“Litz” Blitz 2013 Top Articles in Pediatric Hospital Medicine

1. “Litz” Blitz 2013Top Articles in Pediatric Hospital Medicine Benjamin D. Bauer, MD, FAAP June 1st, 2013 A review of recent literature impacting the practice of pediatric medicine

2. Disclosure Statement • Benjamin D. Bauer: • Has no relevant financial relationships to disclose. • Has no conflicts of interest to resolve. • This presentation will not involve discussion of unapproved, off-label, or experimental interventions or medications.

3. Strategy & Criteria for Article Selection: • Reviewed literature from the past 18 months: • Pediatrics, Hospital Pediatrics, JAMApeds, JAMA, NEJM<, Archives of Pediatrics & Adolescent Med, Journal of Pediatrics, Pediatric Infectious Disease, Journal of Hospital Medicine, Pediatric Emergence Care • Selection based on general interest and potential to impact practice of pediatric hospital medicine • General guidelines of the 3 R’s: • Recent, Relevant and Reputable.

4. Strategy & Criteria for Article Selection: • Final selection of articles, also considered ‘clinical grouping’ based on areas of interest to pediatric hospitalists • Here are the clinical topics that will be covered in today’s talk: • Febrile Neonate / SBI • Fluid management • Failure to Thrive • Gastroesophageal Reflux • Hyperbilirubinemia • Bronchiolitis • Pneumonia

5. Disclaimer: • Literature presented was chosen based general interest of the presenter • No claim made regarding whether these are the most well-designed studies on a given topic • The literature discussed should be critically and individually reviewed before change in practice is implemented • Feel free to throw rotten fruit… but kindly wait until the end of the presentation

6. The Febrile Infant

7. Background • Serious Bacterial Infection (SBI) evaluation remains a challenge • SBI Rates as high as 10-12% <3mo of age • UTI accounts for majority of SBI • Bacteremia and meningitis are less common • Risk stratification strategies have been developed; remain controversial • Even those suggesting less invasive strategies push for LP prior to starting antibiotics

8. Background / Study Objective • Rochester Criteria for Febrile Infants: • Infant appears well • Infant has been previously healthy • No evidence of skin, bone, joint or ear infection • Labs: WBC 5K – 15K; Bands < 1,500; < 10 WBCs in U/A; No pus in stool • When ALL criteria met; NPV for SBI is 98.9% • Study Aim: Necessity of performing routine LP in well appearing 30-90 day old febrile infant with U/A suggestive of UTI

9. Study Methods • Retrospective Study • Tertiary care children’s hospital ED; 200 pt/day • 4 year period; October 2001 – August 2005 • Identified all febrile infants 30-90 days of life: • underwent full sepsis work-up: LP for culture, blood culture, urine culture and urinalysis. • Exclusion Criteria: Premature (<35wk), chronic conditions, pre-culture antibiotics, or localizing infection on presentation

10. Results: N = 392 30-90 day febrile infants full sepsis evaluation • Highlights: • 392 patients included • 61% male (241/392) • Mean age 56 days • Overall Rates of Infection: • SBI: 60/392 (15.3%) • UTI: 52/392 (13.3%) • Sepsis: 13/392 (3.3%) • Meningitis: 4/392 (1%) • Only 1 patient with both abnormal U/A and Meningitis 1 + Culture 52 patients 2 + Cultures 7 patients 3 + Cultures 1 patient Blood & Urine 5 patients CSF, Blood & Urine 1 patient CSF, Blood & Urine 1 patient Blood, Urine & CSF 1 patient Urine only 46 patients Urine & Blood 5 patients Urine, Blood & CSF 1 Patient CSF & Blood 2 patients Blood only 5 patients Blood & CSF 2 patients CSF only 1 patients

11. Results • 1 patient with both abnormal U/A and meningitis • 71 day old female: • Urinalysis: LE+, Nitrite+, 4WBCs/HPF • WBC: 2.9 x 109 • Cultures: E. coli (Blood, Urine and CSF) • Clinical: 38.5◦C, irritable, lethargic, mottled • NOT Low Risk by Rochester: Based on signs/sx would have undergone full sepsis work up

12. Patients with meningitis

13. Results • Of the 388 infants without meningitis: • 56 (14%) had an abnormal U/A • 51 (13%) had a culture positive UTI • Negative Predictive Value (NPV): • 98.2% NPV • 100% NPV, if Rochester ‘low risk’ criteria are met • Does not change the overall NPV of the Rochester criteria, but does potentially add to discussion regarding risk of meningitis

14. Study Limitations • May not generalize: Tertiary Care ED vs..outpatient • Small sample size: Decreases power to identify the potential case of meningitis in this population • Retrospective design: Impossible to confirm that all “NON-low risk” infants actually underwent full septic work-up. • Underestimates downstream impact: Does not acknowledge difficulty for those making decisions regarding management, if LP not done at antibiotic initiation.

15. Clinical Bottom Line • Study confirms findings of others: • Combined UTI and meningitis is uncommon in infants <90 days of age ( 0% – 0.3%) • Routine LPs may not be necessary in infants 30-90 days of life, if otherwise low-risk based on Rochester criteria • If any uncertainty, or patient not well appearing then an LP MUST BE DONE prior to starting antibiotics

16. In search of the 24 hour discharge…

17. Background • The management of the febrile infant is evolving • Still common for infants with fever and no clear source to remain in hospital receiving empiric treatment for 48hrs while culture results mature • Some institutions have used available evidence to push the LOS envelope for these patients…

18. Evidence Based Care Process Model

20. Study Objectives • To determine if bacterial cultures in young infants would produce results in <36 hours • With enough reliability to allow for discharge of otherwise healthy infants earlier than the standard 48 hour observation period

21. Methods • Retrospective chart review • Oct 2007 – Feb 2011 (3 yrs 4 months) • All positive culture results (Blood, Urine, CSF) • Drawn on infants 0 – 90 days of age during the evaluation of SBI in ED or as inpatient • Exclusion: Any indwelling lines, shunts, catheters; any cultures drawn while in ICU setting; significant underlying condition; repeat cultures taken from same patient during same stay

22. Results • 283 patients with positive cultures • 2092 Blood cultures were drawn • 38% (38/101) of blood cultures = true pathogens • Mean time to detection (TTD) 13.3 hours (vs.. 25 hrs) • 2283 Urine cultures were drawn • 58% (111/192) of urine cultures = true pathogens • Mean TTD 21 hours (vs.. 26.7 hrs) • 1159 CSF cultures were drawn • 50% (7/14) of CSF cultures = true pathogens • Mean TTD 28.9 hours (vs.. 57.7 hrs)

23. Time To Detection of Bacterial Cultures

24. Bottom Line • This article adds to existing data about management of febrile neonate • Already excellent data to help with risk stratification (Rochester criteria…) • Those infants admitted to the hospital as ‘Low Risk’ have SBI rates in range of 1-3% • In the appropriate clinical and social context • May consider discontinue antibiotics therapy at 36 hours

25. Fluids Management

26. Background • Hospital acquired hyponatremia is common • Neurologic morbidity and death have been documented as a result of iatrogenic hyponatremia • Has raised questions regarding 50yr standard of using Holliday-Segar recommendations for calculating parenteral maintenance fluids • Growing evidence emerging that the use of isotonic fluids may decrease risk

27. Study Objectives • Fully blinded, randomized controlled trial • Determine whether isotonic solution administered as maintenance IV fluids decrease the risk of hyponatremia when compared to hypotonic fluids • Population: euvolemic pediatric patients in the acute post-operative period, with non-emergent reasons for surgery; requiring MIVF for 48hrs

28. Study Methods • IRB approved, Blinded, RCT • Tertiary care children’s hospital, Canada • Randomly assigned to receive base parenteral maintenance solution (PMS) of either 0.45% saline (hypotonic) or 0.9% saline (isotonic) • Dextrose (D5) present in both • Potassium added according treating MD request • 6mo – 16yrs; euvolemic; within 6hrs of non-emergent surgery; likely to need MIVF >24hrs

29. Study methods / Outcome measures • Plasma sodium, Urine sodium/potassium and ADH measured every 12 hours • Intervention was started immediately post-op and continued for maximum of 48hrs • Primary Outcome: Hyponatremia; ≤ 134mmol/L • Secondary Outcomes: Severe hyponatremia (≤ 129mmol/L), hypernatremia (≥ 146mmol/L), plasma ADH levels, adverse events, and patients who changed fluids during study (reason)

30. Results • 3/2008 – 12/2009 • 728 patients screened • 427 eligible • 258 were enrolled • 128 randomized to isotonic fluid • 130 randomized to hypotonic fluid • 4 patents from each group withdrew during study • 32 patients lacked data 14 lacked data 18 lacked data

31. Baseline characteristics • between groups is similar • 77 of 258 (29.8%) admitted • to ICU postoperatively • No differences in baseline • sodium or fluid intake • Only 16 (6%) had pre-op • sodium levels ordered • Median time to starting fluid • intervention was 22minutes • post operatively (6hrs max) • Most common surgery: • Orthopedic, General, Urologic

32. Results: Primary Outcome • Primary Outcomes: Risk of hyponatremia was higher in the hypotonic fluid group:

33. Results: Secondary Outcomes • Plasma ADH levels on POD#1 elevated in both groups, but no difference (P= .208) • Subgroup analysis showed PICU patients at NO higher risk after adjusting for fluid type (P= .105) • 15 pts changed to open-label isotonic fluids • 12 (9.2%) vs.. 3 (2.3%); P = .036 (Hypotonic) (Isotonic) • with ‘Hyponatremia’ most common cited reason • 1 (0.8%) vs.. 7(5.4%); P = .033 (Hypotonic) (Isotonic)

34. Study Limitations • Well-designed, blinded, randomized trial • May Not Generalize: Did not include patients requiring emergency surgeries; did not include non-surgical patients • Baseline Comparison Data: Most patients in study did not have ‘baseline’ lab values prior to enrollment • Missing Data: Not all patients included in study had all planned samples drawn.

35. Clinical Bottom Line • Risk of hyponatremia is significantly higher in post-op patients receiving hypotonic fluids • Relative risk reduction of 44% with isotonic fluid • NNT to prevent 1 case of hyponatremia = 6 • Isotonic fluid use does not appear to increase adverse events or lead to hypernatremia • Current standard of post-operative fluid management should be re-evaluated… • Isotonic fluid may be safer!

36. Failure to Thrive

37. Background • Failure to Thrive (FTT) is common • As many as 10% of general pediatric patients • Outpatient management of failure to thrive “is fraught with difficulties because trying to organize a cohesive approach… is logistically challenging.” • Often assumed that admission may be the more efficient approach, with goal of coordinating multiple resources needed to diagnose and treat • FTT: Up to 5% of all admissions for children less than 2 years of age

38. Background • Heavy resource utilization for these patients: • Labs, imaging, speech, nutrition, social work, and subspecialist consultation • Limited access to many of these resources during the weekend; even at large tertiary referral centers • Is the weekend the best time to admit these patients to the hospital?

39. Study Objectives • To evaluate whether weekend admission of Failure to Thrive: • Affects the length of stay (LOS) • Affects the overall cost of the admission

40. Methods • PHIS database • Administrative data from 43 free-standing children’s hospitals • Inclusion Criteria: • 2003-2011 (9 years of data) • All Children <2 years with primary admit diagnosis of Failure to Thrive • Data: Demographics, LOS, day of admit, diagnoses, procedures, tests, charges/costs

41. Results • 23,332 patients met inclusion criteria • Median age: 7.5 months • 43.8 % (10,222) less than 6 months of age • Weekend admissions STAYED LONGER • LOS increased by 1.93 days (IRR: 1.20 [95% CI 1.18-1.22] • Weekend admissions COST MORE • Mean cost increase of $2785 per admission

42. FTT on Weekends: Cost More, Stay Longer

43. Results

44. Limitations: • PHIS database limitations • Used surrogate data to make assumptions about how ‘sick’ patients were • Institutional bias in financial reporting is possible

45. Author Bottom Line • Acknowledging that some of the weekend admissions had medical issues requiring immediate inpatient attention… • If HALF of the weekend admissions over the study period were simply converted to Monday admissions: • total savings in health care dollars would be in excess of $500,000 per year • or > $3.5 Million over the study period

46. Gastroesophageal Reflux

47. Background • Diagnosis and management of GERD remains challenging for families and pediatricians • From 1999 to 2004, 7-fold increase in use of prescription medication in infants with GERD • Growing evidence that acid reducing medications are NO BETTER than placebo in treating symptoms of GERD • Growing concern regarding safety of these agents in both adults and children

48. Mechanism for increased infection Risk? • Gastric Acid is a known non-selective barrier to infection • Most pathogens will not survive at pH < 4 (normal gastric acidity) • Suppression of acid production may allow bacterial colonization and overgrowth (including pathogenic organisms) • PPIs & H2 Blockers may also directly inhibit leukocyte activity; thereby blunt immune response

49. Objectives & Methods • Review of literature • Evaluate potential serious adverse effects associated with acid-suppressing medications in the pediatric population • PubMed Search: English Language, 0-18 yrs • Limited to original placebo controlled studies OR studies with comparison to non-acid suppression which specifically evaluated adverse events as part of study

50. Results • 14 studies met inclusion criteria • 6 NICU studies • 5 PICU studies • 3 Non-Critical Care Population Studies • Both H2 Blockers and PPIs represented • Associate adverse events primarily ‘infectious’ in nature