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Are we measuring what we think we are?

Posted by ashriner on November 17, 2015

pulse oxReviewer:  Andrew Shriner, MD

Article:  Cunningham S, et al.  “Oxygen saturation targets in infants with bronchiolitis (BIDS):  a double-blind, randomised, equivalence trial.”  Lancet.  2015 Sep 12;386(9998):1041-8.  doi: 10.1016/S0140-6736(15)00163-4.

Link to Article:  click here

Why this article?:  The advent of pulse oximetry has been implicated as one of the main reasons why we have seen such a dramatic increase in hospitalization for infants with bronchiolitis over the last 20-30 years (without any other signs of increasing morbidity/mortality associated with the infection).  And, oxygen saturation has been cited as one of the main determinants for LOS for children admitted with bronchiolitis.  With differing recommendations between the US and UK on target oxygen saturation for these children (90% and 94%, respectively), the authors of this study aimed to assess whether a target of starting oxygen supplementation at SpO2 <90% was equivalent to a higher threshold of <94%.

Methods:  The study was carried out by enrolling infants hospitalized at several different children’s hospitals in the UK over a span of 2 bronchiolitis seasons.  They included infants ages 6 weeks to 12 months of age (corrected for prematurity) who were clinically diagnosed with bronchiolitis.  Infants were excluded from the study if they had any of the following issues:

  • born at < 37 weeks gestation and received oxygen within 4 weeks of admission
  • cyanotic or hemodynamically significant heart disease
  • CF or interstitial lung disease
  • immunodeficiency
  • admitted to ICU

Children were randomized to a standard pulse oximeter or a modified pulse oximeter which displayed a value of 94% if the measured SpO2 was actually 90%.  Infants were to be started on supplemental oxygen if the displayed oxygen saturation was < 94%.

The primary outcome for equivalence was time to resolution of cough.

Other outcomes measured included:

  • time to feed adequately (> 75% usual)
  • time to parental perception of “back to normal”
  • SpO2 measured at 28 days
  • timing of readiness for discharge and actual discharge
  • adverse events (PICU transfers, readmits, etc)

Results:  There was a total of 615 patients included in the study:  308 in the standard group, 307 in the modified group.  The modified group did include significantly more boys than girls and also had more preterm infants than the standard group.  Otherwise, there were no differences between groups.

  • Median time to cough resolution was 15 days in both groups.
  • SpO2 values at day 28 were not different between the groups.
  • Infants in the modified group returned to adequate feeding 2.7 hrs sooner and were considered “back to normal” by parents one day sooner.*
  • Transfers to ICU were greater in the modified group (13 vs. 8)*
  • Readmissions to the hospital were higher in the standard group (26 vs. 12)*
  • Supplemental oxygen was given to 73% of infants in the standard group and to 56% of infants in the modified group.  Oxygen was used for significantly longer periods of time in the standard group (27.6 hrs vs. 5.7 hrs).
  • Infants in the modified group were ready for discharge sooner (30.2 hrs vs. 44.2 hrs ) and were discharged sooner (40.9 hrs vs. 50.9 hrs).

*Not statistically significant

Conclusions:  The authors conclude that using a target SpO2 of 90% or higher is as safe and effective as one 94% or higher and they also report some findings which indicate that outcomes may actually be better.  But…the study probably deserves a little closer scrutiny.

Discussion:  I think the first thing that needs to be addressed is the primary outcome:  Time to resolution of cough.  I was (and still am wondering) exactly why this was chosen as the primary outcome as I have a hard time seeing how modifying our threshold to start oxygen is going to impact the disease course (i.e. length of cough) for children with bronchiolitis and would not have expected a difference in the first place.  The authors briefly address this stating that cough is “associated with airway inflammation and might be influenced by hypoxia.”  Two articles are cited at that point, which upon my reading, both appear to outline the mechanisms of airway inflammation for children with viral LRTIs, with neither one commenting on the role of hypoxia as a factor.  Using this measure as a primary outcome to determine equivalency seems very odd and is concerning when it is used to argue that the SpO2 targets are not only equivalent, but equally safe.

There are also a few other things I would’ve liked to have seen measured to make the study a little more robust.  One thing that I would have loved to see would have been measures of clinical severity to ensure the groups were equal in disease severity, which would have an impact on many of their secondary outcomes.  They could have also looked at other interventions to ensure there wasn’t any other possible confounding variables between the groups (such as frequency and method of nasal suctioning).  While harder to measure, looking at patient comfort level could have also been considered to ensure infants weren’t being too bothered by a nasal cannula when their pulse ox was 92% while also ensuring they weren’t overly distressed by mild hypoxia of 90% which would have been treated with oxygen in the standard group.

When looking at other outcomes measured in this study, I think we should give some pause as far as the claim for safety goes with the higher rate of PICU transfers noted in the modified group (though this wasn’t statistically significant and if we’re keeping track of insignificant results, there were also 2 deaths in the standard group vs. 0 deaths in the modified group).  Neurocognitive effects of hypoxia is usually brought up as a safety concern as well, but I tend to side with the authors on this that most of the evidence we have to date is encouraging that children with mild and brief hypoxia during short-lived illnesses is unlikely to cause any long-term consequences.

Despite having some concerns about the choice of primary outcome for this study, overall, my takeaway is that there appears to be no clear safety concerns and more potential benefits to having a lower threshold for starting oxygen; including having kids on oxygen less, discharging patients home sooner, parents feeling like their children get better faster, having children resume usual feeds sooner and having fewer readmissions.

Lastly, as I side note…I was impressed at the low rates of both antibiotic and bronchodilator use on arrival that was reported for this cohort of patients (about 8% and 5%, respectively)!  Would like to know how they did that!

Posted in bronchiolitis, pulse oximetry | Leave a Comment »

Evidence is Snot Clear for Hypertonic Saline Use in Bronchiolitis

Posted by ashriner on October 7, 2015

bronchiolitis%20don%27t%20do%20muchReviewer: Richelle Baker, MD

Article: Zhang, L et al. “Nebulized Hypertonic Saline for Acute Bronchiolitis: A Systematic Review.” Pediatrics. 2015 Oct; 136 (4): 687-701.

Linkclick here

Why this article? Bronchiolitis season is upon us again! I know you’re all wondering, “Isn’t there anything I can do besides supportive care and nasal suctioning?” The 2014 AAP guidelines for bronchiolitis state that hypertonic saline (HS) may be administered to hospitalized children but not given to patients in the ED. This (weak) recommendation is based on randomized controlled trials with inconsistent findings, which showed HS might shorten hospital stay if LOS is greater than 72 hours. I chose this article to investigate whether there is any recent evidence to support the use of HS.

Methods:  This article describes a systematic review and meta-analysis of randomized control trials (RCTs) or quasi-RCTs of infants up to 24 months of age with the diagnosis of acute bronchiolitis. Articles were found in PubMed and the Virtual Health Library of the Latin American and Caribbean Center on Health Sciences Information. They looked at inpatients and patients in the ambulatory care unit or ED, comparing those who received nebulized HS alone or mixed with a bronchodilator versus nebulized normal saline (NS) alone or mixed with a bronchodilator or versus standard treatment.

Results:  A total of 24 trials involving 3209 patients were included in the review. 22 of these trials were included in the meta-analyses. Of note, a few of the included RCTs were also used for the 2014 AAP guidelines and 14 of the 24 articles were published before 2014. Here are the basic results of the primary and secondary outcomes of the study:

  • Length of stay (LOS): The results of 15 trials (1956 inpatients) showed a statistically significant shorter mean LOS among patients treated with HS versus those with NS or standard care (mean reduction of 0.45 days). There were widely varying results between studies though, and the most recent 8 trials did not show a significant difference. The trials that showed significant effects had an unclear or high risk of selection bias.
  • Improvement in Clinical Severity Scores (CSS): They reviewed 11 inpatient trials which overall did show a significant improvement in CSS with the use of HS, with mean difference in CSS of -0.99, -1.45, and -1.44 on day 1, day 2 and day 3 of admission, respectively.  Nine outpatient trials were analyzed and did not show significant improvement in CSS when HS used.
  • Admission Rate: The seven trials included showed a reduced risk of hospitalization by 20% when compared with NS. There was a reduced risk of hospitalization when three or more doses of HS were given in comparison to less than three doses.
  • Rate of Readmission to the Hospital or ED: The meta-analysis of 5 trials did not show significant effects of HS in reducing the risk of readmission to the hospital or the ED.
  • Oxygen saturation, duration of oxygen supplementation, measurement of respiratory rate and heart rate, radiograph scores, duration of tube feeding and parental perception of improvement and quality of life– No significant differences seen for these outcomes. Two studies reported a shorter duration of respiratory symptoms and signs when treated with HS.
  • Safety of Nebulized NS: 21 of the 24 studies included safety data, and there were no significant differences between adverse effects. Meta-analysis could not be completed due to variation in reporting. Most adverse effects were mild and resolved spontaneously.

Conclusions/Discussion: This article showed that there is still not enough evidence to show any clear benefits to nebulized hypertonic saline use in inpatients with bronchiolitis. Although there was a significant difference in LOS for hospitalized patients with bronchiolitis, there was a lot of heterogeneity between studies to consider, along with the fact that the newest studies did not favor HS.  The mean reduction in LOS was also only half a day. The study did however show that nebulized HS appears safe, so it may be worth the risk to attempt in sick patients. Few trials also showed a decreased rate of admission from the ED when HS was used, which conflicts with the 2014 guidelines. There still needs to be larger, multicenter trials completed in order to accurately evaluate the effects of nebulized HS in children with bronchiolitis. Who wants to get one started?

Posted in bronchiolitis, hypertonic saline | 1 Comment »

Rule-out sepsis, rule-out breastfeeding?

Posted by ashriner on September 21, 2015

BF rocksReviewer:  Pat Clements, MD

Article:  Mukhopadhyay S, et al.  “Effect of early-onset sepsis evaluations on in-hospital breastfeeding practices among asymptomatic term neonates.”  Hosp Pediatr.  2015 Apr;5(4):203-10. doi: 10.1542/hpeds.2014-0126.

Link:  Click Here

Why this article:  For newborns, I feel the area of suspected neonatal sepsis and chorioamnionitis is full of variations in practice. From variations in what obstetricians label as “chorio” to how long we keep infants in the special care nursery (SCN) while on antibiotics, the literature doesn’t have a lot of definitive information to offer. There are many times in the newborn/NICU setting where breastfeeding takes a backseat to other interventions. This is one of the first studies that looks at the link between early-onset sepsis evaluation and delays in breastfeeding.

Methods:  The study was a secondary observational analysis of data from a previous study looking at epidural analgesia at Brigham and Women’s and Massachusetts General Hospitals. The study group included 820 first-time mothers who intended on breastfeeding after birth. The goal was to look at rates of breastfeeding initiation within the first 2 hours of birth and the use of supplementation in the first 24 hours after birth. Infants were all well-appearing and full term. Infant’s excluded from the study were those with any issues of hypoglycemia or an NPO order. Of the 692 dyads enrolled, 101 infants were separated from their mothers for early-onset sepsis (EOS) evaluation. Criteria for EOS were based on the GBS prevention guidelines from the CDC (including maternal fever >100.4, inadequate GBS treatment, membrane rupture >18 hrs), as well as OB diagnosis of chorioamnionitis. Infants were assessed to be well appearing and had blood cultures and labs drawn, and antibiotics started if necessary. All infants were returned to mom’s room after initial workup initiated, and received antibiotics in the postpartum room if required.

Results:  Of the 101 babies evaluated who were separated from their mother for EOS evaluation after birth, 47% of them had delayed onset of breastfeeding (classified as first feed >2 hrs after birth). Only 13% of infants who were not separated had delays in breastfeeding. The group looked at multiple other variables related to EOS, such as degree of maternal temperature, membrane rupture time etc, and no factors related to the clinical picture itself seemed linked to delayed onset of breastfeeding. The main factor related to delayed onset of breastfeeding was the amount of time child was separated from mother within the first 2 hours after birth. Formula supplementation in the first 24 hrs was also significantly associated with separation for EOS evaluation, with 19% of infants separated ultimately receiving supplementation compared to 10% of infants who were not separated.

Conclusion:  The authors concluded that separation of infants from their mothers in the first 2 hours after birth for EOS evaluation caused delays in breastfeeding and increased the likelihood of receiving formula supplementation. They discussed limitations to the length of the supplementation data being only 24 hrs after birth, as many of the babies in this study were discharged between 24-48 hrs. They did point out, however, other studies which have shown that breastfeeding within 1 hour of birth and avoiding supplementation were strong predictive factors for exclusive breastfeeding at 6 weeks for infants. They also discussed the challenge with generalizing this data to other populations, as each hospital may have their own protocols and criteria for which babies require EOS evaluations.

Discussion:  I felt this study examined some fairly interesting questions. In terms of methods I was a little leery about subjective declaration of “chorio” by OB’s, as there seems to be wide variations in practice (at least at our hospitals). In the end the authors concluded that it wasn’t the EOS evaluation itself that seemed to matter with breastfeeding and supplementation, but rather the act of being separated from mom in general. This made sense to me, and also gave me caution in thinking of all the disruptive activities that take place in the first two hours of birth that might also disrupt breastfeeding (from newborn meds and obtaining measurements to the throng of excited relatives rushing in to visit). I was also interested in how the group kept well-appearing infants in the postpartum room with mom after labs were drawn and IV’s were placed. In our group’s practice I feel even healthy appearing infants may stay in the NICU for 12-24 hours of “observation” while on antibiotics. If this study showed the potential disruptive power of a 1-2 hr separation from mom, it makes me fear what the effects of longer disruptions would be. It would also be interesting to see other data on breastfeeding longer than 24 hrs (i.e do babies that received supplementation in the hospital related to EOS evaluations go on to successfully breastfeed after discharge?) Obviously metrics and predictive tools for neonatal sepsis could be the topic of a whole other journal club. Hopefully this article will remind us to not let breastfeeding be pushed to the back burner!

Posted in Breastfeeding | 1 Comment »

Top 10 articles from PHM 2015

Posted by ashriner on September 2, 2015

Top 10Reviewer:  Emily Webber, MD

What is this?  The Top 10 articles in pediatric hospital medicine presentation is always well attended at the annual PHM conference. Not only is the lecture known for its witticisms, entertainment value and plated lunch, but it also helps paint a picture of the articles that have shaped inpatient pediatric practice of the preceding 12 months.   Two of our own, Dr. Michele Saysana and Dr. Ben Bauer, presented in this venue in 2012 and 2013, respectively.

For the last 3 years, I have worked with the other ‘social media’ faculty to chronicle the links and articles via Twitter, which is convenient for later reflection. What you have in this post is a curated collection of those tweets for your review.

Complex medical research should never be reduced to a mere 140 characters, so the tweet is just the hook to the real article.   They are grouped by theme; I found the hyperbilirubinemia, dehydration and antibiotic overuse articles most relevant to my own practice. If you want to look at some of the other images and discussion from the lecture, search #PHM15 and the feed for @PHMConf. Thank you to everyone who helped attendees attend #PHM15, get send your work in for the #PHM16 submissions process – it’s in Chicago next year!

Enjoy, and please respond to the quiz at the end!


Fevers and antibiotics

  1. Fever w/o source: Biondi et al BCx Time to Positivity in Febrile Infants w Bacteremia , from the PRIS network. …
  2. Antibiotic overuse: Keren et al Comp effectiveness IV vs PO abx in post-d/c tx acute osteomyelitis in children. …
  3. Schroeder/Ralston review article: IV abx duration for common bact infxn in kids …


  1. Bronchiolitis mgmt: Schuh et al Effect of Oximetry on Hospitalization in Bronchiolitis …
  2. The CPG that Shall Not Be Named: Ralston et al. Diagnosis, Management, and Prevention of Bronchiolitis …


  1. Readmissions: Gay et al Rates. impact of pot. preventable readmits @ child hosp …

Venous Thrombus Embolism (VTE)

  1. VTE prophylaxis: Meier et al. Venous thromboembolism in hospitalized adolescents …

Surgery co-management

  1. Another one: Rappaport et al. Pediatric hospitalist comanagement of surgical patients …


  1. Hyperbilirubinemia: Wu et al. Risk for Cerebral Palsy in Infants w/ TS Bilirubin Levels ≥ Exch Tfxn Threshold
  2. Hyperbilirubinemia: Kuzniewicz et al. Incid, Etiol, Outcomes of Nwbrn Hazard Hyperbili …

Complex Care

  1. Medically Complex Children: Bogetz et al Challenges, Sol’ns to Educating Learners About Pediatric Complex Care …
  2. Nolan et al; Diff Percepxn re: QoL, Inpt Tx Goals for Children w/ Severe Disabilities …

Dehydration and IVF

  1. IV Fluids: McNab et al NS vs 0.45NS maint IV fluids for children in hospital @TheLancet …
  2. IV Fluids: Friedman et al isotonic vs hypotonic IV maintenance fluids (in children) …

Honorable mention

Auger et al Summary of STARNet: Seamless Transitions and (Re)admissions Network …


Posted in Uncategorized | Leave a Comment »

Hey, here’s your discharge. So I’ll call you, maybe?

Posted by ashriner on August 5, 2015

Ped phone call

“Oooooooh….so I’m supposed to take that THREE times a day?!”

Reviewer:  Andrew Shriner, MD

Article: Heath J, Dancel R, and Stephens JR.  “Postdischarge phone calls after pediatric hospitalization:  An observational study.”  Hosp Pediatr.  2015 May; 5 (5):241-8.  doi:  10.1542/hpeds.2014-0069. (Link)

Why this article?  Transition of care for children after a hospitalization has been a focus of a significant amount of research in an attempt to reduce issues such as misunderstanding of discharge instructions, difficulty filling prescriptions or giving medications appropriately or readmissions.  While there’s ongoing debate about the preventability of pediatric readmissions, with recent healthcare changes, this focus is unlikely to shift in the near future and there are certainly other ways that patients and families may benefit from efforts to improve the transition of care process.

Methods:  Over a 12-month period, the hospitalists in this study implemented a standardized attending physician phone call to the family of all discharged patients within 72 hours of discharge to check in on any problems with the transition of care.  Charts were reviewed for any difficulties identified, readmissions (14 and 30-days), ED visits, patient satisfaction scores.  Findings were compared to patient’s discharged over the preceding 12 months.

Results:  There were 661 discharges over the study period and 606 discharges in the comparison group from the prior year.  Seventy-eight percent of families (n = 513) were reached via phone call during the study period (up from 50% prior to their intervention).  A problem was identified in nearly 20% of the families who were reached with about half of the issues being related to medication issues.  About 1/3 of the problems identified were found to need a significant action to be taken by the physician (such as contacting another provider or calling in a new prescription).

There were no statistically significant reductions in ED visit rates, readmissions or patient satisfaction scores, but there was a trend towards improvement in all of these outcomes.

Conclusions/Discussion:  This was an interesting study on looking at how to reduce the risk of poor outcomes after inpatient discharges for pediatric patients.  There are some things that made it difficult to determine the impact of this intervention, including the low patient numbers to determine a significant difference on an overall unlikely complication like readmission and the fact that many providers in the group were already performing post-discharge phone calls, so their comparison group was sub-optimal in that respect.

Whenever I read articles like this, I always try to imagine what this would look like if implemented at Riley.  While I think the results noted are encouraging, thinking of the possibility of applying this to our practice seems somewhat overwhelming.  While I’m not sure of our exact number of discharges per year, I would estimate that it would be up to 3-4 times that of the numbers in this study.  The time needed to make all of these phone calls (some of which would undoubtedly require multiple attempts) could quickly become overwhelming on top of the existing demands on our time.  One potential way to get around this issue would be to try to identify groups of patients who are at higher risk for difficult transitions and focus on at-risk groups for follow-up phone calls.  Issues like this are also part of the reason why we aim to communicate with patients’ PCP after a hospitalization and have children follow-up in the office within a few days after discharge – it would be interesting to know what the typical follow-up plans are for patients from the study group as a follow-up phone call may be less helpful if the patient has already been seen their PCP where they theoretically could have these same concerns addressed.

Posted in Discharge planning, readmission to the hospital | Leave a Comment »

Pour Some Sugar on Me: Dextrose Bolus in Pediatric Gastroenteritis

Posted by ashriner on June 23, 2015

Sugar BearReviewers:  Bethany Beard, MD and Angela Dietrich-Kusch, MD


  1. Levy, JA, et al. “Intravenous Dextrose for Children With Gastroenteritis and Dehydration: A Double Blinded Randomized Controlled Trial.” Annals of Emer Med. Vol 61. No3. Mar 2013.  doi: 10.1016/j.annemergmed.2012.08.007 (Link)
  2. Levy JA, Bachur RG, et al. “Intravenous dextrose during outpatient rehydration in pediatric gastroenteritis.” Acad Emerg Med. 2007; 14:324-331.  doi: 10.1197/j.aem.2006.10.098 (Link)

Why this topic?  Imaging you are caring for a 3 year old female with abdominal cramping, diarrhea, and vomiting for the past 72h. She is refusing oral intake and has urinated only once in the past 24hr. On exam, she has dry oral mucosa, sunken dark eyes, and generally appears weak. You’ve learned in medical school and residency that you should only bolus with normal saline. However, you wonder if a bolus of dextrose could make the patient feel better and decrease the chance that mom will bring her back to your emergency department. However, you aren’t confident that dextrose containing fluid bolus is safe and effective when used as a bolus. You perform a literature search to answer your question.

  • P: pediatric patients with gastroenteritis
  • I: dextrose containing IV fluid bolus
  • C: normal saline bolus
  • O: decrease return ED visits/admissions

Literature search: Dr. Beard performed a Pubmed and Ovid search with the search terms ‘dehydration/glucose/or gastroenteritis’, ‘emergency services’, ‘intravenous or infusion’ and limited for children ages 0-18yr, humans, and English language. In total, 21 articles were found to be relatively pertinent to the question and two were selected to answer the specific question.


Article 1: “Intravenous Dextrose for Children With Gastroenteritis and Dehydration: A Double Blinded Randomized Controlled Trial”

Methods: This was a randomized controlled trial of children ages 6mo-6yrs with gastroenteritis at Boston Children’s Hospital. Subjects were randomized to receive a single 20ml/kg bolus of either 5% dextrose in normal saline or normal saline alone. Serum ketone levels and glucose were measured before bolus and again at 1 and 2hr intervals after the fluid bolus. Primary outcome was hospitalization rates. Secondary outcomes were change in serum ketone levels over time.

Results: 188 children were enrolled. The proportion of children hospitalized did not differ between groups (35% in D5 group, 44% in NS group) although there was a trend towards less admission in the dextrose group. Those children who received D5 had a greater reduction in mean serum ketone levels both at 1hr and 2hr. Of those children discharged, 30% of patients in the normal saline group and 11% of patients in the D5 group required unscheduled medical care after discharge home.

Conclusion: The study showed no significant difference in admission rates, however, there was a decrease in ketone levels in the D5 bolus group. Although there was a significant decrease in ketone levels, this did not seem to show any clinical difference in outcomes. Although the study outcome did not specifically study outpatient medical needs, it appears that the D5 group might have experienced less ongoing symptoms and need for medical care (i.e. PCP appointments) once released from the hospital however more research is needed. This may also translate into less repeat ED visits, however, this was not a study outcome in this paper.


Article 2: “Intravenous dextrose during outpatient rehydration in pediatric gastroenteritis”

Methods: This is a case control study of children aged 6mo to 6yr who presented to an urban ED with acute gastroenteritis and dehydration and who received IV rehydration before ED discharge. The study looked at whether the amount of IV dextrose administered at the initial visit was related to return visit admission (RVA).

Results: A total of 168 children diagnosed with gastro and discharged from the ED were studied (56 cases and 112 controls). Cases were defined as children who returned and were admitted within 72hr of initial ED visit and discharge. Patients who had a RVA received significantly less IV dextrose than those who did not have a RVA. Those who received no dextrose had a 3.9 greater odds of having a RVA. The study also found that those who received more dextrose containing IV fluids were 1.9 times less likely to have a RVA. Also, the study found that patients who had been ill for <24hr were more likely to have return visits than those ill for 1-2 days. No other demographic, clinical, or lab factors were associated with greater odds of having a return visit.

Conclusion: Larger amounts of IV dextrose is associated with reduced RVA in children with gastro and dehydration. Those that are sicker for shorter period of time may need to be more highly considered for admission.

Limitations: This was a retrospective study and the degree of symptoms could not be evaluated. It is therefore not known if patients who received more dextrose were sicker. Also, confounding variables influencing the primary outcome measure (return visit in 72hr) could not be controlled. Finally, the patient disposition regarding discharge or admission as well as the original diagnosis of dehydration was not standardized by the physician.


Take Home Points:

Physiologically, it makes sense that patients with dehydration from gastro will have metabolic acidosis with higher ketone levels which could contribute to symptom severity. However, both studies above shown that ketone levels do not contribute to re-admission rates. More research needs to be done to determine if ketone levels actually contribute to symptoms. A bolus with dextrose containing fluids appears to be safe and cheap and seems to show a decrease in re-admission rates as well as outpatient medical care needs. There also needs to be more research in the actual volume and dextrose dose, which has yet to be determined. In patients with very limited oral intake and signs of dehydration I will consider dextrose IV fluid boluses as part of the ED management plan based on the results of these two studies.

Additional Comments from Dr. Dietrich-Kusch:

From the inpatient side of things, I would really love to see bigger study on this. As a hospitalist admitting the children who still fail outpatient management of their gastroenteritis it seems like the use of D5 boluses lead to more labs because nearly always the patients end up with glucosuria and ketonuria on their UA and then people get concerned about DM, which leads to further labs (Hgb A1C, fasting glucose, repeat UA, etc). I personally wonder if there is a smaller amount of glucose that would be just as beneficial, but wouldn’t shoot up the blood sugar so much that they started spilling glucose into their urine.

Posted in diarrhea, fluid/electrolytes | Leave a Comment »

Prednisone vs. Dexamethasone for Treatment of Acute Asthma Exacerbation in Children

Posted by ashriner on May 20, 2015

“Hear me now and believe me later. Dexamethasone is as effective as prednisone for treatment of acute asthma exacerbations in children.” ~ Hans and Franz

Reviewer:  Andrew Shriner, MD

Article:  Meyer JS, Riese J, Biondi E.  “Is dexamethasone an effective alternative to oral prednisone in the treatment of pediatric asthma exacerbations?”  Hosp Pediatr.  2014 May;4(3):172-80. doi: 10.1542/hpeds.2013-0088.

Link:  click here

Why this article?  I’ve started noticing a trend in children being admitted for asthma exacerbations in which they are given either IM or PO dexamethasone as opposed to a dose of oral prednisolone which had been the norm that I was used to.  The reasons that I’d heard were that a 2-day course of dexamethasone had been shown to be at least as effective as a 5-day course of prednisone and that the hope was to improve compliance and side-effects with fewer doses.  I wanted to see for myself what the evidence showed and found an article in Hospital Pediatrics from last year that reviewed some of the recent pediatric literature.

Methods:  Authors performed a Medline search to find studies comparing the use of dexamethasone vs. prednisone in the treatment of asthma exacerbations.  Meta-analysis was performed to assess the rate of revisits to a healthcare provider and symptomatic improvement in the 2 groups after the initial ED visit.

Results:  Six articles were ultimately included in the review and broken down as follows:

  • IM Dexamethasone Studies
    • 3 studies.  Sample sizes of 42, 32 and 143.
    • all studies compared a single dose of IM dexamethasone with doses ranging from 0.3 mg/kg (max 15 mg) to 1.7 mg/kg (max 36 mg) vs. 3-5 days of prednisone with doses of 2 mg/kg/day (but max doses ranging from 50-100 mg/day)
    • Limitations:  lack of blinding, exclusion of patients who were “too sick”, small sample sizes, reliance on subjective reports of symptom improvement
    • No significant differences found between the groups.  Outcomes assessed included:
      • improvement of symptoms, clinical asthma scores through day 5, % returning to baseline by day 5, relapse rates at 28 days, daily albuterol use on day 5, admission rates, unplanned physician visits
  • PO Dexamethasone Studies
    • 3 studies.  Sample sizes of 533, 110, and 89.
    • one study compared one dose of oral dexamethasone to 5 days prednisone.  The other two compared two daily doses of oral dexamethasone to 5 days of prednisone.
      • dexamethasone doses were 0.6 mg/kg in all studies with a max of 16 mg in two and 18 mg in another.
      • prednisone doses were all a total of 2 mg/kg/day, two with a max of 60 mg/day and one with a max of 80 mg/day.
    • No significant differences found between the groups.  Outcomes assessed included:
      • Relapse rates, rates of admission to hospital, mean days to return to baseline, mean patient self-assessment scores at 5 days
  • Meta-analysis results
    • There was no significant difference between the dexamethasone vs. prednisone groups in regards to number of unscheduled physician visits after discharge or the time for symptom improvement back to baseline.
  • Adverse Effects
    • Mixed results with one study showing increased vomiting in the prednisone group while in the ED (but no difference in vomiting rate at home).  Another found no difference in rate of vomiting between groups.
  • Compliance
    • Difficult to tell due to design of some of the studies, but one study found that 17% of children in the study refused > 75% of their prednisone doses and 24% missed between 30-50% of their doses.

It seems like there is mounting evidence that there is likely no significant difference in clinical outcomes when comparing the use of dexamethasone to prednisolone when treating children for asthma exacerbations.  While there was a great deal of variation in the study designs, doses of meds and formulations used; there was never any statistical difference noted between treatments.  What is still unclear to me is what the ideal dexamethasone regimen would be based on these studies.  A dose of 0.6 mg/kg seems to be a good starting point, as we’re used to giving this dose to children with croup and the majority of studies used this as well.  (But, the range of max dosing was anywhere from 16 mg to 36 mg per dose!)  When it comes to dosing, the studies used either one-time dosing or daily x 2 days.  Given all of the variability in the studied regimens, it would be really nice to see a large, high-quality, randomized controlled trial to clarify the ideal treatment regimen and to help ensure that we’re not missing any important differences between treatment with dexamethasone vs. prednisone due to biases from the study design or due to small sample sizes before completely changing our routine management for these patients.

BUT, we’re already seeing some patients who are started on these treatment courses in the ED before they get to us, so we need to at least start thinking about how we are going to handle these situations going forward.  The current dosing schemes that have been in practice at Riley include either a one-time po dose in the ED (usually up to 12 mg max) and for those admitted, sometimes an additional dose 2-3 days later (not the next day as in the protocols in the studies reviewed here).  This makes more sense to me from a pharmacokinetic standpoint, but would likely reduce the positive impact of improved compliance with this regimen if patients needed to go home with a prescription.

IF we’re comfortable saying that 1-2 doses of dexamethasone are equally efficacious as 5-days of prednisolone, I do think there are compelling reasons to switch to dexamethasone, primarily the potential for improving compliance with the prescribed treatment regimen.  The authors also tout advantages of lower cost, fewer adverse effects and better palatability.

I question some of this, though.  While I’m not a connoisseur of medicines, I do have a trusted contact from pharmacy who tells me that liquid dexamethasone is NOT more palatable than liquid prednisolone as one of the studies quoted by the authors suggests.  I can’t find an obvious reason for the discrepancy when looking at the articles they cite, though there was a difference between males and females with males being more likely to prefer dexamethasone to prednisolone (though there was a preference towards dexamethasone regardless of sex).  If we wanted to decide for ourselves which is more palatable, we can make arrangements for a taste testing at one of our next staff meetings if there’s enough interest.

To wrap it up:  I think it’s an interesting shift in practice and one worth looking into, but certainly one with a lot of questions about how best to move forward.  What do you think?

Posted in asthma | Leave a Comment »

Etiology and Incidence of CAP in Hospitalized Children

Posted by ashriner on April 1, 2015

Dr Evil - pneumonia

Or for many children:  “viral lower respiratory tract infections”

Reviewer: Keith Chitty, MD

Article: Jain S et al.  “Community-Acquired Pneumonia Requiring Hospitalization in U.S. Children.” N Engl J Med 2015 Feb 26; 372:835.  DOI: 10.1056/NEJMoa1405870


Why this article? As hospitalists, we take care of patients with pneumonia on a routine basis. We know that both bacteria and viruses can cause pneumonia, but it is difficult to decide which patients not to treat with antibiotics, and which patients to treat empirically for atypicals. This multi-center study provides the newest data regarding the incidence and microbiologic causes of community-acquired pneumonias requiring hospitalization in children.

Methods: This is a prospective, multi-center, population-based, active-surveillance study conducted by the CDC and entitled the Etiology of Pneumonia in the Community (EPIC) study. It took place from 1/1/10-6/30/12 in children’s hospitals in Memphis, Nashville, and Salt Lake City. Children were included in the study if they had evidence of acute infection (fever, chills, hypothermia, leukocytosis or leukopenia), evidence of an acute respiratory illness (new cough, sputum production, chest pain, dyspnea, tachypnea, abnormal lung exam, or respiratory failure), and evidence consistent with pneumonia as assessed by chest radiography within 72 hours before or after admission.

Exclusion criteria were:

  • Recent hospitalization
  • Already enrolled in EPIC study within previous 28 days
  • Resided in an extended-care facility
  • Had an alternative diagnosis of a respiratory disorder
  • Were a newborn who never left the hospital
  • Had a tracheostomy tube, cystic fibrosis or cancer with neutropenia
  • Had received a transplant within the previous 90 days
  • Had active Graft Versus Host Disease or bronchiolitis obliterans
  • Had HIV infection with CD4 count < 200

Laboratory testing included Gram’s stain and bacterial culture from blood samples, pleural-fluid samples, endotracheal aspirates, and bronchoalveolar lavage specimens. PCR for S. pneumoniae and S. pyogenes were performed on whole blood and pleural fluid. Pleural fluid PCR was also done for H. influenzae, S. aureus, S. angiosus and S. mitus. PCR was performed on nasopharyngeal and oropharyngeal swabs for adenovirus, C. pneumoniae, coronaviruses, HMPV, rhinovirus, influenza A and B, M. pneumonia, parainfluenza (1, 2, and 3), and RSV. Serologic testing for adenovirus, HMPV, influenza A and B, parainfluenza, and RSV was performed on available paired acute-phase and convalescent-phase serum specimens.

Results: 2358 children were enrolled in the study and had radiographic evidence of pneumonia. The median age of the children was 2 years. 45% were girls. 40% were white, 33% were black, 19% were Hispanic, and 8% were of another ethnic group. 51% of the children had an underlying condition, with asthma or RAD the most common condition. The median length of stay in the hospital was 3 days.  Overall, 497 children (21%) required ICU care, and 3 (<1%) died. Thirty percent of children 6 months and older had received one or more doses of influenza vaccine for the concurrent season. Eighty-seven percent of children 19 months to 12 years of age had received 3 or more doses of Prevnar. A total of 88% of children received antibiotics during hospitalization.

A nasopharyngeal or oropharyngeal swab was obtained from 96% of the children, blood culture from 90%, whole blood for PCR assays from 87%, paired serum specimens from 44%, pleural fluid from 4%, BAL specimen from 1%, and endotracheal aspirate from 1%. For calculation of proportions of specific pathogens, data were included from only the 2222 (94%) children with radiographic pneumonia who had blood, pleural fluid, endotracheal aspirate, or a BAL specimen available and who also had a nasopharyngeal or oropharyngeal swab or paired serum specimens available.

A pathogen was detected in 81% of children in the study – viruses in 66%, bacteria in 8%, and both bacterial and viral pathogens in 7%. The most commonly detected pathogens were:

  • RSV (28%)
  • Rhinovirus (27%)
  • HMPV (13%)
  • Adenovirus (11%)
  • S. pneumoniae (8%)
  • Parainfluenza (7%)
  • Coronavirus (5%)
  • M. pneumoniae (4%)
  • S. aureus (1%)
  • S. pyogenes (1%)

RSV (37% vs. 8%), adenovirus (15% vs. 3%) and HMPV (15% vs. 8%) were detected more commonly in children younger than 5 years of age than in older children. M. pneumoniae was detected more commonly in children 5 years of age or older than in younger children (19% vs. 3%). Pneumonia peaked in the fall and winter.

A control group was also tested and all pathogens with the exception of rhinovirus were detected in 3% or less of controls. When adjusted for age, rhinovirus was detected in 17% of controls compared with 22% of children with pneumonia.

The annual incidence of hospitalization for pneumonia was 15.7 cases per 10,000 children. Incidence of hospitalization for children younger than 2 years was 62.2 cases per 10,000 children; for 2-4 years of age it was 23.8 cases per 10,000 children; incidence continued to decrease with increasing age.

Discussion: This study reinforced some established knowledge regarding pneumonia; I am also taking away several learning points:

We’ve been taught since medical school that viruses are a common culprit in pneumonia, but I have a new appreciation for that fact after looking at this study. The authors are quick to concede that bacterial culture-based diagnostic tests have limited sensitivity and that bacteremia is detected in a minority of pneumococcal pneumonias. However, this study used state-of-the-art diagnostic testing and only detected bacteria in 15% of cases. Does this mean that we only need to use antibiotics for 15% of our inpatients with pneumonia? Probably not, but especially in the subset of young patients with clinical bronchiolitis and an infiltrate on CXR, I am becoming less excited about treating with antibiotics.

Mycoplasma was detected twice as often as Strep pneumonia overall. However, in children 5 years of age and older Mycoplasma’s detection rate far exceeded that of Streptococcus. I have always considered atypical coverage strongly in older patients, but going forward I think my practice will change to empiric double coverage in that age group.

Lastly, I am interested in the incidence of rhinovirus positive controls. As PCR-based viral testing becomes more commonplace we will see more positive results for rhinovirus/enterovirus. I’ll keep this data in mind; in patients whose hospital courses aren’t typical, these positive results could be a red herring.

Posted in pneumonia | 2 Comments »

Rethinking the rebound bilirubin

Posted by ashriner on March 16, 2015

reboundsReviewer:  Andrew Shriner, MD

Article:  Berkwitt A, Osborn R, Grossman M.  “The utility of inpatient rebound bilirubin levels in infants readmitted after birth hospitalization for hyperbilirubinemia.”  Hosp Pediatr.  2015 Feb;5(2):74-8. doi: 10.1542/hpeds.2014-0074.

Link:  click here

Why this article?  Its been a while since the release of the 2004 AAP guidelines for neonatal hyperbilirubinemia, but one thing that seems to have not been widely adopted is the idea that infants admitted for phototherapy do not need to stay in the hospital after phototherapy is discontinued to check a “rebound” bilirubin level.  I thought this was a nice opportunity for us as a group to stop and ask ourselves a couple of questions:  “Do I routinely order rebound bili levels before discharge after discontinuing phototherapy?”  And, if so, “Why?”

Methods:  This was a retrospective cohort study conducted on infants admitted to 1 tertiary care children’s hospital for hyperbilirubinemia between 1/2007 and 4/2014.  Patients were included in the study if they were > 35 weeks GA and were re-admitted after discharge from newborn nursery for phototherapy to treat indirect hyperbilirubinemia

Exclusion criteria included:

  • history of phototherapy in first 24 hrs of life
  • ICU admission
  • exchange transfusion
  • direct hyperbilirubinemia
  • evidence of sepsis

Children were divided into two groups, those who had repeat bilirubin levels drawn < 12 hours after cessation of phototherapy and those who did not have repeat levels drawn.

Results: 226 infants were included in the final analysis, 130 in the rebound group and 96 in the no-rebound group.  Bilirubin levels were higher in the rebound group at initiation  (19.5 vs. 18.8) as well as at cessation (13.7 vs. 13.0) of phototherapy.  The rebound group also had a significantly shorter duration of phototherapy (15.1 h vs. 17.7 h).  There were 9 re-admissions within 72 hrs from the cohort (5 from the rebound group and 4 from the no-rebound group).  Mean LOS was increased in the rebound group (about 4 hrs longer) as was the mean discharge time.  In the rebound group, there was not a significant difference in mean bilirubin levels at phototherapy cessation and mean rebound bilirubin levels.  Five infants who did have rebound bilirubin levels checked received repeat phototherapy during the same admission – all having had bilirubin levels > 14 at the time of initial phototherapy cessation.  (1 infant had cephalohematoma and 2 had ABO incompatibility)

Infants with bilirubin levels < 14 at the time of phototherapy cessation were significantly less likely to need repeat phototherapy (1.6% vs. 12.4%).

Conclusions: This study was definitely not the most robust in terms of numbers of infants included and is limited by its retrospective design, but I still think there’s a lot that can be taken away from this.  The results were in line with previous studies looking at early rebound bilirubin levels and finding no significant increase after phototherapy cessation.  Re-admissions rates were essentially the same, but LOS was lower and discharge time was earlier in the group not subjected to rebound bilirubin checks prior to discharge.  It was interesting that the group of infants who had rebound levels checked were more likely to have higher bilirubin levels at initiation of phototherapy and at cessation, but received significantly shorter durations of phototherapy (and, by the way, also spent more time in the hospital as well).  I’m inclined to agree with the authors conclusions that our aim should be to follow the AAP recommendations and have a goal of bilirubin levels of 14 or less prior to stopping phototherapy.  Also, this paper is just further evidence that rebound bilirubin levels are probably not going to offer much clinical utility and are not necessary in the majority of patients.  I do still think there may be utility in checking rebound bilirubin levels in a subset of infants who have either been slower to improve on phototherapy than we would expect or have underlying conditions which may put them at higher risk for worsening hyperbilirubinemia after stopping phototherapy, such as significant bruising, cephalohematoma or hemolytic disease.  But, these infants tend to be more the exception than the rule.

Posted in Hyperbilirubinemia | Leave a Comment »

Newborn Weight Loss Nomograms

Posted by ashriner on February 24, 2015

Who doesn't love a good nomogram?

Who doesn’t love a good nomogram?

Reviewer: Melissa Klitzman, MD

Article: Flaherman, VJ., et al. “Early Weight Loss Nomograms for Exclusively Breastfed Newborns.” Pediatrics. 2015. January 1; DOI:10.1542/peds.2014-1532

Link:  click here

Why This Article?: Exclusively breastfed infants lose weight daily while mother’s mature milk is coming in, more so than those receiving any amount of formula. This article studies the weight loss a large cohort of exclusively breastfed infants and presents two nomograms based on delivery modality similar to the Bhutani nomogram for hyperbilirubinemia. This could be a potentially useful tool in identifying those newborns at greater risk for weight loss and therefore earlier intervention.

Methods: This is a retrospective, multicenter cohort study evaluating the daily weight loss of exclusively breastfed newborns greater than or equal to 36 weeks during their initial newborn hospitalization between January 2009 and December 2013. Newborns were in 1 of 14 Kaiser Permanente Northern California hospitals.

Exclusion criteria:

Level II or III NICU care, < 36 week gestation, birth weight <2000g or >5000g, multiple birth, implausible weight loss (>10% in first 24 hours or >15% after first 24 hrs), implausible weight gain (>5%), missing/discrepant data (delivery modality, weight, feeding), and infants were censored if they started formula feeding.

Newborns were included in final analysis if any weight was obtained after 6 hours of age and before exclusive breastfeeding was discontinued. Nomograms stratifying weight percentiles (50th, 75th, 90th and 95th) for weight loss for hours of life were produced based on delivery modality. Vaginal delivery nomogram is between 6-72 hours of life and 6-96 hours of life for the cesarean nomogram.

Additional demographic information was obtained (i.e. maternal race/ethnicity).

Results: In the final analysis, there were 108,907 newborn with 76.6% delivered vaginally and 23.4% delivered by cesarean. There were ~ 1.3 weights recorded per newborn for vaginal deliveries and 2.1 weight per newborn recorded Forty-three percent of the mothers were white non-Hispanic, 24% Hispanic, 24% Asian, 7% black non-Hispanic, and 3% unknown.

The analysis also included examination of the nomograms to see if it was affected by inclusion of late preterm, post term, SGA and LGA. Nomograms were produced by removing those infants and comparing the nomograms (see supplemental Figure 5).

Imputed nomograms were generated (see supplemental figure 6) for those infants censored (removed) from the study due to initiation of formula because of large amounts of weight loss. Weights were included for these newborns up until formula feeding was initiated but then data from an uncensored matched newborn was used. The assumption is that the weight loss history of the matched uncensored newborn approximates the weight loss for the censored newborn.

Discussion: The weight percentile loss nomograms for exclusively breastfed infants will be useful in the initial newborn hospitalization period similar to how the Bhutani nomogram is useful for hyperbilirubinemia. They can help assess the need for more lactation support, supplementation, timing of discharge, and timing of follow-up. There is also a handy-dandy website ( to plug in values similar to bilitool for hyperbilirubinemia.

What I find particularly useful is the stratification of weight loss percentiles based on delivery modality. For instance, a 5% weight loss at 24 hours puts that newborn in the ~75% in the vaginal delivery nomogram, whereas the same % weight loss in an infant born via cesarean would only put that infant in the ~50%. That being said 10% weight loss still seems to be the magic number by 48 hours of life for both vaginal (95%) and cesarean (90%) deliveries.

The imputed nomograms (see supplemental figure 6) overlying the original curves are essentially unchanged for vaginal and cesarean deliveries until ~72 hours of life. Also the nomograms generated excluding late preterm, post term, LGA and SGA (see supplemental Figure 5) are essentially unchanged for both delivery modalities. This lends to reliability of the nomograms.

Approximately 87% of the collected weight data are within the first 36 hours of life for vaginal deliveries and ~90% within the first 60 hours for cesarean. Passed these hours of life the data is less reliable as reflected in the 95% confidence interval nomograms (see supplemental figure 3).

This study also has a smaller white, non-Hispanic infant population and a large non-white infant population compared to the latest US Census data. Therefore the nomogram might be less reliable in population with less racial and ethnic diversities.

While I might not use the nomogram for every infant I see in the well newborn nursery, I have and will continue to use it for infants whose percent weight loss are increased.

Posted in Breastfeeding, neonate | Leave a Comment »


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