Subtle Signs in Safeguarding: Giles Armstrong at DFTB19

Cite this article as:
Team DFTB. Subtle Signs in Safeguarding: Giles Armstrong at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22259

Giles Armstrong reminds us that curiosity is needed for all of our young patients and that without it, we cannot truly care for them. We have to be the detectives and be prepared to ask the questions, not just to the routine questions, but to the unspoken ones. Giles presents us with some challenging, but very realistic scenarios, in which it is easy to miss the subtle clues if you don’t look for them.

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

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The febrile infant conundrum

Cite this article as:
Dani Hall. The febrile infant conundrum, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28850

It’s fair to say that febrile infants can be challenging. Often presenting with insidious symptoms but looking reasonably okay, they may still have life-changing or life-limiting illnesses like sepsis or meningitis. You could argue that we should take the view of eliminating risk, performing septic screens on all febrile babies, and admitting for IV antibiotics until their cultures are returned. The vast majority will have a benign viral illness but at least you can rest assured you didn’t miss a seriously sick infant.

And that’s what we did when I started my paediatric training back when the dinosaurs roamed the earth – every baby under 6 months (yes, you heard it right, 6 months) with a fever got a full septic screen, including lumbar puncture, and was admitted to the ward for at least 48 hours pending cultures. But, from a health economics point of view, this is, let’s just say, perhaps not the best way to allocate healthcare resources.

Over the years, researchers have tried to rationalise our approach to febrile infants. 2013 saw the first NICE fever in under 5s guideline; a year later a group from Spain published the Step by Step approach to identifying young febrile infants at low risk for invasive bacterial infection; and last year, the PECARN group published a clinical prediction rule for febrile infants under 60 days, which had excellent sensitivity and negative predictive values to rule out serious bacterial infections.

Last month, the Spanish group published an article looking at the external validity of the PECARN rule in their dataset.

Velasco R, Gomez B, Benito J, et al. Accuracy of PECARN rule for predicting serious bacterial infection in infants with fever without a source. Archives of Disease in Childhood Published Online First: 19 August 2020

PICO image

Before we plunge into the paper, let’s stop and think about a couple of important definitions here:

Serious bacterial infection (SBI) is used to describe bacteraemia, meningitis and urinary tract infections, also including infections such as pneumonia, skin, bone and joint infections, bacterial gastroenteritis and sometimes ENT infections.

Invasive bacterial infection (IBI) are infections where bacteria are isolated from a normally sterile body fluid, such as blood, CSF, joint, bone etc. An IBI is a type of SBI in a sterile site.

Who did they study?

Velasco’s group looked back at their registry of infants with a fever without source from a busy paediatric ED (> 50,000 presentations a year) in a tertiary hospital. To match the cohort in the PECARN paper, they used the following inclusion and exclusion criteria:

Inclusion: infants younger than 60 days who presented with a recorded fever, or history of recorded fever, of >38 C over an 11 year period between 2007 (when they started measuring procalcitonin) and 2018.

Exclusion: any infants whose history and/or examination pointed towards a focus, whose results didn’t include those used in the PECARN rule (absolute neutrophil count, PCT, urine dip), who didn’t have culture results, who were critically ill on presentation or who had a past history of prematurity, unexplained jaundice, previous antibiotics or other significant past medical history.

What were they looking for?

The group were interested to see how the PECARN rule fared in their dataset by looking at how many infants were predicted to be low-risk and yet had an SBI or IBI to assess the external validity of the rule.

What did they find?

1247 infants were included in this study. Of these, 256 (20.5%) were diagnosed with an SBI, including 38 (3.1%) with an IBI.

Of the 256 infants with an SBI, 26 (10%) were considered low risk by the rule. Of the 38 with an IBI, 5 were considered low risk (13.2%) by the rule. The PECARN rule would have missed 10% of infants with an SBI.

The PECARN rule’s sensitivity dropped from 97.7% in the original study to 89.8% and specificity dropped to from 60% in the original study to 55.5%.

So, how did Velasco’s group calculate the sensitivities and specificities of the PECARN rule for different groups in their dataset? They’ve nicely shown their data in 2 x 2 contingency tables in their figures. This is the data for SBI.

Table of data from Velasco study

So, we can see that sensitivity (those patients testing positive for the SBI as a proportion of all patients who definitely have SBI) = 230 / 256 = 89.8%. This means that 10.2% are falsely negative.

Specificity (those patients who test negative for SBI as a proportion of all of those who don’t have SBI) = 550 / 991 = 55.5%. This means that 44.5% are falsely positive.

What about infants with a really short duration of fever?

When the group looked at infants with a history of less than 6 hours of fever (n=684, a little over half of the cohort), the sensitivity dropped further to 88.6%.

Why did the PECARN rule perform less well in this study?

The authors offer up a number of suggestions, some of which are outlined below.

The populations may be slightly different. Although the authors attempted to exclude ‘critically ill’ infants from this study (as the PECARN study excluded ‘critically ill infants’), a precise definition wasn’t coded in the original Spanish registry. Instead, they excluded infants from this study if they were ‘not well looking’ or admitted to ICU. Because of the way the data was coded, some critically ill infants may have been included in this study’s dataset, skewing the results.

The Spanish database was of febrile infants without a source, excluding babies with respiratory symptoms, which may explain why the rates of SBI and IBI were much higher in this study than the PECARN database of febrile infants. So, although the PECARN rule was highly sensitive in their group of febrile infants, as in this study it may not perform so well in febrile infants without a source.

This study showed that the PECARN rule performed less well in infants with a short duration of fever. Overall, infants in the PECARN study had a longer history of fever at presentation – over a third of the PECARN infants had fever >12 hours compared to 11% in this study. Over half of the infants in this study presented within the first 6 hours. Blood tests are less sensitive in the first few hours of a febrile illness and this may well partially explain why the rule performed less well outside the PECARN dataset.

It’s important not to ignore this study’s limitations. The PECARN dataset recruited infants from multiple centres, while the registry for this study came from only one ED. As this study was a secondary analysis of a dataset, a power calculation wasn’t performed. Generally, a minimum of 100 cases is recommended for validating a model, but only 38 infants in this study had an IBI.

Study bottom line

This study showed that in the Spanish dataset of infants under 60 days with a fever without source, the PECARN rule performed less well than in the original study. This was especially true for infants with a short history of less than 6 hours of fever.

Clinical bottom line by Damian Roland

In Kuppermann et al’s original 2019 study febrile infants 60 days and younger were demonstrated to be at low risk of SBIs using 3 laboratory test results: Urinalysis, Absolute Neutrophil Count (ANC), and serum procalcitonin (PCT) levels. The study was well designed and therefore compelling in providing a framework in which to manage these challenging presentations. However, with respect to knowledge translation, external validity is critical. The availability of PCT is a significant limiting factor to being able to show the PECARN approach could be reproduced internationally. While PCT is used in Europe and Australia, it’s certainly not widespread in the UK where I practice, and then it is only used routinely in a very small number of hospitals. This makes Velasco and colleagues’ work really important as they were able to replicate the requirements of the original study and helps answer an important question: should centres start introducing PCT into their diagnostic pathology panels? The results of this study will be interpreted differently by different observers as ultimately the question is of risk tolerance. Personally, a 10% false-negative rate (if this is indeed the case) for an outcome that could result in long term disability feels uncomfortable. Counselling a parent that they could return home without treatment knowing this would probably be quite challenging. I am not sure many departments would be rushing to buy point of care PCT.

However, there are two very important caveats.  Firstly, is the validation cohort different from my own local cohort? The prevalence of disease has a huge bearing on the accuracy of any test. Knowing the local incidence of SBI and IBI in your own institution is important (but actually getting the numbers is harder than you may think!). It is likely that the PECARN approach may perform more effectively in other centres. Importantly the original paper highlights that implementation may be more effective in the second month of life due to the impact of HSV and other peri-natal infections present at 0-30 days. Secondly, what is the threshold for undertaking the blood tests in the first place? Fever in an infant less than 3 months is an interesting area as it’s one of the very few presentations in which a solitary symptom or sign is independently predictive of risk. Regardless of how the child appears to a health care professional, there is a risk of SBI and IBI (of anywhere between 2-10%) just by having a fever. This does mean that sometimes there is variation in approaches when there is a history of fever rather than a documented fever (for fear of not wanting to do a battery on tests on a neonate who in front of you appears completely well and has normal observations). But more importantly, this has led to an approach where although blood tests are taken, the results are often disregarded as an LP will be done and antibiotics will be given regardless. There are many cultural practices that have evolved around the management of the febrile neonate both within individuals and institutions. While in a study situation these are controlled for, their influence in the real world can not be underestimated and this is why it’s so important we have some pragmatic studies in this area.

This study makes me more determined to define our incidence of SBI locally and work out what impact new approaches to management may have. I think all centres should probably be doing this. However knowing the potential uncertainty in the sensitivity of the PECARN approach means it’s unlikely to be adopted in the immediate future without further validation.  

**post blog addendum 1st September 2020**

While this blog was in post production phase Kuppermann and colleagues have released further data on implementing their original predictive rule. This work has been summarised by Dr. Kuppermann below (click on to go to the original thread) and provides useful context to the discussion about external validity and implementation – DR.

Picture of ambulance

The paediatric prehospital primer

Cite this article as:
Team DFTB. The paediatric prehospital primer, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28860

Here at Don’t Forget The Bubbles, we’re delighted to be collaborating with some incredible prehospital clinicians to bring you posts about providing excellent care to children before they get to hospital. While we work away behind the scenes to curate these posts, we wanted to bring some of our published archive together in our very first prehospital paediatric primer.

We hope you enjoy these posts. Keep an eye out for more of our prehospital posts and if you’d like to contribute to our growing prehospital library, please get in touch!

Prehospital analgesia: part 2

Cite this article as:
Joe Mooney + Dani Hall. Prehospital analgesia: part 2, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27501

You’re in the rapid response vehicle, having just handed over a 2 year old with a femoral fracture. As you clear the hospital, a call comes in: 8 year old, fall from slide, deformed left arm, conscious and breathing. When you arrive in the house you find him lying on the sofa, with bruising and deformity of his left elbow. The paracetamol and ibuprofen given by his mother has not controlled his pain*, so you take out a methoxyflurane inhaler and explain to him to suck in and blow out through ‘the whistle’. After a few breaths he begins to relax.

Methoxyflurane is a fluorinated hydrocarbon, used as an inhaled anaesthetic in the ’60s and early ’70s, until it fell out of favour after case reports describing renal failure at anaesthetic doses. But, when given in small doses, methoxyflurane has excellent analgesic properties, with no nephrotoxic side effects. It has been used extensively in Australia and New Zealand by prehospital clinicians as a self-administered analgesic for short-term pain relief in adults and children. After being licenced in 2015 in the UK and Ireland for the emergency relief of moderate to severe pain in conscious adults with trauma, methoxyflurane was included in the Irish prehospital CPG for EMTs, paramedics and advanced paramedics with permission under the seventh amendment to allow its use in children.

Added as a liquid to a Penthrox® inhaler, methoxyflurane vaporises, to be inhaled on demand. It has revolutionised prehospital pain control due to its quick onset and easy, pain free administration and, because of its light weight, crews can carry it over rough ground easily. Known as ‘the green whistle‘, each 3ml dose is quoted to last between 20 and 30 minutes, but in practice can sometimes last up to 45 minutes or an hour, depending on a child’s respiratory rate and depth and the way in which they self-administer. The Irish prehospital CPGs allow two inhalers to be administered in 24 hours to a patient, so when there’s an extended journey time, methoxyflurane inhalers used back-to-back can provide up to two hours of analgesia, which can be supplemented by the simple analgesics, paracetamol and ibuprofen, or morphine, fentanyl and ketamine, as needed.

But what’s the evidence for methoxyflurane in children?

Pop methoxyflurane in the PubMed search bar, and a lot comes up. It’s safe, it works, but there are surprisingly few randomised controlled trials (RCTs) that include children. A couple of observational studies are noteworthy. An Australian study in the prehospital setting, published in 2006 by Franz Babl and colleagues, describes an observational case series of 105 children, ranging in age from 15 months to 17 years, who received methoxyflurane while by being conveyed to hospital by ambulance. The children’s pain scores dropped from 7.9 to 4.5, with few side effects, although there was a tendency towards deep sedation in the under 5s. The following year Babl’s team published an ED-based observational case series of 14 children aged 6 to 13 years with extremity injuries who received methoxyflurane for painful procedures in the hospital setting. Although methoxyflurane was a useful analgesic agent, Babl’s team found it did not work as well as a procedural analgesic for fracture reduction.

The first double-blind RCT of methoxyflurane in children was published almost two decades ago by Chin et al in 2002. Forty-one children over the age of 5 with upper limb fractures were randomised to receive either methoxyflurane or placebo. Unsurprisingly, methoxyflurane resulted in a lower pain score at 10 minutes than placebo. Adverse events weren’t reported, but the apparent safety and efficacy of methoxyflurane demonstrated in this study paved the way the some bigger and better RCTs.

A better known, and more recent, RCT involving children was the STOP! trial, published in the EMJ in 2014. This randomised, double-blind placebo-controlled trial was conducted at six EDs in the UK. Three hundred patients, 90 between the ages of 12 and 17, with minor trauma (such as burns, fractures, dislocations and lacerations), were randomised to receive either methoxyflurane or saline via an inhaler. In a nifty way to keep the patients, doctors and nurses blinded to which drug was being administered, a drop of methoxyflurane was added to the outside of every inhaler so both drug devices smelled the same. Pain scores dropped significantly lower in the methoxyflurane group, with a median onset of action of 4 minutes. But what about those adolescents? Although 45 12 to 17 year olds were included in each group, their data wasn’t analysed separately, and children under the age of 12 were excluded from the study, so although we can probably assume methoxyflurane works well and is safe in adolescents, more trials would be helpful.

Segue to the Magpie trial, which is currently recruiting in the UK and Ireland via the PERUKI network. This international multi-centre randomised, double-blind placebo-controlled trial is specifically investigating the efficacy and safety of methoxyflurane in children and young people so that its UK license can be extended to include children. Like STOP!, participants are being randomised to either methoxyflurane or placebo (again saline) via an inhaler. To ensure younger children are well represented in the study data, the study team are aiming to recruit higher numbers of 6 to 11 year olds than adolescents, with a recruitment target of 220 children and adolescents in total. We’re awaiting the results eagerly…


*A top tip on top up dosing

This child had been given 500mg of paracetamol and 280mg of ibuprofen by his mother before the crew arrived. He was 8 years old, with an estimated weight of 31kg. Based on Irish CPGs allowing a paracetamol dose of 20mg/kg (620mg) and ibuprofen dose of 10mg/kg (310mg) he was underdosed. It’s important to top-up simple analgesics as part of your approach to pain relief in children.


But what happened to the 8 year old?

You check CSMs (circulation, sensation and movement) before and after applying a splint and transfer him to the ambulance on a stretcher. His pain is very well controlled, and he asks his mother to take a photo for his friends. This sentence is hard for him to say and he gets the giggles. You transfer him uneventfully to hospital where he’s diagnosed with a supracondylar fracture.

Read more about assessing pain, prehospital analgesia in children and the evidence behind intranasal fentanyl in part 1 of the DFTB prehospital analgesia series.

References

Hartshorn, S., & Middleton, P. M. (2019). Efficacy and safety of inhaled low-dose methoxyflurane for acute paediatric pain: A systematic review. Trauma21(2), 94–102. https://doi.org/10.1177/1460408618798391

Babl FE, Jamison SR, Spicer M, Bernard S. Inhaled methoxyflurane as a prehospital analgesic in children. Emerg Med Australas. 2006;18(4):404-410. doi:10.1111/j.1742-6723.2006.00874.x

Babl FE, Barnett P, Palmer G, Oakley E and Davidson A. A pilot study of inhaled methoxyflurane for procedural analgesia in children. Pediatric Anesthesia. 2007;17:148-153. doi:10.1111/j.1460-9592.2006.02037.x

Chin, R, McCaskill, M, Browne, G A randomized controlled trial of inhaled methoxyflurance pain relief in children with upper limb fracture. J Paediatr Child Health 2002; 38: A13–A13.

Coffey F, Wright J, Hartshorn S, et al. STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain. EMJ 2014;31:613-618

Hartshorn, S., Barrett, M.J., Lyttle, M.D. et al. Inhaled methoxyflurane (Penthrox®) versus placebo for injury-associated analgesia in children—the MAGPIE trial (MEOF-002): study protocol for a randomised controlled trial. Trials 20, 393 (2019). https://doi.org/10.1186/s13063-019-3511-4

POCUS: Russ Horowitz and Cian McDemott at DFTB19

Cite this article as:
Team DFTB. POCUS: Russ Horowitz and Cian McDemott at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22174

Where would the world of paediatrics be without POCUS? We’d still be trying (and failing) to cannulate chubby toddlers by feel alone, we’d still be using radioactive waves to determine if the child in front of us has pneumonia and we wouldn’t have this eye-opening talk from Russ and Cian.

©Ian Summers

 
Russ and Cian co-ordinated the wonderful pre-conference ultrasound workshop in London.  Here is one of our favourite pearls is you want to help identify the bladder before performing a SPA. The bladder, looking just like a slice of toast, makes the perfect target.
 
 
 
If this talk has whetted your appetite then why not sign up for one of the www.dftb20.com ultrasound workshops.

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

iTunes Button
 

Selected References

Sii F, Barry RJ, Abbott J, Blanch RJ, MacEwen CJ, Shah P. The UK Paediatric Ocular Trauma Study 2 (POTS2): demographics and mechanisms of injuries. Clinical ophthalmology (Auckland, NZ). 2018;12:105.

Bubble Wrap Live + Connected

Cite this article as:
Team DFTB. Bubble Wrap Live + Connected, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28816

In just a few short days we will be hosting our first virtual conference, DFTB Live + Connected. If you haven’t checked out the program yet then head over to www.dftblive.com. There is still time to get a ticket and support DFTB.

The conference proper starts at 0600 UK / 0800 KENYA / 1500 SYDNEY / 1700 FIJI / 0100 NY

Our Bubble Wrap Live panel is hosted by Damian Roland, and comprises of the talented :-

  • Ben Wachira
  • Dani Hall
  • Simon Craig
  • Alison Boast
BubbleWrap Live start times

To give you a head start and allow you to join in the conversation at #DFTBLive here are the papers they are going to discuss.