History and exam

Key diagnostic factors

Have a higher index of suspicion for sepsis when a patient presents with signs of infection and acute illness and falls into an at-risk group:

  • Age older than 65 years (and particularly older than 75 years)[3][9][36][51] 

  • Immunocompromised (e.g., chemotherapy, sickle cell disease, AIDS, splenectomy, long-term steroids)[3][36][37][52][53]

  • Indwelling lines or catheters[3]

  • Recent surgery (in previous 6 weeks).[3] The risk of sepsis is particularly high following oesophageal, pancreatic, or elective gastric surgery[38] 

  • Haemodialysis[36]

  • Diabetes mellitus[36]

  • Intravenous drug misuse[3]

  • Alcohol dependence[36][54]

  • Pregnancy (and the 6 weeks after delivery/termination/miscarriage)[3]

  • Breaches of skin integrity (e.g., burns, cuts, blisters, skin infections).[3]

Age younger than 1 year is also a strong risk factor.[3] See our topic Sepsis in children.

Be aware of the risk of sepsis in women who are pregnant, have given birth, or have had a termination or miscarriage in the past 6 weeks. Risk factors for the development of sepsis in these groups include:[3][62]

  • Obesity

  • Gestational diabetes or diabetes mellitus

  • Impaired immune systems (due to illness or drugs)

  • Anaemia

  • History of pelvic infection

  • History of group B streptococcal infection

  • Amniocentesis and other invasive procedures (e.g., instrumental delivery, caesarean section, removal or retained products of conception)

  • Cervical cerclage

  • Prolonged rupture of membranes

  • Vaginal trauma

  • Wound haematoma

  • Close contact with people with group A streptococcal infection (e.g., scarlet fever).

Practical tip

When weighing up whether a patient who is acutely ill with symptoms or signs of possible infection can be safely managed in the community, it is important to consider whether they fall into one or more of the at-risk groups.[3]

Practical tip

Pay particular attention to the patient’s family/carers when taking a history. They will know the patient well and might be able to offer insight into acute behavioural changes as well as changes to their respiration or circulation, compared with the norm. Consider how they may describe the result of changes in physiology that are likely to have affected the patient’s vital observations, for example:[61] 

  • Altered mental state – ‘confused’, ‘drowsy’, ‘not themselves’

  • Fever – ‘warm to touch’, ‘shivery', ‘burning up’

  • Hypotension – ‘dizzy’, ‘faint’, ‘lightheaded’

  • Tachypnoeic – ‘out of breath’, ‘breathless’

  • Tachycardic – ‘heart is racing’, ‘heart is pounding’.

The most common sources of infection are:[60]

  • Respiratory tract (cough/pleuritic chest pain)

  • Urinary tract (flank pain/dysuria)

  • Abdominal/upper gastrointestinaI tract (abdominal pain)

  • Skin/soft tissue (abscess/wound/catheter site)

  • Surgical site or line/drain site.

Signs and symptoms of possible infection sources

Use the history to identify factors for acquiring infection and clues to infection sites to guide choice of antimicrobial therapy.[21]

  • Ask specific questions, including:

    • When was the last time you passed urine?

      • And how often over the past 18 hours?[3]

    • Do you take any medication?

    • Have you recently taken antibiotics?

    • Have you recently been in hospital and/or had surgical procedures?

    • Have you travelled abroad recently?

    • Have you had contact with animals?

    • Have you had any contact with anyone infectious?

  • Ask about the patient’s lifestyle, including:

    • Drug misuse

    • Alcohol intake

    • Housing situation.

Practical tip

Pay particular attention to the patient’s family/carers when taking a history. They will know the patient well and might be able to offer insight into acute behavioural changes as well as changes to their respiration or circulation, compared with the norm. Consider how they may describe the result of changes in physiology that are likely to have affected the patient’s vital observations, for example:[61] 

  • Altered mental state – ‘confused’, ‘drowsy’, ‘not themselves’

  • Fever – ‘warm to touch’, ‘shivery', ‘burning up’

  • Hypotension – ‘dizzy’, ‘faint’, ‘lightheaded’

  • Tachypnoeic – ‘out of breath’, ‘breathless’

  • Tachycardic – ‘heart is racing’, ‘heart is pounding’.

Practical tip

Check to see whether there are any microbiological samples already in the lab (e.g., urine sent by the GP) or other available test results (bloods, x-rays etc).

The Extended Prevalence of Infection in Intensive Care (EPIC II) study provides the best recent evidence on the infectious causes of sepsis in an intensive care setting.[20]

The study gathered extensive data from more than 14,000 adult patients in 1265 intensive care units from 75 countries on a single day in May 2007.

Of the 7000 patients classified as ‘infected’, the sites of infection were the:

  • Lungs: 64%

  • Abdomen: 20%

  • Bloodstream: 15%

  • Renal or genitourinary tract: 14%.

Of the 70% of infected patients with positive microbiology:

  • 47% of isolates were gram-positive (Staphylococcus aureus alone accounted for 20%)

  • 62% were gram-negative (20% Pseudomonas species and 16% Escherichia coli)

  • 19% were fungal.

Other studies tend to broadly concur on the relative frequencies of sources of infection. The graph below shows the results of the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) report in 2015.[60]The relative frequencies of sources of infection in sepsis[Figure caption and citation for the preceding image starts]: The relative frequencies of sources of infection in sepsisCreated by the BMJ Knowledge Centre; based on 'NCEPOD. Just say sepsis! Nov 2015 [Citation ends].

Evidence from studies in people over age 65 years shows the genitourinary tract is the biggest source of infection.[21][22] 

Early identification of sepsis relies on systematic assessment of any acutely ill patient who presents with presumed infection to identify their risk of deterioration due to sepsis. By the time sepsis is at an advanced stage, with multiple abnormal physiological parameters, the risk of mortality is very high.[41]

In any patient in whom sepsis is a possibility, use a systematic process to check vital observations and assess and record the risk of deterioration.[41][42][43] Remember that no risk stratification process is 100% sensitive or 100% specific; therefore, you must use your clinical judgement

Consult local guidelines for the recommended approach for assessing acute deterioration.

  1. In hospital: use the National Early Warning Score 2 (NEWS2) or an alternative early warning score.[41][42][44] NEWS2 is endorsed by NHS England for use in this setting.[41]

  2. In the community: use an early warning score such as NEWS2, which is recommended by NHS England[41] and the Royal College of General Practitioners in the UK,[50] or the UK National Institute for Health and Care Excellence (NICE) high-risk criteria.[3]

    • None are validated in primary care.[50]

NEWS2 is the most widely used early warning score in the UK National Health Service and is endorsed by NHS England.[41] NHS England: Sepsis  In a patient with a known or likely infection, a NEWS2 score of 5 or more is likely to indicate sepsis.[42]

Arrange urgent assessment by a senior clinical decision-maker (CT3/ST3 or higher in the UK, or a trained nurse with prescribing rights in acute care) for any patient with an aggregate NEWS2 score of 5 or more.[41]

  • The higher the resulting aggregate NEWS2 score, the higher the risk of clinical deterioration.[41][42]

  • If necessary (e.g., NEWS2 score of 7 or more) arrange emergency assessment by a critical care specialist. 

Following the introduction of the NICE risk stratification criteria, there has been ongoing debate around their advantages and drawbacks. There is significant overlap between the NEWS2 scoring system and the NICE risk stratification criteria, with many of the same clinical observations used in both. A key difference is that the risk category a patient falls into under NEWS2 generally depends on an aggregate score across all the vital observations, whereas under the approach recommended by NICE this risk categorisation depends on a score on a single parameter.

  • The decision as to whether to use the NEWS2 or NICE approach for recognition of suspected sepsis may be made at individual institution, clinical commissioning group, or regional level. What is important is that implementation of either approach should lead to more systematic assessment and recording of the vital observations that can help identify patients at risk of deterioration whose care needs escalating immediately.

  • Whichever tool you use, it should only ever be in addition to (and never a replacement for) your clinical judgement.

  • For example, NHS England has concluded that the complexity of the NICE risk stratification criteria make them difficult to translate into practice and has recommended the alternative NEWS2 approach as more pragmatic for frontline clinicians, both in hospital and community settings.[41]

  • Concern has also been raised about the low threshold for suspecting sepsis using the NICE criteria, which could lead to so many patients being referred to hospitals as emergencies that assessment and treatment could be delayed for those at the very highest risk. One small study that retrospectively reviewed admissions to an acute medical unit found the NICE criteria identified 69% of adult patients as requiring a review within 1 hour by a senior clinician.[75]

  • It is important to remember that none of these criteria negate clinical judgement and they should only be assessed in patients with suspected infections.[3]

  • The National Quality Board and NICE have recommended further evaluation of the use of NEWS2 in primary care and recognise the value of a 'common language' to communicate the severity of a patient's acute illness.[41]

Although not specifically intended to be used for identifying suspected sepsis, several studies have highlighted how the National Early Warning Score (NEWS) may support earlier identification of patients with sepsis and septic shock.[68][70][71]These data relate specifically to NEWS, a previous iteration of NEWS2.

  • An analysis of audit data from 20 emergency departments in the UK, which included a total of 2003 patients, found a single NEWS score calculated from the patient’s initial observations to be strongly predictive of adverse outcomes in sepsis.[71]

    • Total NEWS scores were grouped into four categories: 0-4, 5-6, 7-8, and 9-20.

    • Each rise in NEWS score category was associated with an increased risk of mortality when compared with the lowest category (0-4):[71]

      • 5-6: odds ratio (OR) 1.95 (95% CI 1.21 to 3.14)

      • 7-8: OR 2.26 (95% CI 1.42 to 3.61)

      • 9-20: OR 5.64 (95% CI 3.70 to 8.60).

  • A further study of 30,677 adults admitted via emergency departments in the US with suspected infection found that the NEWS score performed better than either the Modified Early Warning Score (MEWS) or qSOFA scores in predicting the risk of death or need for an intensive care unit transfer.[68]

  • In a retrospective observational study, an aggregate NEWS score of 3 or more at emergency department triage was found to have a sensitivity of 92.6% (95% CI 74.2% to 98.7%) and a specificity of 77% (95% CI 72.8% to 80.6%) for detecting patients at risk of severe sepsis and septic shock.[70]

Practical tip

It is important to be aware that no scoring system has been validated for use in pregnant women; in practice, seek senior input to determine the best approach in a pregnant patient.

Examples of scores that have been developed but are yet to be universally accepted include the following.

  • A modified qSOFA has been proposed by the Society of Obstetric Medicine Australia and New Zealand (SOMANZ) for use in pregnant women. The SOMANZ score includes systolic blood pressure 90 mmHg, respiratory rate >25 per minute, and altered mental status.[72]

  • The Sepsis in Obstetrics Score uses a combination of maternal temperature, blood pressure, heart rate, respiratory rate, peripheral oxygen saturation, white blood cell count, and lactic acid level as predictors of intensive care admission for sepsis.[73]

A common non-specific sign of sepsis;[3][21][43] typically, respiratory rate >20 breaths/minute. 

Although changes in body temperature are often seen in people with sepsis, temperature should not be used as the sole predictor of sepsis and should not be used to rule sepsis either in or out. Be aware that some people with sepsis will present with a normal temperature.[3][41][42] 

Practical tip

Never rule out sepsis on the basis of a normal temperature reading. Fever is a common presenting sign but some patients are apyrexial or have hypothermia.[3]

  • Always assess the patient’s temperature in the context of their wider clinical picture.

  • Hypothermia at presentation is associated with a poorer prognosis than fever.[63]

  • People who are older (>75 years) or very frail (regardless of age) are particularly prone to a blunted febrile response and may present with a normal temperature.[3][64]

  • Other groups that are less susceptible to temperature fluctuations and so may not develop a raised temperature with sepsis include:[3]

    • Infants or children

    • People with cancer receiving treatment

    • Severely ill patients.

A common feature of sepsis;[21][43] typically heart rate >90 beats per minute (bpm).

Practical tip

Always interpret the vital signs that you take as part of the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) assessment in relation to the patient’s known or likely baseline for that parameter; take account of the patient in front of you and the full clinical picture. For example:

  • A fall in systolic blood pressure of ≥40 mmHg from the patient’s baseline is a cause for concern, regardless of the systolic blood pressure reading itself[3]

  • Although tachycardia can be an indicator of potential risk of sepsis developing, when assessing heart rate you should consider:[3]

    • Pregnancy

      • In pregnant people, heart rate is usually 10 to 15 bpm faster than normal

    • Older people

      • Older people may not develop tachycardia in response to infection and are more at risk of developing new arrhythmias (e.g., atrial fibrillation)

    • Medications

      • Some drugs, such as beta-blockers or rate-limiting calcium-channel blockers, may inhibit a tachycardic response to infection 

    • Baseline

      • The baseline heart rate in young people or people who are very physically fit (e.g., athletes) may be lower than the norm. The rate of change of heart rate may therefore be more important (to reflect the severity of infection) than the actual rate.

Determine the patient’s baseline mental state and establish whether there has been a change.[3] Use a validated scale (e.g., the Glasgow Coma Scale or AVPU ['Alert, responds to Voice, responds to Pain, Unresponsive'] scale). [ Glasgow Coma Scale ] [3] As well as checking response to cues, you should ask a relative or carer (if available) about the patient’s recent behaviour.[3]

Practical tip

Change in mental state is a commonly missed sign of sepsis, particularly in older patients in whom dementia may co-exist. Change in mental state is often due to non-infectious causes (e.g., electrolyte disturbances). It can manifest in many ways, which makes it challenging to recognise as part of a short clinical consultation.

  • The term ‘confusion’ can be unhelpful and instead you should attempt to identify any change from the patient’s normal behaviour or cognitive state.[3]

  • A collateral history – if friends, family members, or carers are available – is key. They might describe the patient as ‘not themselves’.

  • In people with dementia, change in mental state may present as irritability or aggression,[3] but equally could present with hypoactive delirium (e.g., with lethargy, apathy).[59]

  • In addition, sepsis may be signalled by a deterioration in functional ability (e.g., a patient newly unable to stand from sitting).[3]

Low oxygen saturation is often seen in people with sepsis:[21][43] systolic blood pressure <90 mmHg, mean arterial pressure <65 mmHg, or reduction in systolic blood pressure >40 mmHg from baseline. 

Practical tip

Difficulty obtaining peripheral oxygen saturations may be a red flag for possible shock.[3]

  • Peripheral oxygen saturations can be difficult to measure in a patient with sepsis if the tissues are hypoperfused.

    • This may occur in the later stages of the condition, as earlier in the disease process the circulation is usually hyperdynamic.

    • Some conditions such as meningococcal sepsis can present early with poor peripheral perfusion. These patients often have profound myocardial depression on presentation. In others, there may be a hyperdynamic central circulation concurrent with poor peripheral perfusion and a subsequent uncoupling of blood flow.

  • You should have a high index of suspicion for shock if you are unable to measure oxygen saturations.

  • See our topic Shock.

Hypotension is commonly seen in people with sepsis.[21][43]

Beware septic shock, a subtype of sepsis with a much higher mortality.[1][42]

  • Characterised by profound circulatory and metabolic abnormalities.

  • Presents with persistent hypotension and serum lactate >2 mmol/L (>18 mg/dL) despite adequate fluid resuscitation, with a need for vasopressors to maintain mean arterial pressure ≥65 mmHg.[1]

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]

Signs of circulatory insufficiency are thought to indicate peripheral perfusion, with a longer capillary refill time suggesting reduced capillary perfusion.[125]

Capillary refill time. Top image: normal skin tone; middle image: pressure applied for 5 seconds; bottom image: time to hyperaemia measured[Figure caption and citation for the preceding image starts]: Capillary refill time. Top image: normal skin tone; middle image: pressure applied for 5 seconds; bottom image: time to hyperaemia measuredFrom the collection of Ron Daniels, MB, ChB, FRCA; used with permission [Citation ends].

A common non-specific sign of sepsis.[21][43] 

Other diagnostic factors

Commonly seen in people with sepsis.[21][43]

Commonly seen in people with sepsis.[21][43] 

A very late sign of possible organ dysfunction; may be seen on presentation.

Severe purpura fulminans; classically associated with meningococcal sepsis but can occur with pneumococcal sepsis[Figure caption and citation for the preceding image starts]: Severe purpura fulminans; classically associated with meningococcal sepsis but can occur with pneumococcal sepsisFrom the collection of Ron Daniels, MB, ChB, FRCA; used with permission [Citation ends].

A sign of possible organ dysfunction.

A rare sign of organ dysfunction unless it is associated with a specific source of infection (biliary sepsis).

Use of this content is subject to our disclaimer