While 3 month old Hamish’s parents were enjoying their favourite Scottish drink, they suddenly looked over and noticed that Hamish had gone blue in the face. They were terrified, but fortunately it resolved quickly and Hamish is back to his normal, bonny self. They’ve rushed him to see you in hospital. Could the answer have been right in front of them?
Sarah McNab, Director of General Paediatrics at the Royal Children’s Hospital in Melbourne, takes us through an interactive case of a child with an apparent, life-threatening event. At least that is what we used to call it. Is it a BRUE or is it something more serious? Should parents buy a home apnoea monitor? The guidelines say ‘No’ but Sarah offers an alternative view.
The American Academy of Pediatrics updated its guidelines in 2016 for babies with unexplained episodes that you might know as ALTEs.
An ALTE, or acute life-threatening event was first described in 1986. The definition is:
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 broad definition 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 entirely well. ALTEs, by definition, were subjective, making their management of them tricky. Often these babies had overnight admissions to hospital for observation.
A systematic review in 2013, looked at 1400 ALTEs (Tieder et al). However, the authors found that there was such a wide variation in the interpretation of the definition that no conclusions could be drawn.
In short, the term ALTE doesn’t really help anyone.
This guideline suggests a new term, BRUE – a brief, resolved, unexplained event.
What is a BRUE?
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
If your patient has had a BRUE, then the guideline suggests assessing them to see if they would qualify as being low risk.
Which patients are at low risk?
- Age >60 days
- Gestational age ≥32 weeks and post-conceptional age ≥45 weeks
- Occurrence of only 1 BRUE (no prior BRUE ever and not occurring in clusters)
- Duration of BRUE <1 minute
- No cardiopulmonary resuscitation by trained medical provider required
- No concerning historical features
- No concerning physical examination findings
What should I do with a low risk BRUE patient?
You can see the entire flowchart and all the evidence base here. But you don’t need to be doing bloods, LPs, echos, x-rays, or EEGs. You should educate the parents about BRUEs and implement a discharge/follow-up plan, so they are happy, and make sure to point them in the direction of CPR training resources.
You should take a history that includes assessing social risk factors for NAI. Getting an ECG and observing on a pulse ox monitor for 1-4 hours is reasonable but not mandatory. You may also consider doing a PCR for pertussis if the history suggests exposure is likely, particularly if mum did not get her antenatal booster immunisation.
The authors make a weak recommendation that low-risk infants need not be admitted overnight solely for cardiorespiratory monitoring; they make a moderate recommendation that clinicians should engage in shared decision-making. So you don’t have to admit, but you do have to make sure the parents are comfortable with your plan.
It is also worth noting that when the authors said “discharge” what they meant was follow up by a paediatrician for repeat history and exam within 24hrs.
CAUTION: This guideline does not tell us to ignore babies with ALTEs (or BRUEs). It does tell us to take a very careful history and examination and reassures us that in low risk babies we can rely on those assessments.
(We should ensure that the person conducting the history/examination has sufficient clinical experience to make a decision that there is no underlying cause.)
Investigations are useful only when specifically indicated from the clinical assessment and prolonged observation may be offered for either clinician or parental reassurance.
But do we actually follow the guidelines?
This paper in Pediatrics by the team at the Children’s Hospital of Pittsburgh and the University of Pittsburgh tried to answer that question.
Ramgopal SR, Noorbakhsh KA, Callaway CQ, Wilson PM, Pitetti RD. Changes in the management of children with brief unresolved unexplained events (BRUEs). Pediatrics.
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, a database with all information from presentations and admissions in hospitals across 26 states in the USA.
Patients were included if they were under one year old and were diagnosed with either an ALTE or BRUE between 2015 and 2017.
Patients were excluded if they 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 period.
This was an appropriate choice of patient group, and using a control cohort was useful. Sample size estimates were not stated explicitly but were alluded to.
The limitation here is the reliance on coding. However, the authors could not determine if the diagnosis was correct or if the patient could be classified as a low-risk BRUE. These assessments required a history and examination.
9,501 patients were used for the cohort analysis (5508 patients 0-60 days old, and 3993 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.
There were 1.4 million patients 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 years.
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 three 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 approach was published.
The authors were clear on what was measured and how it was measured. The follow-up was for 30 days, so it should have picked up most complications. However, the measurements were reliable and valid, and the primary data was adequately described.
What were the author’s conclusions?
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. Fewer patients were 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 data justify the conclusions.
Will this paper change my practice?
Changing practice is challenging; changing a definition is a little easier.
This study is an excellent 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 a beneficial clinical impact. We see an overall decline in admission and investigations with no apparent harm (returns don’t increase).
There are a few caveats that are important to consider, though. First, 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 more significant 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. 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 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 under 60 days old. This wasn’t the intention of the initial guidance. While this group’s re-admission rates didn’t increase, this study wasn’t powered (or designed) to determine whether the re-admission changes would be significant. The fact that it appears safer is a statistical construct, not a clinical one. This means a type II error is possible (there is 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 rationalise your investigation and management pathways without causing additional harm. The challenge for those outside the United States is whether national organisations 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)