Investigations
1st investigations to order
blood cultures
Test
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.[46]
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
serum lactate
Test
Measure serum lactate, on a blood gas, to determine the severity of the sepsis and monitor response to treatment.[3][43][47]
Lactate is a marker of stress and may help to provide an overall picture of someone’s prognosis (as a reflection of the degree of stress).[3] Raised serum lactate highlights the possibility of tissue hypoperfusion and may be present in many conditions.[75][76]
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:[77]
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.
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. Lactate helps to provide an overall picture of a patient's prognosis but you must take into account the full clinical picture of the individual patient in front of you including their NEWS2 score to determine when/whether to escalate treatment.[3]
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.[78][79][80]
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, ScvO 2, 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)
hourly urine output
Test
Assess the patient’s urine output.[3][47]
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.
A 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) is at high risk of severe illness or death from sepsis.[3]
Result
may be markedly decreased
full blood count
Test
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.[92]
Persistent thrombocytopenia is associated with an increased risk of mortality.[92]
Lymphocytopenia is increasingly recognised as a useful sign in a patient with sepsis.
The WBC count is neither sensitive nor specific for sepsis.[93]
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)
urea and electrolytes (including creatinine)
Test
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[94]
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
serum glucose
Test
Measure serum glucose on blood gas, in venous blood through venepuncture, or via capillary blood with bedside testing.[3]
Depending on the patient’s baseline glucose level, hyperglycaemia may be associated with increased morbidity and mortality in patients with sepsis.[95]
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.[96]
Glucose levels may be elevated, with or without a known history of diabetes mellitus, due to the stress response and altered glucose metabolism.[95][97] Drug therapy (e.g., with corticosteroids and catecholamines) may also lead to elevated glucose.
Result
may be elevated or, more rarely, low
C-reactive protein
serum procalcitonin
Test
Baseline serum procalcitonin is increasingly being used in critical care settings to guide decisions on how long to continue antibiotic therapy.[43][103][104][105]
Procalcitonin is a peptide precursor of calcitonin, which is responsible for calcium homeostasis.
The Surviving Sepsis Campaign suggests using procalcitonin alongside clinical evaluation to decide when to discontinue antimicrobials.[43]
Result
may be elevated
clotting screen
liver function tests
blood gas
Test
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.[76] 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 PCO 2 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
ECG
Test
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
urine analysis
Test
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.[109]
Result
may show evidence of infection (nitrates; leucocytes; blood/protein)
chest x-ray
Test
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]
Result
may show evidence of infection, such as consolidation or pleural effusion, cardiac abnormalities, or a pneumothorax
cultures from multiple sources
Test
Consider taking cultures from multiple sources to determine the site and/or organism responsible for the infection, including:[43]
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
lumbar puncture
Test
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]
This should never delay treatment, particularly the administration of antibiotics.
Do not perform a lumbar puncture if any of the following contraindications are present:[3][112]
Extensive or spreading purpura
Infection at the lumbar puncture site
Risk factors for an evolving space-occupying lesion
Any of these symptoms or signs, which might indicate raised intracranial pressure:
New focal neurological features (including seizures or posturing)
Abnormal pupillary reactions
A Glasgow Coma Scale (GCS) score of 9 or less, or a progressive and sustained or rapid fall in level of consciousness.
How to perform a diagnostic lumbar puncture in adults. Includes a discussion of patient positioning, choice of needle, and measurement of opening and closing pressure.
Result
elevated WBC count, presence of organism on microscopy, and positive culture
computed tomography
Test
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).
Involve the relevant surgical team early on if surgical or radiological intervention is suitable for the source of infection.[3][45] The surgical team or interventional radiologist should seek senior advice about the timing of intervention and carry the intervention out as soon as possible, in line with the advice received.[3]
Result
findings vary depending on systems affected but may include: a hidden collection (e.g., a visceral abscess or effusion); free air (perforation)
ultrasound
Test
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.[3][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)
urine antigen testing
Test
Carry out legionella and pneumococcal urine antigen testing in all patients with suspected or confirmed community-acquired pneumonia.[119]
Result
may show evidence of infection
viral swabs
Test
Consider rapid respiratory viral polymerase chain reaction in people with suspected respiratory aetiology.[120]
Result
may show evidence of respiratory infection
HIV screen
Test
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.[121]
Key risk factors for contracting HIV infection include intravenous drug use and unprotected sexual intercourse (heterosexual and homosexual).
Result
may be positive for HIV
echocardiogram
Test
Consider echocardiogram (echo) for a more detailed assessment of the causes of the haemodynamic issues. 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, and to guide fluid resuscitation.[43]
Result
inadequate left ventricular filling suggests hypovolaemia; vegetations, if endocarditis is cause of sepsis
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