Pediatric Fever in the ED

Marc Francis FRCPC R4

PEM Fellow year 1

Consultant Level Physician: Dr Jeff Grant

Objectives

Determination of a fever Case based look at fever in the ED A rational and evidence based approach to the 3 major

groups of kids with fever 0-30days 1 month to 3 months 3 months to 3 years

Determining the significance of fever in the era of new vaccinations

Evaluation of the work-up for fever and the utility of each variable

Treating Fever in the ED

Why do we care?

Febrile infant can be a challenging situation in the ED

Fever is the CC in up to 20% of visits to the ED Fever is commonly misunderstood While the vast majority of kids will have self-

limiting viral illnesses a few will have serious bacterial infections

300+ articles have been written about the evaluation and management of the febrile child

Useful stuff when working with Dr. Bryan Young Fever

– Host response mediated by cytokines

– Endogenous pyrogens IL-1, IL-6, TNF, interferon-alpha

– It is IL-6 which triggers the hypothalamic centers to increase body temp set point

– Increased metabolic rate, muscle tone and activity and ↓ heat loss through ↓ skin perfusion

PGE2 is likely responsible for the myalgis and arthralgias

Fever: Friend of Foe?

Friend– Integral part of

inflammatory response

– Role in fighting infection?

– Decreased length of symptomatology?

– Growth or survival of some pathogenic bacteria is impaired in range of 40°C

Foe– Like many defense

mechanisms it can go awry

– Metabolic changes detrimental in the context of shock or significant illness

– Can aggravate cerebral injury

– Makes pts uncomfortable

– Febrile convulsions

Case #1

5 month old MalePreviously HealthyNo medications, Vaccines UTD

HPI 2 day history of tactile fever at homeThis AM axillary temp of 38.8 °C by momChild more lethargic and decreased PO intakeURTI symptoms of rhinorrhea and unproductive

cough

Case #1 con’t

P/E– Well appearing child – given tylenol 15mg/kg at triage– T 37.5 °C, HR 120, RR 24, BP 71/52, Sat 98%– Exam normal– ENT

Rhinorrhea oralpharynx injected, no exudateTMs clear x 2

Questions

Does this child even have a fever? What is the definition of a fever? What is the best method to measure a

temperature in this child? Should the measured fever at home factor

into your decision making at all?

Determination of a fever

What constitutes a fever is debatable Studies by Wunderlich

1 Million measurements in 25,000 ptsDetermined the upper limits of normal

– For infants a rectal temp > 38.0 °C

> 100.4 °F

Determination of a fever

Tactile Fever is useless Otic thermometers

– Not used under 6 months of age

Axillary temp Unreliable Elevated temp is indicative of a fever Low or normal is not useful

An infant determined to be febrile at home by a reliable method must be presumed to have been febrile even if the temp later in the ED is normal

What about this thing?

Temporal Artery Thermometer

Computes temporal arterial temperature by a heat balance method

infrared sensor Uses rapidly repeated measurements

(1,000/second) of ambient and temple skin surface temperatures

Painless and rapid measurement Appealing for use in children

Assessed agreement between rectal and noninvasive temporal artery temperature in infants and children

275 subjects– average age was 11.2 months– range from 0 to 24 months

Results

Results

Conclusions– Temple temperatures do not reliably predict

rectal temperatures– Can be used as an effective screen for clinically

important rectal fever in children 3-24 months old

– Findings do not support use of temple temperatures to screen young infants for rectal fever >38.0°C

Approach to the Febrile Child

Caveats

The toxic child always mandates aggressive work-up, abx and admission

Studies of febrile infants exclude pts with complicating risk factors

Immunocompromised Indwelling medical devices Currently on abx Prolonged fevers >5days

In kids < 3 mths with a temp ≥40°C, 38% will have a serious bacterial infection

Stanley R, Pagon Z, Bachur R. Hyperpyrexia among infants younger than 3 months. Pediatr Emerg Care 2005;21(5):291 –4.

Case #2

22 day old F PMHx

Term baby of uncomplicated pregnancy Vaginal delivery GBS negative mother No prolonged ROM Discharged home less than 48hrs

HPI Public health nurse saw the child and temp of 38.4 rectally

recorded – sent in to ED

Case #2 cont

HPI Child doing well at home Gaining weight appropriately No lethargy or irritability Feeding well, BMs normal, good u/o

Exam T 38.6, HR 155, RR 35, Sat 99% RA Child examines very well Tone normal, good strong suck No focus for fever found

Questions

Could this be a serious bacterial infection? How do you want to manage this child?

Issues in the <30d old

High riskExposure to pathogens in birth canal without

passively transferred maternal antibodies Immature immune system Exhibit few if any classic signs of sepsisLimited behavioral repertoiremay deteriorate rapidlyMay not even be able to mount a fever

Children born premature are at even greater risk

Issues in the <30d old

Immature immune system– Decreased opsonin activity– Decreased macrophage activity– Neonatal neutrophils have reduced ability to

migrate from blood to sites of infection

Issues in the <30d old

The majority will go on to a diagnosis of nonspecific viral illness

12% of all febrile neonates presenting to a peds ED will have serious bacterial illness*

Typically more virulent bacteriaMore likely to develop significant sequelae

*Baker MD, Bell LM. Unpredictability of serious bacterial illness in febrile infants from birth to 1 month of age. Arch Pediatr Adolesc Med 1999;153(5):508–11

*Kadish HA, Loveridge B, Tobey J, et al. Applying outpatient protocols in febrile infants 1–28 days of age: can the threshold be lowered? Clin Pediatr (Phila) 2000;39(2):81 – 8.

Management

Full Septic W/U– CBC with Diff

– Blood culture

– Urinalysis and culture

– LP

– Stool culture and fecal leukocyte count if diarrhea present

– +/- Chest radiograph

Admission

IV Abx

Antibiotics

Pathogens: First few weeks

GBS E. coli Listeria Monocytogenes

Community Strep Pneumo H flu Neisseria Meningitidis

Rarely Staph aureus Salmonella

Antibiotics:

Ampicillin 3rd generation

cephalosporin +/- Acyclovir

? Ceftriaxone

ACEP Clinical guidelines:

Level A recommendations– Infants between 1 and 28d with a fever should

be presumed to have a serious bacterial infection

Case #3

2 month old Male Previously healthy, no medications and vaccines

are UTD HPI

– 48hr history of fever– Decreased PO intake and occasional vomiting– Some lethargy noted at the breast– Otherwise well– No diarrhea, no rash, no cough, no URTI symptoms

Case #3 cont

Exam T 38.9 tympanic, HR 136,

RR 38, Sat 98% RA Generally looks well and

appropriate CVS – normal Resp – no distress, clear

bilaterally

Abd – soft and nontender no HSM

Derm – no rash Neuro – good tone, strong

suck, interacting well ENT – throat clear, TM’s

normal, no adenopathy

Questions?

Does this child need a full septic work-up too?

Is this child high or low risk?– How can you risk stratify him?

What degree of work-up does this child need for his fever without a source?

How would you manage this child

Issues in the 1mth to 3mth old

Significant amount of research in this area Give more clinical clues to their degree of

wellness than the <30d olds Clinical criteria alone do not give adequate

accuracy to detect a significant infection Determination requires clinical and

laboratory investigations

Lab evaluation of FWS

CBC with diff Urinalysis

– Boys <6mths– Girls <2yrs

Stool for leukocytes if diarrhea Chest radiograph if respiratory symptoms

Approaches

Need to identify the high risk pt

Criteria for same are well documented Pick one and stick to it

– The Rochester Criteria are well recognized– Advantage of no CSF criteria!!!

Use your clinical judgment if you are experienced– Good research to show that experienced

clinicians are good predictors

Rochester Criteria

Dagan and colleagues Stratifies children less than 60d old into High or

low risk categories– Clinical and lab criteria

Low-risk group were unlikely to have serious bacterial infection– NPV of 98.9%

Jaskiewicz JA, McCarthy CA, Richardson AC, et al for the Febrile Infant Collaborative Study Group. Febrile infants at low risk for serious bacterial infection–an appraisal of the Rochester criteria and implications for management. Pediatrics 1994;94(3):390– 6.

Rochester Criteria

1) previously healthy term infant with uncomplicated nursery stay

2) well appearance

3) No focal infection (except OM)

4) WBC 5,000-15,000/mm3

5) Band count <=1,500/mm3

6) U/A normal (<=10 WBC/hpf)

7) stool <=5WBC/hpf (if diarrhea)

Rochester Criteria

Low risk if none High risk if look toxic or fail the criteria Numerous studies have shown an increase in

serious bacterial infections missed when applied to infants age 1 – 28 days

-Ferrera PC et al Neonatal fever: utility of the Rochester criteria in determining low risk for serious bacterial infections. Am J Emerg Med. 1997;15:299-302-Kadish et al. Applying outpatient protocols in febrile infants 1-28 days of age: can the threshold be lowered? Clin Pediatr. 2000;39:81-88-Baker MD, Bell LM. Unpredictability of serious bacterial illness in febrile infants from birth to 1 month of age. Arch Pediatr Adolesc Med. 1999;153:508-511

High risk management?

Look toxic or fail the criteria– Full septic work up– Hospital admission– Empiric antibiotics

Clear CSF: 24hr empiric ceftriaxoneUrine positive: amp/gent pending culturesCSF pleocytosis: 48hrs on amp/ceftriaxone and

consider Vanco

Low risk infants 30d to 90d

2 management strategies:

1) blood, urine and CSF cultures

single dose of IM ceftriaxone

re-evaluation within 24hrs

2) Urine culture obtained

No abx therapy

Careful observation

Should you LP?

Prevalence of bacterial meningitis in febrile infants < 3 months is 4.1/1000 pts

Neither the clinical exam or WBC is reliable in diagnosis

The LP should be strongly considered If you forego the LP do not give antibiotics

– Confounds the evaluation for meningitis if still febrile on follow-up exam

Disposition is Key

Outpatient Reliable follow-up

within 24hrs Immediate access to

health care if required Good parents Careful plan derived

with parents

Do these clinical guidelines actually help the experienced clinician?

Prospective cohort study Aim to characterize the management and clinical

outcomes of febrile infants N= 3066 infants ≤ 3mths with temp >38°C Office based practice of 573 practitioners in 44

states (PROS) Outcome measures assessed:

Management strategies Illness frequency Rates and accuracy of treating bacteremia

Results:– Hospitalized 36% of infants– Lab testing in 75%– Bacteremia detected in 1.8% and bacterial

meningitis in 0.5%

In the initial visit physicians treated 61/63 cases of bacteremia/bacterial meningitis with abx

Conclusions:– Peds clinicians in the US use individualized

clinical judgment– Neither current guidelines or any other clinical

model performed with greater accuracy than observed practitioner management

– Current guidelines would not have resulted in improved care with more hospitalizations and lab testing

Case #4

2yo M Previously well, no meds, vaccines UTD HPI

– 3 day hx of fever responsive to advil prn– Decreased activity level as per parents– poor po intake of solids, but drinking– Good u/o, no diarrhea or vomiting– No URTI symptoms

Case #4 con’t

Exam – Well appearing child– T39.1°C, HR 115, RR 24, BP 80/48, Sat 98%– CVS – normal– Resp – Clear and no distress– Abd – soft and nontender– Derm – no rash– ENT - normal

Questions

What is the concern in this age group? What defines a significant fever in this age

group? What diagnostic test are indicated in this

scenario? How would you manage this child?

Issues in the 3mth to 3yo child

Remains controversial (surprised?) Have been considered at risk for occult

bacteremia This age group where widespread

vaccination has had its greatest effect Important to obtain a detailed vaccination

history to assess risk

The 3mth to 3yo child

Your exam finally matters!!!– Well appearance does not exclude bacteremia

but…..– Children who appear unwell are far more likely

to have serious illnessToxic appearing = 92% Ill appearing = 26%Well appearing = 3%

McCarthy PL, Sharpe MR, Spiesel SZ, et al. Observation scales to identify serious illness in febrile children. Pediatrics 1982;70(5):802 –9

The 3mth to 3yo child

A temp ≥ 38°C defines a fever in younger children beyond which diagnostic testing in initiated

In this age group a temp ≥ 39°C is commonly used as the threshold

This higher cutoff is used because of increased risk of occult bacteremia with increasing temp

Kuppermann N, Fleisher G, Jaffe D. Predictors of occult pneumococcal bacteremia in young febrile children. Ann Emerg Med 1998;31(6):679–87.

Occult bacteremia

In the mid 1990s the overall prevalance of bacteremia in young febrile children was estimated at 1.6-1.9%

The reason to screen is to minimize the low but worrisome risk of serious complications

Septic arthritis, osteomyelitis, meningitis, sepsis

In retrospective studies of culture + pts, empiric abx reduced the rate of

Complications Persistent fever Hospitalisation

In a majority of pts bacteremia will resolve spontaneously

Occult Bacteremia

H. flu previously presented a significant burden of disease

With vaccination H influenza type B has been virtually eliminated

Corresponding with this decrease was an increase in the % of invasive disease caused by Strep Pneumo

83% to 93% of + blood cultures in young febrile infants in the 1990s in the US

Recent heptavalent vaccination has further changed the landscape

What are predictors of bacteremia?

Hx and PE are poor discriminators There is ↑ risk of bacteremia with ↑ WBC

Sensitivity of WBC >15,000 is only 80% to 86% Specificity of WBC >15,000 is 69%-77%

Absolute Neutrophil Count (ANC) >10,000 is a stronger predictor

8% of pts with ANC >10,000 have occult bacteremia 0.8% of pts with ANC <10,000 have occult bacteremia

Kuppermann N, Fleisher G, Jaffe D. Predictors of occult pneumococcal bacteremia in young febrile children. Ann Emerg Med 1998;31(6):679–87

Approaches

Conservative:

Well appearing and no identified focus:

• Urinalysis• No other

investigations• No antibiotic

treatment

Aggressive:

Well appearing and no identified focus:

• CBC if Temp >39.0°C• If WBC > 15000 then

blood culture and empiric ceftriaxone

Aggressive theory

Well child with FWS may fail to identify occult Strep pneumoniae resulting in possible S. pneumo meningitis– Introduction of the Prevnar vaccine in July 1,

2002 should have drastically decreased this risk– Meningovax addition to the vaccination

schedule further reduces the risk

PREVNAR (PCV7)

Offered in Alberta since July 1, 2002 Previous vaccine was T-independent antigen Conjugated heptavalent pneumococcal vaccine

Polysaccharide conjugated to protein Allows T-dependant response Substantial primary response among infants and children

Serotypes covered include – 4, 6B, 9V, 14, 18C, 19F and 23F

Good antibody response in 90%-100% of children to all seven vaccine serotypes after 3 doses

CASPER STUDY(Calgary Area Streptococcus pneumoniae Epidemiology Research)

Dr. J. Kellner Tracking disease incidence and serotypes in

Alberta before and after introduction of routine childhood vaccination in 2002

Preliminary results have shown a 62% decrease in IPD incidence among children between 6 and 23 months of age

Between 1998-2004 only one child receiving 1 or more doses of PCV7 developed invasive pneumococcal infection

16 month old who had 3 doses of PCV7

Recommendations

The reduced likelihood of occult bacteremia with S. Pneumonia makes routine CBC and blood cultures in this population excessive

Not cost-effective Careful follow-up is required if patients are

discharged home

Rational Approach

Consider using ANC over WBC as a better predictor

Case #5

3yo M previously healthy presents with 3 day history of fever >39°C

lethargy and poor po intake Father has not been treating the fever with

anything at home Received tylenol at triage and fever

responded well and now 37.2°C

Question

Does a response to antipyretic indicate a lower likelihood of a serious bacterial infection?

Response to antipyretic

Trials performed over the last 20yrs have consistently found no correlation

Case #6

16 month old F with fever x 48hrs Pmhx: healthy, vaccines UTD URTI symptoms but no other source identified Exam

Generally looks unwell T=39.1 rectal, HR 130, RR 36, BP 71/48, Sat 95% CVS: nil acute Resp: comfortable, clear throughout, no retractions, no stridor

or nasal flaring, no cough Abd: soft + nontender Derm: no rash

Case #6 Con’t

You order cultures and some investigations The nurse asks you if you want to include a

Cxray in your work-up? Question:

What are the indications for a chest radiograph during the work up of pediatric fever?

The issue

Estimated that 7% of children <2yo with temp >38°C will have pneumonia

Occult pneumonia with no clinical evidence can be seen in up to 26% of children with FWS and WBC>20,000

Many of these will be viral Interobserver reliability of cxray findings of

bacterial pneumonia is poor

Meta-analysis to determine the need for cxray in the febrile infant work-up

N= 617 infants ≤ 3 mths from 3 different study populations

Evaluated clinical findings as predictors of pneumonia diagnosed radiographically

Potential clinical markers

Results

361 febrile infants had no evidence of pulmonary disease on Hx or PE and had normal xrays

256 febrile infants had at least one clinical finding of pulmonary disease

85 (33.2%) of these had + chest radiograph for pneumonia

95% CI that a positive cxray in a child with no pulmonary symptoms would occur 1.02% of the time

Conclusions– The policy of obtaining Cxray in work up of all

febrile infants should be discontinued– Chest xrays should be obtained only in febrile

infants with clinical indications of pulmonary disease

So what about urine cultures?

Do all children require urine cultures for w/u of fever without a source?

The issues

UTI is an important cause of fever in young children

Prevalence of UTI in kids age 2m – 2yo with no identifiable source for fever is ~3-7%

Estimated that 75% of children <5yo with febrile UTI have upper tract disease

Potential for renal scarring

Who is at risk?

Prevalence of UTI in Children < 1yo6.5% in girls3.3% in boys

Between age 1-2yo8.1% in girls1.9% in boys

Uncircumcised boys at increased risk

Clinical decision rule to identify febrile young girls at risk of urinary tract infection

Gorelick MH et al. Arch Pediatr Adoles Med 2000;154(4):386-390

Prospective cohort study Development of a clinical decision rule to identify

febrile young girls requiring urine culture N= 1469 females <2yo presenting to the ED with

fever >38.3°C without an unequivocal source of fever

Multiple logistic regression after screening variables for univariate association and reliability

Clinical Decision Rule

Presence of 2 or more of the following 5 variables:

1) Less than 1 yo

2) White race

3) Temp 39°C or higher

4) Fever for 2 days of more

5) Absence of another source of fever on exam

Results

Prediction of UTI– Sensitivity 0.95 (95% CI 0.85-0.99)– Specificity 0.31 (95% CI 0.28-0.34)

With their study population and an overall prevalence of UTI of 4.3%– PPV of score ≥2 was 6.4%– NPV of score <2 was 0.8%

What about boys?

No clinical decision rule exists Due to higher prevalence in boys <6mths

and higher prevalence in uncircumcised boys general guidelines are:– Urine cultures for all boys < 6mths– Urine cultures for uncircumcised boys <12mths

Case #7

You have just finished diagnosing your 8th viral URTI in the last hour

You recommend fluids, antipyretics and that they find somewhere else to go next time

As you are about to send the child home, the mother asks what is better to treat the fever with Tylenol or Ibuprofen???

Questions

Is there evidence that Acetaminophen or Ibuprofen is more efficacious in the treatment of childhood fever?

Is there any difference in the safety profile of the two drugs in children?

Meta-analysis published in 2004 Extensive search of multiple databases

found 127 potential studies 17 blinded, randomized controlled trials

with children <18yo selected Compared the efficacy in pain, fever and

the safety profile of the two drugs

Compared Ibuprofen 4-10mg/kg Acetaminophen 7-15mg/kg Included only data for the first dose in multi-dose studies

Outcome measures were– Mean temp difference between drugs at 2,4 and 6 hrs

– Mean temp difference from baseline at 2, 4 and 6 hrs

Safety measures were– Risk ratio of minor and major harm between the drugs

Results– All point estimates of the mean weighted effect

size favored ibuprofen at all times2hrs 0.19 (95% CI, 0.05-0.33)4hrs 0.31 (95% CI, 0.19-0.44)6hrs 0.33 (95% CI 0.19-0.47)

– All confidence intervals were fairly narrow and none crossed 0

– The relative superiority was more pronounced at 4 & 6hrs after treatment

Safety Profiles:– Point estimates for risk ratio of harm were

calculatedA ratio of 1 indicates the drugs did not differ in safetyRR > 1.0 indicate that Ibuprofen was less safe

– ResultsRR minor harm = 0.96 (95% CI, 0.68-1.36)RR major harm = 1.00 (95% CI, 0.55-1.82)

– Both data sets had confidence intervals crossing 1

Conclusions:– Ibuprofen 5-10mg/kg (especially a 10mg/kg

dose) is a more efficacious pediatric antipyretic– There is no indication that the drugs differ in

safety from each other Limitations

– Clinical significance of the difference – Did not look at repeat dosing– Did not look at using both in combination

Take Home Points I

Approach to a fever:< 1 month old

Full septic w/u, admission and abx for all

1 month to 3 months Use documented criteria to determine if high or low risk and

management based on same If you are experienced use your clinical judgment

3 mths to 3 years With new vaccinations the incidence of occult bacteremia is so

low that routine investigations in the well child is of no utility

Take home points II

How you measure a temp does matter especially in young kids

Remember that your clinical exam can be misleading in very small children

Reserve Chest xray for those with resp symptomatology only

Ibuprofen may be more effective than Acetaminophen in reducing fever

Questions?

I’m Feeling a little warm

Further case

You decide that you are not an “experienced clinician” and you’re going to use the Rochester Criteria to work up a fever without source in a 2 month old

Your colleague asks you why you are using the WBC when we know it is such a terrible marker for significant infection?

Questions

What is the sensitivity and specificity of the WBC for diagnosing bacterial infection?

Are there markers that we can be using that are better predictors?

WBC as a marker

Clearly associated with increased risk of bacteremia at values < 5000 (likelihood ratio of 3.9) >15,000 (likelihood ration of 2.0)

However known to have poor sensitivity and specificity and thus inaccurate

Because of its low predictive value and the low prevalence of bacteremia– Results in unnecessary treatment in 85-95% of cases

Other potential markers

Band counts ANC Band to Neutrophil ratio ESR C reactive Protein Pro-calcitonin

CRP

Acute-phase reactant Sensitive indicator of infection Shown to have a better predictive value

than WBC or ANC for bacterial infection A CRP < 5 mg/dl (50mg/L) effectively

ruled out serious bacterial infection

Pulliam PN, Attia M, Cronan K. C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection. Pediatrics. 2001;108:1275-1279.

CRP performance