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The 73rd Bubble Wrap

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With millions of journal articles published yearly, it is impossible to keep up.  

Our team have scoured what’s new (well, mostly new!) in the paediatric literature. One reviewer has returned to an oldie but a goodie to answer a clinical question!

Article 1: Does rapid diagnostic testing for Malaria work?

Bird C, Hayward GN, Turner PJ, Merrick V, Lyttle MD, Mullen N, Fanshawe TR. A Diagnostic Accuracy Study to Evaluate Standard Rapid Diagnostic Test (RDT) Alone to Safely Rule Out Imported Malaria in Children Presenting to UK Emergency Departments. J Pediatric Infect Dis Soc. 2023 May 31;12(5):290-297. doi: 10.1093/jpids/piad024

What’s it about? 

Microscopy is the gold standard for diagnosing malaria. However, it is a labour-intensive process requiring trained personnel and up to 3 negative films to rule out malaria. This puts a high financial and resource cost on front-line settings. Rapid diagnostic testing (RDT) forms the mainstay of diagnosis in areas without access to high-quality microscopy.

This paper aimed to evaluate the use of RDT for diagnosing or ruling out malaria in paediatric patients with typical presentations. Plasmodium falciparum accounts for approximately 75% of cases in the UK and is the dominant species causing malaria in sub-Saharan Africa (>99% of cases and deaths in this subcontinent).

This was a multi-centre, retrospective diagnostic accuracy study carried out by the PERUKI network and required sites to routinely perform both microscopy for malarial parasites and RDT. Children and young people <16 were included who had travelled to an endemic area, as defined by the website (www.travelhealthprog.org.uk. Anonymous data was collected around patient characteristics, area of travel, result of RDT, blood film, number of films, parasitemia in falciparum cases, Hb, platelet count, discharge diagnosis and reattendance within 30 days.

15 PERUKI sites gave data with 1,414 eligible patients, 615 (43%) females and a median age of 4. There were 47 (3.3%) cases of malaria in this group. P. falciparum totaled 36 (77%). The sensitivity of RDT to detect P. falciparum was 100%, with a specificity of 98.8% and a negative predictive value of 100%. However, malaria caused by any Plasmodium species was 93.6%, with a specificity of 99.4%.

The RDTs held a 15% false positive rate and three false negative cases using the RDT caused by different Plasmodium species. At the prevalence of malaria detected in the study, the authors extrapolated that they would expect an RDT to give a false negative once per 470 patients tested.

Standard practice dictates that three films be used to rule out malaria. In this study, only 15% of cases had three films. This potentially could have missed a positive malaria case. (However, 46 out of 47 confirmed cases in this study were confirmed on the first film alone).

Why does it matter?

Using quicker diagnostic tools for malarial infection could significantly reduce repeat attendance to emergency departments and laboratory time and equipment costs.

UK estimates are that around 10% of all imported malaria cases are found in children.

Clinically Relevant Bottom Line

Despite the RDT having a 100% sensitivity for P. falciparum, it only has 93.6% for all Plasmodium species and a high number of false negatives for non-Falciparum species, approximately 25% of cases are non-Falciparum. There’s no current scope for a change in practice in the UK moving away from microscopy as the gold standard.

Reviewed by: Graham Clarke

Article 2:  A Quest for Better Intraosseous Placement

Chung, SunHee; Phelps, Andrew; Chan, Daniela K. I. A Quest for Better Strategy in Pediatric Intraosseous Placement Using Radiographic Measurements in Patients Younger Than 2 Years. Pediatric Emergency Care March 15, 2023. | DOI: 10.1097/PEC.0000000000002933

What’s it about? 

This retrospective study used lower limb radiographs, taken as part of patients’ clinical care, in children under two years of age to determine the most appropriate site for inserting intra-osseous (IO) needles. Radiographs from children with fractures, or disease processes affecting bone growth, were excluded. For the remaining images, a paediatric radiologist measured bone and soft tissue thickness 10mm from the femoral and tibial physes. Minimum and maximum penetration depths required for the IO needle tip to sit within the bone were determined from measurements around the physes. These were then used to create 95% confidence intervals to maximise the likelihood of satisfactory IO placement.

141 radiographs were included from a population of 58% male participants. 95% confidence intervals for minimum and maximum acceptable penetration were compared to the standard lengths of EZ-IO needles. This produced a malposition rate for each needle size, further stratified by patient age.

Malposition was minimised for children under six months old with a 25mm needle at the femoral site and a 15mm at the tibial site (with 45.7% and 57.1% appropriate position rates, respectively).

There was no standard needle size for children, which minimised malposition at the femoral site for children between 6 and 24 months. A 25mm needle, however, minimised malposition in the tibial site for all children between 6 and 24 months (with 81%, 87.5% and 91.1% appropriate position rates in 6-12 months, 13-18 months, and 19-24 month age groups respectively).

Although the study utilised a large image set, it did have some limitations. For example, all images were plain radiographs in which distance measurement can become distorted. Additionally, all images were taken from a single centre, and a single radiologist made measurements. The study measurements were taken under the assumption that the needle was placed to the hub at the skin level without compression- however, the authors do note that it is a common practice that there can be insertion to the hub with skin compression (despite this being against manufacturing advice). The measurements may have changed If they had been inserted in this way.

Why does it matter? 

Children under two years have the highest rate of IO access attempts, likely due to difficulty in rapidly establishing vascular access in this population, and recent studies have shown that a large percentage of IO needles are malpositioned in this age group (maybe as high as 64%). There is scarce information about the most appropriate sizes for IO needles at each access site in younger children, so this paper may help reduce IO malposition and the number of required attempts.

Clinically Relevant Bottom Line

For children under six months old, a 15mm (pink) needle at the tibial site or a 25mm (blue) needle at the femoral site achieved the highest likely success rates (57.1% and 45.7%, respectively)

For children aged 6 – 24 months old, a 25mm needle at the tibial site achieved the highest likely success rates (81%, 87.5% and 91.1% in 6-12 month, 13-18 month, and 19-24 month age groups respectively)

Reviewed by: Cameron Morrice

Article 3: Baa Baa Black Sheep, what should we make the PEEP?

Probyn, M.E., Hooper, S.B., Dargaville, P.A., McCallion, N., Crossley, K., Harding, R., Morley, C.J. (2004) Positive end expiratory pressure during resuscitation of premature lambs rapidly improves blood gases without adversely affecting arterial pressure. Paediatric Resus. Volume 56(2): pp198-204. doi: 10.1203/01.PDR.0000132752.94155.13.

What’s it about?

Current Neonatal Resuscitation guidelines suggest a Positive End Expiratory Pressure (PEEP) of 5 to 8cmH20 at delivery for resuscitation and stabilisation, so what happens to the premature lungs at delivery once PEEP is applied? 

This study, which is nearly 20 years old, demonstrated the importance of an effective PEEP on premature lungs, ventilation parameters, arterial pressures and blood gases.

Despite being 20 years old, this study is one of the driving forces for our guidelines. The author reviewed this article after having a burning desire to question where the guidance came from!

The researchers delivered premature lambs at 125 days gestation (term being 147 days) and proceeded to intubation and drainage of lung fluid. The lambs were placed on a ventilator (Dräger Babylog) in volume guarantee mode, with Tidal Volume (Tv) set at 5mL/kg and a maximum Peak Inspiratory Pressure (PIP) of 70 cmH2O. The lambs were randomized to receive a PEEP of 0, 4, 8, or 12 cmH2O (with 4 or 5 lambs in each group).  They were ventilated for 15 minutes (resuscitation period), followed by 2 hours of stabilization at the same PEEP. The researchers measured tidal volume, peak inspiratory pressure, PEEP, arterial pressure, oxygen saturation, and blood gases. In addition, respiratory system compliance and alveolar/arterial oxygen differences were calculated.


Why does it matter?

Lambs who received a PEEP of 0 cmH2O did not oxygenate adequately, with lower oxygen saturations at 15 minutes and 2 hours. These lambs also had less compliance, requiring higher PIPs, Fraction of Inspired Oxygen (FiO2) and Mean Airway Pressures to maintain less-than-ideal oxygenation levels. On the other end of the spectrum, lambs who received a PEEP of 12 cmH2­O had improved oxygenation; however, they developed pneumothoraces, and all the subjects in the group died.

Lambs who received a PEEP of 4 cmH2O had improved oxygenation compared with those who received a PEEP of 0 cmH2O; however, it was not statistically significant. Lambs who received a PEEP of 8 and 12 cmH2O had significantly improved oxygenation compared with PEEPs of 0 and 4 cmH2O. The compliance of the respiratory system was significantly higher at PEEPs of 4 and 8 cmH2O. No significant differences were found in blood gases or arterial pressures between PEEPs of 4, 8 and 12 cmH2O. There was no evidence of cardiorespiratory compromise at 4 and 8 cmH2O.

So, the sweet spot for PEEP seems to be around 8 cmH2O regarding optimising oxygenation, lung compliance and avoiding iatrogenic harm. However, it seems a little crazy that this is one of the studies that has formed the basis of our guidelines based on a different species and was done >20 years ago!

Clinically Relevant Bottom Line

Neonatology is a field which requires constant research and updating of guidelines, particularly as the gestational age for viability and resuscitation continues to lower. Animal studies help understand the physiology of neonates and lays the foundation for further research in safely optimising the resuscitation and stabilisation of premature neonates.

Reviewed by: Tina Abi Abdallah

Article 4: Tickly cough? Maybe Winnie the Pooh can help!

Kuitunen I, Renko M. Honey for acute cough in children – a systematic review. Eur J Pediatr. 2023 Jun 25. doi: 10.1007/s00431-023-05066-1. Epub ahead of print. PMID: 37355498. (open access) https://link.springer.com/article/10.1007/s00431-023-05066-1

What’s it about?

Persistent coughing is a common reason for ED presentation. Previous reviews in adults have demonstrated the benefits of honey, but there is no recent paediatric review. So, could simple honey be used to treat these troublesome coughs? Kuitunen et al. undertook a systematic review of studies of children over one year (don’t forget the risk of botulism- spores in honey can be a cause of botulism in children under one!)  to see if there is any benefit in using honey to treat a cough compared to nothing or to over-the-counter medicines (excluding comparisons to antibiotics). Due to variations in the studies and lacking key information, a review of 10 studies (including all continents except South America and Antarctica) was done without meta-analysis.

Why does it matter?

This study is relatively weak regarding good quality evidence, as two studies were at high risk of bias, and another six had some concerns. They demonstrated that compared to other cough syrups or placebo, children found sleeping easier and had a decreased cough frequency. However, up to 14.3% worryingly showed adverse side effects- including nausea and vomiting.  The authors summarised that there is a benefit to using honey, but with low to very low-quality evidence to back this up.

Clinically Relevant Bottom Line

In children over one, honey may help a cough compared to over-the-counter medicine, but more quality research is required.

Reviewed by: Laura Riddick

Article 5: Does giving antipyretics in ED to improve vital signs help us to rule out a serious bacterial infection?

Wittmann S, Jorgensen R, Oostenbrink R, Moll H, Herberg J, Levin M, Maconochie I, Nijman R. Heart rate and respiratory rate in predicting risk of serious bacterial infection in febrile children given antipyretics: a prospective observational study. Eur J Pediatr. 2023 May;182(5):2205-2214. doi: 10.1007/s00431-023-04884-7. Epub 2023 Mar 3. PMID: 36867236; PMCID: PMC10175419.

What’s it about?

This study examined if administering antipyretics masked heart rate and respiratory rate in serious bacterial illness (SBI) in children presenting to the emergency department.  A cohort of 1455 children between 1 month and 16 years old presenting with fever and at least one warning sign of SBI were recruited (715 HR and 740 RR). SBI was defined using various methods, including cultures, microbiology and virology results, findings on imaging, and an expert panel of clinicians. The study found that persistent tachypnoea after achieving a temperature in the normal range was a predictor of pneumonia, especially if it remained above the 97th percentile (OR 1.92), but not other forms of bacterial infection. Persistent tachycardia did not independently predict the presence of SBI.

In this study cohort, after a single dose of antipyretic, 30% of children met the threshold for tachycardia as per APLS adjusted for age compared to 13% on repeat observations (on temperature-adjusted age centile charts).  

The data was collected from only one centre, which is a significant limitation. Some important exclusions have resulted in missing significant patient groups; patients triaged as ‘red’ category patients as per the Manchester Triage System, patients with significant co-morbidities, and non-UK residents were some of the exclusions.

Why does it matter?

Febrile children are a common sight in the paediatric emergency department. They are often also tachycardic and tachypnoeic. Bacterial illnesses are only diagnosed in about 10% of children presenting with fever. Weeding out these patients from children presenting with self-limiting viral illnesses can be challenging.

Previous studies have shown that children presenting and being discharged with tachycardia are more likely to return; however, it did not increase the chance of admission or significant intervention.

Clinically Relevant Bottom Line

Persistent tachypnoea in an afebrile child is a useful predictor of pneumonia. There appears to be limited benefit in giving antipyretics and awaiting normalisation before discharge in well-appearing febrile children with tachycardia and no other abnormal findings. Persistent tachycardia alone does not appear to be linked to a higher incidence of underlying bacterial infection.

Reviewed by: Demetris Athanasiou

If we missed something useful or you think other articles are 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 were reviewed and edited by Vicki Currie.

Author

  • Vicki is a Paediatric Registrar in the West Midlands in the UK , starting PEM in September 2021. Vicki 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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