History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors include immunodeficiency, comorbidities, and younger age (especially neonates). Risk factors in neonates include perinatal risk factors for infection (e.g., maternal fever, prolonged rupture of membranes, maternal carriage of group B streptococci, chorioamnionitis, fetal distress, poor 5-minute Apgar score), and health-care-associated factors (e.g., indwelling vascular catheters).[47][48]
fever or low body temperature
Fever is defined as elevated body temperature above the normal daily variation (i.e., above 37.5°C [99.5°F]).[82] For the diagnosis of sepsis, consensus criteria state that the core temperature must exceed 38.5°C (101°F).[3] However, a lower threshold is required in neonates and neutropenic patients, where sepsis should be considered if the core temperature is >38°C (>100°F).[83]
Occasionally, children with sepsis will present with an abnormally low core temperature (<36°C [<97°F]).[3] Although an abnormal temperature is common (high or low), it should not be used as the sole predictor of sepsis and should not be used to rule sepsis either in or out. In addition, rapid transitions from high to low temperature should not be erroneously interpreted as a sign of improvement.
tachypnoea
Defining tachypnoea and tachycardia in children in various age groups has always been a challenge. There are no uniform definitions of tachycardia and tachypnoea and they overlap between various ages. A raised respiratory rate (usually 2 standard deviations above the age-standardised norm) is a common feature of sepsis.[3][84] Apnoea, grunting, or nasal flaring may be observed in neonates and infants.[83] Clinical diagnosis must precede any formal classification or parameters in the emergency setting.
tachycardia
Tachycardia (usually 2 standard deviations above the age-standardised normal heart rate) is a common feature of sepsis.[3][84]
It is particularly suggestive of sepsis if the tachycardia does not resolve after resolution of fever (e.g., after receiving antipyretics). However, tachycardia may be the result of confounding factors (e.g., pain, discomfort, or a cardiac lesion).
bradycardia (neonates and infants)
Infants (<1 year) and neonates with sepsis may present with bradycardia (heart rate <10th percentile for age).[3] Clinical diagnosis must precede any formal classification or parameters in the emergency setting.
altered mental state or behaviour
In sepsis or septic shock, decreased cerebral oxygen delivery may result in altered consciousness, manifesting as a spectrum of decreased consciousness (e.g., drowsiness, obtundation, delirium, lethargy, floppiness).[3] Altered mental state or behaviour in neonates and young infants may manifest as irritability, non-responsiveness to social cues, poor handling, or apnoeas.
A weak high-pitched or continuous cry in neonates and infants is a high risk criterion for suspected sepsis.[50]
Often improves transiently with initial fluid resuscitation.
decreased peripheral perfusion
Most infants and young children with septic shock acquired in the community typically present with vasoconstrictive ('cold') shock (cold peripheries, prolonged capillary refill time, increased core-toe temperature gap, and weak pulses).[3]
change in usual pattern of activity or feeding in a neonate
The clinical signs and symptoms of sepsis in neonates are often vague and nonspecific.
Any change in the normal trends of vital signs and activities for a neonatal patient should alert the clinician to possible sepsis.
Typical features include temperature instability, new onset feed intolerance, abdominal distension, apnoeas, and bradycardic episodes.[83]
dry nappies/decreased urine output
Decreased urine output is common in acutely ill children and often reflects a degree of dehydration (due to decreased intake, excessive fluid losses, or both). This is not a specific finding in sepsis, but is commonly present, especially if there has been a prodromal viral illness prior to the onset of sepsis.
mottling of the skin, ashen appearance, cyanosis
Signs of circulatory insufficiency
low oxygen saturation
Sign of circulatory insufficiency
uncommon
vasoplegia
Clinicians need a high index of suspicion to detect older children and children with healthcare-associated septic shock who may present with vasodilatory ('warm') shock (vasoplegia with 'flash' capillary refill, warm peripheries, and bounding pulses).
non-blanching purpuric rash
Purpura fulminans is a widespread non-blanching purpuric rash classically seen in meningococcaemia, but it may also be associated with sepsis from Streptococcus pneumoniae.
Other diagnostic factors
uncommon
hypotension
Children and young people often maintain normal blood pressure, even in late stages of shock; therefore, normal blood pressure should not exclude sepsis. Hypotension is often a terminal sign in septic shock.
Hypotension in children is determined by age-specific standards. In children aged ≥12 years, systolic blood pressure <90 mmHg or a reduction in systolic blood pressure >40 mmHg from baseline are high-risk criteria for sepsis.[50]
specific focal signs and symptoms reflecting underlying pathology
Certain symptoms and signs may point the clinician to the source of infection. Younger children and neonates tend to present with no focus of infection, whereas older children may demonstrate a clinical focus (e.g., bronchopneumonia or meningitis).
Risk factors
strong
immunodeficiency
A wide range of causes of immunodeficiency have been described in children, including malignancy, immunosuppressive medications (e.g., corticosteroids, chemotherapy and conditioning for haematologic stem cell transplant), primary immunodeficiencies (e.g., severe combined immunodeficiency), acquired immunodeficiencies (e.g., HIV), and malnutrition.[41] The natural history and degree of susceptibility to sepsis will vary among these conditions, but all are at increased risk of sepsis.
Clinicians should be alerted to the possibility of an underlying immunodeficiency if patients present with serious, prolonged, unusual, or recurrent infections.
The location and type of infection can also provide clues towards the category of immunodeficiency. For example, recurrent infection with encapsulated organisms such as Neisseria species is suggestive of a complement deficiency; whereas failure to clear live vaccines or an early-onset severe fungal infection (such as Candida) are features of severe combined immunodeficiency.
comorbidities
The incidence of sepsis is higher in children with comorbidities (defined as any medical condition that can be reasonably expected to last at least 12 months unless death intervenes, and to involve either several different organ systems or one organ system severely enough to require specialty paediatric care) compared with otherwise-well children.[42]
In a large epidemiological study of approximately 10,000 cases of 'severe sepsis', approximately half had an underlying comorbidity,[14] and mortality rates were significantly higher in this group of children.
The association of sepsis with comorbidities is intuitive to understand, as many comorbidities will have a direct or indirect effect on host defence (e.g., neutropenia in cancer patients receiving chemotherapy, poor cough and protective respiratory reflexes in a child with severe neuromuscular disease).
It is noteworthy that the rates of chronic conditions in the paediatric populations in the developed world are rising year on year.[43]
younger age (especially neonates)
In general, the risk of sepsis in children decreases with increasing age. Data from 1995 showed that the incidence of 'severe sepsis' in infants (age <1 year) was about 10 times greater than the incidence in children of all ages combined (5.16 cases per 1000 population per year versus 0.56 cases per 1000 population per year). The high rate of sepsis in infants was mainly due to the high incidence of neonatal 'severe sepsis' cases.[14]
The higher incidence of sepsis in this age group is due to multiple factors, including immaturity of cellular and humoral immunity, and poor integrity of natural barriers such as mucosal surfaces.[45]
The increased risk of sepsis in neonates is exacerbated by prematurity. Compared with term infants, all preterm infants are at greater risk of sepsis, including nosocomial sepsis.[45] The risk increases with the degree of prematurity,[46] with very low birth weight posing a significant risk.[15]
perinatal risk factors for infection (neonates)
The following risk factors related to birth are associated with an increased risk of neonatal sepsis:[47][48] maternal factors such as maternal fever, prolonged rupture of membranes (>18 hours), maternal carriage of group B streptococci, and chorioamnionitis; fetal factors include fetal distress and poor 5-minute Apgar score (i.e., ≤6).
healthcare-associated factors (neonates)
Preterm infants in the intensive care unit are exposed to greater risk of late onset sepsis through various healthcare-associated interventions, many of which breach natural barriers (e.g., indwelling vascular catheters). The most significant of these are parenteral nutrition, mechanical ventilation, chronic central venous access, and use of vascular catheters (arterial, central venous, or peripheral).[49]
recent surgery or other invasive procedures
Risk of sepsis is high in children following surgery or other invasive procedures.[50]
breached skin integrity
Risk of sepsis is higher in children with any breach of skin integrity (e.g., cuts, burns, blisters, or skin infection).[50]
weak
male sex
The incidence of sepsis is significantly higher in boys than girls. This effect is seen most robustly in very young children, particularly in children aged under 1 year (infants), where the incidence of 'severe sepsis' in male infants was 1.3 times higher than in female infants.[14]
The reasons for this sex difference are not clear, but the phenomenon is consistent with previous studies demonstrating worse broader clinical outcomes for male sex in premature infants.[44]
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