Silvija Petuchauskaitė^{1, 2}, Virginija Žilinskaitė^{1, 3}

¹Vilnius University, Faculty of Medicine, Vilnius, Lithuania

²Vilnius University, Faculty of Medicine, Clinic of Children ‘s Diseases – Institute of Clinical Medicine, Vilnius, Lithuania

³Vilnius university Hospital Santaros Klinikos, Pediatric Emergency – Intensive care and Anaesthesiology CenterPediatric Intensive Care Unit, Vilnius, Lithuania

Abstract

Backgroundand aim. Despite medical advances and the rapid development of diagnostic and treatment methods, the problem of paediatric sepsis is still relevant. The problem of sepsis also remains relevant because of changing etiologic factors related to the introduction of new vaccines, the global antimicrobial resistance, and the rise of new resistant strains of microorganisms. The relevance of the sepsis problem is also related to the complicated early suspicion of sepsis, diagnosis, and emergency response. It is medically proven that the outcome of sepsis directly depends on early diagnosis and the proper treatment in the first hour. review aim is to analyse the sepsis problem in children and present the early diagnosis and treatment guidelines.

Materials and methods. The most recent scientific literature was reviewed on paediatric sepsis prevalence, early diagnosis and treatment.

Results. Sepsis is still one of the most common causes of death in children today. The definition of sepsis is still evolving, and it is difficult to accurately understand the epidemiologic situation and the changing aetiology of sepsis in children. The most important factor that can determine a good outcome is the early treatment of sepsis.

Conclusion. Sepsis in children remains one of the greatest burdens on healthcare systems worldwide. Much research is needed to better understand the problem of sepsis. A good outcome of the disease can only be expected if sepsis in children is diagnosed and treated in a timely manner.

Keywords: pediatric sepsis, sepsis early diagnostic, sepsis early management, paediatric sepsis outcomes.

Full article

https://doi.org/10.53453/ms.2023.5.10

The problem of sepsis in children, the relevance of diagnosis and

treatment

Silvija Petuchauskaitė

1,2

, Virginija Žilinskaitė

1,3

1

Vilnius University, Faculty of Medicine, Vilnius, Lithuania

2

Vilnius University, Faculty of Medicine, Clinic of Children ‘s Diseases – Institute of Clinical Medicine, Vilnius,

Lithuania

3

Vilnius university Hospital Santaros Klinikos, Pediatric Emergency – Intensive care and Anaesthesiology Center-

Pediatric Intensive Care Unit, Vilnius, Lithuania

Abstract

Background and aim. Despite medical advances and the rapid development of diagnostic and treatment methods,

the problem of paediatric sepsis is still relevant. The problem of sepsis also remains relevant because of changing

etiologic factors related to the introduction of new vaccines, the global antimicrobial resistance, and the rise of

new resistant strains of microorganisms. The relevance of the sepsis problem is also related to the complicated

early suspicion of sepsis, diagnosis, and emergency response. It is medically proven that the outcome of sepsis

directly depends on early diagnosis and the proper treatment in the first hour. review aim is to analyse the sepsis

problem in children and present the early diagnosis and treatment guidelines.

Materials and methods. The most recent scientific literature was reviewed on paediatric sepsis prevalence, early

diagnosis and treatment.

Results. Sepsis is still one of the most common causes of death in children today. The definition of sepsis is still

evolving, and it is difficult to accurately understand the epidemiologic situation and the changing aetiology of

sepsis in children. The most important factor that can determine a good outcome is the early treatment of sepsis.

Conclusion. Sepsis in children remains one of the greatest burdens on healthcare systems worldwide. Much

research is needed to better understand the problem of sepsis. A good outcome of the disease can only be expected

if sepsis in children is diagnosed and treated in a timely manner.

Keywords: pediatric sepsis, sepsis early diagnostic, sepsis early management, paediatric sepsis outcomes.

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Medical Sciences 2023 Vol. 11 (4), p. 85-92, https://doi.org/10.53453/ms.2023.5.10

85

1. Introduction

Sepsis is one of the main causes that cause the

highest cost of re-hospitalization in all hospitals

in the world, and it requires the most economical

expenses in healthcare system. Therefore, the

problem of sepsis is one of the primary priority

to the World Health Organization (1). Sepsis in

children can be caused by any infection of the

body, but the majority of the identified

pathogens are bacteria (2) Having reviewed the

early clinical diagnosis of sepsis in children, it is

clear that early recognition of sepsis in children

is crucial and that it is important to know the

criteria and signs of the systemic inflammatory

syndrome that give rise to suspicion of sepsis

(3,4). Currently, guidelines for the diagnosis and

treatment of sepsis are still not widely applied,

although only their timely application can

improve the outcome of the disease (5,6). Sepsis

in children is still a major health care systems

problem despite advances in medical science.

More research is needed to better understand

sepsis in children and to provide even more

accurate diagnostic and treatment guidelines.

Early diagnosis and treatment remain a major

challenge, and the high mortality rate means that

the problem of sepsis is still relevant today.

2. Materials and methods

This literature review reflects on paediatric

sepsis, which remains a major problem due its

high mortality in children, and analyses the

guidelines for early management.

3. Results - the problem of sepsis

3.1. Epidemiology

Because of the changing definition of sepsis and

its difficult diagnosis, it is difficult to determine

the exact number of annual cases – it is estimated

that sepsis is affects approximately 47 to 50

million people worldwide each year (7).

Worldwide, sepsis causes an average of 19 % of

deaths in the population, most of which are

children younger than 5 years (8). In the

paediatric group, the mortality rate after sepsis

diagnosis is 25 %, and worldwide, on average,

about 8 million children die from sepsis each

year (9–12). Among children, most deaths are

neonates, infants, and children with chronic

diseases. Sepsis mortality in children has

declined not only because of improved

diagnostics, but also because of vaccination,

antibacterial treatment and better availability of

health services (13). The spread of vaccines has

not only reduced the number of sepsis cases in

older children, but also changed the aetiology of

sepsis in children.

3.2. Aetiology

Sepsis can be caused by practically any infection

in the human body - the most commonly

identified agents are bacteria and viruses, but

fungi and parasites can also occur (2). In

studying the aetiology of sepsis in children it was

found that in nearly 43 % of cases of paediatric

sepsis, the causative agents were not

identified (14). In the study of neonates and

infants up to 3 months of age, the most common

disease-causing bacteria were found to be

Staphylococcus aureus, group B Streptococcus,

Escherichia coli and Listeria, and sometimes the

Herpes simplex virus may be the cause of the

disease (2,15,16). Sepsis in older children is

usually caused by Haemophilus influenzae,

Neisseria meningitidis, Klebsiella spp. and

Streptococcus pneumoniae (2,15,17). In children

with febrile neutropenia, the most common

microorganisms are Staphylococcus aureus,

Streptococcus pneumoniae, Pseudomonas

aureus, Escherichia coli, Klebsiella (18). The

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most common cause of hospital-acquired sepsis

is coagulase-negative staphylococci, gramme-

negative bacteria (18). The most commonly

identified microorganisms causing community-

acquired sepsis are bacteria - N. meningitidis, S.

pneumoniae (19–21). Overall, the aetiology of

sepsis in children is very diverse and variable,

influenced by the age of the sick child, his

comorbidities or existing chronic diseases, as

well as vaccinations and excessive use of

antibacterial drugs.

3.3. The definition of paediatric sepsis.

In recent decades, the concept of sepsis

undergone major changes, mainly due to the

increasing understanding of pathophysiologic

processes that occur in the human body during

infection. In 2002 the first sepsis guidelines for

children were published, highlighting the

differences between paediatric and neonatal

sepsis and sepsis in adults. In 2005, the

International Paediatric Sepsis Conference

published definitions in paediatric systemic

inflammatory response syndrome, sepsis, septic

shock, and multiple organ dysfunction

syndrome (3,4). In 2020 guideline on sepsis and

septic shock in children were published, but to

date the question remain whether the definition

of sepsis in adults can be applied to children, and

therefore the formal definition of paediatric

sepsis has yet to be updated (2,16). In 2005, the

International Paediatric Sepsis Definition

Consensus Conference defined sepsis as a

systemic inflammatory response syndrome,

caused by an existing, confirmed or suspected

infection based on clinical, laboratory, or

imaging studies (4). The definitions currently

used are not sufficient for early diagnosis; they

are more relevant for research related in

paediatric sepsis. But much more important than

the definition is to know and understand what the

basic criteria for early diagnosis of sepsis are so

that paediatricians can recognise this life-

threatening condition as soon as possible.

3.4. The importance and possibilities of

diagnosis on paediatric sepsis

Sepsis in children is one of the most common

causes of death despite scientific advances in

treatment, but only timely recognition can lead

to a good outcome of the disease (18). Sepsis

mortality in children ranges from 4 to 50 % in

various literature sources - most of these deaths

occur within the first 48 to 72 hours of treatment,

so early diagnosis and treatment are paramount

to good outcomes (22). Early recognition of

sepsis in children is difficult because the disease

begins non-specifically and progresses

variably (5). Unlike adults, children have large

physiologic reserved, so the child's condition can

be compensated for at the onset of illness, is

clinically silent, and later decompensates very

rapidly. Therefore, early diagnosis of sepsis in

children poses challenges (1).

3.5. Clinical diagnosis

Often, sepsis in children resembles a simple viral

infection in the early phase of the disease,

making it very difficult for physicians to

diagnose the disease in time (23). The clinical

manifestation of sepsis in children can vary

widely- slowly progressive or sudden and

dramatic (3). A thorough examination of a sick

child should include recording of vital signs and

evaluation of clinical signs important for

suspicion of sepsis. If sepsis is at least minimally

suspected, the patient should be constantly

monitored (3,24). According to the criteria of

systemic inflammatory response syndrome,

body temperature, heart rate, state of

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consciousness, oxygen saturation level, arterial

blood pressure, and capillary refill time must be

measured. It is also important to collect data on

the patient's diuresis during the last 18

hours (25). Paediatric sepsis "red flags"

described in the medical literature to raise

suspicion of sepsis are altered body

temperature (> 38.3°C or < 36°C), tachycardia,

tachypnoea, changes in heart rate or capillary

refill time, hyperglycaemia, purpura or pathecia

below the nipple line, macular erythema

anywhere on the body (3,16,26). After

reviewing the early clinical diagnosis of sepsis

in children, it is clear that early sepsis

recognition in children is crucial. It is important

to know the systemic inflammatory response

syndrome criteria and signs that help to suspect

sepsis. The authors emphasize the triad of

clinical symptoms of sepsis that many patients

present with: fever, tachycardia, and

vasodilatation with altered consciousness or

capillary refill time greater than 2

seconds (17,27).

3.6. Laboratory diagnosis

For a long time, complete blood count test was

important for the early laboratory diagnosis of

sepsis. However, leukocyte and neutrophil

counts have low sensitivity or specificity for

bacterial infection to determine the absolute

neutrophil count can still be used to identify the

bacterial infection in younger infants under 60

days of age with fever (6). Although these tests

can confirm the suspicion of bacterial infection

in febrile infants, they have little prognostic

value in the diagnosis of paediatric sepsis (6).

Acute phase C-reactive protein is the most

common and oldest known sepsis marker (28).

For early diagnosis of sepsis, it is important that

CRB does not begins to rise until after 12 hours

and does not rise significantly until 20-72 hours

after the onset of inflammation (29). Therefore,

a procalcitonin test is currently recommended

for the early diagnosis of sepsis, based of

scientific evidence (6,16,29,30). C-reactive

protein and procalcitonin not routine tests, the

main indications for their performance are

suspected severe bacterial infection or sepsis in

febrile infants and young children when the

source of infection is unclear - these markers

have a high prognostic value in the diagnosis of

sepsis (18,31). Blood culture is considered the

gold standard sepsis diagnosis in children, but

it has low specificity and sensitivity for

pathogen identification (30). The result of

blood culture is an extraordinary value for the

choice of optimal antimicrobial therapy and the

duration of its administration (6,23,30).

Currently, early laboratory diagnosis of sepsis

in children is increasingly supporter by

polymerase chain reaction (PCR). A blood

culture usually is not informative. In neonatal

population, PCR and blood cultures have been

observed during the same period of the disease,

the PCR test was positive in a higher percentage

of patients, so this study shows the importance

of PCR in early diagnosis of paediatric sepsis

nowadays (32). Thus, the early diagnosis of

sepsis in children is based on clinical symptoms

suggestive of sepsis and the totality of

laboratory markers - this is also shown by the

systemic inflammatory response syndrome

criteria. Clinical symptoms alone are not

sufficient to confirm the diagnosis of sepsis, but

the main laboratory markers of sepsis (C-

reactive protein, procalcitonin, etc.) are

performed only in the presence of a clinical

manifestation of sepsis in children and the

acquire the diagnostic value.

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3.7. Early first-hour sepsis treatment in

children

Research shows that early treatment of sepsis in

children can significantly reduce

mortality (6,33). Guidelines for early treatment

of sepsis in children are not yet conclusive, but

their use leads to better outcomes in the disease

(5,34,35). It is known that the main goals of

treatment in the first hour of sepsis in children

are to ensure and manage airway, optimize

oxygenation and ventilation, restore and

maintain perfusion to organs as needed, ensure

early empiric antibiotic therapy (3,17). The goal

of the early treatment is to correct the child's vital

signs and normalize the state of consciousness,

shorten capillary refill time (<3 s), and ensure

greater diuresis than 1 ml/kg/hour (3,5,16). In

the first hour, begin treatment of sepsis in

children with high-flow oxygen therapy via

nasal cannulas or 100% oxygen delivery via

mask, however, oxygen saturation should not

exceed 97 % to avoid adverse events,

hyperoxygenation, and free radical

formation (3,18). At the same time, an

intravenous catheter or an intraosseous needle

should be inserted within 5 minutes (3,36). After

puncturing a vein or bone marrow, it is important

to do a blood culture and perform the main

laboratory tests: common blood count, c-reactive

protein and procalcitonin, coagulation

indicators, blood gas test, calcium and other

electrolytes, glucose and lactate tests (3).

Empiric antibiotic therapy should be initiated at

the maximum recommended dose no later than 1

hour after clinical suspicion of sepsis (3,5,36).

Antibiotic therapy should not be delayed

because of obtaining a blood culture, but in any

case, an attempt must be made to obtain a blood

culture before the first antibiotic administration,

because delayed antibiotic therapy is one of the

risk factors for organ dysfunction or the

progression of the disease (5,37). Patients with

suspected sepsis should be monitored

continuously - body temperature taken at least

every 30 minutes, arterial blood pressure and

oxygen saturation should be measured every 15

as well as other vital signs (3). Fluid therapy

should be administered to the patient within the

first 5-10 minutes into a vein or bone with rapid

crystalloid agents in boluses of 10-20 ml/kg for

children (up to 1000 ml) and 10 ml/kg in

neonates depending on the patient's weight; if

necessary, the bolus may be repeated up to

60 ml/kg/hour (3,5). If the above first-hour

management steps do not produce the expected

results, a paediatric intensivist should be

consulted immediately for advice and the

administration of inotropic medications should

also be considered. Only if the paediatric sepsis

treatment guidelines are applied within the first

hour (establishment of a blood culture, broad-

spectrum antibacterial treatment, and

administration of fluids as part of infusion

therapy), the good outcome of disease can be

expected to prevent the patient's death or long-

term health consequences.

4. Conclusion

The problem of sepsis in children is still relevant

due to its high incidence and mortality rate in

children worldwide. Data on sepsis prevalence

data are imprecise because there is no unified

definition of sepsis in children. The aetiology of

sepsis in children is very diverse and variable.

Early diagnosis of sepsis in children is based on

clinical symptoms, which are usually

nonspecific to sepsis, and on a number of

laboratory markers, such as C-reactive protein or

procalcitonin. These markers are only valuable

for diagnosis when the clinical manifestations

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are characteristic of sepsis in children. Treatment

protocols for the first hour of suspected sepsis

help manage sepsis for a better outcomeThe

sepsis problem is multifactorial, but it is obvious

that the most important thing for a good outcome

of paediatric sepsis is the timely application of

early diagnosis and treatment guidelines.

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