With millions of journal articles published yearly, it is impossible to keep up. This month, the team from The Bridge will give us a whistle-stop tour of what’s new in Paeds literature.
The Bridge is a Postgraduate Doctor in Training (PGDiT)- led paediatric research forum in Yorkshire and Humber, UK, with the aim of bridging the gap in research access among PGDiT. Led by Dyanne Imo-Ivoke, this bubble wrap is from Doctors working at Hull Royal Infirmary.
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: Should we rely on WBC to predict serious bacterial infection in children?
Kemps N, Vermont C, Tan CD, et al. The value of white blood cell count in predicting serious bacterial infections in children presenting to the emergency department: a multicentre observational study Archives of Disease in Childhood 2025;110:191–196.
What’s it about?
This was a secondary analysis of the Management and Outcome of Fever in Children in Europe (MOFICHE) study. It was an observational multi-center study including >17,000 febrile children aged 0-18 across 12 European EDs over 1 year.
It aimed to assess the diagnostic value of WBC count in predicting SBI in children in A&E, comparing its value with that of CRP and absolute neutrophil count (ANC), and its use in combination with CRP. The primary outcome measure was SBI, and 1854 children included were diagnosed with an SBI. Definite SBI was defined as a positive culture from a sterile site, probable infection was a bacterial syndrome with no bacteria identified and CRP >60.
A raised WBC count >15×10^9/L count was significantly associated with SBI (aOR of 1.5, 95% CI 1.7-2.1). ANC performed similarly. However, WBC count only showed moderate sensitivity, with a count >15×10^9/L having a sensitivity of 0.56 (95% CI 0.54 to 0.58) and a specificity of 0.74 (0.73 to 0.75).
A CRP >20mg/L demonstrated a higher sensitivity (0.87, 95% CI 0.85 to 0.88) but lower specificity (0.59, 0.58 to 0.59), but higher CRP levels (>60mg/L) performed better, and levels >80mg/L best; sensitivity 0.55 (95% CI 0.52 to 057) and specificity 0.91 (0.90 to 0.91). Combining CRP and WCC didn’t improve performance compared to CRP alone.
For more on CRP testing, check out Can Point-of-Care CRP testing identify children with serious infection? – Don’t Forget the Bubbles.
A significant limitation is that WCC was not performed for every child- in those that were deemed to be ‘least ill’ this creates a bias.
Why does it matter?
There was a lack of literature comparing WBC count to CRP or ANC, when all three biomarkers are routinely (and easily) performed when taking blood from a febrile child. Previous systematic reviews have been focused on single center studies, shown poor performance of WCC in children, and tended to focus on children <5 yrs.
In acute paediatric settings, we are often faced with diagnostic uncertainty, and the use of relatively inexpensive, quick diagnostic tests that allow us to predict or rule in/rule out serious conditions can greatly aid decision-making.
Clinically Relevant Bottom Line
Raised WBC count is significantly associated with SBI, however CRP outperforms WBC count as a predictor for SBI in febrile children and should be favoured over the two.
In reality, children having blood taken in the ED for fever will likely have both an FBC and CRP taken. This reminds us that we should not fixate on ANC or WCC if we are worried about SBI and suggests instead being guided by the clinical picture in conjunction with CRP.
Reviewed by Dr Faye Leggott
Article 2: Does fluid overload increase mortality in children with sepsis?
Fernández-Sarmiento J, Sierra-Zuñiga MF, Salazar González MP, Lucena N, Soares Lanziotti V, Agudelo S. Association between fluid overload and mortality in children with sepsis: a systematic review and meta-analysis. BMJ Paediatr Open. 2023 Nov;7(1):e002094. doi: 10.1136/bmjpo-2023-002094. PMID: 37989355; PMCID: PMC10668252.
What’s it about?
The article is a systematic review and meta-analysis examining the association between fluid overload (FO) and mortality in children with sepsis. It analyses data from nine observational studies covering 2,312 paediatric patients. It evaluates the impact of FO (defined as >10% fluid accumulation within 24 hours of ICU admission) on mortality, mechanical ventilation (MV) requirements, multiple organ dysfunction syndrome (MODS), and length of hospital stay.
Some limitations of the study were that only observational studies were included that described a correlation between FO and mortality—which does not always imply causation. Some special patients (burns and trauma) were not described in the study. Lack of fluid monitoring throughout the PICU stay led to underreporting of MODS resulting from late-onset FO.
Why does it matter?
Sepsis is a significant cause of mortality in children, and fluid resuscitation is a key treatment strategy. However, excessive fluid administration can lead to fluid overload, which has been linked to worse clinical outcomes.
Children with sepsis are more prone to interstitial fluid accumulation due to factors like increased vascular permeability, endothelial activation, and glycocalyx degradation. This results in disturbances in both macrocirculation (e.g., cardiac output, heart rate, arterial pressure), and microcirculation.
FO was any positive fluid balance greater than 10% at any time after admission to paediatric critical care calculated by the formula:
[Total fluid intake in litres – total fluid output in litres)/admission weight in kilograms] × 100
The study highlights the importance of monitoring and managing FO to avoid complications. It also emphasizes the need for better fluid management strategies, including early de-resuscitation in high-risk patients.
The primary outcome was to evaluate the impact of % FO in paediatric patients with sepsis or septic shock at any time after PICU admission. The secondary outcome was children who required mechanical ventilation. This study revealed that children with FO had a higher mortality than patients without FO (46% VS 26%).
41% of patients with septic shock had MODS. 36% of patients with FO had MODS vs 47% of children without FO. Children who required mechanical ventilation (83% vs 57%) were more frequent for children with FO.
Clinically Relevant Bottom Line
In paediatric sepsis, fluid overload of more than 10% is significantly associated with higher mortality (46% vs. 26%), increased need for mechanical ventilation, and longer intensive care unit stays.
However, FO was not directly linked to MODS in this analysis. Prolonged fluid overload may still contribute to organ dysfunction over time. The findings suggest that clinicians should carefully monitor fluid balance, personalize fluid resuscitation strategies, and consider stopping fluids early when necessary to improve outcomes in children with sepsis.
Reviewed by Dr Sadia Irshad
Article 3: Updates on the management of sepsis and shock
Long B, Gottlieb M. Emergency medicine updates: Management of sepsis and septic shock. Am J Emerg Med. 2025 Apr;90:179-191. doi: 10.1016/j.ajem.2025.01.054. Epub 2025 Jan 22. PMID: 39904062.
What’s it about?
This paper provides an evidence-based update on the management of sepsis and septic shock in the emergency department. It discusses the latest recommendations for antimicrobial therapy, fluid resuscitation, vasopressor use, and adjunctive therapies. It emphasises the importance of early recognition, source control, and targeted resuscitation to improve patient outcomes.
This narrative review summarizes the evidence and evidence-based updates for clinicians; therefore, it is a summary of recent evidence rather than novel evidence. The limitation of this is that the evidence is presented with key points from multiple sources that are presented by the authors without an in-depth review.
Why does it matter?
Sepsis remains a leading cause of mortality and morbidity worldwide, with early treatment significantly impacting survival rates. This update reviews recent research and guidelines, supporting emergency physicians in making timely, evidence-based clinical decisions. It reinforces key principles in managing sepsis, including early recognition and rapid administration of antibiotics, balanced fluid resuscitation, early use of vasopressors, and steroid therapy for refractory shock.
There is a recognition in the paper that source recognition is ED is accurate in 85% of cases with a pulmonary source, 80% of those with a urogenital source, 68% of those with an intraabdominal source. This highlights the importance of a broad spectrum of ABX. The paper suggests cefepime and piperacillin-tazobactam as effective empiric choices for sepsis. However, NICE guidelines recommend Ceftriaxone as a first-line agent for sepsis.
Ceftriaxone is administered as an infusion (it takes time) and is not recommended in neonates because of the risk of hyperbilirubinaemia. However, local antimicrobial sensitivities must be reviewed before the recommended antibiotics are adopted.
In terms of time to ABX, evidence suggests that it should occur within 1 hour for patients who are haemodynamically unstable. Patients who are stable can have delayed administration within 3 hours. Both of these time frames have been considered based on available evidence and adverse outcomes.
There needs to be more emphasis on blood pressure checks in children, as they are not always performed in practice. During resuscitation, a mean arterial pressure (MAP) of> 65 mmHg should be targeted and tailored by responsiveness. This can be achieved using balanced fluids, normal saline, and norepinephrine as the first-line vasopressor. Higher MAP can have adverse effects: severe vasoconstriction, impair microcirculation and organ injury. Peripheral administration of vasopressors is safe with appropriate monitoring; vasopressors may improve preload and systemic perfusion.
Critical illness corticosteroid insufficiency may be more common: the recommendations are not as a routine practice in septic shock, but those with ongoing need for vasopressor therapy corticosteroids can be considered (specifically hydrocortisone).
To level up your sepsis knowledge, check out SIRS, Sepsis and Shock Module – Don’t Forget the Bubbles
Clinically Relevant Bottom Line
Early identification and management of sepsis should be encouraged, as this has a significant impact on survival. The sepsis screening tool in paediatric emergency departments can help.
Reviewed by Dr Luke Dim
Article 4: Supporting and improving the involvement of parents in child death review processes.
*Garstang JJ, Spry J, Routledge G, et al. Developing a toolkit to support parents’ involvement in child death review: an experience-based co-design study. Archives of Disease in Childhood. 2025;**110:*276-282.
What’s it about?
This is an experience-based co-design methodology and survey-based research aimed at improving the Child Death Review (CDR) process. It surveyed the CDR process of some paediatric intensive care units (PICU) and palliative care services in the UK. There were 29 survey responses, with a 62% response rate from PICU and a 28% response rate from palliative care.
This was followed by interviews of 21 professionals (from 5 different units with varying CDR processes to gain a wide range of practice). 10 of the professionals interviewed had key worker duties. There was also an interview of 23 bereaved parents of 22 children (aged 0 -18 years) who died between January 2021 and December 2022, either during hospital admission or under palliative care (at home or hospice). The parents were recruited through various channels, including charities, hospitals, and social media, and they received ongoing support throughout the process. Infants who died while in a neonatal care unit were excluded (these have a well-defined process of review using the Post Mortem Review Tool, PMRT).
Following the interviews, meetings were held to set the priorities of professionals and parents. Some of the parental priorities were for all families to have access to key workers, training for key workers, available resources for key workers, and proactive bereavement support for families. Professional priorities, in addition to those mentioned, were providing equitable service for all bereaved families and providing adequate resources to conduct reviews and support families.
A joint meeting was conducted to co-design a toolkit for enhancing parental involvement in CDR. This toolkit was developed by 10 parents and 23 professionals, including 8 key workers. The toolkit comprises training videos, a defined pathway, feedback forms, a leaflet, and a video on the importance of parental involvement. The toolkit is available at https://www.ncmd.info/guidance/parents-cdr-toolkit/
The automatic allocation of a keyworker based on the location of the child’s death was a point raised during the interview, as some key workers didn’t have a good understanding of the CDR process, and this provides a potential area for further work.
Some further limitations to the study included a low response rate initially to the professional survey. This was due to the difficulty in identifying palliative care teams that conduct CDRM, as there is no national list. The study relied on Child Death Overview Panels (CDOP) to inform of their local contacts. The study also had to be extended due to recruitment delays.
Why does it matter?
In England, there is a statutory CDR process for all children who die before their 18th birthday (About 3500 children/year). Parental involvement is an essential component of the CDR process, and bereaved parents should be informed about the process and contribute to the feedback. This can be particularly challenging for families, and guidance is often lacking on how best to support them.
Understanding why their child died is an integral part of the grieving process, and parents need to be able to ask questions and raise concerns about their child’s care. While there is guidance for parental involvement following neonatal or sudden unexpected death, this does not exist for the deaths of children following a chronic illness or anticipated deaths in hospital, thus impacting the ability of healthcare professionals and systems to learn from these deaths and support grieving parents.
Good communication is crucial to parents feeling they are well supported after their child’s death and having a positive experience of their child’s review process. All health professionals caring for children should be familiar with the CDR process and be aware of the key worker’s role in supporting bereaved families.
Check out this post on communicating with families in life-or-death situations: A short story about death… – Don’t Forget the Bubbles.
The toolkit developed through this study provides this guidance, represents best practice, and is suitable for use in all child deaths. This study demonstrates the importance of including patients, parents and carers in developing resources and toolkits and the feasibility of using co-design for sensitive topics such as child death.
Clinically Relevant Bottom Line
The support families need after the death of a child will depend on their circumstances and the circumstances surrounding their child’s death. Their input in the CDR process is valuable and often highlights learning that would be missed by health professionals alone.
Reviewed by Dr Anna Fox
Article 5: Does the antibiotic choice impact patient outcome in severe orbital infections?
Association of empiric antibiotic selection and clinical outcomes in hospitalised children with severe orbital infections: a retrospective cohort study. Krueger C, et al. Arch Dis Child 2024;109:932–940
What’s it about?
This is a Canadian multi-centre, retrospective, observational cohort study of children aged between 2 months and 18 years who were hospitalised for more than 24 hours with severe orbital infection between January 1, 2009, and December 31, 2018, in 7 Canadian hospitals and 3 community hospitals. It investigated the association between the choice of broad-spectrum antibiotics for children hospitalised with severe orbital infections, length of stay and need for surgery.
The study included 1421 patients with severe orbital infections, with a median age of 5.5 years. 60% of the patients were male, and half (51.7%) had received antibiotics before visiting the ED.
The median length of stay was 86.4 hours, and 180 patients (12.7%) received surgical intervention. Less than 10% of these children required ICU admission (2%) or developed orbital infection complications (5.2%)
The most commonly occurring organism in 175 (12.3%) children with positive culture was Streptococcus anginosus, followed by group A strep (see full paper for full breakdown).
Children receiving broad-spectrum empiric antibiotics had an increased median length of stay, ranging from an additional 13.8 hours (third-generation cephalosporin and anaerobic coverage) to 19.5 hours (third-generation cephalosporin, staphylococcal, and anaerobic coverage). No antibiotic regimen was associated with a change in the odds of surgical intervention. These findings were similar in patients with severe illnesses.
The percentage of patients receiving the broadest empiric antibiotic regimens increased from 17.8% in 2009 to 40.3% in 2018, while the proportion of patients receiving vancomycin doubled from 8.5% in 2009 to 18.1% in 2018, despite low MRSA rates. Empiric antibiotic use poses a significant concern with antimicrobial stewardship.
Unlike Canada, the UK has the UK Paediatric Antimicrobial Stewardship (UK-PAS) guideline, which recommends ceftriaxone for orbital cellulitis with the addition of clindamycin or metronidazole if >7 years of age.
For a deep dive on orbital infections, see Peri-orbital vs orbital cellulitis – Don’t Forget the Bubbles.
Why does it matter?
Antimicrobial resistance is a significant public health concern, and concerted efforts are underway to improve antimicrobial stewardship (AMS). Understanding the local prevailing organisms and sensitivity patterns can help enhance AMS.
Clinicians are often faced with making difficult decisions, comparing the benefits of treatments against the risks, and determining the best course of treatment. Severe orbital infections carry a significant risk of complications, and there is often no clear consensus on the antibiotic choice for them. Blood cultures are rarely positive in the paediatric population (4.3% locally), and pus is only available when children undergo surgery, which they usually don’t.
Broad-spectrum antibiotics, including third-generation cephalosporins (such as ceftriaxone), are used increasingly frequently, with their use doubling between 2009 and 2018 in this cohort. This may be due to their better brain penetration abilities. However, this increases the risk of antimicrobial resistance.
This is a retrospective cohort study; it’s observational and can’t study the effects of an intervention – its findings that broad-spectrum antibiotic use is associated with longer hospitalisation may have been affected by other variables. Timing of surgical intervention was not included and patients with a stay <24 were not included.
However, there was no significant difference in complications or need for surgery. This may be a sign that we are simply adjusting our prescribing practices, opting for a broader spectrum (which may not be necessary) while potentially contributing to antibiotic resistance.
Clinically Relevant Bottom Line
In this study, broad-spectrum ABX was associated with a longer length of stay than targeted treatment.
Reviewed by Dr Maddy Hover
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.