Pediatric Dehydration

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Pediatric Dehydration. Marc Francis FRCPC Emergency R4 PEM Fellow year 1 Preceptor – Dr Phil Ukrainetz. Objectives. Background to dehydration, diarrhea and vomiting Approach to the dehydrated patient Case based review of the evidence for the above approach A sodium review (sorry!!!) - PowerPoint PPT Presentation

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Pediatric DehydrationMarc FrancisFRCPC Emergency R4PEM Fellow year 1

Preceptor – Dr Phil Ukrainetz

Objectives• Background to dehydration, diarrhea

and vomiting• Approach to the dehydrated patient• Case based review of the evidence

for the above approach• A sodium review (sorry!!!)• Series of practical cases to enforce

your new evidence based approach

Pediatric Dehydration• Questions,

discussion and random humour to be inserted by Dr Ukrainetz

Why is this a peds problem?

• Sick kids = decreased intake

• Higher percentage TBW

• Neonate 75%• Child 65%• Adult 60%

• Fever increases fluid needs

• Higher metabolic rate in kids

• less tolerance to fluid and electrolyte changes

• Poor renal concentration mechanisms at young age

Dehydration is not a disease

1) Decreased intake2) Increased output

– Insensible losses– Renal losses– GI losses

3) Translocation– Burns– Ascites

Causes of Dehydration• Diarrhea• Vomiting• Gastroenteritis• Stomatitis or

pharyngitis• Febrile illness• DKA• DI• Burns

Diarrhea• Leading cause of death worldwide in

children < 4yo• Diarrhea in the United States

• 300 children < 5yo die per year• 2-3 million office visits• 200,000 hospitalizations

• In North America • children < 5yo have on average 2 episodes

of gastroenteritis per year• Costs > 2 billion/year

Diarrhea• DDx

– Gastroenteritis– Malabsorption– IBD– IBS– Drug side effects– Thyrotoxicosis– Infections– Endocrine disorders

Diarrhea• Indications for

stool studies– Toxic appearance– Immunocompromised– Bloody or invasive– Duration > 5days– Suspected parasites

• Travel• Camping• Poor Water

• Etiology– Viral 60%– Bacterial 20%– Parasites 5%– Parental illness 10%– Unknown 10%

Vomiting

“Vomiting without diarrhea should prompt a thorough search for another cause other than gastro”

Vomiting• GI

– Obstruction– Pancreatitis– Appy– Pyloric stenosis– Volvulus– Intussusseption

• GU– UTI– Pyelo– RTA

• Toxic– Drug ingestion– Drug side effects

• ID– Pneumonia– Sepsis

• Endocrine– Addisons– CAH

• Neuro– Meningitis/Encephalitis– ↑ ICP

Case #1• 5 mo Male• HPI

– Non-bloody profuse watery stool 7 days– 10-15 stools per day – foul smelling– Child eager to take water until this AM– Now less interested in drinking and more

lethargic• Exam

– Quiet and tachypneic– Sunken eyes and a dry mouth– Tachycardic at 165 bpm– Cap refill is 3 seconds– Skin turgor prolonged

Case #1• How do you want to manage this

patient?• What are some of the potential

pitfalls in managing this patient?• Do you have an approach to this

patient?• Would you like one?

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

The gospel according to Rob Hall

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Initial Resuscitation• ABCs• Initial fluid bolus

• 20cc/kg of NS or Ringers• Appropriate in all types of dehydration• Reassess q5mins and repeat x 3

• Initial hypoglycemia• 5cc/kg of D10W in infants• 2cc/kg of D25W in children

• Think about Shock DDx if unresponsive to 3 attempts at NS bolus

Initial Resuscitation• Fluid Controversy…

– Theoretical risk of acidosis with NS• “Dilutional acidosis” with addition of NaCl to

the extracellular fluid– Ringers lactate has some HCO3

• Harder to find in our department• Potential delay in fluid resuscitation

– No evidence to guide you

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Case #2• 20 mo F• HPI

– 2 days of vomiting and diarrhea– Not eating and will not drink– 8 stools today but dad does not think there

were any diapers with urine in them– Afebrile

• Exam– Appears mildly ill– Tears +– Vitals are normal including RR– Mouth is Dry– Cap Refill time is 2.0 seconds

Survey• How dehydrated is

this child?3-5%6-9%>10%

• Who wants to do bloodwork?

• Who wants to start an IV to rehydrate?

Determine % Dehydration

• The CPS, AAP, CDC and WHO all have treatment guidelines for gastroenteritis

• These are based on the clinical assessment of dehydration

• Mild <5%, Moderate 6-9%, Severe >10%• Gold standard is pre and post weight• What are the markers that we use to assess

this?• Clinical• Laboratory

• How reliable and precise are these markers?

Determine % Dehydration

What are the best clinical markers?

• Prolonged cap refill• Sunken eyes• Poor overall appearance• Sunken fontanelle• Absent tears• Increased HR• Weak Pulse• Dry mucous membranes• Abnormal resp pattern• Abnormal skin turgor or tenting

Tenting

• Systematic review• precision and accuracy of symptoms, signs

and lab tests for evaluating pediatric dehydration ≥ 5%

• 1603 potential articles• 26 contained the original data

required• 13 were eliminated due to lack of

diagnostic standard or limited study design

• Results– Large variability in observations and elicited

signs– Ranging from chance to good agreement

• Conclusions– Tests are imprecise with only fair to

moderate agreement– The best 3 individual examination signs

were: •Prolonged Cap refill time•Abnormal Skin turgor•Abnormal resp pattern

Validity and reliability of clinical signs in the diagnosis of dehydration in

childrenGorelick MH, et al. Pediatrics 1997;99:E6• Prospective cohort study

• Urban pediatric hospital ED• N= 186 children

• Age range 1 month to 5 years• With diarrhea, vomiting, or poor oral fluid intake• admitted or followed as outpatients

• The diagnostic standard for dehydration was fluid deficit as determined from serial weight gain after treatment

Validity and reliability of clinical signs in the diagnosis of dehydration in

childrenGorelick MH, et al. Pediatrics 1997;99:E6

• All children were evaluated for 10 clinical signs before treatment

• Decreased skin turgor• Cap refill time >2 sec• General appearance• Absence of tears• Abnormal respirations• Dry MM• Sunken eyes• Abnormal radial pulse• Tachycardia >150bpm• Decreased urine

output

Validity and reliability of clinical signs in the diagnosis of dehydration in

childrenGorelick MH, et al. Pediatrics 1997;99:E6• Results

– 63 children (34%) had dehydration• defined as a deficit of 5% or more of body

weight– At this deficit, clinical signs were already

apparent (median = 5)– Individual findings had generally low

sensitivity and high specificity– parent report of decreased urine output

was sensitive but not specific

Validity and reliability of clinical signs in the diagnosis of dehydration in

childrenGorelick MH, et al. Pediatrics 1997;99:E6• Results:

– For detection of ≥ 5% dehydration• Presence of 3 or more signs

Sensitivity of 87%Specificity of 82%Positive LR of 4.9 (3.3-7.2)

• Presence of 7 or more signsPositive LR 8.4 (5.0-14.3)

Validity and reliability of clinical signs in the diagnosis of dehydration in

childrenGorelick MH, et al. Pediatrics 1997;99:E6• Further logistic regression analysis

showed most of the predictive power was in the following 4 signs

1) Prolonged cap refill2) Dry MM3) Absence of tears4) Abnormal appearance

• 2/4 had positive LR of 6.1 (3.8-9.8)

Validity and reliability of clinical signs in the diagnosis of dehydration in

childrenGorelick MH, et al. Pediatrics 1997;99:E6• Conclusions

– Conventionally used clinical signs of dehydration are valid and reliable

– Individual findings lack sensitivity – Diagnosis of clinically important

dehydration should require at least three clinical findings

Case #3• You see a 17 month

old child with a 3 day history of non-bloody D/V

• Your clinical assessment is that he is only mildly dehydrated

• You discover the CC has sent bloodwork prior to your arrival:

ABG 7.34/33/84/17Na 133Cl 103K 3.5Cr 34BUN 4.2 mmol/L

Determine % Dehydration

• Does lab work help you in determining the degree of dehydration?

• What lab values do people use to assess severity of dehydration?

• Results

• Conclusions•Tests such as BUN and bicarbonate

are only helpful when results are markedly abnormal

•A normal bicarbonate concentration reduces the likelihood of dehydration

•No lab test should be considered definitive for dehydration

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Case #4• 6 day old Female

• First child born at term• GBS negative mother• Normal preg and delivery D/C’d within 24 hrs• Exclusively breastfed

• HPI• Mom says child is a “poor feeder” • Not sure if her breastmilk has come in fully• Child much more listless today • Having to wake to feed• No urine output or stools noted in the last

48hrs

Case #4 con’t• Exam

• Vitals = HR 160, RR 38, T36.9°C, Sats 94%, BG4.1

• Generally – difficult to rouse but irritable upon awakening

• CVS – normal pulse and cap refill • Resp – clear• Hydration – MM dry, no tears noted, skin is

noted to be very soft and doughy

Case #4 con’tLabs• CBC

– WBC 4.8– Hgb 179– Plt 433

• Lytes– Na 167 – K 6.8– Cl 132– Bicarb 16

• BUN = 7mmol/L• Creatinine = 90umol/L

• What type of dehydration is this?

• What is the most likely cause?

Define the type of dehydration• Three major classes of dehydration

based on relative losses of Na and Water

1) Isonatremic dehydration (80%)2) Hypernatremic dehydration (15%)3) Hyponatremic dehydration (5%)

Thanks to Rob Hall for any details

Body FluidsICF (mEq/L) ECF (mEq/L)

• Sodium 20 135-145• Potassium 150 3-5 • Chloride --- 98-110• Bicarbonate 10 20-25• Phosphate 110-115 5• Protein 75 10

Isonatremic dehydration• By far the most common• Equal losses of Na and Water• Na = 130-150• No significant change between fluid

compartments • No need to correct slowly

Hypernatremic Dehydration

• Water loss > sodium loss• Na >150mmol/L• Water shifts from ICF to ECF• Child appears relatively less ill

• More intravascular volume• Less physical signs• Alternating between lethargy and

hyperirritability

Hypernatremic Dehydration

• Physical findings– Dry doughy skin– Increased muscle tone

• Correction– Correct Na slowly– If lowered to quickly causes

•massive cerebral edema• intractable seizures

Hyponatremic Dehydration

• Sodium loss > Water loss• Na <130mmol/L• Water shifts from ECF to ICF• Child appears relatively more ill

• Less intravascular volume• More clinical signs• Cerebral edema• Seizure and Coma with Na <120

Hyponatremic Dehydration

• Correction– Must again be performed slowly unless

actively seizing– Rapid correction of chronic hyponatremia

thought to contribute to….Central Pontine Myelinolysis

• Fluctuating LOC• Pseudobulbar palsy • Quadraparesis

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Case #4• 18 mo M

• previously heatlhy• HPI

• Diarrhea and vomiting for 3 days • Mom says stools are liquid and foul smelling

with no mucous or blood• 6 episodes of diarrhea and 4 episodes of

vomiting per day • not feeding well and activity level ↓• He seems weak and tired• Decreased number of wet diapers

Case cont• Exam

• VS = T 37.0, P 110, RR 25, BP 100/75, 11.3 kg• Generally: alert, crying, looks tired• HEENT: minimal tears, lips dry, mucous

membranes tacky• CVS: mild tachycardia, no murmurs• RESP: clear, no distress• ABDO: flat, soft, and non-tender with

hyperactive bowel sounds• Hydration: capillary refill time is 2-3 seconds

and his skin turgor is slightly diminished

Determine the type and rate of rehydration fluids

• Oral Rehydration Therapy (ORT) vs Intravenous therapy (IVT)

“ To poke or not to poke, that is the question”

ORT• Oral rehydration therapy

• Appropriate for mild to moderate dehydration• Safer• Less costly• Administered in various clinical settings

• Fluid replacement should be over 3-4hrs

• 50ml/kg for mild dehydration• 100ml/kg for moderate dehydration

• 10ml/kg for each episode of vomiting or watery diarrhea

ORT• Contraindications to ORT

• Severe dehydration (≥10%)• Ileus or intestinal obstruction• Unable to tolerate (Persistent vomiting)• Signs of shock• Decreased LOC or unconscious• Unclear diagnosis• Psychosocial situations

ORS• Oral rehydration solutions contain

• 45-90 mmol/L Na• 74-140 mmol/L glucose

• Commercial preparations• Pedialyte• Infalyte• Rehydralyte• WHO rehydration salts

Oral rehydration solutions (ORS)

 OsmolesmOsm/L

Glucosemmol/L

NamEq/L

ClmEq/L

HCO3mEq/L

KmEq/L

WHO formulation 330 110 90 80 30 20Pedialyte 270 140 45 35 30 20

AJ 730 690 5 x x 32Sports drink 330 255 20  x 3 3D5W / 0.45% saline 454 300 77 77 0 0

ORT

“Show me the evidence!!!”

• Objective– To test the hypothesis that the failure rate of

ORT would not be more than 5% greater than that of IVT

• RCT– Non-inferiority study design– N=73 pts

• ED based study– Children 8 weeks to 3 years old– Moderate dehydration on validated scale– With viral gastroenteritis

• Methods– Patients were randomized to receive either ORT

or IVT during the 4-hour study– Treating physicians were blinded– Patients were assessed before randomization

and at 2 and 4 hours of therapy– Successful rehydration at 4 hours was defined as

• resolution of moderate dehydration• production of urine• weight gain• absence of severe emesis (>5 mL/kg).

• Results:– Half of both the ORT and IVF groups were

rehydrated successfully at 4 hours with no statistical differences

• Results:– The time required to initiate therapy was less in the ORT

group– Less than one third of the ORT group required

hospitalization, whereas almost half of the IVF group was hospitalized

– No difference in parental preference of therapy

Oral versus intravenous rehydration for treating dehydration due to gastroenteritis in children

Hartling, L. et al. Cochrane Database of Systematic Reviews. 4, 2006

• RCTs comparing IVT with ORT in children up to 18 yo with gastroenteritis

• 17 trials of poor to moderate quality were included

• N = 1811 pts• Six deaths occurred in the IVT group and

two in the ORT groups (4 trials)

Oral versus intravenous rehydration for treating dehydration due to gastroenteritis in children

Hartling, L. et al. Cochrane Database of Systematic Reviews. 4, 2006• Results:– No clinically important differences

between ORT and IVT groups• ORT group did have a higher risk of paralytic

ileus• The IVT group was exposed to risks of

intravenous therapy • For every 25 children (95% CI 14 to 100)

treated with ORT one would fail and require IVT

Case Continued• You institute a strict regiment of ORT

therapy using Pedialyte• Mom says every time he takes the

fluids he vomits within a few minutes!!!

• What do you tell her?• What are your options now?

NGT???• Is there a role for nasal gastric tube

oral rehydration?

• Recent UK evidence based guidelines indicate

• When caregivers are unwilling to perform ORT or when it is required overnight continuous nasogastric tube infusion is preferred over intravenous infusion

• Level V evidence

When to start feeding again?

Case #4• 9 month old Male

• Previously healthy • Weight 10kg

• 5 day hx of severe diarrhea with intermittent vomiting

• Mother says stool like liquid• Has been aggressively rehydrating him with water at

home• Today is much more lethargic and difficult to rouse• By ambulance to the ED

Case #4• Exam

• Vitals = HR 172, RR 41, BP 65/40, Temp 37.2,

• Child is minimally responsive to pain• He is Tachycardic and Tachypneic• Cap refill time is >3 seconds• As you are examining him he begins to have

a seizure• What do you want to do now?• Investigations?• Cap gas comes back and the patients

sodium is 115

Severe Dehydration• Management of severe dehydration

requires IV fluids• Fluid selection and rate should be

dictated by • The type of dehydration• The serum Na• Clinical findings

• Aggressive IV NS bolus remains the mainstay of early intervention in all subtypes

Isonatremic Dehydration• Calculate the fluid deficit

•Deficit (cc’s) = % dehydration x body wt• D5½NS is fluid of choice• (½ deficit – the bolus) over the first 8hrs

• Add maintenance and any ongoing losses to above

• Further ½ the deficit replaced over the next 16hrs• Monitor electrolytes and U/O

Hypernatremic Dehydration

• Fluid deficit =(Current Na/Desired Na – 1) x 0.6 x body wt• Replace with D50.2%NS• Replace over 48hrs• Reduce sodium by no more than 10mEq/L/24hrs

• (½ deficit – the bolus) over the first 24hrs– Add maintenance and any ongoing losses to above– Further ½ the deficit replaced over the next 24hrs

Hyponatremic dehydration

• Na deficit =(Nadesired- Nacurrent) x 0.6 x Weight (kg)

• Divide above by Na in mEq/L within the replacement fluid

• 154 mEq in NS• 77 mEq in D5½ NS • 513 in 3% saline

• divide by deficit x 2 to determine rate at 0.5mEq/L/hr

Hyponatremic Dehydration

• If seizing • Correct with 3% Saline bolus• Target a Na of 120• Further correction beyond this with D5½ NS

• If not Seizing• Correct with D5½ NS • Target a Na of 130

• Watch for Central Pontine Myelinolysis• More likely in chronic hypo-Na with less Sx• Correct slowly at rate of 0.5mEq/L/hr

Back to our case• Exam

• Vitals = HR 172, RR 41, BP 65/40, Temp 37.2, • Child is minimally responsive to pain• He is Tachycardic and Tachypneic• Cap refill time is 5 seconds• Fontanelle and eyes are sunken• As you are examining him he begins to have a seizure

• What do you want to do now?• Investigations?• Cap gas comes back and the patients sodium is

115!!!

Case cont• Initial bolus

• 20cc/kg of NS• Seizing

• Correct Na to 120 with 3% saline bolus• (120 – 115) x 0.6 x 10kg = 30mEq• 30mEq ÷ 513mEq/L = 58cc bolus

• Further correction after above• Correct Na to 130 with D5½ NS• (130-120) x 0.6 x 10kg = 60mEq• 60mEq ÷ 77mEq/L = 780cc• 780 ÷ (10 x 2) = 39cc/hr to correct at 0.5mEq/L/hr

Want to make life easier?

• http://www.medcalc.com/pedifen.html

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Final considerations• Does and Acid-Base Deficit exist?

• Does a potassium disturbance exist?

• What is the patients renal function?

Does and Acid-Base Deficit exist?

• Acidosis• Lactate• Ketones• Loss of Bicarb in diarrhea

• Most will resolve with simple rehydration

• Consider HCO3 for pH<7.0• Controversial

Does a potassium disturbance exist?

• K+ losses• GI• Renal

• Remember that K shifts with acidosis and certain therapies

• Always insure renal function prior to IV replacement

What is the patients renal function?

• Asses for underlying renal dysfuction

• Pre-renal vs renal failure

• Renal dysfuction• Fluid overload• Hyperkalemia• Need for Dialysis?• Nephro consultation

Rapid Fire Cases

Feel free to use the new approach

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Answers• Initial resuscitation

• deferred• % dehydration

• 5-9%• moderate

• Dehydration Type• Likely Isonatremic

• Rehydration fluids• ORT• Pedialyte

• Rate and volumes• Moderate

dehydration 100cc/kg = 1400cc

• Replace over 3-4hrs• Further 10cc/kg with

ongoing losses• Final

considerations• None

Case• 8mo M (8kg)• 4 day hx of severe

diarrhea and vomiting– No further ongoing

losses

• Exam • Limp and cold• Mottled with weak

rapid pulse• Sunken eyes and

fontanelle• Cap refill 5s• Tenting of skin

• LabsNa = 170K = 3.1HCO3 = 18

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Answers• Initial resuscitation

• 160cc NS bolus• % dehydration

• >10%• Severe

• Dehydration Type• Hypernatremic

• Rehydration fluids• IV fluids• D50.2NS

• Rate and volumes• Volume deficit =

640cc• Correct slowly over

48hrs• 39cc/hr over first

24hrs• 45cc/hr over next

24hrs• Final considerations

• Add 20 mEq K to IV fluids

Case• 16mo F• 3 day Hx of vomiting and diarrhea

• Tolerating fluids not solids• Good u/o

• Exam • Appears well with normal vitals• Tears + • MM moist• Cap refill <2s• Skin turgor normal

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Answers

Send this kid home!!!

Case• 2 yo M (16kg)• 4 day Hx of vomiting

and diarrhea• Exam

• Appears drowsy but not lethargic

• Good tone• Tachycardiac and

tachypneic• BP normal• Very Dry MM• Cap refill 3s

• LabsNa = 134K = 3.1HCO3 = 16

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Answers• Initial resuscitation

• 320cc of NS• % dehydration

• >10%• Severe

• Dehydration Type• Isonatremic

• Rehydration fluids• D5½ NS

• Rate and volumes• Volume deficit =

10% x 16kg= 1600mls

• 110cc/hr over first 8hrs

• 100cc/hr over next 16hrs

• Final considerations• Add 20 mEq K to IV

fluids• Watch for metabolic

acidosis to resolve

Case • 1yo F (10kg)• 4 day Hx of severe

diarrhea and vomiting

• Exam• Lethargic and limp• Weak rapid pulse• Fontanelle sunken• Cap refill 5s• Cool and mottled• Tenting of skin

• Labs– Na = 114 – K = 3.4– HCO3 = 18

• During your exam the patient starts Seizing

Approach to Peds Dehydration

1) Initial Resuscitation2) Determine % dehydration3) Define the type of dehydration4) Determine the type and rate of

rehydration fluids5) Final considerations

Answers• Initial resuscitation

• 200cc NS• % dehydration

• >10%• Severe

• Dehydration Type• Hyponatremic

• Rehydration fluids• IV • Initially 3% saline• D5½ NS after above

• Rate and volumes• Initially correct to Na

of 120 with 3%= 70cc bolus• Then correct to Na of

130 with D5½ NS at rate of 0.5mEq/L/hr

= 39cc/hr• Final

considerations• Add 20 mEq K to IV

fluids

Final Case• You are working the overnight at the ACH

with Dr. Hodsman• You scan REDIS looking for anything other

than vomiting and diarrhea…• You find nothing• You note that all the kids you are treating are mild-

moderate dehydration• Some have failed ORT already tonight and or on IVs

• You start to wonder if there is anything that we could give these kids to help speed things up?

• Double blind RCT• Comparing

ondansetron to placebo in children with gastroenteritis

• American centre• N = 215 children

• Age 6m – 10y with gastro

• Mild-Moderate dehydration

• Ondansetron vs placebo

• 2mg for 8-15kg• 4mg for 15-30kg• 8mg for >30kg

Outcomes:• Primary

• Proportion of children who vomited while receiving ORT

• Secondary• Number of vomiting episodes during ORT• Rates of IV rehydration and hospitalization

Results:• NNT= 5 to prevent

one episode of vomiting

• (95% CI 3.2-10.6)• NNT=6 to prevent

one episode of IV rehydration

• (95% CI 3.6-17.0)

• Mean length of stay in the ED was reduced in the Ondansetron group

• 12% reduction (P=0.02)

• No statistical difference in hospitalization rates

• Issues:• Pharmaceutical sponsored• Used un-validated dehydration scoring

system• Lower threshold to treat with IV in their

patient population than our setting?• Side effects and cost

Questions?

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