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The 82nd Bubble Wrap


With millions of journal articles published yearly, 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. This time the PICSTAR team, in association with DFTB, are taking over…..

PCISTAR is the trainee-led collaborative network for Paediatric Critical Care Society (PCCS). So these articles have a critical care twist!

Happy Reading 🙂

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

Article 1: Which is better prophylaxis for status epilepticus in traumatic brain injury – levetiracetam or phenytoin?

Ahmed N, Russo L, Kuo YH. Levetiracetam or Phenytoin as Prophylaxis for Status Epilepticus: Secondary Analysis of the “Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial” Dataset, 2014-2017. Pediatr Crit Care Med. 2024 May 8. doi: 10.1097/PCC.0000000000003526. Epub ahead of print. PMID: 38717237.

What’s it about? 

Status epilepticus (SE) is the most common paediatric neurological emergency worldwide. Approximately 10% of patients with a traumatic brain injury (TBI) will go on to develop SE, increasing their risk of permanent neurological damage and death. The use of prophylactic antiepileptic drugs (AEDs) is therefore recommended, with phenytoin and levetiracetam most frequently used.

This case-control study was a secondary analysis of the dataset of the Approaches and Decisions in Acute Paediatric TBI Trial (ADAPT) trial.

Patients under 18 with a severe TBI (GCS ≤8) were included if they received either phenytoin or levetiracetam no later than day 2 of their PICU admission. Patients receiving both drugs or phenobarbital were excluded. Propensity score matching was used to compare different AEDs. This is a strength of the study, reducing bias due to confounding patient, injury, and treatment variables. Unfortunately, the timing of concurrent sedative infusions was not analysed, which may have had a confounding effect.

Of the 516 qualifying patients, 72% received levetiracetam, with the remaining ~28% receiving phenytoin. There was no association between any particular prophylactic AED and the occurrence of SE or mortality at 30 or 60 days. However, Levetiracetam use was associated with a longer PICU stay (p < 0.001). Phenytoin was associated with greater odds of a more favourable neurological outcome at 6 months (p = 0.003).

To read a bit more on traumatic brain injury, check out this post: Predicting paediatric traumatic brain injuries – Don’t Forget the Bubbles (

Why does it matter? 

SE is the second most common reason for emergency admissions to UK PICUs, yet there is no consensus on the best second-line anticonvulsant for patients with traumatic brain injury. In the ADAPT dataset, levetiracetam and phenytoin were used as prophylaxis, and the secondary analysis provided further insight into medication choice, utility, and areas of future study.

Levetiracetam was the most common AED choice, potentially due to its more favourable side-effect profile and fewer interactions than phenytoin. Although there was no significant difference in outcomes (SE or mortality) between AEDs, there was a trend towards a greater prevalence of SE and mortality with levetiracetam. Therefore, this study could not exclude the possibility that levetiracetam may be associated with worse outcomes.

Clinically Relevant Bottom Line

The jury is still out on which AED is superior prophylaxis against SE in patients who have suffered a traumatic brain injury. More comparative effectiveness trials within the paediatric population are needed.

Reviewed by: Manisha Kumar

Article 2: Recurrent Intensive Care Episodes and Mortality Among Children With Severe Neurologic Impairment

Nelson KE, Zhu J, Thomson J, et al. Recurrent Intensive Care Episodes and Mortality Among Children with Severe Neurologic Impairment. JAMA Netw Open. 2024;7(3): e241852. Doi:10.1001/jamanetworkopen.2024.185

What’s it about? 

This was a single-centre Canadian study between 2002 and 2019 of 4774 children with ‘severe neurologic impairment (SNI).’ These children are defined as patients who carry neurologic or genetic diagnoses with functional impairments and medical complexity. Previous studies have shown that these children frequently require Paediatric Critical Care (PCC). This study looks at the association between admission to PCC and long-term survival. Children with SNI account for a quarter of all PCC admissions and are more likely to be readmitted than children with other chronic conditions.

The study tested the hypothesis that more frequent admissions to PCC in the preceding year would be strongly associated with a higher risk of death. Children were excluded if they stayed in PCC for less than 48 hours (about 2 days) post-operatively. 

The authors used a large population-based sample, improving the validity and generalizability of the results. Amongst the population, 4774/27,731 (17.2%) had critical illness episodes requiring PCC admission.

10-year survival after the initial episode was 81% for children younger than 1 year of age and 84% for children one year of age or older. Short-term survival decreased with the increased number of recent high-risk critical illness episodes requiring admission, from 90% after the first discharge to 81% after the fourth.

Non-neurologic complex chronic conditions were associated with increased mortality (adjusted hazard ratio [AHR] of 1.70). Medical technology assistance was also associated with higher mortality (AHR of 2.32).

Regardless of the number or severity of admissions, conditional one-year mortality was <20%.

Why does it matter? 

This is the first study to quantify the association between recurrent PCC admissions and subsequent mortality for children with severe neurological impairment.

We, as paediatricians, should be aware that these children are at risk of repeat admission, but these episodes may not necessarily indicate a poor prognosis. We also need to consider the presence of non-neurologic complex chronic conditions and medical technology assistance. These are associated with increased mortality and should guide decision-making regarding PCC admission and management strategies.

Contrary to the hypothesis, recurrent PICU admissions were not strongly associated with subsequent increased mortality.

Clinically Relevant Bottom Line

There was a modest association between admission to PCC and short-term mortality among children with severe neurological injury, which increased with the number of illness episodes requiring PCC admission.

Reviewed by: Sofia Cuevas-Asturias

Article 3: Getting a Head Start: The Application of Cerebral Oximetry in In-Hospital Cardiac Arrest

Raymond TT, Esangbedo ID, Rajapreyar P, et al. Cerebral Oximetry During Pediatric In-Hospital Cardiac Arrest: A Multicenter Study of Survival and Neurologic Outcome. Crit Care Med. 2024;52(5):775-785. doi:10.1097/CCM.0000000000006186

What’s it about?

Cerebral oximetry, otherwise referred to as Near Infrared Spectroscopy (NIRS), is a non-invasive device that uses infrared light to estimate cerebral regional oxygen saturation (crSO2). It’s like a saturation probe, but it doesn’t require pulsatile flow, and is applied on the forehead.

This multicentre prospective observational study, conducted in the United States by the Paediatric Resuscitation Quality (pediRES-Q) collaborative, looked at the relationship between crSO2 during CPR and Return Of Spontaneous Circulation (ROSC), Survival to hospital discharge (SHD), and Favorable Neurological Outcome (FNO).

They collected data over a 7-year period from 2015 to 2022, and among 3212 in-hospital cardiac arrests, only 123 events met inclusion criteria in 93 patients. The median age was 0.3 years; 56% were male, and 31% had cyanotic congenital heart disease.

Overall, 80/123 (65%) achieved sustained ROSC, 26/123 (21%) achieved ROSC with ECMO, and 17/123 (14%) did not survive their arrest. Of the 93 patients, 54 (58%) survived to hospital discharge, 37 (40%) did not survive til discharge and 2% were still hospitalised at the time of data analysis. Of the 54 survivors, 36 (67%) had a favourable neurological outcome at discharge.

ROSC, FNO, and SHD were associated with higher crSO2 (above 30%) throughout the CPR event.

Limitations of this study include a small study population, potential monitoring bias (96% of the events used a single brand of NIRS), and patient selection bias (the largest cohort of patients being represented by cardiac patients). Also, while this was multicentre, only three hospitals in a 56-hospital collaborative contributed data.

Why does it matter?

Cerebral oximetry may potentially guide treatment and decision-making during CPR, possibly in combination with other established measures such as end-tidal carbon dioxide (ETCO2).

Most PICUs routinely use ETCO2; however, NIRS is typically only used in the paediatric cardiac cohort in intensive care. NIRS monitoring can be rapidly applied, with detectable readings appearing in less than 20 seconds after powering on the device. This may lend the application of NIRS to any in-hospital cardiac arrest. NIRS may have a role as a noninvasive predictor of ROSC for IHCA.

Clinically Relevant Bottom Line

Cerebral regional oxygen saturation (crSO2) has the potential to be useful as a marker of CPR quality and cerebral perfusion during a cardiac arrest, but more research is needed to determine which resuscitative actions improve crSO2 and whether or not crSO2-guided resuscitation results in observable benefits for survival and neurologic outcomes. 

Reviewed by: Chris Black

Article 4: Is a randomised control trial on ‘metabolic resuscitation’ for sepsis feasible?

Schlapbach LJ, Raman S, Buckley D, et al. Resuscitation With Vitamin C, Hydrocortisone, and Thiamin in Children With Septic Shock: A Multicenter Randomized Pilot Study. Pediatr Crit Care Med. 2024;25(2):159-170. doi:10.1097/PCC.0000000000003346

What’s it about?

This study was an investigator-initiated pragmatic, multicentre, randomized, open-label, parallel-group pilot trial conducted to test the hypothesis that a trial of ‘metabolic resuscitation’ with high-dose vitamin C, thiamine, and hydrocortisone would be feasible in children admitted with septic shock to PICU.

From August 2019 to March 2021, children between 28 days and 18 years admitted to PICU with presumed septic shock on inotropes for ≥ 2 hours but less than 24 hours were deemed eligible.

They were randomized into two groups in a 1:1 pattern. The intervention arm received adjunctive therapy with vitamin C, hydrocortisone, and thiamine. The control arm received standard care as per institutional protocols. No blinding occurred as it was difficult to do so (the intervention arm involved three drugs, one of which had a distinct yellow colour).

The primary feasibility outcomes included recruitment rates and time to initiation of the intervention. The primary clinical efficacy outcome was defined as survival free of organ dysfunction censored at day 28 after randomisation.

The median time from screening to randomisation was 15 (IQR 0 -40) minutes. Vitamin C, thiamine and hydrocortisone were administered in 100% of patients in the intervention group at a median of 44 (IQR 29 – 120) minutes after randomisation.  There were also point estimates towards survival free from organ dysfunction, shorter PICU length of stay and earlier shock reversal for those in the intervention groups; however, as this was a small feasibility study, no conclusions can be drawn from these currently.

Check out this module on sepsis and SIRS:SIRS, Sepsis and Shock Module – Don’t Forget the Bubbles (

Why does it matter?

Critically Ill children with sepsis have a high metabolic turnover and deplete vitamin C stores rapidly, and low levels on admission to PICU have been associated with multi-organ dysfunction.  ‘Metabolic resuscitation’ with hydrocortisone, vitamin C, and thiamine may have antioxidant and anti-inflammatory effects and reduce bacteraemia associated with thiamine deficiency.  Some PICUs have been using this strategy off-label despite there being no current robust data from randomised control trials.

Recruiting patients for RCTs when they are critically ill with sepsis can be challenging. This study demonstrated high parental consent rates and that the intervention could be administered rapidly.

Clinically Relevant Bottom Line

This pilot trial protocol was feasible. It compared high-dose vitamin C, hydrocortisone, and thiamine to standard care. The findings from this study may inform the designs of a full randomised control trial.

Reviewed by: Abhilash John Konnakottu

Article 5: Readiness to receive paediatric trauma patients

Melhado CG, Remick K, Miskovic A, et al. Emergency department pediatric readiness of United States trauma centers in 2021: Trauma center facility characteristics and opportunities for improvement. J Trauma Acute Care Surg. Published online May 13, 2024. doi:10.1097/TA.0000000000004387

What’s it about?

Emergency department (ED) paediatric readiness is associated with lower mortality for children presenting with trauma. But what about non-trauma centres?

The National Paediatric Readiness Project (NPRP) is an initiative led by the Emergency Medical Services for Children (EMSC) program. Its goal is to enhance Emergency Department (ED) readiness and provide quality emergency care for paediatric patients.

This study aimed to assess paediatric readiness within US trauma centres using a cohort of centres that provided data to the ACS National Trauma Data Bank® (NTDB) and responded to the NPRP national assessment in 2021.

The authors calculated a weighted paediatric readiness score (WPRS) (range, 0-100, with higher scores indicating higher readiness).

Hospitals with paediatric trauma centre designation were likelier to have a higher wPRS and more resources available (e.g., paediatric staffing, paediatric speciality wards).

A higher volume of paediatric trauma patients was directly related to higher wPRS.

One way to prepare is to think about your trauma leadership skills. Check this out: An introduction to trauma team leadership – Don’t Forget the Bubbles (

Why does it matter?

Emergency department (ED) paediatric readiness has been associated with lower mortality for children presenting with trauma. Results showed variation between US trauma centres and revealed areas for improvement.

Clinically Relevant Bottom Line

Emergency departments treating children presenting with trauma should focus on improving ED paediatric readiness. Low-volume centres that do not routinely care for children should be prioritized, and educational initiatives should be implemented.

Reviewed by: Spyridon Karageorgos

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.

PICSTAR team coordinated by Owen Hibberd. Vicki Currie, DFTB Bubble Wrap Lead, reviewed and edited all articles.


  • Vicki is a consultant in the West Midlands in the UK. She 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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