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

Surviving Sepsis Campaign International Guidelines

Cite this article as:
Damian Roland. Surviving Sepsis Campaign International Guidelines, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.23460

The lens with which you view sepsis is dependent on the environment and emotion in which you associate the term. For a parent, this may be the spectrum from having never heard the term before “Your child is well enough to go home, we’ve ruled out sepsis and other serious conditions” to the anguish of being told, “I’m afraid your child died of sepsis“. This spectrum remains equally wide for health care professionals. A family doctor or general practitioner may never see a case of confirmed sepsis, and an emergency clinician can potentially go years between seeing a truly shocked child. An intensivist, however, may deal with the consequences on a weekly basis. Even in the last month, we have seen two papers from the same publishing group; one highlighting the global burden of sepsis and the other challenging the current hype surrounding its recognition and management.

Regardless of your viewpoint, the publication of the Surviving Sepsis campaign’s international guidance will have been of interest.

 

Weiss, S.L., Peters, M.J., Alhazzani, W. et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med 46, 10–67 (2020). https://doi.org/10.1007/s00134-019-05878-6

 

It is important to recognize two features of this publication which should carry an important health warning in its interpretation.

The first is that the authors are clear that they are focusing on severe sepsis or septic shock. While in adult practice definitions have changed, these have not been formalized or ratified for children:

 

“For the purposes of these guidelines, we define septic shock in children as severe infection leading to cardiovascular dysfunction (including hypotension, need for treatment with a vasoactive medication, or impaired perfusion) and “sepsis-associated organ dysfunction” in children as severe infection leading to cardiovascular and/or non-cardiovascular organ dysfunction.”

 

The authors clearly recognize that the absence of a clear definition of paediatric sepsis is challenging health care providers and organizations. The group has steered away from suggesting management options in the ‘pre-sepsis’ group i.e. those children with potential infections that may result in sepsis and have physiological instability but without organ dysfunction. They suggest that management practices for this group aren’t radically different, however:

 

Even though these guidelines are not intended to address the management of infection with or without SIRS when there is not associated acute organ dysfunction, we recognize that sepsis exists as a spectrum and some children without known acute organ dysfunction may still benefit from similar therapies as those with known organ dysfunction

 

The second is that this is a consensus document. It is neither a systematic review nor a clinical practice guideline (in a local hospital sense). It comprises the opinions of an expert group of clinicians (49 in fact) from a variety of international settings using the best available evidence. The publication is essentially a list of recommendations. This approach is valid in situations where evidence may be heterogeneous and that randomized controlled trials can not be performed for all possible permutations of clinical practice. As with all things in science, however robust the data is, it still needs interpreting and that interpretation is subject to all manner of explicit and implicit bias.

 

The panel supports that these guidelines should constitute a general scheme of “best practice,” but that translation to treatment algorithms or bundles and standards of care will need to account for variation in the availability of local healthcare resources.

 

Without becoming meta it’s important that this blog itself needs a health warning. It’s an interpretation of an interpretation of evidence.

So the big-ticket items

1. A child was defined as beyond 37 weeks gestation and up to 18 years old.

2. They apply to children with severe sepsis or septic shock as defined by the 2005 International Pediatric Sepsis Consensus Conference or inclusive of severe infection leading to life-threatening organ dysfunction.

2005 definition:

  • greater than or equal to two age-based systemic inflammatory response syndrome (SIRS) criteria
  • confirmed or suspected invasive infection, and cardiovascular dysfunction
  • acute respiratory distress syndrome (ARDS), or greater than or equal to two non-cardiovascular organ system dysfunctions

Septic shock was defined as the subset with cardiovascular dysfunction, which included hypotension, treatment with a vasoactive medication, or impaired perfusion.

3. Panel members were selected through recommendations from chairs and vice-chairs of the 12 worldwide member organizations. Each panel member was required to be a practicing healthcare professional with a focus on the acute and/or emergent care of critically ill children with septic shock or other sepsis-associated acute organ dysfunction. There was lay representation and the final membership was felt to be demographically diverse with regard to sex, race, and geography.

4. The panel was assisted by various methodological experts and split into six groups

  • recognition and management of infection
  • hemodynamics and resuscitation
  • ventilation
  • endocrine and metabolic therapies
  • adjunctive therapies
  • review research priorities in pediatric sepsis

5. A list of critical questions was developed in the PICO format (Population, Intervention, Control, and Outcome) which was then rigorously searched for by a specialist medical librarian and the resulting literature assessed according to GRADE criteria a well-recognized methodology for systemically presenting summaries of evidence.

6. Following discussion and debate recommendations would be made:

 

We classified recommendations as strong or weak using the language “We recommend…” or “We suggest…” respectively. We judged a strong recommendation in favor of an intervention to have desirable effects of adherence that will clearly outweigh the undesirable effects. We judged a weak recommendation in favor of an intervention to have desirable consequences of adherence that will probably outweigh the undesirable consequences, but confidence is diminished either because the quality of evidence was low or the benefits and risks were closely balanced.

 

The paper goes into considerable detail (which is why it is 55 pages long) into the rationale behind the recommendations. They are all summarised in the appendix (commencing page e102). It is beyond the scope of this blog to explore all the recommendations in detail, and it is important that health care providers read the paper itself. The following highlights some of the areas which may prompt debate or query.

 

‘Screening’ remains in

For those in emergency and acute care, this recommendation may have come as a surprise given a large amount of anecdotal feedback and experience suggesting that current screening mechanisms for the un-differentiated child are neither specific nor sensitive. It is worth nothing again the panel was looking at severe sepsis or shock and the evidence for ‘bundles’ of care i.e. targeted or mandated treatments once recognized is relatively robust. There is a further section on protocols/guidelines for treatment but it may have been useful to separate the afferent limb (recognition) from the efferent limb (response) in relation to collated evidence. This is important as the evidence for ‘bundles’ is cited under screening, with minimal evidence of screening approaches alone put forward (or to be fair to the panel perhaps of insufficient quality to make a judgment on).

Although subtle I think the panel recognized how important local buy-in is in relation to quality improvement. Of note, there is nothing on national guidance for recognizing sepsis. They also highlight how blindly integrating screening with any other scoring system may not be as beneficial as believed.

Ultimately no one particular screening system is recommended.

 

There is no target lactate

There appears to be a palpable sense of regret that the evidence didn’t support any particular threshold for lactate. Despite evidence of rising mortality with increasing lactate, the panel was not able to determine a specific level.

However, no RCTs have tested whether initial or serial measurement of blood lactate directly informs evaluation and/or management in children. Lactate levels should, therefore, be interpreted as a part of a more comprehensive assessment of clinical status and perfusion.

 

Take blood cultures but don’t delay treatment to obtain them

Appreciating this isn’t a particularly scientific response, but well, duh.

 

One hour time to treatment for those in shock but up to three hours without it. 

This is the potential game-changer from this body of work. While the evidence shows a temporal relationship between the administration of antibiotics and outcome in severe sepsis some pooled data demonstrated that it was unlikely the hour alone made the difference. Given the numerous papers showing a linear relationship between time to administration and outcome the ‘golden hour” was maintained. In the absence of shock, the panel felt, based on data showing a three-hour threshold effect, this would be a reasonable time point. This will be a welcome relief for those working in areas where there are associated penalties for not reaching the hour window and hopefully will remove some of the gaming associated with this target.

 

Broad spectrums antibiotics, but narrow when pathogens available

Little controversy here. The panel highlight that 48 hours should be the maximum time that is allowed to pass before re-evaluation in the absence of culture growth rather than a standard time to elapse.

If no pathogen is identified, we recommend narrowing or stopping empiric antimicrobial therapy according to clinical presentation, site of infection, host risk factors, and adequacy of clinical improvement in discussion with infectious disease and/or microbiological expert advice.

There are a number of recommendations on immunocompromised children and source control which appear pragmatic.

 

Bolus if intensive care available, if not then don’t unless documented hypotension

In units with access to intensive care, 40-60ml/kg bolus fluid (10-20ml/kg per bolus) over the first hour is recommended. With no intensive care, and in the absence of hypotension, then avoiding bolus and just commencing maintenance is recommended. It is not clear how long access to intensive care has to be to switch from fluid liberal to restrictive.

**Post-publication note (13/02/20): A more correct description of no intensive care would be “in health systems with no access to intensive care”. The guidance states, “For children with septic shock without signs of fluid overload in low-resource settings where advanced supportive and intensive care is not available, the panel recommends against bolus fluid administration,”. This question is raised in the comments section below as for units in without intensive care on site but it will resourced health systems then ‘access’ to intensive care should be assumed**

For purposes of this weak recommendation, hypotension can be defined as:

 

The panel suggests crystalloids, rather than albumin, and balanced/buffered crystalloids rather than 0.9% saline. They recommend against using starches or gelatin.

 

Use advanced haemodynamic variables, not bedside clinical signs in isolation

The evidence didn’t support a target mean arterial blood pressure but suggested avoiding using clinical signs to differentiate into cold and warm shock. No one monitoring approach was advised but included cardiac output, cardiac index, systemic vascular resistance, and central venous oxygen saturation.

 

Intensive care vasoactive and ventilation management is given but acknowledged as weak recommendations 

There is a list of suggestions regarding vasoactive infusion and ventilatory strategies that are very specific to intensive care management. While a number of recommendations are given (epinephrine rather than dopamine for septic shock for example) these are generally based on the panels summation of weak evidence.

There are further suggestions on corticosteroid management, nutrition, and blood products which will be of interest to those in intensive care and anaesthetic settings.

 

Summary

This is a very rich piece of work that is well structured and easy to read (even if you are not an expert on a particular field of practice). For most paediatricians there is unlikely to be an immediate change in practice but the softening of antibiotic time to delivery in the non-shocked child and emphasis of local review of sepsis incidence and performance will be welcome. How these filter into national guidance will be determined country by country but it is unlikely that radically different views can be drawn from the available evidence. What is still sorely needed is a working definition for the non-hypotensive child with sepsis (or an acknowledgment that perhaps this isn’t really a clinical entity…)

 

Bronchiolitis guidelines

Cite this article as:
Tessa Davis. Bronchiolitis guidelines, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.17023

Up to 48% of infants admitted to Australian hospitals with bronchiolitis receive treatment that has no evidence of benefit. Bronchiolitis remains the most common reason for admission to hospitals in Australia and New Zealand for infants, and yet our practice in treating these patients remains variable.  The PREDICT network have conducted a systematic review to produce Australia’s first bronchiolitis guideline based on a robust systematic review. These guidelines broadly agree with the American Academy of Pediatrics and NICE guidelines.

 

O’Brien S, Wilson S, Gill FJ, Cotterell E, Borland ML, Oakley E, Dalziel SR, Paediatric Research in Emergency Departments
International Collaborative (PREDICT) network, Australasia. The management of children with bronchiolitis in the Australasian hospital setting: development of a clinical practice guideline. J Paediatric Child Health, 2018. doi:10.1111/jpc.14104

 

The authors have produced 22 recommendations based on their robust evidence review. Let’s take a look at their key recommendations.

 

What investigations should we do?

  • Routine blood and urine testing is not recommended.
  • Viral swabs are not recommended (although the authors mention that further study needs to be done to determine the benefit of cohorting in wards i.e. when all babies with the same virus are put in the same bay together to avoid spread).
  • The authors note that in infants under 2 months old with bronchiolitis there is an increased risk of a concurrent UTI.

Therefore in babies under 2 months old with pyrexia, likely bronchiolitis but some clinical uncertainty – send a urine for m, c, & s

 

What treatments are effective?

  • Salbutamol – there is no benefit in using salbutamol in infants with bronchiolitis (and some evidence of adverse effects)
  • Nebulised adrenaline – no benefit
  • Nebulised hypertonic saline – there is weak evidence of a reduction in length of stay of 0.45 days. However when two studies were removed, both of which used a different discharge criteria than most hospitals, there was no benefit. This is not recommended routinely, although the authors suggest that it should be used only as part of an RCT
  • Glucocorticoids – no benefit
  • Antibiotics – not recommended

The risk of a secondary bacterial infection is very low, and there is potential harm from giving antibiotics

  • Oxygen – no evidence of benefit in infants with no hypoxia, and low level evidence that maintaining the sats over 91% with oxygen actually prolongs the length of stay. There are no reports of long-term adverse neurodevelopmental outcomes in infants with bronchiolitis, however there is also no data on the safety of targeting sats <92%

Commence oxygen therapy to maintain sats over 91%

  • Sats monitoring – there is moderate evidence suggesting that continuous sats monitoring increases the length of stay in stable infants
  • High flow – there is low to very-low level evidence of benefit with high flow
  • Chest physiotherapy – not recommended
  • Saline drops – routine saline drops are not recommended but a trial with feeds may help
  • Feeds – both NG and IV are acceptable routes for hydration

 

This is the first robust Australasian acute paediatric guideline on bronchiolitis. It provides clear guidance for the management of patients seen in Australasian EDs and general paediatric wards with bronchiolitis and is in line with US and UK recommendations. Our current practice often deviates from this evidence-based, and hopefully these guidelines will start the shift towards unifying evidence-based practice in managing infants with bronchiolitis.

 

 

References

American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics 2006; 118: 1774–93.

Ricci V, Delgado Nunes V, Murphy MS, Cunningham S; on behalf of the Guideline Development Group and Technical Team. Bronchiolitis in children: Summary of NICE guidance. BMJ 2015; 350: h2305.

Fasting guidelines

Cite this article as:
Andrew Tagg. Fasting guidelines, Don't Forget the Bubbles, 2018. Available at:
https://doi.org/10.31440/DFTB.14046

Some things in emergency medicine go together like peanut butter and chocolate – take monkey bars and supracondylar fractures, for example. Jack fell off the monkey bars after school and has an obviously deformed arm. With the help of some inhaled methoxyflurane and intranasal fentanyl, he has been placed in an above elbow backslab and is awaiting theatre. The orthopaedic team is on the way down to consent him and want to know when he last ate. Jack had emptied his lunch box by the middle of the morning but was still starving. So hungry was Jack, that his mother had gone to the local drive-through and picked up some fries. Time slows down to a crawl, the scream of “Nooooooooooooooooooo” on your lips as he crams a fistful of the salty delights into his face…

Paracetamol poisoning in children

Cite this article as:
Andrew Tagg. Paracetamol poisoning in children, Don't Forget the Bubbles, 2015. Available at:
https://doi.org/10.31440/DFTB.7530

Earlier this month the MJA published the latest consensus guidelines for the management of paracetamol (acetominophen) poisoning.  Whilst there is very little that is new for those of us used to dealing with this problem in adults, the document now makes some recommendations regarding the management of paracetamol overdose in children.