The 50th Bubble Wrap

Cite this article as:
Currie, V. The 50th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:
https://dontforgetthebubbles.com/the-50th-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: Are steroids of any use in pre-school wheeze?

Wallace A, Sinclair O, Shepherd M, et alImpact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trialArchives of Disease in Childhood 2021;106:339-344

What’s it about? 

This paper looks at a common problem and one where there is huge variation in practice; should we give oral steroids to pre-school children who present to the emergency department with wheeze?

This was a double-blinded, randomised, placebo-controlled trial based in three hospitals in New Zealand. Children were either allocated 3 days of oral prednisolone or a placebo of similar colour, taste and viscosity (yuk!).  The primary outcome was measured by a change in Preschool Respiratory Assessment Measure (PRAM) score at 24 hours, although several interesting secondary outcomes were also measured.  The authors looked at 24–59 month-olds in order to exclude bronchiolitis cases. 3247 children were identified as being eligible with 477 children making it to the intended to treat analysis.

Why does it matter? 

In 2009 Panikar et al found there was no reduction in duration of hospitalization when giving steroids for pre-school wheeze, looking at children from 10 months to 6 years of age. However, in 2018 Foster et al found that giving oral steroids for children aged between 2 and 6 years old reduced their average length of stay from 540 to 370 minutes.

The authors of this paper found no difference in PRAM score at 24 hours between the groups (their primary outcome measure) and also no difference in the number of doses of salbutamol administered, length of stay for those admitted or representation rates within 7 days. A novel finding was that at 24 hours the median PRAM score was 0 for both groups and only one child still had severe disease (PRAM 9-12).  This might be the fact that 218 children were excluded for ‘severe disease’ despite this not being in the exclusion criteria, as well as 175 children excluded for previous life-threatening asthma and 123 excluded for chronic respiratory or cardiac disease.

However, the authors did find that the prednisolone group had less respiratory distress 4 hours after medication administration and reduced requirement for hospital admission, additional corticosteroid or intravenous treatment.

Clinically Relevant Bottom Line:

The results of this study suggest that giving oral steroids for pre-school wheeze is of limited benefit. However it may explain why there is perceived benefit, children clinically respond in the first 4-6 hours even if the overall outcome isn’t altered. It’s not clear from the study how long after arrival steroids were given and this may be an interesting area of further study.

Many centres now give single-dose dexamethasone which concords with the findings of this study in that 3 days of prednisolone may not be necessary given the median PRAM score of 0 at 24 hours. Some clinicians may find the reduced need for intravenous medications or hospital admission sufficient benefit to give a single dose of dexamethasone in the PED and so it is unlikely the debate about which pre-school children should receive steroids has been put to bed.

Reviewed by: James Thyng

Article 2: This is just how I cope

Herrick SS, Hallward L, Duncan LR. “This is just how I cope”: An inductive thematic analysis of eating disorder recovery content created and shared on TikTok using #EDrecovery. International Journal of Eating Disorders. 2021 Apr;54(4):516-26.

What’s it about? 

This Canadian study investigated the impact of eating disorder (ED) recovery videos shared on the social media platform TikTok.

The study completed a thematic analysis of the first150 TikTok posts under the hashtag #EDrecovery (Eating Disorder recovery) in June 2020 (454.5 million views as of June 2020 and around 1,500 posts with this hashtag).

Five themes were identified: ED awareness (N=32), Inpatient story time: “ED unit tings” (N=28), Eating in recovery (N=27), Transformations: “how about a weight gain glow up?” (N=27) and Trendy gallows humour: “let’s confuse people who have a good relationship with food” (N=36).

In around 1 in 5 of the posts creators shared different aspects of recovery to encourage a better understanding of recovery and ED’s. Four subthemes were found: recovery victories, reality of recovery, education and sharing positivity within these raising awareness posts.

Although the #EDrecovery videos raised awareness about eating disorder, some videos contain content which blur the line between ED recovery and pro-ED content and may be harmful to some TikTok users.

Why does it matter? 

Social media channels such as TikTok has a large impact on its user base, the majority of which are children and teenagers. TikTok formed in 2017 is one of the fastest growing mobile apps- with over 2 billion downloads (as of January 2020) and a whopping estimated 80 BILLION active users, the majority being children and young adults.

TikTok can be used to spread ED awareness and build a supportive community for ED recovery users. It is important to explore whether TikTok can be used as a tool to assist in ED recovery.

Clinically Relevant Bottom Line:

A fine line exists between ED recovery and pro-ED content. Some users find #EDrecovery videos helpful, while others may misinterpret the videos as triggering their ED behaviour.

Reviewed by: Jessica Win See Wong

Article 3: Do rapid diagnostic methods improve antibiotic prescribing in bacteraemia?

Faugno, AK., Laidman, AY., Perez Martinez, JD., Campbell, AJ., & Blyth, CC. (2021). Do rapid diagnostic methods improve antibiotic prescribing in paediatric bacteraemia? J Paediatr Child Health, 57(4), 574–580. https://doi.org/10.1111/jpc.15272

What’s it all about?

Rapid diagnostic methods are being developed to identify causative pathogens earlier to optimise early antibiotic therapy for patients with bacteraemia. The authors performed a retrospective study of 255 bacteraemia cases at a tertiary referral hospital in Western Australia. They compared patient outcomes in cohorts receiving antibiotics before and after the implementation of two rapid diagnostic tests: matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) and GeneXpert Xpert MRSA/SA.

The median time taken to administer optimal therapy was not significantly different between those undergoing rapid diagnostic testing and those who did not (39.1 vs 44.4hrs, p= 0.66). Similarly, there was no significant difference in hospital length of stay (7 vs 9 days), number of ICU admissions (20 vs 15) or all-cause mortality (1.6 vs 1.6%).

Why does it matter?

It is well-established that timely administration of empirical antibiotic therapy in cases of sepsis can reduce mortality and morbidity. In fact, one-third of paediatric deaths within intensive care units are associated with sepsis or septic shock. What’s more, the prolonged use of broad-spectrum antibiotics and delay in targeting optimal therapy can potentiate antibiotic resistance.

Adult studies have already shown that timely identification of pathogens can improve appropriate antibiotic therapy but there is little known about its effect in paediatric populations who present with a difference clinical and microbiological profile.

The Bottom Line:

The lack of significant difference in this clinical outcome data suggests that there is no beneficial impact of implementing rapid diagnostic testing in paediatric populations with bacteraemia. The authors suggested possible reasons for this, such as the lack of explanations or training in interpreting rapid diagnostic test results for treating doctors, and therefore the need for a real-time programme to support clinical decision making. 

However, it would be interesting to compare this data to other paediatric hospitals through a multi-centre study, given that other regions may have higher rates of antimicrobial resistance and candidaemia which can alter the effectiveness of empiric antibiotic therapy. Moreover, changes to hospital guidelines for empirical therapy may be better captured through prospective studies in the future.

Reviewed by: Ivy Jiang

Article 4: What’s the time, Mr Wolf?

Stellman, R., Redfern, A., Lahri, S., Esterhuizen, T., Cheema, B. (2021) How much time do doctors spend providing care to each child in the ED? A time and motion study. Emergency Medicine Journal, Published Online First: 15 April 2021. doi: 10.1136/emermed-2019-208903

What’s it about?

The authors conducted a cross-sectional observational study over a 5-week period in two EDs – a tertiary centre and a large district hospital, both with separate paediatric ED areas – in the Western Cape of Africa. The “time and motion” methodology was used, where a single trained, independent observer was placed in the ED and observed and timed Doctors’ interaction with patients that met inclusive criteria. Criteria included age (0-13 years), unplanned presentation (not referred  by another source) and had an initial assessment by a qualified medical officer employed by that site. The patient triage category, as per the South African Triage Scale, was also recorded. Primary objective: to measure the total time taken by doctors to assess and manage each of a series of paediatric patients. Secondary objective: whether acuity of patient—as estimated by triage category affected the average time taken, and to compare these averages to the estimated benchmarks used to calculate hospital staffing allocations in the region.

A total of 100 patients were included and the median DTPP (doctor time per patient) for each triage category was as follows:

  • Green (routine; see within 4 hours): 31 minutes (Target set for staffing calculations are: 15 minutes for green)
  • Yellow (urgent; see within 1 hour) 39 minutes (Target 40mins/ patient)
  • Orange (very urgent; see within 10 minutes) 48 minutes (Target 50min/patient)
  • Red (emergency; see immediately) 96 minutes (Target 50min/ patient)

These time frames were compared with the local hospital benchmarks (developed to guide assigning ED staffing) and found that the median timing for patients triaged as green and red were significantly higher (p=0.001 and p=0.002, respectively). 

Why does it matter?

Time often seems warped inside the Emergency Department (ED) – some shifts fly by while others seem to drag on. Sometimes, you see a new patient every 30 minutes, and other times, you spend 3 hours with just one patient! Whilst most ED have audits to monitor Key Performance Indicators (KPI) looking at waiting times, time to treatment, time to admission / time to discharge etc few studies actually look at the (DTPP), which is the time spent assessing and managing a patient. This value depends on a large number of medical and psychosocial variables but if it can be accurately measured, it could be used to determine the right staffing required in a department.

The bottom line

Even with the limitations of this study (small sample size, only a single observer collecting data for a short period of observation per day), the DTPP was found to be significantly higher than the local expected time frame for the highest and lowest triage categories. This study could be repeated at your local ED (with the limitations addressed) and the information could be useful in determining whether your ED is adequately staffed, which would in turn improve a variety of KPIs.

Reviewed by: Tina Abi Abdallah

Article 5: Is the use of excessive non-resuscitation fluid associated with worse outcomes?

Barhight MF, Nelson D, et al.Non-resuscitation fluid in excess of hydration requirements is associated with higher mortality in critically ill children [published online ahead of print, 2021 Mar 17]. Pediatric Research. 2021;1-6.

What’s it about?

This study looks at whether giving excessive non-resuscitation fluid to critically unwell children is associated with a worse clinical outcome.

The authors conducted an observational study in PICUs of two large American hospitals between 2010 and 2018. They reviewed 14,483 patients and calculated their daily fluid balance for the first 3 days of their stay. This included all fluid given that wasn’t prescribed as a ‘bolus’. They then used the cumulative fluid balance at the end of day 3 to work out a percentage fluid overload (FO) which they stratified into <10%, 10-20% and >20%. The primary outcome was in-hospital mortality and the secondary outcome was ventilator-free days at 28 days.

For each FO category, the volume of fluid that was given in excess of the estimated requirement (using the Holliday-Seger method) was calculated. This demonstrated that excess non-resuscitation fluid was given in just over 1 in 2 of the patients and that maintenance fluid and nutrition were the largest contributors to fluid input. The number of patients receiving excess fluid increased with each FO category and equated to an excess of 164ml/kg in the >20% group.

Analysis was performed for each FO strata to look for an association between % FO and mortality, adjusting for confounders such as age and illness severity. This demonstrated an increase in adjusted odds of death when compared to the <10% group of 1.8 times in the 10-20% group and 2.6 times in the >20% group.

The authors also found that for every 10ml/kg of excess fluid given, there was 1.01 times higher odds of death. There was also a 1% decrease in likelihood of having a ventilator free day.

As this is an observational study, it can only demonstrate associations and not causality.

Why does it matter?

In the adult population studies have shown that almost 60% of the fluid administered to patients was in the form of maintenance fluids and “fluid creep” (the combined volume used from medications, electrolytes, and continuous infusions used to keep access lines open).

Even though this study relates to critically unwell children, maintenance fluids are something we prescribe routinely within paediatrics, and this study highlights the need for a carefully considered approach to their use in all children, with frequent readjustment according to fluid balance so as not to cause harm.

Further studies are required to examine whether our current prescribing practices should be modified, but nevertheless, this study should make us think more carefully about how much fluid we are giving to our patients.

Clinically Relevant Bottom Line:

 This study shows that non-resuscitation fluids are frequently given to patients in excess of their hydration requirements and could represent potential iatrogenic harm. 

Reviewed by: Laura Duthie

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

The 49th Bubble Wrap

Cite this article as:
Currie, V. The 49th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:
https://dontforgetthebubbles.com/the-49th-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: The associations between initial serum pH value and outcomes of paediatric out-of-hospital cardiac arrest

Okada A, Okada Y, Kandori K, Nakajima S, Okada N, Matsuyama T, Kitamura T, Hiromichi N, Iiduka R. Associations between initial serum pH value and outcomes of pediatric out-of-hospital cardiac arrest. Am J Emerg Med. 2021 Feb;40:89-95. doi: 10.1016/j.ajem.2020.12.032. Epub 2020 Dec 17. PMID: 33360395.

What’s it about? 

This paper reviewed the association between initial pH, obtained via intra-arrest VBG, and patient outcomes to evaluate if pH can be used to prognosticate in paediatric out of hospital cardiac arrest.

The authors reviewed a large, multicentre, prospective register of out-of-hospital cardiac arrests in 87 hospitals in Japan. They included paediatric out-of-hospital cardiac arrest patients younger than 16 between June 2014- December 2017 (458 patients included in the analysis – however over 35,000 listed in the registry). The primary outcome was 1-month survival. They divided the patients into four groups (based on initial pH on blood gas) and compared this to the patient’s ultimate outcome.

Interestingly, the median age of the patients was one year of age. Just over 6 in 10 of the patients were male. In 7 out of 10 patients, the first monitored rhythm was asystole. Cardiogenic arrest occurred in 4 out of 10 patients.

Mortality, and survival with good neurologic function, were lookd for. The overall survival rate at one month was just over 1 in 10 patients. In the group with pH > 6.82 survival rate was around 4 in 10 patients. However, with a pH< 6.47, thesurvival rate was 1 in 100 patients.

Of particular interest, in the entire study population of 458 patients, there were no patients who survived with good neurological function with a pH <6.8.

Why does it matter? 

Deciding when to stop resuscitation in a paediatric cardiac arrest can be difficult. Guidance is sparse and there are no universally recommended measures to help providers decide when to stop resuscitative measures. This is a stark contrast to adult cardiac arrest management where there are many validated termination of resuscitation rules based on measurements such as end-tidal CO2 s.

This is the first study to assess the association between pH and prognosis in paediatric out-of-hospital cardiac arrest. It presents robust evidence to support an objective, easily obtained measure that can be used to assist decision making around the termination of resuscitation. Important exclusions in this study were patients where resus was not attempted at a hospital, unknown age, traumatic or arrest secondary to hanging and those with no pre-hospital data.

This is an exciting paper providing guidance in an area sorely lacking any previous data. It gives providers a valuable tool that can substantially assist when making a difficult decision.

Clinically Relevant Bottom Line:

In out of hospital paediatric cardiac arrest, according to this study, no patients with a pH <6.8 survived with a neurologically favourable outcome. Survival in general was significantly lower in patients with an initial pH <6.8.

Reviewed by: Sean Croughan

Article 2: Should we be using focused cardiac ultrasound to guide therapy in children with sepsis?

Arnoldi s, Glau CL et al. integrating focused cardiac ultrasound into Pediatric septic shock assessment. Pediatr Crit Care Med. 2021 mar 1;22(3):262-274

What’s it about? 

This paper looks at whether the integration of FCU (focused cardiac ultrasound) in clinical assessment of children with sepsis would alter clinician’s evaluation of their haemodynamic characteristics.

The authors conducted a retrospective, observational study from January 2014 – December 2016 in a large PICU in America. They reviewed 74 PICU patients who received FCU within 72 hours of sepsis pathway initiation. Assessment by clinicians prior to FCU was compared to assessment after FCU in 46 patients, to determine if there was a difference in the haemodynamic characterisation of patients.

They demonstrated that incorporation of FCU changed the clinician characterisation of haemodynamic assessment made prior to FCU in more than 2 out of 3 of cases. The most common new finding identified post-FCU was myocardial dysfunction in (7 out of 22) cases. The most commonly ruled-out physiologies by clinician after FCU performance were obstructive physiology (5 in 8 cases), fluid responsiveness (13 in 26 cases).

Why does it matter? 

Sepsis in children continues to be one of the leading causes of mortality and morbidity worldwide.  Most children who die of sepsis suffer from refractory shock and/or multiple organ dysfunction within the initial 48 -72 hours of treatment, thus demonstrating the need for early and targeted interventions.

The previous method of classifying patients as having either ‘warm shock’ or ‘cold shock’ to guide therapy has been demonstrated to have poor correlation with cardiac function and systemic vascular resistance, and has not led to improved outcomes. It is now recommended that more advanced techniques such as focused cardiac ultrasound (FCU) be used alongside clinical assessment to identify haemodynamic status and direct therapy.  This is already widely the case in adult practice and algorithms have been created for its integration into patient management. 

Although this is a small study, it makes us think about the use of cardiac ultrasound alongside clinical assessment of children with sepsis in order to understand the haemodynamic characterisation of these patients.

This may be particularly useful in relation to fluid responsiveness, as half of the children who were thought to be fluid responsive pre-FCU, were found not to be after a FCU was performed. We know that children with sepsis often receive significantly more fluid per kilogram than adults which is associated with worse outcomes.

Clinically Relevant Bottom Line:

FCU, when incorporated into shock assessment, has the potential to identify myocardial dysfunction earlier and could result in reduced fluid administration as well as more targeted therapy based on haemodynamic status. However, further work is needed to determine how this can be used within paediatric practice.

Reviewed by: Laura Duthie

Article 3: Don’t forget the planet

Di Cicco, M.E., Ferrante, G., Amato, D., Capizzi, A., De Pieri, C., Ferraro, V.A., Furno, M., Tranchino, V., La Grutta, S. (2020) Climate Change and Childhood Respiratory Health: A Call to Action for Paediatricians. Int J Environ Res Public Health, Vol 24;17(15):5344

What’s it all about?

The authors conducted a systematic review looking at papers which examined the connection between respiratory illnesses in children aged 0 – 18 years. Keywords used separately and in combination were (allergic rhinitis, rhinitis, asthma, bronchitis, pneumonia, infections) and key environmental phrases (climate change, pollution, particulate matter, ozone, nitrogen dioxide, allergen, pollen). There was no limitation on the date of paper or country of origin.

Whilst much of the research at this stage is not completely conclusive key points from the review include:

  • Several studies from different countries found a connection between the increased prevalence of rhinitis and asthma, as well as the frequency of symptoms with increased global temperatures, which has changed many plant species’ lifecycles and led to longer pollen seasons
  • Positive correlations between the incidence of pneumonia and other acute respiratory tract infections in the context of increased extreme weather events such as heatwaves, fires and floods
  • Positive associations between the increased relative humidity and increased activity of respiratory viruses such as respiratory syncytial virus

Why does it matter?

Climate change is the long-term shift in weather conditions (temperature, humidity, winds and extreme weather events) and is often talked about in regards to protecting our wildlife or preventing further damage to our oceans and forests. It is less talked about when considering the impact on our own health. A child born in 2020 will live in a world that is more than 4 degrees warmer than the pre-industrial average, and subsequently will be at greater risk of a variety of acute illnesses as well as long term health consequences.

The Bottom Line:

More research needs to be done to accurately define the burden of climate change on our health. In the interim, we can all be environmental champions, from making changes in our own lives to reduce our carbon footprint as well as educating and influencing our colleagues and patients to do the same.

 …And for those with spare time; conducting research into the direct effects of climate change on specific health conditions along with contributing to government policies to create change at a higher level and reducing the carbon footprint of our healthcare systems are excellent places to start! 

Reviewed by: Tina Abi Abdallah

Article 4: Domo arigato, Mr Roboto

Littler BKM, Alessa T, Dimitri P, et al Reducing negative emotions in children using social robots: systematic reviewArchives of Disease in Childhood  Published Online First: 08 March 2021. doi: 10.1136/archdischild-2020-320721

What’s it about?

The paper looks at a number of studies that have used social robots in paediatric outpatient settings to interact and provide multi-sensory experiences to patients. The author postulates that using social robots provides better interaction and distraction for children, thus reducing anxiety and distress during the visit.

This systematic review managed to find ten studies that used social robots ranging from humanoid-based robots to ones simulating toy bears, dinosaurs and seals. The robots interact verbally and physically, and can respond to patient cues and tactile stimulation. They were used before or during the intervention. The studies included randomised controlled trials, exploratory trials, pilot and an observational study, with patient numbers varying from 2 to 73 (320 in total).

Why does it matter?

For lots of children a visit to the hospital can be a stressful and anxiety inducing event. There has been research to suggest that social robots have a positive impact on supporting adults with dementia and in children with autism they have been a useful tool in conducting therapy. The outcomes of this study were measured by observation, and by recording levels of distress, anxiety, pain and emotion using a variety of behavioural questionnaires. Overall, the feedback from the studies showed positive engagement from patients with their robots, reducing negative emotions, distress and pain.

The bottom line

There is promising data to suggest that robots may improve the experience of children in the healthcare environment. However, the evidence is weak due to the nature of the studies, lack of uniformity in the measurements, and low patient numbers. More research is needed on this topic to be able to really change practice but this sci-fi intervention may well become a reality in the not so distant future.

Reviewed by: Laura Riddick

Article 5: Children visiting the Paediatric emergency department during Ramadan

Sawaya,R., Wakil, C., et al (2021) Pediatric emergency department utilisation during Ramadan: a retrospective cross- sectional study. Archives of Disease in Childhood 2021;106:272-275.

What’s it about?

 This study looks to investigate the impact of Ramadan on patient characteristics, diagnoses and metrics in the paediatric emergency department (PED). There is limited data on how Ramadan impacts paediatric ED’s.

Why does it matter?

The authors looked at patient and illness characteristics as well as PED metrics including peak patient load, presentation timings, length of stay, time taken to order tests, receive samples and reporting of results to see how these were affected during the months of Ramadan and those before and after. 

This is a retrospective cross-sectional study on paediatric patients from 0 – 18 years presenting to a PED tertiary centre in Lebanon. Data was collected from all PED visits with any complaint at any time during Ramadan and the months (30days) before and after in 2016 and 2017. A bivariate analysis was performed between the Ramadan and non-Ramadan groups. The main outcomes were illness severity, chief complaints, final diagnoses, PED metrics including peak patient load, presentation timings, length of stay, and PED efficiency metrics such as time to order tests, times to samples being received and reported. 5711 patients were included and 1672 of these presented during Ramadan. There was no significant difference between age, gender or illness severity between the Ramadan or non-Ramadan group. This study found a significant difference in the number of GI complaints during Ramadan (39%) compared with the non-Ramadan group (35%). 

Trauma related complaints increased during Ramadan (3 in 100) vs (2 in 100) in non-Ramadan periods. Especially during the non-fasted periods of Ramadan (4 in 100) vs (2 in 100) during the fasted period of Ramadan. The number of daily visits during Ramadan (28.3) was reduced compared with non-Ramadan attendances (31.5). The Ramadan group did not have to wait longer for tests to be ordered or to have samples collected. 

This study was a single centre- and the charts that were reviewed did not have information on the patients individual fasting status. This would be interesting to see if the patient’s individual status affected diagnosis. The team used months immediately before and after Ramadan to reduce the confounding effects of seasonal bias.

Clinically Relevant Bottom Line:

This study revealed that there were some changes in GI and trauma presentations during the Ramadan period. There was also a reduction in cases presenting in this centre- this could help to influence staffing during this time if the patient population reflected that of the population in this study.

Reviewed by: Vicki Currie

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

The 48th Bubble Wrap

Cite this article as:
Currie, V. The 48th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:
https://dontforgetthebubbles.com/the-48th-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: An update on PIMS-TS/MIST-C

Flood J, Shingleton J, Bennett E, Walker B, Amin-Chowdhury Z, Oligbu G, Avis J, Lynn RM, Davis P, Bharucha T, Pain CE. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020. The Lancet Regional Health-Europe. 2021 Apr 1;3:100075.

What’s it about? 

During the first breakout of PIMS-TS, Public Health England (PHE) and the British paediatric surveillance unit (BPSU) requested reports of PIMS-TS, Toxic shock syndrome (TSS) and Kawasaki Disease (KD) to be submitted for prospective national surveillance. This study looks at patients under the age of 16 who presented with symptoms between 1st March and 15th June 2020. The symptoms for the diagnosis of PIMS-TS was set out as per RCPCH guidance (fever >38, CRP>100, no infection proven and evidence of one at least system dysfunction) along with strict criteria for KD and TSS. From these reports, patients were excluded if they did not meet any PIMS-TS resulting in 268 cases of PIMS-TS meeting diagnostic criteria.

Why does it matter? 

Children have made up a small proportion of direct clinical burden due to COVID-19. However, cases all over the world began to appear of PIMS-TS associated with SARS-CoV-2 infection and more information was needed to be able to map this disease process and use clinical data to explain clinical characteristics of PIMS-TS and the epidemiology between these overlapping clinical conditions.

The results of the study showed the median age to be 8 years with PIMS TS/KD subgroup younger (5 years) and PIMS TS/TSS older (8 years) than PIMS TS only cases (7years). 60% of the population were male and patients from the BAME community seem to be disproportionately affected, especially within London.

Patients who exhibited PIMS-TS with features of TSS as well seemed to fair worse with a larger number of interventions, longer hospital stay and severity of illness. 35 cases were felt to be clinically in keeping with PIMS-TS despite not meeting the CRP criteria. Parental occupation was reported in just under half of the cases and more than 2 out of 3 were reported as healthcare workers. Just over 1 in 3 of the children had evidence of current or previous SARS-CoV-2 infection.

Clinically Relevant Bottom Line:

Presentations of PIMS-TS are strongly linked with SARS-CoV-2 infection, and those with features similar to toxic shock syndrome tend to be more unwell. Children in London, and in the BAME population, seem to be disproportionately represented, with the most having severe presentations. The epidemiological links are similar to that of other countries.

Reviewed by: Laura Riddick

Article 2: Screening adolescents for the risk of suicide attempts

Pediatric Emergency Care Applied Research Network (PECARN) King CA, Brent D, Grupp-Phelan J, et al., (2021) Prospective Development and Validation of the Computerized Adaptive Screen for Suicidal Youth. JAMA Psychiatry. 2021 Feb 3:e204576

What’s it about? 

A prospective 2-part study with data collection being undertaken at different ED’s in the United States, which are part of the PECARN network. Introduction of computerised adaptive testing (CAT) which put simply is a tool that takes individuals responses to questions and determines their standing on the measured trait e.g., risk of suicide attempt. This offers the possibility of a more individualised, accurate screening tool.

Two studies ran independently:

Study 1(2015-2016): used CAT to develop a screening tool (computerised adaptive screen for suicidal youth CASSY) that targets items to the individuals personal risk profiles to provide a continuous risk score for the likelihood of suicide attempt (SA) within 3 months.

Study 2 (2017-2018): Prospectively validated CASSY.

In Study 1, adolescents aged 12 – 17 years who presented to ED were offered to complete the Ask Suicide Questions (ASQ) and Columbia Suicide Severity Rating Scale (C-CSSR). Depending on these responses the participants were stratified into low medium/ high risk for suicide attempt. Then a random selection of these were assigned to follow up which was done by interviewers who were blinded to the baseline data were responsible for the 3-month telephone follow up which assessed the number of suicide attempts made by the patient during this time.

CASSY was then developed using questions from these screening tools (questions which were identified to have high suicide attempt predictive value) and was cross validated in Study 1, before it’s use in Study 2. Subsequently, adolescents aged 12 – 17 years who presented to ED were offered to complete CASSY.

The authors have used a multivariate logistic regression model to predict suicide attempt during the 3 months follow up. Based on this, the Receiver Operating Characteristic (ROC) curve demonstrates a sensitivity of 82.4% for predicting suicide attempts using the CASSY score, at a specificity of 80% with an area under the curve (AUC) of 0.87 [95% CI, 0.85-0.89].

For a reminder on these type of stats take a look at this DFTB post.

Some important exclusions in this study population were being a ward of the state (e.g. adolescent in foster care) and non-English speaking participants which from previous studies are shown to be important risk factors for altered mental health.

Why does it matter? 

Data from Australia (and around the world) show that our adolescent population are suffering from increasing levels of mental health issues such as anxiety and depression. With those illnesses often comes suicidal ideation, and when these patients reach crisis point, they present to our emergency departments (ED). One of the biggest challenges to all suicidal risk screening is the accurate identification of young people at risk in a setting that efficiency is required. Existing screening tools such as (ASQ) have shown moderate sensitivity to predicting suicide risk, meaning some individuals at risk were not identified.

Clinically Relevant Bottom Line:

This study shows the CASSY tool has a good sensitivity (ability to pick up) those at risk of suicide attempt. Early and accurate recognition of mental health illnesses and suicidal ideation in primary health care settings and emergency departments is an essential first step in managing these issues.

Reviewed by: Tina Abi Abdallah

Article 3: The use of minimally invasive surfactant therapy

Roberts CT, Halibullah I, Bhatia R, Green EA, Kamlin CO, Davis PG, Manley BJ. Outcomes after Introduction of Minimally Invasive Surfactant Therapy in Two Australian Tertiary Neonatal Units. The Journal of Pediatrics. 2021 Feb 1;229:141-6.

What’s it all about?

This 18-month prospective audit collected data on patient demographics and clinical outcomes following the introduction of minimally invasive surfactant therapy (MIST) in two neonatal intensive care units (NICUs) in Australia. Infants were eligible for MIST if they received CPAP support with clinical or radiological diagnosis of respiratory distress syndrome (RDS), and were excluded if they had major congenital anomalies, circulatory compromise, recent apnoeas or a diagnosis other than RDS.

Why does it matter?

MIST is a less invasive method of administering exogenous surfactant for the treatment of RDS in premature infants compared to previous surfactant administration by endotracheal tube. Previous meta analysis highlighted that MIST is associated with reduced need for mechanical ventilation, and adverse events such as bronchopulmonary dysplasia and death compared to endotracheal intubation. However, it is difficult to make clear conclusions about the efficacy of MIST versus endotracheal tubing for surfactant administration, as a range of other factors can affect success rate. These include gestational age, surfactant dose and timing of procedure (as prophylactic after birth versus an early rescue approach within the first 24 hours of life. As MIST and endotracheal intubation require laryngoscopy, the authors stress the continued need to adequately train junior staff and suggest the use of routine video laryngoscopy regularly to allow for second operator confirmation and potentially increased rates of success.

135 MIST procedures were performed. The median gestation was 30 weeks, and median birth weight being 1439 grams. All infants received supplementary oxygen before MIST. The most common adverse event was peripheral oxygen desaturation to <80% which occurred in 3 out of 4 of MIST procedures. Other events included bradycardia <100 beats per minute (13 out of 100) and the need for positive pressure ventilation (1 in 10). Positively, over 2/3rds of infants treated with MIST did not require further intubation and mechanical ventilation and senior clinicians had higher rates of procedural success. Surfactant administration was successful in all but one MIST procedure due to patient apnoea requiring intubation.

The Bottom Line:

The authors determined that MIST can be successfully adopted into clinical practice in such settings where staff have limited prior experience. Rates of adverse events, mentioned above, were comparable to results from previous randomized trials. Over 2/3rd of infants in this study with MIST did not require further intubation and ventilation. 

Reviewed by: Ivy Jiang

Article 4: Can we perform phototherapy at home?

Pettersson M, Eriksson M, Albinsson E, Ohlin A. Home phototherapy for hyperbilirubinemia in term neonates—an unblinded multicentre randomized controlled trial. European Journal of Pediatrics. 2021 Jan 19:1-8.

What’s it about?

Within the first week of life, 60% of term babies and 80% of pre-term babies will have some degree of jaundice. This study looked at well term babies and if delivering phototherapy at home, with daily hospital reviews, would be an acceptable alternative to inpatient phototherapy.

This was an unblinded, randomised control trial of 147 jaundiced neonates across 6 hospitals in Sweden. To be included babies had to be well, >48 hours old, have a gestational age >36+0 and have a raised serum bilirubin (SBR). Parents also had to be capable to perform phototherapy at home and agree to return daily for review and blood tests. Babies were excluded if they had a high bilirubin result (>400µumol/L), weight loss of >10% of birth weight, any ongoing infection or illness, or if there was blood group incompatibility.

Babies were randomly selected to receive home phototherapy (78) vs hospital phototherapy (69). Babies in both groups were reviewed daily in the hospital, and a daily SBR and weight. Home treatment was done by Bilisoft (Bilibed) that was provided with eye protection and clear instructions. This study could not find any statistically significant differences that suggested that either therapy was superior to the other. Only 3 in 78 babies of the home phototherapy neonate were converted to hospital treatment. No one across either group had SBR’s high enough to require IVIG or blood exchange. There was no statistically significant difference regarding the duration of phototherapy, time until discharge, amount of blood tests, weight loss or adverse events.

Why does it matter?

Jaundice is one of the most common reasons for prolonged postnatal hospitalisation and readmissions in the postnatal period. Hospital management of jaundice can negatively impact bonding and attachment, it can be inconvenient for families and is associated with a significant cost to the healthcare system.

The bottom line

This study shows that with daily reviews and monitoring, home phototherapy could be an effective and safe alternative to hospital phototherapy for otherwise healthy, term, neonates. When determining appropriateness for home phototherapy bilirubin levels, geographic location and ability to commute, parental anxiety and the capability of parents/carers must all be considered.

Reviewed by: Phoebe Campbell

Article 5: How is procedural sedation performed in Europe?

Sahyoun C, Cantais A, Gervaix A, Bressan S, Löllgen R, Krauss B. Pediatric procedural sedation and analgesia in the emergency department: surveying the current European practice. European journal of pediatrics. 2021 Jan 28:1-5.

What’s it about?

 

This cross-sectional study of european paediatric procedural sedation and analgesia (PSA) was endorsed by the Research in European Paediatric Emergency Medicine (REPEM) network, with data collection between November 2019 and March 2020. 

The study aimed to describe PSA practice across europe, perform a needs assessment-like analysis and also identify barriers to PSA implementation.

Online questionnaires were distributed to a target number of either 10 or 5 emergency departments within each country (depending on their population size), via country specific lead research coordinators. The survey included a clinical case scenario with subsequent questions covering 8 key themes. These ranged from the management of a patient requiring PSA, protocols and safety and barriers limiting PSA implementation. The questionnaire was revised several times following input from each country lead, accounting for variations in relevance, language, and grammar between each country, until a consensus was achieved containing 30 questions. Questionnaires were completed by a senior clinician at each site with 171 hospitals contributing data from 19 countries. The UK and Ireland were not included due to a similar project running in these locations simultaneously.

Midazolam (100%) and Ketamine (91%) were the most available PSA medications, followed by propofol (67%), nitrous oxide (56%) and intranasal fentanyl (47%). 8 in 10 of sites reported sedation being performed by general paediatricians. However just over 1 in 3 of sites stated all staff performing PSA were paediatric advanced life support certified and only 1 in 2 required PSA specific course completion. Safety and monitoring guidelines for PSA were present in most  sites (7out of 10) and 1 in 2 had pre-procedural checklists in place, with these sites most likely to perform IV sedation. Capnography was present in just under half of the sites.

Barriers to PSA implementations included lack of physical space (1 in 2 of sites) and shortages of both nurses and clinicians (both more than 2/3rds of sites). Interestingly half of the sites reported nurse-led triage protocols in use for paracetamol and ibuprofen administration, with these sites experiencing the highest number of patient visits per year.

Why does it matter?

PSA is used widely across europe, however there is a large variation in the standard medications and safety measures in use.

Clinically Relevant Bottom Line:

 This study highlights the need for sharing of best-practice amongst sites with the potential for future trials to determine optimal staff training, medication use, procedural checklists and guidelines, nurse-led triage and staff and physical space allocation for PSA. The network generated as a consequence of this study could be used to facilitate such work in the future.

Reviewed by: Joshua Tulley

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

The 47th Bubble Wrap

Cite this article as:
Currie, V. The 47th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:
https://dontforgetthebubbles.com/the-47th-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: The safety profile of ceftriaxone

Zeng, L., Wang, C., et al., (2020) Safety of ceftriaxone in paediatrics: a systematic review. Archives of Disease in Childhood. Oct;105(10):981-985. doi: 10.1136/archdischild-2019-317950

What’s it about? 

Ceftriaxone is one of the most commonly prescribed antibiotics for children. It is a broad spectrum third generation cephalosporin, used as a first line empirical agent for meningitis, sepsis and useful against many bacterial infections. It has an elimination half-life of 8 hours and can be given once every 24 hours IV or IM, giving us options when that cannula is particularly tricky! Whilst it is well known that using ceftriaxone in the newborn is contraindicated due to biliary sludging, the authors of this paper delved into the literature to identify other adverse reactions (ADRs) to ceftriaxone.

What did they do?

The authors performed systematic searches across several databases looking for studies to evaluate the type of ADR, the incidence of ADRs in patients aged 0 – 18 years old and to identify any potential risk factors for serious ADRs. A total of 112 studies were identified (22 RCTs, 61 case reports, 19 prospective studies, 7 retrospective studies, 2 case series and 1 case control study) which reported on ADRs of ceftriaxone use (although it was not a primary outcome measurement in any of the studies).

Looking at the RCTs, prospective and retrospective studies, gastrointestinal side effects were the most common ADR (specifically, diarrhoea). The second most common ADR identified amongst these studies was hepatobiliary (biliary sludging and cholelithiasis). These ADRs were all transient, and usually self-resolved after cessation of ceftriaxone. The case reports and case studies identified the more serious ADR of immune haemolytic anaemia, which carries a risk of death, especially for patients with an underlying diagnosis of sickle cell disease.

Clinically Relevant Bottom Line:

Transient gastrointestinal side effects are generally tolerable, and we should closely monitor patients for evolving symptoms of gallstones. Most importantly, we should be mindful and cautious when prescribing ceftriaxone in patients with underlying haematological conditions such as sickle cell anaemia, due to the uncommon but significant risk of immune haemolytic anaemia. Ceftriaxone is really a great antibiotic, and as long as we remember the clinical spectrum of ADRs, we will not cause significant patient harm.

Reviewed by: Tina Abi Abdallah

Article 2: Kawasaki Disease vs Septic Shock: Early Differentiating Features Despite Overlapping Clinical Profiles

Power A, Runeckles K, Manlhiot C, Dragulescu A, Guerguerian AM, McCrindle BW. Kawasaki Disease Shock Syndrome Versus Septic Shock: Early Differentiating Features Despite Overlapping Clinical Profiles. J Pediatr. 2020 Dec 5:S0022-3476(20)31482-7. doi: 10.1016/j.jpeds.2020.12.002. Epub ahead of print. PMID: 33290811.

What’s it about? 

According to literature around 6-7% *of patients with Kawasaki disease present with shock and this can provide a challenge in differentiating Kawasaki disease from septic shock. This paper looks to compare clinical features, resuscitative measures and haemodynamic response to treatment between those presenting with Kawasaki disease shock syndrome and children with septic shock.

*Kanegaye JT, Wilder MS, Molkara D, Frazer JR, Pancheri J, Tremoulet AH, et al. Recognition of a Kawasaki Disease Shock Syndrome. Pediatrics 2009;123:e783-9.

What did they do?

This was a retrospective chart review of patients under the age of 18 over a 10-year period admitted to a tertiary centre in the USA. The charts of children who met the criteria for Kawasaki disease shock syndrome (as defined by the American Heart Association) were analysed and children meeting the criteria for septic shock were used as controls. Over the 10-year period >1000 children were admitted to the centre with Kawasaki disease. Of these 9 met the criteria for Kawasaki disease shock syndrome. They were case matched with 18 controls who were admitted with septic shock.

The study found that children with Kawasaki disease shock syndrome were less likely (1 in 9) to have an underlying significant medical illness than the septic shock group (11 in 18). All the patients in the Kawasaki group had at least one of the five classic features of Kawasaki disease at presentation (rash, conjunctivitis, mucous membrane changes, cervical lymphadenopathy and extremity changes). With rash found in 7 of 9 of the patients either at presentation or during the admission. 5 in 9 of the Kawasaki disease cohort had cardiac involvement with zero of the control group with any cardiac involvement.

The length of stay for children in the Kawasaki disease shock syndrome group was a median of 9 days vs 28 days in the septic shock group, with no difference found in ICU length of stay. Biochemical markers were compared, and this study found a lower platelet count (median 140 vs 258) in the Kawasaki group. Interestingly in children with Kawasaki disease shock syndrome the duration of illness prior to admission was much longer (9 days vs 3 days) than the control group.

There have been no studies that directly compare children with Kawasaki disease shock syndrome and septic shock, so this acts as a starting point. However, it is a very small cohort (only 9 patients out of >1000 presentations of Kawasaki disease with Kawasaki shock syndrome); perhaps a multi- centre trial within a network could be done to increase the numbers.

Clinically Relevant Bottom Line:

This study has found that when compared to children with septic shock children with Kawasaki disease shock syndrome are more likely to have a lower platelet count on admission, a longer duration of illness prior to admission, cardiac involvement if an echo is performed and have a longer stay in hospital. All the patients in this study had at least one of the classic features of Kawasaki disease with rash being the most common here. As clinicians who review these children at the front door perhaps a child with a rash and low platelets fever >5 days will continue to make us think about Kawasaki disease.

Reviewed by: Vicki Currie

Article 3: Is it necessary to evaluate urinary tract infection in children with lower respiratory tract infection?

Kim JM, Koo JW, Kim H-B. Is it necessary to evaluate urinary tract infection in children with lower respiratory tract infection? Journal of Paediatrics and Child Health. 2020 Dec;56(12):1924-1928

What’s it all about?

Lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs) are common childhood infections that previous literature has reported to have a concomitance rate of 3 to 10 per 100 children. While LRTIs are often self-limiting viral infections, UTIs are often caused by a bacterial source that can have long term implications if not adequately treated.

What did they do?

This was a retrospective review of 1574 patients’ medical records under 36 months of age who were hospitalised for a LRTI over a 2 year period in a South Korean hospital. 278 of patients had a fever and underwent a subsequent urine evaluation performed either by catheterisation (<24mo) or voided urine (24-36mo).

Patients with a congenital airway or kidney disease, absence of fever at presentation or whose parents refused or failed to undergo a urinalysis were excluded from the analysis.

The overall prevalence rate of a concomitant UTI with LRTI in this population was 1 in 10 in children <36mo and 13 in 100 in children <24mo. Mean age was significantly younger in the UTI group 7 months vs 12 months in the non UTI group. There was a greater prevalence rate of UTIs in boys (n=23) compared to girls (n=7). The most common organism cultured in the UTI group was Escherichia coli which were all treated with a third-generation cephalosporin. The positive rate of virus detection was 93.3% in the UTI group, and 89.9% in the non-UTI group. Most frequently detected co-infections were adenovirus, rhinovirus, and RSV.

The Bottom Line:

LRTIs and UTIs are common childhood infections that have up to a 1 in 10 concomitance rate.  A child presenting with a LRTI and concomitant UTI may present to ED with early respiratory and non-specific symptoms of a UTI (fever, lethargy and irritability), which may lead clinicians to presume a respiratory source of infection and not perform or delay a urinalysis. Hence a diagnosis of an underlying UTI may be missed. Failure to diagnose and promptly treat an underlying UTI can lead to renal morbidity including renal scars, hypertension and chronic kidney disease. Considering the ease of diagnosing and treating a UTI, this study further reiterates the importance of excluding a UTI in children with LRTIs under 36 months of age, especially of male gender. However, given the nature of this single centre study in South Korea, these findings cannot be generalised to a global population and must be taken in context to the population you encounter in clinical practice.

Reviewed by: Emma Chan

Article 4: Why don’t kids get sick with COVID-19?

Zimmermann P, Curtis N., Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections Arch Dis Child 2020;0 1-11

What’s it about?

A review article analyzing the possible mechanisms for reduced severity of COVID-19 in paediatric patients. The debate about if children have a lower rate of COVID-19 infection continues but it is known that children are less severely affected (in contrast to other respiratory viruses). This appears to be true even in paediatric patients with immune suppression or preexisting conditions e.g. IDDM. What we don’t know is why. The authors look at the evidence for multiple hypotheses but the two they favor are:

1)     Age related endothelial damage and increased coagulability. This fits the clinical profile of COVID-19 which features endotheliitis, micro thrombi, thrombotic complications and vasculitic skin manifestations. It could also explain COVID-19 being more severe in conditions which damage the endothelium e.g. hypertension and diabetes.

2)     Age related changes to the immune system. There is a decline in innate and adaptive immunity in the elderly compared with children who have not gone through this decline. The chronic proinflammatory state (which predisposes to the cytokine storm seen in severe COVID-19) increases with age. Additionally the authors hypothesize that the effect of chronic CMV infection on T-cells may explain the worsening of COVID-19 with age.

The authors concluded that these were the only two hypotheses which fit with the age-gradient in COVID-19 with mortality and morbidity rising steeply after 60-70.

The bottom line

If we could figure the ‘magic formula’ protecting children against severe COVID-19 we could use this to target treatment in adults. However, this paper is very much exploring theories and cannot yet be extended to clinical treatments.

The interplay between a lack of endothelial damage, lack of propensity to hyper-coagulation and their not yet declined immune system are most likely to protect children from severe COVID-19 infection.

Reviewed by: Sarah Reynolds

Article 5: A Gut Feeling: Abdominal Symptoms as an Initial Presentation of EVALI

Christel Wekon-Kemeni, MD, Prathipa Santhanam, MD, Pallav Halani, MD, Lauren Bradford, MD, Ceila E. Loughlin, MD.A Gut Feeling: Abdominal Symptoms as an initial presentation of EVALI, Paediatrics Volume 147, number 1, January 2021.

What’s it about?

 

Vaping or electronic cigarette use associated lung injury (EVALI) is a syndrome resulting from electronic cigarette use which causes predominantly respiratory symptoms, such as shortness of breath.

This case report describes an American 13-year-old male presenting, on two occasions primarily with abdominal symptoms of pain, nausea and vomiting. Initially, he was managed as a case of gastroenteritis, and had been noted to have borderline saturations. Initial abdominal CT report described bilateral lung pathology (lower lobe consolidation and atelectasis) in addition to mild jejunal loop thickening. However, after a second admission with similar symptoms plus raised inflammatory markers and fever, further workup was commenced. 

Repeat abdominal CT excluded appendicitis and evidence of inflammatory bowel disease. CXR revealed bilateral changes and a Thoracic CT identified multifocal ground-glass changes and infiltrates bilaterally with scattered septal thickening and dependent bibasal opacities.

Following a review of the patient by the respiratory team, a year long history of e -cigarette use preceding this patient’s symptoms was discovered, identifying EVALI as the potential diagnosis.

The patient was started on intravenous methylprednisolone which, following an improvement in all symptoms, was converted to a  course of oral corticosteroids. Repeat thoracic CT one month following discharge showed almost complete resolution of the initial changes. 

Why does it matter?

EVALI is a relatively new syndrome, mostly documented in North America, with the potential to increase in prevalence as we see the popularity of e-cigarette use continuing to rise.

Given this patient’s initial symptoms of nausea and vomiting, detailed smoking history to include e-cigarette use may not have been taken. Thus, a workup for abdominal pathology was justifiably completed. However, considering published case reports of EVALI describing nausea and vomiting as common symptoms, this diagnosis should still be considered in patients presenting without respiratory involvement initially. The data available describing EVALI in the paediatric population is sparse, nevertheless in adult’s progression to respiratory failure requiring invasive ventilatory support is reported.

Clinically Relevant Bottom Line:

 Although challenging, obtaining an accurate smoking history to include e-cigarette use in young people is important for the consideration of EVALI as a diagnosis. We still don’t completely understand the pathophysiology of e-cigarettes, or how much damage they are causing to the young people we see who smoke them, but remembering to ask about this as part of your history is a step we can take to improve knowledge and understanding.

Reviewed by: Joshua Tulley

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.

The 46th Bubble Wrap

Cite this article as:
Currie, V. The 46th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:
https://dontforgetthebubbles.com/the-46th-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: Ten Tips for Breaking Bad News

Brouwer, M.A., Maeckelberghe, E.L.M., van der Heide, A., et al., Breaking bad news: what parents would like you to know (2020) Archives of Disease in Childhood Published Online First: 30 October 2020. doi: 10.1136/archdischild-2019-318398

What’s it about? 

Difficult conversations in paediatrics often revolve around conditions which reduce life expectancy, such as oncological, metabolic, cardiac and neurological diagnoses. In the case of new diagnoses, difficult discussions may happen in the emergency department – an environment that is not designed for sensitive and long (ideally interruption free) discussions. 

This article reviews the experiences of parents who were involved in difficult conversations surrounding their child’s care or condition and provides practical advice on how to provide empathic, timely and optimal communication.

Based in the Netherlands, the authors recruited bereaved and non-bereaved parents of children aged between 1 and 12 years with life threatening conditions. Between November 2016 and October 2018, face to face interviews with the parents were conducted and transcribed verbatim.

Using transcripts, key themes and ten clear barriers to the communication of bad news were identified. The authors then reviewed the transcripts at length to identify positive feedback when breaking bad news; with the key aspects being where and when conversations took place, who was present for the conversation, and the honesty and information that was given.

Why does it matter? 

Breaking bad news or caring conversations are part of our every day work. But for the families and children receiving the information, the high emotional and practical significance means that they remember these conversations for a long, long time. The onus on us as professionals is to develop and grow the insight and skill to thoughtfully, effectively and compassionately communicate during these conversations.

Clinically Relevant Bottom Line:

Communication skills remain the cornerstone of medical practice. Feedback from patients and family often revolves around communication with the team caring for them, and whether it was “good” or “bad”. This article highlights some important factors to optimise communication when breaking bad news, which can be (and should be) utilised on a daily basis.

Reviewed by: Tina Abi Abdallah

Article 2: Risk of traumatic intracranial haemorrhage in children with bleeding disorders

Bressan, S., Monagle, P., Dalziel, S.R., Borland, M.L., Phillips, N., Kochar, A., Lyttle, M.D., Cheek, J.A., Neutze, J., Oakley, E., Dalton, S., Gilhotra, Y., Hearps, S., Furyk, J., Babl, F.E. (2020). Risk of traumatic intracranial haemorrhage in children with bleeding disorders. J Paediatr Child Health, 56: 1891-1897.

What’s it about? 

This multi-centre prospective observational study aimed to assess the rate of  CT use and frequency of diagnosing intracranial haemorrhage (ICH) on CT, in children with bleeding disorders presenting with head trauma.

20 137 children were evaluated in Australian and New Zealand EDs for head trauma, with or without bleeding disorders between April 2011 and November 2014. Congenital or acquired bleeding disorders were present in 0.5% of this population. Head CT use was significantly higher in children with bleeding disorders than those without (3 in 10 vs 1 in 10) despite the latter group presenting more frequently with severe mechanisms of head injury. Children with bleeding disorders who received CT were more likely to present with milder mechanisms of injury as well as clinical signs of vomiting and abnormal behaviour reported by parents, compared to children with bleeding disorders who did not receive CT scans . Only one child with a bleeding disorder had an ICH requiring neurosurgical intervention and no children without CT imaging had evidence of ICH on follow-up.

Why does it matter? 

Minor head injuries present frequently to paediatric EDs. Children with bleeding disorders are at increased risk of ICH following a minor head injury than those without bleeding disorders. Patients with severe haemophilia are reported to have the highest risk of traumatic ICH within this heterogenous disease group. It is important to detect ICH early in order to avoid long term disability and potentially fatal outcomes whilst balancing the decision for imaging against the risks of repeated radiation exposure. Previous clinical decision rules have supported ED clinicians in making judgements on CT use for paediatric head injuries but there is little evidence or guidance on its use for children with bleeding disorders.

Clinically Relevant Bottom Line:

The low incidence of ICH in children with bleeding disorders receiving CT imaging suggests that CT scans may not be routinely necessary in children with congenital or acquired bleeding disorder. The authors suggest a more selective approach to CT decision-making, combining a period of clinical observation with the severity of injury mechanism and the underlying bleeding disorder, rather than a “CT all” strategy.

However, the study is limited in its analysis by the low number of children with bleeding disorders. It would also be interesting to note from Bressan et al.’s study whether the rate of CT use varied with patients’ GCS scores or age of presentation, given the wide age window of children < 18 years.

 Nonetheless, current head injury rules such as PECARN were designed with the explicit exclusion of children with bleeding disorders. This study can therefore support the development of targeted neuroimaging guidelines for children with bleeding disorders.

Reviewed by: Ivy Jiang

Article 3: Can we safely send paediatric head injuries home from triage?

Aldridge, P., Castle, H., Phillips, C., Russell, E., Guerrero-Luduena, R., Rout, R. (2020). Head home: a prospective cohort study of a nurse-led paediatric head injury clinical decision tool at a district general hospital. Emergency Medicine Journal.

What’s it all about?

Head injuries are a common presentation to emergency departments internationally. Recent Australian data has shown that in >19,000 attendances with head injury only 3 in 100 had a traumatic brain injury on CT or a clinically important brain injury.

This study group set out to assess whether children under 17 years could safely be discharged by triage nurses following a pre-set clinical decision tool (HIDATq- Head Injury Discharge At Triage questionnaire). HIDATq was developed using PECARN and NICE guidelines. For a recap on Head Injury Decision tools see Anna Ing’s ‘Head Injury- who to scan?’ on DFTB.  HIDATq was implemented over a 6-month period in children who presented with a head or facial injury to a DGH in the UK.

Over 1700 patients were assessed, and data was analysed retrospectively. 61% were HIDATq negative and 1 in 5 of these patients were felt to be safe for discharge from triage without further investigation or management. A further 3 out of 10 children in the HIDATq negative patients were found to be eligible for discharge following minor wound management. 4 % of patients underwent CT scans (only 1 patient from the HIDATq negative group).

Why does it matter?

Head injuries are a common presentation to the paediatric ED. This study has revealed a patient group who might be eligible, using this screening tool, for a safe discharge from triage that would potentially have a large impact on ED crowding and pressures.

Clinically Relevant Bottom Line:

There were no adverse outcomes and the clinical decision tool used produced a high sensitivity and specificity for determining the need for CT after head injury. More than half of the children who had a negative HIDATq were potentially suitable for a safe discharge from triage.

This study did however have a highly selective population- it was not a major trauma centre so by default likely to have had less severe presentations of head injury. A larger multi centre trial is needed to provide validation for the tool. However, this study provides a useful starting point and identifies possible ways to improve patient management and ED departmental pressures.

Reviewed by: Brent Stevenson

Article 4: Should POC blood ketones be used as a triage tool to assess dehydration and predict likely admission?

Durnin, S., Jones, J., Ryan, E., Howard, R., Walsh, S., Dawkins, I., Blackburn, C., O’Donnell, S.M. and Barrett, M.J., 2020. The utility of ketones at triage: a prospective cohort study. Archives of Disease in Childhood105(12), pp.1157-1161.

What’s it about?

This is a small non-blinded prospective cohort study looking at 198 patients aged 1m-5yrs over a 12-month period. The eligibility criteria were presentation with vomiting/diarrhea/decreased fluid intake or clinical concerns of possible hypoglycaemia. Patients had finger prick blood ketones measured at triage, along with a Gorelick 4-point dehydration score. Repeat ketone measurement at 4hrs later or at discharge, clinical assessment and a 10-point Gorelick dehydration score (a Gorelick score is a validated tool to predict significant dehydration for children aged 1 month to 5 years).

The authors found a weak correlation between POC ketone level and the 10-point Gorelick dehydration scale (a more detailed assessment) and no correlation between POC ketones and Gorelick 4-point dehydration scale score.

Ketone level at triage was not predictive of admission however repeat measurement at 4hrs was weakly predictive; meaning, a larger proportion of the discharged cohort showed a reduction in ketones after rehydration compared to the admitted cohort.

Why does it matter?

Assessing dehydration is an inexact science and an accurate POC test for dehydration would simplify and potentially improve patient care. The Gorelick 4-point scale has previously shown to be oversensitive for assessing percentage dehydration but scales are better than unstructured assessment. This study rules out blood ketones as a tool for assessment of degree of dehydration or for predicting admission in this patient group.

The bottom line

Blood ketones are of little use as a triage tool for assessing degree of dehydration or predicting hospital admission in children with reduced fluid intake / D&V. There is no benefit to routine measurement of blood ketones at triage in patients with dehydration who do not have concerns about potential DKA.

Reviewed by: Sarah Reynolds

Article 5: Is loop-mediated isothermal amplification a useful tool for early identification of invasive meningococcal disease?

Waterfield, T., Lyttle, M.D., McKenna, J., Maney, J.A., Roland, D., Corr, M., Woolfall, K., Patenall, B., Shields, M. and Fairley, D., 2020. Loop-mediated isothermal amplification for the early diagnosis of invasive meningococcal disease in children. Archives of Disease in Childhood105(12), pp.1151-1156.

What’s it about?

A point of care test: Loop mediated isothermal amplification (LAMP) is a potential test for early identification of invasive meningococcal disease (MD).  (LAMP) is a form of rapid nucleic acid amplification and a commercially available LAMP test (using oropharyngeal swabs) can test for all serotypes of Neisseria meningitidis. This study looked to evaluate the diagnostic accuracy of LAMP for identifying invasive (MD) in children and to compare LAMP testing with more familiar tests like CRP and white cell counts (WCC).

 263 children under the age 18 with fever and signs or symptoms of meningococcal septicaemia were included over a 2-year period in 3 ED’s across the UK. 97% of participants were appropriately vaccinated as per UK vaccination schedule with over 1 in 2 of these children having had the Men B vaccination and over 2 in 3 children who had received the Men C vaccine.

Less than 2 per 100 children had confirmed cases of invasive MD. There were 14 positive LAMP tests, and all the confirmed cases of invasive MD were within these. In all the children with negative LAMP tests NONE had invasive MD. The LAMP test in this population performed better than other more commonly used tests (CRP, WCC or neutrophil counts).

Why does it matter?

Whilst vaccination programmes have thankfully made invasive MD more uncommon, it is still a significant cause of morbidity and mortality in children when it does occur. 

Early diagnosis is challenging, meaning potential overuse of broad-spectrum antibiotics or false reassurance for the clinician.

A point of care test for N. meningitidis, which is easy to do, with a low false negative rate has the potential to change this. However, false positives, meaning asymptomatic carriage must be considered.  The study included mostly young children and adolescents who are known to have higher asymptomatic carriage rates of N. meningitis, meaning false positive could be higher in this group.  It has the potential to be used as an adjuvant to PCR and blood culture, but the optimum patient group selection is yet to be determined and it could not be used as a rule out test in low prevalence areas like the UK.

Clinically Relevant Bottom Line:

LAMP testing for IMD, is a potentially useful test to identify children with invasive MD rapidly. However, clinical utility is yet to be determined.

Reviewed by: Sarah Kapur

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.

Septic for sure…

Cite this article as:
Deirdre Philbin. Septic for sure…, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.31704

Febrile children can pose a real challenge to clinicians in the Emergency Department. Identifying and trying to predict those who are at high risk of serious or invasive bacterial infection is particularly important as there are huge implications for altering the course of their illness, as well as for resource allocation and research initiatives. 

There are many clinical scores in use but, so far, their predictive performance for poor outcomes in undifferentiated febrile children is unknown.

Long E, Solan T, Stephens DJ, et al. Febrile children in the Emergency Department: Frequency and predictors of poor outcome. Acta Paediatr. 2020; 00: 1– 10 

What was the aim of this study?

This retrospective, observational study set out to determine the frequency of poor outcomes in undifferentiated children presenting to the ED with fever as well as evaluate predictors of poor outcome. The authors defined  ’poor outcome’ as the development of new organ dysfunction and the requirement for organ support therapy. They included initial vital signs, initial blood tests, and clinical scores as predictor variables.

What was the study design?

This is a retrospective cohort study. It was conducted in the ED in a large tertiary referral centre (single centre study) and full ethical approval was obtained.

Who were the study participants?

All children with ‘fever’ in their triage description or an initial triage temperature of >38.0°C were included, with no exclusion criteria.

How was the study performed?

Data was extracted from electronic medical records. This included demographic data, vital signs, blood test results, diagnosis, disposition, organ support therapies, organ dysfunction scores for patients admitted to PICU and mortality.

To ensure accuracy, one hundred electronic medical records were randomly selected and manually checked. 

What were the study team looking for?

The primary outcome of this study was the frequency of new organ dysfunction and requirement for organ support therapy in the study population, two indicators of severe illness. 

The study team examined the following variables to see if any could predict children at risk of poor outcome:

  • vital signs: heart rate, respiratory rate, blood pressure, and GCS
  • blood tests: venous lactate, creatinine, white cell count, platelet count, and INR
  • clinical scores: SIRS, qSOFA, and qPELOD-2

What kind of statistics did they use?

The chart above can be really helpful when thinking about statistical analysis. The type of data collected determines the most appropriate means of analysis. This study included both continuous and categorical variables.

For continuous variables, descriptive statistics were used i.e.  data was reported using median and inter-quartile ranges. 

In this study, continuous variables refer to demographic data such as age, sex, weight, vital signs (temperature, heart rate, blood pressure, respiratory rate, Glasgow coma score) and blood results (including lactate, creatinine, INR, platelet count and white cell count). The use of median and inter-quartile ranges is most appropriate for this type of data. The median is the value that is in the “middle” of the distribution, with 50% of the scores having a value larger than the median, and 50% of the scores having a value smaller than the median. The interquartile range (IQR) is the range of values within which reside in the middle 50% of the data. 

Frequency with percentage was used for categorical variables

For this study, categorical variables refer to the clinical scores used i.e. SIRS, qSOFA and qPELOD scores. Describing the data in this way is appropriate as it means the frequency that the data occurred may be expressed as a percentage. 

The association between initial vital signs, blood tests, clinical scores and the development of new organ dysfunction and requirement for organ support therapy were reported as odds ratios (OR) with 95% confidence intervals (CI). 

Odds ratios are usually used to compare the relative odds of the occurrence of the outcome of interest (e.g. development of new organ dysfunction), given exposure to the variable of interest (e.g. initial vital signs). The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. The confidence interval (CI)  is used to estimate the precision of the odds ratio and may be thought of as a way to measure how well your sample represents  the population you are studying.  A large CI indicates a low level of precision of the OR, whereas a small CI indicates a higher precision of the OR. This study uses 95% confidence intervals which means that there is a 95% probability that the confidence interval will contain the true population mean and in practice, is often used. 

The discriminative ability of predictor variables was measured using the area under the receiver operating characteristics curve (AUROC), with sensitivity and specificity calculated for each variable. i.e. vital signs, blood tests and clinical scores. 

The Receiver Operating Characteristic (ROC) curve is commonly used in statistics and can be confusing. Put simply, the curve is used to plot sensitivity versus false positive rate for several values of a diagnostic test. It is a graphical measure which illustrates the trade-off between sensitivity and specificity in tests that produce results on a numerical scale, rather than as an absolute positive or negative result. In this study, the AUROC is used to determine the sensitivity and specificity of each of the variables used. 

What were the results? 

Over the 6-month study period, 6217 (13.8%) children presented to the ED with a febrile illness. This represented  just over one-eighth of the overall presentations to the ED. Approximately two-thirds of these children were discharged home (65.4%), a third were admitted to hospital (34.6%), with 0.5% (32 of the 6217 children in the study) admitted to PICU. Slightly more than half of the children, at 58.3%, were under the age of 3. 

New organ dysfunction was very rare, in (0.4% or 27 children). 10 required organ support therapy (inotropes for 0.2%, mechanical ventilation in 6, renal replacement therapy in 1, and extra-corporeal life support in 1). 

The best performing ED predictors of new organ dysfunction were: GCS <11, INR≥ 1.2, lactate ≥ 4.0mmol/L, and qPELOD-2 (SBP) score ≥ 1.

The best performing predictors of the requirement for inotropic support were: initial hypotension using qPELOD 2 (SBP), lactate ≥4mmol/L, INR ≥ 1.2, and qPELOD (SBP) score ≥  1

The best predictors of the requirement for mechanical ventilation were: GCS <11, lactate ≥4mmol/L, INR ≥ 1.2 and qSOFA=3.

The bottom line

The bottom line from this study was that all predictor variables had poor test characteristics for the development of new organ dysfunction and the requirement for organ support therapy.

This is a good study; the results are easy to follow and, importantly, they meet the study aims.  The sample size is large, giving this study good internal validity, i.e. the extent to which the observed results represent the truth. 

Overall, this study supports our clinical experience. Poor outcomes in febrile children are, thankfully, rare. Less than half a percent of children in this study developed new organ dysfunction. Even fewer required organ support therapy. The infrequency of these outcomes in the study population however means that the use of “predictor variables” is not particularly helpful. A few take-home messages:

Vital signs – Elevated heart rate and respiratory rate were common findings in undifferentiated febrile children. This did not confer an increased risk for the development of organ dysfunction or the requirement for organ support therapy.

Take abnormal GCS seriously though – in this study, very few children had a GCS <11, but when it was low, GCS score was a strong predictor of the requirement for mechanical ventilation.

Blood tests – Remember to check lactate! Elevated venous lactate significantly increased the odds for the development of new organ dysfunction and the requirement for organ support therapy (both mechanical ventilation and inotropic support), with increasing risk the higher the lactate climbed. Elevated initial creatinine and initial INR also signified increasing severity of illness. 

Clinical scores – in this study, clinical scores performed variably. They can be helpful but may be more useful in the PICU setting. 

The external validity of this study is also strong; the results seem to be generalisable to our own population. Given the lack of exclusion criteria, the results of this study may be applied to any setting where undifferentiated febrile children are cared for. 

Were there any limitations to this study?

This is a retrospective, observational, single centre study using data extracted from an electronic medical record. Retrospective studies may be subject to information bias (by missing information) or by selection bias (because individuals are selected after the outcome has occurred). This study limited selection bias however by including all patients with fever. 


In addition, a single centre study may be limited by the use of local policies and guidelines rather than disease severity, reducing external validity / generalisability of the findings. 

The outcomes measured in this study are rare, but the authors attempted to overcome this by using a large sample size of over 6000 children. However, because the outcomes were so uncommon, the predictor variables had wide confidence intervals. 

Will this study change my practice?

This study is unlikely to change our practice. However, it does provide food for thought. It is in keeping with our clinical experience that the development of new organ dysfunction and the requirement for organ support therapy is rare among febrile children presenting to the ED. 

This study emphasises that predicting poor outcome in this patient group is difficult. Vital signs, blood tests and clinical scores were poor predictors. This highlights the importance of remaining particularly vigilant with respect to undifferentiated febrile children. 

A final comment from the authors – Elliott Long and Franz Babl

Thank-you for the opportunity to comment on our article titled ‘Febrile children in the Emergency Department: frequency and predictors of poor outcome’. The associated review covered all of the major aspects of the study.

A few additional points that may have been buried in the data: 

  • Though the study was primarily focused on severe infection (sepsis), we included a broader cohort of undifferentiated children with febrile illness presenting to the ED. This was somewhat exploratory, as we suspected that many children would be treated for sepsis (i.e.- admitted to hospital for IV antibiotics and one or more fluid bolus), but would not receive the diagnosis of sepsis. Interestingly, this was borne out in the study findings. The majority of children treated for sepsis did not receive the diagnosis of sepsis. This included the ‘severe end of the spectrum’ of children admitted to ICU; the most common diagnosis in this group of children was ‘acute febrile illness’. We interpreted this finding as being due to the hesitancy of clinicians to label undifferentiated febrile children with the diagnosis of ‘sepsis’ early in their treatment. Prospectively, we all hope kids will ‘turn the corner’ and physiologically improve after basic resuscitative measures… until they don’t! Also, children with more specific diagnoses, such as appendicitis or pneumonia, were more likely to receive these as working (admission) diagnoses even when at the severe end of the spectrum and receiving treatment consistent with sepsis. 
  • The majority of febrile children admitted to ICU did not require (new) organ support. These children included those with meningitis <2months of age, children with croup requiring multiple doses of nebulised adrenaline, children with pneumonia with large pleural effusions, and children on ventricular assist devices. These ICU admissions were based on local policy and procedure, and may not be generalisable to other health services. Studies using ICU admission as an outcome measure should be interpreted with this in mind. 

From a ‘big picture’ perspective, this study highlights two major issues for clinicians and researchers when dealing with sepsis.

  • Clinicians caring for children with febrile illness at different stages of their hospitalisation have different frames on the same disease that we all call sepsis. From an ED and acute care perspective, children with fever are un-differentiated, the majority have a mild, self-limited illness, and can be safely discharged home. The challenge for front line clinicians is early recognition of severe disease- finding the needle in the haystack. From an ICU perspective, children with fever are differentiated, the majority have severe disease and require close monitoring and/or organ support. The challenge in ICU is risk stratification. Understanding these differences in perspective is crucial for communication between clinicians caring for children at different stages of their hospital journey, and for researchers designing studies involving children with sepsis. 
  • As a result of poor outcomes being so rare, interventional trials that aim to capture patients at the entry point of acute care – before they are differentiated – will need to be pragmatic, large, and use composite outcomes. An example of such a study is PROMPT Bolus, which compares 0.9% saline to balanced fluids for sepsis resuscitation and initial maintenance. The study will include pragmatic entry criteria: patients receiving treatment for sepsis (IV antibiotics and >1 fluid bolus). The study will enrol >8000 patients from 3 research networks (PECARN in the United States, PREDICT in Australia / New Zealand, and PERC in Canada), and will use the composite outcome of Major Adverse Kidney Events on day 30 (MAKE30) as the primary outcome. This is probably the model that will be required to answer fundamental questions regarding early sepsis therapies in future.