#4: Things We Do For No Reason in Pediatrics

August 5, 2020 | By Justin Berk

Why nebulizers, 48-hour rule outs, and “asthmonia” diagnoses may be wasted breath

Summary

If you’re looking to bring your clinical game to the next level, look no further than this next episode where we’ll discuss three huge areas of medical overuse. By the end of the episode, you’ll know not to give antibiotics in an asthma exacerbation, why it may be okay to discharge a well-appearing infant undergoing sepsis rule-out at 24 hours, and how to expertly use metered-dose inhalers in the inpatient setting. We welcome Drs. Leonard Feldman (@DocLennyF) and Carrie Herzke, both @TWDFNR authors, to explore and educate us on these topics. Listen along here, and follow us @TheCribsiders on #MedTwitter!

Credits

• Written, Produced, and Infographic by: Nicholas Lee, MD
• Infographic: Nicholas Lee, MD
• Cover Art: Chris Chiu, MD
• Hosted and Produced by: Justin Berk, MD; Chris Chui, MD
• Editor: Justin Berk MD; Clair Morgan of nodderly.com
• Guest(s): Leonard Feldman, MD & Carrie Herzke, MD

Keywords: high value care, pediatrics, asthma, febrile infant, sepsis rule out, 48 hour, asthmonia, pneumonia, TWDFNR, things we do for no reason

Time Stamps

• Intro, disclaimer, guest bio 1:00
• Guest one-liner 3:30
• Introduction to “Things We Do For No Reason” 9:00
• #1: Nebulizers v MDI inhalers for asthma in the hospital 13:45
• The “48 hour rule-out” for the febrile infant 26:30
• When you should keep a child in the hospital for longer observation 24:00
• Overall recommendation for sepsis rule out in febrile infant 38:50
• The diagnosis of “asthmonia” 43:45
• The causes of pediatric pneumonia 46:45
• Does bacteria cause an asthma exacerbation? 48:00
• Evidence regarding the treatment of mycoplasma pneumonia 51:24

TWDFNR Pearls

1. When you’re given a clinical pearl in the hospital, consider whether it is “religion versus evidence” and evaluate the evidence surrounding the claim when making clinical decisions.
2. 97% of negative cultures at 36 hours will continue to be negative for true pathogens in neonatal sepsis rule-out.
3. There is no evidence that bacteria incite asthma exacerbations in young children; therefore, there is no indication to prescribe these children antibiotics.
4. There is no evidence suggesting that nebulized beta-agonists perform better than MDIs, and using an MDI can help teach good technique for when they are discharged and won’t have access.
5. A good rule of thumb is 2.5mg and 5mg of nebulization solution is equal to 4 and 8 puffs of albuterol MDI.

Sponsors

Pediatrics On Call podcast by the American Academy of Pediatrics

If you provide medical care to children, Pediatrics On Call — the new podcast from the American Academy of Pediatrics — will help you do it better. Each week, hear the latest news and research on children’s health, on topics from obesity and mental health to keeping the kiddos safe when they’re stuck at home. Subscribe from your favorite podcast provider or find the latest episodes here.

VCU Health CE

We are excited to announce that the Curbsiders are now partnering with VCU Health Continuing Education to offer continuing education credits for physicians and other healthcare professionals. Check out cribsiders.vcuhealth.org and create your FREE account!

The History of Things We Do For No Reason

Started in 2012 at Society of Hospital Medicine Annual Meeting, “Things We Do For No Reason™” was a talk that covered 3 – 4 new topics each year – “the low hanging fruit of high value care.”  Topics include practices that have no evidence behind them, don’t help patients, and are things we should, for the most part, get rid of. These topics have now become a regular series in the Journal of Hospital Medicine.  The goal is for learners to become more skeptical and question norms rather than accept practices without evidence.

Nebulizers versus Metered Dose Inhalers (MDI)

Definitions

A nebulizer works by taking a solution and aerosolizing it for the patient to inhale. Oftentimes, this is administered by a respiratory therapist (RT) in the hospital. A metered dose inhaler sprays a pre-specified dose either directly into the patient’s mouth or into a spacer to be inhaled by the patient. (Fun fact: there used to be a syrup form of beta-agonists that Dr. Feldman and Herzke remember taking when there were children; sadly, this formulation is no longer available.)

Nebs v MDI

Efficacy

In terms of efficacy, there are several reviews that demonstrate that the efficacy of these therapies are similar (Dolovich 2005; Cates 2013). MDIs are associated with decreased levels of tachycardia and tremulousness (Cates 2013; Kerem 1993; Schuh 1999), and they are also associated with decreased time spent in the Emergency Department compared to nebulizers (Cates 2013). Both therapies are likely efficacious in the in-patient setting.

Effectiveness

While both therapies are efficacious, patients will eventually be discharged from the hospital and be dependent on a MDI for control of mild symptoms. The literature has demonstrated that oftentimes children and adults do not know how to properly and effectively use their MDIs once they are not supervised, even if they state that they are confident in how to use it (Alexander 2016). This, unsurprisingly, leads to patients having worse control of their asthma as an out-patient. Switching to MDIs while inpatient allows for significant instruction on how to appropriately use their inhaler.

Using MDIs – How many puffs to give?

In nebulizers, you are delivering a higher dose than an MDI typically. If you want them to be equivalent, a rule of thumb is that 2.5 / 5mg of nebulizer is equal to 4 / 8 puffs of MDI.

Limitations to this TWDFNR

Critically ill patients, such as patients in status asthmaticus, were excluded from all the above analyses, so the commentary regarding MDIs does not apply to this patient population.

Recommendations to Change Practice

At UCSF there was a successful study to use nebulizers for the first 24 hours if necessary then transition to MDI therapy for the remainder of the hospital stay (Moriates 2013).

The “48 Hour Rule-out” for Well-Appearing Febrile Infants

History of the 48-hour rule-out

The 48 hour rule-out is based on studies that were performed in the 1970s, and there are two main reasons why they are not necessarily relevant anymore. First, this was a time-period when culture plates were physically examined by a human to check for growth; therefore, they were only checked once a day (Rowley 1986), meaning that the time to positivity (TTP) was artificially long. (They could turn positive at 25 hours but not be read as positive until 48 hours.) Now, we have specific machines that can detect growth of bacteria in blood cultures (mainly through CO2) and notify staff to be checked for growth at that time. Second, these studies were overly broad and do not include our typical 48-hour rule-out patient, which is a previously healthy infant that has been discharged from the hospital. Their studies included NICU infants and ICU admissions that often grow atypical organisms, such as fungi, that need longer to grow out, which inflated the time to positivity of their cultures (Rowley 1986; La Scolea 1981; Pichichero 1979).

Current time to positivity of cultures

Recent studies of healthy febrile infants with new culture monitoring systems report that TTP for 97% of bacteria treated as true pathogens is ≤36 hours (Evans 2013). Additionally, after 36 hours, the rate of identifying a contaminant increases by 8-fold. No difference was found in infants ≤ 28 days versus those aged 0-90 days. Overall, the mean TTP in infants aged 0-90 days was 15.4 hours, and only 4% of possible pathogens were identified after 36 hours. In other words, you would have to monitor 1,250-2,778 infants past 36 hours in order to catch one bacteremic infant.

How to determine a low-risk infant & limitations

There are well documented clinical criteria via the Rochester (Jaskiewicz 1994), Boston (Baskin 1992), and Philadelphia (Baker 1993) studies that can be used to formally decide (Herzke 2018). Dr. Herzke considers monitoring an infant for longer than 36 hours if there is a clinical suspicion for HSV, abnormalities on CSF/urine studies, and/or if the child is not well-appearing.

Recommendations to Change Practice

• Use any of the above scores that you would prefer to determine if your infant is low risk
• If your infant fits the criteria and is well-appearing, you can feel comfortable discharging them at 24 to 36 hours
• If you have good follow-up, you can consider discharge as early as 24 hours
• Expert opinion: Dr. Herzke occasionally gives a dose of ceftriaxone if she is discharging a patient at 24 hours for additional coverage
• Be wary of positives after 36 hours since there is an 8-fold increase in contaminants

“Asthmonia”

The co-existence of asthma and pneumonia

Overall, there is data that asthma and pneumonia are co-diagnosed per records review, but the true question is whether they actually co-exist. From 2007-2012, out of 42 hospitals, 43% of patients with a community acquired pneumonia (CAP) diagnosis were also diagnosed with an asthma exacerbation (Wilson 2015). The evidence, especially in small children, that these are bacterial CAP triggering asthma flares is quite slim. First, bacteria are a rare etiology of pneumonia, especially in children < 5 years old with viruses causing up to 80% of pneumonia (Jain 2015). This suggests that it is unlikely that bacteria are causing pneumonia in young children – let alone causing a pneumonia that is inciting an asthma exacerbation.

In older children and adults, what bacteria could potentially be at play?

Breakdown of bacteria

In children and adults, there are studies that compare the bacterial populations of patients with asthma exacerbations versus controls. There was no significant difference in S. pneumoniae; the only difference between the two groups was in the rates of Mycoplasma, which were more present in the group with asthma exacerbations (Lieberman 2003).

Mycoplasma is the cause then?

Not quite. First, children that test positive for Mycoplasma often test positive for other viruses that are much more likely to trigger an asthma exacerbation (Duenas Meza 2016). Additionally, it is, again, quite uncommon for young children to have a pathogenic Mycoplasma infection, and there are meta-analyses that demonstrate that treating Mycoplasma does not necessarily improve clinical outcomes (Biondi 2014). Expert opinion: Dr. Feldman states that the one population that he considers treatment in are adolescents that have a clinical history consistent with a walking pneumonia.

Azithromycin: Treating Mycoplasma or inflammation?

Antibiotics may improve peak-flow and symptoms (Stokholm 2016). Per Dr. Feldman, it’s “kind of like taking hydroxychloroquine for COVID.” Dr. Herzke also points out that you are going to give a steroid burst anyway that should resolve the inflammation quite well.

Recommendations to Change Practice

• Don’t take a chest x-ray in asthma exacerbation! If there is a slight fever, it is likely due to the virus triggering the asthma exacerbation and not a bacterial pneumonia. If you don’t take the CXR, you won’t treat empirically for CAP.
• Resist the urge to treat with antibiotics, even if they were initiated in the ED.
• Expert opinion: In an older adolescent with history consistent with walking pneumonia, can consider empiric treatment.

Links

1. Things We Do For No Reason article series by JHM

Goal

Listeners will explain three clinical scenarios of low-value care and be able to more effectively manage these scenarios in the future.

Learning objectives

After listening to this episode listeners will…  

1. Plot a path towards high value care
2. Describe the benefits of using an MDI in the in-patient setting compared to nebulizer
3. Educate families why nebulizers may not provide additional benefit compared to inhalers
4. Explain why a 48 rule-out may not be necessary given recent literature
5. Apply a framework for approaching possible consolidations in asthma exacerbations

Disclosures

Dr. Feldman and Herzke report no relevant financial disclosures. The Cribsiders report no relevant financial disclosures. 

Citation

Herzke C, Feldman L, Lee N, Chui C, Berk J. “Things We Do For No Reason in Pediatrics”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ August 5, 2020.

References

1. Dolovich MB, Ahrens RC, Hess DR, Anderson P, Dhand R, Rau JL, Smaldone GC, Guyatt G. Device selection and outcomes of aerosol therapy: evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest. 2005 Jan 1;127(1):335-71. PMID: 15654001.
2. Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta‐agonist treatment of acute asthma. Cochrane database of systematic reviews. 2013(9). PMID: 24037768.
3. Kerem E, Levison H, Schuh S, O’Brodovich H, Reisman J, Bentur L, Canny GJ. Efficacy of albuterol administered by nebulizer versus spacer device in children with acute asthma. The Journal of pediatrics. 1993 Aug 1;123(2):313-7. PMID: 8345434.
4. Schuh S, Johnson DW, Stephens D, Callahan S, Winders P, Canny GJ. Comparison of albuterol delivered by a metered dose inhaler with spacer versus a nebulizer in children with mild acute asthma. The Journal of pediatrics. 1999 Jul 1;135(1):22-7. PMID: 10393599.
5. Alexander DS, Geryk L, Arrindell C, DeWalt DA, Weaver MA, Sleath B, Carpenter DM. Are children with asthma overconfident that they are using their inhalers correctly?. Journal of Asthma. 2016 Jan 2;53(1):107-12. PMID: 26366974.
6. Moriates C, Novelero M, Quinn K, Khanna R, Mourad M. “Nebs no more after 24”: a pilot program to improve the use of appropriate respiratory therapies. JAMA internal medicine. 2013 Sep 23;173(17):1647-8. PMID: 23877555.
7. Rowley AH, Wald ER. The incubation period necessary for detection of bacteremia in immunocompetent children with fever: implications for the clinician. Clinical pediatrics. 1986 Oct;25(10):485-9. PMID: 3757393.
8. La Scolea LJ, Dryja D, Sullivan TD, Mosovich L, Ellerstein N, Neter E. Diagnosis of bacteremia in children by quantitative direct plating and a radiometric procedure. Journal of clinical microbiology. 1981 Mar 1;13(3):478-82. PMID: 6787069.
9. Pichichero ME, Todd JK. Detection of neonatal bacteremia. J Pediatr. 1979;94(6):958‐960. PMID: 376806.
10. Evans RC, Fine BR. Time to detection of bacterial cultures in infants aged 0 to 90 days. Hospital Pediatrics. 2013 Apr 1;3(2):97-102. PMID: 24340409.
11. Jaskiewicz JA, McCarthy CA, Richardson AC, White KC, Fisher DJ, Powell KR, Dagan R. Febrile infants at low risk for serious bacterial infection—an appraisal of the Rochester criteria and implications for management. Pediatrics. 1994 Sep 1;94(3):390-6. PMID: 8065869.
12. Baskin MN, O’Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. The Journal of pediatrics. 1992 Jan 1;120(1):22-7. PMID: 1731019.
13. Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever in selected infants. New England Journal of Medicine. 1993 Nov 11;329(20):1437-41. PMID: 8413453.
14. Wilson KM, Torok MR, Localio R, McLeod L, Srivastava R, Luan X, Mohamad Z, Shah SS. Hospitalization for community-acquired pneumonia in children: effect of an asthma codiagnosis. Hospital pediatrics. 2015 Aug 1;5(8):415-22. PMID 26231631.
15. Jain S, Williams DJ, Arnold SR, Ampofo K, Bramley AM, Reed C, Stockmann C, Anderson EJ, Grijalva CG, Self WH, Zhu Y. Community-acquired pneumonia requiring hospitalization among US children. New England Journal of Medicine. 2015 Feb 26;372(9):835-45. PMID: 25714161.
16. Lieberman D, Lieberman D, Printz S, Ben-Yaakov M, Lazarovich Z, Ohana B, Friedman MG, Dvoskin B, Leinonen M, Boldur I. Atypical pathogen infection in adults with acute exacerbation of bronchial asthma. American journal of respiratory and critical care medicine. 2003 Feb 1;167(3):406-10. PMID: 12426232.
17. Duenas Meza E, Jaramillo CA, Correa E, Torres-Duque CA, Garcia C, González M, Rojas D, Hernández A, Páez AM, Delgado MD. Virus and Mycoplasma pneumoniae prevalence in a selected pediatric population with acute asthma exacerbation. Journal of Asthma. 2016 Mar 15;53(3):253-60. PMID: 26799194.
18. Biondi E, McCulloh R, Alverson B, Klein A, Dixon A, Ralston S. Treatment of mycoplasma pneumonia: a systematic review. Pediatrics. 2014 Jun 1;133(6):1081-90. PMID: 24864174.
19. Stokholm J, Chawes BL, Vissing NH, Bjarnadóttir E, Pedersen TM, Vinding RK, Schoos AM, Wolsk HM, Thorsteinsdóttir S, Hallas HW, Arianto L. Azithromycin for episodes with asthma-like symptoms in young children aged 1–3 years: a randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. 2016 Jan 1;4(1):19-26. PMID: 26704020