World Sepsis Day 2022 Improving outcomes for sepsis in children

The global magnitude of the impact of sepsis has been difficult to quantify, but recent data suggests that sepsis kills 11 million people each year, many of them children [1]. In the UK, 5 people die with sepsis every hour and 40% of all sepsis survivors are left with permanent, life-changing after effects [2].

The enormity of sepsis is undeniable. However, sepsis is also the number one preventable cause of death. That’s why World Sepsis Day, falling on the 13th September 2022, aims to raise awareness and provide education that can help reduce the worldwide burden of sepsis. Understanding the signs and symptoms, acting quickly, and securing a quick diagnosis and treatment can save lives.

The stages of sepsis
Sepsis proceeds through four stages: infection, onset of symptoms, rapid deterioration and finally, septic shock.

In the first stage of sepsis, a person gets an infection. From bacterial to viral, mild to severe, or undergoing treatment to undiagnosed, it is important to keep in mind that sepsis can develop from any type of infection [3].

Next, the body will mount an immune response to target and attack the infection. For reasons that are not entirely clear, sepsis occurs when this response gets out of control and targets the host as well as the infection. Sepsis manifests as a wide range of symptoms that come on suddenly and in any order.

The organisation behind WSD 2022 the Global Sepsis Alliance, has a helpful mnemonic to remember the symptoms to look out for:
Slurred speech or confusion
Extreme shivering or muscle pain
Passing no urine (in a day)
Severe breathlessness
It feels like you’re going to die
Skin mottled or discoloured

From this point, sepsis can develop very quickly. Untreated sepsis can worsen within just a few hours and vital organs can quickly become irreversibly damaged. Commonly the lungs and kidneys are damaged first, so difficulties breathing and passing urine are symptoms to look out for.

In the final stage, sepsis can develop into sepsis shock. Toxins from the infection build up and damage small blood vessels leading to fluid leakage into tissues [4]. An accompanying massive drop in blood pressure means the heart can’t pump enough blood to essential organs. Sepsis shock carries the highest risk of mortality and intensive care interventions are essential [4].

By recognising the symptoms of sepsis and quickly seeking medical attention to secure a rapid diagnosis, patients can be managed promptly, helping to avoid septic shock, multiple organ failure, and ultimately, death.

Symptoms of paediatric sepsis
Sepsis disproportionately affects vulnerable populations including new-borns and children. In fact, almost half of the 49 million cases of sepsis each year occur among children, leading to 2.9 million deaths [5]. Sadly, most of these could have been prevented with early diagnosis and appropriate clinical intervention [5].
The Global Sepsis Alliance advise that a child may have sepsis if he/she displays any of the following symptoms:

• Is breathing very fast
• Has a ‘fit’ or convulsion
• Looks mottled, bluish, or pale
• Has a rash that does not fade when you press it
• Is very lethargic or difficult to wake
• Feels abnormally cold to touch

Or if children under 5 are:

• Not feeding
• Vomiting repeatedly
• Have not passed urine for 12 hours

However, sepsis is particularly dangerous for children because their symptoms can be subtle, vary a great deal and may be difficult to identify [6]. Moreover, any delay to the diagnosis and treatment of sepsis represents a huge clinical risk. (Figure 1).

Figure 1: Sepsis progression in children (courtesy of Sylvester Gomes [7])

The complexity of paediatric sepsis
In a recent webinar, Dr Sylvester Gomes, Paediatric Emergency Consultant and Paediatric Sepsis Lead at Guy’s & St Thomas’ NHS Foundation Trust , highlighted the inconsistency of symptoms in children with several cases when patients were brought in to the Guy’s & St Thomas’ Hospital Paediatric emergency department [7].

In one example, a 3-month-old patient displayed atypical behaviour and had an elevated temperature, yet all other basic observations were within normal range. Despite only mild symptoms, the patient did in fact have sepsis. This complexity of symptoms can make diagnosis difficult.

Confounding diagnosis further is the lack of a single test for sepsis. A combination of laboratory tests are typically required to diagnose and ensure its effective treatment. During peak hours and out-of-hours periods, lengthy waits on laboratory results could delay the commencement of appropriate treatment.

Testing for sepsis
C-reactive protein (CRP) as a marker for inflammation is a common blood test used to support clinical decision-making, particularly as a proxy indicator for the presence or absence of bacterial infection. When combined with full blood count (FBC) with white blood cell differentiation, it can aid the distinction between bacterial and viral illnesses.

Both CRP and FBC are used commonly in conjunction in paediatric emergency care to assist with clinical decision-making. With their immune system not yet fully developed, new-borns are particularly susceptible to bacterial infection. As CRP does not cross the placenta, it presents an unbiased parameter to indicate infection in new-borns, with no interference from maternal blood. The test is normally performed in the laboratory, and once received, the time to result
can be up to 90 minutes. However, the time from needle to result can be considerably longer depending on patient and laboratory locations.

As discussed, it is crucial to exclude bacterial infection and sepsis quickly in emergency care in order to obtain a swift diagnosis for appropriate therapy. This in turn also supports antimicrobial stewardship, not only for cost savings by reducing antibiotic usage but also addressing antimicrobial resistance (AMR) challenges. For these reasons, the rapid availability of laboratory-quality combined CRP and FBC measurements within a few minutes at the point of
care (POC) can be beneficial, even lifesaving.

Finding clarity in complexity
In the case of Dr Gomes’s 3-month-old patient, rapid diagnosis and appropriate clinical management were made possible by POC CRP analysis using HORIBA’s Microsemi CRP haematology analyser (Figure 2).
Figure 2: HORIBA’s Microsemi CRP POC haematology analyser supports the rapid diagnosis of sepsis

This compact POC analyser can provide a laboratory-accurate, three-part differential full blood count combined with CRP to support the rapid near-patient diagnosis of patients with sepsis. Therefore, the doctors at Guy’s & St Thomas’s Hospital Paediatric emergency department were quickly able to determine that the white blood cell count (WBC), neutrophil count, and CRP were extremely high, indicating sepsis. This enabled prompt diagnosis and facilitated rapid, potentially life-saving decisions about treatment of the 3-month-old patient, despite the initial apparent mildness of symptoms.

Small quantities can support big decisions
Not only can new-borns and children present with confusing symptoms, it can also often be difficult to collect large blood samples for analysis from them. Therefore, taking blood from them in the least invasive way possible is highly beneficial.

Since the Microsemi CRP haematology analyser requires just 10μL of whole blood for a full blood count, and 18µL for FBC+CRP analysis, it is ideal for paediatric diagnostics using capillary blood from heel- or finger-prick samples.

Supporting sepsis diagnosis
As evidenced by Dr Gomes’s emergency paediatrics case study, the Microsemi CRP haematology analyser can enable fast diagnosis of sepsis at the POC to support quick clinical decision making. Also making it ideal for this environment is the fact that it is compact and user friendly, with minimal sample requirements. Furthermore, it is a unique analyser as it can deliver simultaneous measurements of FBC, including a 3-part differential, and C-reactive protein within just four minutes.

There is considerable pressure in emergency departments to deliver high level healthcare and maintain patient flow through the department while managing a busy and often, overcrowded environment. Because point of care tests (POCT) such as Microsemi CRP enables more rapid clinical decision making in the process of diagnosis, not only does this support the early detection of sepsis to save lives, but it also represents an approach that assists operational decision making and resource utilisation – ultimately, further improving patient care.
Discover more about the Microsemi CRP analyser from HORIBA here.
References:

1. World Health Organization (2020). Global report on the epidemiology and burden of
   sepsis: Current evidence, identifying gaps and future directions; Available from:
   https://www.who.int/publications/i/item/9789240010789
2. World Sepsis Day (2022). Sepsis Fact Sheet; Available from:
   https://www.worldsepsisday.org/toolkits.
3. NHS Inform (2020). Sepsis; Available from: https://www.nhsinform.scot/illnesses-and-conditions/blood-and-lymph/sepsis.
4. NHS Inform (2020). Septic shock; Available from:
   https://www.nhsinform.scot/illnesses-and-conditions/blood-and-lymph/septic-shock.
5. World Health Organization (2020). WHO calls for global action on sepsis – cause of 1 in 5 deaths worldwide; Available from: https://www.who.int/news/item/08-09-2020-who-calls-for-global-action-on-sepsis—cause-of-1-in-5-deaths-worldwide
6. Yale Medicine. Pediatric Sepsis: Symptoms, Diagnosis & Treatment; Available from:
   https://www.yalemedicine.org/conditions/sepsis-in-kids
7. Gomes, S (2022). The utility of point of care testing in a paediatric emergency department. HORIBA CONNECT webinar series; Available from:
   https://www.horiba.com/gbr/medical/support/webinars/horiba-connect-webinar-series-enabling-a-better-point-of-care-diagnosis/

For any enquiries, contact us at: enquiries.uk@horiba.com