It’s time for pediatrics to screen sepsis ‘screening’

Despite the success of vaccinations against organisms such as Haemophilus influenza type B and Neisseria meningitidis,1 mortality and morbidity related to these invasive infections remain high. One in five deaths among children was associated with infection before the pandemic.2 This includes newborns who are particularly vulnerable due to an immature immune system and in whom, worldwide, infection rates have increased over the past 20 years.3 The sequelae of infection can lead to long-lasting morbidity, through limb amputation, chronic respiratory disease and organ damage, as well as death. As such, an aggressive approach is often taken to manage infection in children, particularly in the preschool period, including a low threshold for many investigations and empiric antibiotics.

The practice of investigating febrile children has become so commonplace that its own terminology, “screening for sepsis”, has developed into the pediatric vernacular. The origin of “sepsis screening” (which incorporates blood inflammatory markers, blood culture, urine, and cerebrospinal fluid for microscopy, culture, and sensitivity) is unclear. The first it appears in the literature concerns newborns considered to be at high risk of sepsis.4

Over the past decade, another shorthand description, “sepsis screening,” has emerged from the process by which patients were quickly identified as being at risk for sepsis. Sepsis screening is a concept in both adult and pediatric practice in which physiological measurements are recorded and if certain thresholds are reached, the patient is considered to need urgent clinical examination. The development of sepsis red flags, including the National Institute for Health and Care Excellence,5 provided thresholds that health care providers can use. The provision of sepsis screening has been identified as a national priority through the creation of financial targets for their implementation.6

However, in our view, “sepsis screening” and “sepsis screening” are inaccurate and unnecessary terms. Neither is, and could ever be, a test for “sepsis”. Pediatric sepsis is inherently difficult to define, however, the most recent definition of sepsis for adults is “a life-threatening organ dysfunction caused by a dysregulated host response to infection.”7 The critical element of sepsis is that the life-threatening nature of the disease is due to the body’s response to the infection, not the infection itself. Bacteremia is a serious illness; however, it is not synonymous with sepsis. Although it is common to have sepsis and bacteremia, it is also possible to have sepsis without bacteremia in children (indeed, the majority of cases of sepsis may have no positive culture8), and vice versa. The combination of a culture of blood, urine, and cerebrospinal fluid does not diagnose sepsis, but merely confirms or rules out the presence of a bacterial infection at these sites.

Moreover, “screening”, by definition, requires that the patient be asymptomatic. However, many patients undergoing ‘screening for sepsis’ are symptomatic, for example children presenting with fever and coryza. This makes the term “screening” imprecise and problematic for a number of reasons. This creates confusion and misconceptions about the important differences between bacteremia and sepsis, both among healthcare professionals and families of children. Many families are now familiar with the term sepsis as a result of widespread awareness campaigns and tragic cases where the seriousness of a child’s clinical condition has not been properly recognized. This awareness is useful for families to be able to overcome an often difficult hierarchical gradient if a professional dismisses their concerns,9 but may cause inappropriate reassurance if the screening “test” is found to be negative or unnecessary anxiety when poorly specific vital signs point to the presence of sepsis when it is not.ten

The term sepsis screening triggers a set of observations or investigations to be carried out, often without first thinking about their purpose. The results of a sepsis screening can lead to harm due to the risk of false positive tests from blood cultures11 and urine cultures12 resulting in a longer stay for the patient, additional investigations often painful for the child13 and the risk of iatrogenic harm.14

Campbell and his colleagues15 have highlighted when considering whether to perform a test, one should:

1. Decide which diagnosis they are investigating

2. Determine the pre-test probability of the condition in question

3. Decide if they are looking to confirm or rule out a diagnosis

4. Decide what they will do if the test is positive or negative, and most importantly

5. Consider whether performing the test could harm the patient.

Outside of the neonatal period when the decision to treat invasive infections can be made on the basis of risk factors alone, application of Campbell’s rules would suggest that “screening for sepsis” is not useful for diagnosing sepsis. sepsis, which is a clinical syndrome. In order to help us detect febrile children who may have or show early signs of sepsis, we need to develop a system to identify children who are at higher risk for sepsis. This could either be by identifying validated risk factors earlier (e.g. very young age and comorbidities) as suggested by the Kaiser Permanente calculator,16 or undertake interventions in children with clear signs of sepsis, or who are at high enough risk to warrant further investigation or intervention. It should be noted that the current NICE approach has not been validated to be effective in children17 and sepsis risk thresholds based on presentation criteria have not yet been established.

Ultimately, for children with potential sepsis, there is no screening, as all patients come to us with signs or symptoms. We must then make clinical judgments based on the individual patient scenario and perform targeted testing that provides high value care. This approach is supported by the sepsis guidelines recently published by the Academic of Medical Royal Colleges18 which moved from screening to a clinical decision support framework with the aim of balancing risk (based on a set of clinical characteristics) and response (urgency of clinical examination and intervention). This recognition has also been incorporated into the new Surviving Sepsis guidelines for children, which have expanded the window for initiating antimicrobials to less than three hours in the absence of shock to enable more judicious use of investigation and treatment.19

In our opinion, it is time to remove the term “sepsis screening” from the pediatric lexicon. Instead, we need to focus on identifying infected patients at high risk for sepsis and providing targeted, patient-centered management based on individual risk profiles.