FeverA Reintroduction to an Old Friend

Erich C. Maul, DO, FAAPAssistant Professor of PediatricsPediatric Hospitalist

Objectives

fi f• Define fever• Discuss management of Fever Without

Locali ing Signs in children from birth to 3 earsLocalizing Signs in children from birth to 3 years• Discuss other conditions in which fever plays an

important roleimportant role.

What is Fever?• fever [L febris] 1 Abnormal elevation of temperature The normal • fever [L. febris] 1. Abnormal elevation of temperature. The normal

temperature taken orally ranges from about 97.6° to 99.6°F, although there is individual variation. Rectal temperature is 0.5° to 1.0°F higher than oral temperature. Normal temperature fluctuates during the day and is lowest in the morning and highest in the late afternoon; these variations are maintained during a fever. The expended basal energy is estimated to be increased about 12% for each degree centigrade of fever.

◦ Taber's® Cyclopedic Medical Dictionary - 21st Ed. (2009)Taber s® Cyclopedic Medical Dictionary 21st Ed. (2009)

• (fē’-ver) A complex physiologic response to disease mediated by pyrogenic cytokines and characterized by a rise in core temperature, generation of

t h t t d ti ti f i t SYN f b i acute phase reactants, and activation of immune systems. SYN: febris, pyrexia

• Stedman's Medical Dictionary - 28th Ed. (2006)

What is Fever?• Fever is a controlled increase in body temperature over the normal values • Fever is a controlled increase in body temperature over the normal values

for an individual. Body temperature is regulated by thermosensitive neurons located in the preoptic or anterior hypothalamus that respond to changes in blood temperature as well as to direct neural connections with cold and warm receptors located in skin and muscle. Thermoregulatory responses include redirecting blood to or from cutaneous vascular beds, increased or decreased sweating, extracellular fluid volume regulation (via arginine vasopressin), and behavioral responses, such as seeking a warmer arginine vasopressin), and behavioral responses, such as seeking a warmer or cooler environmental temperature. Normal body temperature also varies in a regular pattern each day. This circadian temperature rhythm, or diurnal variation, results in lower body temperatures in the early

i d t t i t l oC hi h i th l t ft morning and temperatures approximately 1oC higher in the late afternoon or early evening.

• Kliegman: Nelson Textbook of Pediatrics, 18th ed.

• I can’t say it any better…

Practically speaking

i ( )• Fever is a (rectal) temperature >38oC (100.4oF)• Most common reasons for visits to pediatrician’s

offices or Emergenc Departmentsoffices or Emergency Departments• Fever is a sign, not a diagnosis• Fever is not necessarily a bad thing• Fever is not necessarily a bad thing

Pros and Cons of Fever

Benefits Drawbacks

• Slows bacterial reproduction • Increased metabolic demand • Slows bacterial reproduction and growth

• Slows viral replication• Enhanced neutrophil

• Increased metabolic demand and oxygen consumption

• Increased insensible fluid losses• Enhanced neutrophil

production and T-lymphocyte proliferation

• Aids acute phase reaction

losses• Lower seizure threshold• Parental anxiety and Fever

Phobia• Aids acute phase reaction• Steady income (HaHaHa)

Phobia

Fever Phobiai d b h i i• Coined by Dr Barton Schmitt in 1980

• Showed parents have many misconceptions about fe erabout fever▫ 52% thought fever of up to 40oC will cause serious

neurological sequelae or DEATHneurological sequelae or DEATH▫ 85% gave antipyretics▫ Fever phobia counseling should be a part of

routine care• Revisited by Crocetti in 2001

h bi i d b▫ Fever phobia persists and may even be worse

Alternating Antipyretics

“ h i i ffi i id• “…there is insufficient evidence to support or refute the routine use of combination treatment with both acetaminophen and ibuprofen with both acetaminophen and ibuprofen. Practitioners who choose to follow this practice should counsel parents carefully regarding should counsel parents carefully regarding proper formulation, dosing, and dosing intervals and emphasize the child’s comfort instead of reduction of fever.”

• Sullivan, J.E. and H.C. Farrar, Fever and antipyretic use in children. Pediatrics, 2011. 127(3): p. 580-7.

Bottom Line…

d i d j b h• Not sure we are doing a good job across the country with managing fever phobiaWe are probabl feeding this problem b • We are probably feeding this problem by recommending alternation of antipyretics

• Or by doing so many labs when kids have fevers• Or by doing so many labs when kids have fevers▫ Speaking of that…

NOT Fever of Unknown Origin (FUO)NOT Fever of Unknown Origin (FUO)

Definition

k f i lf• Speaks for itself▫ <7 days durationCl i ll di id d i t 3 t i• Classically divided into 3 categories▫ Neonates (0-28 d)▫ Young infants (1-3 mo)▫ Young infants (1-3 mo)▫ Older infants/toddlers (3-36 mo)

Why worry about this?

b h l i f i b i l• Fever may be the only sign of serious bacterial illness (SBI)

Meningitis bacteremia UTI pneumonia ▫ Meningitis, bacteremia, UTI, pneumonia, gastroenteritis, osteomyelitis

▫ Vaccinations have helped change this Vacc at o s ave e ped c a ge t s epidemiology Hib, PCV 7/13

• Clinical exam alone, may not be sufficient to detect SBI in certain age groups

H&P Pearls

h ld b l• Should be rectal temperature▫ But believe what you have

Get away from adding/subtracting▫ Get away from adding/subtracting• Bundling will not increase core temperature• Believe a fever at home even if no fever in the • Believe a fever at home, even if no fever in the

office• Underlying medical conditionsUnderlying medical conditions▫ Heart dz, lung dz, metabolic dz, past illnesses,

premie, unimmunized, ill contacts, etc

H&P Pearls

i h f f l i h• Height of fever may correlate with SBI▫ >40oC may have higher rate of SBIIll i i f t t i k f h i • Ill appearing infants are more at risk for having a serious infection…DUH!

• Let’s look at each age group and discuss what to dodo

0-28 days of life

The Nuts and Bolts

f f b il h h• Up to 28% of febrile neonates who present to the Ed have an SBIEscherichia coli Listeria monocytogenes group • Escherichia coli, Listeria monocytogenes, group B Streptococcus (S. agalactiae), HSV

• UTI and bacteremia are most common• UTI and bacteremia are most common• No “criteria” predict risk in this group

The Decerebrate Evaluation

l d i l• Blood, Urine, CSF cultures• CBC with differential

UA ( th t bi )• UA (catheter or suprapubic)• IV antibiotics

Hospital admission until culture negative or • Hospital admission until culture negative or pathogen identified

• Consider• Consider▫ HSV PCR▫ Chest XR▫ Stool cultures

Drugs for Bugs

i illi [ i i f i ]• Ampicillin AND [gentamicin OR cefotaxime]• Avoid ceftriaxone in neonates unless treating

ophthalmia neonatorumophthalmia neonatorum• Consider acyclovir▫ Toxic pleocytosis on CSF seizure apnea ▫ Toxic, pleocytosis on CSF, seizure, apnea,

cutaneous vesicles

29-56 or 90 days

A Sticky Wicket

h b d h l if i k i hi• We have better data to help stratify risk in this age groups

Philadelphia Rochester Boston Criteria▫ Philadelphia, Rochester, Boston Criteria• Still requires some invasive testing

PrematurityPrematurityProlonged neonatal hospitalizationUnderlying medical conditionsIndwelling medical devicesFever >5 daysAlready on antibiotics

Ishimine, P., The evolving approach to the young child who has fever and no obvious source. Emerg Med Clin North Am, 2007. 25(4): p. 1087-115, vii.

2 or 3-36 months

Background

i• Trigger temperature now 39oC, not 38oC▫ From the concern for occult bacteremia at higher

tempstemps▫ No study post-PCV7 has validated this

• Big three SBI’s in this groupBig three SBI s in this group▫ UTI, bacteremia, pneumonia

• This may be a place for rapid viral testingy p p g▫ Influenza especially▫ Not much occult RSV out there

Occult Bacteremia• Most of the data we have on occult

b i i f Cbacteremia is from pre-PCV7• Changing epidemiology▫ E. coli bacteremia is just a common

as S pneumoniae nowas S. pneumoniae now▫ E. coli common in 3-12 m/o▫ S. pneumo common in 6-24 m/o PCV7 has decreased this 4 fold7 4

• CBC not very sensitive or specific74-86% 55-77%

• Use of antibiotics awaiting cultures is controversial, but we all should do it▫ No data to support or refute which

approach is better: abx or wait and seesee

▫ For more details, see the Ishimine 2007 article in References

Occult Bacteremia• ALL kids with positive blood culture

need to be re-examined• If ill appearing▫ Repeat cultures, LP, IV abx and

admission• If afebrile and well appearing▫ Repeat blood culture▫ Repeat abx (IM or PO)

Occult UTIOccult UTI

• Prevalence of 2-5%• Urine dipstick or urinalysis alone p y

cannot detect all UTI’s▫ MUST get cultures along with UA

• Treat if suggestive and wait for ggcultures▫ MUST get cultures…did I forget to

mention that?

Occult Pneumonia• Remember pneumonia is a clinical as well

a radiographic diagnosis▫ Does not require both

• Very poor data looking at this entity• If there is an occult pneumonia, treatment

is still amoxicillin or azithromycin▫ Would only use azithromycin if pt is type 1

PCN allergic

Notice some things that are not Notice some things that are not here?

l i i• CRP or procalcitonin• Evidence is growing for using these screens

L b f S it l d h i• Lab-score from Switzerland shows promise• CRP and PCT are not readily available at most

hospitalshospitals▫ Need to get these tests back as quick as a CBC or

UA before useful• Hope to see recommendations/studies in the US

in the near future

What not to miss when it comes to infants with fevers and what are some of the zebrasare some of the zebras

Medically Fragile Patients

b bl h h ll i di i• Probably the greatest challenge in pediatrics• Includes neurologically impaired children,

oncolog patients children ith CVC’s or VPS’soncology patients, children with CVC’s or VPS’s• In this patient population, better to overtest and

observe than tell parents to just “wait it out”observe than tell parents to just wait it out• Patients with indwelling devices▫ All are infected until you prove it otherwiseAll are infected until you prove it otherwise▫ Generally need to culture the devices

HSV Encephalitis

i h f i• May present with fever, seizures, cutaneous vesiclesHas HORRIFIC outcomes for CNS and • Has HORRIFIC outcomes for CNS and disseminated diseases▫ 60% mortality in disseminated and severe 60% mortality in disseminated and severe

neurologic sequelae for almost all• Think of this EVERY SINGLE TIME you LP a y

child

Other Things to Think About

U t ti f i f ti• Uncommon presentation of common infections• Kawasaki disease• Febris iatrogenica (don’t look this up in a dictionary you won’t find it)• Febris iatrogenica (don t look this up in a dictionary, you won t find it)

▫ Drug side effects▫ Parental side effects i.e. Medical child abuse,

Munchausen’s• Malignancy• Collagen vascular disease• Collagen vascular disease• Uncommon infections▫ TB, rickettsial infections, HIV, zoonoses, , , , ,

endocarditis, rheumatic fever

Must ReadsI hi i P Th l i h h hild • Ishimine, P., The evolving approach to the young child

who has fever and no obvious source. Emerg Med Clin North Am, 2007. 25(4): p. 1087-115, vii., 7 5(4) p 7 5,

• Sullivan, J.E. and H.C. Farrar, Fever and antipyretic use in children. Pediatrics, 2011. 127(3): p. 580-7.

A J R A t f P di t R 2009 30(1) • Avner, J.R., Acute fever. Pediatr Rev, 2009. 30(1): p. 5-13

References• Andreola, B., et al., Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial

infections in febrile infants and children in the emergency department. Pediatr Infect Dis J, 2007. f f f g y p f26(8): p. 672-7.

• Avner, J.R., Acute fever. Pediatr Rev, 2009. 30(1): p. 5-13; quiz 13.

• Claudius, I. and L.J. Baraff, Pediatric emergencies associated with fever. Emerg Med Clin North Am, 2010. 28(1): p. 67-84, vii-viii.

C tti M N M hb li d J S i t F h bi i it d h t l i ti b t • Crocetti, M., N. Moghbeli, and J. Serwint, Fever phobia revisited: have parental misconceptions about fever changed in 20 years? Pediatrics, 2001. 107(6): p. 1241-6.

• Galetto-Lacour, A., et al., Validation of a laboratory risk index score for the identification of severe bacterial infection in children with fever without source. Arch Dis Child, 2010. 95(12): p. 968-73.

• Ishimine, P., Fever without source in children 0 to 36 months of age. Pediatr Clin North Am, 2006. , , 3 f g ,53(2): p. 167-94.

• Ishimine, P., The evolving approach to the young child who has fever and no obvious source. Emerg Med Clin North Am, 2007. 25(4): p. 1087-115, vii.

• King, C., Evaluation and management of febrile infants in the emergency department. Emerg Med Clin North Am 2003 21(1): p 89 99 vi viiNorth Am, 2003. 21(1): p. 89-99, vi-vii.

• Manzano, S., et al., Markers for bacterial infection in children with fever without source. Arch Dis Child, 2011.

• Schmitt, B.D., Fever phobia: misconceptions of parents about fevers. Am J Dis Child, 1980. 134(2): p. 176-81.

• Sullivan, J.E. and H.C. Farrar, Fever and antipyretic use in children. Pediatrics, 2011. 127(3): p. 580-7.

We’ll save questions until the end…