Investigations
1st investigations to order
FBC with differential
Test
Abnormal WBC count (i.e., above or below normal range for age or >10% immature white cells) is one of the core diagnostic criteria for systemic inflammatory response syndrome.[3] However, elevated or depressed WBC count is not specific for the diagnosis of sepsis.
Thrombocytopenia (i.e., platelet count <80,000/microlitre or a decrease by 50% from highest value in past 3 days) in the context of sepsis may suggest the onset of disseminated intravascular coagulation, if associated with coagulopathy.
Result
variable
serum glucose
Test
Threshold definitions for hypoglycaemia: moderate hypoglycaemia is blood glucose level of 2.0 to 3.0 mmol/L [36 to 45 mg/dL]; severe hypoglycaemia is blood glucose level <2.0 mmol/L [<36 mg/dL].[85]
Hyperglycaemia is common as part of the stress response to sepsis. It can also occur as a side effect of corticosteroid treatment. Hypoglycaemia may also occur as a result of depleted glycogen stores.
Result
variable
blood culture
Test
Many infants and young children with sepsis have a primary bacteraemia, so blood culture is an important investigation.[9][60][61]
Should be undertaken as soon as possible when sepsis is suspected, and ideally before administration of antibiotics.
The sensitivity of blood culture is proportional to the volume of blood taken. When using a neonatal aerobic culture bottle in neonates, a minimum of 1 mL of blood from venipuncture or freshly inserted vascular catheter (arterial or venous) is likely to be adequate to diagnose bacteraemia.[9]
When standard aerobic culture bottles are used, a minimum of 4 mL of blood is required for a valid negative culture at 48 hours. Two sets of cultures are sometimes recommended to encourage clinicians to take the culture from an indwelling line (e.g., central line) and a peripheral site.
Blood culture results should be reviewed every 12 to 24 hours; most positive results will be detectable within 48 hours, and many will be positive within 24 hours.[62]
Result
positive blood culture may confirm bacteraemia and provide information on pathogen, including sensitivities to antibiotics
urinalysis
Test
Urinalysis should be considered in older children with symptoms suggestive of urinary tract infection.
Result
may be positive for nitrites and/or leukocytes in urinary tract infection
urine culture
Test
Urine sample for nitrites, microscopy, Gram stain, and culture should be considered as an initial test in all neonates with sepsis (although in the first week of life, a positive urine culture may simply reflect a severe bacteraemia).
May not be possible until after fluid resuscitation.
Result
positive urine culture may confirm bacterial urinary tract infection and provide information on pathogen including sensitivities to antibiotics
blood gases
Test
Although children rarely have arterial blood gases taken in the accident and emergency department, it is often possible to obtain clinically useful information from capillary or venous blood gases.
Large base deficit is a key marker of sepsis and may be the first marker to give a clue to the severity of illness.
Hypercapnia or hypoxaemia are supportive of a diagnosis of respiratory dysfunction.[3]
Hypoxaemia: P/F ratio (PaO₂/fraction of inspired oxygen [FiO₂]) <40 (in absence of cyanotic heart disease or pre-existing pulmonary disease).
Hypercapnia: PaCO₂ >8.64 kPa (>65 mmHg), or 2.66 kPa (20 mmHg) above the baseline level.
High FiO₂ requirement is indicative of sepsis-related respiratory failure.[3]
Result
large base deficit; hypoxaemia and/or hypercapnia
serum lactate
Test
Elevated serum lactate is a marker of illness severity in sepsis. It is caused by beta-adrenoreceptor stimulation from endogenous catecholamines upregulating glycolysis leading to production of a high quantity of pyruvate. This production exceeds the utilisation capacity of the tricarboxylic acid cycle and excess pyruvate is converted to lactate. Lactate is often elevated in sepsis or septic shock. In certain situations lactataemia may represent decreased oxygen delivery.[67] The severity of elevated lactate at presentation to intensive care may indicate impending acute kidney injury.[86]
Lactate is most reliably assessed using an arterial sample, so venous and capillary lactate should be interpreted with caution.
Result
elevated levels are a marker of illness severity in sepsis and suggestive of septic shock
serum electrolytes
Test
Serum electrolytes are frequently deranged. Should be measured at baseline and regularly until the patient improves.
Result
deranged
serum creatinine
Test
Elevated serum creatinine (i.e., serum creatinine >2 times upper limit of normal or increase in serum creatinine >2 times baseline level) is indicative of sepsis-related acute kidney injury.[3]
Result
elevated
LFTs
Test
Elevated bilirubin (outside the neonatal age-range) and/or elevated alanine aminotransferase in the presence of confirmed or suspected infection is suggestive of sepsis-related liver dysfunction.[3]
Result
abnormal
coagulation studies
C-reactive protein (CRP)
Test
A biomarker that may be useful for the diagnosis and monitoring of sepsis and septic shock. Not as specific as serum procalcitonin, but more commonly available. There might be a lag period between the onset of sepsis and a rise in CRP.
Result
elevated
chest x-ray
Test
Infants and small children with respiratory distress in the context of suspected sepsis should undergo chest x-ray to assess for pneumonic changes (e.g., lobar consolidation in bronchopneumonia).
Often deferred until ventilator support is established.
If symptoms are not suggestive of the origin of suspected sepsis then chest x-ray would also be an appropriate initial investigation.[81]
Result
may reveal focus of infection, especially in older children
Investigations to consider
lumbar puncture
Test
If meningitis is suspected, and there is no purpuric or petechial rash, clinicians should consider a lumbar puncture (for cerebrospinal fluid protein and glucose concentrations, microscopy with Gram stain, and bacterial culture) when the child is stable and can safely undergo the procedure.[9][46][87] Blood glucose should be measured immediately before lumbar puncture, so that the cerebrospinal fluid to blood glucose ratio can be calculated.[87]
The National Institute for Health and Care Excellence sepsis guidelines recommend a lumbar puncture if sepsis is suspected in infants aged <1 month, and in all infants aged 1 to 3 months who appear unwell or have a WBC count <5×10⁹/L or >15×10⁹/L.[50]
Lumbar puncture is usually contraindicated in children with sepsis until the patient is stabilised.
Result
positive cerebrospinal fluid culture may confirm bacterial meningitis and provide information on pathogen including sensitivities to antibiotics; protein may be elevated; glucose may be low
meningococcal polymerase chain reaction analysis
Test
May be considered to help confirm the diagnosis in equivocal or suspected clinical cases of meningococcal sepsis.
Result
positive in Neisseria meningitides infection
bronchoalveolar lavage culture
Test
Bronchoalveolar lavage sampling for microscopy and culture may be considered for a child in intensive care with a suspected ventilator-associated pneumonia.
Result
positive culture may confirm bacterial infection and provide information on pathogen including sensitivities to antibiotics
herpes simplex virus (HSV) polymerase chain reaction (blood and cerebrospinal fluid)
Test
Neonatal herpes simplex infection (either in the central nervous system or disseminated) is a very rare, but important consideration in children with sepsis.
Consider ordering if neonatal herpes simplex infection is a possibility.
Result
positive (central nervous system or disseminated HSV infection)
CT chest
Test
CT may play an important role in the evaluation of patients with suspected sepsis. The increased exposure to radiation with this investigation should be considered.[81]
Result
may reveal focus of infection
Abdominal ultrasound
Test
If symptoms are not suggestive of the origin of suspected sepsis consideration of abdominal ultrasound may be appropriate.[81]
Result
may reveal focus of infection
Abdominal CT
Test
If symptoms are not suggestive of the origin of suspected sepsis consideration of abdominal CT may be appropriate.[81]
Result
may reveal focus of infection
Emerging tests
serum procalcitonin
Test
A key issue (particularly in intensive care) is the problem of distinguishing sepsis from systemic inflammatory response syndrome (or organ dysfunction) without infection, where clinical signs may not be helpful. The 2 biomarkers most frequently used for this purpose are CRP and serum procalcitonin. Serum procalcitonin shows the most potential in this area, showing greater accuracy for diagnosis of sepsis compared with CRP in neonates and older children.[69][70][71][72][73][74] There is also evidence that procalcitonin trends can be used to reduce the duration of antibiotic therapy and the hospital length of stay.[75]
Result
elevated
emerging biomarkers
Test
Other biomarkers (e.g., CD64, interleukin [IL]-6, IL-8, IL-18, mass spectrometry, specific mRNA expression) are considered emerging and are not widely used or validated, although offer significant promise.
Result
positive
PhenoTest™ BC Kit
Test
Can identify 14 species of bacteria and 2 species of yeast that commonly cause bloodstream infections, while also providing guidance on antibiotic sensitivity.
Compares the organism's DNA to a database, and then uses time-lapse images to analyse the organism’s response to antibiotics.
Can identify a positive blood culture in 1.5 hours and guide antibiotic treatment in 6.5 hours.
Has been associated with false positive results.[66]
Result
may be positive for organism and guide antimicrobial therapy
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