertrophy Tremors Hypomagnesemia Acne Leukopenia Thrombocytopenia Anemia Increased risk of 2nd lymphomas
1. Additive nephrotoxicity with NSAIDS, amphotericin, acyclovir, aminoglycosides, and other potentially nephrotoxic medications 2. Levels may be decreased by carbamazepine, phenytoin, primidone, phenobarbital, nafcillin, rifampin, rifabutin, and trimethoprim 3. Levels may be increased by methylprednisolone, macrolides (azithromycin is OK), tacrolimus, calcium channel blockers (amlodipine and isradipine are OK), and azole antifungals. 4. Increases toxicity of digoxin
Therapeutic ranges (trough levels): 1. Post transplant: Kidney: 100-200 mg/dL BMT: 100-250 mg/dL Liver: 100-400 mg/dL 2. Liver Disease, IBD: 150-250 mg/dL High fat meals increase volume of distribution of cyclosporine. Grapefruit may increase cyclosporine concentrations
Sedation Seizures Photosensitivity Tachycardia Depression Appetite stimulation Dry mouth Urinary retention Blurred vision
1. Additive sedative effects with other CNS depressants and anticholinergics Administer with food 2. Decreases efficacy of SSRIs and increases adverse effects of MAOIs
Diphenoxylate/ atropine
Lomotil
(as diphenoxylate) Children: 0.3-0.4 mg/kg/day divided BID-QID -or< 2yrs: Not recommended 2-5 yrs: 2 mg TID 5-8 yrs: 2 mg QID 8-12 yrs: 2 mg 5 doses/day Adults: 5 mg TIDQID
diphenoxylate 2.5 mg and atropine sulfate 0.025 mg per 5 mL soln diphenoxylate 2.5 mg and atropine sulfate 0.025 mg tabs
Tachycardia Sedation Pruritus Nausea/Vomiting Urinary retention Blurred vision Respiratory depression Dependence with prolonged use
Docusate (OTC)
Colace
Infants: 5 mg/kg/day divided 50 mg, 100 mg caps QD-QID 4 mg/mL syrup 10 mg/mL liquid Children: <3 years: 10-40
Abdominal cramping, diarrhea
1. May cause hypertension with MAO inhibitors 2. Increases effects of CNS depressants and alcohol 3. Additive effects with anticholinergic agents 4. Effects are antagonized by naltrexone and nalaxone 5. St. Johns Wort increases side effects Concurrent administration increases hepatic uptake of mineral oil, possibly
Administer with food to avoid GI upset
Onset: 24-72 hrs. Ensure adequate fluid intake for best results. May administer liquid (not syrup) with milk or juice to mask taste.
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mg/day divided QDQID 3-6 years: 20-60 mg/day divided QDQID 6-12 years: 40-120 mg/day divided QDQID Adults: 50-400 mg/day divided QD QID

resulting in intestinal, liver, or spleen inflammation.
Erythromycin
EES and others
Prokinetic: Children: 1mg/kg/dose QID
Cholestatic Hepatitis (0.1% children, 0.25% adults) estolate 125, 250 mg Prolonged QT interval, arrhythmias tabs; Ototoxicity ethysuccinate 250 mg Nausea tabs Vomiting Diarrhea
Esomeprazole
Nexium
Children: dosing not established Adults: 20-40 mg PO QD
20 mg, 40 mg capsules
Heachache Diarrhea Nausea Abdominal pain
Famotidine
Pepcid, Pepcid AC
Children: 1-2 mg/kg/day PO/IV divided Q 8-12 h Adults: 20-40 mg/day PO/IV divided QD-BID Maintenance: 20 mg PO QD
Pepcid: 10 mg, 20 mg, 40 mg tabs 0.4 mg/mL inj ?? 40 mg/5 ml suspension Pepcid AC: 10 mg chewable tabs
Headache Dizziness Thrombocytopenia Leukopenia Constipation/Diarrhea Elevated LFTs CNS depression Euphoria Drowsiness Nausea/Vomiting Constipation Urinary retention Sedation Erythema, pruritus Respiratory depression Miosis
1. Contraindicated with Cisapride, Astenizole, Terfenadine 2. Increases Metabolized in liver; do not use in significant liver impairment theophylline and digoxin levels 3. Potentiates anticoagulant effect of warfarin 1. Clarithrymicin, amoxicillin: increase Proton pump inhibitor, optical isomer of esomeprazole levels. omeprazole. Take at least one hour before eating. 2. Markedly Capsule may be opened and granules increases levels of given whole in applesauce. diazepam See comments for omeprazole. 3. Food decreases absorption 1. Bioavailability slightly decreased by antacids 2. Decreases Take one hour before eating or drinking when using for prophylaxis. bioavailability of ketoconazole and itraconazole, delavirdine
Fentanyl
Sublimaze
Sedation for minor procedure Children: 1-3 ug/kg/dose IV 0.05 mg/mL inj repeated q30-60 min Adults:0.5-1 ug/kg/dose IV repeated q30-60 min Children: No published data but this is the ESRD protocol at Texas Childrens Hospital: 12.5 mg elemental <20 kg: 15.6 mg IV Fe/ml for 10 doses (9 mg of benzyl 20-40 kg: 31.2 mg alcohol per 5 ml) IV for 10 doses > 40 kg: 62.5 mg IV for 10 doses Adults: 125 mg IV daily for 8-10 days. Iron deficiency Anemia Children 5 - 15 kg: (IM/IV) Dose (mL) = 0.0476 x Wt x (desired Hb observed Hb) + (1 ml/ 5 kg Wt) Max daily dose IM < 5 kg child: 25 mg 5-10 kg: 50 mg Max TOTAL dose 14 50 mg/ml ml Children >15 kg and Adults (IM/IV): Dose (mL) = 0.0476 x LBW x (desired Hb observed Hb) + (1 ml/ 5 kg LBW) Max daily dose IM > 10 kg: 100 mg (LBW=Lean Weight in Kg) Dose expressed as Feosol: 325 mg (65 elemental iron mg elem iron) tab Children: 44 mg/mL (8.8 mg Prophylaxis: 1-2 mg elem iron/mL) liq or elem iron/kg/day elixer divided QD-BID Fer-in-sol: 125 mg/mL Moderate deficiency: (25 mg/mL elem iron)
Adverse effects may be potentiated by CNS depressants, alcohol, MAO inhibitors, St Johns wort phenothiazines, and tricyclics
Caution: an opioid antagonist, resuscitative and intubation equipment must be available when administering fentanyl. Dose adjust for renal impairment.
Ferric Gluconate Injectible
Ferrlecit
Anaphylaxis very rare (immediate or delayed) Hypotension, hypertension Hyperkalemia, hypoglycemia Headache, fever, fatigue Skin discoloration if given SC
Infusion rate should not exceed 12.5 mg/min (test dose no longer required) Do not give SC Contraindications: Hemachromatosis Hemolytic anemia
Ferric Dextran
Dexferrum Infed
Anaphylaxis (immediate or delayed) Hypotension Skin discoloration if given SC
Do test dose 1 hr prior to giving dose: Infants: 0.25 ml Children and adults: 0.5 ml Max infusion rate 25 mg/min Do not give SC Contraindications: Hemachromatosis Hemolytic anemia
Ferrous Sulfate
Feosol, Ferin-sol
Nausea, diarrhea, constipation, dark stools, discoloration of urine, liquid preps may stain teeth
1. Concurrent administration results in decreased absorption of tetracycline, levothyroxine, and certain quinolones.
Take with food Hemoglobin values increase in 2-4 weeks Do not crush sustained release products.
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3 mg elem oral drops iron/kg/day divided 90 mg/5mL syrup QD-BID contains 18 mg elem Severe deficiency: 4- iron/5mL 6 mg elem iron/kg/day divided BID-TID Adult: Prophylaxis: 60-100 mg elem iron PO QD Deficiency: 60-100 mg elem iron PO BID Children: 0.01 mg/kg over 15 seconds(max 0.2 mg), then 0.005-0.01 mg/kg (max 0.2 mg) every minute until a max total cumulative 0.1 mg/mL inj dose of 1 mg Adults: 0.2 mg IV over 15 sec. Repeat up to 5 times (Max dose=3 mg/hour) Children: > 1 month 5-8.8 mg/kg/day PO divided Q6H (Max dose=400 mg/day) 100 mg tab Adults: 100 mg PO 3.3 mg/mL susp QID Do not use in infants <1 month due to possibility of hemolytic anemia

Space drugs by two hours. 2. Fe absorption decreased by cimetidine, other H2 blockers and antacids 3 Vit C increases iron absorption
Flumazenil
Romazicon
Decreases duration of thiopental Arrhythmias, bradycardia, tachycardia, anesthetic effects. fatigue, hot flashes, nausea, vomiting, Supplemental doses pain at injection site, blurred vision of thiopental may be necessary.
For reversal of benzodiazepine induced sedation. Does not antagonize nonbenzodiazepine GABA agonists or reverse the effects of opiates.
Furazolidone
Furoxone
Nausea/Vomiting/Diarrhea Disulfiram reaction Hypotension Drowsiness, dizziness Headache Urine discoloration (brown tint)
1. Hypertensive effects of the following medications may be potentiated: sympathomimetic amines, tricyclic antidepressants SSRIs, and MAO inhibitors 2. Caution: tyramine-containing foods may cause hypertension
Caution: Do not administer with alcohol and alcohol containing products due to disulfiram reaction. Contraindication: G-6-PD deficiency due to possibility of hemolytic anemia
Furosemide
Lasix
Children: 1-2 mg/kg/dose PO/IM/IV BID Adults: 20-80 mg PO/IM/IV QD - BID (increase to max of 600 mg/day)
Orthostatic hypotension Dizziness Vertigo Urticaria Hypokalemia 20 mg, 40 mg, 80 mg Hyponatremia tabs Hypomagnesemia 10 mg/mL, 8 mg/ml hypocalcemia oral soln Alkalosis 10 mg/mL inj Hyperuricemia Increased calcium excretion Photosensitivity Ototoxicity Nephrocalcinosis
1. Effects decreased by NSAIDS and Salicylates 2. Decreases excretion of lithium 3. Increases May cause ototoxicity particularly with ototoxicity of renal insufficiency and/or use of aminoglycosides and aminoglycosides ethacrynic acid 4. monitor drugs effected by potassium i.e. digoxin Increased toxicity with amphotericin B, loop diuretics, vancomycin, cisplatin, indomethacin, cyclosporin, and tacrolimus and other nephrotoxic medicines 1. Increased anticoagulant effects of warfarin. 2. Insulin-releasing effects are inhibited by phenytoin. 3. Hyperglycemic effects may be inhibited by Propranolol and other beta blockers. No data reported
Gentamicin
Garamycin
Endocarditis Prophylaxis (high risk) Children: 1.5 Ototoxicity mg/kg IM/IV 30-60 10 mg/mL, 40 mg/mL Nephrotoxicity min before procedure inj Neuromuscular blockade with ampicillin or vancomycin Adults: 1.5 mg/kg IM/IV (120 mg max. dose) Children: 0.03-0.1 mg/kg/dose IV (max dose = 1 mg) Repeat in 20 min if needed 1mg, 10 mg inj Adults: 0.5-1 mg/dose IV Repeat in 20 min if needed One application 1-2 100 mg/60 mL times/day for 2-3 weeks Children: 5 mg/kg/dose IV infused over a minimum of 2 hours; (range of 1-10 mg/kg 100 mg/20 ml inj IV) Adults: 5 10 mg/kg IV infused over a minimum of 2 hours Children: 3 million units/M2 TIW x 1 3 million units/ml week, then 6 mu/M2 TIW thereafter
Therapeutic levels for traditional dosing: Peak: 6-10 ug/mL Trough: < 2 ug/mL
Glucagon
Glucagon
Hypoglycemia, urticaria, nausea, vomiting, respiratory distress, hypersensitivity reactions
Antihypoglycemic Agent Relaxes smooth muscle May be used as a diagnostic aid during endoscopy. 1 mg=1 unit
Hydrocortisone enema
Cortenema
Discontinue slowly by decreasing use to QOD for 2-3 weeks, if used for more than 3 weeks
Infliximab
Remicade
Anaphylaxis Severe, delayed hypersensitivity reactions Headache Fatigue Fever Nausea Diarrhea Abdominal pain Flu-like symptoms Fatigue/malaise depression thyroid dysfunction
No data reported
Use: Refractory severe or fistulizing Crohns Disease Some centers premedicate with acetaminophen and diphenhydramine 30 minutes prior to infusion to decrease side effects
Interferon alpha 2b Intron A
Reduces clearance of Consider cotreatment with ribavirin for theophylline chronic hepatitis C. Additive Premedicate with acetaminophen myelosuppression decrease flu-like symptoms.
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Adults: Chronic Hepatitis B: 10 million units IM/SC TIW Chronic Hepatitis C: 3 million units IM/SC TIW x 6-12 mo. Intestinal Amebiasis: Children: 30-40 mg/kg/day PO divided TID x 20 days 210 mg, 650 mg tabs (max dose=1.95 g/24 hrs) Adults:650 mg PO TID x 20 days (max 2 gm/day) Hepatic Encephalopathy: Adjust dosage to produce 2-3 soft stools per day Infants: 2.5-10 mL/day PO divided TID-QID Children: 40-90 mL PO QD divided TID666 mg/mL syrup QID Adults: 30-45 mL/dose PO TID-QID Constipation: Children:1 mL/kg (up to adult dose) QD-BID titrate to response Adults:15-30 mL PO QD (max 60 ml/day)

anorexia with zidovudine leukopenia elevated aminotransferases Neurotoxicity Confusion DeliriumTachycardia, arrhythmias, SVT (<1%) Skin eruptions Nausea/Vomiting/Diarrhea Headache agitation Ataxia Thyroid enlargement Optic neuritis/optic atrophy myalgia EKG recommended prior to and during treatment for patients with preexisting cardiac disease.
Iodoquinol
Yodoxin
Take with food. Protein bound iodine levels may be increased during treatment and interfere with the results of certain thyroid function tests Contraindication: hypersensitivity to iodine, hepatic or renal impairment, pre-existing optic neuropathy.
Lactulose
Duphalac, Kristalose
Cramping Flatulence Nausea Vomiting Diarrhea
1. Oral antibiotics may interfere with desired degradation of lactulose by eliminating key GI Administer with juice, milk, or water bacteria 2. Effectiveness may be decreased by antacids and laxitives
Lamivudine
Epivir-HBV 3TC
Hepatitis B infection: Children: 3 mg/kg PO QD, max 100 mg 100mg tabs daily 5 mg/ml solution Adults: 100 mg PO QD
Lactic acidosis Hepatomegaly with steatosis Headache Fatigue Insomnia psychomotor disorders Nausea vomiting anorexia Feeding problems Pancreatitis (14%) Musculoskeletal pain Hyperglycemia Neutropenia Abdominal pain Elevated LFTs Paresthesias Peripheral neuropathy Fatigue Dizziness Rash Abdominal Pain Nausea Increased serum transaminases Tinnitus Proteinuria Angina Hypertension Hypotension Sedation Fatigue Dizziness Rash Nausea/Vomiting Constipation Cramping
Bactrim increases lamivudines AUC
Synthetic nucleoside analog. Increases rate of HbeAg loss, ALT normalization, and HBV DNA decrease in one pediatric trial, but frequent relapse. YMDD mutations of HBV may increase during treatment Dose adjust for renal impairment
Lansoprazole
Prevacid
Children: 1-2 mg/kg PO divided QD-BID Adults:15-30 mg 15, 30 mg caps PO QD-BID Higher doses may be required in ZollingerEllison syndrome
Loperamide
Children: 0.4-0.8 mg/kg/day PO divided BID-QID Imodium, (max 2mg/dose) Imodium AD Adults: 2 mg/dose PO (max Dose=16 mg/day) Children:1-2 mL/kg/dose PO BID Adults: 30-60 mL PO QD; Take with fluids
2 mg cap & tab 0.2 mg/mL soln
Magnesium hydroxide
Milk of magnesia
2.67 mEq/mL
Fluid/Electrolyte imbalance
1. Absorption may be delayed and decreased by 30% by sucralfate 2. May decrease the absorption of Keto/Itraconazole due to acid suppression 3. Increases theophylline clearance by 10% Additive CNS toxicity with CNS depressants, phenothiazines, tricyclic antidepressants, and alcohol See drug interactions for aluminum hydroxide. Separate from other meds. by 2 hours. 1. May cause amenorrhea and galactorrhea when administered with Bromocriptine
Capsules may be opened and granules swallowed in applesauce. Slightly longer half-life than omeprazole. Granules may be administered cautiously through some feeding tubes. See comments for omeprazole.
40% of dose is absorbed systemically. Contraindication: patients with colitis to avoid toxic megacolon.
Onset: 0.5-3 hrs. Osmotic laxative
Megestrol
Megace
Children:10 mg/kg/day PO divided BID 20, 40 mg tabs Adults: 160-320 40 mg/ml suspension mg PO QD (max 800 mg PO QD) Children: 1-2 mg/kg/dose PO/IM/IV q3-4h as
Meperidine
Demerol
Thrombophlebitis Alopecia Decreased glucose tolerance Adrenocortical insufficiency when withdrawn abrubtly Edema Breakthrough bleeding and amenorrhea 50 mg, 100 mg tabs Hypotension 10 mg/ml syrup Bradycardia/tachycardia 50 mg/mL multi-dose Respiratory depression
Indications: anorexia, FTT Pharmacology: a progestagen with some glucocorticoid effects
1. Analgestic effects Caution: renal or hepatic impairment. Normeperidine, an active metabolite decreased by may accumulate and result in seizures, Phenytoin
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needed Adults:50-150 mg/dose PO/IM/IV q3-4h as needed Decrease dose in renal or hepatic impairment. inj 10 mg, 25 mg, 50 mg, 75 mg, 100 mg single dose inj Nausea/vomiting Constipation Pruritus Urinary retention Miosis Drowsiness CNS depression Seizures Nausea/Vomiting/Diarrhea Bone marrow suppression Hypersensitivity reactions Hepatotoxicity Stomatitis Pancreatitis Hyperuricemia

2. Analgesic effects tremors, or twitches. increased by CNS depressants 3. Effects greatly potentiated by MAO inhibitors
6-Mercaptopurine
Purinethol
IBD: Children and 50 mg tab Adults: 1-1.5 mg/kg PO QD
Mesalamine
Asacol, Pentasa, Rowasa
IBD: Children: 25-50 mg/kg/day PO divided BID-TID Adults:2-4.8 gm/day PO divided TID-QID Capsules may be opened for administration. Tablets must be swallowed whole
Asacol:400 mg enteric coated tab Pentasa: 250 mg controlled release cap Rowasa: 500 mg supp 4 g/60 mL enema
Headache Diarrhea Abdominal pain Cramps Nephropathy Proteinuria Hepatitis
Methotrexate
IBD: Children and Methotrexate Adults:15-25 mg PO/SC/IM Q week (low dose therapy)
2.5 mg tab 25 mg/ml, 50 mg/ml inj
Hepatotoxicity Myelosuppression Pulmonary toxicity Colitis Infection Anorexia Vomiting
1. Bone marrow suppression potentiated by allopurinol 2. Decreases anticoagulant effect of warfarin 3. May potentiate liver toxicity of hepatotoxic drugs 1. Decreases bioavailability of Digoxin 2. Salicylate-class drug interactions 3. Possible risk of developing Reyes Syndrome when given with varicella vaccine 4. May delay clearance of methotrexate 1. Clearance may be delayed by salicylates 2. May be displaced from binding sites by sulfonamides 3. Nephrotoxicity increased by NSAIDS and penicillins 4. Elimination may be decreased by Probenecid
Food decreases bio-availability. Do not administer with meals. Can monitor metabolite levels.
Caution: sulfasalazine hypersensitivity. Capsules distribute dose primarily to the distal small intestine and colon
Indication: Induction of remission in refractory Crohn's disease. Consider liver biopsy after 1.5 gm cumulative dose Caution: peptic ulcer disease, renal or hepatic insufficiency, preexisting bone marrow suppression
Methylcellulose
Citrucel
Children (6-12 years): 1/2 adult dose PO with 4 oz of cold water 1-3 2 gm/heaping TBSP times/day Adults:1-2 Tablespoons PO with 8 oz of cold water 13 times/day
Diarrhea, fluid/electrolyte imbalance
No data reported
Onset 12-24 hrs Does not ferment, therefore may produce less flatulence than psyllium
Methylprednisone
Solu-Medrol
IBD: Children: 1-2 mg/kg PO/IV/day divided QD - BID (max Dose 40-60 mg/day)
1. Clearance Hyperglycemia increased by Hypertension Barbiturates, 2 mg, 4 mg, 8 mg, 16 Nausea/Vomiting phenytoin and mg, 24 mg, 32 mg Increased appetite rifampin 1.25 times more potent than tabs Immunosuppression 2. Effectiveness and prednisone 40 mg, 125 mg, 500 Peptic ulcers toxicity may be mg, 1000 mg, 2000 Transient leukocytosis increased by oral mg inj Long-term treatment: contraceptives, Risk of osteoporosis, cataracts, growth ketoconazole, and suppression erythromycin
Metoclopramide
Reglan
Metronidazole
Flagyl
Prokinetic agent;: Children: 0.1-0.2 mg/kg/dose PO/IM/IV QID Adults:10-15 mg PO/IM/IV QID Post-Op Nausea/Vomiting: 0.1-0.2 mg/kg/dose PO/IM/IV TID-QID Chemotherapyinduced Nausea/Vomiting: 1-2 mg/kg/dose PO/IM/IV every 2-4 hours Give intravenous doses slowly (over 15-30 min) Anaerobic Infection: 7.5 mg/kg/dose IV/PO q 6h (max dose= 4 g/24 hours) Giardia: 5-10 mg/kg/dose PO TID for 7-10 days Clostridium Difficile: 20-30 mg/kg/day PO
Drowsiness Agitation 5 mg,10 mg tab Extrapyramidal reactions 1 mg/mL syrup (sugar Irritability free) Lower seizure threshold 5 mg/mL inj Fatigue Gynecomastia Urinary frequency
1. Decreases absorption of Digoxin and cimetidine 2. Increases enteral absorption of Cyclosporine 3. anticholinergic effects Effects decreased by Levodopa
Renal elimination Dosage adjustment may be needed in renal impairment. Premedicate with diphenhydramine if needed to prevent extrapyramidal reactions, however, such anticholinergics may antagonize metoclopramide effects. Administer 30 minutes before meals
375 mg caps 750 mg extended release 250 mg, 500 mg tabs 5 mg/mL inj 10 mg/mL susp Recipe for preparation: 250 mg tabs x 8
1. Increases Nausea anticoagulant effects Dizziness of warfarin Taste disturbances 2. Increases serum Headache concentrations of Tongue coating lithium Disulfiram reaction 3. Metabolism may Peripheral neuropathy (with prolonged be increased and use) effectiveness
Caution: do not administer with alcohol or alcohol-containing products due to disulfiram reaction Food delays and decreases peak concentrations. Take with food only if GI upset occurs. Dose adjust for renal impairment and severe hepatic impairment.
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divided TID for 10-14 Levigate in 50 mL days glycerin. Add Cherry Syrup for a Total Volume of 200 mL (NO Alcohol)

decreased by barbiturates
Midazolam
Versed
Conscious sedation: Children and Adults: 0.05 mg/kg/dose IV 30 minutes prior to procedure. 0.4-0.5 mg/kg/dose PO (Max dose=10 mg PO)
Respiratory depression 1 mg/mL, 5 mg/mL inj Nausea 1 mg/ml oral syrup Vomiting May use IV prep for Hiccups oral administration. Amnesia
Mineral oil
Children:1-3 mL/kg/day PO Kondremul, divided QD-BID Fleet mineral initially, titrated to oil produce soft stools Adults: 5-45 mL/day NSAID ulcer prevention: Adults: 200 ug PO QID If not tolerated; may decrease to 100 ug PO QID or 200 ug PO 100 ug, 200 ug tabs BID WITH FOOD Gastric or duodenal ulcers: Adults: 100-200 ug PO QID or 400 ug PO BID
Fluid/Electrolyte imbalance Nausea/Vomiting/Diarrhea Lipid pneumonitis (with aspiration)
1. Additive effects with CNS depressants 2. Effects increased by cimetidine, diltiazem, verapamil, omeprazole, clarithromycin, erythromycin, May use higher doses with appropriate protease inhibitors, monitoring. and azole Antidote-flumazenil antigungals Grapefruit-increases serum 3. Hepatic concentration of midazolam metabolism increased and effectiveness decreased by rifampin, phenytoin, and carbamazepine. 4. Theophylline may antagonize the effects of midazolam 1. May decrease absorption of fatOnset: 6-8 hrs soluble vitamins Caution: in infants, neurologically 2. Surfactant impaired, and in setting of laxatives (i.e. docusate) facilitate gastroesophageal reflux due to risk of aspiration. absorption thus increasing toxicity of mineral oil.
Misoprostol
Cytotec
Nausea Vomiting Diarrhea Flatulence Abdominal pain Vaginal bleeding Menstrual irregularities Headache Constipation flatulence
1. Increased incidence of diarrhea when administered with Magnesiumcontaining products 2. Absorption may be decreased by antacids
Contraindication: In pregnancy or in women of child-bearing age unless negative pregnancy test has been obtained
Mycophenolate
Cellcept
Naloxone
Narcan
Octreotide
Sandostatin
Nausea/Diarrhea Constipation Bone Marrow Suppression Hypertension Transplant: Headache Children: 600 Insomnia mg/m2/dose PO BID 250 mg caps, 500 mg Hepatitis or 30 mg/kg/day tabs Pancreatitis divided Q12hrs 200 mg/ml susp Neutropenia, Adults: 1-2 g PO anemia, BID thrombocytopenia Back pain, Hyperglycemia hypomagnesemia Children: 5-10 ug/kg/dose IV Q2-3 0.02 mg/mL, 0.4 Hypotension, hypertension, nausea, min x 1-3 doses mg/mL, 1 mg/mL inj vomiting Adults:0.4-2 mg/dose IV Q2-3 min up to 10 mg GI Bleeding: Children: 1 ug/kg IV bolus, then 1 Bradycardia ug/kg/hour Arrhythmias continuous infusion Diarrhea Secretory Diarrhea: Hypoglycemia Children: 1 0.05 mg/mL, Hyperglycemia 0.1 mg/mL, 0.2 Gallbladder abnormalities ug/kg/dose IV/SC BID-TID Advance as mg/mL, 0.5 mg/mL, 1 Flushing, mg/mL inj tolerated. Dose edema, poorly established. chest pain (max dose 500 ug Nausea Q8hr) vomiting Adults: 50-1500 constipation ug/day IV/SC divided TID Adults: 0.5-1.5g PO divided BID Children usually 250 mg caps dosed proportionally lower Nausea Diarrhea Abdominal cramping Headache Can exacerbate colitis through local idiosyncratic effect.
1. Absorption decreased by antacids and cholestyramine 2. May increase serum concentrations of acyclovir and ganciclovir due to competition for tubular secretion 3. Levels increased by acyclovir and ganciclovir
Use: Purine synthesis inhibitor that is alternative immunosupressive agent for liver transplantation. Dose adjust for renal impairment Hold or reduce dose if patient experience neutropenia (ANC < 1300)
Temporarily attenuates antiDuration of action: hypertensive effects 1-4 hours of Clonidine
Increases levels of cyclosporine
Caution: in renal impairment May decrease vit B12 levels and decrease absorption of dietary fats
Olsalazine
Dipentum
1. Possible risk of developing Reyes Syndrome when given with Varicella vaccine 2. May potentiate bone marrow
Contraindication: salicylate hypersensitivity Take with food Does not distribute 5-ASA to small bowel
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suppression of 6mercaptopurine 1. Enhances and prolongs effects of Benzodiazepines 2. Increased risk of toxicity from Carbamazepine 3. Decreases absorption of Azole antifungals (ketoconazole and itraconazole); iron and ampicillin 4. May increase serum levels of digoxin, phenytoin, and warfarin 5. decrease elimination of methotrexate
Omeprazole
Prilosec
Children: 0.5-1.5 mg/kg PO divided QD-BID see additional information for expanded dosing range Adults: 10-20 mg PO QD-BID Higher doses may be required in ZollingerEllison syndrome
10 mg, 20 mg caps 2 mg/mL susp Recipe for preparation: 20 mg capsule x 1 Open capsule and mix with 10 mL of sodium bicarbonate Inj (1 mEq/mL). Stable for 14 days at room temp
Headache Vertigo insomnia Nausea Diarrhea Rash Constipation Discoloration of feces Agranulocytosis, thrombocytopenia Elevated LFTs
Capsules may be opened and added to applesauce for PO administration. Animal studies raised concern of gastric cancers with long term use. This risk was not supported by several longterm studies in humans. Range of effective doses in the literature 0.7-3.5 mg/kg/day (Hassall, 2000)
Ondansetron
Zofran
Pancreatic enzyme supplements
Pancrease, Ultrase, Creon, Viokase, Zymase, Kuzyme
Chemotherapyrelated nausea: Children 4-11years: (30 minutes before chemo):4 mg PO Q4h 4 and 8 mg, 24 mg x 3 doses, then repeat Q8 h tabs 2 mg/ml inj. OR: 0.15 mg/kg IV Q4-8 4 mg/5ml soln hours x 3 doses Zofran ODT (orally 12 years adult: disintegrating tablets): 4 mg and 8 mg (30 minutes before chemo): 8 mg PO Q4h x 3 doses then repeat Q8 h OR: 32 mg IV x 1 OR: 0.15 mg/kg IV Q4h x 3 Infants: 2000-4000 units lipase per 120 ml of formula or breast milk (450-900 units lipase per gram of fat ) Children: Initial Dose 1- 4 yrs: 1000 units lipase/kg/meal > 4 yrs: 500 units lipase/kg/meal (1/2 dose with snacks) Adults: 4000-16000 units lipase/meals May increase dose if signs of malabsorption. If dose > 2500 units lipase/kg/meal, check 72h fecal fat, change brands or add a H2 blocker or PPI
Constipation Blurred vision Rare cardiovascular effects and dystonic reactions.
None reported
In severe hepatic dysfunction, max dose 8 mg/day Pharmacology: a 5 HT receptor antagonist. Extensive hepatic metabolism; renal excretion. Use slightly lower doses for postoperative associated nausea (0.1 mg/kg/dose)
Colonic strictures (fibrosing colonopathy) with high doses > 6000 units/kg/meal lipase in children < 12 years.
1. Decreased absorption of iron 2. Effectiveness reduced by antacids (CaCarb and MgOH) 3. Absorption and effectiveness increased by H2 blockers and PPI
Capsules may be opened and mixed with applesauce or other non alkaline food for younger children. Do not crush microcapsules or store in food. Consider using Viokase powder if patient on feeding tube
Paroxetine
Paxil
Children: Initial dose: 2.5-5 mg PO/day Maintenance: If >12 yo, may slowly 10 mg, 20 mg, 30 mg, increase dose to 10 40 mg tabs mg/day if no 2 mg/ml suspension untoward side effects Adults: 20 mg/day. Increase as needed weekly by 10 mg/day ( max: 50 mg/day)
Anticholinergic, antihistaminic, and alpha-adrenergic effects. GI distress headache, dizziness sexual dysfunction, fatigue insomnia disinhibition (30%) Anemia leukopenia skeletal weakness tremors paresthesias
1. Can displace Warfarin, valproate, and phenytoin, increasing levels abrubtly. 2. Inhibit cytochrome P450, increasing blood Some success in treating chronic levels of tricyclic recurrent abdominal pain / IBS in antidepressants, adults. Some evidence of success in benzodiazepines, omeprazole, and treating alpha-IFN-induced depression (NEJM, 3/01). cyclophosphamide 3. Danger of Paroxetine has shorter half-life than Serotonin syndrome fluoxetine (Prozac) so may be better if used with MAO choice for young patients. inhibitors (allow a 14 May take 1-4 weeks to notice day wash out period antidepressant effects. is switching between Use with caution in patients with liver agents) or renal impairment 4. Cycloheptadine decreases effects of paroxetine 5. Paroxetine decreases digoxin levels by 15% 6. Avoid St.Johns wort
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Wilsons Disease: Children: <6 months: 250 mg PO QD 6 mos 12 years: 250 mg PO BID-TID Adults & children >12 years: 250 mg PO QID Aplastic anemia Neutropenia Glomerulonephritis Lupus-like reaction 125 mg, 250 mg caps, Rash 250 mg titratabs flu-like symptoms hemolytic anemia peripheral neuropathy Optic neuritis

1. Absorption decreased by iron salts, zinc and antacids 2. decreases serum digoxin levels 3. Cross-sensitivity reaction if patients allergic to penicillin 1. Additive CNS and respiratory depression from benzodiazepines 2. Decreases concentrations of cyclosporine, corticosteroids, metronidazole, cimetidine, tacrolimus, phenytoin, tricyclic antidepressants, and others * 3. Levels increased by valproic acid, felbamate, methylphenidate, felbamate, propoxyphene, and ritonavir
Penicillamine
Cuprimin, Depen
Also give pyridoxine 25 mg/day to avoid B12 deficiency. Do not give with milk or food. Dose adjust for renal impairment
Phenobarbital
Choleretic: 5 mg/kg/day PO divided BID Phenobarbital For HIDA Scan:5 mg/kg/day PO divided BID for 5 days
20 mg/mL elixir 8 mg, 15 mg, 16 mg, 30 mg, 32 mg, 60 mg, 65 mg, 90 mg, 100 mg tabs 65 mg/mL inj Alcohol content of elixir varies
Sedation Rash Hypotension Respiratory depression Dyskinesia Megaloblastic anemia Elevated LFTs
Also decreases serum levels of beta blockers, protease inhibitors, warfarin, ethosuximide, oral contraceptives, and other drugs metabolized by the cytochrome c3A4 system.
Polyethylene glycol electrolyte solution
Bowel prep for colonoscopy or constipation: Children:75-100 mL/kg PO As prep, infuse 25-50 Golytely, ml/kg/hr until rectal Colyte, effluent is clear Nulytely, (<10 kg: 50 mL/kg Miralax (for over 4 hrs then constipation ) reassess) Adults: 4-6 L PO May use smaller doses for maintenance treatment of constipation Adults: 17 GM (about 1 heaping teaspoonful) of powder per day in 8 ounces of water. IBD: Children and Adults: 1-2 mg/kg/day PO divided BID Max dose = 40-60 mg/day. Dose depends on condition being treated and response of patient IBD: Children and Adults: 1-2 mg/kg/dayPO divided BID Max dose = 4060 mg/day. Dose depends on condition being treated and response of patient Premature and newborn: 2 mg/kg/day PO divided Q12h; 1.5-2 mg/kg/day IV divided Q12h Children: 2-6 mg/kg/day PO divided Q 8-12h; 3-4 mg/kg/day IV divided Q 6-8h (max: 50 mg/dose) Adults:150 mg PO BID 50 mg IV Q6-8H Pruritis of cholestasis: Children:10-20 mg/kg/day PO/IV divided BID Adults:150 mg PO
Nausea Vomiting Abdominal cramps Abdominal distention
Oral medications should not be given within 1 hour of starting polyethylene glycol electrolyte solution
The addition of flavoring agents is not recommended. If flavoring agent is required, use one without bright color (i.e.use lemonade flavor)
Polyethylene Glycol Miralax 3350 powder
Nausea Abdominal bloating No specific drug Cramping Two to 4 days may be required to interaction have Flatulence produce a bowel movement been demonstrated. dehydration and hypokalemia reported in children 1. Increases risk of peptic ulcer disease from Salicylates and Take with food NSAIDs 2. Effectiveness May decrease vaccine effectiveness decreased by Phenytoin and rifampin 1. Increases risk of peptic ulcer disease from salicylates and NSAIDs Take with food May decrease vaccine effectiveness 2. Effectiveness decreased by phenytoin and rifampin
Prednisolone
Pediapred, Prelone
Immunosuppression Hypertension Pediapred 1 mg/mL Peptic ulcers elixir Bone resorption Prelone 3 mg/mL elixir Increased intracranial pressure Cataracts
Prednisone
Liquid Pred
1 mg/mL elixir 1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg, 50 mg tabs
Immunosuppression Hypertension Peptic ulcers Bone resorption Increased intracranial pressure Cataracts
Ranitidine
Zantac
15 mg/mL elixir 75 mg, 50 mg tabs 25 mg/mL inj Elixir Alcohol Content = 7.5%
Constipation, headache, dizziness, fatigue, irritability, diarrhea, lethargy, thrombocytopenia, elevation of transaminases
1. Absorption may be decreased by antacids. Space administration by two hrs. 2. Decreases bioavailability of ketoconazole and intraconazole
Doses of up to 10 mg/kg have been used in dose-ranging trials with a concomitant increase in efficacy and no apparent adverse effects. Continuous IV infusion at same daily dose is preferred to IV boluses for active bleeding. Dose adjust for renal impairment
Rifampin
Rifadin
150 mg, 300 mg caps 600 mg inj 10 mg/mL susp can be made, but is not commercially available.
Nausea/Vomiting Heartburn Headache Ataxia Hepatitis Blood dyscrasias
1. Induces hepatic microsomal enzymes and thereby reduces Food decreases absorption levels of some hepatically metabolized drugs
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NASPGHAN
BID-TID

Increased BUN Discoloration of secretions, urine and feces Drowsiness, fatigue confusion Rash Interstitial nephritis Myalgia arthralgia including warfarin, digoxin, azole antifungals, phenytoin, and corticosteroids, calcium channel blockers, theophylline, warfarin, cyclosporine, tacrolimus 2. Reduces effectiveness of oral contraceptives. Add to parenteral nutrition if on for long term use (> 3 months). Deficiency may result in myocarditis. Component of glutathione peroxidase
Selenium
Selenium
Senna
Senokot
Sodium phosphate/ Fleet Enema bisphonate enema
Children and Adults: 1-2 ug/kg PO QD; 2 ug/kg IV QD x 1 dose followed by 1 ug/kg/day maintenence Children: 0-1 yr: 1.25-2.5 mL PO HS (max: 5ml/day) 1-5 yr: 2.5-5 mL PO HS (max: 10 ml/day) 5-15 yr: 5-10 mL PO HS (max: 20ml/day) Adults: 2 tabs PO HS (max 4 tablets BID) -OR- 2-3 tsp PO HS (max 6 tsp/day) OR- Granules: 1 tsp PO HS (max 4 tsp/day) Avoid in infants Children:One pediatric enema PR Adults: One adult enema PR Children: 1-4 mg/kg/day PO divided BID Adults: 25-100 mg/day PO divided QD - BID (Max dose=200 mg/day)
40 ug/mL inj Various oral preps available
Lethargy, discoloration of hair, vomiting abdominal pain, garlic odor breath tremors perspiration
No data reported
43.6 mg/mL syrup 187 mg, 217 mg, 600 Abdominal pain Discoloration of urine mg tabs Electrolyte and fluid imbalance 652 mg supp 326 mg/tsp granules
No data reported
Senokot is chocolate flavored liquid and contains 7% alcohol. Generic senna liquid products vary in flavor and alcohol content. Prolong-use may lead to dependence
Pediatric: 67 mL Adult: 133 mL
Hypocalcemic tetany (in infants or with excessive doses)
No data reported
May create gross and histologic changes mimicking colitis if used prior to colonoscopy.
Spironolactone
Aldactone
25 mg, 50 mg,100 mg tabs Make 5 mg/mL susp. with tablets levigated with a small amount of water and qs to final volume with cherry syrup
Hyperkalemia, hyponatremia, myperchloremic, metabolic acidosis Rash Gynecomastia, amenorrhea Nausea Vomiting
Sucralfate
Carafate
Children: 40-80 mg/kg/day PO 1 g tab divided QID 100 mg/mL susp Adults: 1 g PO QID
Constipation, dry mouth
1. Additive hyperkalemic effect with other medications that increase potassium levels 2. May decrease anticoagulant effects of warfarin 1. May decrease absorption of other medications; separate administration from meds and food by 12 hours. 2.. May result in renal failure due to aluminum toxicity when given with aluminumcontaining antacids
Contraindication: acute renal failure Onset of Action: 3-5 days Dose adjust for renal impairment
Requires an acidic environment to form protective barrier in GI tract. Therefore, medications that decrease acidity of GI tract (e.g. ranitidine) may decrease effectiveness of sucralfate.
Sulfasalazine
Azulfidine
Children: 50-70 mg/kg/day PO q 4-6 hr Adults: 3-4 g/day PO divided TID
Tacrolimus
Prograf
Transplant: 0.15-0.3 mg/kg/day PO divided BID IBD study:0.2 mg/kg/day PO divided BID (IV 0.1 mg/kg/day) continuous infusion: rarely used as is very toxic IV. Use the lower end of dosing range for larger patients. Dose
Incidence higher with high doses (>4 gm/day) and if pt has slow acetylation of sulfapyridine: Nausea 500 mg tab Headache 500 mg extended Diarrhea release tab Alopecia Suspension may be Colitis made at 100 mg/mL Photosensitivity Recipe: Crush 80 Male infertitility (doserelated) sulfasalazine 500 mg Pancreatitis tabs, qs to 400 mL Folate deficiency with cherry syrup. Rash Shake well. Blood dyscrasias Elevated LFTs Tinnitus, nephrotoxicity Serum-like sickness 1 mg, 5 mg caps Immunosuppression Suspension may be Neurotoxicity (tremor), seizures made at 0.5 mg/mL Nephrotoxicity Recipe: Headache Empty contents of 12 Hypertension tacrolimus 5 mg caps Hyperglycemia into mortar. Add 20 Hypomagnesiemia mL of Ora-Plus and Hyperkalemia mix well. Pour into Nausea amber bottle. Add Vomiting another 40 mL OraDiarrhea Plus and 60 mL Simple constipation syrup to bottle for 120 Anemia
May potentiate the effects of methotrexate and sulfonylureas Decrease effects of iron, folic acid, digoxin and PABA or PABA metabolites of drugs
Contraindicated in sulfa allergy. Patients should receive folate supplements. Monitoring of CBC and LFTs recommended May cause orange-yellow discoloration of urine and skin
1. Additive nephrotoxicity with cyclosporine, aminoglycosides, NSAIDs and amphotericin 2. Levels decreased by carbamazepine, phenytoin, phenobarbital, rifampin, and rifabutin 3. Levels increased
Trough Levels: 10-15 Initial (1st yr) 5-10 Maintenance (Post transplant or IBD) Avoid Grapefruit juice
Page 60
NASPGHAN
should be adjusted mL based on drug levels.

thrombocytopenia leukocytosis Elevated AST, ALT and LDH Increased risk of 2nd lymphomas by metoclopramide macrolides (azithromycin is OK), cisapride, cimetidine, calcium channel blockers (amlodipine and isradipine are OK), and azole antifungals Absorption may be reduced by antacids and cholestyramine. Space medications by 2 hours if possible Recipe: Empty contents of 12 Ursodiol mg caps into mortar. Add 5 mL glycerin to wet powder and titrate to fine paste. Add 15 mL of simple syrup, mix and transfer to bottle. Rinse mortar with 20 mL of simple syrup twice and add to bottle for final concentration of 60 mg/mL.
Ursodeoxycholic acid
Children: 10 Actigall: 300 mg caps 30mg/kg/day PO Urso: 250 mg tabs Actigall, Urso divided BID Suspension may be Adults : 300 mg PO made at 60 mg/mL BID (see info section) C. Difficile: (Metronidazole is drug of choice) 20-40 mg/kg/day PO divided QID x 7-10 days Endocarditis Prophylaxis (PCN allergic patients): Children: 20 mg/kg (Max 1 g) IV over 1 hour (with gentamicin) Adults: 1 gm GI Bleeding: Children:0.2-0.5 Unit/1.76m2/min IV Adults: 0.2-0.5 Unit/min IV Optional loading dose of 20 units in adults Cholestasis: 5,000-15,000 IU PO QD Cystic Fibrosis: 5,000 IU PO QD RDA: 500-1000 IU PO QD Cystic Fibrosis: 0-1 yr: 1 mL PO QD 1-2 yr: 2 mL PO QD 2-12 yr: 1 tablet PO QD > 12 yr: 2 tablets PO QD Children: 0.0150.040 ug/kg PO QD Adults: 0.25-2 ug/day PO QD 3-5 ug/kg PO QD Cholestasis: 5000-8000 IU PO QD Cystic Fibrosis: 400 IU PO QD RDA: 400 IU PO QD Cholestasis: LiquiE: 15-25 IU/kg PO QD Aquasol E: 50-400 IU PO PO Cystic Fibrosis: Aquasol E: 25-400 IU PO QD Cholestasis: 2.5-5 mg PO/IM/SC/IV QD or QOD
Diarrhea/constipation Nausea Vomiting Headache Rash Arthralgias
Vancomycin
Vancocin
125 mg, 250 mg caps oral soln (powder): 50 mg/ml (1gm); 83.3 Ototoxicity (high peak) mg/ml (10 gm) Nephrotoxicity (high trough) 500 mg, 1000 mg inj Red man syndrome (rapid infustion) Dilute injection to 5 mg/mL
Additive nephrotoxicity with aminoglycosides and other nephrotoxic medications
Infuse over 1 hour. Draw levels 1 hour after the end of a 1 hour infusion. Therapeutic Range: Peak: 25-40 ug/mL Trough: 5-10 ug/mL Extend interval in patients with renal impairment
Vasopressin
Pitressin
20 Units/mL inj
Hypertension, hyponatremia, oliguria
Antiduretic effect decreased by lithium, epinephrine, Octreotide preferred for GI bleeding demeclocycline, heparin, and alcohol 1. Decreases seroconversion of measles vaccine in Sign of deficiency: Xeropthalmia younger infants Therapeutic Levels: 2. Increased 20-80 ug/dL incidence of pseudotumor cerebri with Minocycline May increase or decrease anticoagulant effects of warfarin Contents: Vitamin A: 4000 IU/tab, 1500 IU/mL Vitamin D: 400 IU/tab, 400 IU/mL Vitamin E: 150 IU/tab, 40 IU/mL Vitamin K: 150 ug/tab, 100 ug/mL and other water soluble vitamins Signs of deficiency: rickets, osteoporosis Signs of deficiency: rickets, osteoporosis Therapeutic Levels: 25-OH Vit D = 9-75 ng/mL
Vitamin A
Aquasol A
5,000 IU= 0.1 ml= 3 drops 25,000 IU, 50,000 IU caps 50,000 IU/mL inj
Papilledema Dry skin Sore tongue Hyperostoses
Vitamin ADEK
ADEK
Tablets, drops
Vitamin D 1,25-OH (Calcitriol)
Rocaltrol
Calcitriol: 0.25 ug, 0.5 ug caps 1 ug/mL inj Calcifediol = Vit D3: 20 mcg, 50 mcg caps
May antagonize Hypercalcemia, polyuria, nepholithiasis, effects of calcium nausea, vomiting, constipation channel blockers May antagonize Hypercalcemia, polyuria, nepholithiasis, effects of calcium nausea, vomiting, constipation channel blockers
Vitamin D 25-OH (Calcifediol)
Calderol
Vitamin D2 (ergocalciferol)
Drisdol
(D2=ergocalciferol) 8000 IU=1 mL= 40 drops 40 units = 1 mcg
May antagonize Hypercalcemia, polyuria, nepholithiasis, effects of calcium nausea, vomiting, constipation channel blockers
Signs of deficiency: rickets, osteoporosis
Vitamin E (D-alpha tocopherol)
LiquiE, Aquasol E
LiquiE: 1 mL=25 IU Muscle Weakness Aquasol E: 1 ml=50 IU Nausea LiquiE better absorbed Diarrhea than Aquasol E
1. Increases anticoagulant effect of Warfarin 2. May antagonize Vitamin K
Signs of deficiency: ataxia, weakness, hemolysis Therapeutic Levels: 5-20 mg/L Measure ratio Vit E : total lipid Deficient if <0.6 mg/gm
Vitamin K1 (phytonadione)
Mephyton
Cystic Fibrosis: 2-5 mg/week PO if < 5 mg tabs 1yr. Increase to BIW 10 mg/mL inj if on antibiotics. Treat patients > 1yr if on antibiotics or if liver disease present. Vit K deficiency: 1-2 mg IM/SC/IV
Flushing Hypotension GI upset Pain at injection site Precautions: Anaphylactoid ReactionsRare severe hypersensitivity reactions have occurred after IV use. Severe hemolytic anemia and hyperbilirubinemia has been reported rarely in neonates following large doses (10-20 mg) of phytonadione.
May decrease or eliminate anticoagulant effect of warfarin
Sign of deficiency: coagulapathy Precaution: may cause anaphylaxis if infused intravenously . Administer IV as a last resort. If given IV, give slowly over 30 minutes. Avoid IV in patients with prior history of vitamin K use. Monitor PT and PTT
Page 61
NASPGHAN
Liver Failure: 1 mg/year of age up to 10 mg (Dose expressed as mg of elemental zinc) Supplement in TPN (IV): Infants: Prematures: 400 ug/kg/day <3 months: 300 ug/kg/day >3 months and children <5 yr: 100 ug/kg/day (max: 5 mg/day) Children >5 yrs: 25 mg/day Deficiency: Children:1 mg/kg/day elemental zinc PO divided BIDTID Adults: 25-50 mg elemental zinc/dose PO TID
Zinc sulfate (23% zinc)
Zinc sulfate
110 mg (25 mg elem zinc), 220 mg (50 mg elem zinc) capsule 66 mg (15 mg elem zinc), 110 mg (25 mg elem zinc), 200 mg (45 mg elem zinc) tablet 10 mg/mL solution
Nausea Vomiting Neutropenia leukopenia With excessive doses: Hypotension hypothermia Tachycardia Jaundice pulmonary edema Blurred vision
1. Decreases absorption of tetracycline and quinolones 2. Absorption decreased by iron.
Serum reference range: 70-130 ug/dl Add to parenteral nutrition solution if long term use (> 3 months) Consider zinc level and supplement in patients with chronic diarrhea Signs of deficiency: Poor growth, decreased taste, hypogonadism, perioral skin changes. Do not administer undiluted by direct injection into a peripheral vein, may cause phlebitis
Page 62

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NASPGHAN

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology, Hepatology and Nutrition Handbook Author List

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Chemotherapy, motility disorders, GERD

5-HT3 Receptor Antagonists: Ondansentron, granisetron

5-HT3 receptor blockade mainly in enteric nervous system

Pediatric Gastroenterology Hepatology and Nutrition Handbook

NASPGHAN D. Algorithm for evaluation and management of Dysphagia in Children

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Algorithm for Evaluation and Management of Dysphagia in Children

Medical and Feeding History Physical examination Observational feeding trial

Oral Phase: drooling, choking, respiratory distress

Pharyngeal Phase: Dysphagia while swallowing

Esophageal Phase: Dysphagia after swallowing, +/- pain

Exclude nasopharyngeal, oral cavity, laryngeal and oropharyngeal defects

Exclude anatomical defects, motility disorders and oropharyngeal incoordination

Exclude neurological disorders

Dysphagia to solids only: Anatomic/ mucosal lesion

Dysphagia to solids liquids: exclude motility disorder

Consider ENT consultation

Videofluoroscopy (modified barium swallow and/or UGI series)

Consider Neurology consultation

UGI series Upper endoscopy Con. Eso. Manametry consider chest CT

Eso. Manometry UGI series upper endoscopy

Consider direct laryngoscopy and enteral tube feeds

Speech and swallow consultation to optimize safe feeds

Pediatric Gastroenterology Hepatology and Nutrition Handbook

III. Functional Constipation & Encopresis

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Systemic infection Urinary Tract Infection Acute appendicitis

Pediatric Gastroenterology Hepatology and Nutrition Handbook

VI. Chronic Diarrhea

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Therapy 1. General/ a) b) c) d) e) f) 2. Medical a)

Pediatric Gastroenterology Hepatology and Nutrition Handbook

IX. Lower Gastrointestinal Bleeding

C. Lower GI Bleeding Chart

C. Lower GI Bleeding (UGI bleeding ruled out)

Signs of Systamic or liver

Signs of Systamic or liver

Massive and/or paroxysmal

Infant: APT Downey test, consider change of formula

CBC, blood typing and crossmatch Meckel scan bleeding scan

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology Hepatology and Nutrition Handbook

NASPGHAN l) m) n) o) C. Hemolytic anemia IVC Hyperalimentation Protein-calorie malnutrition Letterer-Siwe Disease

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology Hepatology and Nutrition Handbook

XI. Neonatal Cholestasis

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Cholestasis in Children and Adolescents

Pediatric Gastroenterology Hepatology and Nutrition Handbook

Pediatric Gastroenterology Hepatology and Nutrition Handbook

XIII. Biochemical Tests of the Liver

Pediatric Gastroenterology Hepatology and Nutrition Handbook