BRUE v ALTE – have the new guidelines made a difference?

Cite this article as:
Roland D, Davis T. BRUE v ALTE – have the new guidelines made a difference?, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20773

This week sees the publication of a new paper in Pediatrics by the team at the Children’s Hospital of Pittsburgh and the University of Pittsburgh.

Ramgopal SR, Noorbakhsh KA, Callaway CQ, Wilson PM, Pitetti RD. Changes in the management of children with brief unresolved unexplained events (BRUEs). Pediatrics.

Why was this study needed?

In 2016, the American Academy of Pediatrics published a guideline which renamed and redefined ALTEs (acute life-threatening event). The new term was BRUE (brief resolved unexplained event).

ALTE was initially coined in 1986 and the definition was:

an episode that is frightening to the observer and that is characterised by some combination of apnoea (central or occasionally obstructive), colour change…marked change in muscle tone (usually marked limpness), choking, or gagging. In some cases, the observer fears that the infant has died.

This was a broad definition and caused some difficulties for those of us assessing babies in hospitals. Although an ALTE could indicate a serious underlying problem – NAI, infection, seizure – commonly the infant was completely well. ALTEs by definition were subjective and this made the management of them tricky. Often these babies had overnight admissions to hospital for observation.

The new definition for BRUE is:

A BRUE has occurred if the observer reports a sudden, brief, and now resolved, unexplained episode of ≥1 of the following:

  • cyanosis or pallor
  • absent, decreased, or irregular breathing
  • marked change in tone (hyper- or hypotonia)
  • altered level of responsiveness

As well as the new definition, the guideline also stratifies patients and recommends management for those in the low-risk group.

Read our DFTB summary of the change in guidance here.

It has now been three years since the change from ALTE to BRUE. The aim of this study was to see whether the new guidance has affected rates of admission, investigations, or outcomes.

The objectives of the study were cleared stated and relevant to paediatric emergency medicine.

Who were the patients?

Patients were taken from the Pediatric Health Information System, which is a database with all information from presentations and admissions in hospitals across 26 states in the USA.

Patients were included if they were under 1 year old and had a diagnosis coded of either ALTE or BRUE between 2015 and 2017.

Exclusions were if patients had been transferred from another hospital, or had ambulatory surgery.

A control cohort was also used from all ED presentations of children under one year old during the inclusion period with no diagnosis of ALTE and BRUE (same exclusion criteria). The aim of the cohort group was to check whether there were any confounding trends in admissions/investigations during that time period.

This was an appropriate choice of patient group and the use of control cohort was beneficial. Sample size estimates were not stated explicitly but were alluded to.

The limitation here is the reliance on coding. However, additionally the authors were unable to determine if the diagnosis was correct, or if the patient could be classified as a low-risk BRUE as these assessments require a history and examination.

9,501 patients were used for the cohort analysis (5508 patients 0-60 days old, and 3993 who were 60 days to 1 year old). This group was split into a 2015 cohort (i.e. before the new guidelines) and a 2017 cohort (after the introduction of the new guidelines)

A second analysis was an interrupted time series analysis to look at trends in admissions over time. 13,977 patients were included in this group.

1.4 million patients were in the control cohort.

What analysis was carried out on these groups?

The cohort analysis looked at the rate of admissions as the primary outcome. Secondary outcomes included revisits and investigations performed. A comparison was also conducted by using the control cohort.

The interrupted time series analysis looked at whether admission rates changed over time following the introduction of the guideline. Admission rates were analysed in one-week batches throughout the three year time period.

The subjects were all accounted for and appropriate outcomes were considered.

What were the findings?

Admissions: the proportion of admissions in the 61-365 day old group was 86.2% in the 2015 cohort and 68.2% in the 2017 cohort. The admissions were also significantly lower in the 0-60 days group – 89.9% in the 2015 group and 84.1% in the 2017 group.

Investigations: the 2017 group had significantly lower rates of EEG, MRI, CXR, FBC, U+Es, LFT, and urinalysis. Those in the 0-60 day old group (2017) had significantly lower rates of blood gas measurement, blood sugar testing, head CT, metabolic studies, and lumbar puncture.

Revisits: in the 0-60 day old group, revisits within 3 days were significantly lower in the 2017 group (3.7%) than in the 2015 group (5.2%). The rest of the revisit rates were similar.

Analysis of the control cohort here suggested that the decreased rates of these outcomes were independent of other trends over time.

Interrupted time series analysis: in the 0-60 day old group the introduction of the guideline did not affect trends in admissions rates. However, in the 61-365 day old group, the admission rates decreased each week after the guideline was published.

The authors were clear on what was measured and how it was measured. Follow up was for a 30 day period so should have picked up most complications. The measurements were reliable, valid, and the basic data was adequately described.

What did the authors conclude?

Between 2015 and 2017 there has been a significant reduction in the rates of admission and investigations for patients with ALTE/BRUE. This rate decreased steadily following the guideline publication.

The authors note that this reduction is seen in the 0-60 day old group, even though that age group would be stratified as higher risk in the new guidelines. The fact that BRUE is a diagnosis of exclusion, whereas ALTE was all-encompassing may mean that this diagnosis is being applied to a smaller, safer group over time, which might explain the findings. There were less patients diagnosed with ALTE/BRUE in 2017 compared to 2015.

The results are discussed in relation to existing knowledge and the discussion seems balanced and not biased. The conclusions are justified by the data.

Will this paper change my practice?

Changing practice is challenging, changing a definition is a little easier.

This study is a great example of how to review the impact of guideline change and determine whether the outcomes have improved for patients without unintended consequences. At face value the BRUE approach has had beneficial clinical impact. We see an overall decline in admission and investigations with no obvious harm (returns don’t increase).

There are a few caveats that are important to consider though. This study was from a chain of hospitals likely working with similar cultures and convergent working practices. A random selection of children’s hospitals may have interpreted the AAP guideline with a greater degree of variance (and therefore application). With this in mind the relevance of quite a profound change in coding should be highlighted. In a similar timescale 25% of patients with a prior diagnosis of ALTE are no longer coded as such and it appears that these patients are not replaced with a BRUE code (as there was a 25% reduction overall in either code). This means that either the guidance has been successful in making staff think hard about about the underlying reason for the infant’s presentation or that perhaps initial coding was not as precise as it could have been (“I’m not sure what happening here so I’ll just call it an ALTE“). Of note the return rate isn’t supplied for those not coded as BRUE or ALTE so we don’t know if the cohort of patients now coded as something else have actually come to increased harm. It is also interesting to note the significant fall in admissions for those less than 60 days old. This wasn’t the intention of the initial guidance and while this group’s re-admission rates didn’t increase this study wasn’t powered (or designed) to look at whether the re-admission changes would be significant or not. The fact that it appears safer is a statistical construct, not a clinical one. This means a type II error is possible (there is actually a problem but we aren’t seeing it).  

Ultimately, while these risks are real, and do need investigation in future study, it is likely that altering to using BRUE will effectively rationalize your investigation and management pathways without causing additional harm. The challenge for those outside the United States is whether national organizations are happy to formally endorse the BRUE concept as staff may feel uncomfortable applying new rules without official sanction. Locally certainly, we use the BRUE criteria in our risk assessment and this study only further endorses that approach.

Post-publication commentary from one of the authors

This is a really wonderful summary and analysis of the study. The findings do suggest that patients in the low risk cohort identified by the AAP BRUE guidelines are being discharged safely without an increase in return visits. It is important to note that this narrower definition of BRUE has not excluded all high acuity conditions, as patients with high acuity co-diagnoses were identified in both age groups after the practice guideline publication.
 
Overall, I think our findings support continued clinical application of the BRUE definition and guidelines. While not within the scope of our study, the results did make us wonder about the impact of guidelines published by a national medical organization. How much of the change we saw in a three-year period were due to influence by the AAP and how much was because the medical community was ready for a change in ALTE management? Finally, we hope that our findings are able to support further research into management of both low-risk and high-risk BRUE and into understanding what has changed in the management of infants who are now excluded from the BRUE diagnosis.
 
Katie Noorbakhsh (author)

Here’s a printable A4 summary of the paper & our thoughts:

Changes in the management of children with Brief resolved unexplained events (BRUEs)

Practice made perfect?

Cite this article as:
Sonia Twigg. Practice made perfect?, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20694

Okay, perhaps  not perfect but we think these bite sized chunks of simulation from Children’s Health Queensland are pretty good! They are free to download and play with. You can find access to all current OPTIMUS resources here. Enjoy!

 

Introducing BONUS – A Bank of Independently Useful Sims

 

 

 

What are they?

OPTIMUS BONUS is an ongoing project driven by Children’s Health Queensland involving the creation of simulation education packages on topics in paediatric resuscitation.  Each package contains;

  • An introduction by an expert explaining why the topic is important.
  • A simulation with clear learning objectives, instructions and hints for debriefing.
  • Pre-reading resources for participants. These are fun and easy to read resources including podcasts, videos, guidelines and apps.
  • An infographic summarising the topic. QR codes on the posters link to Just In Time Training resources including videos and guidelines.  Just point the camera on your smart phone at the poster and a link will appear to the website to see the video.

 

Who writes them?

The STORK team (Simulation Training Optimising Resuscitation in Kids) from Children’s Health Queensland provides simulation based education throughout Queensland.  We provide two courses as part of our OPTIMUS curriculum; Optimus CORE (for first responders) and Optimus PRIME (for mid phase care while awaiting retrieval).

 

 Why did we make them?

 

What we love about them

  • They’re free to download, expert reviewed, repeatedly tested and assessed by a statewide advisory group to ensure we’re providing a quality product.
  • Our infographics look awesome, summarise the key messages, are easy to share on social media and easy to store on your phone.
  • Some packages contain Just in Time Training JITT resources and videos via QR codes to give you the info you need when you need it :
    • Just scan the QR codes on your phone to see refresher videos before you go and perform that skill
  • We’ve curated great open access #FOAMed resources on paediatric topics for each Simulation, so you can deep dive into more learning before or after the Sim!

 

Love the simulations and want to help out?

Thanks!  We need your help to share these simulations and infographics online any way you can. Shout out to @childhealthqld @LankyTwig @Caroelearning @paedsem and @symon_ben on twitter if you’re using them!

The other thing that REALLY helps is getting good feedback.  So, if you have thoughts on them to share fill out the surveys via the QR codes in the package so we can keep making better simulations to share with the world.

If you’d like to know more, email us at stork@health.qld.gov.au

Other than that, retweet them, share them widely, and help us improve paediatric care everywhere in the world.

 

Enjoy!

Sonia and the BONUS team

Dr Sonia Twigg (@LankyTwig), Dr Benjamin Symon (@symon_ben), Dr Carolina Ardino Sarmiento (@caroelearning), Dr Ben Lawton (@paedsem) Ms Louise Dodson and Mrs Tricia Pilotto.

 

Selected references

Case, Nicky, “How to remember anything forever-ish.:  Oct 2018.  Available at: https://ncase.me/remember/

Cheng et al, “Resuscitation Education Science: Educational Strategies to Improve Outcomes from Cardiac Arrest; A Scientific Statement from the American Heart Association.”Circulation 2018; 138: e82-e122. Available at: https://www.ahajournals.org/doi/10.1161/CIR.0000000000000583

Cheng et al, “Highlights from the 2018 AHA Statement on Resuscitation.” June 2018.  Available at: https://canadiem.org/aha-scientific-statement-on-resuscitation-education/

Dubner S.“Freakonomics Radio.  How to become great at just about anything (Ep 244).” Apr 2016.  Available at: https://freakonomics.com/podcast/peak/

Ericsson A,“Peak” Vintage 2017.

Seat Belt Injuries

Cite this article as:
Keith Amarakone. Seat Belt Injuries, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20575

A 10 year old boy presents to your emergency department following a high speed MVA – car vs tree. He was seated in the rear middle seat.  On arrival he is noted to have significant bruising across his lower abdomen from the seat belt but otherwise appears well.

He’s always sick: ENT infections and immunodeficiency

Cite this article as:
Alasdair Munro. He’s always sick: ENT infections and immunodeficiency, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20243

Otis is a 3yr old boy presenting to the emergency department with fever, and purulent discharge from his left ear. He otherwise looks well, however, his mother mentions this is his third ear infection since he was born, and he always seems to have a cough and a cold. She asks you if there could be a problem with his immune system?

Some children seem to have constant ear, nose or throat infections during childhood. We know that for a small, but important minority of children this may be the presenting feature of a primary immunodeficiency. Let’s look at how these may present, when to think of it, and what to do about it.

Primary immunodeficiency is rare

It’s worth stating from the outset, that the majority of children with recurrent ENT infections will not have a primary immunodeficiency. There is a relatively common phenomenon called “physiological immunodeficiency of infancy”, where-by there is a natural nadir in immunoglobulin levels as maternal immunoglobulin fades, and the child’s own immune system has only just become able to produce immunoglobulin for itself. This is at its lowest between 3-6 months and normally resolves by age 1. However, fully developed protection against encapsulated organisms doesn’t reach maturity until between 2-5 years, and IgA production doesn’t reach adult levels until adolescence. It can be completely normal for young children to suffer 4-11 respiratory infections a year (depending on exposure, e.g. siblings, nursery, etc.)

When should I suspect immunodeficiency?

When considering the characteristics of infections that should trigger suspicion for immunodeficiency, we should be thinking about:

More severe infections than is usual

Combined immunodeficiency disorders (affecting both cellular and humoral immunity), such as severe combined immunodeficiency (SCID), present in the first 3-6 months with severe, life-threatening infection. Unusually aggressive infections should prompt further investigation

Infections with unusual organisms

Infections with certain pathogens can point towards specific diagnoses, including respiratory infections with Pseudomonas aeruginosa (think cystic fibrosis or primary ciliary dyskinesia), oral/oesophageal candidiasis (think HIV or chronic granulomatous disease), upper respiratory infections with Pneumocystis carinii (think HIV or other T cell deficiencies) or recurrent otitis/sinusitis with Neisseria meningitidis (think complement deficiency).

Finally, to a lesser extent:

Frequency of infection

This is the least predictive of immunodeficiency, given the discussion above. Very frequent sinopulmonary infections in younger children with encapsulated bacteria can be the presenting feature of the rare condition X-linked agammaglobulinaemia (XLA: boys who produce no immunoglobulins). In late childhood and adolescence, the same presentation in a milder form may be a sign of combined, variable immunodeficiency (CVID), which is a heterogeneous group of disorders of antibody production.

Other, rare conditions include chronic granulomatous disease (CGD) which may present with deep abscesses of the outer ear or mastoid, or HIV presenting with recurrent otitis media (normally with other associated features)

 

When to refer

Some general guidelines have been produced by the Jeffrey Modell foundation for when to consider referral for immunodeficiency workup:

  • Four of more new ear infections within 1 year
  • Two or more serious sinus infections within 1 year
  • Two or more months on antibiotics with little effect
  • Two or more pneumonias within 1 year
  • Failure of an infant to gain weight or grow properly
  • Recurrent, deep skin or organ abscesses
  • Persistent thrush in the mouth or fungal infection on skin
  • Need for intravenous antibiotics to clear infections
  • Two or more deep-seated infections including septicaemia
  • A family history of primary immunodeficiency

Although having a low specificity, they provide a useful framework when thinking of children with more severe infections than usual.

 

Should I do some tests?

If considering referral, there are definitely some basic tests are useful to do first (if the child is severely unwell, don’t wait for tests to refer).

Full blood count

This is useful for ANY suspected immunodeficiency. Persistent lymphopaenia in a child <2yrs should prompt screening for SCID.

NB: It can be normal to have transient lymphopaenia or neutropaenia in isolation in young children following a viral illness. Incidental neutropaenia does not need repeat testing if there are no concerns about underlying immunodeficiency.

Immunoglobulins

IgG, IgM and IgA levels are useful to investigate children with recurrent ENT/airway infections.

It is also worth considering an HIV test if symptoms are consistent, but ensure you have a discussion with parents before testing.

If both FBC and immunoglobulins are normal in the setting of recurrent infections, it is perfectly acceptable to wait for 3 -6 months to see if the condition improves before referral.

 

Conclusions

  • Primary immunodeficiencies are rare but important, and ENT infections may be the presenting feature
  • The severity of infection and presence of opportunistic pathogens are a much stronger predictor than the frequency of infections
  • Basic tests such as FBC and Immunoglobulins should be performed in children prior to/pending referral if they are not severely unwell
  • Consider investigation and referral for primary immunodeficiency early in children with severe infections and failure to thrive, or those with family history

Further reading: https://www.entmasterclass.com/ENT_Journal_2019_Interactive.pdf page 9

Unlucky dip: Rational diagnostic testing for infections

Cite this article as:
Alasdair Munro. Unlucky dip: Rational diagnostic testing for infections, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20311

We see lots of children with suspected infections. Modern microbiology techniques have opened up a huge array of tests: some new and expensive, but we are often still reliant on good old fashion microscopy and culture.

With so many tests so readily available, we need to think hard about diagnostic stewardship. This means testing the right patients for the right reasons. We must be wary of over-diagnosis, preventing confusion, anxiety or unnecessary treatment, and making choices that represent good value. Many tests can be expensive and are often not necessary to make management decisions.

With that in mind, let’s take a look at some of the most common diagnostic tests for infections, and when we should (or shouldn’t!) be deploying them.

 

Urine dips and MC&S

Urinary tract infections (UTIs) are the most common serious bacterial infection in high-income countries. There are many departments where it is routine to set up every febrile child to get a “clean catch” urine as soon as they arrive. This is unwise, because it is VERY EASY to contaminate a urine sample from a clean catch. We have all seen children or parents putting their hands/feet/face in the bowl, and let’s be honest – if the child is sitting on the container, it’s basically directly under the body’s primary waste pipe.

Accepting a decent risk of false positives, we must aim to test only those who need the test. So when should we do it?

Fever without a source

This is the primary indication for doing a urine dip, and it is a sensible one. However, still not every child with fever and no source needs a urine dip. Older children can report urinary symptoms, and the absence of these makes a UTI much less likely. In addition, by school age, UTIs in males with normal renal tracts become very rare, so urine testing also becomes less useful.

As a framework, urine dips should be performed in the following groups with fever and no source (assuming they have no risk factors for UTIs and have no red flags):

Outside of these groups, use your clinical discretion to decide if the pre-test probability justifies the risk of a false positive – take into consideration the child’s age, gender, duration of symptoms, how unwell they appear, and obviously if they have known risk factors such as renal abnormalities or previous UTIs.

Symptoms of UTI

This seems obvious – but it’s worth stating that once urinary symptoms are present (increased frequency, dysuria) you should dip the urine to check for infection, and it may be worth sending samples for MC&S even if they are dip negative in this scenario (you can withhold treatment pending results).

It is worth taking more care for children with non-urinary symptoms, such as abdominal pain or vomiting (which is probably not predictive of UTI). Once at school age (particularly in boys) these symptoms are unlikely to be a symptom of a UTI so a higher threshold for testing should be adopted.

Some people say that all children with rigors require urine testing. Rigors are not evidenced to have any influence on the risk of UTI (or any significant risk of bacterial infection). If there is another source of the fever, urine dip is certainly not indicated on the basis of a rigor alone.

For more information on relative risks for UTIs in younger children, the supplementary materials to the UTI risk calculator study make an interesting read.

What about hot babies with bronchiolitis?

This becomes a slightly more controversial topic, and decisions require risk stratification based on the age of the child. For example, a febrile neonate with bronchiolitis might be lucky to escape the full shebang of a septic screen anyway – and a quick in/out catheter is unlikely to yield a false positive.

The literature on this topic is a bit confusing because of varying definitions of UTI and bronchiolitis (some studies including any child with RSV detected in their nose). The most recent meta-analysis with more stringent criteria for diagnosing UTI found a rate of concomitant UTI with bronchiolitis of 0.8% – low enough that testing is not advised.

Bottom line: if an infant has a fever and a clinical diagnosis of bronchiolitis, then urine dip is not necessary in most instances – however this should be given strong consideration in infants <60d and should be performed in neonates.

 

Blood culture

For a full myth busting exercise in blood cultures, please read the recent DFTB post on this topic. Some things to bear in mind if you’re thinking of taking a blood culture:

  • You are testing for bacteraemia. If you do not suspect bacteraemia, do not send a blood culture.
  • Blood cultures are extremely low yield in uncomplicated skin/soft tissue infection and pneumonia and should be avoided.
  • You do not need to wait for a fever to take a blood culture – it has no influence on the likelihood of obtaining a positive result. If you suspect bacteraemia, take the culture now.
  • If you are going to take a blood culture, aim to inoculate at least 1ml of blood per year of the child’s age. Less than this and you increase the risk of contamination and decrease the sensitivity.

 

Wound swab

When it comes to swabbing for microscopy, culture and sensitivity (MC&S), there is a golden rule*:

Do not swab any non-sterile site that you have not already clinically diagnosed as being infected.

A skin swab, throat swab, eye swab etc. will grow bacteria 100% of the time, because these places are non-sterile. They will often grow pathogens, because many pathogens are quite happy just being colonisers a lot of the time, and actually some of them are more often found as bystanders than as trouble-makers (Pseudomonas aeruginosa is a prime example – it is very rarely pathogenic in non-sterile sites). A positive swab does not diagnose infection.

YOU have to diagnose infection; a swab will just tell you what bacteria is causing it.

I would like to give a special shout out to gastrostomies at this point – just because they are “mucky” is not a good reason to swab. If you do swab it, you will find good old Pseudomonas (it loves playing in wet stuff). Skin and soft tissue infections are red, hot and inflamed +/- a bit of pus. Yellowish clearish greenish stuff is normally just serous fluid, so don’t worry about it and don’t swab it!

The same goes for babies sticky eyes. If you swab it, it will grow bacteria, but this tells you nothing about whether they are infected. Look for inflammation, if you find it then diagnose infection, treat empirically and send a swab if you are concerned about resistant bacteria.

*there are some exceptions to the golden rule, including burns and chronic wounds in immunosuppressed patients.

 

Throat swabs

Before starting – let’s remember that you cannot diagnose a bacterial throat infection with a swab alone. If you are considering swabbing a throat for MC&S, you must have already clinically diagnosed infection.

Guidelines vary quite widely in their recommendations to swab or not swab when diagnosing tonsillitis. It is worth considering that a throat swab has a reasonable sensitivity for group A Strep, if performed correctly. Sadly – we are all dreadful at performing throat swabs in children (who are usually very good at not wanting a throat swab), and often get a good dose of tongue and palate. Not good.

A further thing to consider is that approximately half of all throat swabs positive for group A Strep just indicate carriage – you’ve found the bug, but it’s just a bystander.

This means that if you swab and haven’t found the bacteria, it might be there but you’ve missed it, and if you have found it, there’s a 50% chance it’s not causing the illness anyway…

If it’s extremely important you detect the presence of group A Strep (for example in populations high risk for rheumatic fever) then I would definitely do a swab. If it’s not (and it usually is not), then make your decision to treat or not on clinical grounds alone.

Also, remember that in children <4yrs group A Strep tonsillitis is rare and almost never causes complications, so if you’re thinking of doing a throat swab for a child in this age group you need to have a very good reason.

 

Respiratory virus testing

Respiratory tract infections are extremely common in children. There is a fair amount of controversy and disagreement about the role for respiratory virus testing. It can have several roles:

  1. Local epidemiology. Some big/university hospitals like to keep track of what’s circulating, and will often have guidelines on who and when they want these tests performed.
  2. Cohorting. In bronchiolitis season, some hospitals might fill one bay with RSV and another with Rhinovirus. This is an evidence free zone.
  3. Fever without a source. Influenza in particular can cause horrible febrile illnesses in children without the classic respiratory prodrome. The idea is to detect the flu to prevent unnecessary antibiotics.

A group of children you should not test for respiratory viruses is anyone with cough and coryza. They do not need a test – they can be safely diagnosed clinically, and the presence or absence of a virus on testing does not change anything.

What about in lower respiratory tract infections? We can imagine that the discovery of a virus would prevent unnecessary antibiotics. However, respiratory viruses are common (even among non-hospitalised populations) and co-infection with bacteria is also common in viral infections. The presence of a virus does not preclude a bacterial infection. As such, their use in this context is contentious, and they do not appear to reduce antibiotic use.

For a thorough look at the principles and evidence of respiratory virus testing in children, I would recommend this excellent review paper.

 

Conclusions

  • Not every child with fever and no source needs a urine dip. Do it in infants, young girls and children with fever persisting >48hrs. Otherwise, use clinical discretion.
  • You probably don’t need to urine dip febrile children with clinical bronchiolitis.
  • Only do blood cultures if you suspect bacteraemia, and take lots of blood if you do.
  • Only send a swab for MC&S from a non-sterile site if you’ve already diagnosed infection.
  • Throat swabs are usually not useful. Only do them for high risk groups.
  • Respiratory virus testing is not useful in most circumstances. Only do it if you have a definite plan for how it will change your management.
  • When in doubt – if you can’t explain how the test will change your management, don’t do the test.

Parental Grief: Liz Crowe at DFTB18

Cite this article as:
Team DFTB. Parental Grief: Liz Crowe at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20208

Grief is complex and individual. It would be foolish to expect everyone to respond in the same way. Everyone is different. Just like there is no such thing as a normal sense of humour, there is also no such thing as normal grief.

Trauma, Teams and Tribes: Vic Brazil at DFTB18

Cite this article as:
Team DFTB. Trauma, Teams and Tribes: Vic Brazil at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20194

Victoria Brazil is a senior staff specialist at the Gold Coast University Hospital. She is a world renowned expert in the role of simulation in medical education.

Emerging infectious diseases : Mike Starr at DFTB18

Cite this article as:
Team DFTB. Emerging infectious diseases : Mike Starr at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20158

Mike Starr is not, despite what he tells you, the bassist for Alice in Chains. He is a general paediatrician and paediatric infectious diseases specialist at the Royal Children’s Hospital in Melbourne. He also happens to be a consultant in paediatric emergency medicine and plays a key role in the group that creates and collates the RCH clinical guidelines.

What is the evidence for high flow in bronchiolitis?

Cite this article as:
Tessa Davis. What is the evidence for high flow in bronchiolitis?, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20191

Over recent years, the use of high flow nasal cannula in the treatment of bronchiolitis in infants has increased. Whilst it used to be mainly used in PICU, it is now widely used in EDs and on the wards. The recent PARIS trial examined whether delaying starting high flow in infants with bronchiolitis led to a worse outcome (it didn’t). See Alasdair Munro’s excellent analysis here.

But is high flow actually useful in these patients, and if so when? Should we be using it in our Emergency Departments at all?

The PREDICT research group published an updated systematic review this month in the Journal of Paediatrics and Child Health.

High flowing controversy: A return ticket to PARIS

Cite this article as:
Alasdair Munro. High flowing controversy: A return ticket to PARIS, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20129

Today we are all familiar with high flow nasal cannula (HFNC) as respiratory support. We see it in our emergency departments, on our wards and in the PICU. People rave about it, and people rant about it. People talk about it so much that there must be some high-quality evidence about it, right?

There certainly wasn’t until last year, when the much-anticipated Paediatric Acute Respiratory Intervention Study (PARIS) was published in the prestigious New England Journal of Medicine (if you haven’t read about the trial, most of this will make little to no sense to you. Have a quick read of the DFTB run down here, or read the article itself in full here).

This RCT of HFNC in bronchiolitis has stirred up strong opinions in some, and a few pretty convincing and controversial myths have arisen from it over the past year.

This take on HFNC and the PARIS trial may be a little controversial, so buckle your seatbelts (and please comment if you disagree).

 

Myth 1 – PARIS was a badly conducted study

If you hate HFNC and are looking for a take-down of the PARIS trial, I’m afraid this isn’t it. PARIS was a fantastically well-conducted trail, with an impressive write up. It was performed to the highest standards of clinical research and it has been clearly analysed. Most importantly, it finally provided the first attempt at high-quality evidence about an intervention which has already become a standard of care, despite having no evidence to support its use. The authors should be congratulated.

If PARIS was so well conducted, where have these myths come from? Almost all stem from a misunderstanding of myth number 2…

 

Myth 2 – Paris was a trial of HFNC vs standard oxygen therapy

This is a confusing myth, as the publication of the study states this is the case in the methods section and throughout the article. If this is what the authors say it is, how can this be untrue?

It can be argued that PARIS cannot be a trial of HFNC vs standard oxygen therapy, for two reasons:

  • In both groups, 100% of escalated children get HFNC at some point (you cannot compare HFNC vs something else if everyone gets HFNC).
  • The primary outcome for the two arms, despite being called the same thing, are actually different. For both arms the outcomes are called “escalation of care”, but for the HFNC group this means escalation to PICU, whereas for the standard O2 group this means escalation to…you’ve got it – HFNC.

You don’t have to be a research wizard to realise that having two different outcomes for your groups is a no-no. It means you cannot compare outcomes between the two groups, as you are not comparing like with like. The HFNC group has apples, and the standard O2 therapy group has oranges.

 

So, what is PARIS a trial of?

PARIS is a trial of a strategy of immediate HFNC for hypoxaemia in bronchiolitis, vs a strategy of rescue HFNC for hypoxaemia when standard oxygen therapy fails.

If we are not comparing the original primary outcomes, what should we compare?

In PARIS we should compare treatment escalation to PICU, as this is an equal outcome for both arms.

If we assess the study this way, we can see quite clearly that when comparing these two strategies, there is no difference in outcome of escalation to PICU (9% of standard therapy, 12% of HFNC, p=0.08). In fact, when we discount the original primary outcome definition, there is no difference in any other outcome between the two groups (except that the HFNC group were sicker when they got escalated).

The PARIS trial was an amazing piece of clinical research, but the write up has asked a strange question of the data and described the groups in a confusing way.

 

Myth 3 – PARIS demonstrated immediate HFNC is superior

Based on a misunderstanding of the above, plus a frequently stated statistic from the trial that:

The NNT of HFNC vs standard oxygen therapy to prevent one episode of escalation of care is 9

Some people have taken home the message that a strategy of immediate HFNC is superior to standard oxygen, as it prevents treatment failure. However, as we have already discussed, treatment escalation for the standard oxygen therapy group consists of being started on HFNC. All this means then, is using HFNC is superior for preventing you from later putting the patient on HFNC. Obviously, this makes no sense at all.

If we are discounting this mind-bending interpretation, and (as above) we see that an immediate strategy of HFNC changed no outcomes compared to a strategy of rescue HFNC, how do we decide which is better?

This is simple: when faced with two interventions which provide equivalent outcomes, you always pick the one which is cheapest and least invasive. Here, a strategy of standard oxygen therapy with rescue HFNC is the winner.

 

Myth 4 – PARIS tells us HFNC is effective in bronchiolitis

Sadly, PARIS cannot tell us anything about HFNC in and of itself, because we did not compare HFNC to no HFNC. Everyone got HFNC in the end, so there is no true control group. Although we can try and guess what would have happened in the standard oxygen therapy arm if there was no HFNC available, we can’t say this for sure as it didn’t happen.

Many people certainly believe that HFNC works and prevents PICU admission (which it may well do), but unfortunately PARIS cannot answer that question for us, and as yet no trial has done so.

What PARIS CAN tell us about HFNC is that it is safe. There were very few adverse events, of which it is unlikely any were related to HFNC.

 

If PARIS cannot tell us if HFNC is effective, how do we find out?

We want to design a study to tell us if HFNC is useful in bronchiolitis. First, we need to decide what we actually want HFNC to do. We are not expecting it to save lives, as children rarely die of bronchiolitis, and if they look like they might die then we have an effective intervention, which is to send them to PICU and intubate them. We also don’t expect HFNC to get children home any quicker, as it doesn’t treat the underlying disease process.

So, what do we want from HFNC? I would argue it is to keep children out of PICU, and on the ward. This is cheaper, nicer and less invasive. A win all around.

So how could we tell if HFNC keeps children out of PICU? We need a trial which compares rescue HFNC (which PARIS has demonstrated is preferable to immediate HFNC, as there’s no difference between the two), to standard care – basically normal treatment of bronchiolitis without using HFNC at all (hard to remember a time when this was the norm…). You then see if there is any difference between how many children go to PICU, or how long they stay there. Let’s put our dream study in a PICO:

P – Infants with bronchiolitis with hypoxaemia

I – Standard care + HFNC as treatment escalation

C – Standard care (no HFNC)

O – Admission to PICU/ PICU LOS

If the above looks strange to you, it’s worth remembering that not too long ago there was no HFNC, and there is certainly no way that the same number of children we currently put on HFNC all used to go to PICU instead.

 

Why hasn’t this trial happened?

If that’s the dream trial, where is it?

Unfortunately, because medical devices are not regulated in the same way as drugs, there is no requirement to prove their efficacy or added value prior to them being approved for any indication. HFNC made its way into every paediatric unit faster than a bronchiolitic baby can sneeze, and quickly became the standard of care without ever having any evidence it was effective. The horse has now left the stable, and there is no way of convincing people to run a trial in which half of the children do not get HFNC.

In the absence of any evidence, the world has now been split into a group of “HFNC believers” and “HFNC non-believers”, neither of which have any evidence that they are right (but many getting confused about the PARIS trial and sometimes misusing it to confirm their opinions).

 

Myth 5 – But I’ve SEEN HFNC work

Some people may read all this, and think,

“Yes, but who cares. I use HFNC and I have seen it help children and stop them go to PICU. We don’t need a trial, because we can SEE it works”.

Sadly, we have learnt from previous experience that even when people believe they have seen interventions work, sometimes when the evidence is finally produced it turns out we were wrong all along. This is particularly a problem for medical devices, due to the way they are regulated. Just look at the recent NEJM study for IVC filters to prevent pulmonary emboli, or the mind blowing ORBITA trial last year for coronary stenting for chronic angina. This is why randomised controlled trials are so vital. They have demonstrated millions of pounds have been wasted on ineffective procedures and devices in these scenarios, even when health professionals truly believed that they had seen them work. Time has proven again and again that we will often just see what we want to see.

 

Conclusion

  • PARIS was a fantastically well conducted trial
  • PARIS was NOT a trial of HFNC vs standard care. It was a trial of immediate HFNC vs rescue HFNC, and no differences between the two were demonstrated.
  • When two interventions provide the same outcome, you always pick the cheapest and least invasive option, which in this case is rescue
  • PARIS cannot answer questions about HFNC efficacy, but did demonstrate its safety
  • To demonstrate efficacy, we require a trial of rescue HFNC vs standard care (without HFNC), with an outcome of PICU admission/LOS
  • Current problems with device regulation mean they can be instituted without evidence of efficacy, and following widespread implementation it becomes very difficult to test their effects. We owe our patients better than that.

Additional reading

A recent meta-analysis of HFNC in bronchiolitis, including (and heavily weighted by) the PARIS trial, was recently published in the Journal of Paediatrics and Child Health. You can read our analysis here.

Anticoagulation in children : Fiona Newall at DFTB18

Cite this article as:
Team DFTB. Anticoagulation in children : Fiona Newall at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20144

Professor Fiona Newall is Director of Nursing Research at the Royal Children’s Hospital in Melbourne and has a special interest in anticoagulation in children. If you think that the only patients in a hospital that need anticoagulation are old people then you should watch this talk from DFTB18.