Erich C. Maul, DO, FAAP Assistant Professor of Pediatrics

Assistant Professor of Pediatrics Pediatric Hospitalist. ... [L. febris] ] 1. ... • Think of this EVERY SINGLE TIME you LP a...

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Fever A Reintroduction to an Old Friend Erich C. Maul, DO, FAAP Assistant Professor of Pediatrics Pediatric Hospitalist

Objectives • Define fi ffever • Discuss management of Fever Without Locali ing Signs in children from birth to 3 years Localizing ears • Discuss other conditions in which fever plays an important role. role

What is Fever? • fever [L. [L febris] 1. 1 Abnormal elevation of temperature. 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 Taber's® 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 acute t phase h reactants, t t and d activation ti ti off iimmune systems. t SYN SYN: ffebris, b i pyrexia • Stedman's Medical Dictionary - 28th Ed. (2006)

What is Fever? • 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 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 morning i and d ttemperatures t approximately i t l 1oC higher hi h in i the th late l t afternoon ft or early evening. • Kliegman: Nelson Textbook of Pediatrics, 18th ed. • I can’t say it any better…

Practically speaking oF) • Fever is i a (rectal) temperature >38oC (100.4 ( ) • Most common reasons for visits to pediatrician’s offices or Emergenc Emergency Departments • Fever is a sign, not a diagnosis • Fever is not necessarily a bad thing

Pros and Cons of Fever Benefits

Drawbacks

• Slows bacterial reproduction and growth • Slows viral replication • Enhanced neutrophil production and T-lymphocyte proliferation • Aids acute phase reaction • Steady income (HaHaHa)

• Increased metabolic demand and oxygen consumption • Increased insensible fluid losses • Lower seizure threshold • Parental anxiety and Fever Phobia

Fever Phobia • Coined i db by Dr Barton Schmitt h i iin 1980 • Showed parents have many misconceptions about fever fe er ▫ 52% thought fever of up to 40oC will cause serious neurological sequelae or DEATH ▫ 85% gave antipyretics ▫ Fever phobia counseling should be a part of routine care

• Revisited by Crocetti in 2001 ▫ Fever phobia h bi persists i and d may even b be worse

Alternating Antipyretics • ““…there h iis iinsufficient ffi i evidence id to support or refute the routine use of combination treatment with both acetaminophen and ibuprofen ibuprofen. Practitioners who choose to follow this practice 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… • Not sure we are doing d i a good d jjob b across the h country with managing fever phobia • We are probably probabl feeding this problem b by recommending alternation of antipyretics • Or by doing so many labs when kids have fevers ▫ Speaking of that…

NOT Fever of Unknown Origin (FUO)

Definition • Speaks k for f itself i lf ▫ <7 days duration

• Classically Cl i ll di divided id d iinto t 3 categories t i ▫ Neonates (0-28 d) ▫ Young infants (1-3 mo) ▫ Older infants/toddlers (3-36 mo)

Why worry about this? • Fever may be b the h only l sign i off serious i b bacterial i l illness (SBI) ▫ Meningitis Meningitis, bacteremia bacteremia, UTI UTI, pneumonia pneumonia, gastroenteritis, osteomyelitis Vaccinations at o s have ave helped e ped change c a ge this t s ▫ Vacc epidemiology  Hib, PCV 7/13

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

H&P Pearls • Should h ld b be rectall temperature ▫ But believe what you have ▫ Get away from adding/subtracting

• Bundling will not increase core temperature • Believe a fever at home, home even if no fever in the office • Underlying medical conditions ▫ Heart dz, lung dz, metabolic dz, past illnesses, premie, unimmunized, ill contacts, etc

H&P Pearls • Height i h off ffever may correlate l with i h SBI ▫ >40oC may have higher rate of SBI

• Ill appearing i iinfants f t are more att risk i k ffor h having i a serious infection…DUH! • Let’s look at each age group and discuss what to do

0-28 days of life

The Nuts and Bolts • Up to 28% off ffebrile b il neonates who h present to the h Ed have an SBI • Escherichia coli, coli Listeria monocytogenes, monocytogenes group B Streptococcus (S. agalactiae), HSV • UTI and bacteremia are most common • No “criteria” predict risk in this group

The Decerebrate Evaluation • • • • •

Blood, l d Urine, i CSF cultures l CBC with differential UA (catheter ( th t or suprapubic) bi ) IV antibiotics Hospital admission until culture negative or pathogen identified • Consider ▫ HSV PCR ▫ Chest XR ▫ Stool cultures

Drugs for Bugs • Ampicillin i illi AND [[gentamicin i i OR cefotaxime] f i ] • Avoid ceftriaxone in neonates unless treating ophthalmia neonatorum • Consider acyclovir ▫ Toxic Toxic, pleocytosis on CSF, CSF seizure seizure, apnea apnea, cutaneous vesicles

29-56 or 90 days

A Sticky Wicket • We have h b better d data to h help l stratify if risk i k iin this hi age groups ▫ Philadelphia, Philadelphia Rochester Rochester, Boston Criteria

• Still requires some invasive testing

Prematurity Prolonged neonatal hospitalization Underlying medical conditions Indwelling medical devices Fever >5 days Already 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 • Trigger i temperature now 39oC, not 38oC ▫ From the concern for occult bacteremia at higher temps ▫ No study post-PCV7 has validated this

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

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

Occult Bacteremia • Most of the data we have on occult b bacteremia i iis ffrom pre-PCV7 C • Changing epidemiology ▫ E. coli bacteremia is just a common as S. S pneumoniae now ▫ E. coli common in 3-12 m/o ▫ S. pneumo common in 6-24 m/o  PCV7 7 has decreased this 4 fold

• CBC not very sensitive or specific 74-86% 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 see ▫ 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 UTI • Prevalence of 2-5% p or urinalysis y alone • Urine dipstick cannot detect all UTI’s ▫ MUST get cultures along with UA • Treat if suggestive gg and wait for cultures ▫ 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 here? • • • •

CRP or procalcitonin l i i Evidence is growing for using these screens L b Lab-score f from S Switzerland it l d shows h promise i CRP and PCT are not readily available at most hospitals ▫ 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 zebras

Medically Fragile Patients • Probably b bl the h greatest challenge h ll iin pediatrics di i • Includes neurologically impaired children, oncolog patients oncology patients, children with ith CVC’s or VPS’s • In this patient population, better to overtest and observe than tell parents to just “wait wait it out out” • Patients with indwelling devices ▫ All are infected until you prove it otherwise ▫ Generally need to culture the devices

HSV Encephalitis • May present with i h ffever, seizures, i cutaneous vesicles • Has HORRIFIC outcomes for CNS and disseminated diseases ▫ 60% mortality in disseminated and severe neurologic sequelae for almost all

• Think of this EVERY SINGLE TIME yyou LP a child

Other Things to Think About • Uncommon U presentation t ti off common iinfections f ti • Kawasaki disease • Febris iatrogenica (don (don’tt look this up in a dictionary dictionary, you won’t won t find it) ▫ Drug side effects ▫ Parental side effects i.e. Medical child abuse, Munchausen’s

• Malignancy • Collagen vascular disease • Uncommon infections ▫ TB,, rickettsial infections,, HIV,, zoonoses,, endocarditis, rheumatic fever

Must Reads • IIshimine, hi i P., P The Th evolving l i approach h to the h young child hild who has fever and no obvious source. Emerg Med 7 25(4): 5(4) p p. 1087-115, 7 5, vii. Clin North Am,, 2007. • Sullivan, J.E. and H.C. Farrar, Fever and antipyretic use in children. Pediatrics, 2011. 127(3): p. 580-7. • Avner, A J.R., J R Acute A t ffever. P Pediatr di t R Rev, 2009 2009. 30(1): 30(1) p. 5-13

References •

• • • • • • • • • •

Andreola, B., et al., Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial f in febrile f infants f and children in the emergency g y department. p Pediatr Infect f Dis J, 2007. infections 26(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 Crocetti, tti M., M N. N Moghbeli, M hb li and dJ J. S Serwint, i t Fever F phobia h bi revisited: i it d h have parental t l misconceptions i ti about b t 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. 36 months off age. g Pediatr Clin North Am,, 2006. Ishimine,, P.,, Fever without source in children 0 to 3 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 Am, 2003 2003. 21(1): p. p 89-99, 89 99 vi-vii. 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…