Davis, T. Top 5 Papers in PEM, Don't Forget the Bubbles, 2019. Available at:
This post is based on a talk I presented at the RCEM Spring Conference in April 2019 – Top 5 papers in PEM.
Kylie and Jason are enjoying their time at home with their first baby. The highs of being new parents is at its peak and true sleep deprivation is yet to set in. Jayden is two weeks old and is simply perfect. They spend hours staring at him each day marvelling at the perfect human they have created.
As we follow Jayden through his journey to adulthood, we’ll encounter some common paediatric problems. The 5.5 papers I have chosen were selected because: they cover common presentations; they use large patients groups; and they were conducted by well-respected and highly regarded research groups. But back to our story…
One night Jayden seems a bit more unsettled than normal. When they check his temperature it’s 38.4. They get in the car and bring Jayden to ED
Febrile neonates are a huge source of concern – we know that they can deteriorate quickly and we usually err on the side of caution by doing a full septic screen, IV antibiotics, and admission. Actually many of these babies don’t have a serious bacterial infection. Is there a way to tell which ones do?
When you see Jayden in your ED, you ask yourself is…should I do a full septic screen?
Paper 1 - Kupperman et al, 2019, A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections, JAMA Pediatrics
This paper aimed to derive and validate a highly accurate prediction rule to identify infant at low risk of SBI. The patients were febrile infants 60 days and younger (who had a rectal temp of >38 in the ED or a fever at home within the preceding 24 hours)
They excluded those who were critically ill, who had antibiotics in the preceding 48 hours, those born premature, and those with other medical conditions.
There were 1821 febrile infants included.
The authors considered clinical suspicion of SBI. They then look at various markers: blood culture; urine culture and urinalysis; CSF; FBC; and procalcitonin levels. The outcomes considered were serious bacterial infection – that is bacterial meningitis, bacteraemia, or urinary tract infection.
Overall, the rates of SBI in this group was 9%. The authors formulated a rule with a very high sensitivity (97.7%) for identifying those at low risk of serious bacterial infection. They were low risk if they fulfilled three criteria:
- negative urinalysis
- neutrophil count of less than 4/mm3
- procalcitonin of less than 0.5ng/ml
61.3% of their patient group were low risk.
Interestingly their low risk rule does not include use of lumbar puncture – 67.4% of the low risk group had a lumbar puncture that would not have been necessary.
Key take away: There may be some febrile neonates that are low risk, and therefore we could avoid a lumbar puncture and full work up. In practical terms, this is unlikely to change our practice at the moment. Many of us cannot send a procalcitonin in the ED, and we might have to wait several hours to get a neutrophil count back. However this does bode well for the future in identifying which of these well febrile neonates are low risk.
Jayden does get a full septic screen. He has IV antibiotics for 48 hours and remains well. His blood cultures are negative so his antibiotics are stopped and he is discharged.
Jayden is growing well. At 7 months of age, he is looking great and developmentally normal. Dad, Jason, smokes, but reassures you that he never does so in the house. Jayden develops a cough and two days later starts breathing very quickly and noisily. They head to the emergency department.
Jayden has bronchiolitis. This is very common and your departments and wards have no doubt been filled with these children over the winter. We know that little works with these children. So you force yourself to hold back the ‘trial of salbutamol’ because it won’t make any difference.. But high flow does seem to be the one thing (along with oxygen) that might make a difference.
You ask yourself the question...should I start high flow?
Paper 2 - Franklin et al, A Randomized Trial of High-Flow Oxygen Therapy in Infants with Bronchiolitis. NEJM. 2018. 378(12):1121-1131
This study looks at infants under 12 months old with a clinical diagnosis of bronchiolitis and a need for supplemental oxygen. 1472 were included (after exclusions). Patients were excluded if: they had an alternative diagnosis; they had cyanotic heart disease; or they were on home oxygen.
Patients were randomised to either high flow or low flow. The high flow group were given heated humidified high flow oxygen – 2L/kg/min via Optiflow. The oxygen was then weaned to achieve target saturations, and they were taken off high flow once they had been on air for four hours. The low flow group were given wall oxygen via nasal cannulae at 2L/min max.
The outcome was escalation of care. This meant who in the low flow group was escalated to high flow, and who in the high flow group was escalated to BiPAP or was intubated. Treatment failure was based on: an increase in heart rate; if the respiratory rate increased or didn’t drop; if they were needing oxygen in >2L/min of flow or >0.4 FiO2 to maintain their saturations; or if they achieve a high early warning score. Clinicians could also escalate care themselves (34% were escalated in this way).
Escalation of care occurred much more commonly in the low flow group – with 12% being escalated in the high flow group and 23% in the low flow group.
Interestingly there was no difference in the length of stay between the two groups.
Key take away: High flow does reduce the need for escalation. Escalation itself is significant – it requires increased nursing attention for low flow patients while they are transferred onto Optiflow. There may be less medical staffing on the wards if the child deteriorates on high flow overnight. Although they aren’t comparing like with like, escalation itself is an important clinical event. They also demonstrated that high flow does not increase the number of adverse events (for example there was no difference in the number of pneumothoraces between the groups). High flow is safe to use and we should consider starting it early in ED.
You start Jayden on high flow in ED and he stabilises. 12 hours later he is weaned off on the ward and is discharged the following day.
Jayden is now a healthy 3 year old boy. He loves Paw Patrol. He hates vegetables and won’t eat any food that is the colour green or yellow. Kylie and Jason are expecting their next child, and Jason has finally quit smoking. Unfortunately Jayden is prone to wheezy episodes and now has his very own inhaler which he hates using. The change in weather in London, from quite cold to…colder, seems to have triggered something and he’s now pretty wheezy and short of breath. They head into their favourite emergency department.
Jayden is now firmly in the realm of viral-induced wheeze. Yes, it’s all on a spectrum, but he’s now 3 years old with an inhaler. You asses him and think he should have a salbutamol burst.
As you are writing the salbutamol up, your SHO asks you – should I give him steroids?
Paper 3 - Foster SJ, Cooper MN, Oosterhof S, Borland ML. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. 2018 Jan 17.
This paper aimed to assess the efficacy of oral prednisolone in children presenting to an ED with viral wheeze.
The patients included were 2-6 years old. They were excluded if: saturations were less than 92% in air; they had a silent chest; they had sepsis; there was a previous PICU admission for wheeze; they had prematurity; or they had recently had steroids.
605 patients were included and they were randomised to receive either prednisolone or placebo. The prednisolone group received 1mg/kg prednisolone once a day for three days. The placebo group received a placebo medication (matched for volume and taste to prednisolone) once a day for three days.
Patients were assessed for their wheeze severity using a validated pulmonary score.
The outcome measures were length of stay (until clinically fit for discharge). They also considered re-attendance, readmission, salbutamol usage, and residual symptoms.
The results are tricky to interpret. Those who were discharged from ED within four hours did not benefit from prednisolone. However there may be some benefit in the mild to moderate wheeze group, and some in those who used salbutamol at home prior to presenting to ED. Interestingly this paper did not support our previously held belief that those children with atopy respond better to prednisolone.
Key take homes: Some pre-schoolers are steroid responsive, but identifying which ones is a challenge. As Damian Roland discusses here, it is likely that we are seeing lots of children presenting with the same symptoms (wheeze) but with different pathology behind it. Once we can identify the pathology we can start to target specific groups of patients with management that works.
You decided not to give Jayden prednisolone and after his salbutamol burst he stretches to 4 hours and is discharged home.
Jayden is 5 years old and in his excitement of building the new Hogwarts Lego castle he accidentally swallows a Lego head. Kylie and Jason aren’t sure whether to worry or not? So they take him into ED.
Children ingesting random objects is a common presentation to ED.
When you see Jayden in the department, his parents ask you…should I search through his poo?
Paper 3.5 - Tagg, A. , Roland, D. , Leo, G. S.Y., Knight, K. , Goldstein, H. , Davis, T. , DFTB, (2018), Everything is awesome: Don’t forget the Lego. J Paediatr Child Health. doi:10.1111/jpc.14309
Myself and 5 of my fearless, and brave, paediatric colleagues swallowed a Lego head each to see how quickly it passed. The paper was generously published in the Journal of Paediatrics and Child Health.
To ensure serious scientific rigour, we put together some scoring systems.
The Stool Hardness and Transit time (the SHAT score) took into account how hard our stools were, and whether that impacted (no pun intended) on the time to retrieve the Lego head.
And out main outcome was the Found And Retrieved Time (the FART score). This was the time to get our Lego heads back, and the average FART score was 1.71 days.
Unfortunately one of the six of us didn’t find his Lego head. After valiantly searching through his own faeces for two weeks, he gave up. And it may still be up there.
Key take home: Don’t search through poo, it’s gross.
Jayden heads home happily to finish building his Lego Castle.
Jayden is 6 years old. He thinks Paw Patrol is for losers. Fortunately he still loves Lego and Harry Potter. He also enjoys climbing. Unfortunately, two days ago he fell off the ladder coming down from his bunk bed. He seemed okay at the time, and Kylie and Jason had other plans that evening, so they decided to keep him at home. Now, two days later, he has a massive egg on his head and has been complaining of a headache. He also vomited yesterday. They bring him to ED.
We have fabulous head injury guidance for kids thanks to PECARN, CHALICE, and CATCH. But actually PECARN and CATCH specifically exclude injuries more than 24 hours old, and CHALICE doesn’t publish data on this group. So, for Jayden you need to put the NICE guideline away because it doesn’t apply. This is a common grey area.
The question you ask is….should I scan his head?
Paper 4 - Borland M, Dalziel SR, Phillips N, Lyttle M, Bressan S, Oakley E, Hearps SJC, Kochar A, Furyk J, Cheek J, Neutze J, Gilhotra Y, Dalton S, Babl F. Delayed Presentations to Emergency Departments of Children With Head Injury: A PREDICT Study, Annals of Emergency Medicine, DOI: https://doi.org/10.1016/j.annemergmed.2018.11.035
This paper aimed to establish the prevalence of traumatic brain injuries in children presenting more than 24 hours after the head injury.
Traumatic brain injury (TBI) was defined as: intracranial haemorrhage; contusion; cerebral oedema; diffuse axonal injury; traumatic infarction; shearing injury; or a sigmoid sinus thrombosis.
The also looked a clinically significant traumatic brain injury (cTBI) – this included death, intubation for more than 24 hours, neurosurgery, or admission for 2 or more nights to hospital.
The patients were from the Australian Paediatric Head Injury Study Cohort which was 20,137 patients. 5% of these presented over 24 hours after the injury. 981 children were included in this study.
The authors considered the injury characteristics and demographics, trying to find an association between mechanism and delay in presentation. Those presenting were more likely to have: a non-frontal scalp haematoma; headache; vomiting; and assault with NAI concern. Those with loss of consciousness and amnesia were more likely to have presented within the first 24 hours.
The CT rates were much higher in the late presentation group – 20.6% being scanned in the delayed group and only 7.9% in the early group. This probably reflects the lack of evidence in this area, and therefore we feel safer doing more scans.
But the rates of TBI also varied. 3.8% in the delayed presentation group had a TBI, whereas only 1.2% in the early presentation group did.
The rates cTBI were the same between the groups at 0.8%
Key take homes: There is an increased risk of TBI when presenting more than 24 hours after a head injury injury. The authors found that risk is increased if the patient has a non-frontal scalp haematoma or a suspicion of a depressed skull fracture.
You decide to scan Jayden’s head, but it turns out to be normal and he is discharged home.
Jayden is 8. He’s been drinking a LOT of water over the last few weeks and seems to be weeing constantly. His clothes seem a bit big for him too. He looks so bad one day (and has vomiting and abdominal pain) that Jason finally reneges and takes him into ED.
Jayden has DKA. The debate about over-zealous fluid administrations and its relationship to the dreaded cerebral oedema is long-standing. Previous research suggested a link but only by association, not causality.
You ask yourself…how fast should I give IV fluids?
Paper 5 - Kupperman et al. Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis NEJM 2018 vol 378 (24) pp 2275-2287
The study examines the causal effect between fluid resuscitation and cerebral oedema.
They included 1389 episodes of DKA. Exclusions were mainly due to too much management prior to contact with the study team, as well as children with a GCS<12. The median age was 11. It should be noted that the very young and the very sick are probably lost in this cohort.
Patients were randomised to received either fast or slow rehydration, and then were split again into received either 0.9% NaCl or 0.45% NaCl.
The fast rehydration group received 20ml/kg bolus and then replacement of 10% deficit, half over 12 hours and rest over next 24 hours. The slow rehydration group received a 10ml/kg bolus and then replacement of 5% deficit over 48 hours. Maintenance fluids and insulin were given in addition.
The outcomes looked at were deterioration of neurological status within first 24 hours of treatment. They also assessed short term memory during treatment, and IQ 2-6 months after the episode of DKA.
In short, they found no difference between the groups. There was a 0.9% rate of brain injury overall and it didn’t matter which type of fluids or how fast. Patients were more likely to get hyperchloraemic acidosis in the 0.9% NaCl group but this is of debatable clinical significance.
Key take homes: The evidence does not support our traditionally cautious approach to DKA. The speed of IV fluids does not seem to be the cause of brain injury in DKA.
You resuscitate Jayden and send him off to the ward. He is discharged a few days later with good support from the Endocrine team for management of his diabetes.
Jayden is now 16 years old and next time he comes to ED, he’ll be in the harsh world of Adult ED. We have navigated him through his common childhood presentations to ED and answered the key questions we ask ourselves every day in the Paeds ED.
Should I do a full septic screen on this hot baby?
Should I start high flow on this infant with bronchiolitis?
Should I give prednisolone to this 2 year old with wheeze?
Should I scan this child with a head injury?
How fast should I give fluids to my DKA?
And most importantly, do I ever need to sift through my child’s poo, or my own ever again?