Investigations

1st investigations to order

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Take bloods immediately, before antibiotics are started (although sampling should not delay the administration of antibiotics).[3][43]

Ideally, take peripheral blood cultures (aerobic and anaerobic) from at least two different sites.[43]

  • Prioritise filling the aerobic bottle before filling the anaerobic one.

  • To improve yield, ensure these samples are incubated as soon as possible.

If you suspect a line infection, remove the line and culture the tip.

Practical tip

Take blood cultures and measure serum lactate at the same time.

Take cultures of blood and other fluids at the first opportunity as they may take up to 48 to 72 hours to yield sensitivities of causative organisms (if identified). It is usually possible to take cultures first without this causing any delay to administration of antibiotics. This is important as cultures are far less likely to be positive if delayed until after giving antimicrobials.

Result

may be positive for infection-causing organism

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Measure serum lactate, on a blood gas, to determine the severity of the sepsis and monitor response to treatment.[3][43][46]

  • Lactate is a marker of stress and may be a marker of a worse prognosis (as a reflection of the degree of stress). Raised serum lactate highlights the possibility of tissue hypoperfusion and may be present in many conditions.[77][78] 

  • Lactate may normalise quickly after fluid resuscitation. Patients whose lactate levels fail to normalise after adequate fluids are the group that fare worst.

  • Lactate >4 mmol/L (>36 mg/dL) is associated with worse outcomes.

    • One study found in-hospital mortality rates as follows:[79]

      • Lactate <2 mmol/L (<18 mg/dL): 15%

      • Lactate 2.1 to 3.9 mmol/L (19 to 35mg/dL): 25% 

      • Lactate >4 mmol/L (>36 mg/dL): 38%.

Practical tip

Take blood cultures and measure serum lactate at the same time.

Sepsis guidelines from the National Institute for Health and Care Excellence (NICE) in the UK and NHS England recommend escalating treatment depending on lactate level.[3][41] Alert critical care immediately if the patient is acutely unwell and has persistent lactate >4 mmol/L (>36 mg/dL)[3] despite fluid resuscitation.

Do not be falsely reassured by a normal lactate (<2 mmol/L [<18 mg/dL]).

  • This does not rule out the patient being acutely unwell or at risk of deterioration or death due to organ dysfunction. You must take into account the full clinical picture of the individual patient in front of you including their NEWS2 score.

Practical tip

Lactate is typically measured using a blood gas analyser, although laboratory analysis can also be performed.

Traditionally, arterial blood gas has been recommended as the ideal means of measuring lactate accurately. However, in practice, in the emergency department setting it may be more practical and quicker to use venous blood gas, which is recommended by NICE although this recommendation is not supported by strong evidence.[3] Evidence suggests good agreement at lactate levels <2 mmol/L (<18 mg/dL) with small disparities at higher lactate levels.[80][81][82]

Be aware that persisting raised lactate may not be recognised until after initial resuscitation has been given. In the patient with persisting raised lactate, ensure:

  • Adequate source control; remove any suspected septic or necrotic focus

  • The patient is adequately filled (their central venous pressure ‘goes up and stays up’)

  • The patient’s cardiac output and blood pressure are adequate for their tissue needs (a low central venous oxygen saturation, ScvO2, serves as a good indicator of impaired tissue oxygenation). 

Practical tip

Persistent raised lactate should incite efforts to identify other hidden causes including thiamine deficiency, adrenaline or other drugs, and liver failure.

Result

may be elevated; persistent levels >2 mmol/L (>18 mg/dL) associated with adverse prognosis; even worse prognosis with persistent levels >4 mmol/L (>36 mg/dL)

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Assess the patient’s urine output.[3][43][46] 

  • Ask the patient or their carer about urine output over the previous 12 to 18 hours

  • Consider catheterising the patient on presentation if they are shocked, confused, oliguric, or critically unwell

  • Ensure arrangements are in place for urine output to be monitored once an hour.

A low urine output may suggest intravascular volume depletion and/or acute kidney injury and is therefore a marker of sepsis severity.

  • The UK National Institute for Health and Care Excellence sepsis guideline categorises any patient who has not passed urine in the previous 18 hours (or for catheterised patients passed less than 0.5 mL/kg of urine per hour) as being at high risk of severe illness or death from sepsis.[3]

Result

may be markedly decreased

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Carry out a venous blood test to determine the patient’s full blood count.[3]

Thrombocytopenia of non-haemorrhagic origin may occur in patients who are severely ill with sepsis.[94]

  • Persistent thrombocytopenia is associated with an increased risk of mortality.[94] 

Lymphocytopenia is increasingly recognised as a useful sign in a patient with sepsis.

The WBC count is neither sensitive nor specific for sepsis.[95]

  • WBC count was one of the diagnostic criteria for sepsis under the old systemic inflammatory response syndrome (SIRS) definition but this has been superseded by the 2016 Sepsis-3 diagnostic criteria, which rely on demonstrating organ dysfunction.[1]

Practical tip

Non-infectious (e.g., crush) injury, surgery, cancer, and immunosuppressive agents can also lead to either increased or decreased WBC counts.

Result

WBC count >12×10⁹/L (12,000/microlitre) (leukocytosis); WBC count <4×10⁹/L (4000/microlitre) (leukopenia)

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Request urea and electrolyte tests;[3] use to: 

  • Evaluate the patient for renal dysfunction 

    • Patients with acute kidney injury due to sepsis have a worse prognosis than those with non-septic acute kidney injury[96]

  • Determine whether the patient would benefit from haemofiltration or intermittent haemodialysis[43]

  • Identify sodium, potassium, calcium, magnesium, and chloride abnormalities.

Result

serum electrolytes frequently deranged; blood urea may be elevated; creatinine may be elevated

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Measure serum glucose on blood gas,[3]in venous blood through venepuncture, or via capillary blood with bedside testing.

  • Depending on the patient’s baseline glucose level, hyperglycaemia may be associated with increased morbidity and mortality in patients with sepsis.[97]

    • Bear in mind that studies have shown that people with diabetes show no clear association between hyperglycaemia during intensive care unit stay and mortality and markedly lower odds ratios of death at all levels of hyperglycaemia.[98]

  • Glucose levels may be elevated, with or without a known history of diabetes mellitus, due to the stress response and altered glucose metabolism.[97][99] Drug therapy (e.g., with corticosteroids and catecholamines) may also lead to elevated glucose.

Practical tip

Spontaneous or iatrogenic hypoglycaemia also poses significant dangers.[100][101] Persisting hypoglycaemia may suggest acute liver failure.[102]

Result

may be elevated or, more rarely, low

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Carry out a venous blood test to determine the patient’s level of C-reactive protein.[3]

Reasonably sensitive, but not specific, for sepsis.[3][103][104]

Result

elevated

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Baseline serum procalcitonin is increasingly being used in critical care settings to guide decisions on how long to continue antibiotic therapy.[43][105][106][107]

  • Procalcitonin is a peptide precursor of calcitonin, which is responsible for calcium homeostasis.

  • It is currently excluded from key guidelines, but increasingly used in practice. 

Result

may be elevated 

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Include prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen.[3]

  • Use to determine whether the patient has established coagulopathy in the presence of sepsis. This is associated with a worse prognosis.[108]

Result

elevated PT; elevated PTT; elevated D-dimer; elevated fibrinogen

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Use liver function tests, notably bilirubin, to evaluate for organ dysfunction.[109][110] Liver dysfunction may also be a cause of a coagulopathy.

Result

elevated bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transpeptidase

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Use either arterial blood gas (ABG) or venous blood gas (VBG) evaluation.[3] Use ABG to optimise oxygenation and assess metabolic status (acid-base balance), particularly with regard to the arterial carbon dioxide level (PaCO2).

  • In ventilated patients, this may help to determine the positive end-expiratory pressure (PEEP), while minimising adverse levels of inspiratory pressure and unnecessarily high fraction of inspired oxygen (FiO2).

Practical tip

VBG is increasingly being used in preference to ABG in the emergency department, particularly if a respiratory cause seems unlikely. VBG is less invasive and less painful than ABG and evidence shows there is good concordance between venous and arterial values for pH, bicarbonate ion concentration, base excess, and lactate.[78] ABG will be used instead of VBG if the patient is escalated to critical care as an arterial line is usually inserted for ease of access.

Be aware that venous PCO2 may be artificially high if taken from a tourniqueted limb.

Result

PaCO₂ <4.3 kPa (32 mmHg) is one of the diagnostic criteria for systemic inflammatory response syndrome; may be hypoxaemia, hypercapnia

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Request a baseline ECG for any patient with suspected sepsis, as you would for all acutely ill presentations, to:

  • Rule out differential diagnoses: for example, myocardial infarction, pericarditis, or myocarditis

  • Detect arrhythmias (e.g., atrial fibrillation); commonly seen in older people with sepsis.[3]

Result

may show evidence of ischaemia, atrial fibrillation, or other arrhythmia

Investigations to consider

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Consider a dipstick test in any patient who has suspected sepsis to help add weight to a suspected urinary source of infection.[3]

Always interpret urine analysis in the context of the wider clinical assessment.

  • Bear in mind that this does not definitively confirm a urinary source, particularly as urine analysis has a low specificity.[111]

Result

may show evidence of infection (nitrates; leucocytes; blood/protein)

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Consider a chest x-ray (CXR) in any patient with suspected sepsis to help add weight to a suspected respiratory source (the most common source) of infection.[3]

Practical tip

A CXR is always indicated after central venous catheterisation (jugular or subclavian position) and/or endotracheal tube placement to rule out malposition and complications.[112][113] 

Result

may show evidence of infection, such as consolidation or pleural effusion, cardiac abnormalities, or a pneumothorax

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Consider taking cultures from multiple sources to determine the site and/or organism responsible for the infection,[43] including:

  • Urine

  • Sputum (if accepted by the laboratory)

  • Stool

  • Cerebrospinal fluid

  • Pleural fluid

  • Ascitic fluid

  • Joint fluid

  • Abscess aspirate

  • Swabs from open wounds or ulcers.

Result

may be positive for infection-causing organism

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Perform a lumbar puncture if you suspect meningitis or encephalitis, provided there is no suspicion of raised intracranial pressure (a computed tomography scan should be performed prior to lumbar puncture if you suspect raised intracranial pressure) or other risk to performing the procedure.[3][43]

  • This should never delay treatment, particularly the administration of antibiotics.


Diagnostic lumbar puncture in adults: animated demonstrationDiagnostic lumbar puncture in adults: animated demonstration

Result

elevated WBC count, presence of organism on microscopy, and positive culture

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A computed tomography (CT) scan of the chest and/or abdomen and pelvis provides cross-sectional imaging of the body to attempt to identify the source of sepsis.[3] Consider early CT if you suspect gastrointestinal (GI) infection in particular as, in practice, outcomes tend to be worse with GI sepsis compared with other sites of infection. 

  • A CT scan can help to identify a hidden collection (e.g., an intra-peritoneal abscess or effusion) in a patient presenting with ‘acute abdomen’, which may not be readily apparent on ultrasound or chest x-ray.

  • CT can also be used to identify free air (perforation).

  • If you suspect intra-abdominal or pelvic infection, involve the surgical or gynaecological teams early in case the patient needs surgical intervention.[3]

Result

findings vary depending on systems affected but may include: a hidden collection (e.g., a visceral abscess or effusion); free air (perforation)

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Consider ultrasound scanning to help locate the source of the infection, particularly if you suspect an abdominal source or where the source of infection is not clear after the initial clinical examination and tests.[43]

  • In particular, use ultrasound to identify:

    • Abscesses in the liver or skin

    • Free fluid (peritonitis)

    • Hydronephrosis (pyelonephritis). 

  • Ultrasound has a reasonable false negative rate; absence of positive findings on ultrasound does not rule out any given infection source.

Result

may identify: abscess; free fluid (peritonitis); common bile duct dilatation (cholangitis); areas of infarction secondary to emboli (e.g., infective endocarditis); hydronephrosis (pyelonephritis)

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Carry out legionella and pneumococcal urine antigen testing in all patients with suspected or confirmed community-acquired pneumonia.[120]

Result

may show evidence of infection

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Consider rapid respiratory viral polymerase chain reaction in people with suspected respiratory aetiology.[121]

Result

may show evidence of respiratory infection

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Consider performing a screen for HIV infection, particularly in patients presenting with recurrent infections or atypical infections and those considered to be in high-risk groups.[122]

  • Key risk factors for contracting HIV infection include intravenous drug use and unprotected sexual intercourse (heterosexual and homosexual).

Result

may be positive for HIV

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Consider echocardiogram (echo) for a more detailed assessment of the causes of the haemodynamic issues.[43] Use echo to assess (left and/or right) ventricular dysfunction, which may be caused by sepsis, and to detect endocarditis. Echo can also be used to assess inferior vena cava collapsibility, which is a marker of hypovolaemia.

Result

inadequate left ventricular filling suggests hypovolaemia; vegetations, if endocarditis is cause of sepsis

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