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The 52nd Bubble Wrap

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

Article 1: Does Rapid Respiratory Virus Testing Influence Care?

Rao S, Lamb MM, Moss A, et al. Effect of rapid respiratory virus testing on antibiotic prescribing among children presenting to the emergency department with acute respiratory illness: a randomized clinical trial. JAMA Netw Open. 2021;4(6):e2111836.

What’s it about? 

This was a single-centre randomized clinical trial of paediatric patients aged one month to 18 years presenting with influenza-like illness (ILI) to a large paediatric emergency department in Colorado. Presentations from December 1, 2018, to November 30, 2019 (pre-COVID-19) were reviewed to determine if rapid respiratory panel (RRP) tests could decrease antibiotic prescribing. ILI was defined as a temperature ≥ 37.8°C and at least one of the following symptoms: cough, sore throat, rhinorrhea, or nasal congestion.

Children were excluded if they had an Emergency Severity Index of ≥2, had respiratory symptoms for more than two weeks or were seen in nurse-only visits. The BioFire FilmArray RP2 Panel was performed on 908 children. Just over 8 in 10 of the children were positive for enterovirus/rhinovirus, influenza, and respiratory syncytial virus, with adenovirus being the most common. They were randomized into two groups. The intervention group had RRP results provided to the ED clinician and family. The control group was not given RRP results. However, this randomization was complicated because some patients from the intervention group left before RRP results (just under 4 in 10 children), and some patients in the control group had alternative respiratory viral testing that resulted (around 1 in 10). 

The primary outcome was an antibiotic prescription. Secondary outcomes included antiviral prescription, ED length of stay, hospital admission, and recurrent health visits. During follow-up, roughly one-third of patients from the intervention and control groups were lost. 

The authors analyzed results in multiple ways: intention-to-treat (ITT) analysis, modified ITT analysis, and per-protocol analysis. 

With ITT analyses, patients in the intervention group were more likely to receive antibiotics than the control group (relative risk 1.31; 95% CI 1.03-1.68), and there was no significant difference in secondary outcomes. With adjusted ITT analysis, there was no significant difference in antibiotic prescriptions. Children in the intervention group were more likely to receive antivirals (relative risk 2.5; 95% CI 1.5-4.2) but had longer ED length of stay and hospitalization rates.

With modified ITT analyses, there was no significant difference between groups. Children for whom RRP results were known were more likely to receive antivirals (relative risk 2.6; 95% CI 1.6-4.5), have longer ED stays, and be hospitalized.

Clinicians changed their clinical decisions based on RRP results 17% of the time.

There are many limitations in this study. They did not include patients with very low acuity. There seemed to be an imbalance between control and intervention groups that resulted in patients being more likely to have been diagnosed with an indication for antibiotic therapy (sepsis, shock, pneumonia, pharyngitis, otitis media) in the intervention group. One-third of patients from each group were lost to follow-up. Intervention group patients left before RRP results, and control group patients received alternative RRP tests. This study was conducted within a single healthcare system and should be investigated at other institutions.

Why does it matter? 

Coughs, colds, and sniffles are common complaints in paediatric patients. Most are due to viruses and require only supportive care. Rapid respiratory panels may reveal the viral aetiology 85% of the time but often do not change management or decrease antibiotic therapy in this study.

Clinically Relevant Bottom Line:

RRPs are sensitive and expensive tests that may provide the family and provider with an aetiology for an ILI, but the results do not often impact clinical care. I would stick with the more cost-effective rapid influenza test during flu season for a result you might act on.

Reviewed by: Dennis Ren

Article 2: Is lung US any use for patients going to PICU?

Sachdev A, Khatri A, Saxena K, et al. Chest sonography versus chest radiograph in children admitted to paediatric intensive care. Tropical Medicine 2021; 0(0):1-5

What’s it about? 

This prospective, double-blinded observational Indian study planned to compare and correlate the performance of point of care lung ultrasound (POCUS) versus routine bedside chest radiograph (CXR) in the paediatric intensive care unit (PICU) setting. Children between the ages of 1 month and 18 years were included in the study. Those with morbid obesity, chest wall oedema or burns and inability to turn were excluded due to the physical barrier to an ultrasound-based approach (n=18).

Chest X-rays were conducted according to PICU protocol and reported by a radiologist who was unaware of previous ultrasonography findings. The same patients would then undergo a chest US by an off-duty paediatric intensivist with at least five years of POCUS experience within three hours of taking the CXR. The intensivists did not have access to the patient’s clinical details or CXR report.

From October 2018 to May 2019, 413 patients were enrolled, and 1002 CXRs were compared with corresponding chest US. The US findings were immediately available, and the average CXR requisition and reporting time was 4.5 hours +/- 3.5 hours. Of the 1002 episodes, 451 (just under 1in 2 patients) had a normal chest US, and 512 (just over 1 out of 2) had a normal CXR. Pulmonary oedema, pneumothorax and pleural effusion were diagnosed in a significantly higher number of patients using US than CXR (p=0.001). Both modalities demonstrated equal efficacy in detecting consolidation and atelectasis.

Why does it matter? 

Chest US was shown to be a reliable diagnostic modality, if not better, with certain pathologies compared to the standard CXR and with the provision of immediate results. This is particularly beneficial in pneumothoraces, where delayed diagnosis could be fatal. With pleural effusions, it has the additional benefit of deciphering the optimal placement of drains and or thoracentesis. Chest US also obviates the need to expose children to unnecessary radiation, which can be easily repeated.

This does not currently form part of the general paediatric curriculum as a required skill- courses focusing on paediatric POCUS are available. Still, work is required to increase the number of clinicians who can perform this skill.

Clinically Relevant Bottom Line:

If paediatricians were to receive lung US training as part of standard training, this skill could be used to diagnose pleural and parenchymal lung abnormalities. This can be done quickly, reliably and with reduced risk to the patient and increased sensitivity in certain conditions compared to CXR. However, ultrasound can have limited use in the presence of emphysema, obesity, and bandages.

Reviewed by: Melanie Ranaweera

Article 3: Should you use mannitol or hypertonic saline for children with raised ICP?

Kumar N and Jaiswal A Comparative Assessment of Hypertonic Saline versus Mannitol in the treatment of raised intracranial tension in children. European Journal of Molecular and Clinical Medicine. 2020; 10 (7) : 3968-3974

What’s it all about?

This observational, prospective Indian study compared mannitol to 3% hypertonic saline in paediatric patients with clinical signs and symptoms of raised intracranial pressure (ICP). 220 children between the ages of 2 and 18 were included in this study and randomly allocated to the mannitol arm (Group A n=110) or the 3% hypertonic saline arm (Group B n=110). Patients with compromised renal function, diabetic ketoacidosis and cerebral malaria were excluded from the study.

In both groups, the loading dose (5ml/kg) of either mannitol or 3% hypertonic saline was followed by a maintenance dose (2ml/kg) every 6 hours for two days. Mean arterial pressure (MAP) was measured at admission and 6 hourly after the intervention. Serum electrolytes and osmolality were measured every 12 hours post-treatment initiation. CT scans or MRI heads were conducted for six hours to assess intracranial pressure.

The decrease in MAP was highly significant ( p<0.001) at 0 hours in males and 0, 6 hours in females in the hypertonic saline group. Moderate significance in MAP reduction was noted at 12,36 hours in females and 6,24,42 hours in males in the hypertonic saline group. Serum chloride and sodium levels significantly increased in the hypertonic saline group but were within acceptable levels. A decrease in coma hours was a significant finding in the 3% hypertonic saline arm ( p<0.001). There was no difference in overall mortality between both groups.

Why does it matter?

3% hypertonic saline and mannitol are both still used in clinical practice to treat intracranial hypertension, but there is no universal consensus on the definitive treatment choice. This study adds to the growing evidence of the benefits of 3% hypertonic saline compared to mannitol in its ability to significantly reduce mean arterial pressure and coma hours.

This study does not discuss any limitations- and there is limited information on the criteria by which CT/ MRI head was performed. The wording of when CT/ MRI scans were completed is unclear- and could be read as multiple CT head scans were completed- without any mention of the long-term effects of this.

The Bottom Line:

3% hypertonic saline demonstrates more effective immediate and longer-term benefits for raised ICP than mannitol and has a good safety profile. Further studies that offer direct methods of measuring ICP are required to fully substantiate these findings.  More research is also required to determine when to initiate treatment and how long to continue it.

Reviewed by: Melanie Ranaweera

Article 4: The burden of rheumatic heart disease

Wyber, R, Wade, V, Anderson, A, Schreiber, Y, Saginur, R, Brown, A, & Carapetis, J. (2021). Rheumatic heart disease in Indigenous young peoples. The Lancet Child & Adolescent Health, 5(6), 437–446. https://doi.org/10.1016/S2352-4642(20)30308-4

What’s it about?

We briefly discussed how reduced rheumatic fever incidence has reduced invasive URTIs in our 51st Bubblewrap.

However, there remains an inequitable burden of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in Aboriginal and Torres Strait Islander populations. The authors review the key information in the epidemiological burden of RHD, the lived experience, causes and contributors, preventative techniques and national disease control initiatives for young people in Australia, New Zealand and Canada.

Key facts were highlighted. From 2015 to 2017, newly diagnosed ARF occurred 89% of the time in Aboriginal and Torres Strait Islander peoples, and 79% were in people younger than 25, with the highest burden in the states of Northern and Central Australia. In New Zealand, up to 93% of people admitted to hospitals with ARF were Maori or Pacific people.

Major determinants in how RHD affects lives are strongly intertwined with access to health systems (such as timeliness to primary care, poor medical communication, cultural inappropriateness, and institutionalised racism within systems) and socioeconomic and environmental circumstances (such as housing inequity, crowding and inadequate plumbing). While national research and government initiatives have been signalled in Australia and New Zealand, there are no comprehensive disease control initiatives in Canada, and funding to implement long-term plans is yet to be finalised.

Why does it matter?

It is well known that the RHD burden reflects biological aetiology, such as group A streptococcus skin infections and socio-political contexts. The burden is most clearly documented in Australia, New Zealand and Canada where more research resources are readily available.

The bottom line

Reducing the burden of RHD for Indigenous peoples requires not only clinical best practices but also a societal commitment to addressing prevention and tertiary care for RHD in a manner that is acceptable, accessible, and culturally responsive. Political support and leadership to advocate action on indirect determinants of the disease, such as the disempowerment and separation of land and family, to accelerate the reduction in disease burden.

Available data does suggest a disproportionate burden of rheumatic heart disease. However, excluding marginalised indigenous communities, even with available studies, may underestimate the true rheumatic heart disease burden. Furthermore, research in low to middle-income countries with fewer research resources and a larger number of competing health priorities may help us further understand the true burden and drivers of RHD elsewhere.

Reviewed by: Ivy Wei-Jiang

Article 5: Can melatonin be used for non-procedural sedation?

 Ahmed J, et al. Melatonin for non-operating room sedation in the paediatric population: a systematic review and meta-analysis Arch Dis Child 2021;0:1–8. doi:10.1136/archdischild-2020-320592

What’s it about?

This was a systematic review and meta-analysis with a comprehensive systematic search. Randomised and non-randomized studies were included that looked into one of the prespecified outcomes in the review. Children from birth to 18 years require melatonin for non-operating room sedation or diagnostic procedures such as EEG, BERA (Brainstem Evoked Response Audiometry), MRI, nuclear scan and electrophysiological studies.

Twenty-five studies (5587 subjects) in which melatonin was used for procedural (e.g. MRI, EEG) sedation met the inclusion criteria. Primary outcome: successful procedure. Secondary outcomes were sedation failure, sleep latency period (time taken to fall asleep), sedation duration, the procedure yield, supplemental sedation required and adverse events. With regards to sedation for EEG, there was no significant difference in procedural success between melatonin and sleep deprivation (RR 1.06 CCI 0.99-1.12), chloral hydrate (RR 0.97 CI 0.89-1.05) or combined melatonin and sleep deprivation (RR1.03 CI 0.97-1.10). Failure rates were significantly higher (RR 1.55 CI 1.02-2.33) for melatonin alone compared to sleep deprivation and melatonin combined.  No serious adverse events were reported. The authors could not perform a meta-analysis on studies relating to brainstem evoked potential or MRI.

Why does it matter?

Safe yet adequate procedural sedation is an ongoing challenge in paediatrics, with commonly used agents such as chloral hydrate having limited efficacy. Inadequate sedation can delay the required investigation, which in turn delays diagnosis and management, in addition to increasing costs.

Melatonin is a sleep hormone secreted by the pineal gland and used in patients with sleep disorders owing to its sedative properties. However, data on its use for procedural sedation is limited. Still, it lacks the major side effects (e.g. respiratory depression, slow onset and unpredictable duration of action) of chloral hydrate or benzodiazepines, so it has potential as an alternative agent.

Clinically Relevant Bottom Line:

Melatonin is safe but not particularly effective, so sadly, we will have to keep using chloral hydrate.

Reviewed by: Sarah Reynolds

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 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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