Searching for sepsis

Cite this article as:
Anna Peters. Searching for sepsis, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.31160

The child with “fever” is one of the most common paediatric presentations to the emergency department. Most of these children are managed conservatively with parental reassurance and discharged home with a safety net identifying red flags. However, failing to identify those with “sepsis” has devastating consequences. How often do we get it wrong or worry about getting it wrong? We’d all love an evidence-based clear cut path for flagging and managing febrile children at risk of sepsis. Currently the approach in the UK is predicated on the NICE SEPSIS (NG 51) screening system which has anecdotally performed poorly with concerns it is poorly specific (i.e lots of false positives). Nijman and colleagues aimed to objectively assess the impact of the NICE Sepsis screening approach in children.

Nijman RG, Jorgensen R, Levin M, Herberg J and Maconochie IK. Management of Children With Fever at Risk for Paediatric Sepsis: A Prospective Study in Paediatric Emergency Care. Frontiers in Pediatric Care 2020; 8:548154. doi: 10.3389/fped.2020.548154

The lead authors looked at the various warning signs of serious infections in febrile children presenting to PED. Their aim was to then determine these children’s risk of having sepsis and to evaluate their subsequent management.

Who did they study?

Over 5000 children (5156 to be exact) aged 1 month to 16 years old presenting with fever over a period of 9 months from June 2014–March 2015 in a single PED at St Mary’s Hospital, UK were analysed.  Febrile children with no warning signs of sepsis were then excluded from the final cohort. The second largest group excluded from the final cohort was children with a complex medical history (n=119).  The decision to exclude this particular cohort is important given that ‘complex medical patients’ are more likely to have sepsis. The authors make the valid point that this group has features very different from the intended cohort, such as having different management plans in the context of fever. After these exclusions, plus a few further exclusions (lack of consent, lack of complete data or excluded because the child didn’t have any warning signs) the final cohort was of 1551 children. 

What did they do?

They first looked at the numbers of febrile children with tachycardia and tachypnea by using APLS and NICE (the National Institute of Healthcare Excellence) thresholds.  Subsequently, they looked at the numbers of febrile children fulfilling sepsis criteria by using well-known sepsis screening tools (NICE traffic light guidelines, SIRS, qSOFA, Sepsis Trust UK trigger criteria).

All the data for this study (vital signs, clinical signs and symptoms, tests, working diagnosis, need for hospital admission, timeliness of interventions) were collected electronically, having been recorded prospectively for all febrile children.

What did they look for? 

As a primary outcome the study determined:

  1. The incidence of febrile children who present with warning signs of sepsis 
  2. How often these children fulfilled paediatric sepsis criteria 
  3. How frequent invasive bacterial infections (IBIs) occurred in this population 
  4. How frequent PICU admissions occurred in this population.

Secondary outcomes included the compliance of clinicians with the paediatric sepsis 6 care bundle (PS6), what clinical interventions were and were not used from this care bundle and the timeliness of the interventions that were undertaken

What did they find? 

Almost a third of children aged 1 month to 16 years who presented to the PED had fever (28% to be exact).

41% of these febrile children had one or more warning signs (our study population).

The incidence of IBI was 0.39%. Of these children, only 0.3% required PICU admission.

This meant that using the sepsis guideline recommendations, 256 children would need to be treated to catch one IBI. Another way of saying this is the number needed to treat was 256. NNT for any serious outcome was 141.

How did the sepsis guidelines fare?

The thresholds for tachycardia and tachypnoea yielded a high false positive rate.

Adding sepsis criteria to predict the presence of a serious bacterial infection (SBI), IBI or PICU admission was also unreliable, with a lot of false positives.

Lactate levels were not significantly associated with the decision to give IV fluid bolus or presence of SBI, IBI or PICU admission. There WAS, however, a significant association between lactate levels and hospital admission.

Looking at the Paediatric Sepsis 6 Interventions, although many children triggered, two-thirds (65%) of the children with PS6 warning signs had none of PS6 interventions. And when it came to the ‘golden hour? Only a third (36%) of children with IBI or PICU admission received all PS6 interventions in the ‘golden hour with only 39 children (2%) receiving a fluid bolus

What does this all mean?

It is important to note that this study was only conducted in one single PED and in a time period that was before the NICE sepsis guidelines were formally implemented into practice.  The data was collected for this study via an electronic interface. While large amounts of data can be collected rapidly there can sometimes be gaps, either due to extraction issues or brevity on the behalf of clinicians that don’t give a comprehensive picture. Data were also only taken from initial triage and not from any clinical deterioration in the ED.  Given that acuity changes over time, especially in children with fever, this may have missed subsequent clinical change although is a pragmatic approach given the way that sepsis screening tools are applied in nearly all Emergency Departments. 

Numbers needed to treat were exceptionally high. Despite the allure of a protocol-based screening and management pathway,  the benefits of catching true sepsis early must be weighed against the possible unwanted effects of overtreating or overdiagnosing mostly well children in a potentially resource-stretched PED. The study really does highlight the difficulties we face when screening for a septic child in a generally well cohort, the ‘needle in a haystack’.

Essentially, what this study shows us is that serious infections are rare and most children who are categorised as ‘at risk of sepsis’ can in fact be managed conservatively with little intervention other than observation. It is clear that our current guidelines have very poor specificity; and while they tell us to investigate and treat lots of children, a lot of the time we as clinicians choose to rely on our clinical judgement and essentially ‘do nothing’. Observation and good clear red flagging must not be underestimated.  Instead of continuing to research more and better early predictors of sepsis, such as point of care biomarkers, perhaps we should be looking at this from another angle. The focus of the lens can also be flipped; we also need more research on how it can be safe NOT to do anything too. 

We’ll end with some thoughts from the authors

The Infections in Children in the Emergency Department (ICED) study is a single centre, prospective observational study. The study describes unique and carefully curated clinical data of febrile children with warning signs of sepsis, from a period prior to the implementation of the NICE sepsis guidelines. 

Our results confirm what many paediatricians dealing with acutely unwell febrile children already suspected: that many febrile children have warning signs of sepsis, but that the large majority have non-life threatening infections. 

Our findings will hopefully contribute to ongoing discussions about the use of sepsis screening tools in paediatric emergency medicine. Our study makes it clear that current tools lead to a high number of false positive cases, and their usefulness in routine clinical care in paediatric emergency medicine should be questioned. Escalation to senior decision makers of all children with warning signs of sepsis should be aspired, but is seldomly feasible in clinical practice and with unproven impact on reducing missed cases and optimising clinical care for the total cohort of febrile children. 

Although all children with serious infections would have been detected by the various sepsis tools, it is now evident that we need better tools to more selectively identify children at the highest risk of sepsis. Future studies should explore the utility of machine learning as well as the potential of combining clinical signs and symptoms with point of care biomarkers.

Ruud Nijman

DFTB/ADC Journal Club – The Rules

Cite this article as:
Andrew Tagg. DFTB/ADC Journal Club – The Rules, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.16905

We all know that it can take up to 17 years for knowledge to go from benchside to bedside. One of the things we pride ourselves on at DFTB is our ability to cut down this knowledge translation window. We do this in the form of our monthly Bubble Wrap, critical appraisals of key literature and engagement with key thought leaders via Twitter.

Now we are going to try something new – a monthly twitter journal club as a collaboration with Archives of Disease in Childhood.

Can Point-of-Care CRP testing identify children with serious infection?

Cite this article as:
Tessa Davis. Can Point-of-Care CRP testing identify children with serious infection?, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.15806

As paediatric emergency clinicians, a large part of our job is identifying the child with a serious infection. The utility of blood tests in helping with diagnosis in this group of children is debatable. Could point-of-care CRP testing help identify children with serious infection?

Ears looking at you, kid

Cite this article as:
Andrew Tagg. Ears looking at you, kid, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.10936

Earache is a leading cause of grumpiness in children.  A recent paper in the New England Journal of Medicine has suggested that a 10 day course of antibiotics is more effective than a 5 day course in treating acute otitis media and, as such, should be considered in infants under 2 years with otitis media. But is this right?

Can you see what I see?

Cite this article as:
Andrew Tagg. Can you see what I see?, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.10302

When it comes to imaging children we are all about the ALARA (as low as reasonably achievable) approach. One of the best ways to do this is not to use radiation at all. Unfortunately not all of us can be Casey Parker, and so we might need some help with our ultrasound skills.

An apple juice a day?

Cite this article as:
Andrew Tagg. An apple juice a day?, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.8616

Pippi, aged 3, has been a little bit unwell of later.  Most of her family have had viral gastroenteritis and she has now got it too.  She’s been vomiting for the last 24 hours and is struggling to keep anything down.  Her parents are concerned that she is becoming dehydrated so they bring her into the ED.  She gets a sublingual ondansetron wafer and tries some oral rehydration solution.  “Yeuch!” she says as she spits it out, “That tastes disgusting.” You wonder if there is anything else you can try.

Today we are going to take a look at the following paper:-

What population did they look at?

Children aged 6 to 60 months that presented to the study a centre who met these inclusion criteria

  • 3 or more episodes of diarrhoea or vomiting in the preceding 24 hours
  • less than 96 hours of symptoms
  • weighed more than 8kg
  • had minimal dehydration

The exclusion criteria essentially rule out children who have a number of pre-morbid conditions or who may have more serious underlying pathology.

What was the intervention they tried?

The intervention group had half-strength apple juice.

What did they compare this too?

This was compared to a standard apple-flavoured, sucralose sweetened paediatric electrolyte solution.

What were their outcome measures?

The primary outcome was treatment failure. This was a composite measure defined as any of the following occurring in the 7 days following enrolment.

  • hospitalization
  • intravenous hydration
  • subsequent unscheduled physician encounter for the same illness
  • protracted illness
  • physician request to crossover groups
  • 3% or more weight loss or a worsening of Clinical Dehydration Score

It’s easy to read the abstract of a trial and just agree with the conclusion but we should be more sceptical of what we read.  Using a validated tool such as that from the Best Evidence in Emergency Medicine group can help with critical appraisal.

Let’s go through the quality appraisal checklist for a randomized, control trial.

Does the study population focus on the Emergency Department?

Yes.  The children all presented to a tertiary care paediatric hospital in Ontario, Canada.

Were the patients adequately randomized?

Children were randomized using computer-generated block allocation.

Was the randomisation process concealed?

Block randomisation took place with allocation in identical, opaque, numbered envelopes that were kept in a locked cupboard.

Were the patients analyzed in the groups to which they were assigned?

Yes.  An intention-to-treat analysis was performed.

Were the study patients recruited consecutively?

No. Patients were recruited 12 hours a day, 6 days a week, between the months of October and April of 2010 through to 2015. Interestingly, over the course of the study 3668 children were eligible but this was whittled down to just 647 after exclusions. 1297 patients were not enrolled as study personnel were not available.

Were the patients in both groups similar with respect to prognostic factors?

Yes, they were.

Were all participants unaware of group allocation?

No. Whilst initial enrollment was concealed the parents were aware of which group they child belonged to.  Once they were discharged from hospital the group that received half-strength apple juice were encouraged to give their children their drink of choice (other than balanced electrolyte solutions) whereas the standard group were to continue with usual rehydration solutions.

It is also impossible to disguise the taste of the liquid they were given.

Were all groups treated equally except for the intervention?

Yes, they were.

Was follow-up complete?

Follow-up data was available for an impressive 644/647 patients. The majority of this was by telephone.

Were all patient-important outcomes considered?

Absolutely. Nobody wants their child to have to return to the ED for IV rehydration.

Was the treatment effect large enough and precise enough to be clinically significant?

This study was designed as a non-inferiority trial and powered appropriately.

So we can see that the trial appears to hold up to scrutiny with regard to its method and analysis.  What we really want to know is whether diluted apple juice is as good as the usual rehydration solution. The bottom line, according the study authors, is this:-

Among children with mild gastroenteritis and minimal dehydration, initial oral hydration with dilute apple juice followed by their preferred fluids, compared with electrolyte maintenance solution, resulted in fewer treatment failures.

In order to reduce the need for intravenous rehydration the team focussed both on stopping the vomiting (with sublingual ondansetron) and replacing potential losses. Interestingly, 68% of the children in the study had no clinical evidence of dehydration equating to a Clinical Dehydration Score of zero but still received oral rehydration solution or diluted apple juice.  Here lies the catch in this study.  Many of the patients we see in Australian paeds EDs are minimally or mildly dehydrated and thus the results of this study can probably be extrapolated to them.  ORS was designed for children with Cholera who had significant dehydration, ongoing fluid loss, and pathology that affected their ability to absorb enteral fluid (remember those glucose-sodium co-transporters from med school?).  ORS is safe and effective in pretty much any degree of dehydration whereas this study only demonstrates diluted juice is useful in the mildest of cases.  So by all means start handing out the dilute juice to many of the patients you see but don’t chuck out the Gastrolyte just yet!

References

Freedman SB, Willan AR, Boutis K, Schuh S. Effect of Dilute Apple Juice and Preferred Fluids vs Electrolyte Maintenance Solution on Treatment Failure Among Children With Mild Gastroenteritis: A Randomized Clinical Trial. JAMA. Published online April 30, 2016. doi:10.1001/jama.2016.5352 Full text here

Jauregui J, Nelson D, Choo E, Stearns B, Levine AC, Liebmann O, et al. (2014) External Validation and Comparison of Three Pediatric Clinical Dehydration Scales. PLoS ONE 9(5): e95739. doi:10.1371/journal.pone.0095739 Full text here