With millions of journal articles published yearly, it is impossible to keep up. This month, the team from Royal Manchester Children’s ED highlights the diversity of current paediatric literature, ranging from air pollution, wheeze, trauma, surgery, to sadly but inevitably, child death.
Royal Manchester Children’s Hospital (RMCH) is a tertiary and major trauma centre in the North-West of England. Approximate annual attendance is 50,000. RMCH serves an incredibly diverse ethnic and socioeconomic population in the UK. This month, the team from ED highlights the diversity of current paediatric literature to reflect the versatility of RMCH ED.
Led by Kene Maduemem, Paediatric Emergency Consultant with interests in health equity, allergy, and medical education.
Happy Reading 🙂
If you or your team want to submit a review, please contact Dr. Vicki Currie at @DrVickiCurrie1 or vickijanecurrie@gmail.com.
Article 1: Is inhaled salbutamol safe in children under two presenting with acute wheeze?
Pierantoni L, Muratore E, Cerasi S, et al. Salbutamol safety in children under 2 years of age with acute wheezing: a meta-analysis of randomised controlled trials. Archives of Disease in Childhood 2025;110:111-119.
What’s it about?
A recent systematic review and meta-analysis examined the short-term safety of inhaled salbutamol in children under two presenting with acute wheeze. The authors focused on randomised controlled trials (RCTs) published in English that included infants with wheezing, including those diagnosed with bronchiolitis. They assessed the effects of inhaled salbutamol across various clinical settings.
The review identified 24 RCTs investigating the use of inhaled salbutamol in this age group. Nebulised salbutamol was the most common route, used in 21 studies, while five studies assessed salbutamol delivered via metered-dose inhaler (MDI), and two studies evaluated both methods. When comparing MDI salbutamol to control groups, there was no significant difference in the incidence of adverse drug reactions (ADRs). However, in five studies with low heterogeneity, nebulised salbutamol was linked to a higher incidence of ADRs (OR 6.76, 95% CI 2.01–22.71; p=0.002), raising questions about its safety profile in this population.
Analysing ADR: No study reported severe cardiac side effects that warranted withdrawal of salbutamol. A study that used nebulised salbutamol reported severe tremulousness, which resulted in withdrawal.
Limitations—Only eight studies evaluated salbutamol ADRs as the aim or primary objective. The analysis potentially has a high risk of bias as the studies assessed specific ADRs while excluding ADRs deemed clinically irrelevant.
For more on pre-school wheeze, check out this talk (an oldie but a goodie): Katie Reeves: Viral and Pre-School Wheeze at DFTB17—Don’t Forget the Bubbles.
Why does it matter?
The use of inhaled salbutamol in children under 2 years of age is controversial.
Clinicians are often uncertain about the benefits and safety of salbutamol in children of this age group, particularly because it is not recommended for bronchiolitis (a common cause of wheezing in children under two).
Clinically Relevant Bottom Line
Short-term use of salbutamol appears to be safe for children under two with acute wheeze, with the MDI-spacer route emerging as the preferred method. This delivery method is associated with fewer adverse drug reactions and may also offer greater effectiveness compared to nebulisation, making it a more favourable option in this age group.
Reviewed by Rayhaan Hossen
Article 2: Does air pollution impact the burden of childhood respiratory diseases?
de Souza AP, Souza Gomez CC, Gonçalves de Oliveira Ribeiro MA, Dornhofer Paro Costa P, Ribeiro JD. Correlations between ambient air pollution and the prevalence of hospitalisations and emergency room visits for respiratory diseases in children: a systematic review. Arch Dis Child. 2024 Nov 19;109(12):980-987.
What’s it about?
This systematic review examined 15 observational studies from around the world, exploring the relationship between increasing air pollution levels and the rate of hospitalisations and emergency department visits for respiratory illnesses in children. The review aimed to assess how air pollution contributes to paediatric respiratory morbidity, highlighting the potential health risks associated with poor air quality.
Most studies in this review used quasi-Poisson regression with a general additive model to analyse the association between air pollution and respiratory-related hospital visits. Only studies that reported relative risk (RR) or odds ratios (OR) with 95% confidence intervals for each 10 µg/m³ increase in air pollution were included.
Among pollutants, PM2.5 was the most extensively studied in 14 of the 15 papers. Short-term exposure to PM2.5 was significantly linked to an increase in hospital admissions in five studies and emergency department visits in nine.
However, the findings of this review are limited by the quality of the source data. Over half (53.3%) of the included studies had a moderate or high risk of bias, and due to the heterogeneity of study designs and outcomes, a meta-analysis could not be performed. Several key confounders—such as influenza outbreaks, smoking, and socio-economic factors—were not accounted for in many of the studies. Additionally, only one study originated from Europe, limiting the external validity of the findings in different healthcare settings.
Why does it matter?
Air pollution has now overtaken tobacco and diet as the second leading risk factor for death globally, with fine particulate matter (PM2.5) being a major contributor to its health impacts. Children are particularly vulnerable, with their developing lungs and immune systems making them more susceptible to respiratory illnesses and long-term complications. In 2021 alone, air pollution was responsible for over 700,000 deaths in children under five worldwide.
Despite its profound impact on child health, air pollution remains an under-recognised issue in medical education and health promotion. It is rarely emphasised in clinical training, public health messaging, or routine paediatric care, leaving a significant gap in both awareness and action.
Clinically Relevant Bottom Line
Despite its limitations, this systematic review provides statistically significant evidence that rising ambient pollution levels are linked to an increase in acute hospital attendance in children. The findings reinforce the urgent need to address air pollution as a public health priority, particularly for paediatric populations.
However, despite the World Health Organization (WHO) recognising air pollution as a global emergency, there remains a significant lack of high-quality research, particularly from the UK and Europe. This gap in evidence limits both awareness and policy change, underscoring the need for better data and stronger advocacy to protect children’s health.
Reviewed by Anna Russell
Article 3: Can prophylactic ondansetron reduce ketamine-associated vomiting in procedural sedation?
Efficacy of prophylactic ondansetron versus placebo or control in reducing vomiting in children undergoing ketamine procedural sedation in the emergency department. Jack L Hudson, Julian Wong, Michael Durkin, Vinay Gangathimmaiah, Jeremy Furyk. 2024 Jan 14.
What’s it about?
This review article examines the effectiveness of ondansetron as a prophylactic treatment compared to placebo in preventing ketamine-associated vomiting (KAV) in children undergoing procedural sedation in the emergency department. The primary outcome measured was the incidence of KAV, assessing whether ondansetron, administered via any route, reduced vomiting both during the ED stay and up to 24 hours post-discharge..
Five randomised controlled trials met the eligibility criteria with a total analysed sample size of 856. Two trials administered oral ondansetron, while intramuscular and intravenous routes were used in two other trials. Another trial provided either intravenous or oral ondansetron. Overall, prophylactic ondansetron significantly reduced the incidence of ketamine-associated vomiting, with an odds ratio of 0.51 (95% confidence interval: 0.36–0.73). The strongest effect was seen when both ketamine and ondansetron were given intravenously, with an odds ratio of 0.33 (95% confidence interval: 0.17–0.64).
The length of stay in the emergency department was unaffected, though this may have been influenced by the duration of post-procedural recovery from sedation. The impact on parental satisfaction could not be determined. However, the review was limited by a significant risk of bias due to missing outcome data and a lack of information on opioid co-administration.
Why does it matter?
Ondansetron, a 5-HT3 receptor antagonist, is commonly used in children to manage vomiting associated with gastroenteritis and postoperative recovery. Its potential role as a prophylactic agent in procedural sedation has been explored, particularly in reducing nausea and vomiting.
Ketamine is widely recognised for its high efficacy as an anaesthetic agent in paediatric procedural sedation, offering effective pain control with a favourable safety profile. However, ketamine-associated vomiting remains one of its most frequently reported side effects, prompting interest in preventative strategies such as ondansetron.
For a deeper dive into procedural sedation check out Procedural sedation – Don’t Forget the Bubbles and Sedation – DFTB Digital
Clinically Relevant Bottom Line
Prophylactic IV ondansetron is most beneficial in reducing ketamine-associated vomiting. The oral route has unclear benefits.
Reviewed by John Chukwuma Martin-Agba
Article 4: Does acute appendicitis in preschool children present differently from school aged children?
Paran, M. et al. (2024) ‘Diagnostic challenges of acute appendicitis in preschool children: A comprehensive case‐control study’, Journal of Paediatrics and Child Health [Preprint]. doi:10.1111/jpc.16748.
What’s it about?
This case-control study examined differences in the presentation of acute appendicitis between preschool-aged children (under 5 years old) and school-aged children (5 to 10 years old). A total of 184 preschoolers and 187 school-aged children were included, all with a postoperative diagnosis of appendicitis.
Preschool-aged children were less likely to present with abdominal pain (91.8% vs. 99.5%) but more likely to have symptoms such as vomiting (67.9% vs. 47.8%), fever (65.8% vs. 27.4%), and diarrhoea (27.2% vs. 8.6%). They also had a longer duration of symptoms before diagnosis (2.59 vs. 1.68 days).
The study found that complicated appendicitis was significantly more common in preschool-aged children (73.2% vs. 31.8%), along with a higher need for intraoperative drain placement (33.3% vs. 11.2%). These children also had higher rates of ICU admission (6.0% vs. 0.5%) and a longer hospital stay (7.3 vs. 4.1 days), indicating a more severe disease course in this age group.
However, the study had limitations. The control group did not include adolescents, meaning the findings may not represent disease patterns in older children. Additionally, because controls were randomly selected rather than matched for disease severity, direct comparisons between groups may be less precise.
Check out Paediatric Appendicitis – Don’t Forget the Bubbles for more on appendicitis.
Why does it matter?
Acute appendicitis is a common paediatric surgical emergency. It presents atypically in the preschool age group, leading to delayed diagnosis and a higher incidence of complications.
Clinically Relevant Bottom Line
In preschool-aged children presenting with non-specific symptoms such as fever, diarrhoea, and vomiting, appendicitis should remain an important differential diagnosis, even when abdominal pain is not a prominent feature. This study highlights the need for greater diagnostic awareness and recognition of atypical presentations in younger children to facilitate earlier diagnosis and reduce morbidity.
Reviewed by Megan Littlewood
Article 5: Has the incidence of sudden unexplained death in childhood changed in England and Wales?
Garstang JJ, Tosyali M, Menka M, Blair PS. Incidence of sudden unexplained death in childhood for children aged 1-14 years in England and Wales during 2001-2020: an observational study. Arch Dis Child. 2024 Nov 18:archdischild-2024-327840
What’s it about?
This observational study analysed the incidence and trends of sudden unexplained death in childhood (SUDC) in England and Wales between 2001 and 2020 among children aged 1 to 14. Using ICD-10 codes and UK census data, the study found that SUDC is far more common in children aged 1 to 4 than in older age groups.
Despite a near 50% reduction in overall child mortality over the two decades (from 1,482 deaths in 2001 to 826 in 2020), the absolute number of SUDC deaths remained unchanged. Consequently, SUDC became a proportionally larger contributor to child mortality, rising from 1.96% of all child deaths in 2001 to 3.03% in 2020. These findings highlight the need for further research into the causes and potential prevention of SUDC in young children.
Why does it matter?
Sudden unexplained death in childhood (SUDC) is defined as the sudden and unexpected death of a child aged 1 to 18 years that remains unexplained after a thorough case investigation, including a complete autopsy and ancillary testing. Despite advancements in forensic investigations, there remains a need for more advanced diagnostic techniques to uncover potential genetic or pathological causes.
While the increasing incidence of SUDC may be partly attributed to improved reporting, the underlying causes and modifiable risk factors remain largely unknown. Research into SUDC is significantly lacking compared to sudden infant death syndrome, with only 71 peer-reviewed publications on SUDC since 2005 compared to over 17,000 on SIDS. This study highlights the urgent need for greater focus on SUDC and advocates for including a distinct category for SUDC in the next revision of the ICD classification (ICD-11). This change could enhance global surveillance, improve classification accuracy, and streamline future research efforts.
Check out this post When ROSC feels wrong – Don’t Forget the Bubbles for further information.
Clinically Relevant Bottom Line
SUDC accounts for an increasing proportion of child deaths, especially in children aged 1-4 years, with a profound impact on bereaved families.
Clinicians should ensure that all unexplained child deaths are subject to thorough investigation and accurate reporting.
Reviewed by Hannah Mechie
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 our reviewers for scouring the literature so you don’t have to.
Vicki Currie, DFTB Bubble Wrap Lead, reviewed and edited all articles.
