Febrile ChildMark Bromley PGY 2Adam Oster FRCPC

Agenda

1. Pathophysiology (briefly)1. Pathophysiology (briefly)

3. Neonates (Birth – 1 month)3. Neonates (Birth – 1 month)

2. Young Infants (1 – 3 months)2. Young Infants (1 – 3 months)

4. 3 months – 3 years4. 3 months – 3 years

What is Fever?

• An elevation of body temperature?

• Fever is an ↑ temperature as part of a specific biological response, mediated and controlled by the CNS

• Not heat stress • Not heat illness

NORMAL BODY TEMPERATURE• Varies over the course of the day (circadian rhythm) • Normal daily temperature variation is 0.5 ºC

• ↑ after an illness

• Is controlled by the thermoregulatory center located in the anterior hypothalamus

(Pyrogens)Infectious agents / Toxins / Mediators of inflammation• Cellular sources: monocytes, neutrophils,

lymphocytes– Many others, when stimulated

Infectious• Most exogenous pyrogenic substances are

from • Bacterial • Fungal• Viruses

– Induce pyrogenic cytokines by infecting cells

Non-Infectious• Inflammation • Trauma• Antigen-antibody complexes

Infectious agents / Toxins / Mediators of inflammation(Pyrogens)

stimulate

Monocytes / Macrophages / Endothelial cells / Other cell types

release

Pyrogenic cytokines - IL- 1, TNF, IL- 6, IFNs

stimulate

Anterior hypothalamus (Mediated by PGE2)

results in

Elevated thermoregulatory set point

leads to

Increased Heat conservation (Vasoconstriction/ behaviour changes)

Increased Heat production(involuntary muscular contractions)

result in

F E V E R

(Antipyretics/ NSAIDs act here) 

Temperature Regulation

Heat Loss

Muscle

LungsSkin

Liver

Heat Gain

HYPOTHALIMUS

ClothingBehaviour

Case•2 month ♂

–Previously well–No meds–Vaccines are up to date

•HPI–2 day history of fever–This AM he is more irritable & ↓PO intake–Rhinorrhea and non-productive cough

•Baby looks good…but you think you should probably check vitals

How would you like to check temp?

What is a fever

• Wunderlich •1 million measurements in 25,000 patients•Determined the upper limit of normal

• Infants•Rectal temp >38oC

What is a Fever• Rectum: Gold Standard

• > 38oC to > 38.2oC ….depending on the study and local custom• Not influenced by ambient temperature and its use

is not limited by age• It is frightening for small children and may be

psychologically harmful for older children. • Discomfort and is painful for patients with peri-

rectal infxn / irritation • Varies depending how deeply the thermometer is

inserted into the rectum, local blood flow, and the presence of stool and diarrhoea

• May lag behind a rapidly changing core temp ?poor blood flow to the rectum

• In the presence of shock, perfusion of the bowel, including the rectum, may be markedly impaired, and RT will lag significantly behind changing core temp

What is a Fever•TACTILE

–Oldest and still the most widely used method of evaluating body temp –Inaccurate, mainly because of the lowering of skin temp during the early phase of fever–Operator dependent

•Medical staff 42% accurate•Mothers 80% accurate

•Axilla–Safe, easily accessible, and reasonably comfortable –requires supervision in case displacement occurs–takes longer than rectal or sublingual measurement (5min mercury 40–80s electronic)–inaccurate–Fever » vasoconstriction » skin temperature cooling as the core temperature rises–Sweating and evaporation cause the AT to be lower than the core body temperature–Rectal temperature and AT differed by up to 3°C and AT was occasionally very low

What is a Fever•Oral

–generally 0.6 ºC lower than rectal temp b/c of mouth breathing

•Tympanic–60% of total heat loss from the body occurs via radiation in the form of infrared heat rays–↑ during fever –As the tympanic membrane receives its blood supply from the carotid artery, its temperature may reflect that of blood flowing into the hypothalamus–A suitable detector without a probe contact can measure the infrared rays emitted by the tympanic membrane

•Benefits: –Fast and easy to use –No risk of cross infection –Not influenced by environmental temp

•Deficits: –Inaccurate in children < 3 years

What about this guy?

• Subjects: Children < 2y presenting to an acute care site• Each child had 6 temps taken

• Temporal: 3 by nursing + 2 by parents• Rectal: 1 by nursing

• Results:• Good correlation

• Conclusions: • Variability too high for infants < 3months• Max temp of 3 taken may be a useful screening

measure

• Design: Cross-sectional agreement emergency department study

• Subjects: 327 children <24 months of age

• Methods: Temp measured rectally & Temporally by a single nurse

• Outcome Measures: – Temp cut-off to detect rectal fever ≥38.0°C and ≥

38.3°C– Sensitivities of >=90% and >=95% was determined

• Results: – The mean difference between the rectal minus TAPM

was -0.19°C ± 0.66°C – The sensitivities of TAPM temperature of ≥37.7°C to

detect rectal fever – ≥ 38.0°C / 90% (95% confidence interval: 0.83; 0.94) – ≥ 38.3°C / 97% (95% confidence interval: 0.92; 0.99)

• Conclusions: – The TAPM thermometer cannot replace the rectal– TAPM temperature of <37.7°C can be safely used as a

screen to exclude rectal fever ≥ 38.3°C in infants 3 to 24 months

What do we do at the ACH?

• Under 3 months rectal• Temporal for the rest

Case Continued

• Vitals: 125 25 80/46 37.8oC • What do you want to do?• Are you worried?• Is this kid hiding bacteria?

• Does Mom’s tactile fever count?

•N=292 infants •Age < 2 months with a Hx of fever who were admitted for possible sepsis

•Among the 19 infants with serious bacterial infection, all exhibited abnormal clinical and/or laboratory features on evaluation that were suggestive of underlying serious infection

N=292?Sepsis

Tactile Fever(48)

Rectal Fever(244)

Fever @ presentation(22)

Afebrile @ presentation(26)

Fever @ presentation(204)

Afbrile @ presentation(40)

Serious Bacterial Infxn (1)

Serious Bacterial Infxn (4)

30 days - 3 months

Case

• 2 month male• Sniffles and loosening stools x

2days • ↓feeding • PMHx: previously well• Birth history

– SVD at term– Maternal GBS status negative– No maternal history of STI – Unremarkable nursery course

• What is your approach?• Is this a low risk kind of baby?

…high risk kind of baby

HISTORY• Associated symptoms (resp, GI) • Behaviors (feeding, irritability, activity) • Sick contacts (siblings, babysitters, day

care) • Previous illness, or antibiotics• Birth history

– maternal fever, – maternal group B streptococcus status

(prophylaxis)– maternal history of STI (HSV, gonorrhea &

chlamydia) – PROM – the infant's nursery course

• Relying solely on clinical exam results in missed SBIs in this age group

• Lab testing is required

• We are looking for the high risk children

…ideally a rule with– Great sensitivity– Good specificity

• Excellent for those of us with limited clinical experience

Boston (Low Risk) CriteriaBoston (Low Risk) Criteria

•≥ 37 weeks gestation•Infant was previously well•Infant was well appearing

•(no soft tissue / ear / bone infections)

• WBC ≤ 20/uL• Urinalysis < 10 WBC/hpf (No Bacteria)• CSF ≤ 10 WBC/mm3

• Stool < 5 WBC/hpf• CXR – Normal

LAB

Fever ≥ 38.0 oCHISTORY 29-89 days old

When Obtained

Boston Criteria• Low Risk

• Ceftriaxone 50mg/kg• Discharged with follow-up

• Results: • 27 patients (5.4%) had a SBI

– 9 (1.8%) had bacteremia– 8 (1.6%) had urinary tract infections w/o bacteremia– 10 (2.0%) had bacterial gastroenteritis w/o bacteremia

• 476 (94.6%) did not

• Conclusions:• Of the 27 infants with SBIs Clinical screening criteria did

not enable discrimination between infants with and without SBI

• All infants with SBI received an appropriate course of ABx and were well at follow-up

• One infant had osteomyelitis diagnosed 1 week after entry into the study, received an appropriate course of IV ABx, and recovered fullyOutpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone Pages 22-27 Marc N.

Baskin, Edward J. O'Rourke and Gary R. Fleisher

hilidelphia (Low Risk) hilidelphia (Low Risk) CriteriaCriteria

• ≥ 37 weeks gestation• Infant was previously well• Infant was well appearing

• (no soft tissue / ear / bone infections)

• WBC ≤ 15/uL (band:neutrophil ≤ 0.2)• Urinalysis < 10 WBC/hpf (No Bacteria)• CSF ≤ 8 WBC/mm3

• CXR – Normal• Stool < 5 WBC/hpf & no blood

LAB

Fever ≥ 38.2 oCHISTORY 29-56 days old

When Obtained

hilidelphia Criteria•Low Risk

•Discharged with follow-up

•Results: •N=422 •43 patients (10%) had a SBI – all were “High Risk”•Low Risk: 101 – no SBIs

•Conclusions:•Of the 27 infants with SBIs Clinical screening criteria did not enable discrimination between infants with and without SBI•All infants with SBI received an appropriate course of ABx and were well at follow-up •One infant had osteomyelitis diagnosed 1 week after entry into the study, received an appropriate course of IV ABx, and recovered fully

Byington CL, Rittichier KK, Bassett KE, et al. Serious bacterial infections in febrile infants younger than 90 days of age: the importance of ampicillin-resistant pathogens. Pediatrics 2003;111(5 Pt 1):964–8.

Rochester (Low Risk) CriteriaRochester (Low Risk) Criteria

• ≥ 37 weeks gestation• Infant was previously well• Infant was well appearing

• (no soft tissue / ear / bone infections)

• WBC 5–15/uL• Urinalysis < 10 WBC/hpf (No Bacteria)• Stool < 5 WBC/hpf• CXR

LAB

Fever ≥ 38.0 oCHISTORY < 60 days old

When Obtained

•High Risk: Hospitalized + Emperic Abx•Low Risk: Sent Home

•(reasonable follow-up)

N=931?Sepsis

Low Risk437 (47%)

High Risk494 (53%)

Serious Bacterial Infxn 5 kids

NPV = 98.9%(CI: 97-100%)

Neonatal fever: utility of the Rochester criteria in determining low risk for serious bacterial infections

•Design: retrospective study •Population: 134 patients younger than 29 days

…fever without a source evaluated in the ED •Results:

•Employing the Rochester criteria to the fully cultured neonates who could be risk-stratified, the sensitivity 86.4% •specificity 46.4% •positive predictive value 26.8% •negative predictive value 93.8%

N=134?Sepsis

Low Risk48

High Risk71

Serious Bacterial Infxn 3 kids6.3%

Not Classifiable15

Serious Bacterial Infxn 0 kids

0%

Serious Bacterial Infxn 19 kids26.8%

Neonatal fever: utility of the Rochester criteria in determining low risk for serious bacterial infections. Ferrera PC; Bartfield JM; Snyder HS Am J Emerg Med 1997 May;15(3):299-302.

ApproachApproach

LowRisk

High Risk

TermWell AppearanceNo Focus of InfxnWBC < 15Urinalysis<10/hpf

CXR – no infiltrateStool – no blood few WBCs

Age < 28d*Look ToxicFail Criteria

When Obtained

*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?High risk management?

• Full septic work up• Hospital admission• Empiric antibiotics

•CSF clear : 24h ceftriaxone•CSF pleocytosis: 48h

Amp/Ceftriaxone …consider Vancomycin

•Urine positive: Amp/Gent (cultures)

Low risk managementA) • Blood/urine/CSF

cultures• Ceftriaxone IM

• single dose

• Re-evaluation in 24h

B) • Urine culture • No abx therapy• Careful

observation

Lumbar Puncture

• Boston/Phily Criteria require it• Rochester does not

• Bacterial meningitis is rare (4.1/1000)

• PE and peripheral WBC are unreliable

∴ strongly consider LP

• ?Antibiotics

Management of febrile (38ºC) healthy infant 28-90 days

without source

Case• 20 day malePMHx

•SVD at term•GBS negative Mom•Apgars 9/9•Discharged at 24 hours

HPI• Mother took a temp at 38.2oC• He has been feeding well with good

weight gain• Not irritable or lethargic

In the ED38.3oC 140 80/45 24

• Looks well / active / bright• Normal tone

• Are you worried?• What would you like to do?

Birth – 30 days

Issues in the 0-30 day old

• Immature immune system• Improves steadily in the first three

months of life • The immunologic task switches at

birth from this coexistent state (graft preservation) to protection from invading pathogens

• Neonates are more susceptible to SBI than older infants

Issues in the 0-30 day old

• Exposure to pathogens in the birth canal

• Do not exhibit classic signs of sepsis

• May deteriorate quickly• May not be able to mount a fever

• ++ with prems

Etiology• Viral (most common)*

• HSV• Varicella• Enterovirus• Influenza• Adenovirus• RSV

• Bacterial* ~12%– Maternal Flora

• GBS• Gram negative organisms ( E Coli)

– Listeria– Strep Pneumo– H. Influenza

↑ Prevalence with Age

Vertical TransmissionFamilyHospital workers

*Baskin, MN. The prevalence of serious bacterial infections by age in febrile infants during the first 3 months of life. Pediatr Ann 1993; 22:462.

*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.

Sources of (SBI) Infection

Bacteremia

Bacterial Gastroenteritis

Bacterial Meningitis

Cellulitis

UTI

UTI

Bacteremia

BacterialGastroenteritis

Bacterial Meningitis

Cellulitis

Baker, MD, Bell, LM, Avner, JR. Outpatient management without antibiotics of fever in selected infants. N Engl J Med 1993;

329:1437.

Infants ages 29 to 56 days who presented to an ED with rectal temperatures ≥38.2ºC

• The young febrile infant may demonstrate few, if any, interpretable clues to the underlying illness

• Infants between 1 and 28 days old with a fever should be presumed to have a serious bacterial infection (Level A)

Case• 8 day ♀• Presents with fevers, irritability and

poor feeding• PMHx:

• SVD at term• No Maternal Risk Factors

• PE: No obvious source• CBC: WBC 8.6

…The nurse asks “do we really need to do the LP? What are the chances of meningitis with a normal WBC?”

[Ann Emerg Med. 2003;41:206-214] • Methods: logistic regression modeling and receiver operating

characteristic curve analysis of peripheral blood WBC count and cerebrospinal fluid WBC count

• Subjects: 3-89 day-old infants undergoing a sepsis evaluation

• Results: 22 of 5,353 infants had bacterial meningitis– For diagnosing acute bacterial meningitis, the peripheral blood WBC

count was poorly discriminating and significantly inferior to the cerebrospinal fluid WBC count

– When relying on single and interval-based high-risk thresholds of peripheral blood WBC counts alone, the majority of infants with acute bacterial meningitis would have been missed.

• Conclusion: Decisions to perform or withhold lumbar puncture should not be based on prevailing interpretations of the total peripheral blood WBC counts to maximize detection of bacterial meningitis in young infants

Peripheral WBC

• …not sufficient to differentiate between patients with SBIs and those who do not*

∴ Cultures should be ordered on everyone

*Bonsu BK, Harper MB. A low peripheral blood white blood cell count in infants younger than 90 days increases the odds of acute bacterial meningitis relative to bacteremia. Acad Emerg Med 2004;11(12):1297–301.

Bonsu BK, Harper MB. Identifying febrile young infants with bacteremia: is the peripheral white blood cell count an accurate screen? Ann Emerg Med 2003;42(2):216–25.

UTI Testing

• Various rapid tests•Urinalysis•Urine dipstick•Enhanced urinalysis

• None detect ALL UTIs*∴ urine cultures should be ordered

• Urine bags are associated with high rates of contamination

*GorelickMH,Shaw KN. Screening tests for urinary tract infection in children: a meta-analysis. Pediatrics 1999;104(5):e54.

Shaw KN, McGowan KL, Gorelick MH, et al. Screening for urinary tract infection in infants in the emergency department: which test is best? Pediatrics 1998;101(6):e1.

Recommendations

•Rectal temperature 38ºC •blood, urine, and CSF cultures•regardless of clinical appearance•CXR if signs of Resp dz

•Admit to hospital and treat with Abx •Amp/Gent or Amp/Cefotaxime•Acyclovir

–(vesicles, seizures, CSF pleocytosis, ↑ liver transaminases)–Culture first

Case• 2 wk ♂ presents with runny nose and

sneezing• ↓Feeding ↑Irritability• Sick contacts – 2yr brother has a snotty

nose• PMHx unremarkable• 38oC 125 60/37 30• OE: Expiratory wheezes

• Rapid antigen test: (+) RSV

We’ve found our source!…no need to poke him, right?

Management• Full septic work-

up• CBC with Diff• Blood culture• Urinalysis & culture• LP

• If diarrhea present• Stool culture • fecal leukocyte

count

• If resp Sx present• CXR

• Admission

• IV Abx

AntibioticsPathogens:• First few weeks

• GBS• E. coli• Listeria Monocytogenes

• Community• Strep Pneumo• H flu• Neisseria Meningitidis

Antibiotics• Ampicillin• 3rd generation

cephalosporin• +/- Acyclovir

…Ceftriaxone?

• Rarely• Staph aureus• Salmonella

Question

• What is the risk of SBI in neonates with an identified viral source?

•Methods: 3-year multicenter, prospective, cross-sectional study–Determined RSV status by antigen testing of nasopharyngeal secretions –Evaluated infants with blood, urine, cerebrospinal fluid, and stool cultures

•Subjects: N=1248 Febrile infants who were < 60 days•Results. The overall rate of SBIs was 11.4%

The rate of SBIs –RSV-positive infants 7.0% (17 of 244; 95% CI: 4.1%-10.9%) –RSV-negative infants 12.5% (116 of 925; 95% CI: 10.5%-14.8%)

The rate of UTI –RSV-positive infants 5.4% (14 of 261; 95% CI: 3.0%-8.8%) –RSV-negative infants 10.1% (98 of 966; 95% Ch 8.3%-12.2%)

The rate of Bacteremia–RSV-positive infants 1.1% –RSV-negative infants 2.3%

No RSV-positive infant had bacterial meningitis•Conclusions. The rate of SBIs is significant in febrile RSV(+) infants is significant

3 months -3 years

Issues in the 3 month – 3 year olds

• History is often helpful• Patients are more communicative• Well appearance does not exclude

bacteremia but it is more closely correlated

•Toxic 92% SBI• Ill 26% SBI•Well 3% SBI

Issues in the 3 month – 3 year olds

• ↑temp = ↑ risk of SBI / occult bacteremia

• In this age group 39oC is often used as a threshold for investigation

HistoryHistory

• Immunization status– Specifically PCV7 – ↓Risk of Invasive Pneumococcal Disease

• Exposures to known infectious agents• Sx of focal infections

– Ear Pulling– Cough– Vomiting– Bloody Stool– Crying with voids

Physical ExamPhysical Exam• Abnormal vital signs (including pulse ox)• Toxic appearance

• (irritable, inconsolable, ↓perfusion, ↓tone, ↓activity, lethargy)

• Localized infection • (omphalitis, joint/skin swelling or mm lesions c/w

HSV)

• Bacterial meningitis • (∆ sleep, ↓PO intake, ↑↓thermia, paradoxic irritability) • Bulging fontanel – late sign • ↑ localization to CNS with age• Nuchal rigidity is present in only

– 0-6 months - 27% of patients – > 19 months - 95 % of patients Bacterial

Meningitis

LabsLabs

• CBC and differential• Urinalysis – culture

– Boys <6mths– Girls <2yrs

• Chest X-Ray • (RR>50, rales, rhonchi, retractions,

wheeze, grunt, stridor, nasal flaring, cough)

• Stool for leukocytes • (if diarrhea)

PREVNAR (PCV7)PREVNAR (PCV7)• Pneumococcal conjugate vaccine …

Streptococcus pneumoniae• Before universal immunization in the US

• S. pneumoniae caused ~17,000 cases of invasive dz/year

• 700 cases of meningitis • 200 deaths • the most frequent cause of bacteremia, pneumonia,

meningitis, sinusitis, and acute otitis media

• Since pneumococcal conjugate vaccine • the incidence of invasive pneumococcal disease

has ↓ 60-90 % in children < 2 years

• Prevnar is a 7-valent vaccine (PCV-7)

• It contains the cell membrane sugars of seven serotypes of pneumococcus, conjugated with Diphtheria proteins

• Recommended… • for all children <2 years•and for unvaccinated children between 24

and 59 months old who are at high risk for pneumococcal infections

• …will PCV-7 ↑ IPD from non-vaccine serotypes

•METHODS: –laboratory-based data from Active Bacterial Core surveillance to measure disease caused by antibiotic-nonsusceptible pneumococci from 1996-2004 –Cases of invasive disease were identified in 8 surveillance areas –Isolates underwent serotyping and susceptibility testing

•RESULTS: –penicillin-nonsusceptible strains and

•1999 6.3 cases per 100,000 •2004, 2.7 cases per 100,000 (↓ of 57%; 95% CI, 55 to 58%)

–strains not susceptible to multiple antibiotics •1999 4.1 cases per 100,000 •2004, 1.7 cases per 100,000 (↓ 59%; 95% CI, 58 to 60%)

–Children < 2 years (penicillin-nonsusceptible strains) •(↓ 81%; 95% CI, 80 to 82%).

–> 65 years of age (penicillin-nonsusceptible strains) •(↓ 49%)

•CONCLUSIONS: The rate of antibiotic-resistant invasive pneumococcal infections ↓ in young children and older persons after the introduction of the conjugate vaccine.

PREVNAR (PCV7)PREVNAR (PCV7)

• Heptavalent Pneumococcal Vaccine

Fever of Uncertain SourceFever of Uncertain Source

• Most children have a virus• How common is occult bacteremia?

• What tools can we use?

CBC (pre-PVC7 data)CBC (pre-PVC7 data)

• WBC > 15/L » 3-4% bacteremia•Sens 74-86%•Spec 55-77%

• WBC > 20/L » 8-10% bacteremia

• Varies with the organism•EColi ↑WBC compared with controls•Salmonella/Staph/N.Meningitidis Ø∆

• CBC is not super helpful in identifying unsuspected bacteremia in febrile kids

LowRisk

High Risk

≥2 PCV7 vaccinesNo High risk criteria

Temp ≤40oC<2 PCV7 vaccinesContact with meningococcal dzPetechiaeProlonged gastroenteritisAbnormal Urinalysis

Urine CultureUrine Culture

• UTI is common• FUS in 2 month – 2 year olds

•UTI ~3-7%*

• Febrile UTI in children <5y •75% have upper tract disease**

• Renal scarring 9-38%***• hypertension• chronic renal failure• toxemia in pregnancy

* Hoberman, A., H. P. Chao, D. M. Keller, R. Hickey, H. W. Davis, and D. Ellis. 1993. Prevalence of urinary tract infection in febrile infants. J.Pediatr.123:17–23.

**

*** Benador, D., N. Benador, D. Slosman, B. Mermillod, and E. Girardin. 1997. Are younger children at highest risk of renal sequelae after pyelonephritis? Lancet 349:17–19.

CaseCase•18 month ♀•Fever for 3 days

•No alternative source of fever

CaseCase•18 month ♀•Fever for 24 hours

•No alternative source of fever

CaseCase•11 month ♂•Fever for 3 days•Uncircumsized

•No alternative source of fever

Who do we screen?

• UTI Symptoms:– Dysuria/Frequency/Urgency – Suprapubic discomfort– Flank pain

• But young kids present non-specifically– poor feeding– Vomiting– Irritability– Jaundice (in newborns)– Fever alone

UTI UTI History•Diarrhea/Vomiting•Strong smelling urine•Abd/Flank Pain

•Failure to thrive•Fever•New incontinence

Risk Factors Male•Uncircumcised•<6 months•Caucasian Race•Fever ≥ 39oC

Female•<2 years•Caucasian Race•Fever ≥ 39oC

Screening tests for urinary tract infection in children: a Screening tests for urinary tract infection in children: a meta-analysismeta-analysis

• Objective:  To develop a clinical prediction rule to identify febrile young girls needing urine culture for evaluation of UTI

• Design:  Prospective cohort study • Setting:  Urban children's hospital emergency department • Patients:  Girls younger than 2 years (N=1469) presenting to the

emergency department with fever (temperature 38.3°C) and without an unequivocal source

• Main Outcome Measures:  – UTI - defined as a catheterized urine culture with pure growth of 104

colonies/mL– Clinical prediction rules were developed using multiple logistic regression

• Results:  The presence of 2 or more… • < 12 months old, • white race• temperature of 39.0°C or higher• fever for 2 days or more• absence of another source of fever on examination—

…predicted UTI with a sensitivity of 0.95 (95% CI, 0.85-0.99) and specificity of 0.31 (95% CI, 0.28-0.34)

• Conclusion:  Using this clinical decision rule, a strategy of obtaining urine cultures from girls younger than 2 years with a score of 2 or more would lead to identification of 95% of children with UTI and elimination of 30% of unnecessary urine cultures.Gorelick, M. H., and K. N. Shaw. 1999. Screening tests for urinary tract infection in children: a meta-analysis. Pediatrics 104:e54.

Urine Culture•Girls 2-24 months

•Boys – No Decision Rule …that I could find

Chest X-rayChest X-ray

• Children less than 2 yrs•Temp >38o

•Prevalence X%

• ?Occult pneumonia• Viral vs Bacterial• Cost of CXR

• Methods: n=197 Febrile infants ≤3months• Hx, PE• CXR• …other labs

?Combined these results with the results from 2 other studies

• N(total)=617 infants

•Results:

•Chance of a CXR finding in an asymptomatic child 1.02% (95%CI)

•Conclusions: CXRs are not useful in asymptomatic kids

N=617

No Clinical Evidence of Pulmonary Disease(361)

Clinical Evidence of Pulmonary Disease

Normal CXR(361)

Abnormal CXR(0)

Response to Anti-PyreticResponse to Anti-Pyretic

• The use of antipyretics should be noted

• However, a response (or lack thereof) to antipyretic medications does not predict whether the underlying cause is bacterial or viral

Baker MD, Fosarelli PD, Carpenter RO. Childhood fever: correlation of diagnosis with temperature response to acetaminophen. Pediatrics 1987;80(3):315–8.Baker RC, Tiller T, Bausher JC, et al. Severity of disease correlated with fever reduction in febrile infants. Pediatrics 1989;83(6):1016–9.Huang SY, Greenes DS. Effect of recent antipyretic use on measured fever in the pediatric emergency department. Arch Pediatr Adolesc Med 2004;158(10):972–6.Torrey SB, Henretig F, Fleisher G, et al. Temperature response to antipyretic therapy in children: relationship to occult bacteremia. Am J Emerg Med 1985;3(3):190–2.Yamamoto LT, Wigder HN, Fligner DJ, et al. Relationship of bacteremia to antipyretic therapy in febrile children. Pediatr Emerg Care 1987;3(4):223–7.

Case

• 6 week ♀• Tactile fever measured by Mom• In the ED

•Baby looks good•Now: afebrile

• Mom asks “could this be from bundling little Emily too tightly?”

Bundling

• Can cause ↑ in skin temp• Should not cause ↑ in rectal temp

• If you are concerned, unbundle the child and repeat the measurement in 15-30 min• Believe it if…

•The kid looks good•Has not received antipyretics•The parents are reliable

Grover G, Berkowitz CD, Thompson M, et al. The effects of bundling on infant temperature. Pediatrics 1994;94(5):669–73

Thanks

• Dr. Adam Oster• Dr. Marc Francis

Acetaminophen

Infectious agents / Toxins / Mediators of inflammation(Pyrogens)

stimulate

Monocytes / Macrophages / Endothelial cells / Other cell types

release

Pyrogenic cytokines - IL- 1, TNF, IL- 6, IFNs

stimulate

Anterior hypothalamus (Mediated by PGE2)

results in

Elevated thermoregulatory set point

leads to

Increased Heat conservation (Vasoconstriction/ behaviour changes)

Increased Heat production(involuntary muscular contractions)

result in

F E V E R

(Antipyretics/ NSAIDs act here) 

Fever Good?• Many pathogenic bacteria require iron for their

growth• fever is associated with:

– ↓ serum iron – ↑ in the iron-binding protein, Ferritin – Therefore ↓ free iron in the blood

• In vitro: – ↑ lymphocyte transformation response to mitogen– ↑ bactericidal activity of polymorphonuclear

leukocytes– ↑ production of interferon with ↑ temperature

– However, as temperature approached 40 ºC (104 ºF) in these experiments, most of the functions fell to below baseline levels

Fever Good?

Fish and Lizards• Cold-blooded (poikilotherms) • Develop fever in response to infection by

moving to the warmest external environment available – Fever can be prevented – No confounding with ASA

• ↑ mortality when the febrile response is prevented by denying the animals access to a warmer environment

Fever Good?Rabbits• Infected with Pasteurella multocida • Found that survival increased with moderate

fever• However, fevers greater than 2.25 ºC >

baselinesurvival rates decreased

Fever Good?

Rats • infected with Salmonella enteritidis • Demonstrated ↑ mortality in those with

high fever induced by cooling the hypothalamus

• It seems that while fever of moderate degree can enhance certain immunologic responses, these effects may be diminished or even reversed at high body temperatures

What about Kids?

• Design: Randomized, double-blind, placebo-controlled trial

• Setting: Office- and hospital-based pediatric practices• Patients: 72 children between 1-12 years of age

– 31 received placebo and 37 received acetaminophen• Interventions: Acetaminophen 10 mg/kg/dose, was

given at 8 am, 12 pm, 4 pm, and 8 pm for 4 days. Placebo was given to the control group.

• Measurements and main results: The following results were better in the placebo group (p<.05): – time to total scrabbing

• 5.6 days (SD 2.5) versus 6.7 days (SD 2.3) – itching on day 4 in the placebo group

• (symptom score 2.9 (SD 0.20) vs 2.2 (SD 0.26))• Conclusions: Acetaminophen does not alleviate

symptoms in children with varicella and may prolong illness

Fever Bad?

• ↑ metabolic rate • ↑ oxygen consumption• ↑ carbon dioxide production• ↑ demands on the CV and pulmonary systems

– ↑ demands may be detrimental and may offset any immunologic benefit from the fever

• Fever can aggravate cerebral injury

• Fever often makes patients uncomfortable• Fever can precipitate febrile convulsions

– Disturbing – May lead to invasive procedures such as lumbar

punctures

Relationship of Hypothalamic Set Point to Body Temperature

 Normal temperatures at different sites

Body site Type of thermometer Normal range, mean (°C) Fever (°C)

Axilla Hg in glass, electronic 34.7–37.3, 36.4 37.4

Sublingual Hg in glass, electronic 35.5–37.5, 36.6 37.6

Rectal Hg in glass, electronic 36.6–37.9, 37.0 38.0

Ear Infrared emission 35.7–37.5, 36.6 37.6