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The 51st 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 PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: Anti-coagulation in CRRT

Chen Z, Wang H, Wu Z, Jin M, Chen Y, Li J, Wei Q, Tao S, Zeng Q. Continuous Renal-Replacement Therapy in Critically Ill Children: Practice Changes and Association With Outcome. Pediatr Crit Care Med. 2021 May 7. doi: 10.1097/PCC.0000000000002751. Epub ahead of print. PMID: 33965990.

What’s it about? 

This paper focuses on the paediatric patient outcomes for anticoagulant therapies used in continuous renal replacement therapy (CRRT) (heparin versus citrate).

The authors conducted a retrospective single centre audit over a 10-year period from 2010 to 2019 (289 patients included in the analysis) in Guangzhou, China. The median age of the patients was 4 years of age with a median fluid overload (FO) percentage at the initiation of the CRRT of 5.4%, and overall mortality of 46.3%.

Interestingly in 2015, the CRRT anticoagulant therapy practice was changed from heparin to citrate. There was no direct head-to-head comparison of the anticoagulants and in the paper 8 out of 10 patients received citrate anticoagulation. This paper assessed if the change in practice of anticoagulant had an impact on patient mortality.

The most common indications for CRRT in the paper were cytokine clearance 40%, acute kidney injury 23% and metabolic disease at 22%. In the paper, the heparin cohort had a higher mortality of 65% versus 47% in the citrate cohort. Interestingly if CRRT was initiated later (greater than 24 hours) then patients had a higher proportion of receiving vasoactive medication support, required longer mechanical ventilation days and had a greater fluid overload percentage.

Some limitations are that this is a single centre study, and the way in which they determined CRRT initiation time was time from admission to PICU to CRRT initiation time- which is not the usual way of evaluating early vs late CRRT.

Why does it matter? 

CRRT provides life-saving kidney support and assists with removal of electrolytes, fluid, and toxins from the body. Citrate anticoagulation in CRRT has offered patients an alternative to heparin. Heparin has the risk of heparin induced thrombocytopenia.

The emergence of citrate anticoagulant in CRRT over the last decade has offered promise for patients in this high-risk group and decreased mortality.

Clinically Relevant Bottom Line:

Paediatric patients presenting to hospital who require CRRT have a high risk of mortality. This paper concluded that a lower mortality with CRRT was associated with fluid overload % < 10%, CRRT initiation in less than 24 hours, and the use of citrate anticoagulant.

Reviewed by: Michele Cree

Article 2: It’s not always COVID

Snelson E, Roland D, Munro APS Throat and ear infections in children: URTI in the time of COVID-19Archives of Disease in Childhood – Education and Practice 2021;106:172-174.

What’s it about? 

This piece, prompted by restrictions presented by the COVID19 pandemic, discusses an alternative approach to the management of upper respiratory tract infections (URTI – tonsillitis and otitis media) in the UK.

The reduction in rheumatic fever incidence and vaccination against Haemophilus and Pneumococcus has resulted in a reduction in invasive URTI. The primary complications of URTIs are now mostly limited to peritonsilar abscess formation or mastoiditis. The incidence of both of these is not reduced significantly by antibiotic use (NNT >4000) and remain rare in children. The duration of tonsillitis symptoms following antibiotic treatment is only 18hours less, on average, and only if treatment is initiated before day 3 of symptom onset. In addition to this, antibiotics are demonstrated to cause many side effects including GI disturbance, allergy, and increased incidence of atopy and autoimmune conditions later in childhood.

The UK (NICE) guidance for otitis media was clarified in 2019. It now provides a graded approach of observation, delayed prescribing or same-day prescribing depending on the presence of systemic features, complications or in patients <2 years of age with bilateral AOM. Similarly, sore throat presentations are risk-stratified using FeverPAIN or CENTOR scoring – the former has not been validated in patients <3yrs and the latter was derived in an adult population.

Due to these guidelines frequently using the term ‘consider’ before suggested actions, the variation in clinical practice is not a surprise. This results in frustration for both clinicians in doubt and families expecting prescriptions..

Why does it matter? 

There is growing evidence that antibiotic use in URTI does not reduce symptom duration, and that the incidence of URTI associate complications is declining. This unfortunately has not detached clinicians’ hopes of reducing symptoms as a key factor in decision making.

COVID19 had a dramatic impact on clinical practice with the rise of virtual consultation and changes in health-seeking behaviour following government advice.

The Royal Children’s Hospital of Melbourne implemented a binary approach to reduce decision fatigue and improve antimicrobial guardianship. In this model, after the exclusion of sepsis and complications of URTI, AND if the patient is not classified as high risk (e.g. immunocompromised) then antibiotics are not immediately prescribed.

Clinically Relevant Bottom Line:

The proposed binary approach to decision making regarding antibiotic provision in URTI aims to reduce decision fatigue, unify the approach of clinicians, aid antimicrobial stewardship and efforts to inform health seeking behaviours.

For a round- up of the most up to date COVID literature in paediatrics why not visit

Reviewed by: Joshua Tulley

Article 3: A dipstick for diarrhoea?

Cotter JM, Thomas J, Birkholz M, et al. Clinical Impact of a Diagnostic Gastrointestinal Panel in Children. Pediatrics. 2021;147(5):e2020036954

What’s it all about?

This was a multicentre cross sectional-study of paediatric patients, in Colorado, who had stool testing from 2013 to 2017. The study looked at two time periods: 24 months before the introduction of rapid multiplex polymerase chain reaction gastrointestinal panel (GIP) and 24 months after the introduction of GIP. The GIP detects 22 enteric pathogens, including bacteria, viruses, and parasites with an aim to provide antibiotic susceptibilities. Stool cultures were additionally performed when the GIP was positive for Shigella or Salmonella.

The authors compared test use, pathogen detection and time to results. Among children who were hospitalized, they compared length of stay (LOS), ancillary testing including labs and imaging studies, time to treatment, and hospital charges.

After GIP was introduced, there was an increase in stool testing of 21%. There was a higher percentage of positive results (40% vs 11%). Among the 1,986 hospitalized children, only 3% received antimicrobials to treat bacteria/parasitic causes for diarrhoea. There was a significant decrease in time to result (4 vs 31 hours) and time to treatment (11 vs 35 hours). There was also a significant decrease in LOS by 2 days (3.1 vs 5.1 days). However, there was no statistical difference in LOS, ancillary testing, or charges in the overall population.

I would have liked to see whether there was a difference in rate of associated complications or adverse events in the pre and post GIP era among hospitalized children with community-acquired diarrhoea. This study was also conducted within a single healthcare system and in an ideal world should be investigated at other institutions.

Why does it matter?

Children get diarrhoea… a lot. Common culprits include viruses, bacteria, parasites and the occassional non-infectious aetiology. GIP allows for the testing of multiple organisms with faster turnaround of results, but it is also expensive.  We need to be judicious about which patients should undergo testing with GIP and determine whether results will impact clinical care.

The Bottom Line:

GIP may allow for faster turnaround of results, faster time to treatment, and decrease in LOS for a small subset of patients. Although the GIP yielded positive results in 4 out of 10 patients, most positive tests were due to viruses and 6 out of ten of GIP results were negative. Given that most cases of diarrhoea are self-limiting and can be managed with supportive care, the routine use of GIP does not seem cost-effective. Consider GIP (if available in your institution) if the pre-test probability for an actionable and treatable aetiology is high.

For more information on gastroenteritis why not visit Angharad Griffiths’ post at

Reviewed by: Dennis Ren

Article 4: Oxygen in African children with pneumonia

Maitland K, Kiguli S, Olupot-Olupot P et al. Randomized controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia. Intensive Care Medicine 2021;47(5):566-576

What’s it about?

This multicentre African study investigated which delivery method of oxygen support, children (age 28 days to 12 years) admitted with confirmed pneumonia (deemed severely hypoxic (Sp02 80-91%) or hypoxic (Sp02< 92%)) would need to decrease mortality. The trial was named COAST (The Children’s Oxygen Administration Strategies Trial). Those in the severely hypoxic arm (n=388) were randomised to high flow nasal therapy (HFNT) (n=194) or low flow oxygen (LFO) (n=194). Patients in the hypoxic arm (n=1454) were randomised to HFNT(n=363), LFO(n=364) or permissive hypoxia (n=727). HFNT was delivered by AIRVO2– initiated at room air and LFO was oxygen delivered by nasal cannula or standard masks. Ethical approval was sought.

Primary endpoints were mortality at 48 hours and up to day 28 post-randomisation. The entire trial was prematurely stopped due to a campaign in Uganda that deemed permissive hypoxia unethical.  Of the data collected, in the severely hypoxic group, 48 hours mortality was better using HFNT 9.3% vs 13.4% for LFO, demonstrating a 40% risk reduction in the HFNT arm.  For the hypoxic group, there was similar mortality at 48 hours across all arms (1.1% for HFNT, 2.5% for LFO and 1.4% for permissive hypoxia). Similar patterns were demonstrated at 28 days mortality. However, interpretation of the statistical significance of these results was severely limited by the inability to adequately power the study, due to early trial termination.

(For more information on High Flow see Padmanabhan Ramnarayan’s post on High Flow- When and How available at:  

(In addition to this great learning module on Pneumonia by Ellis Collins and Michelle Alisio:

Why does it matter?

In developing countries, the supply and demand of oxygen in hospitals can be financially and logistically challenging. Studies that explore the rationalisation of oxygen therapies that are clinically safe, as well as reduce cost burden are beneficial. This is also relevant, in recent times with the increased demand for oxygen therapy in the COVID-19 pandemic.

Although oxygen therapy is deemed a standard pneumonia treatment, there is evolving evidence of oxygen toxicity with over-use, thus needs more careful consideration.

The bottom line

The use of HFNT vs LFO vs permissive hypoxia in children admitted to hospital with pneumonia in low resource settings still remains unclear.  Although this study does not provide definitive data to inform treatment guidelines, it supports the need for future, adequately powered studies of a similar design to explore this further. Until then, clinicians should be guided by the World Health Organisation (WHO) ‘Hospital Care for Children’ guidance for best practice.

Reviewed by: Melanie Ranaweera

Article 5: Splenic injury? Off you go

Leah Plumblee et al, J Trauma Acute Care Surg.Isolated low-grade solid organ injuries in children following blunt abdominal trauma: Is it time to consider discharge from the emergency department?  2020;89: 887–893 DOI: 10.1097/TA.0000000000002899 PMID: 32769952

What’s it about?

In this study, the authors examine the rate of “major” intervention (surgery, angiographic embolization, or blood transfusion) received by patients with grade I-III solid organ injuries from blunt trauma. The authors performed a secondary analysis of data gathered from two previously conducted trials (PECARN Network). Their hypothesis was that patients with isolated grade I-III solid organ injuries would be unlikely to receive interventions, which would indicate that these patients could be managed by simple observation in the ED, followed by discharge instead of the traditional pathways of admission for overnight observation.

A total of 517 patients were assessed of whom 34 underwent a major intervention. None of the patients with isolated grade I-II solid organ injuries and only 2.6% of the isolated grade III injuries received a major intervention. Almost 1 in 10 had multiple low-grade injuries, and this did not increase the risk of intervention.

It should be noted however, that in the original studies, only 3% of these patients were discharged from the ED directly by the treating clinicians, suggesting that there was something pushing the original clinicians to admit most of these cases. The median length of stay was 2 days.

Additionally, it is important to highlight some patients were excluded from the original trial if they had a CT at their original institution before being transferred to a participating centre. This could be an important source of bias, if the original clinician was concerned enough to transfer a low-grade injury, then the likelihood of intervention is probably higher; but we do not know, as these patients were excluded from the original studies.

Why does it matter?

In contrast to adults, the majority of paediatric solid organ injuries are managed conservatively, particularly low-grade injuries from blunt trauma. The authors conclude that it is likely safe to discharge patients with grade I and II injuries without other significant injuries from the ED after a brief period of observation. While I agree it is unlikely that these patients would require what the authors define as “major” interventions. This definition is too narrow and there are a lot of important therapeutic interventions that are reasons to admit patients that have been excluded from the trial by this definition. Additionally, there were no attempts made to assess for other important factors addressed by admission such as follow up, MDT input and patient satisfaction. As a result, I find that I cannot agree with the sentiment expressed by the authors, while they have shown that this may be a safe option, they have provided insufficient evidence to demonstrate that it is an option that we should pursue. The author’s conclusions are unsupported by the evidence provided and represent too big of a leap. We have no idea what other services patients will miss from inpatient services.

Clinically Relevant Bottom Line:

Caution must be taken when discharging patients from the ED who have evidence of solid organ injury based on the conclusions of this study alone.

Reviewed by: Sean Croughan 

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!

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.

All articles reviewed and edited by Vicki Currie


  • Vicki is a consultant in the West Midlands in the UK. She is passionate about good communication in teams and with patients along with teaching at undergraduate and postgraduate level. When not editing Bubble wrap Vicki can be found running with her cocker spaniel Scramble or endlessly chatting with friends.

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