The FCG Institute for ContinuingEducation gratefully acknowledges anunrestricted educational grant fromWyeth Lederle Vaccines in support of thiscontinuing medical education activity.

Offers 1 Free Hour of AMA Category 1 CME Credit

Family PracticeRecertification®

April 2002Vol. 24, No 5

A peer-reviewed clinical journal for primary care physicians

A Supplement to

Provided by

Family Practice Recertification® (ISSN 0163-6642) is published monthly by Medical World Business Press, Inc., 241 Forsgate Drive, Jamesburg, NJ 08831-0505. Telephone: (732) 656-1140. Subscription rates: USA—$5.50 per copy, $66 per year; Canada—$7.17 per copy, $86 per year; foreign—$86 per year.Copyright © 2002. Medical World Business Press, Inc./A division of Medical World Communications, Inc. Printed in USA. All rights reserved. FamilyPractice Recertification® is a registered trademark of Medical World Business Press, Inc. Periodicals postage is paid at Monroe Township, NJ08831 and at additional mailing offices. Postmaster: If undelivered, please send form 3579 to Family Practice Recertification, Data Control, OneBroad Avenue, Fairview, NJ 07022-1570. PROJ M303

Gastroenteritis in Primary Care:Treatment Guidelines and Options

GASTROENTERITIS

Learning Objectives

After completing this educational activity, participants should be able to:

• Recognize the prevalence of gastroenteritis and appreciate its potential for morbidity and mortality • Compare andcontrast degrees of dehydration • List the current rehydration and refeeding guidelines • Describe the neurologicalbasis of nausea and vomiting • Identify risks and benefits of available antiemetics • Assess several gastroenteritiscase scenarios

This activity is provided by The FCG Institute for Continuing Education. The FCG Institute for Continuing Education gratefullyacknowledges an unrestricted educational grant from Wyeth Lederle Vaccines in support of this continuing medical educa-tion (CME) activity. The FCG Institute for Continuing Education is accredited by the Accreditation Council for ContinuingMedical Education to provide continuing medical education for physicians.This CME activity is intended for family practice physicians and pediatricians who routinely evaluate patients and diagnosecommonly occurring infectious diseases within their community.To receive CME credit, you must read this journal supplement, take the CME Self-Study Examination found at the end of thissupplement, complete the Evaluation and Credit Request Form, return the form to The FCG Institute for ContinuingEducation, and score at least 70% on the test. The FCG Institute for Continuing Education will mail a certificate for CMEcredit to each participant who successfully completes this activity. There is no fee to receive credit for this CME activity.This activity was originally released on April 1, 2002. The last review date was March 13, 2002. This activity will expire April1, 2003. This activity should take approximately 60 minutes to complete.

Disclosure StatementIt is the policy of The FCG Institute for Continuing Education to ensure independence, balance, objectivity, scientific rigor, andintegrity in all its CME activities. Faculty must disclose to the participants any significant relationships with commercial com-panies whose products or devices may be mentioned in faculty presentations or with the commercial supporter of this CMEactivity. The information is for participant information only; it is not assumed that these relationships will have a negativeimpact on the presentations. Disclosures made by the authors and faculty of the roundtable discussion can be found below. Carla J. Anderson, MD has disclosed that she has no interest or relationship to report. Warren A. Daniel, Jr., MD, FAAP, AAFP hasdisclosed that he has no interest or relationship to report. Forrest A. Eisenrich, MD has disclosed that he has no interest or rela-tionship to report. Aziz K. Ibrahim, MD, FAAP, MRCP, DCH has disclosed that he has participated on the Speakers Bureau forAventis Pharmaceuticals and that he has received honoraria from Schering-Plough Corporation, Novartis PharmaceuticalsCorporation, and Ortho-McNeil Pharmaceutical, Inc. Thomas C. Joseph, MD has disclosed that he has no interest or relationshipto report. Thomas E. Lockard, DO has disclosed that he has no interest or relationship to report. George P. Shaw, Jr., MD, DABFPhas disclosed that he has received honoraria from Merck & Co., Inc. and Schering Corporation.

Unlabeled Use DisclosureThe FCG Institute for Continuing Education, the faculty, and Wyeth Lederle Vaccines do not endorse the use of any product out-side the U.S. Food and Drug Administration (FDA)-labeled indications. Physicians should not use the procedures, products, ordiagnosis techniques discussed during this activity without evaluation of their patients for contraindications or dangers of use.This CME activity may include discussions of products or devices that are not currently labeled for use by the FDA. The use ofpromethazine for nausea and vomiting due to gastroenteritis is not approved. The indications for the antiemetics discussed inthis monograph are listed in Table 2 of the article “Gastroenteritis Treatment in Practice.”

Note the following disclaimer from Wyeth Lederle Vaccines: Do not use promethazine in children under 2 years of age.Antiemetics are not recommended for the treatment of uncomplicated vomiting in children. Their use should be limited to pro-longed vomiting of known etiology. The recommended dose for promethazine is 25 mg.

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VOL. 24, NO. 5, APRIL 2002 • 1

GASTROENTERITIS

ContentsGastroenteritis: Presentation and Risk 2

Gastroenteritis Treatment in Practice 8

Case Studies 14

CME Self-Study Examination 18

AuthorsWarren A. Daniel, Jr., MD, FAAP, AAFP, Family Practitioner, Glenwood Family Practice Clinic, WestMonroe, Louisiana

Aziz K. Ibrahim, MD, FAAP, MRCP, DCH, Pediatrician, Sherwood Family Medical Center, Sherwood, Arkansas

Roundtable FacultyWarren A. Daniel, Jr., MD, FAAP, AAFP, Family Practitioner, Glenwood Family Practice Clinic, WestMonroe, Louisiana

Aziz K. Ibrahim, MD, FAAP, MRCP, DCH, Pediatrician, Sherwood Family Medical Center, Sherwood, ArkansasCarla J. Anderson, MD, Family Practitioner, Sherwood Family Medical Center, Sherwood, ArkansasForrest A. Eisenrich, MD, Family Practitioner, Comanche County Medical Clinic, Comanche, TexasThomas C. Joseph, MD, Private Practitioner, Pediatric Associates, P.A., Camden, South CarolinaThomas E. Lockard, DO, Family Practitioner, Gill Family Medicine, Decatur, AlabamaGeorge P. Shaw, Jr., MD, DABFP, President, LaFayette Family Practice, LaFayette, Georgia

Definition and EpidemiologyGastroenteritis is an intestinal pathology charac-

terized by nausea, vomiting, diarrhea, abdominalpain, or a combination of these signs and symp-toms. Severity may range widely from self limitingto life threatening, depending on the association ofdehydration, malnutrition, or other complicationsthat can accompany gastroenteritis. The conditionis usually self limited in the United States, affectingthe very young and very old most seriously.Mortality statistics vary from fewer than 325 child-hood deaths to 10,000 gastroenteritis-relateddeaths in all ages in the United States yearly.1,2

Internationally, mortality rates range from 3 to 10million annually.2,3 Deaths are mostly due to dehy-dration and related hypovolemic shock. Directcosts for hospitalization and outpatient care areestimated to exceed $2.0 billion a year in theUnited States.4 The disease is most prevalent inchildren younger than 3 years of age. Incidencedecreases throughout childhood with increasingimmunity to various enteric pathogens.Gastroenteritis is usually transmitted through thefecal-oral route either through person-to-person

contact or contact with contaminated objects orthrough ingestion of contaminated water or food.5-7

Rotavirus is the most common cause of severegastroenteritis in children. In the United Statesand other areas with primarily temperate cli-mates, rotavirus disease follows a winter seasonalpattern with epidemics occurring annually fromNovember through April.8-10

Etiology and PathogenesisGastroenteritis can be caused by bacterial and

parasitic organisms (Table 1), but is primarily ofviral origin, the most frequent of which in infantsand young children is rotavirus.11 Virtually all chil-dren are infected with rotavirus within their first 5years of life and may have two or more episodes.12

Rotavirus can infect neonates, older children, andadults, and is the leading cause of severe gastroen-teritis and hospitalization in the United States andthroughout the world.11,13-15 Because rotavirus isshed in stool, infection is readily transmitted

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Gastroenteritis: Presentation and Risk

Viruses: AstrovirusCalicivirus or Norwalk-like virusEnteric adenovirusRotavirus

Bacteria: Bacillus cereusCampylobacter jejuniClostridium difficileClostridium perfringensEscherichia coli speciesListeria monocytogenesSalmonella speciesShigella speciesStaphylococcus aureusYersinia enterocolitica

Parasites: Cryptosporidium parvumCyclospora cayetanensisGiardia lamblia

Table 1Common gastroenteritis etiologic agents

In the United States, mortality statistics rangefrom 325 gastroenteritis-related childhood deathsto 10,000 gastroenteritis-related deaths annuallyin all age groups. Throughout the world, mortali-ty rates range from 3 to 10 million annually, usu-ally due to diarrhea and vomiting-induced dehy-dration. Although the advent of oral rehydrationtherapy has been recognized as one of the mostsignificant medical breakthroughs of the 20thcentury, differences of opinion exist regardingthe reintroduction of normal diet and pharma-cotherapy in the treatment of gastroenteritissymptoms. This continuing medical education(CME) activity will familiarize physicians withcurrent guidelines and explore treatment options.

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through diaper contact in pediatric hospital wardsand child care centers. Rotavirus infects matureenterocytes of the small intestine, producing alter-ations in the cytoskeleton and causing functionaland structural damage to these cells, which resultsin diarrhea and malabsorption.16,17 In animal mod-els, rotavirus infection has been demonstrated todamage the villi, causing a reduction in amino aciduptake in the small intestine, resulting in signifi-cantly reduced length of villi.18 Motility distur-bances also may be involved.19 Mucosal damageand/or loss of the villous surface results in alteredcell permeability in the small intestine, and subse-quent increased fluid, sugar, electrolyte, and nutri-ent secretion, and decreased absorption.20 Luminalcontent is increased, leading to diarrhea, dehydra-tion, and nutritional loss. Vomiting may precedediarrhea. Although these are the typical gastroen-teritis complications, fatal disseminated rotaviralinfection based on a diffuse endothelialitis andconcomitant tissue damage in two children wasreported in the United States in early 2001.21

Astroviruses have been categorized as secondonly to rotaviruses as leading causative agents ofgastroenteritis.22 Although astrovirus-associatedgastroenteritis is not as predictably seasonal asrotavirus infection, most cases have reportedlyoccurred from March through June.22 Astrovirus ismore likely to occur in younger patients than isrotavirus. Symptoms are similar to those ofrotavirus, but are less severe, with greater dehydra-tion occurring in rotavirus-infected patients.23

Norwalk-like viruses (NLVs) are implicated inmany nonbacterial gastroenteritis outbreaks asso-ciated with contaminated food and water inrestaurants, nursing homes, hospitals, schools,child care centers, and vacation spots.24-29 MostNLV-associated gastroenteritis is foodborne.30

Secondary and tertiary infections occur throughperson-to-person contact. The virus is highly con-tagious. Characteristically, NLV gastroenteritishas a 12-hour to 2-day incubation period, lastsfrom 12 hours to 21/2 days, and presents with acuteonset nausea, vomiting, abdominal cramps, anddiarrhea. Patients may exhibit vomiting alone as asymptom. Headache, fever, chills, and myalgiaalso are frequently reported. Dehydration anddeath due to NLV gastroenteritis are rare but canmore likely occur among the elderly and debilitat-ed, who are more susceptible to gastroenteritisthan younger individuals because of decreasedhumoral and cellular immunity, decreased motili-ty, and decreased gastric acid production.31 Other

viral etiologic agents include enteric adenovirus,which has a clinical presentation similar to astro-virus infections.

Bacterial enteropathogens include, but are notlimited to, Staphylococcus aureus, Salmonellaspecies, Shigella species, Campylobacter species,Bacillus cereus, Clostridium perfringens, Yersinia ente-rocolitica, and Escherichia coli O157:H7. Gastro-enteritis of bacterial etiology is identifiablethrough culture of the organism from stool and isoften associated with foodborne outbreaks. A bac-terial cause may indicate large-intestinal involve-ment as opposed to viral gastroenteritis, whichaffects the small intestine. Typical Salmonella infec-tion, for example, involves both the ileum and thecolon, and the bacteria that invade these tissuesmay colonize distal sites such as the mesentericlymph nodes, liver, and spleen.32 About 500 deathsoccur yearly in the United States from Salmonellainfection.33 Vomiting due to bacterial gastroenteri-tis, however, is less common. Patients with a bac-terial infection may present with bloody stoolsand more frequent bowel movements of smallervolume, and fever. High fever is also a more likelyindicator of bacterial involvement. E coli O157:H7-associated gastroenteritis (referred to as hemor-rhagic colitis) may be particularly toxic and ischaracterized by bloody diarrhea and abdominalpain, and may occur in isolated groups of patientswho have eaten contaminated food. Up to 10% ofchildren with hemorrhagic colitis may develophemolytic uremic syndrome, which is more com-mon in children younger than 6 years of age.3,34,35

Parasites causing gastroenteritis includeCryptosporidium, Giardia lamblia, and Cyclospora.These are important etiologic agents that shouldnot be overlooked in assessing suspected gas-troenteritis.

Dehydration and Nutritional DeficitsDehydration and malnutrition due to vomiting

and diarrhea are significant risks in people withgastroenteritis. The resultant small intestinalmucosal damage associated with variable degreesof villous atrophy and high permeability ratiosassociated with many enteropathogens (ie, usuallyviral and protozoal) characterize the structuraland functional breakdown leading to osmoticdiarrhea, dehydration, and electrolyteimbalances.36 In gastroenteritis, sustained vomit-ing contributes significantly to dehydration andmay lead to hypokalemic metabolic alkalosis

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resulting from loss of hydrochloric acid in gastricsecretions.37

Assessing dehydration involves assigning thepatient to one of three categories based on degreeof dehydration (Table 2). Weight loss can be a sig-nificant measure of dehydration; however, arecent, accurate weight measurement is required,and current opinion is not in agreement withregard to assigning a patient to a specific dehydra-tion category based on a percentage of weight loss.Infants and young children are particularly suscep-tible to dehydration because of their large bodysurface area to volume ratio, dependency on adultsfor hydration, frequent vomiting associated withgastroenteritis, and high daily water turnover rate(Figure).

All available patient history, clinical data, andlaboratory information should be considered inmaking an evaluation of dehydration because tra-

ditional signs are not always reliable, categories ofdehydration are only estimates, and vomiting anddiarrhea of mixed or unknown proportions mayyield confusing findings. In addition, failure topromptly recognize and appropriately correctdehydration may lead to different sequelae includ-ing death.

A combination of three or more of the indicatedfindings (Table 2) is most likely to provide evidencethat dehydration is present. Generally, a combina-tion of fewer than three of the indicated findings inTable 2 correlates to dehydration less than 5%;three or more correlate to dehydration of 5%-9%;and six to seven findings correlate to dehydrationdeficits of 10% or greater. A subset of these findings(dry mucous membranes, absent tears, capillaryrefill, and general appearance) has demonstrateddiagnostic accuracy nearly equal to that of theentire set.38

Table 2Degree of dehydration

Mild Moderate Severe(3%-5%) (6%-9%) (10% or greater)

Variable

Blood pressure (BP) Normal Normal Normal to reducedSystolic BP Normal Decreased Perhaps unevaluablePulse quality* Slight rate increase; Rapid and weak Rapid, feeble, perhaps

normal strength impalpableHeart rate* Normal Increased Increased†

Skin turgor* Slightly decreased Decreased Decreased (pinch retracts > 2 seconds)

Fontanelle Normal Sunken SunkenMucous membranes* Slightly dry Dry DryTears* Absent Absent AbsentEyes* Normal Sunken orbits Deeply sunken orbitsExtremities/capillary refill* Warm/refill Capillary refill Cool, mottled

≤ 1.5 seconds 1.5-3.0 seconds > 3.0 secondsGeneral appearance Alert, restless, normal Normal, restless, Normal to limp, drowsy, and mental status* or lethargic comatose, cyanotic

extremitiesUrine output* Slightly decreased Less than Considerably less than

1 mL/kg/hr 1 mL/kg/hrThirst Slightly increased Moderately Markedly increased or too

increased lethargic to indicateBUN 10-20 mg/dL 21-25 mg/dL Above 25 mg/dLRespiratory rate* Slightly increased Increased Deep, rapid

*The occurrence of 3 or more of these clinical findings corresponds generally to dehydration of 5%-9% [Liebelt 1998].†Possible bradycardia in children.BUN = blood urea nitrogen.Sources: Burkhart DM. Am Fam Physician 1999;60:2555-2563; Liebelt EL. Curr Opin Pediatr 1998;10:461-469.

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Rehydration and Refeeding GuidelinesOral rehydration therapy. The development of

balanced glucose and electrolyte solutions for oralrehydration therapy (ORT) has been referred to aspotentially the most significant medical advance inthe 20th century.39 Various formulations of oralrehydration solutions are readily available for oralrehydration, which is recognized as being as effec-tive as intravenous (IV) rehydration in treatingmild-to-moderate dehydration in children (Table3).40 Although these formulations have differentsodium contents and osmolalities, all have an

appropriate carbohydrate-to-sodium ratio neces-sary for optimal absorption. All of the formulationscontain carbohydrate because water absorption inthe small bowel is mediated through an activecotransport process involving glucose or other car-bohydrate and sodium. This process remains func-tional even during episodes of acute diarrhea.40 Allof the solutions are efficacious and safe in treatingrehydration. Although not readily available in theUnited States, the World Health Organization(WHO) oral rehydration solution packets have thehighest osmolality and sodium content. Most of therecommended formulations readily available in theUnited States contain about half the sodium of theWHO formulation and are appropriate for use inthe United States.

A “clear liquid” approach to rehydration of dehy-drated children is not recommended. Sports drink,ginger ale, cola, and apple juice are sufficiently highin carbohydrate to contribute to osmotic diarrheaand sufficiently low in sodium to contribute tohyponatremia. Tea contains little sodium, is devoidof carbohydrate, and also contains caffeine, which isdiuretic. Chicken broth contains no carbohydrate, ishigh in sodium while having little potassium and nobicarbonate, and is hyperosmolar. None of these flu-ids should be considered appropriate rehydrationtherapy for dehydration (Table 4).

The American Academy of Pediatrics (AAP)Practice Guideline is the acknowledged treatmentstandard for oral rehydration, maintenance, andnutritional therapy of children with gastroenteri-tis.41 When dehydration is not present, current rec-ommendations do not require oral rehydrationunless the patient is not eating or taking other flu-ids, during which time oral rehydration solution at10 mL/kg per each loose stool is recommended.41 Inmild dehydration, ongoing fluid loss should beestimated every 2 hours. Initially 50 mL/kg shouldbe given, and ongoing fluid losses should bereplaced every 4 hours. Fluid loss estimates shouldinclude the volume of emesis and 10 mL/kg foreach loose stool. The regimen for moderate dehy-dration comprises 100 mL/kg plus replacement ofongoing fluid loss over a 4-hour period. Re-evalua-tion and ongoing fluid loss estimates should contin-ue hourly. Severe dehydration requires IV therapywith an initial 20 mL/kg IV bolus of normal salineor Ringer’s lactate repeated until hemodynamic sta-bility is achieved and shock resolves. Considercauses of shock other than dehydration if shockdoes not resolve after one or two boluses. When thepatient is alert and stable, oral rehydration can be

Figure Daily fluid turnover

Ingest 2,000 mL/day

water

Saliva 1,500 mL/day

Gastric secretions

2,000 mL/day

Bile 500 mL/day

Pancreaticjuices

1,500 mL/day

Intestinal secretions 1,500 mL/day

Small intestine absorbs

3,500 mL/day

Colon absorbs 400 mL/day

≈ 100 mL/day water excreted

The ratio of water excreted in stool/water ingested by mouth perday in the adult is about 5%. Daily fluid turnover is about 25% inchildren. Reprinted with permission from Berne RM, Levy MN, eds.Physiology. St. Louis, MO: Mosby; 1983.

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initiated, but the IV line should be maintained untilnormal drinking patterns are re-established.

Age-appropriate diet reintroduction. The reintro-duction of an age-appropriate diet immediatelyafter successful rehydration is recommended bothby the AAP and the European Society of PaediatricGastroenterology and Nutrition Working Group onAcute Diarrhea.41,42

In the past, reduced lactase levels, malabsorp-tion, and an early reintroduction of an age appro-priate diet were thought to contribute to vomitingand diarrhea. A meta-analysis of clinical trials con-cluded that in the majority of cases, undiluted non-human milks do not need to be discontinued.43 It isnow believed that early refeeding may decreaseinfection-induced small bowel permeabilitychanges and promote enterocyte healing, reducethe duration of diarrhea, and restore nutritionalbalance. Dietary restrictions may actually prolong

symptoms.44 The AAP practice parameter recom-mends early refeeding with milk or food after rehy-dration. It is not recommended to use condensed orevaporated milk.

References1. Glass RI, Lew JF, Gangarosa RE, et al. Estimates of morbid-

ity and mortality rates for diarrheal diseases in Americanchildren. J Pediatr 1991;118:S27-S33.

2. Diskin A. Gastroenteritis from Emergency Medicine.eMedicine Journal [serial online]. 2001;2:1-11. Available at:http://www.emedicine.com/EMERG/topic213.htm.Accessed May 15, 2001.

3. Eliason BC, Lewan RB. Gastroenteritis in children: princi-ples of diagnosis and treatment. Am Fam Physician1998;58:1769-1776.

4. Burkhart DM. Management of acute gastroenteritis in chil-dren. Am Fam Physician 1999;60:2555-2563.

5. Barwick RS, Levy DA, Craun GF, et al. Surveillance forwaterborne-disease outbreaks—United States, 1997-1998.MMWR Morb Mortal Wkly Rep 2000;49:1-35.

Table 3Appropriate oral replacement solutions

*G = glucose; R = rice syrup solids.†Available from Jianas Brothers Co., 2533 Southwest Blvd., Kansas City, MO 64018-2395; phone 816-421-2880; fax 816-421-2883;www.rehydrate.org/resources/jianas.htm.WHO = World Health Organization; ORS = oral rehydration solution.

Carbohydrate* Sodium Potassium Base Osmolality Calories(g/L) (mEq/L) (mEq/L) (mEq/L) (mOsm/L) (cal/100 mL)

Laboratory profile of diarrhea contents – 50-100 25-35 25-40 250-300 –

WHO packets† G: 20 90 20 30 310 8

WHO ORS G: 20 90 20 30 300 8

Pedialyte G: 25 45 20 30 260 10

Infalyte R: 30 50 25 34 210 12

Pedialyte-RS G: 25 75 20 30 310 –

Table 4Inappropriate oral replacement solutions

Carbohydrate* Sodium Potassium Base Osmolality Calories(g/L) (mEq/L) (mEq/L) (mEq/L) (mOsm/L) (cal/100 mL)

Gatorade G: 50 20 3 3 330 10

Chicken broth 0 250 5 0 450 0

Cola F/G: 50-150 2 0.1 13 550 12-16

Apple juice F/G/S: 100-150 3 30 0 700 15-18

Tea 0 0-1 0-1 0 0-5 0

*F = fructose; G = glucose; S = sucrose.

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6. Centers for Disease Control and Prevention. Diagnosis andmanagement of foodborne illnesses: a primer for physi-cians. MMWR Morb Mortal Wkly Rep 2001;50:1-69.

7. Olsen SJ, MacKinon LC, Goulding JS, et al. Surveillance forfoodborne disease outbreaks—United States, 1993-1997.MMWR Morb Mortal Wkly Rep 2000;49:1-51.

8. American Academy of Pediatrics. Rotavirus infections. In:Pickering LK, ed. 2000 Red Book: Report of the Committee onInfectious Diseases. 25th ed. Elk Grove Village, IL: AmericanAcademy of Pediatrics; 2000:493-495.

9. Kapikian AZ, Chanock RM. Rotaviruses. In: Fields BN,Knipe DM, Howley PM, eds. Fields Virology. 3rd ed.Philadelphia, PA: Lippincott-Raven; 1995:1657-1708.

10. Kapikian AZ. Gastroenteritis viruses. In: Evans AS, KaslowRA, eds. Viral Infections of Humans: Epidemiology andControl. 4th ed. New York, NY: Plenum; 1997:285-344.

11. Perez-Schael I. The impact of rotavirus disease inVenezuela. J Infect Dis 1996;174:S19-S21.

12. Velazquez ER, Matson DO, Calva JJ, et al. Rotavirus infec-tion in infants as protection against subsequent infections.N Engl J Med 1996;335:1022-1028.

13. Chiu TF, Lee CN, Lee PI, et al. Rotavirus gastroenteritis inchildren: 5-year experience in a medical center. J MicrobiolImmunol Infect 2000;33:181-186.

14. Steele JC Jr. Rotavirus. Clin Lab Med 1999;19:691-703.15. Centers for Disease Control and Prevention. Rotavirus vac-

cine for the prevention of rotavirus gastroenteritis amongchildren. Recommendations of the Advisory Committee onImmunization Practices (ACIP). MMWR Morb Mortal WklyRep 1999;48:1-20.

16. Perdue MH. Mucosal immunity and inflammation. III. Themucosal antigen barrier: cross talk with mucosal cytokines.Am J Physiol 1999;277:G1-G5.

17. Jourdan N, Brunet JP, Sapin C, et al. Rotavirus infectionreduces sucrase-isomaltase expression in human intestinalepithelial cells by perturbing protein targeting and organi-zation of microvillar cytoskeleton. J Virol 1998;72:7228-7236.

18. Katyal R, Rana SV, Vaiphei K, et al. Effect of rotavirusinfection on small gut pathophysiology in a mouse model.J Gastroenterol Hepatol 1999;14:779-784.

19. Goodgame RW. Viral infections of the gastrointestinaltract. Curr Gastroenterol Rep 1999;1:292-300.

20. Hochwald C, Kivela L. Rotavirus vaccine, live, oral,tetravalent (RotaShield). Pediatr Nurs 1999;25:203-204, 207.

21. Morrison C, Gilson T, Nuovo GJ. Histologic distribution offatal rotaviral infection: an immunohistochemical andreverse transcriptase in situ polymerase chain reactionanalysis. Hum Pathol 2001;32:216-221.

22. Dennehy PH, Nelson SM, Spangenberger S, et al. Aprospective case-control study of the role of astrovirus inacute diarrhea among hospitalized young children. J InfectDis 2001;184:10-15.

23. Herrmann JE, Taylor DN, Echeverria P, Blacklow NR.Astroviruses as a cause of gastroenteritis in children. N Engl J Med 1991;324:1757-1760.

24. Centers for Disease Control and Prevention. Norwalk-likeviruses: public health consequences and outbreak manage-ment. MMWR Morb Mortal Wkly Rep 2001;50:1-18.

25. Morse DL, Guzewich JJ, Hanrahan JP, et al. Widespreadoutbreaks of clam- and oyster-associated gastroenteritis.Role of Norwalk virus. N Engl J Med 1986;314:678-681.

26. Lieb S, Gunn RA, Medina R, et al. Norwalk virus gastroen-

teritis. An outbreak associated with a cafeteria at a college.Am J Epidemiol 1985;121:259-268.

27. Kuritsky JN, Osterholm MT, Greenberg HB, et al. Norwalkgastroenteritis: a community outbreak associated with bak-ery product consumption. Ann Intern Med 1984;100:519-521.

28. Kappus KD, Marks JS, Holman RC, et al. An outbreak ofNorwalk gastroenteritis associated with swimming in apool and secondary person-to-person transmission. Am JEpidemiol 1982;116:834-839.

29. Kaplan JE, Gary GW, Baron RC, et al. Epidemiology ofNorwalk gastroenteritis and the role of Norwalk virus inoutbreaks of acute nonbacterial gastroenteritis. Ann InternMed 1982;96:756-761.

30. Fankhauser RL, Noel JS, Monroe SS, et al. Molecular epi-demiology of “Norwalk-like viruses” in outbreaks of gas-troenteritis in the United States. J Infect Dis 1998;178:1571-1578.

31. Smith JL. Foodborne illness in the elderly. J Food Prot1998;61:1229-1239.

32. Darwin KH, Miller VL. Molecular basis of the interactionof Salmonella with the intestinal mucosa. Clin Microbiol Rev1999;12:405-428.

33. Centers for Disease Control and Prevention. Intussus-ception among recipients of rotavirus vaccine—UnitedStates, 1998-1999. MMWR Morb Mortal Wkly Rep 1999;48:577-581.

34. Wong CS, Jelacic S, Habeeb RL, et al. The risk of thehemolytic-uremic syndrome after antibiotic treatment ofEscherichia coli O157:H7 infections. N Engl J Med2000;342:1930-1936.

35. Pickering LK, Obrig TG, Stapleton FB. Hemolytic-uremicsyndrome and enterohemorrhagic Escherichia coli. PediatrInfect Dis J 1994;13:459-475.

36. Kukuruzovic RH, Haase A, Dunn K, et al. Intestinal per-meability and diarrhoeal disease in Aboriginal Australians.Arch Dis Child 1999;81:304-308.

37. Quigley EM, Hasler WL, Parkman HP. AGA technicalreview on nausea and vomiting. Gastroenterology 2001;120;263-286.

38. Liebelt EL. Clinical and laboratory evaluation and manage-ment of children with vomiting, diarrhea, and dehydra-tion. Curr Opin Pediatr 1998;10:461-469.

39. Water with sugar and salt [editorial]. Lancet 1978;2:300-301.40. Meyers A. Fluid and electrolyte therapy for children. Curr

Opin Pediatr 1994;6:303-309.41. Practice parameter: The management of acute gastroenteri-

tis in young children. American Academy of Pediatrics,Provisional Committee on Quality Improvement, Sub-committee on Acute Gastroenteritis. Pediatrics 1996;97:424-435.

42. Walker-Smith JA, Sandhu BK, Isolauri E, et al. Guidelinesprepared by the ESPGAN Working Group on AcuteDiarrhoea. Recommendations for feeding in childhoodgastroenteritis. European Society of Pediatric Gastro-enterology and Nutrition. J Pediatr Gastroenterol Nutr 1997;24:619-620.

43. Brown KH, Peerson JM, Fontaine O. Use of nonhumanmilks in the dietary management of young children withacute diarrhea: a meta-analysis of clinical trials. Pediatrics1994;93:17-27.

44. Meyers A. Modern management of acute diarrhea anddehydration in children. Am Fam Physician 1995;51:1103-1118.

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The American Academy of Pediatrics (AAP) andCenters for Disease Control and Prevention (CDC)guidelines provide direction for supportive therapyof children with gastroenteritis.1,2 In Europe, theEuropean Society for Paediatric Gastroenterology,Hepatology and Nutrition (ESPGHAN) recommen-dations for the treatment of gastroenteritis ininfants are comparable. There are no recognizedguidelines that support practice contradictory tothese guidelines. Other sources are available toassist with specific antimicrobial therapy of chil-dren and adults infected with select bacterial andparasitic enteropathogens.3-6

RefeedingWith regard to refeeding, the current AAP

guideline states that nondehydrated childrenshould continue on age-appropriate diets and thatdehydrated children should resume age-appropri-ate diets as soon as rehydration is established. Thisrecommendation is based on studies reviewed in ameta-analysis showing that at least 80% of childrenwith diarrhea can safely tolerate full-strength milk,stool output can be reduced, and that the durationof diarrhea can be reduced by 0.43 days throughearly refeeding. The guidelines further state thatthese benefits are of secondary importance relativeto the benefit of improved nutrition.1

The physicians’ dilemma is appreciating thatpossibly one of five patients (20%) may not toleratefull-strength milk and early refeeding, and deter-mining how to best treat these patients. This minor-ity may demonstrate signs of malabsorption.Further considerations include the fact that not allgastroenteritis pathogens have an equal propensityto cause diarrhea associated with the gastrointesti-nal tract, nor do all patients respond to the samepathogen in exactly the same way. Also, the physi-cian does not always know the identity of theenteropathogen. Given these realities, although theAAP and CDC guidelines are the clearly recog-nized and generally practiced standards of care,individual cases should be treated based on specific

clinical evidence and the individual patient’s char-acteristics and circumstances. These may distin-guish any single treatment or individual patientfrom the norm, as determined by the treatingphysician.

It should not be surprising that individual treat-ments occur in practice that are completely appro-priate, yet do not specifically follow general guide-lines. A recent study of 2,997 physicians wasconducted in 29 European countries comparingcurrent treatment with ESPGHAN recommenda-tions. Eighty-four percent of responding practition-ers said they followed the recommendation to useoral rehydration solution and 77% reported follow-ing the continuation of breast-feeding guidelines.7

Although these numbers reflect general compliancewith these guidelines, further studies comparingcurrent treatment of subpopulations of patients topractice guidelines are needed and might explainthe rationale for deviations from the guidelines.

AntiemeticsThe consensus opinion expressed in the most

recent AAP guidelines is that antiemetic therapy isnot recommended in managing acute gastroenteri-tis in infants and young children. The committeedid not evaluate the use of antiemetic drugs.Concern regarding the use of antiemetics in chil-dren with gastroenteritis is expressed in the guide-lines, stating that the use of antiemetic therapy inchildren may be associated with adverse effects.Although not supporting antiemetic use in gas-troenteritis, the guidelines do acknowledge thatgiven situations may influence some practitioners’opinions to favor antiemetic therapy, especially inolder children, adolescents, and adults.

Studies conducted to determine prehospitaladmission drug therapy in treatment of gastroen-teritis suggest that antiemetic therapy is imple-mented with a degree of regularity in the commu-nity practice setting. In three such studies of 164,231, and 295 (152 evaluable) children, antiemetictherapy had been used in 5.5%, 7%, and 24% of

Gastroenteritis Treatment inPractice

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these patients, respectively, before hospital admis-sion.8-10 A recent study was conducted in the UnitedStates to determine antiemetic prescribing differ-ences between pediatricians, pediatric emergencydepartment, and other emergency departmentphysicians.11 The response to 1,665 surveys was35.6% and showed that 60.9% used antiemetics.Pediatricians (52%) were least likely to useantiemetics, followed by pediatric emergencydepartment physicians (55%), and other emergencydepartment physicians (79%) (P < .000001).Concern about adverse effects was expressed by62%, and concern about masking a more seriousproblem was expressed by 57%. Of those whoresponded, 75% used antiemetics to prevent dehy-dration and 62% included patient comfort in theirrationale for antiemetic therapy. Of the 345 practi-tioners stating a preference, promethazine was pre-ferred by 68%, followed by trimethobenzamide(18%), and prochlorperazine (6%). Rectal supposi-tory was the dosage form preferred by 72% of pre-scribers. Seventy-three responders (20% of thosewho used antiemetics) reported adverse eventsafter a single dose; of the 73 responders, 31 (43%)cited prochlorperazine as the drug administeredprior to observing an adverse reaction.11

Antiemetic use requires a thorough risk-versus-benefits analysis on an individual basis becausethere is risk associated with these agents. Specificpatient information (eg, age, weight, allergy, andunderlying and/or concomitant conditions) mustalways be considered. Hydration status and thelikelihood of dehydration also must be weighedagainst risks (eg, masking symptoms of moresevere disease and undesirable drug side effects).

Nausea, Vomiting, and AntiemeticsThe neuroreceptor basis of emesis. Vomiting is a

reflex action in response to the emetic or “vomit-ing” center, which is located in the lower brainstem or medulla. Although not completely under-stood, the process is mediated through neurorecep-tor stimuli. These stimuli travel through the vagusand splanchnic nerves from the gastrointestinaltract. They also can originate from the chemorecep-tor trigger zone (CTZ), a chemosensitive region inthe area postrema on the upper surface of themedulla or other higher central nervous system(CNS) centers (eg, cerebral cortex, hypothalamus,and thalamus). Receptors and neurotransmissionthrough the labyrinth and pharynx can also pro-vide input to the vomiting center. Stimulus from

the emetic center in response to these stimuli thentriggers deep inspiration, opening of the upperesophageal sphincter, and closure of the glottis.This is followed by an elevation of the soft palate(which usually closes off the internal nares), con-traction of the diaphragm and abdominal muscles,and opening of the lower esophageal sphincter. Thebody of the stomach is relaxed and does not resistthe pressure of the abdominal wall and diaphragmsqueezing against it. Gastric contents are ejected upthe esophagus and through the mouth.12

Vomiting depends on the source of neural stim-uli to the emetic center. In gastroenteritis this maybe mediated peripherally or centrally throughmechanoreceptors and/or chemoreceptors in thegastrointestinal tract or at higher centers (eg, areapostrema). Staphylococcus aureus preformed entero-toxin might initiate vomiting peripherally throughswelling in the large intestine and centrally in thearea postrema through the production of toxins.13

Although serotonergic 5-HT3 mediation is believedto be primarily involved in intestinal distention,cholinergic M1, histaminic H1, and/or dopaminer-gic D2 neuronal pathways also have been identifiedin the periphery and in the CTZ (Table 1).12-14 Theseneurotransmitters may all be implicated in gas-troenteritis-induced dehydration, uremia, and elec-trolyte imbalances.13,14

Antiemetic pharmacology. The precise neuro-transmitter, or combination, responsible for signal-ing the emetic center to initiate vomiting dependson the site at which the neurotransmitter signaloriginates. Although not completely defined orunderstood, the safety, efficacy, and adverse eventprofiles of many antiemetics depend on their abili-ties to effect blockades of these neural pathways.Various monotherapies and combination therapieshave been investigated including anticholinergics,antihistamines, neuroleptics, and tricyclic antide-pressants. Recently, the use of odansetron has beeninvestigated in gastroenteritis-induced vomiting inpediatric patients. Odansetron, a 5-HT3 blocker,proved superior to placebo in preventing emesisassociated with acute gastroenteritis, demonstrat-ing possible involvement of this receptor in thisform of emesis.15 No single pharmacologic entityexists that affects all of the relevant receptors withgreat potency. Selection of the appropriate agentdepends on its efficacy considered against the like-lihood of adverse events in a given circumstance.

The three agents most prescribed for gastroen-teritis-induced emesis are promethazine, trimetho-benzamide, and prochlorperazine. None of these,

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nor any U.S. Food and Drug Administration-approved drug, has a specific indication for gas-troenteritis-induced nausea and vomiting (Table 2).Each agent, however, is used in different capacitiesas an antiemetic. Each differs in its classification,chemical structure, receptor-binding affinities, andits ability to effect specific blockades and produceadverse events.

Antiemetic classification and receptor speci-ficity. Although promethazine is an aliphaticphenothiazine derivative, it differs from the antipsy-chotic phenothiazines by virtue of its branched sidechain and lack of ring substitution. The branchedside chain component of promethazine contributesthe antihistaminic H1 activity to this entity andaccounts for its classification as an antihistamine.The drug retains, however, a degree of anti-dopaminergic D2 activity, approximately one tenththat of chlorpromazine.16 Promethazine also func-tions as a muscarinic M1-receptor blocker.Receptor-binding affinities for promethazine havebeen characterized as histaminic H1 > muscarinicM1 >> dopaminergic D2. Binding affinities forprochlorperazine have been characterized asdopaminergic D2 > histaminic H1 >> muscarinic M1.Compared with prochlorperazine, promethazinehas been characterized as having one sixteenth thebinding affinity for D2 receptors, 33 times the affini-

ty for H1 receptors, and 100 times the affinity formuscarinic receptors.17

There is minimal published information aboutthe binding affinities of trimethobenzamide, whichis a substituted benzamide. Its mechanism of actionis reportedly obscure, but trimethobenzamide isbelieved to affect the CTZ. In dogs trimethobenza-mide inhibits the emetic response to apomorphine,indicating activity in the area postrema. Trimetho-benzamide is apparently unable to block directneurotransmission to the vomiting center and pro-vides little or no inhibition of peripheral afferentemetic stimulus as evidenced by lack of protectionagainst copper sulfate, a gastric irritant.18

Prochlorperazine is a piperazine phenothiazineclassified as an antiemetic and antipsychotic.Although it has the same phenothiazine nucleus aspromethazine, its piperazine side chain distinguishesit pharmacologically from promethazine, making itmore specific in its activity. Its actions are mediatedprimarily through dopaminergic D2 blockade. Thisblockade at the CTZ accounts for its efficacy as anantiemetic. This pathway, however, also mediates themore undesirable side effects of these antiemetics.

Uses, Effects, and Side Effects of the AgentsPromethazine. As with each of these antiemet-

ics, the use and effects of promethazine are based

Table 1Guide to emetic receptor blockade

*Possible target receptor.Sources: Quigley EM, Hasler WL, Parkman HP. Gastroenterology 2001;120:263-286; Peroutka SJ, Snyder SH. Lancet 1982;1:658-659.

Site

Chemoreceptor trigger zone

Emetic center

Labyrinths

Peripheral afferents

Neuroanatomic Site

Area postrema

Nucleus tractus solitarius Nucleus ambiguousDorsal motor nucleus of the vagus

Lateral vestibular nucleus

Gastrointestinal tract

Clinical Stimuli

Cytotoxic drugsMetabolic disorders(dehydration) Bacterial toxins

Cytotoxic drugsMetabolic disorders(dehydration) Bacterial toxins

Motion sicknessInfection Meniere’s disease

Intestinal distentionGastric irritant

Target Receptor

Dopaminergic D2

Serotonergic 5-HT3

Histaminic H1

Cholinergic M1

Serotonergic 5-HT3

Histaminic H1

Cholinergic M1

Serotonergic 5-HT3

Histaminic* Cholinergic*

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on its mechanism of action. The antiemetic effectsof promethazine are primarily mediated throughcentral inhibition of histaminergic and possiblycholinergic pathways.17 As a phenothiazine, how-ever, promethazine also has central antiemeticeffects in the area postrema as a dopaminergic D2

antagonist.13 But its antidopaminergic effects areweak compared with its other effects and muchweaker than the antidopaminergic effects of theother agents.

As an antihistamine, promethazine is used inperennial and seasonal allergic rhinitis, allergicconjunctivitis, mild uncomplicated allergic skinmanifestations, and as adjunctive therapy in ana-phylactic reactions. As a sedative and antiemetic, itis indicated for preoperative, postoperative, orobstetric sedation and control of nausea and vom-iting associated with certain types of anesthesiaand surgery. The average effective dose for nauseaand vomiting in children or adults is 25 mg, orally,parenterally, or by rectal suppository.16 For nauseaand vomiting in children, the usual dose is 0.5 mg

per pound of body weight with adjustment forage, weight, and severity of vomiting. As needed,12.5-25 mg doses can be repeated every 4-6 hours.Use in children younger than 2 years of age is notrecommended.16

After oral administration, clinical effects areapparent within 20 minutes, and duration of activityis about 4-6 hours but may persist as long as 12hours. Absorption is normally faster through par-enteral administration, followed by oral, then sup-pository rectal administration. Pharmacokineticstudies are somewhat conflicting. One clinical trialcomparing two promethazine suppository formula-tions to an oral syrup formulation found no signifi-cant difference in time-to-peak serum concentration(tmax), peak serum concentration (Cmax), and areaunder the serum concentration versus time curve(AUC) between one of the suppository formulationsand the syrup formulation.19 Another more recentstudy found tmax of an oral syrup formulation to beapproximately 2 hours shorter than that of a suppos-itory formulation, whereas AUC was comparable.20

Table 2FDA-approved indications

Control of nausea and vomiting

Control of severe nausea and vomiting

Nausea and vomiting prevention in certain anesthesiaand surgery

Postoperative antiemetic

Preoperative, postoperative, and obstetric sedation

Sedation

Motion sickness

Allergic rhinitis

Vasomotor rhinitis

Allergic conjunctivitis

Mild, uncomplicated urticaria and angioedema

Blood or plasma allergic reactions

Dermographism

Anaphylactic reaction adjunctive therapy

Postoperative analgesic adjunct

Manifestations of psychotic disorders

Nonpsychotic anxiety

Promethazine

*

************

Trimethobenzamide

*Prochlorperazine

*

**

FDA = U.S. Food and Drug Administration.Sources: Phenergan [package insert]. Philadelphia, PA: Wyeth Laboratories; 2000; Tigan [package insert]. Bristol, TN: King Pharmaceuticals,Inc.; 2000; Compazine [package insert]. Philadelphia, PA: SmithKline Beecham Pharmaceuticals; 1999.

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Based on the pharmacologic profile of prometha-zine relative to prochlorperazine and trimethoben-zamide, antihistaminic side effects are of concern inits use as an antiemetic.17 Dry mouth, blurredvision, and general anticholinergic effects also canoccur. Patients with narrow-angle glaucoma, pro-static hypertrophy, and bladder neck obstructionshould be considered cautiously.

Promethazine has been cited for its relativelylow risk of adverse and extrapyramidal sideeffects.21 Although the risk of extrapyramidal anddystonic side effects is relatively low, they canoccur and should not be overlooked.22,23 Oculogyriccrisis, torticollis, and tongue protrusion are exam-ples of these side effects.

Trimethobenzamide. Trimethobenzamide is indi-cated only for control of nausea and vomiting. Itssuggested use is limited to treatment of prolongedvomiting of known etiology.18 Injectable trimetho-benzamide is contraindicated in children, as aresuppositories in premature babies or newborns.Trimethobenzamide is available in capsule, suppos-itory, and parenteral formulations, but the injectableformulation is intended for intramuscular use onlyand not recommended for intravenous use. Thesuppository dose in children who weigh less than30 lbs is 100 mg 3-4 times a day. In children 30-90lbs, the suppository dose is 100–200 mg 3-4 times aday. The adult suppository dose is 200 mg 3-4 timesa day. Capsule and injectable adult formulations aredosed at 200 mg 3-4 times a day.

Trimethobenzamide suppositories contain ben-zocaine. They are contraindicated in patients sensi-tive to benzocaine and any similar local anesthetics.Drowsiness is probably the most common sideeffect. Other possible CNS side effects includeextrapyramidal reactions (EPRs) and otherParkinson-like symptoms; however, these occur-rences are uncommon.

Prochlorperazine. The efficacy of prochlorper-azine as an antiemetic is mediated primarilythrough central blockade of dopaminergic D2

receptors in the CTZ. Its antihistaminic and anti-cholinergic effects are relatively weak. Pro-chlorperazine is indicated for use in controllingsevere nausea and vomiting, such as that associatedwith cytotoxic drugs, and is also indicated for man-agement and manifestation of psychotic disorders.24

Prochlorperazine is available in tablet, capsule,suppository, parenteral, and oral liquid formula-tions. Use in children younger than 2 years of ageor less than 20 lbs is not recommended. Dosage andfrequency of administration should be adjusted

individually based on response to therapy andsymptom severity. Weight-based dosages (20–85lbs) for oral or rectal administration for nausea andvomiting in children range from a one-time dose of2.5 mg to a total daily dose of 15 mg (5 mg, 3 timesa day). Adult antiemetic dosage recommendationsrange from one 5-mg oral tablet to one 25-mg sup-pository twice daily.24

Pharmacokinetic studies concerning prochlor-perazine are scarce. Oral absorption of prochlorper-azine is low and oral bioavailability is also lowaccording to two studies.25,26 Its terminal eliminationhalf-life has been reported as 8 hours (± 2 hours)after one oral dose.27

The more commonly encountered adverseeffects with prochlorperazine are those of the phe-nothiazines, including sedation, orthostatichypotension, and EPRs.13 Anticholinergic effects(eg, blurred vision) also occur, and patients withnarrow-angle glaucoma should also avoidprochlorperazine.

Particular care is emphasized in the use ofprochlorperazine because of its strength as adopamine D2 antagonist. The central blockade ofdopamine receptors is primarily responsible for itsmore serious side effects. EPRs presenting in a vari-ety of manifestations, including epiglottitis, menin-gitis, and psychiatric illness, have been associatedwith prochlorperazine.28-30 Motor restlessness, dys-tonias, pseudoparkinsonism, and tardive dyskine-sia also have been associated with this drug. Thepotential for EPRs outlasts the antiemetic effects ofprochlorperazine.21 The occurrence of neurolepticmalignant syndrome (NMS), a rare though poten-tially fatal symptom complex, also has been recog-nized as a possible side effect.24,31 NMS is difficult todiagnose and can present in various manifestationsincluding hyperpyrexia, muscle rigidity, alteredmental status, and autonomic instability.

References1. Practice parameter: the management of acute gastroenteri-

tis in young children. American Academy of Pediatrics,Provisional Committee on Quality Improvement. Pediatrics1996;97:424-435.

2. Centers for Disease Control and Prevention. The manage-ment of acute diarrhea in children: oral rehydration, main-tenance, and nutritional therapy. MMWR Morb MortalWkly Rep 1992;41:1-20.

3. Anonymous. The choice of antibacterial drugs. Med Letter2001;43:69-78.

4. American Academy of Pediatrics. Drugs for parasitic infec-tions. In: Pickering LK, ed. 2000 Red Book: Report of theCommittee on Infectious Diseases. 25th ed. Elk Grove Village,IL: American Academy of Pediatrics; 2000:693-725.

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5. Pickering LK. Therapy for diarrhea disease in children. In:Infections of the Gastrointestinal Tract. Blaser MJ, Smith PD,Raudin JI, Greenburg HB, Guerrant RL, eds. New York:Raven Press. In press.

6. Guerrant RL, Van Gilder T, Steiner TS, et al. Practiceguidelines for the management of infectious diarrhea. ClinInfect Dis 2001;32:331-351.

7. Szajewska H, Hoekstra JH, Sandhu B. Management ofacute gastroenteritis in Europe and the impact of the newrecommendations: a multicenter study. The WorkingGroup on Acute Diarrhoea of the European Society forPaediatric Gastroenterology, Hepatology, and Nutrition. JPediatr Gastroenterol Nutr 2000;30:522-527.

8. Elliott EJ, Backhouse JA, Leach JW. Pre-admission manage-ment of acute gastroenteritis. J Paediatr Child Health1996;32:18-21.

9. O’Loughlin EV, Notaras E, McCullough C, et al. Home-based management of children hospitalized with acutegastroenteritis. J Paediatr Child Health 1995;31;189-191.

10. Lee WS, Lee SP, Boey CC. Pre-admission management ofacute gastroenteritis in children: Too much or too little?Med J Malaysia 1999;54:22-25.

11. Kwon KT, Rudkin SE, Langdorf MI. Antiemetic use inpediatric gastroenteritis: national survey of prescribingpatterns of emergency physicians, pediatricians, and pedi-atric emergency physicians. Ann Emerg Med 2001;36(suppl):S29.

12. Davis WM. Pathophysiology and pharmacotherapy ofnausea and emesis. Drug Topics 1999;20:96-105.

13. Quigley EM, Hasler WL, Parkman HP. AGA technicalreview on nausea and vomiting. Gastroenterology2001;120:263-286.

14. Peroutka SJ, Snyder SH. Antiemetics: neurotransmitterreceptor binding predicts therapeutic actions. Lancet1982;1:658-659.

15. Cubeddu LX, Trujillo LM, Talmaciu I, et al. Antiemeticactivity of odansetron in acute gastroenteritis. AlimentPharmacol Ther 1997;11:185-191.

16. Phenergan [package insert]. Philadelphia, PA: WyethLaboratories; 2000.

17. Mitchelson F. Pharmacological agents affecting emesis. Areview (Part I). Drugs 1992;43:295-315.

18. Tigan [package insert]. Bristol, TN: King Pharmaceuticals,Inc.; 2000.

19. Stavchansky S, Wallace JE, Geary R, et al. Bioequivalenceand pharmacokinetic profile of promethazine hydrochlo-ride suppositories in humans. J Pharm Sci 1987;76:441-445.

20. Strenkoski-Nix LC, Ermer J, DeCleene S, et al.Pharmacokinetics of promethazine hydrochloride afteradministration of rectal suppositories and oral syrup tohealthy subjects. Am J Health Syst Pharm 2000;57:1499-1505.

21. Carey MJ, Aitken ME. Diverse effects of antiemetics in chil-dren. N Z Med J 1994;107:452-453.

22. DeGrandi T, Simon JE. Promethazine-induced dystonicreaction. Pediatr Emerg Care 1987;3:91-92.

23. Schwinghammer TL, Kroboth FJ, Juhl RP. Extrapyramidalreaction secondary to oral promethazine. Clin Pharm1984;3:83-85.

24. Compazine [package insert]. Philadelphia, PA: SmithKlineBeecham Pharmaceuticals; 1999.

25. Isah AO, Rawlins MD, Bateman DN. The pharmacokinet-ics and effects of prochlorperazine in elderly female volun-teers. Age Ageing 1992;21:27-31.

26. Taylor WB, Bateman DN. Preliminary studies of the phar-macokinetics and pharmacodynamics of prochlorperazinein healthy volunteers. Br J Clin Pharmacol 1987;23:137-142.

27. Isah AO, Rawlins MD, Bateman DN. Clinical pharmacolo-gy of prochlorperazine in healthy young males. Br J ClinPharmacol 1991;32:677-684.

28. Luetzow TJ. Complications in the use of prochlorperazine.Wis Med J 1991;90:64-65.

29. Muniz AE. Prochlorperazine-induced extrapyramidaleffects mimicking meningitis in a child. South Med J 2000;93:629-630.

30. Rodgers C. Extrapyramidal side effects of antiemetics pre-senting as psychiatric illness. Gen Hosp Psychiatry 1992;14:192-195.

31. Pesola GR, Quinto C. Prochlorperazine-induced neurolep-tic malignant syndrome. J Emerg Med 1996;14:727-729.

Case study 1: Gastroenteritis of unknown etiology

Aziz K. Ibrahim, MD, FAAP, MRCP, DCH,who practices pediatric medicine in the suburbs ofLittle Rock, Arkansas, presented the first case. Hediscussed a 21/2-year-old boy who presented witha 2-day history of nausea and vomiting, havingvomited four times with two loose bowel move-ments the morning before the office visit. Thevomitus was negative for blood, mucus, and bile;stool was loose, green, and foul smelling with noobvious blood or mucus. The patient was lethargicwith a temperature of 101ºF, intolerant of fluid orfood, with urinary output slightly decreased.Capillary refill time was less than 3 seconds. Thepatient’s weight was 35 lbs. He was alert, had drylips, moist mucous membranes, and normal skinturgor. Mild, generalized intermittent abdominalpain was evident; the abdomen was soft, not dis-tended or tender, and bowels were slightly hyper-

active. Central nervous system assessment wasnormal.

On the first day of symptoms, the mother hadgiven the child promethazine that remained from aprevious illness and taken him to the emergencydepartment, where he was diagnosed with a viralinfection. Dr. Ibrahim estimated dehydration atapproximately 1%-2%, and started the patient onpromethazine 12.5 mg suppositories, instructingthe mother to continue with that every 4 hours for12-24 hours, then as needed for 24 hours. Heinstructed the mother to provide appropriate liq-uids, things the boy liked such as popsicles orPedialyte (oral electrolyte maintenance solution)freezer pops. Dr. Ibrahim recommended startingthe BRAT (bananas, rice, applesauce, toast) dietafter 24 hours and return to a normal diet after 72hours, excluding dairy products and juice for 3days. If vomiting continued, urination decreased,or lethargy became evident, Dr. Ibrahim recom-mended returning the patient for further assess-ment and treatment. The patient was followed bytelephone within 48 hours. Vomiting had stopped.He continued to have an occasional loose stool, butfull recovery was imminent.

A possibly slow return to age-appropriate dietwas commented on by Warren A. Daniel, Jr., MD, afamily practitioner from West Monroe, Louisiana,who, in appreciation of differing perspectives,asked Dr. Ibrahim to explain his point of view. Notconforming with established guidelines, treatmentof this case was discussed in light of the fact thatthe American Academy of Pediatrics (AAP) nowstates that 80% or more of children with acute diar-rhea can tolerate full-strength milk safely and thatfor children who require rehydration, age-appro-priate diet should be given once the patient hasbeen rehydrated.1

Under the circumstances of this case, Dr.Ibrahim felt the benefits of early refeeding did notoutweigh the potential risk for further dehydration.As he explained, the AAP refeeding guidelines arebased on studies of the enterocyte—the major cellin the gastrointestinal lining—and infection-

Case Studies

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The following is a synopsis of the June 2001Atlanta Antiemetic Roundtable, a discussionamong several leading physicians practicingin the southern United States, an area knownfor its high incidence of gastroenteritis. Thephysicians have family, pediatric, and geriatricpractice experience averaging 20 years perpractitioner.

These highlights focus on actual cases treat-ed by the physicians. They also reflect the doc-tors’ thoughts on topics relevant to gastroen-teritis treatment as expressed throughout theroundtable. Treatment decisions and opinionsexpressed are those of the physicians, and arenot intended to support or refute those of anyprofessional standard, association, or sponsor.

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induced reductions in brush-border lactase levelsassociated with diarrhea. Vomiting, in this case,was a primary concern in the patient’s dehydration.He further stated that although some viruses affectthe villous border more than others, cautionregarding reintroduction to regular diet might ben-efit some patients in some instances. The patientwas at risk for mild dehydration and had notdemonstrated tolerance of either fluid or food, fur-ther complicating any estimation of the timerequired to achieve rehydration. Although viral eti-ology was suspect, the causative agent wasunknown.

From LaFayette, Georgia, George P. Shaw, Jr.,MD, DABFP, a family practitioner, speculated onthe tendency of milk to cause mucus formation andany role this might play in returning a patient to anormal diet. The topic of aspiration was also intro-duced. Concern for quality-of-care issues wasreflected in statements from all participants. Inyoung households in which siblings are not con-cerned about each other’s health and several chil-dren vie for parental attention, physiciansexpressed concern about the potential effects ofvomiting, diarrhea, and dehydration, and whetherthe patient receives appropriate care. It wasexpressed that these households reflect a day careenvironment as they increase in size.

Thomas C. Joseph, MD, of Camden, SouthCarolina, introduced the topic of viral transmission.He discussed the possibility of entire householdsbecoming infected. Parents and caregivers, heasserted, should be advised that diarrhea may last3-5 days, hands should be washed after diaper han-dling, and these viruses are highly transmittable.

The patient assessment regarding current med-ications and the possible effects on gastrointestinalmotility was raised. Specifically, the common use ofcodeine-containing medications and the dangers ofantimotility effects were discussed. Possible fluidpooling, further gastrointestinal irritation, and fur-ther cause for vomiting were mentioned as adverseeffects of codeine-containing medications, whichcould exacerbate gastroenteritis symptoms.

Question about dosage form. Dr. Daniel asked ifthere were specific reasons for the use of the sup-pository in this patient. According to Dr. Ibrahim,in this case it is less painful than an injection, andwith significant risk of dehydration, you havegreater assurance of accurate dosing and treatmentsuccess than with the oral formulation. Cessation ofvomiting cannot be guaranteed, and the use of oralformulations in the presence of vomiting always

raises dosing and absorption issues.Dr. Daniel, who discussed the strengths avail-

able, raised other practical issues concerningdosage form. He emphasized that when pharmacydispensing is involved, promethazine suppositoriesof different strength are easily distinguished by dif-ferent colored foil wrapping. The syrup, availablein two strengths, is typically poured from the origi-nal bottle by the pharmacist. Its strength is thus lesseasily distinguished once poured.

Case study 2: Gastroenteritis and concomitantconditions

Forrest A. Eisenrich, MD, of Comanche, Texas,presented to the roundtable a case in which asth-ma, a common childhood condition, and neurofi-bromatosis were concomitant with the presenta-tion of gastroenteritis. Dr. Eisenrich described a2-year-old girl with a 2-day history of nausea,vomiting, and temperature of 102.6ºF. Her diaperhad been dry for the past 12 hours and repeatedvomiting and dry heaving were reported. Duringthe past 24 hours she had had only two tan-to-clearwatery stools. She was liquid intolerant, becomingprogressively sleepier with episodic awakeningand crying. She weighed 30 lbs. Her physical find-ings were consistent with mild dehydration.Capillary refill time was normal but mucous mem-branes were slightly dry. Her medications includ-ed gabapentin for neurofibromatosis and albuterol,salmeterol, fluticasone, and montelukast for asth-ma. Her mother had given her a 12.5-mg prometh-azine suppository (on hand from a previous ill-ness) 2 hours before examination by Dr. Eisenrich.There had been no significant response to thepromethazine suppository. Laboratory work wasdone as a precaution because of her comorbid con-ditions and was basically within normal limits,showing no electrolyte abnormalities, slightly ele-vated urine specific gravity, and large ketones inthe urine. Dr. Eisenrich admitted the patient to theemergency department for rehydration with nor-mal saline at about 100 mL/hr for 4 hours. He alsoprescribed a 100-mg trimethobenzamide supposi-tory. Before leaving the emergency department,she drank 6 ounces of Pedialyte. She was senthome with trimethobenzamide suppositories andhad two more episodes of vomiting over the next12 hours, then stabilized.

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It was suggested that this was a typical viralinfection such as those encountered in day care set-tings. The patient’s home environment, however,again drew attention to the day care environmentand quality-of-care issues. Two other family mem-bers in the previous 5 days had been ill with similarsymptoms. All of the patient’s siblings, accordingto Dr. Eisenrich, suffered from chronic allergies andfrequent upper respiratory infections. Parentingand quality-of-care issues frequently concern Dr.Eisenrich and often proliferate and exacerbate ill-ness in his area of practice.

Further concern, expressed by Dr. Daniel,addressed this patient’s slightly elevated tempera-ture and white blood cell count, possibly suggestiveof etiology other than common rotavirus. A num-ber of confounding factors contributed to the deci-sion to hospitalize and intravenously rehydrate thispatient. Those factors included unknown etiologyof disease; concomitant conditions; lack of urina-tion in 12 hours yet no electrolyte abnormalities;and lack of response to antiemetic therapy.

Dehydration and the dilemmas of communitypractice. The roundtable physicians openly sharedconcerns about current insurance and related eco-nomic conditions that restrict their practices. Dr.Shaw lamented the economic infeasibility of run-ning a private practice–based laboratory. It is virtu-ally impossible to draw a sample for electrolytesand get results in less than 12 hours because thesample must be analyzed at an outside laboratory.This 12-hour time frame, according to Dr. Shaw, issignificant. In agreement, Dr. Ibrahim added thatin private practice, these temporal windowsbecome more significant with the youth of thepatient.

An associate of Dr. Ibrahim, Carla J. Anderson,MD, remarked on the effects of intravenous (IV)hydration therapy on gastroenteritis symptoms.Her reported experience in resolving gastroenteri-tis symptoms with IV therapy in dehydrated adultpatients is that IV hydration works most impres-sively. Dr. Shaw characterized this response to IVhydration therapy as classic. He shared anecdotalaccounts of adult patients who, with uncontrol-lable nausea and vomiting, realized they needed tobe hospitalized. On initiation of IV hydration ther-apy, he related, it is not unusual for these patientsto report full recovery and a desire to return homeafter only 4 hours. Dr. Shaw expressed his opinionthat rehydration therapy plays the most significantrole in gastroenteritis treatment. This point wasfurther reinforced by Dr. Ibrahim’s affirmation that

once beyond a critical point, only IV hydrationtherapy would reverse symptoms of serious dehy-dration.

Antiemetic therapy in community practice.Further discussion drew the roundtable partici-pants toward defining the role of antiemetics in thetreatment of nausea and vomiting associated withviral gastroenteritis and gastroenteritis of unknowncauses. Dehydration, it was agreed, poses the great-est health risk in gastroenteritis. Although rehydra-tion was considered the primary therapy for dehy-dration, antiemetics were seen as maintaining astrong adjunctive position. Without contention, thephysicians agreed that maintaining hydration andpreventing dehydration justified antiemetic use if,in their opinions, potential benefits outweighedpotential risks, and clinical and patient-specificquality of care had been considered. Maintainingthe patient in an outpatient setting was of primaryimportance to the roundtable panel.

Case study 3: Acute gastroenteritis in a middle-aged adult

A 56-year-old man presented at Dr. Anderson’soffice with a 1-week history of malaise, fever, chills,and muscle aches. The symptoms were initiallyinsidious, then imminent. The patient had nauseaand vomiting 1 day before having diarrhea. Stoolswere nearly liquid, more than six per day, and weremalodorous to him. He had no bright red blood perrectum, no tarry black stools, and some cramping,and water was vomited within an hour of con-sumption. The patient’s pulse rate was 90 and regu-lar, his temperature was subnormal, and bloodpressure was slightly elevated. He appeared toxicand had poor skin turgor. There was no upper orlower right quadrant pain, and no rebound; hisabdomen was soft without localized tenderness.Laboratory analysis revealed clear urinalysis, bloodsugar of 119 mg/dL, normal amylase, normal liverfunction, and normal electrolytes. His white bloodcell count was 6.2. Viral gastroenteritis was suspect-ed. Mild dehydration was assessed with greaterrisk if nausea and vomiting continued. Mild ileussecondary to gastroenteritis was also assessed.

Several roundtable participants commented onthe severity of symptoms exhibited by this patient.Dr. Anderson, unwilling to rule out a gallbladderproblem, did an ultrasound within the week; the

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findings were negative. Patient assessmentrevealed recent travel to New York and exposure toa wide variety of foreign foods. Because this greatlybroadened the potential etiology, the possible pres-ence of bacterial and other pathogens and prescrip-tion of an antibiotic while awaiting stool cultureresults were discussed.

The use of antibiotics in gastroenteritis, accord-ing to Dr. Ibrahim, is very controversial, even inbacterial gastroenteritis. He specifically discussedlack of response to treatment as an issue, statingthat only a day’s time in fever and diarrhea issaved, even with bacterial colitis. The issue ofincreased bacterial resistance in light of minimalbenefit was also discussed.

Disinclined toward immediate, more aggressivetreatment, the patient agreed to an intramuscularinjection of promethazine 50 mg and suppositoriesself-administered once every 4-6 hours as needed athome. Dr. Anderson instructed him to return thenext morning for reassessment. He was adminis-tered IV rehydration therapy on his return, towhich he responded quickly.

Case study 4: Gastroenteritis and irritablebowel syndrome

Dr. Daniel presented a complicated case involv-ing concomitant chronic irritable bowel syndrome(IBS) and a history of narcotic abuse. A 52-year-oldwoman came to his office with a 2-day history ofnausea, vomiting, and diarrhea. She complained ofabdominal discomfort and appeared slightly dehy-drated, with a very slight decrease in skin turgor.

She had general abdominal discomfort and hyper-active bowel sounds. Several abdominal surgerieshad resulted in a number of adhesions and severalsurgeries to lyse the adhesions. Bowel obstructionwas a consideration. Symptoms suggested simplegastroenteritis; however, the patient’s history withhydration problems warranted further investiga-tion. Laboratory work was performed. Her com-plete blood cell count showed a slight viral shift;stool culture was negative. She was within 3-5 lbsof her normal weight.

This patient’s history included a major workupin a university setting in Memphis to further evalu-ate her IBS. As a result, she had an infusion port,through which she infused herself nightly for diar-rhea-induced dehydration. Some of her more seri-ous symptoms had since resolved, and the patientwas no longer rehydrating intravenously.

In this case, Dr. Daniel’s interest was achievinggood hydration and intervening early to preventdehydration. Because promethazine 50-mg suppos-itories had been a mainstay of treating IBS flares, heelected this therapy again. The patient’s history ofnarcotic dependence was also an efficacy consider-ation in selecting the higher-than-normal strength.Dr. Ibrahim’s general impression regardingstrength and dose was that the indicated 25-mgdose works quite well. The patient’s vomitingresolved within the day of therapy; she was able torehydrate without complication.

Reference

1. American Academy of Pediatrics, Provisional Committeeon Quality Improvement, Subcommittee on AcuteGastroenteritis. Practice parameter: the management ofacute gastroenteritis in young children. Pediatrics1996;97:424-435.