Recognising Paediatric Sepsis

Author: Edward Snelson, Hannah Walsh / Editor: Nikki Abela / Code: IP3, NeoC2, RP6, SLO5 / Published: 06/01/2016 / Reviewed: 26/03/2024

Sepsis is a leading cause of morbidity and mortality in children worldwide,¹ and it is still the most common cause of avoidable deaths in children in the UK.²

The number of children attending Emergency Departments (EDs) in the UK is increasing, and febrile illness is one of the most common reasons for attendance.³ Most children who present with illness in the UK do not have sepsis and the number of children with serious bacterial infection are small. However, early recognition and treatment of sepsis in children is crucial as progression to organ failure and shock is often very rapid.

One of the greatest challenges for emergency medicine practitioners is to recognise paediatric sepsis, without over-investigation, over-treatment, or over-referral. Recognising a sick child is a skill, and it is not always easy.

The reality is that no one method of diagnosing sepsis in children has been shown to be sensitive or specific. Recognising sepsis in children is more like doing a jigsaw puzzle. Individual pieces of information are put together to create the bigger picture. We will look at some of the individual parts of the sepsis jigsaw puzzle by delving deeper into these 5 questions:

1. What is different about recognising sepsis in children?
2. What has been shown to be unhelpful in screening for sepsis in children?
3. What has been shown to be valid in my clinical environment?
4. What are the high-risk patient groups or situations I might encounter?
5. What do experienced clinicians believe to be of value?

We will also investigate some common myths that surround paediatric sepsis. The adult myths are covered here.

Myths surrounding paediatric sepsis include:

• The higher the temperature, the more severe the illness.
• A fever that comes down with antipyretics is reassuring.
• Blood tests such as FBC and CRP have a good sensitivity and specificity for sepsis.
• Current available decision rules such as the NICE febrile child traffic light system have a good sensitivity and specificity for sepsis.

 

Definitions

Let’s start by considering, what is sepsis?

Sepsis is difficult to define. Attempts to do so often refer to systemic inflammatory response syndrome (SIRS) in the presence of infection.

In 2005, the International Paediatric Sepsis Consensus Conference published definitions and criteria for paediatric sepsis, severe sepsis and septic shock.⁴

2005 International Paediatric Sepsis Consensus Conference 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.

Whilst Sepsis-3 has led to new adult definitions and criteria, to date there have been no formal revisions to the 2005 paediatric sepsis definitions.⁵ In 2020, the Surviving Sepsis Campaign proposed a definition for septic shock in children: ‘severe infection leading to cardiovascular dysfunction (including hypotension, need for treatment with a vasoactive medication, or impaired perfusion)’.^1,5

The reality is, that when clinicians are talking about sepsis, they usually mean an infection that is having a systemic effect and risks causing morbidity or mortality. This can be caused by any infection and is not restricted to bacterial pathogens.

Sepsis = life-threatening organ dysfunction caused by dysregulated host response to infection.

What is different about recognising sepsis in children?

Sepsis is sepsis, but what is different about recognising sepsis in children?

The first thing to consider when thinking about sepsis in children is that fever is one of the most common presentations to ED. Of these children who present with fever, only 10% have a serious bacterial infection and only 1% have sepsis.² Finding the child with sepsis can feel a bit like trying to find a needle in a haystack, and in the early stages of an infection they often all look the same.

The typical presentation of sepsis varies according to the age of the child.¹ The focus of infection is often apparent in the older child, whereas infants and neonates usually present with non-specific symptoms and signs.

Children have labile physiological responses to minor illnesses. Their immune systems are more aggressive in response to viral infection to compensate for the fact that they do not usually have ready-made antibodies for each new pathogen that they encounter, (neonates are an exception to this rule – see below). These factors mean that there can be large swings in temperature and heart rate with a simple viral upper respiratory tract infection. As a result, experienced clinicians tend to view abnormal physiological parameters as a prompt to look for other signs of sepsis, rather than being evidence of sepsis. When a child is feeling a bit better, they will usually show this by running off to play, whilst tucking into a snack, and this is often considered reassuring.

Recognising the sick child starts with doing the basics well, and we will discuss this in more detail later.

What has been shown to be unhelpful in screening for sepsis in children?

There is currently no point of care test (POCT) which helps to distinguish early sepsis from a simple viral infection in the acute setting.

A raised white cell count has poor sensitivity and specificity, and CRP can be normal despite significant infection. The more acute the infection, the less time the inflammatory markers have had to respond, leading to an increased risk that such tests could be falsely reassuring.⁶

Procalcitonin has been shown to have a more rapid response to infectious insult, and a much quicker decline following resolution. However, the reliability of the result depends on the age group tested, and whether you are trying to diagnose an invasive or non-invasive serious bacterial infection.⁷

Blood lactate can be measured by POCT, often by taking a blood gas. Hyperlactaemia has been shown to correlate with increased mortality in sepsis. However, there is significant variation in patient populations, lactate thresholds and mortality rates.⁸ The Surviving Sepsis Campaign International Guidelines advised that levels should “be interpreted as part of a more comprehensive assessment of clinical status and perfusion” and they were not able to issue a recommendation about using blood lactate to stratify children with suspected sepsis.⁵ We also know that the squeezing of a limb to obtain a capillary blood sample can result in an elevated lactate due to venous stasis and impaired local perfusion.⁹

Interleukin 6 and 10 may be able to predict serious infection in children with febrile neutropenia, and mid regional pro-adrenoedullin (MR pro-ADM) may be a promising biomarker to predict sepsis and septic shock.^10,11 However, research on these biomarkers is ongoing and not yet incorporated into POCT testing in EDs.

To put it simply, the grey area around POCT for paediatric sepsis is still grey. For any given test, we don’t simply want to know whether a child has a bacterial or viral infection, but what the clinical predictor of severity is. Remembering that it is both the severity of infection and the host immune response to that infection, that ultimately leads to sepsis.

What has been shown to be valid in an Emergency Department setting?

Front line clinicians would welcome a decision tool that identified and ruled out sepsis and serious bacterial infection with reasonable sensitivity and specificity.  Unfortunately, no such decision tool exists. The danger of looking at the issue from the endpoint is that it usually involves a very select population, rather than also considering the large numbers of children who do not have sepsis.

The UK-based NICE high-risk ‘Red Flag’ criteria has been shown to have a high sensitivity but limited specificity for detecting sepsis. A 2020 paper by Ruud Nijman showed that 41% of febrile children in PED present with warning signs of sepsis, and 50% of children aged 1-2 years triggered the NICE red high-risk criteria for tachycardia alone(12,13). Although the NICE high-risk criteria might ‘over-trigger’ for sepsis, the high sensitivity does mean that if there are no red flags, this could be reassuring when considering a safe discharge.

The Paediatric Sepsis Six tool provides guidance on how to treat sepsis once suspected, but the diagnostic criteria are so broad that a significant number of children are likely to be over-treated if it was used as an isolated screening tool.¹⁴

The Surviving Sepsis Campaign published comprehensive guidelines in 2020 for the management of sepsis in children.⁵ The key thing to note about these guidelines is that the authors focus on severe sepsis or septic shock. There is no guidance on the management of ‘pre-sepsis’ group of children. When it comes to finding the ‘needle in the haystack’ in a waiting room full of un-differentiated febrile tachycardic children, there are no national recommendations made for recognising sepsis in the early stages.

What are the high-risk patient groups or situations I might encounter?

Most of our guidelines are built around research in healthy children. Certain patient groups have different responses to illness compared to most healthy children and are at higher risk of serious illness.

In terms of risk stratification, it is important to consider whether the guidelines we have directly apply to the child in front of you, or if a different approach is needed.

Recognised risk factors for sepsis in children are¹:

• Age <3 months.
• Recent trauma, surgery, or invasive procedure
• Impaired immunity due to illness or medication
• Maternal infection during the perinatal period
• Indwelling line or catheter
• Any breech of skin integrity: cuts, burns, infection, blisters.
• Abnormalities of behaviour, circulation, or respiration.

As a rule, any child who is not expected to mount a normal immune response, or who may not easily show signs of being unwell, should be considered more carefully for possible sepsis. We will discuss some of these groups in more detail below:

Age <3 months: There is good reason why the NICE febrile child guidelines have special rules for children under 3 months old. This age group relies heavily on the immunoglobulins they have obtained in utero. Full immune maturity is not reached until adolescence and neonates are the most profoundly immunocompromised, with poor innate and adaptive immune responses.¹⁵ In addition, the younger the baby, the less likely they are to give clear signs of illness. More often the indicators are vague, such as reduced feeding or being sleepier. Clinicians should view any sign of illness or fever in the under 3 month old with a high index of suspicion.

Age <1 month: illness should be considered sepsis until proven otherwise. NICE guidelines classify babies <1 month old differently from 1-3 month old babies, with regards to the need for a full septic screen. Children <1 month can appear well and still have bacterial meningitis, and biomarkers perform the worst in this age group. Early onset sepsis, usually defined as <72 hours of age, results from vertical bacterial transmission from the mother during the perinatal period. Late onset sepsis, >72 hours of age, results from postnatal exposure to the infectious agent.¹⁶ There are certain risk factors associated with EOS and LOS that need to be asked about such as: prematurity, prolonged rupture of membranes, and maternal infection including GBS or HSV.

Children with complex medical needs often don’t have the typical signs and symptoms that health care professionals associate with sepsis. Children with neurological conditions are often hypothermic at baseline due to hypothalamic dysfunction. When they get an infection, their temperature goes up to the normal range, which may not trigger a sepsis pathway. Ex-premature infants may have chronic lung disease, making them more susceptible to respiratory infections. Parental concern and expertise in this group of children must play a central role in decision making. Parents of children with complex needs already spend a significant amount of time attending appointments, they do not want to be sat in your emergency department and will only be there because they feel something is wrong with their child.

Children with immunodeficiency have a much higher chance of serious infection and a reduced ability to respond to any infection. This group of children includes known immunodeficiency (acquired or congenital) as well as those caused by treatments such as chemotherapy or long-term steroids. It is important to note that the diagnosis of immunodeficiency may not yet have been made, so treat the child with a significant number of serious infections with caution.

Unvaccinated or incomplete vaccination status must be considered at higher risk of a serious infection which may progress to sepsis.

The child with chickenpox: Varicella infection is usually uncomplicated and, in many cases, causes minimal symptoms.  A small number of children develop sepsis.  If a child is unwell, fever lasts for more than 4 days or getting worse after a few days of chickenpox, sepsis is a real possibility.

What do experienced clinicians believe to be of value when making the decision to discharge or treat?

In addition to the risk factors above, recognising the sick child starts with doing the basics well and a lot of value is placed on simple observation, the course of the illness, and parental concern.

Observation:

• Temperature: may be high or low in sepsis. The presence of a temperature in a previously well child is usually just telling you that there is an infective process. The height of the temperature is a poor marker of severity. Simple viral infections can have temperatures up to 40°C in children, and infections such as meningococcal septicaemia can present with a normal temperature. A fever that comes down with antipyretics simply tells you that the antipyretics have worked and should not be considered a reassuring factor. What antipyretics do allow is an assessment of the child without the presence of a temperature, and most importantly the presence of variation.
• Behaviour: variation is key in the assessment of a child with an infection. Most children with a temperature will look lethargic, tachycardic, mottled and miserable. When the temperature is not there, the child can be running around and eating as normal. The key thing to observe, and to ask parents about, is play and behaviour. Most self-limiting illness will have natural variation in the day. Be aware of the child who has been lethargic and unwell throughout the whole day with no variation.
• Tachycardia: children with a temperature will be tachycardic regardless of the cause. The key is again found the presence of variation. Persistent tachycardia needs to be taken seriously and the underlying cause explored.
• Clinician instinct: ‘gut feeling’ needs to be used with caution. In a study febrile infant <90 days old, 21% of infants with a serious bacterial infection, were felt to have a <1% risk of doing so by the treating clinician.¹⁷ Gut feeling derived from pattern recognition, takes time to develop from multiple patient encounters and should form part of the jigsaw puzzle and not be taken in isolation.
• Parental concern: one common theme in cases of missed sepsis has been the presence of the parental concern that this illness was in some way different to any other illness that the child has had before. One key question to consider asking is: “does this seem like an infection they’ve had before?”

Safety-netting

Even when a diagnosis of sepsis appears unlikely at first presentation, information should be given to parents about the expected course of illness, how to recognise deterioration and when to seek a medical review. Observation over time, and robust safety-netting goes a long way towards a good outcome for the child and family.

References

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2. Emma Lim, Monica Parker. Let’s talk about sepsis. Paediatric sepsis podcasts [Internet] [Accessed Feb 28 2024].
3. Franklin C. Febrile illness associated with paediatric emergency department attendance. NIHR, Applied Research Collaboration. [Internet]. [Accessed Feb 27 2024].
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5. Weiss SL, Peters MJ, Alhazzani W, Agus MSD, Flori HR, Inwald DP, et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med. 2020 Feb;46(Suppl 1):10-67.
6. Segal I, Ehrlichman M, Urbach J, et al. Use of time from fever onset improves the diagnostic accuracy of C-reactive protein in identifying bacterial infections. Archives of Disease in Childhood 2014;99:974-978.
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11. Elke G, Bloos F, Wilson DC, et al. The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis – a secondary analysis of a large randomised controlled trial. Crit Care. 2018 Dec;22(1):79.
12. Nijman RG, Jorgensen R, et al. Management of Children With Fever at Risk for Pediatric Sepsis: A Prospective Study in Pediatric Emergency Care. Front Pediatr. 2020 Sep 17;8:548154.
13. Emma Lim. Sepsis 2020. Don’t Forget the Bubbles, 2021. Last updated 16/10/2023
14. Plunkett A, Tong J. Sepsis in children. BMJ. 2015 Jun 9;350(jun09 10):h3017–h3017.
15. Randolph AG, McCulloh RJ. Pediatric sepsis: Important considerations for diagnosing and managing severe infections in infants, children, and adolescents. Virulence. 2014 Jan;5(1):179–89.
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17. Kuppermann N, Dayan PS, Levine DA, Vitale M, et al. A Clinical Prediction Rule to Identify Febrile Infants 60 Days and Younger at Low Risk for Serious Bacterial Infections. JAMA Pediatr. 2019 Apr 1;173(4):342.