My Baby Has a Fever!

1. My Baby Has a Fever! A case based approach to evidence based guidelines for managing febrile infants Nicole Laney, MD

2. Why does this matter? • What temperatures should I be worried about? • How should I counsel patients on antipyretic use? • Which tests are appropriate? • What are the benefits and harms of treatment? What you need to know

3. Serious bacterial infection (SBI) = illness that can be life threatening and require hospitalization and antibiotics • Urinary tract infection (UTI) • Pneumonia • Bacteremia • Meningitis • +/- bacterial gastroenteritis, bone/joint infections, skin/soft tissue infections • Invasive bacterial infection (IBI) = used by some studies to identify the most life threatening SBIs • Bacteremia • Meningitis • High risk/low risk = hospitalization vs safe for 24 hour outpt follow up • Combine both clinical and laboratory criteria • Philadelphia, Boston, Rochester, lab-score, etc Definitions

4. ~10% of febrile infants <90 days old will have SBI • Fever accounts for approximately 1/3 of presenting pediatric complaints • Parental concern for untreated high fevers • Most common fears: seizures, brain damage, death • Parental misconceptions: • 50% of parents believe a temperature <38° C is a fever • 25% caregivers give antipyretics for temperatures <37.8° C • 50% caregivers administer incorrect doses of antipyretics • Adverse effects of overtreatment Why does this matter?

5. 6 week full term female infant • Temporal artery thermometer 38.3°C at home • Feeding and behaving normally • No change in UOP or stools. • Exam: well appearing infant with rectal temp 37.5°C. All other vitals normal. Case 1: Work up for fever or not?

6. Fever in an infant < 3 months is considered ≥ 38°C rectally • Gold standard = rectal temperature • Used in the majority of studies • May have significant lag with rapidly changing temperatures • Axillary • Sensitivity 48%, specificity 96%1 • Tympanic • Sensitivity 55%, specificity 100%1 • Temporal • Sensitivity 83%, specificity 86%2 • Similar accuracy to tactile assessment • Oral (pacifier) • Sensitivity 48%, specificity 99%2 What is a fever and how do we measure it? 1: Study of 224 children <3 years old, Muma et al. Annals of Emergency Medicine. 1991. 2: Study of 200 infants <3 months old, Callanan. Pediatric Emergency Care. 2003.

7. Retrospective study of 292 infants <2 months old that presented to the ED with a history of fever. • 6.5% were found to have SBI • 27% of which were afebrile on presentation to the ED • Retrospective study of 27 neonates presenting to the ED with a history of fever, but afebrile on presentation. • All admitted for r/o sepsis work up • 37% had identifiable infections • Standard of care = report of fever at home warrants a fever work up, the risk of missing a SBI is too great Fever in the office vs. at home? Bonadio, et al. Correlating reported fever in young infants with subsequent temperature patterns and rate of SBI. Pediatric Infectious Disease Journal 1990 Brown et al. Investigation of afebrile neonates with a history of fever. CJEM. 2004.

8. 20 term newborns. Control group: one blanket in 24°C (75°F) room; experimental group: 5 blankets and a hat in a 26.6° C (80°F) room. Continuous rectal probes measured temps for 2.5 hrs. • Mean change: control (-0.04°C), experimental (+0.56°C) • 2 infants reached 38°C • 64 term newborns. Control: diaper + pajamas; experimental: diaper, pajamas, hat, receiving and thermal blanket. Both groups in 72-75°F room. Rectal and skin temps measured q5 min x65 min. • Mean change rectal temp: control (<-0.01°C), experimental (+0.06°C) • Mean change skin temp: control (+1.5°C), experimental (+2.67°C) • Skin temp returned to within 0.6°C of baseline within 5 min of unbundling But she was bundled! Cheng, et al. Effect of bundling and high temperature on neonatal body temperature. Pediatrics. 1993. Grover, et al. The effects of bundlig on infant temperature. Pediatrics. 1994.

9. A fever is a rectal temp ≥ 38°C, but any temperature reported by caregivers taken by any method that is ≥ 38°C should warrant a work up for fever • Bundling does not discount a fever unless it is under extreme circumstances Case 1: Take Home Points

10. 9 week full term male • ED f/u: diagnosed with a viral respiratory infection and sent home • Somewhat decreased PO intake, but adequate UOP, and is still having occasional fevers and is fussy Case 2: Antipyretics

11. Goals: • Reduce fevers that are >40° • Improve infant comfort and improve dehydration • No evidence to support reduction of morbidity/mortality from fever reduction during a febrile illness • Acetaminophen: • Smaller side effect profile • Narrow therapeutic window • Ibuprofen: • Not recommended for outpt use age <6 months • Greater side effect profile • Combination therapy results in lower body temperatures for a greater duration of time • Unclear if this results in improved patient comfort • Increases risk of medication errors Fever treatment goals

12. Tylenol versus Motrin

13. Sponging with cool water • Rapid temperature reduction, short lasting effect • Uncomfortable for patients • May actually cause heat conservation, and increase the use of body energy (shivering) • Risk of significant adverse effects, not recommended: • Topical rubbing alcohol • Ice packs • Cool enemas Non-medicine options Aluka, et al. Comparison of cold water sponging and acetaminophen in control of fever among children attending a tertiary hospital in South Nigeria. Journal of Family Medicine Primary Care. 2013. Meremikqu, et al. Physical methods for treating fever in children. Cochrane. 2003.

14. Treat fevers with the goal of comfort and reducing dehydration, not treating the numbers • Acetaminophen is the best choice for children <6 months old. For children >6 months old, pick one antipyretic and stick to it. • Make sure parents know the weight based dosing for their children. • Avoid non-medication based methods for reducing fever. Case 2: Take Home Points

15. 7 week full term female • Fussy and decreased PO • Febrile to 38.2° rectally. • Pertinent exam findings: • Temp 38.5° (rectal) all other vitals wnl • Somewhat fussy but consolable, nontoxic appearing • No other focal findings Case 3: Orders, doctor?

16. CBC w/diff • Blood culture • CRP • PCT • CXR • LP • Stool studies • Rapid flu • RSV • Urine analysis • Urine culture Which studies do you want?

17. CBC w/diff • Blood culture • CRP • PCT • CXR • LP • Stool studies • Rapid flu • RSV • Urine analysis • Urine culture Which studies do you want?

18. Goal: find a SBI or stratify pt into high or low risk • High risk = admitted for empiric antibiotics • Low risk = sent home with 24 hour follow up • CBC w/diff • WBC overall poor sensitivity/specificity for SBI, but useful in conjunction with other studies to stratify risk • Blood cultures • Should be obtained in all febrile infants <3 months • Urine studies • UTIs are common in febrile infants • Catheterized specimen only, all sent for culture

19. Increase sensitivity and specificity of work up • Often a component of newer predictive criteria • C reactive protein (CRP): • Longer history of evidence than PCT • Less expensive test • Procalcitonin (PCT): • More specific than CRP • Correlates to severity of SBI Why use inflammatory mediators?

20. Andresola, et al. Procalcitoninand C-Reactive Protein as Diagnostic Markers of Severe Bacterial Infections in Febrile Infants and Children in the Emergency Department. Pediatric Infectious Disease Journal. 2007

21. Gomez, et al. Diagnostic Value of Procalcitonin in Well-Appearing Young Febrile Infants. Pediatrics. 2012

22. 8 week term female • Well appearing • Initial work up is negative, cultures pending • Reliable parents • Discharged home with 24 hr follow up • Parents want to know why she isn’t being treated Case 4: Empiric antibiotic risks

23. Review of 9 studies, including management of 4,497 infants aged 0-3 months: • All infants categorized as low risk, later found to have SBI, were hospitalized and treated without any adverse effects or complications • Review of 10 studies, including infants determined to be at high risk for SBI and treated immediately with antibiotics: • <1% drug related rash • Up to 20% IV infiltration issues Why not treat everyone? Diagnosis and management of febrile infants (0-3 months). AHRQ Publication. 2012.

24. Prospective study of 62 low-risk febrile infants age 29-60d evaluated in the ED: 56 were eventually admitted and treated with IV antibiotics. 2 infants total found to have SBIs (UTI). • Average length of stay: 49 hours • Average cost: $6202 (71% on Medicaid) • 24.5% had diarrhea by discharge day 7 Condra, et al. Charges and complications associated with the medical evaluation of febrile young infants. Pediatric Emergency Care.2010

25. 60 parents interviewed after their infant underwent a rule out sepsis work up: • 36% breastfeeding problems, 18% stopped breastfeeding • 43% financial stress • 35% perceived their child to be less healthy, 33% perceived iatrogenic problems Consider less tangible complications

26. Use appropriate clinic and laboratory values to stratify infants into high and low risk groups • Consider the risks of empiric antibiotic treatment and utilize the high and low risk groups appropriately Case 3 & 4: Take Home Points

27. Aluka, et al. Comparison of cold water sponging and acetaminophen in control of fever among children attending a tertiary hospital in South Nigeria. Journal of Family Practice Primary Care. 2013 Apr;2(2):153-8. • Andreola, et al. Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department. Pediatric Infectious Disease Journal. 2007 Aug;26(8):672-7. • Bachur, et al. Predictive model for serious bacterial infections among infants younger than 3 months of age. Pediatrics. 2001 Aug;108(2):311-6. • Baker, et al. The efficacy of routine outpatient management without antibiotics of fever in selected infants. Pediatrics. 1999 Mar;103(3):627-31. • Bonadio, et al. Correlating reported fever in young infants with subsequent temperature patterns and rate of serious bacterial infections. Pediatric Infectious Disease Journal. 1990 Mar;9(3):158-60. • Brown, et al. Investigation of afebrile neonates with a history of fever. CJEM.2004 Sep;6(5):342-8. • Byington, et al. Costs and infant outcomes after implementation of a care process model for febrile infants. Pediatrics. 2012 Jul;130(1):e16-24. • Callanan, et al. Detecting fever in young infants: reliability of perceived, pacifier and temporal artery temperatures in infants younger than 3 months of age. Pediatric Emergyency Care. 2003 Aug;19(4):240-3. • Cheng, et al. Effect of bundling and high environmental temperature on neonatal body temperature. Pediatrics. 1993 Aug;92(2):238-40. References

28. Condra, et al. Charges and complications associated with the medical evaluation of febrile young infants. Pediatric Emergency Care. 2010 Mar;26(3):186-91. • Diagnosis and management of febrile infants (0-3 months). AHRQ Publication. No 12-E004-EF. March 2012. • El-Radhi, et al. Determining fever in children: the search for an ideal themometer. British Journal of Nursing. 2014 Jan23-Feb12;23(2):91-4. • Evaluation and management of fever in the neonate and young infant (less than three months of age). Up To Date. 2014. • Galetoo-Lacour, et al. Validation of laboratory risk index score for the identification of severe bacterial infection in children with fever without source. Archives of Disease in Childhood. 2010 Dec;95(12):968-73. • Girodias, et al. Approach to the febrile child: A challenge bridging the gap between the literature and clinic practice. Pediatric Child Health. 2003 Feb;8(2):76-82. • Girodias, et al. Approach to the febrile child: A challenge bridging the gap between the literature and clinic practice. Pediatric Child Health. 2003 Feb;8(2):76-82. • Gomez, et al. Diagnostic value of procalcitonin in well-appearing young infants. Pediatrics. 2012 Nov;130(5):815-22. • Greenes, et al. When body temperature changes, does rectal temperature lag? The Journal of Pediatrics. 2004 June;144(6):824-26. • Grover, et al. The effects of bundling on infant temperature. Pediatrics. 1994 Nov;94(5):669-73. References

29. Lacour, et al. A score identifying serious bacterial infections in children with fever without source. Pediatric Infectious Disease. 2008 Jul;27(7):654-6. • Mahajan, et al. Procalcitonin as a Marker of Serious Bacterial Infections in Febrile Children Younger Than 3 Years Old. Academic Emergency Medicine. 2014 Feb;21(2):171-179. • Meremikwu, et al. Physical methods for treating fever in children. Cochrane Database Systemic Reviews. 2003;2:CD0046264. • Muma, et al. Comparison of rectal, axillary, and tympanic membrane temperatures in infants and young children. Annals of Emergency Medicine. 1991 Jan;20(1): 41-44. • Niehues, et al. The febrile child: diagnosis and treatment. DeutschesArzteblatt International. 2013 Nov;110(45):764-73. • Paes, et al. Accuracy of tympanic and infrared skin thermometers in children. Archives of Disease in Childhood. 2010 • Paul, et al. Efficacy of standard doses of ibuprofen alone, alternating and combined with acetaminophen for the treatment of febrile children. Clinical Therapy. 2010 Dec;32(14):2433-40. • Sherman, et al. Current challenges in the diagnosis and management of fever. Current Opinion in Pediatrics. 2012 Jun;24(3):400-6. • Sullivan, et al. Fever and antipyretic use in children. Pediatrics. 2011 Mar;127(3):580-7. • Teagle, et al. Is fever phobia driving inappropriate use of antipyretics. Archives of Disease in Childhood. 2014 Mar. Epub. References