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The 80th Bubble wrap x DFTB MSc in PEM

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With millions of journal articles published yearly, it is impossible to keep up. Our team has scoured the literature, so you don’t have to—or it might spark an interest in reading the full article.

This time, the PEM MSc team from QMUL, in association with DFTB, are taking over…..

If you or your team are interested in an individual or joint review, please contact Dr. Vicki Currie at @DrVickiCurrie1 or vickijanecurrie@gmail.com.

Article 1: Positive urine cultures without pyuria

Wang ME, Jones VG, Kane M, et al. Clinical Course of Children 1 to 24 Months Old With Positive Urine Cultures Without Pyuria. Acad Pediatr. 2024;24(1):111-118. doi:10.1016/j.acap.2023.06.023

What’s it about? 

The presence of pyuria has been used to distinguish urinary tract infection (UTI) from asymptomatic bacteriuria. Pyuria is defined as greater than 5 white blood cells and positive leucocytes on urinalysis. 

This multicentre retrospective cohort study looked at 202 children in California aged 1- 24 months who presented acutely between 2010 and 2021. These children had a negative urinalysis and positive urine culture and were not prescribed antibiotics. Outcomes included clinical status when urine culture was available, subsequent antibiotic treatment within seven days and subsequent UTI within 30 days.

Of the 74.9% of patients with follow-up documentation, 70.8% (95% CI 62.9–77.9) showed clinical improvement without antibiotics. Most children (82%) were started on antibiotics when the culture result was available. This was more likely in those with a previous UTI and if there had been limited clinical improvement. Practitioners may have felt compelled to treat a positive result even with improved or resolved symptoms.

However, in the minority (18%) who were not started on antibiotics, none developed a UTI within 30 days.

Why does it matter? 

Overtreatment of asymptomatic bacteriuria may increase the risk of symptomatic UTI, antibiotic resistance, and side effects. We might also miss an alternative diagnosis. Repeat urine testing and clinical review may be more appropriate than jumping straight to antibiotics.

Clinically Relevant Bottom Line:

The presence of pyuria and clinical assessment should drive the diagnosis of UTI.

Reviewed by: Sarah Gentle and Owen Hibberd

Article 2: Second attempt success in neonatal intubation

Johnson MD, Tingay DG, Perkins EJ et al. National Emergency Airway Registry for Neonates (NEAR4NEOS) investigators. Factors that impact second attempt success for neonatal intubation following first attempt failure: a report from the National Emergency Airway Registry for Neonates. Arch Dis Child Fetal Neonatal Ed. 2024 Feb 28:fetalneonatal-2023-326501. doi: 10.1136/archdischild-2023-326501. Epub ahead of print. PMID: 38418208.

What’s it about? 

Intubation is a common procedure in the neonatal intensive care unit (NICU) and the delivery room. It has a high rate of first-attempt failure and carries the risk of severe procedure-related adverse events. However, intubation guidelines are not standardised across many NICUs.

This multicentre, retrospective cohort study (data from the National Emergency Airway Registry for Neonates (NEAR4NEOS) assessed factors associated with second-attempt success following a failed first attempt at neonatal intubation.

The primary outcome was the successful intubation on the second attempt.

Secondary outcomes included tracheal intubation adverse events (TIAEs) or severe desaturation. TIAEs included cardiac arrest, oesophageal intubation with delayed recognition, pneumothorax, hypotension requiring therapy, laryngospasm, or direct airway injury.

Out of 13126 intubations, 5805 (44%) required a second attempt and had complete data available. 3156 (54%) of these second attempts were successful.

No changes were made in 66% of the second attempts. Where a change was made, the most common was a change in the intubator (18%).

Second-attempt success was more likely with a change of intubator, stylet use, or ETT size (all p<0.001) but not with the type of laryngoscope (p=0.33). None of these changes were associated with an increased risk of severe TIAEs or desaturation.

The retrospective nature of the study cannot preclude potential selection bias. The study included academic NICUs, which may reduce the generalisability of the results. The rationale for the decision to change the intubator or equipment was unknown.

For a deep dive into intubation, see Intubation of the critically unwell Child in the emergency department – Don’t Forget the Bubbles (dontforgetthebubbles.com)

For all things neonatal (lines and tubes), see Neonatal lines and tubes – Don’t Forget the Bubbles (dontforgetthebubbles.com)

Why does it matter? 

An increased number of intubation attempts is associated with an increased risk of adverse events. This study provides data on how to potentially reduce these risks by demonstrating practical factors that increase second-intubation attempt success.

Clinically Relevant Bottom Line:

Successful neonatal intubation on the second attempt was more likely with a change in either intubator, stylet use, or ETT size, and these should be considered following a failed first attempt.

Reviewed by: Tasnim Ransome and Spyridon Karageorgos

Article 3: Which Sepsis Scoring Tools Perform Best? 

Schlapbach, L.J., Goertz, S., Hagenbuch, N., Aubert, B., Papis, S., Giannoni, E., Posfay-Barbe, K.M., Stocker, M., Heininger, U., Bernhard-Stirnemann, S. and Niederer-Loher, A., 2024. Organ Dysfunction in Children With Blood Culture-Proven Sepsis: Comparative Performance of Four Scores in a National Cohort Study. Pediatric Critical Care Medicine25(3), pp.e117-e128.

What’s it about?

This retrospective, observational multi-centre cohort study compared the performance of four paediatric sepsis scoring tools: International Pediatric Sepsis Consensus Conference (IPSCC), Pediatric Logistic Organ Dysfunction-2 (PELOD-2), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Organ Dysfunction Information Update Mandate (PODIUM) scores.

807 patients between the ages of 7 days to 17 years, from the ED, ward and PICU, were included across ten hospitals in Switzerland. Patients required a positive fungal or bacterial blood culture. The primary outcome looked at 30-day mortality, and secondary outcomes looked at a composite of 30-day mortality and PICU length of stay. Each patient was scored using the four sepsis tools. Data collected were the worst values documented within the same calendar day as the blood cultures were obtained. 

The four scoring tools showed no significant difference in predicting 30-day mortality or the secondary outcomes. The study identified major differences in the classification of each scoring tool, but cardiovascular, respiratory, and neurological dysfunction contributed to a higher mortality risk.

Some limitations were noted, such as excluding premature babies and post-bone marrow transplants. Criteria for the sepsis scoring systems were not defined explicitly. Data post 30 days was not reviewed, nor was functional health or quality of health outcomes. The data was collected from a cohort from 2011- 2015 (nearly ten years ago). Is this truly reflective of the current population?

Why does it matter?

 Having an accurate score to evaluate increased mortality in patients with sepsis aids in risk stratification, prioritising and expediting treatment, which ultimately aims to improve patient outcomes. Several paediatric sepsis scoring systems exist, but there is a lack of consensus on which is superior.

For a deeper dive into sepsis and shock see DFTB’s module SIRS, Sepsis and Shock Module – Don’t Forget the Bubbles (dontforgetthebubbles.com)


Clinically Relevant Bottom Line:

Current paediatric sepsis scoring tools (IPSCC, PELOD-2, PSOFA, PODIUM) perform similarly in predicting 30-day mortality. The study highlights that specific body systems carry a higher weight when considering sepsis-related mortality. There may be scope for a new systems-based, simplified sepsis score in the paediatric population. 

Reviewed by: Eimear Haughey and Melanie Ranaweera

Article 4: SpO2 targets in critically ill children receiving invasive mechanical ventilation

Peters MJ, Gould DW, Ray S, Thomas K, Chang I, Orzol M, O’Neill L, Agbeko R, Au C, Draper E, Elliot-Major L. Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial. The Lancet. 2024 Jan 27;403(10424):355-64.

What’s it about?

Typically, we target liberal SpO2 values (95-100%) for critically ill children. However, evidence suggests that this results in oxidative stress and increased mortality. Previous RCTs have suggested that a conservative SpO2 target (88-94%) is safe and clinically effective in infants outside of a PICU context.

This RCT compared conservative (SpO2 88-92%) versus liberal (SpO2 >94%) oxygenation in critically ill ventilated children admitted to the PICU. The study was conducted across 15 centres in the UK and included children aged >38 weeks corrected age up to 16 years of age. Children with uncorrected congenital heart disease, pulmonary hypertension, brain pathology, or injury were excluded. The primary outcome was the duration of organ support at 30 days. Secondary outcomes included 30-day mortality and costs at 30 days.

1872 children (mean age 2.5 years) were included in the final analysis. The mean time to randomisation was 2 hours, which excludes the initial resuscitation window. 65% of participants had underlying LRTI. The conservative group had a significantly lower duration of organ support (106 hours versus 123 hours). However, the mean SpO2 for the conservative group was in the intermediate range (94% versus 97% in the liberal group). This was largely because most participants didn’t require supplemental oxygen while ventilated. Mortality rates and 30-day costs were unaffected. Similar adverse events were reported (3-4%).

The cost implications need to be considered, too—the conservative group costs less than the more liberal group. The clinicians were not masked to the trial (e.g., oxygen was titrated based on saturations), and those in the more conservative group had higher rates of deviation from the protocol—although it was felt that there were similar amounts of deviations seen in similar adult trials.

For a more detailed review of the trial see The Oxy-PICU trial – Don’t Forget the Bubbles (dontforgetthebubbles.com)

Why does it matter?

The study adds to an evolving body of evidence that liberal oxygenation may be harmful in critically-ill ventilated children. However, this study did not include the acute resuscitation period or non-ventilated children.

Clinically Relevant Bottom Line

Once stabilised, critically ill ventilated patients may benefit from a conservative (88-94%) oxygenation target. Further randomised trials, preferably including intermediate SpO2 targets (92-95%), are needed.

Reviewed by: Sean Casey

Article 5:Oral corticosteroids for preschool wheeze

Lee B, Turner S, Borland M, et al. Efficacy of oral corticosteroids for acute preschool wheeze: a systematic review and individual participant data meta-analysis of randomised clinical trials. Lancet Respir Med. Published online March 22, 2024. doi:10.1016/S2213-2600(24)00041-9

What’s it about?

This systematic review and meta-analysis assessed the efficacy of oral corticosteroids in treating preschool wheeze when compared to placebo. Although limited by the wide age range (12 – 71 months), the review had the advantage of comparing seven large studies involving 2172 patients between 12 – 71 months. The primary outcome was a change in ‘Wheeze Severity Score’ (WSS) at 4- and 12-hours post-treatment. Though studies used different scoring systems, the authors of this review were able to obtain individual participant data from most of the studies involved, which allowed them to create the WSS and more easily compare results across studies.

Prednisolone was associated with a greater reduction in WSS at 4 hours and reduced length of hospital stay. This was most marked amongst children with moderate-to-severe wheeze. There was no significant difference in WSS at 12 hours or for differences in rates of return to GP/Emergency department or rehospitalisation, need for additional treatments or time until back to normal. The authors also observed a low risk of adverse events with steroids, with the most common side effect being vomiting.

Some limitations included the varied definitions of pre-school wheeze among the studies. In addition, not all of the studies included an outcome of a reduction in WSS scores by 4 hours.

A bit more on steroids in pre-school wheeze can be seen here. Steroids for pre-school wheeze – Don’t Forget the Bubbles (dontforgetthebubbles.com)

Why does it matter?

While the use of oral corticosteroids to treat wheeze in asthma is well-established, evidence for their benefit in viral-induced wheeze is mixed. Practice can vary widely, reflecting clinical uncertainty about whether to prescribe a treatment that might be effective or withhold treatment with side effects.

This study helps clarify this area of uncertainty, showing the utility of prednisolone in treating moderate-to-severe wheeze. It is equally important to suggest that children with mild wheeze may be provided with safety net advice and discharged without steroids.

Clinically Relevant Bottom Line:

This systematic review supports the use of oral corticosteroids in children with moderate-to-severe wheeze, with a very low rate of adverse events reported.

Reviewed by: Demetris Athanasiou and Owen Hibberd

If we have missed out on 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 who have taken the time to scour the literature, so you don’t have to.

Vicki Currie and Dr Mohomed Ashraf Vahedna reviewed and edited all articles.

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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