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Management of Acute Gastroenteritis (Oral Rehydration and Nutritional Therapy) Ricardo R. Jiménez, MD, FAAP Pediatric Emergency Medicine All Children’s Hospital Objectives Dehydration assessment and diagnosis Oral Rehydration Therapy and Oral solutions options Management of AGE at home and in the ED Dietary Therapy Pharmacological Therapy 2 Acute Gastroenteritis Acute Gastroenteritis (AGE) remains a major cause of morbidity and mortality in the USA • Over 1.5 million outpatient visits • 200,000 hospitalizations • 300 death a year Worldwide diarrheal disease is the leading cause of morbidity and mortality • 1.5-2.5 million deaths annually among children younger than 5 3 Acute Gastroenteritis Direct medical cost in the US reach $ 250 million/year and is estimated to reach 1 billion worldwide Even though the number of death associated to AGE worldwide is still high, a decrease has been noticed since the start of Oral Rehydration Therapy (ORT) campaigns 4 Oral Rehydration Therapy ORT includes two phases: • Rehydration Phase Water and electrolytes are provided via an oral rehydration solutions (ORS) replacing existing losses • Maintenance Phase Replacement of ongoing fluid and electrolyte losses and adequate dietary intake 5 Oral Rehydration Therapy The full benefits of ORT have not been realized in developing countries One of the reasons for the low use of ORT is the ingrained use of IV therapy The vast majority of pediatricians (30-49%) report always using IVF to treat moderate dehydration and 1/3 report using IVF to treat mild dehydration 6 Oral Rehydration Therapy Randomized trials of ORT vs. IV hydration have demonstrated • Shorter ED stays • Greater parental satisfactions • As effective as IV in moderately dehydrated children < 3 years • Faster initiation of rehydration • Lower hospitalization rate 7 Oral Rehydration Therapy Barriers for ORT • Lack of parental knowledge • Lack of training of medical professionals • Cost of commercially available ORS • Preferences among physicians • The practice of continued feeding during diarrheal disease have been hard to establish 8 Physiologic Basis of ORT The stool output in the adult is < 250ml/day, this amount varies by age in children During diarrheal disease the intestinal output increases greatly, overwhelming its reabsorptive capacity Multiple studies done among cholera patient demonstrated an intact Na-couple solute cotransport mechanism allowing efficient salt and water reabsorption 9 Physiologic Basis of ORT This co-transport remains intact even in infections of E. coli, salmonella, shigella and rotavirus The mechanism essential for the efficacy of oral rehydration solution (ORS) is the couple transport of sodium and glucose in the intestinal brush border 10 Physiologic Basis of ORT Water passively follows the osmotic gradient SGLT1- sodium glucose cotransporter which moves Na and glucose from the luminal membrane into the enterocyte 11 Physiologic Basis of ORT GLUT2- glucose transporter, moves the glucose in the enterocyte into the blood Na+ K+ ATPase provides the gradient that drives the process 12 Physiologic Basis of ORT 13 Physiologic Basis of ORT Solutions with high concentration of the cotransporters decrease the water sodium transport into the bloodstream Rehydration solutions with low osmolarity and 1:1 ration glucose to sodium perform optimally 14 Choices of ORS In 1975 the WHO and UNICEF decided to promote a single ORS (WHO-ORS) • It contained (mmol/L) Na 90, K 20, CL 80, base 30 and Glu 111 with an Osm of 311 • This composition allowed for a single solution to be use for treatment of diarrhea caused by a multitude of agents • Has been proven to be effective and safe for over 25 year 15 Choices of ORS New multiple controlled trials has supported the adoption of a lower osmolarity solution Lower osmolarity as been associated to less stool output, less vomiting and reduced need of IV among infants and children with non-cholera diarrhea 16 Choices of ORS In 2002 the WHO announced a new ORS formulation with a lower osmolarity • 2002 WHO-ORS contains 75mEq/L of Na, 75 mmol/L of Glu and an Osm of 245 17 Choices of ORS 18 Solution Carbs (gm/L) Sodium (mmol/L Potassium (mmol/L) Chloride (mmol/L Base (mmol/L) Osmolarity (mOsm/L) WHO-ORS (2002) 13.5 75 30 65 30 245 WHO-ORS (1975) 20 90 20 80 30 311 Pedialyte 25 45 20 35 30 250 Enfalyte 30 50 25 45 34 200 Rehydralyte 25 75 20 65 30 305 CeraLyte 40 50-90 20 N/A 30 220 Gatorade 14 110 30 Apple Juice 120 0.4 44 45 N/A 730 Coca-Cola 112 1.6 N/A N/A 13.4 650 290-303 Management Home Management • Treatment with ORS is simple and enable management of uncomplicated cases at home • The caregiver must be instructed properly on the signs of dehydration and is able to determine if the child is responding or not to ORS • Early administration of ORS leads to Fever office and emergency department visits Fever hospitalization and death 19 Management Home Management • Caregivers should be encourage to start ORT with commercially available ORS as soon as diarrhea or vomiting commence • The most important aspect of the home management is to replace fluid losses and maintain the nutritional intake • Regardless of the fluid use an age-appropriate diet should be continued, including breast feeding 20 Management Home Management • Severity Assessment Caregivers should be trained to recognize signs of illness or ORT failure and to seek medical assistant No guidelines have established a specific age under which medical evaluation is imperative, but the younger the child the lower the threshold 21 Management Recommendations for medical evaluation of children with diarrheal illness •Young age (< 6 months or < 8 kg) •History of premature birth, chronic medical conditions or concurrent illness •Fever > 38°C for infants < 3 months or > 39°C aged 3-36 months •Blood in stool or diarrhea lasting more than 2 wks •High output diarrhea, including frequency and volume •Caregiver’s report of signs consistent with dehydration •Change in mental status •Persistent vomiting •Suboptimal response to ORT or inability of caregiver to provide ORT 22 Management Dehydration Assessment • The goal is to provide a starting point and determine intensity of therapy • Clinical signs and symptoms that can quantify dehydration Sunken anterior fontanel it can be unreliable or misleading Decreased BP is a late finding and it heralds shock, corresponds to >10% of fluids losses Tachycardia and decrease capillary refill are more sensitive Decrease urine output is sensitive but nonspecific Increase of urine specific gravity can indicate dehydration 23 Management Dehydration Assessment • Prior guidelines, CDC’s 1992 and AAP’s 1996 grouped patient in 3 subgroups Mild dehydration (3%-5% fluid deficit) Moderate dehydration (6%-9% fluid deficit) Severe Dehydration ( >10% fluid deficit) 24 Management Dehydration Assessment • New studies that evaluate the correlation of clinical signs of dehydration and post treatment weight gain indicate that • First signs of dehydration might not be evident until 3%-4% fluid loss • Clinical signs more evident at 5% dehydration • Severe dehydration signs not seen until 9%-10% dehydration 25 Management Dehydration Assessment • Distinguishing between mild or moderate dehydration on the basis of clinical signs may be difficult • The new updated recommendations group together patients with mild and moderate dehydration and specify that signs of dehydration may be apparent a wide range of fluid losses (3%-9%) 26 Management Symptom 27 Minimal or no Dehydration (<3%) Mild to Moderate (3%-9%) Severe (>9%) Mental Status Alert Normal, restless, irritable Lethargic, unconscious Thirst Normal PO or refuses Thirsty Drinks poorly or unable Heart Rate Normal Normal to increased Tachycardia Quality of pulses Normal Normal to decreased Weak or impalpable Breathing Normal Normal to fast Deep Eyes Normal Slightly sunken Deeply sunken Tears Present Decreased Absent Oral mucosa Moist Dry Parched Skin fold Instant recoil Recoil in < 2 sec Recoil > 2sec Capillary refill Normal Prolonged Prolonged; minimal Extremities Warm Cool Cool, mottled, cyanotic Urine output Normal to decrease Decreased Minimal Management Utility of Laboratory Evaluation • Supplementary labs, including serum electrolytes are unnecessary • Stool cultures are only indicated with bloody diarrhea 28 Management ED management • Treatment should include two phases Rehydration – fluid is replaced rapidly, over 34 hr Maintenance – calories and fluids are administered – Rapid realimentation, the patient should continue an age-appropriate diet as tolerated – Breastfeeding should continue – Lactose restriction is usually not necessary 29 Management Basic guidelines for the management of dehydration 30 • ORS should be use for rehydration • Oral rehydration should be performed within 3-4 hr • Rapid realimentation, an age-appropriate unrestricted diet is recommended as soon as dehydration is corrected. Gut rest is not indicated • In breastfeed infants, nursing should continue • Diluted formula or special formulas are not indicated • Additional ORS can be administer for ongoing losses • No unnecessary labs or medications (i.e. antidiarrheals) Management ED management • Minimal Dehydration Provide adequate fluid and age appropriate diet ORS should be encourage Fluid intake should be increased to compensate for emesis or diarrhea – 10 ml/kg of additional fluid per every diarrhea or 2 ml/kg per every emesis – As an alternative in children < 10 kg provide 2-4 oz of ORS per diarrhea or emesis and 4-8 oz in children > 10 kg 31 Management ED Management • Mild to Moderate Dehydration The fluid losses should be estimated and rapidly replaced Administer 50-100 ml of ORS/kg during 2-4 hr Additional ORS should be administer for ongoing losses Smaller volumes should be offered first and increase as tolerated using (i.e. 5 ml) More may be offered if the child wants more, but larger amounts have been associated with vomiting 32 Management ED Management • Mild to Moderate Dehydration Clinical trials support the use NG feeding for those patients with persistent vomiting When compared to IV, NG feedings were found to be more cost effective and associated with fewer complications Hydration status should be assess on a regular basis Those children who do not improved with ORT or with high output should be held for observation 33 Management ED Management • Mild to Moderate Dehydration Once dehydration is corrected further management can be implemented at home as long as the caregivers – – – – 34 Have demonstrated comprehension of ORT Understand indications to seek medical attention Have means to seek medical attention Have agreed to follow up with their primary care physician Management ED Management • Mild to Moderate Dehydration A new study demonstrated an increase ORT failure among mild-moderate dehydrated children associated with large ketones in the urine and mental status changes Also children with tachycardia at discharge or with history of severe vomiting are more likely to require a second visit to the ED 35 Management ED Management • Severe Dehydration Constitutes a medical emergency and requires immediate IV rehydration 20 ml/kg of Lactated Ringers or Normal Saline should be administered until pulse, perfusion and mental status returns to normal Electrolytes, BUN, Cr and glucose should be obtained Vitals should be assess on a regular basis 36 Management 37 ED Management • Severe Dehydration Multiple administrations of fluid in a short amount of time may be necessary Severe edema is rare as long as appropriate weight based amounts are provided with close observation With frail or severely malnourish infants smaller amounts (10ml/kg) are recommend because of their reduced ability of increasing the cardiac output No response to IV hydration should raise suspicion for septic shock, metabolic, cardiac or neurologic disorders Management ED Management • Severe Dehydration As soon as the signs of severe dehydration have resolved the patient may be started on ORT Early institution of ORT will encourage earlier resumption of feeding Some studies have shown more rapid resolution of acidosis with ORT than IV 38 Limits of ORT In children with abdominal ileus or signs of intestinal obstruction ORT should be held until surgical evaluation 1% of infants will have carbohydrate malabsorption, were diarrhea may be worsen by ORS or solutions with simple sugars 39 Dietary Therapy Withholding food for 24 hr is unnecessary Once rehydration is achieved patient should continue with their age-appropriate diets Lactose-free or lactose-reduced formulas are not necessary, except in children with severe malnutrition Low ph or reducing substances in the stool without symptoms is not indicative of lactose intolerance 40 Dietary Therapy Clinical trials have indicated that the use of diluted formulas is associated with prolongation of symptoms and delayed nutritional recovery Soy formulas have been marketed to reduce diarrhea, but the added soy reduce the liquid stools without changing the actual output volume 41 Dietary Therapy Children receiving a solid or semisolid diet should continue their usual diet Avoid foods with high simple sugars, which may cause osmotic diarrhea BRAT diets are unnecessary restrictive and provide suboptimal nutrition 42 Dietary Therapy Functional Foods • Foods that have an effect on physiologic processes separate from their nutritional function • Probiotics are live microorganisms in fermented foods promote improved balance in intestinal microflora Most common species studied included Lactobacilli and nonpathogenic Saccharomyces boulardii Mechanism of action include, enhancing host defenses, competition of pathogenic flora for receptor sites and production of antibiotic substances 43 Dietary Therapy Functional Foods • Probiotics Two separate meta-analysis showed the probiotics are safe and efficacious in the treatment of infections and antibioticassociated diarrhea As probiotics are not regulated by the FDA, there may be great variability, wish make an informed recommendation rather challenging 44 Dietary Therapy Functional Foods • Prebiotics are complex carbohydrates that stimulate the growth of health promoting intestinal flora The oligosaccharides contained in breast milk are the prototypic prebiotic Data have associated the oligosaccharides in breast milk to the lowered incidence of acute diarrhea in the breast feed infant 45 Pharmacologic Therapy Antimicrobials • Viruses are the predominant source of AGE in developed countries • Antimicrobials wastes resources and may increases antimicrobial resistance • Even when the cause is suspected to be microbial, usually antibiotics are not indicated as these disease processes tend to be self-limited • Children with special needs or severe disease may benefit from antibiotics if microbial etiology is suspected 46 Pharmacologic Therapy Nonatimicrobial therapies Limited data exist about the efficacy of antimotility agents like loperamide Side effects are well described including – – – – Ileus Nausea Drowsiness Atropine effects Loperamide has been linked to cases of severe abdominal distention and even death 47 Pharmacologic Therapy Nonatimicrobial therapies • Bismuth subsalicylate has limited efficacy in treating diarrhea in children • Ondasetron, a serotonin antagonist antiemetic Effective in decreasing vomiting and facilitates ORT Proven efficacious and safe in children > 6 months Shown to shorten the ED stay Reduction of cost, with one 4 mg ODT tablet costing around $35 and the placement on an IV around $ 124 48 Pharmacologic Therapy Nonatimicrobial therapies • Promethazine, non-selective antihistamine One of the most prescribed antiemetic Not studied in children Increase side effects including drowsiness, respiratory depression, dystonia and neuroleptic malignant syndrome The AAP does not recommend its use in children younger than 2 years 49 Summary The use of appropriate ORS have shown to be effective for the treatment of mild to moderated dehydration Severe dehydration is a medical emergency and IV fluids should not be held Continuation of age-appropriate diet is more effective for the treatment of AGE than gut rest Ondasetron is safe and efficacious for the treatment of AGE in children 50 QUESTIONS? 51 References 1. 2. 3. 4. 5. 52 King C K, Glass R, et al. Managing Acute Gastroenteritis Among Children. CDC MMWR, Nov 2003;52:16 Freedman FB, Adler M, et al. Oral Ondasetron for Gastroenteritis in a Pediatric Emergency Department. The New England Journal of Medicine 2006;354:1698-705 Spanddorfer PR, Alessandrini EA, et al. Oral Versus Intravenous Rehydration of Moderately Dehydrated Children: A Randomized Controlled Trial. Pediatrics 2005;115:295-301 Ozuah PO, Avener JR, et al. Oral Rehydration, Emergency Physicians and Practice Parameters: A National Survey. Pediatrics 2002;109:259-261 Freedman SB, Powel E, Seshadri R. Predictors of Outcomes in Pediatric Enteritis: A Prospective Cohort Study. Pediatrics 2009;123:e9-e16