Topics in Pediatric Gastroenterology Kathleen M. Gura Pharm.D., BCNSP, FASHP Departments of Pharmacy and Division of Gastroenterology/Clinical Nutrition Children’s Hospital Boston Learning Objectives Review to common causes of constipation in the pediatric patient and the methods used to treat and prevent recurrence List the treatment measures used to manage patients with toddler’s diarrhea Constipation Magnitude of the Problem 16% of toddlers, 8% school age children 3% of pediatric outpatient office visits 25% of pediatric gastroenterology consults parental distress Pediatric Constipation Definitions Red flags Testing Management Constipation Definition: - a delay or difficulty in defecation, present for 2 or more weeks - based on stool character, not frequency - any deviation from the norm Occurrence - 3% of GP OPD visits - 25% of pediatric GI consults Etiology - organic (rare) - less than 5% of all affected patients - functional (idiopathic constipation/functional fecal retention/withholding constipation) Definition(s) Too hard Too large Painful Infrequent Constipation Neonates practically unknown in breast fed infant receiving adequate amount of milk rare in formula fed infants fed adequate amounts of formula nature of stool, not frequency, is basis for diagnosis Constipation Formula Fed Infant associated with inadequate intake diet too high in fiber/protein insufficient in bulk increase fluid intake may be sufficient for neonates older infants: add or increase cereal, fiber , vegetables - prune juice 1/2 -1 oz short term remedy Normal Frequency of Bowel Movements/Week by Age 40 35 30 25 5% 20 mean 15 95% 10 5 0 0-3 months 6-12 months 1-3 years >3 years Normal Frequency of Bowel Movements Age BM per week BM per day 0-3 months Breast milk 5-40 2.9 Formula 5-28 2.0 6-12 months 5-28 1.8 1-3 years old 4-21 1.4 >3 years old 3-14 1.0 Adapted from: Acta Paediatr Scan 1989; 78:682-4 Age of Onset of Stooling Problems Neonatal – probably congenital cause < 1 year of age: suggests dietary cause > 18 months: suggests behavioral cause Organic vs Functional Constipation Organic - acute onset Functional - chronic - large caliber stools Organic Constipation Should be ruled out first Examples Anatomic – anorectal abnormalities Neuromuscular disorders Hirschsprung’s disease Dietary factors Medications Always consider sexual assault Family History Constipation Hirschsprung’s Disease Celiac Disease Cystic Fibrosis Thyroid Disease Parathyroid Disease Colon cancer/colonic polyps RED FLAGS History Delayed meconium Poor growth Bloody stools Urinary Incontinence Weight loss Abdominal pain RED FLAGS Physical Exam imperforate/stenotic anus anterior anus sacral dimple or tuft distended abdomen Functional Constipation Most common No evidence of a pathological condition Commonly due to painful BM with subsequent voluntary withholding of feces - causes: toilet training, stress, dietary changes, illness, unavailability of toilets, too busy - leads prolonged fecal stasis in colon, fluids reabsorbed, increased in stool size/consistency Common Withholding Behaviors Squatting Crossing ankles Stiffening of body Holding onto mother, furniture Flushing, sweating, crying Hiding during defecation Evaluation Thorough medical history imperative -time after birth until first BM -family/child’s definition of constipation -length of time the condition present -frequency/consistency/size of BM -medication use Physical exam -external exam of perineum & perianal area Labs (if necessary) Thyroid function test BUN Serum electrolytes Serum calcium Serum magnesium Blood lead level Celiac panel Medications Associated With Constipation anticholinergics aluminum containing antidepressants antacids neuroleptics sucralfate antihistamines calcium supplements iron salts NSAIDs narcotics Diuretics calcium channel Vinca alkaloids blockers Treatment of Constipation in Children< 1 Year of Age Barley malt soup extract - breast fed: 5-10 mL in 2-4 oz. water BID - formula fed: 5-10 mL q 2nd feeding Dark Karo syrup 1 tsp BID if < 2 months old - > 2 months: 2 oz apple or prune juice BID - 6 months: high fiber foods (prunes/plums) Glycerin Osmotic dehydrating agent Increases osmotic pressure, draws fluid into colon and stimulates evacuation Wet suppository first to avoid stinging when inserting Insert suppository high in rectum and retain for 15 minutes Onset of action 15-30 minutes Management of Constipation in Children > 1 Year of Age Education Disimpaction Maintenance Behavioral modification Education Explanation of pathogenesis of constipation Remove negative attributions associated with fecal soiling Parents must be encouraged to maintain a consistent, positive, supportive attitude May be necessary to repeat during different phases of treatment Disimpaction Fecal impaction – hard mass in lower abdomen, dilated rectum filled with large amount of stool, or excessive stool in the colon Disimpaction necessary prior to starting maintenance therapy Oral or rectal medications used alone or in combination Oral Medications Not invasive Gives sense of power to the child Adherence to regimen problematic Examples: - mineral oil - polyethylene glycol electrolyte solutions Magnesium salts/lactulose/senna/sorbital/ bisacodyl laxatives may also be used Mineral Oil Use with caution in patients < 4 years of age due to increased risk of aspiration MOA: eases passage of stool by decreasing water absorption, softens stool, lubricates the intestine Onset of action: 6-8 hours Emulsified form more palatable that non emulsified forms Supplement with MVI is used chronically Dose: 1-2 ml/kg/dose qd -bid 5-11 years: 5-15 mL po qd or in divided doses > 12 years: 15-45 mL po qd or in divided doses Milk of Magnesia Magnesium hydroxide 400mg/5mL Dose: < 2 years:0.5 mL/kg/dose 2-5 years: 1-2mL/kg/dose bid or 5-15mL/day 6-11 years: 15-30 mL/day >12 years: 30-60 mL/day May cause abdominal cramping in higher doses Polyethylene Glycol-Electrolyte Solutions Go-LYTELY, Co-Lyte, MiraLax Usually used in the inpatient setting for bowel cleanout MOA: osmotic effects Dose: Occasional constipation: MiraLax™(oral) Children: 10-30 kg, 8.5 g daily Adults: 17 g (1 heaping tablespoon) daily May need to taper dose over time Onset of action: bowel cleansing 1-2 hrs constipation: 2-4 days Senna Acts as local irritant on the colon, stimulates Auerbach’s plexus to produce peristalsis Docusate may enhance the absorption of senna Can be used in infants > 1 month of age Available as tablet, granules, syrup Tastes awful – mix with plenty of water, juice or milk Avoid prolonged use May discolor urine, feces Onset of action (oral): 6-24 hours Lactulose $$$$$ Laxative Dose: children: 1 ml/kg dose q24 hours or bid 7.5 mL/day (5gm/day) adults:15-30 mL/day (10-20 gm/day), increase to max. 60 mL/day(40gm/d) Monitoring: fluid status, stool output May cause abdominal cramping /flatus Upon d/c of therapy, allow 24-48 hrs for resumption of normal bowel movements Rectal Disimpaction Faster but invasive Therapies - phosphate soda enemas - saline enemas - glycerin suppositories - bisacodyl suppositories Soapsuds/tap water/magnesium enemas should not be used Digital disimpaction Phosphate Enema Exerts an osmotic effect in the small intestine by drawing water into the lumen of the gut, producing distention, promoting peristalsis, and evacuation of the bowel Onset of action: 2-5 minutes Maintenance Therapy Focuses on prevention Typically continued for first several months Goal: 1 soft stool per day Dietary interventions Medication Maintenance Therapy Dietary interventions - increased fluid intake - increase absorbable/nonabsorbable carbohydrate intake (sorbital containing fruit juices: prune, pear, apple juice) - balanced diet of whole grains, fruits, vegetables - increase fiber intake - child’s age + 5 gms = daily fiber intake Docusate Stool softener Reduces surface tension of oil-water interface of the stool, allowing more water and fat to be incorporated into stool Do not administer with mineral oil Docusate with Casanthranol Stool softener and laxative Casanthranol –stimulant laxative - may result in laxative dependence with prolonged use Onset of action: 8 – 12 hours Behavioral Modification Important component Unhurried time on toilet after meals Diary of stool frequency (combine with reward system) Medications Goal: achieve regular bowel movements Optimizes behavioral modification Use laxatives until child can maintain regular toileting Daily treatment -lubricant laxatives (mineral oil) -osmotic laxatives (magnesium hydroxide, lactulose, sorbital) -stimulant laxatives for daily use not recommended Rescue Medications Used to avoid recurrence of impaction Consists of stimulant laxatives - senna - bisacodyl - glycerin suppositories Bisacodyl Stimulant laxative Typically not used in neonates/infants Stimulates peristalsis by directly irritating the smooth muscle of the intestine Tablets- enteric coated – don’t take with milk/antacids or crush Not for regular use Onset of action: oral: 6-10 hours rectal: 15-60 minutes Encopresis Associated with constipation (93%) - responds well to treatment Not associated with constipation (7%) - difficult to treat Encopresis with Constipation Painful bowel movements Withholding stool Colonic dilation/impaction Impaired sensation Overflow incontinence Management Evacuation of impacted stool - repeated mineral oil or Fleets enemas - soap suds, tap water, or herbal enemas should not be used If enemas are not successful, patients may be admitted for oral or NG administration of PEG electrolyte solution Initially, diet should be low in fiber and dairy products Encopresis Suggested Treatment Milk of magnesia - 60 mL q.i.d. x 3 days, then 30 mL q hs Up early, breakfast qd On toilet after each meal Follow up 1 month, then prn Encopresis Management, Later Stages Usual treatment 6 months – 2 years Taper medication gradually - start when no soiling seen 2-3 months - reinstitute immediately if soiling recurs Increase fiber intake when tapering initiated Cases Case 1 A six month old white male infant is brought to the emergency room with a chief complaint of constipation. He was the seven pound product of an uncomplicated full-term pregnancy. He was discharged from the nursery in the first twenty-four hours of life. He has been exclusively breast fed since birth. During the first several weeks of life, he would pass bowel movements approximately once every three to five days. As an infant, his stools were extremely loose, and often quite explosive. More recently he has been passing stools only once every week or so and his abdomen has become more and more distended. He was brought to the Emergency Room because he has not been nursing well for the past two days, and this evening he became quite fussy and had several episodes of vomiting. Physical Exam He is an alert, well-grown male in no distress His examination is remarkable for a very distended abdomen. Inspection of his perineum is normal. On digital rectal exam, he has a tight anal sphincter with a small empty rectum. Immediately after the exam, he produces and explosive watery stool. An abdominal film is performed while he is in the Emergency Room and demonstrates a massively dilated colon filled with stool. Case 2 A 6 year old boy is brought to the office with the chief complaint of being constipated. He was toilet trained without difficulty at 3 years of age and has had no problems with urination. He has been gaining weight and growing well. How would you evaluate this patient? Differential Diagnosis Functional or voluntarily withholding of stools leading to soiling Hirschsprung's Disease- agangliosis Anal stenosis or anal strictures Anteriorly placed anal opening Obstruction of the gastrointestinal tract Hypothyroid disease Hypokalemia Hypercalcemia Neuromuscular and spinal cord diseases Drugs (narcotics/vincristine/antacids) excessive milk in diet, poor fluid intake, lack of bulk in diet Botulism Patient History How often does the child have a bowel movement? What is the consistency of the stool? Is there pain when he goes to the bathroom? Does he have associated abdominal pain? Are the stools so large that they are unflushable? Is there blood in the stools? Does he sit on the toilet? How is his diet? Age when potty trained Physical Findings Abdominal exam palpating for masses or hard stool Rectal exam. In Hirschsprung's disease the ampulla will be empty and in encopresis the ampulla is often full of stool. Anal inspection for fissures that can cause painful stools Reflexes and strength in the lower extremities Inspection of the underwear for soiling Growth and Development Treatment If you suspect Hirschsprung's disease, need surgical consult for biopsy Diet manipulation with plenty of fiber and fluids Stool softeners and gentle laxatives may be helpful. Prune juice or Maltsupex may be tried. If you suspect encopresis…. Discussing the problem with the parents and child is important. - The child should be instructed to sit on the toilet for 10 minutes after all meals. - The goal is not to have a bowel movement at first, but to learn to sit on the potty. The child should be started on mineral oil at night to lubricate the lower intestinal tract and decrease the pain associated with passing stool. Laxatives may also be tried. Enemas may be necessary. Lots of encouragement to the child and the family is important and follow-up should be arranged in 1-2 weeks. Diarrhea Diarrhea Occurs commonly -second only to URI’s as a cause of illness in children < 5 years of age 1-2 episodes/annually for first 5 years of life Risk of severe illness/death due to dehydration still a concern, especially in children < 2 years of age Diarrhea - Definition Many individual variations for normal stooling Noticeable/sudden change in: - number of stools - consistency - fluid content (increased) - color – often green Types of Diarrhea • Osmotic - malabsorption of nutrients/water/lytes - mucosal disease • Secretory - exogenous factors bacterial toxins/laxatives/diuretics - endogenous factors bacterial enterotoxins/hormones/defective transport of sodium or chloride Acute Diarrhea (Gastroenteritis) Background In the US, over 200,000 children < 5 yrs hospitalized annually with gastroenteritis Approximately 300 children <5 die of diarrhea/dehydration Incidence: 1.3-2.3 episodes/yr children <3yrs Caused by virus, bacteria, or protozoa Most common cause viral: Rotavirus Bacterial Diarrhea Abrupt onset Fever Abdominal pain Tenesmus Mucus and/or blood in stool Viral Diarrhea Rotavirus Can occur at any age, most often in children < 2 years Fever rare +/- vomiting Unusual to have leukocytes May include other household members Usually in cooler months (November- May) Parasites More common with increase in world-wide travel May be asymptomatic Consider if diarrhea chronic and accompanied by weight loss Giardia Common in daycare, campers, children taking swimming lessons Persistent diarrhea May see weight loss, poor growth Treatment - metronidazole - 10-20% failures Clostridium Difficile Profuse watery diarrhea, cramps, pain Appears 4-10 days after antibiotics initiated to 4 weeks after antibiotics dc’d Can occur with any antibiotic Most commonly seen with: - clindamycin, cephalosporins, penicillins, erythromycin, trimethoprim/sulfa Diagnosis: + C. difficile toxin assay Treatment: oral metronidazole,oral vancomycin Metronidazole Antibiotic with anaerobic and antiprotozoal coverage as well as an amebicide Dose: 30 mg/kg/day in divided doses - max dose 4 gm/day Interacts with alcohol - review all liquid meds (ex. ranitidine, OTC’s) - avoid alcohol at least 48 hrs after last dose Reduce dose in hepatic insufficiency May cause metallic taste Vancomycin Should not be first line therapy for C. difficle - metronidazole is first line Dose: po: 125-250 mg po QID Available as capsule or oral solution E Coli 0157 Enterohemorrhagic Hemorrhagic colitis Hemolytic uremic syndrome (HUS) Watery diarrhea, cramps, +/- vomiting -diarrhea bloody in 1-2 days HUS (2-13% patients) - 2nd week after diarrhea resolved - hemolytic anemia, thrombocytopenia, renal failure Acute Diarrhea Assessment History Physical Exam Onset/duration Hydration status Frequency, color Tears, weight, mucus I &O membranes, skin turgor, Other symptoms cap refill ? Travel If > 10% dehydration Family history check electrolytes r/o ingestions daycare Diagnosis Microscopic exam for leukocytes Stool cultures if gross or occult blood, diarrhea > 7 days, or if rotavirus (-) and (+) PMN’s Consider wet mount for amoebas if (+) blood Dehydration Fluid Therapy Goals of Therapy Restore circulatory volume Restore combined intracellular & extracellular deficits of water and electrolytes Maintain adequate water and electrolytes Resolve homeostatic disturbances (e.g., acidosis) Replace ongoing losses Calculation of Maintenance Fluids Body weight method: < 10 kg 100 mL/kg/day 10-20 kg 1000 mL + 50 mL/kg (for each kg > 10 kg) > 20 kg 1500 mL + 20 mL/kg (for each kg > 20 kg) Surface area method (for children > 10 kg): 1500 mL/m2/day Oral Rehydration Therapy (ORT) Preferred treatment of fluid/electrolyte losses in children with mild/moderate dehydration Preferred over IV therapy Sodium content 45-50 mmol/liter (less than WHO ORT solution) Contains 2-3 % glucose to facilitate electrolyte absorption Should not be confused with sports drinks Replace fluid/electrolyte losses but has no effect on duration of diarrhea or stool volume AVOID HOMEMADE ORT Comparison of ORT Solutions Solution CHO Na K Base Osmolality mmol/L mmol/L mmol/L mmol/L WHO/ Unicef ORT 111 90 20 30 310 Rehydralate 140 75 20 20 310 Pedialyte 140 45 20 30 250 Infalyte (Ricelyte) 70 50 25 30 200 Naturalyte 140 45 20 48 265 Sports Drinks (not appropriate for 255 20 3 3 330 ORT) Cereal Based ORT Starch, simple proteins co-transport molecules with little osmotic penalty Increase fluid and electrolyte uptake and reduces stool looses Contain rice instead of glucose Not to be confused with rice water Early refeeding can provide similar benefits Early Refeeding If the child is not dehydrated, they should continue to be fed age-appropriate diets. Children who require rehydration should be fed age-appropriate diets as soon as they are rehydrated. When used with ORT, early feeding reduces stool output Fatty foods/foods high in simple sugars should be avoided Milk based formulas can be used Specific Therapy No dehydration – age appropriate feeding + fluids (10 mL/kg for each stool) Mild dehydration – ORT 50 mL/kg + replacement of losses (10 mL/kg for each stool); feeding should resume once dehydration corrected Moderate dehydration – ORT 100 mL/kg + replacement of losses; resume feeds once dehydration corrected Severe dehydration- MEDICAL EMERGENCY correct with bolus IV fluids, use ORT when stable, resume feeds once rehydration complete Lactose Intolerance Seen with gastroenteritis Diarrhea reappears when child is transitioned from ORS to cow’s milk formula Due to mucosal border injury Lactose free diet allows the brush border to repair Antidiarrheal Medications No proven benefit in children Potential for toxic side effects a concern May decrease stool water/electrolyte losses, shorten course of illness, relieve discomfort Passage of formed stool not a measure of therapeutic success, may even cause false sense of security As a general rule, should not be used to treat acute diarrhea Pharmacologic Agents Classified by their mechanisms of action Alteration of intestinal motility Alteration of secretion Adsorption of toxins or fluid Alteration of intestinal microflora Drugs that Alter Intestinal Motility Loperamide Other opiates Anticholinergics Opiates as well as opiate/atropine combination drugs are contraindicated in the treatment of acute diarrhea in children. Alteration of Secretion Bismuth subsalicylate MOA: inhibits intestinal secretion caused by enterotoxicogenic E Coli and cholera toxins Theoretical risk of Reye syndrome The routine use of bismuth subsalicylate is not recommended in the treatment of children with acute diarrhea. Adsorption of Fluid and Toxins Work by adsorbing bacterial toxins and by binding water to reduce the number of stools and improve their consistency Examples: -kaolin-pectin -fiber -attapulgite Disadvantages: absorption of nutrients, enzymes, and antibiotics in the intestine Treatment of Diarrhea in the Older Child Dehydration less of a problem - able to communicate and act on thirst Offer low sugar, non carbonated drinks Continue with regular diet - high starch/complex carbohydrates - low fat - BRAT diet may be too low in energy and protein to be useful Toddler Diarrhea Chronic Nonspecific Diarrhea of Childhood (CNDC) Definition: 1 or more liquid or semi-formed stools per day for 14 or more days Careful H&P imperative Factors that contribute to CNDC - Excessive fluid intake - A diet high in carbohydrate, low in fat - Consumption of fruit juices containing sorbital or fructose Treatment of CNDC Alter the diet to restore balance between fluid, fiber, and fat Reduce fruit juice intake Increase fat intake to 35-40% of total calories Encourage food high in fiber Consult GI if no response or growth failure noted Travelers’ Diarrhea Affects 20-30% travelers to tropics Mostly bacterial; 50% E.coli (not 0157) Prevention imperative -breast feeding, boiling water, no raw fruits/vegetables -good handwashing Medications Used in Travelers’ Diarrhea Prevention: children: co-trimoxazole adults: co-trimoxazole , ciprofloxacin bismuth subsalicylate Treatment: children: co-trimoxazole (? Cipro) + hydration adults: loperamide + cipro (or co-trimoxazole) Cases Case 1 A 10 kg. male presents to your office with watery stools and a low grade fever. There is no blood in the stool and the child is approximately 5% dehydrated. How would workup and treat this child? Evaluation of the child with diarrhea History recent travel known exposures recent use of antibiotics attendance in daycare previous state of health Physical exam previous weight- often not available Assess for level of dehydration Mild dehydration( 3-5%)- mucous membranes are slightly dry but vital signs are normal and there is normal capillary refill and skin turgor. Tears are usually present and child is alert. Moderate dehydration (6-9%)- increased heart and respiratory rate and slightly prolonged capillary refill, and tenting of the skin. Lack of tears and the child isbecoming listless. Severe dehydration(>10%)- blood pressure is decreased and the child is very lethargic. Mucous membranes are very dry. Skin is cold and clammy. Treatment Deficit of 500mL (50mL/kg.) Maintenance requirement of 40mL/hr To correct the deficit after 6 hours, needs about 125mL./hr. 2 tbs./15 minutes will provide the child's needs. Ongoing losses should be corrected with 10cc/kg per stool. Other things to consider Breast feeding – don’t stop BRAT diet ? Drugs? Probiotics – yogurt ? Lactose free formula ½ strength formula Case 2 The parents of a 14 month old boy bring their son to your office with a 2 month history of 2-6 loose, non- foul smelling watery stools per day. At times there is undigested food in the bowel movement. The parents have gone through multiple diet changes and now the boy is only eating a low fat , no dairy products, lots of fruit juices, and minimal protein diet. He has had an extensive workup including negative stool cultures for bacteria and viruses, negative stool for ova and parasites, and no polys or blood in the stool. How would you approach this problem? Assessment of Toddler Diarrhea Age between 6-30 months. Most are better by 4 years of age 2-6 watery stools per day. There can be periods of days without stools. Many stools contain undigested material and may drip down the child's leg from the diaper. Normal weight, height, and head circumference growth curves without falling off No evidence of infection Stools are hematest negative The child looks well and there is no evidence of malnutrition and no history of abdominal pain Growth may be compromised if the diet manipulations that have been tried to control the diarrhea have not been enough calories. There is often a history of colic, gastroesophogeal reflux, and family history of irritable bowel syndrome. Treatment Increase fat in the diet Decrease fluid in the diet Avoid fructose and sorbitol- decrease fruit juices Increase dietary fiber Normal diet for age Reassurance. There is no role for medications. The parents should be told that there is no serious sequelae and this is not a precursor to inflammatory bowel disease, chronic diarrhea as adults, or cancer Most children are better by 4 years of age, and are better by the time they become potty trained. Questions?