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The 33rd Bubble Wrap


With millions upon millions of journal articles being published every year it is impossible to keep up.  Every month we ask some of our friends from DFTB and PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: More evidence for lower dexamethasone dosing in croup

Parker C, Cooper M. Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial. Pediatrics. 2019; 144(3):e20183772 

Why does it matter?

There is a lack of data comparing prednisolone and low-dose dexamethasone for the treatment of childhood croup. Early trials have shown the safety and efficacy of 0.6mg/kg of oral dexamethasone and there have been some studies showing potential efficacy of 0.3mg/kg and 0.15mg/kg dosing. These  studies however have not been adequately powered to detect clinical significance.  It is known that 1mg/kg of prednisolone is effective in croup patients requiring intubation and shortens the time to extubation for patients with croup in intensive care1.

What’s it about?

A prospective, double-blind, noninferiority randomised controlled trial was conducted over two urban emergency centres in Perth, Australia. 1252 children >6 months old, and <20kg with croup were randomised to oral dexamethasone (0.6mg/kg; n=410), low-dose dexamethasone (0.15mg/kg; n=410), or oral prednisolone (1mg/kg; n= 411).  

The Westley Croup Score (WCS), a clinical score based on stridor, retractions, air entry and level of consciousness was assessed at baseline, and then hourly up to 6 hours, and again at 12 hours, if the patients were not yet discharged.  Results showed no statistically significant difference between the 3 groups for the WCS at the 1-hour assessment: 0.03 (95% CI- 0.09 to 0.15; p=0.62) for low-dose dexamethasone and 0.05 (95% CI -0.07 to 0.17; p=0.40) for prednisolone.  Both of these groups fell within the prescribed noninferiority margin of 0.5.  Interestingly, WCS for low-dose dexamethasone was 0.11 higher at 2 hours and 0.23 higher at 3 hours compared to 0.6mg/kg dexamethasone group.  The difference was significant at 3 hours (p=0.04), however, the upper limit of 95% CI (0.45) was within the noninferiority margin. Authors propose that the “ceiling effect,”theory, where steroid effect above a certain threshold does not have additional benefit, may be at a dose higher than 0.15mg/kg for a minority of patients. 

Re-attendance rates (to GP and ED) within 7 days after treatment were 17.8% for 0.6mg/kg dexamethasone, 19.5% (p=0.59) for low-dose dexamethasone and 21.7% (p=0.19) for prednisolone. 

Clinically Relevant Bottom Line

Noninferiority was demonstrated for both low-dose dexamethasone (0.15mg/kg) and single dose prednisolone (1mg/kg) compared with 0.6mg/kg dexamethasone. There was no clinically significant difference on efficacy in the acute period, as well as re-attendance rates to both GP and ED.  

Reviewed by: Lorraine Cheung

1.   Tibballs J, Shann FA, Landau LI. Placebo-controlled trial of prednisolone in children intubated for croup. Lancet. 1992:340 (8822): 745-748

2.   Geelhoed GC, Macdonald WB. Oral dexamethasone in the treatment of croup: 0.15mg/kg versus 0.3mg/kg versus 0.6mg/kg. Paediatric Pulmonology. 1995;20(6):362-368 

Article 2: The dangers of VALI (not the son of Loki)  

Ween MP, Hamon R, Macowan MG, Thredgold L, Reynolds PR, Hodge SJ. Effects of E cigarette E liquid components on bronchial epithelial cells: Demonstration of dysfunctional efferocytosis, Respirology. 2019 Sep 22. doi: 10.1111/resp.13696 [Epub ahead of print]

Why does it matter?

The e-cigarette was released in 2003, being marketed as safer for smokers and everyone around them. The use and popularity amongst adolescents continues to rise, despite new information about Vaping Associated Lung Injury (VALI), as well as injuries related to malfunctioning devices. In Australia, e-cigarettes containing nicotine liquid have been banned, but the base composition of a fruit flavour, vegetable glycerine (VG) and propylene glycol (PG) may still have harmful effects.

What’s it about?

An in vitro study which compared the effects of cigarette smoke extract to apple flavoured E liquid and nicotine (in a VG and PG base). The authors looked at cytokine release, cell necrosis, apoptosis and efferocytosis in healthy bronchial epithelial cells.

The results show that all individually (glycol bases alone, apple flavouring alone, nicotine alone) and combination (apple + nicotine) had significant toxic effects, when compared with the control of cigarette smoke extract. E cigarette components caused apoptosis and necrosis, reduced efferocytosis by down regulation of receptors, and reduced the production of certain inflammatory cytokines.

Clinically Relevant Bottom Line

To the surprise of nobody, e-cigarettes are not harmless. Ongoing research into the effects of first hand and second hand E- Cigarettes vapour, both containing nicotine and nicotine free, will be crucial in determining new policies and regulations, especially to curb the rise of use amongst our young population.

Reviewed by: Tina Abi Abdallah

Article 3:  Optimal fasting regimens – what does the evidence suggest?

Real fasting times and incidence of pulmonary aspiration in children: Results of a German prospective multicenter observational study. Beck et al. Paediatr Anaesth. 2019 Aug 22.

What’s it about?

Unfortunately, prolonged fasting times before a general anaesthesia is still common in paediatrics. The authors hypothesised that shortened fasting times could improve the child’s condition during induction of anaesthesia and improve children’s and parental satisfaction. This prospective observational study in Germany looked at real fasting times and proposed reduced fasting times, but an (adapted) national guideline is lacking. Over 3000 children were included at 10 paediatric centres in Germany. Surprisingly, the real fasting times were 14 hours for large meals, 9 hours for light meals, 6 hours for formula, 5 hours breast milk and 3 hours for clear fluids. The authors report a prolonged fasting (defined as over 2 hours deviation from guideline) for large meals in 88%, for light meals in 55%, for formula milk in 44%, for breast milk in 26% and for clear fluids in 34%.

Eleven cases (0.33%) of regurgitation, four cases (0.12%) of suspected pulmonary aspiration and two cases (0.06%) of confirmed pulmonary aspiration were reported, without any prolonged anaesthetic.

Why does it matter?

Children having an anaesthetic should not be fasted longer than necessary as this negatively impacts tolerability of the child, the parents and their environment. This study shows that prolonged fasting is very common, from large meals to clear fluids. All cases could be extubated after the end of the procedure and recovered without any incidents which may suggest we are too strict with our fasting times.

Clinically Relevant Bottom Line

This study shows that prolonged fasting is still common in paediatric anaesthesia and that complications related to not fasting are rare and that improvements to current local fasting regimens and national fasting guidelines are urgently needed. Short fasting guidelines for children could potentially improve anaesthetic tolerance and satisfaction.

Reviewed by: Anke Raaijmakers

Article 4:  Family Chaos and Asthma Control

Weinstein SM, Pugach O, Rosales G, Mosnaim GS, Walton SM, Marin MA. Family Chaos and Asthma Control. Paediatrics. 2019. Aug;144(2). doi: 10.1542/peds.2018-2758. Epub 2019 Jul 9.

What’s it about?

This cohort study focused on 223 children (5 to 16 years-old) of low-income minority background with poorly-controlled asthma in the United States.  The study explored the relationship between asthma severity and psychosocial factors such as parental and child depression, post-traumatic stress disorder (PTSD) symptoms and family functioning.   Both parents and children showed higher rates of depression and PTSD symptoms compared to the general population. Parental and child depression symptoms were associated with poor asthma control, asthma severity and limitations of activity (P<0.001). PTSD symptoms were unrelated to child asthma outcomes. Family chaos serve as a predictor of poor asthma outcomes and a mediator for the relationship between parental depression and child asthma (P<0.05).  

Why does it matter?

Previous studies have shown a high prevalence of poorly-controlled asthma among school-aged children (6 to 17 years old). Studies have found increased rates of parental depression and anxiety, associated with poor child asthma outcome. Child depression and anxiety symptoms are predictors of poor asthma outcomes, including increased functional impairment, asthma severity and frequency of emotional triggers.

Clinically Relevant Bottom Line

Child and parent depression and family chaos are predictors of uncontrolled asthma. Family chaos also serves as the mediator between parent depression and asthma outcomes. To optimise asthma care, measures to screen youth and parent depression in community settings should be made aware and become part of the clinical guideline.

Reviewed by: Jessica Wong

Article 5:  Mother knows best?

Vanderkooi OG, Xie J, Lee BE, Pang X, Chui L, Payne DC et al. on behalf of Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) and Pediatric Emergency Research Canada (PERC). A prospective comparative study of children with gastroenteritis: emergency department compared with symptomatic care at home . Eur J Clin Microbiol Infect Dis. 2019 Sep 9. doi: 10.1007/s10096-019-03688-8. [Epub ahead of print]

What’s it about?

The “apple juice” paper highlighted that treatment of gastroenteritis can be simple but led many to question why some of the children recruited needed any formal fluid trials at all. This study by the same author (Stephen Freedman) was designed to compare the treatment and outcomes of children with gastroenteritis seen in the Emergency Department with those who were managed at home.

The recruitment strategy was dependent on a national helpline, those in the UK will know this as similar to 111, which triages and directs parents to call to either self-care at home or suggest onward referral.

A cohort of patients presenting to the Emergency Department with gastroenteritis (1317 children, median age 20.8 months) were compared with those who were managed at home (296 children, median age 17.4 months). The groups were essentially similar (both had a high rate of having a rectal swab for bacteria and viruses performed, in the ‘at home’ cohort this was taken by the parents).

Isolated vomiting was higher in the ED group but isolated diarrhea more frequent at the home cohort. While the median dehydration scores in the ED (3 IQR 2-4) were significantly different from at home (1 IQR 0-2) the clinical significance is not clear as both would rank as ‘some dehydration’ and the scale goes up to 8.

Why does it matter?

This could have been a ‘so-what’ study. You would expect that a group of children presenting to an ED with symptoms of gastroenteritis would vomit more than those staying at home and would be more clinically dehydrated. However this study again shows how minor dehydration generally is with gastroenteritis and how isolated vomiting causes concern in parents. 35% of the at home group had norovirus. This means if we can direct public health efforts to further educating parents on managing gastroenteritis it is possible we can further safely reduce ED attendance.

Clinically Relevant Bottom Line

Children are more unwell with gastroenteritis if their parents choose to bring them to hospital. But not by a massive amount and they do successfully look after children with infections often associated with need for admission.

Reviewed by: Damian Roland

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments! We are also looking to expand the Bubble Wrap team so please contact us if you’re interested in this! That’s it for this month. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to. 


  • Grace is a Registrar at Sydney Children's Hospital. She loves innovative medical education and paediatrics. She is on the organising committee for the DFTB18 and SMACC conference. Grace is a former internal director of the AMSJ. She enjoys board games, cooking and graphic design.


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1 thought on “The 33rd Bubble Wrap”

  1. Hi Grace Leo,
    “The 33rd Bubble Wrap” actually wrapped more than 33K thoughts! Thanks for your detail instructions. You really described it in a wonderful way. Very easy to understand. I really expect more pediatrics posts from you.

    Best Regards.