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Sepsis in Adults

Sepsis in adults is a life-threatening condition characterized by organ dysfunction due to a dysregulated response to infection, requiring early recognition and prompt treatment. Key risk factors include age over 65, immunocompromise, and recent surgery, with common sources of infection being the lungs and abdomen. The document emphasizes the importance of clinical judgment and monitoring, particularly using scoring systems like NEWS2, to improve patient outcomes.

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Sepsis in Adults

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ahmed sharaf

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Sepsis in adults

Straight to the point of care

Last updated: Jun 12, 2024

Table of Contents
Overview 3
Summary 3
Definition 3

Theory 5
Epidemiology 5
Risk factors 5
Aetiology 6
Pathophysiology 7
Classification 8
Case history 9

Diagnosis 10
Recommendations 10
History and exam 42
Investigations 53
Differentials 61
Criteria 62

Management 65
Recommendations 65
Treatment algorithm overview 101
Treatment algorithm 103

Follow up 173
Monitoring 173
Complications 174
Prognosis 175

Guidelines 177
Diagnostic guidelines 177
Treatment guidelines 177

Online resources 179

References 180

Images 195

Disclaimer 201
Sepsis in adults Overview

Summary
Sepsis should be suspected in an acutely deteriorating patient in whom there is clinical evidence or strong suspicion of
infection. Have a low threshold for suspicion.

OVERVIEW
Think ‘Could this be sepsis?’ whenever an acutely unwell person presents with likely infection, even if their
temperature is normal. Remember that sepsis represents the severe, life-threatening end of infection.

The key to improving outcomes is early recognition and prompt treatment, as appropriate, of patients with suspected or
confirmed infection who are deteriorating and at risk of organ dysfunction. By the time the diagnosis becomes obvious,
with multiple abnormal physiological parameters, risk of mortality is very high.

Your clinical judgement is crucial to how you approach the individual patient. Be aware that signs and symptoms are
extremely variable and often non-specific.

Assess acute deterioration using your clinical judgement alongside a validated scoring system, such as the National
Early Warning Score 2 (NEWS2); consult local guidelines for the recommended scoring system at your institution.
Arrange urgent assessment by a senior clinical decision-maker for any patient with an aggregate NEWS2 score of 5 or
more.

Within 1 hour of the risk being recognised for patients with critical illness on presentation (including those with septic
shock, sepsis associated with rapid deterioration, or a NEWS2 score #7 on initial assessment in the accident and
emergency department or on ward deterioration): take two sets of blood cultures, measure serum lactate on a blood gas,
and assess the patient’s hourly urine output; give intravenous broad-spectrum antibiotics (after taking blood cultures)
if there is evidence of a bacterial infection, give intravenous fluids if there is any sign of circulatory insufficiency, and
give oxygen if needed.

Ensure any patient with suspected sepsis has frequent and ongoing monitoring (e.g., using NEWS2).

Definition
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection.[1]
The definition of sepsis was updated in 2016 following publication of the Third International Consensus Definitions
for Sepsis and Septic Shock (Sepsis-3).[1] This recommended that organ dysfunction should be defined using the
Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) criteria or the 'quick' (q)SOFA criteria .

The 2016 consensus definitions marked a shift away from the previous systemic inflammatory response syndrome
(SIRS) definition, which classified sepsis as two or more of the following in the context of infection: temperature
>38.3°C (101°F) or <36.0°C (96.8°F); tachycardia >90 beats per minute; tachypnoea >20 breaths/minute or arterial
carbon dioxide level (PaCO#) <4.3 kPa (32 mmHg); hyperglycaemia (blood glucose >7.7 mmol/L [>140 mg/dL]) in
the absence of diabetes mellitus; acutely altered mental status; leukocytosis (white blood cell [WBC] count >12×10#/
L [12,000/microlitre]); leukopenia (WBC count <4×10#/L [4000/microlitre]); or a normal WBC count with >10%
immature forms.[2]

However, the 2016 Third International Consensus Group (Sepsis-3) definitions state that the term 'severe sepsis' should
be made redundant in light of the revisions to the definition of sepsis.[1] Septic shock has also been redefined as a

Septic shock indicates profound circulatory, cellular, and metabolic deterioration, and is associated with a greater risk of
OVERVIEW

mortality than with sepsis alone.[1]

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Sepsis in adults Theory

Epidemiology
There are a lack of reliable sepsis incidence and prevalence data. This is due to the absence of a consistent definition for
sepsis and differences in coding practice between professionals and organisations.[4] [5]

THEORY
In 2017/18, 186,000 hospital admissions in the UK were for people with a primary diagnosis of sepsis.[6]

Sepsis is present in many hospitalisations that culminate in death. In 2015, 23,135 people in the UK died from sepsis,
where sepsis was an underlying or contributory cause of death. [NHS England: Sepsis] The true contribution of
sepsis to these deaths is unknown. Most underlying causes of death in people with sepsis are thought to relate to severe
chronic comorbidities and frailty.[5] [7] [8]

Most epidemiological studies find sepsis to be more common in men than in women. People over 65 years old are
particularly susceptible, with one study finding almost two-thirds of people with sepsis to be in this age group.[9]

Risk factors
Strong
age >65 years
Associated with an increased risk of sepsis (relative risk 7.0, 95% CI 5.6 to 8.7).[36]

Risk of sepsis is particularly high in people aged >75 years or those who are frail.[3]

immunocompromise
Associated with an increased risk of sepsis.

Immunocompromise may arise from treatment (e.g., chemotherapy, corticosteroids, or other

immunosuppressants), underlying disease (e.g., diabetes, sickle cell), or surgery (e.g., splenectomy).[3] [37]
Suspect neutropenic sepsis in patients who have become unwell and (a) are having or have had systemic
anticancer treatment within the last 30 days or (b) are receiving or have received immunosuppressant treatment
for reasons unrelated to cancer.[3]

indwelling lines or catheters

Risk of sepsis is high in people with indwelling lines or catheters.[3]

recent surgery or other invasive procedures

Risk of sepsis is high in people who have had surgery or other invasive procedures in the past 6 weeks.[3]

Risk of sepsis is particularly high following oesophageal, pancreatic, or elective gastric surgery.[38]

haemodialysis
Associated with an increased risk of sepsis (relative risk 208.7, 95% CI 142.9 to 296.3).[36]

diabetes mellitus
Decreased resistance to infections, complications of diabetes, and increased surgical complications play a role
(relative risk 5.9, 95% CI 4.4 to 7.8).[36]

alcohol dependency
THEORY

Associated with an increased risk of sepsis (relative risk 5.6, 95% CI 3.8 to 8.0).[36]

pregnancy
Pregnancy or recent pregnancy is a risk factor for the development of sepsis.[3] In the UK, the estimated
incidence of sepsis in pregnancy has been reported to be 47 cases per 100,000 maternities per year, whereas the
estimated annual incidence among people aged 18 to 19 years in a general population has been reported to be
around 29.6 cases per 100,000.[9] [39]

Risk of sepsis among women may be higher if they have impaired immunity, gestational diabetes, diabetes
(or other comorbid condition), needed invasive procedures during pregnancy (e.g., caesarean section, forceps
delivery, removal of retained products of conception), had prolonged rupture of membranes during pregnancy,
have or have been in close contact with people with group A streptococcal infection (e.g., scarlet fever), or have
continued vaginal bleeding or an abnormal vaginal discharge with odour.[3]

breached skin integrity

Risk of sepsis is high in people with any breach of skin integrity (e.g., cuts, burns, blisters, or skin infection).[3]

Weak
urban residence
May predispose to increased exposure to infections and drug-resistant pathogens (relative risk 2.4, 95% CI 1.2 to
5.6).[36]

lung disease
Weakly associated with sepsis (relative risk 3.8, 95% CI 2.6 to 5.4).[36]

male sex
May be at greater risk (odds ratio 1.28, 95% CI 1.24 to 1.32).[40]

non-white ancestry
May be at increased risk (odds ratio 1.90, 95% CI 1.80 to 2.00).[40]

winter season
Seasonal infections (e.g., respiratory infections in winter) are weakly associated with sepsis.

Sepsis is 1.4 times more likely to occur in the winter than in the autumn.[16]

Aetiology
Causative agents vary significantly, depending on several factors including the region, hospital size, season, and type
of unit (neonatal, transplantation, oncology, or haemodialysis; if acquired in hospital).[10] [11] [12] [13] [14] [15] [16]
[17] [18] [19]

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 prospective study gathered extensive data from more

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Sepsis in adults Theory
than 14,000 adult patients in 1265 intensive care units from 75 countries on a single day in May 2007. Of the 7087
patients classified as ‘infected’, the sites of infection were the:

• Lungs: 64%

THEORY
• 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. In people over 65, the most
common site is the genitourinary tract.[21] [22] A definite source of infection cannot be found in 20% to 30% of people
with sepsis.[9]

Pathophysiology
Sepsis is a syndrome comprising an immune system-mediated collection of physiological responses to an infectious
agent. Clinical signs such as fever, tachycardia, and hypotension are common but the clinical course depends on
the type and resistance profile of infectious organism, the site and size of the infecting insult, and the genetically
determined or acquired properties of the host's immune system.

Immune-system activation:

• Pathogen entry and survival is facilitated by tissue contamination (surgery or infection), foreign body insertion
(catheters), and immune status (immunosuppression).[23]
• The innate immune system is activated by bacterial cell wall products, such as lipopolysaccharide, binding
to host receptors, including Toll-like receptors (TLRs).[24] [25] These are widely found on leukocytes and
macrophages, and some types are found on endothelial cells.[26] At least 10 TLRs have been described in
humans. These have specificity for different bacterial, fungal, or viral surface markers or products. Genetic
polymorphisms are associated with a predisposition to shock with gram-negative organisms.[27]
• Activation of the innate immune system results in a complex series of cellular and humoural responses, each
with amplification steps:[28]

• Pro-inflammatory cytokines such as tumour necrosis factor-alpha and interleukins 1 and 6 are released,
which in turn activate immune cells.
• Reactive oxygen species, nitric oxide (NO), proteases, and pore-forming molecules are released, which
bring about bacterial killing. NO is responsible for vasodilatation and increased capillary permeability,
and has been implicated in sepsis-induced mitochondrial dysfunction.[29]
• The complement system is activated, and mediates activation of leukocytes, attracting them to the site of
infection where they can directly attack the organism (phagocytes, cytotoxic T lymphocytes), identify it
for attack by others (antigen presenting cells, B lymphocytes), ‘remember’ it in case of future infection

The endothelium and coagulation system:

• The vascular endothelium plays a major role in the host’s defence to an invading organism, but also in the
development of sepsis. Activated endothelium not only allows the adhesion and migration of stimulated immune
cells, but becomes porous to large molecules such as proteins, resulting in tissue oedema.
• Alterations in the coagulation systems include an increase in pro-coagulant factors, such as plasminogen
activator inhibitor type I and tissue factor, and reduced circulating levels of natural anticoagulants, including
antithrombin III and activated protein C, which also carry anti-inflammatory and modulatory roles.[31] [32]

Inflammation and organ dysfunction:

• Through vasodilatation (causing reduced systemic vascular resistance) and increased capillary permeability
(causing extravasation of plasma), sepsis results in relative and absolute reductions in circulating volume.
• A number of factors combine to produce multiple organ dysfunctions. Relative and absolute hypovolaemia are
compounded by reduced left ventricular contractility, leading to hypotension. Initially, through an increased
heart rate, cardiac output increases to compensate and maintain perfusion pressures, but as this compensatory
mechanism becomes exhausted, hypoperfusion and shock may result.
• Impaired tissue oxygen delivery is exacerbated by pericapillary oedema. This means that oxygen has to diffuse a
greater distance to reach target cells. There is a reduction of capillary diameter due to mural oedema and the pro-
coagulant state results in capillary microthrombus formation.
• Additional contributing factors include disordered blood flow through capillary beds, resulting from a
combination of shunting of blood through collateral channels and an increase in blood viscosity secondary to
loss of red cell flexibility.[33] As a result, organs may become hypoxic, even though gross blood flow to an
organ may increase. These abnormalities may lead to lactic acidosis, cellular dysfunction, and multi-organ
failure.[34]
• Cellular energy levels fall as metabolic activity begins to exceed production. However, cell death appears to be
uncommon in sepsis, implying that cells shut down as part of the systemic response. This could explain why
relatively few histological changes are found at autopsy, and the eventual rapid resolution of severe symptoms,
such as anuria and hypotension, once the systemic inflammation resolves.[35]

Classification
Third international consensus definitions for sepsis and septic shock (Sepsis-3)
(2016)[1]
• Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection.
• Septic shock is a subset of sepsis in which particularly profound circulatory, cellular, and metabolic
abnormalities are associated with a greater risk of mortality than with sepsis alone. Septic shock can be defined
clinically as a patient diagnosed with sepsis, with persistent hypotension requiring vasopressors to maintain
a mean arterial pressure #65 mmHg, and a lactate level >2 mmol/L (>18 mg/dL), despite adequate fluid
resuscitation.

This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jun 12, 2024.
8 BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on
bestpractice.bmj.com . Use of this content is subject to our disclaimer. © BMJ Publishing Group Ltd 2025. All rights reserved.
Sepsis in adults Theory
• Owing to revisions to the definition of sepsis, the term 'severe sepsis' (as previously defined in the 1991/2001
international consensus definitions) should no longer be used.

THEORY
Case history
Case history #1
A 78-year-old woman presents to hospital for an elective right hemicolectomy. She has a past medical history of
hypertension, angina on exertion, and diabetes mellitus. She is independently mobile, does her own shopping,
and has a 30-pack-a-year history of smoking. The operation was uncomplicated. On day 5 post-surgery, she
becomes confused. On examination, she has a Glasgow Coma Scale score of 14/15. She has a temperature of 38.5°C
(101.3°F), a respiratory rate of 28 breaths/minute, and oxygen saturations of 92% on 2 L of oxygen per minute.
She is tachycardic at 118 beats per minute, and her blood pressure is 110/65 mmHg. On chest auscultation, she has
coarse crackles in the right lower zone. Her surgical wound appears to be healing well and her abdomen is soft and
not tender.

Other presentations
Sepsis may complicate benign primary infections found in any age group and requires a high suspicion for the
clinical signs of systemic inflammatory response (tachycardia, fever, tachypnoea, or respiratory compromise).

Altered mental status may also be a presenting feature, especially in older patients. Mild disorientation or confusion
is common with more severe presentations, including significant anxiety, agitation, and loss of consciousness.

Other features that may be present include reduced urine output; a mottled or ashen appearance; cyanosis of skin,
lips, or tongue; or presence of a non-blanching petechial or purpuric rash on the skin.[3]

Recommendations

Urgent
Suspect sepsis based on acute deterioration in a patient in whom there is clinical evidence or strong suspicion of
infection. [41]

Think ‘Could this be sepsis?’ whenever an acutely unwell person presents with likely infection, even if their
temperature is normal.[3] [41] [42] Remember that sepsis represents the severe, life-threatening end of infection.[4]

• Have a low threshold for suspicion.

• The key to improving outcomes is early recognition and prompt treatment, as appropriate, of patients
with suspected or confirmed infection who are deteriorating and at risk of organ dysfunction.[3] [43]
• By the time the diagnosis becomes obvious, with multiple abnormal physiological parameters, risk of
mortality is very high.[41]

• Your clinical judgement is crucial to how you approach the individual patient.[41]

• Be aware that signs and symptoms are extremely variable and often non-specific.[21] [41] [43]
• No diagnostic test is available that can reliably confirm or exclude sepsis in the timeframe within
which treatment should be started for suspected sepsis.[41]

Whenever an acutely ill patient presents with a known infection, presents with symptoms or signs of infection, or
is at high risk of infection, use a systematic approach to assess the risk of deterioration due to sepsis.[42] [43]
[NHS England: Sepsis]

• Always assess and record temperature, heart rate, respiratory rate, blood pressure, level of consciousness,
hourly fluid balance (including urine output), and oxygen saturations.[3]
• Use the findings to risk stratify patients so that immediate sepsis treatment can be prioritised for those at high
risk of deterioration.[3] [43] Always use your clinical judgement.[3] [41]
DIAGNOSIS

Urgent: in hospital
Consult local guidelines for the recommended approach for assessing acute deterioration. Use your clinical
judgement alongside a validated scoring system such as the National Early Warning Score 2 ( NEWS2) (see
Risk stratification below), which is recommended by NHS England and the National Institute for Health and Care
Excellence (NICE).[3] [41] [43] [44] Determine urgency of initial treatment by assessing severity of illness at
presentation; in the UK, use NEWS2 scores as part of wider clinical assessment.[3] [45] 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 (e.g., ST3 level doctor in the UK) for any
patient with an aggregate NEWS2 score of 5 or more calculated on initial assessment in the accident and
emergency department or on ward deterioration.[3] [41] [45] This review should take place:[3] [45]

• Within 30 minutes of initial severity assessment for any patient with an aggregate NEWS2 score of
7 or more; or with a score of 5 or 6 if there is clinical or carer concern, continuing deterioration or
lack of improvement, surgically remediable sepsis, neutropenia, or blood gas/laboratory evidence of
organ dysfunction (including elevated serum lactate)

• A patient is also at high risk of severe illness or death from sepsis if they have a NEWS2
score below 7 and a single parameter contributes 3 points to their NEWS2 score and a medical
review has confirmed that they are at high risk.

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10 BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on
bestpractice.bmj.com . Use of this content is subject to our disclaimer. © BMJ Publishing Group Ltd 2025. All rights reserved.
Sepsis in adults Diagnosis
• Ensure a senior clinical decision-maker (e.g., ST3 level doctor in the UK) attends in person
within 1 hour of any intervention if there is no improvement in the patient’s condition. Refer
to or discuss with a critical care consultant or team.[3] Inform the responsible consultant.[3]

• Within 1 hour of initial severity assessment for any patient with an aggregate NEWS2 score of 5 or
6.

• The higher the aggregate NEWS2 score, the higher the risk of clinical deterioration.[41] [42]
• Although a senior decision-maker should be involved and aware at an early stage for all patients at high risk
of severe illness or death, review may be carried out by a clinician with core competencies in the care of
acutely ill patients (FY2 level or above in the UK) to urgently assess the person's condition and think about
alternative diagnoses to sepsis.[3]
• Patients with critical illness (septic shock, sepsis associated with rapid deterioration, or NEWS2 score of 7 or
more) are most likely to benefit from rapid administration of antibiotics.[45]

If sepsis is strongly suspected (i.e., new organ dysfunction related to severe infection) in an acutely unwell and
rapidly deteriorating patient with a NEWS2 score of 5 or more, the team should act promptly. Establish venous
access early to enable initial assessment and treatment actions according to the timeframes below:[41] [43] [45] [46]
[47]

• Within 1 hour of initial severity assessment for patients with a NEWS2 score of 7 or more calculated on
initial assessment in the accident and emergency department or on ward deterioration (or with a score of 5 or
6 if there are additional clinical or carer concerns, continuing deterioration or lack of improvement, surgically
remediable sepsis, neutropenia, or blood gas/laboratory evidence of organ dysfunction)

• A patient is also at high risk of severe illness or death from sepsis if they have a NEWS2 score
below 7 and a single parameter contributes 3 points to their NEWS2 score and a medical review has
confirmed that they are at high risk.[3]

• Within 3 hours for patients with a NEWS2 score of 5 or 6.

Carry out the following investigations:[3] [41] [46] [47]

1. Blood cultures: take two sets of blood cultures

DIAGNOSIS
• Take bloods immediately, preferably before antibiotics are started (although sampling should not
delay the administration of antibiotics)[3] [43] [48] [49]
• Prioritise filling the aerobic bottle before filling the anaerobic one
• If a line infection is suspected, it is good practice to remove the line and culture the tip

2. Lactate level: measure serum lactate, on a blood gas, to determine the severity of sepsis and monitor the
patient’s response to treatment

• Lactate is a marker of stress and may be a marker of a worse prognosis (as a reflection of the degree
of stress)

• 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

• 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

3. Hourly urine output: assess the patient’s urine output

• A low urine output may suggest intravascular volume depletion or renal failure
• Consider catheterising the patient on presentation if they are shocked/confused/oliguric/critically
unwell.

Start the following treatments:[3] [41] [46] [47]

1. Broad-spectrum intravenous antibiotics (after taking blood cultures), if there is evidence of a bacterial
infection. Only give antibiotics if they have not been given before for this episode of sepsis.[3]
2. Intravenous fluids, if there is any sign of circulatory insufficiency
3. Oxygen, if needed.[50]

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 at 65 mmHg or above.[1]
• Patients with septic shock are likely to benefit from rapid (within 1 hour of presentation) empirical broad-
spectrum antimicrobials.[45]
• See Shock

Early and adequate source identification and control is critical. Undertake intensive efforts, including imaging, to
attempt to identify the source of infection in all patients with sepsis. [3] [43]

• Consider the need for urgent source control as soon as the patient is stable.
DIAGNOSIS

Urgent: in the community

Use your clinical judgement supported by formal risk stratification (e.g., NEWS2), which is endorsed by NHS
England and supported by the Royal College of General Practitioners in the UK, or use the UK National Institute for
Health and Care Excellence (NICE) high-risk criteria (see Risk stratification below) to identify which patients are at
high risk of deterioration due to sepsis.[3] [41] [51]

• Refer for emergency medical care in hospital (usually by blue-light ambulance in the UK) any patient
who is acutely ill with a suspected infection and is:[3]

• Deemed to be at high risk of deterioration due to organ dysfunction (as measured by risk
stratification)
• At risk of neutropenic sepsis

• See Febrile neutropenia .

• Communicate your concern to the ambulance service and hospital colleagues by using the words 'suspected
sepsis', and offer the outcome of your physiological assessment or NEWS2 score.[51]

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12 BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on
bestpractice.bmj.com . Use of this content is subject to our disclaimer. © BMJ Publishing Group Ltd 2025. All rights reserved.
Sepsis in adults Diagnosis

Key Recommendations
Sepsis is a medical emergency with reported high mortality.[3] [43]

• Sepsis is present in many hospitalisations that culminate in death. In 2015, 23,135 people in the UK died
from sepsis, where sepsis was an underlying or contributory cause of death. [NHS England: Sepsis] The true
contribution of sepsis to these deaths is unknown. Most underlying causes of death in people with sepsis are
thought to relate to severe chronic comorbidities and frailty.[5] [7] [8]

Make all efforts to determine escalation status and appropriate potential limits of treatment; ensure any
initiated treatments are appropriate for the individual patient.

Presentation
Have a high index of suspicionfor sepsis as clinical presentation can be subtle.[3] [21]

• Your patient may present with non-specific or non-localised symptoms (e.g., acutely unwell with a normal
temperature) or there may be severe signs with evidence of multi-organ dysfunction and shock.[3] [21]
• At-risk groups include those who:

• Are aged older than 65 years (particularly patients older than 75 years or who are very frail)[3] [9]
[21] [36] [52]
• Are immunocompromised[3] [36] [37] [53] [54]
• Have indwelling lines or catheters[3]
• Have recently had surgery (in the previous 6 weeks)[3]
• Are undergoing haemodialysis[36]
• Have diabetes mellitus[36]
• Misuse drugs intravenously[3]
• Are alcohol-dependent[36] [55]
• Are pregnant, have given birth, or have had a termination or miscarriage in the past 6 weeks[3]
• Have a breach of skin integrity (e.g., cuts, burns, blisters, skin infections).[3]

• Age younger than 1 year is also a strong risk factor.[3] See Sepsis in children .
• Sepsis may also be signalled by a deterioration in functional ability (e.g., a patient newly unable to stand
from sitting).[3]

DIAGNOSIS
Be aware that any patient with known infection, with symptoms or signs of infection, or who is at high risk of
infection might also have or develop sepsis, even with a NEWS2 score of less than 5. [3] In this group, continue to
be aware of the risk of sepsis and specifically look for indicators that suggest the possibility of underlying sepsis:[3]
[41]

• A single NEWS parameter of 3 or more

• Non-blanching petechial or purpuric rash/mottled/ashen/cyanotic skin
• Responds only to voice or pain, or unresponsive
• Not passed urine in last 18 hours or urine output <0.5 mL/kg/hour
• Lactate #2 mmol/L (#18 mg/dL).

If a single parameter contributes 3 points to a patient’s NEWS2 score, request a high-priority review by a clinician
with core competencies in the care of acutely ill patients (in the UK, FY2 or above), for a definite decision on the
person's level of risk of severe illness or death from sepsis.[3] A single parameter contributing 3 points to a NEWS2
score is an important red flag suggesting an increased risk of organ dysfunction and further deterioration.[3] Clinical
judgement is required to evaluate whether the patient’s condition needs to be managed as per a higher risk level
than that suggested by their NEWS2 score alone. A patient’s risk level should be re-evaluated each time new
observations are made or when there is deterioration or an unexpected change.[3]

Protocolised approaches
Your institution may use a guideline-based care bundle as an aide-memoire to ensure key investigations, and
subsequent interventions, are carried out in a timely way as appropriate for the individual patient. Check local
guidelines for the recommended approach in your area. Examples include the following.

The Sepsis Six resuscitation bundle from the UK Sepsis Trust [47]
Sepsis Six is a practical checklist of interventions that must be completed within 1 hour of identifying a patient with
suspected sepsis with a NEWS2 score of 7 or more or other features of critical illness (lactate >2 mmol/L (>18 mg/
dL); chemotherapy in last 6 weeks; other organ failure evident [e.g., acute kidney injury]; patient looks extremely
unwell; patient is actively deteriorating).[45] [47] The original paper outlining this approach, published in 2011,
remains the only published evidence on Sepsis Six, and was subsequently contested.[56] [57] The six interventions
are:[47]

• Inform a senior clinician

• Give oxygen if required
• Obtain intravenous access/take blood cultures
• Give intravenous antibiotics
• Give intravenous fluids
• Monitor.

In 2022, the criteria for triggering the Sepsis Six bundle were aligned with UK Academy of Medical Royal Colleges
(AOMRC) guidance and in 2024 the bundle was updated to reflect updates to NICE guidance.[3] [45] [47]

The 2018 hour-1 care bundle from the Surviving Sepsis Campaign (SSC) [46]
The SSC proposes a 1-hour care bundle, based on the premise that the temporal nature of sepsis means benefit from
even more rapid identification and intervention. The SSC identifies the start of the bundle as patient arrival at triage.
It draws out five investigations and interventions to be initiated within the first hour:[46]

• Begin rapid administration of crystalloid at 30 mL/kg for hypotension or lactate level greater than or equal to
4 mmol/L (36 mg/dL)
• Start vasopressors if the patient is hypotensive during or after fluid resuscitation to maintain mean arterial
pressure level greater than or equal to 65 mmHg.

Subsequent guidance from the SSC and the UK AOMRC supports a more nuanced approach to investigating and
treating patients with suspected sepsis presenting with less severe illness (e.g., without septic shock, or NEWS2
score less than 7).[43] [45] Although early identification and prompt, tailored treatment are key to the successful
management of sepsis, none of the published protocolised approaches is supported by evidence.[58] [59] Therefore,
your clinical judgement is a key part of any approach. [3] [41]

Oxygen saturation in suspected sepsis

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

• Peripheral oxygen saturations can be difficult to measure in a patient with sepsis if the tissues are
hypoperfused.
• You should have a high index of suspicion for shock if you are unable to measure oxygen saturations.

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Sepsis in adults Diagnosis

Objective evidence of new altered mental state

Determine the patient’s baseline mental stateand 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).
[3] As well as checking response to cues, you should ask a relative or carer (if available) about the patient’s recent
behaviour.[3]

• Change in mental state can manifest in many ways, which makes it challenging to recognise as part of a short
clinical consultation.
• This is even more challenging in older patients, who may also have dementia.

• In people with dementia or learning disability, change in mental state may present as irritability
or aggression, but in dementia could also present with hypoactive delirium (e.g., with lethargy,
apathy).[3] [60]

Full Recommendations
Early recognition
Sepsis is present in many hospitalisations that culminate in death. In 2015, 23,135 people in the UK died
from sepsis, where sepsis was an underlying or contributory cause of death. [NHS England: Sepsis] The true
contribution of sepsis to these deaths is unknown. Most underlying causes of death in people with sepsis are thought
to relate to severe chronic comorbidities and frailty.[5] [7] [8]

• Sepsis is defined as life-threatening organ dysfunction that results from a systemic and dysregulated response
to an infection.[1] The presentation can range from non-specific or non-localised symptoms (e.g., feeling
unwell with a normal temperature) through to multi-organ dysfunction and septic shock.[3] [21]
• Septic shock is a subtype of sepsis in which the patient has persistent hypotension and a 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]
• See Shock .

DIAGNOSIS
Early recognition of suspected sepsis is key to improving outcomes.[3] [43] By the time the diagnosis becomes
obvious, with multiple abnormal physiological parameters, risk of mortality is very high.[41]

Have a low threshold for suspecting sepsis: consider the possibility in any acutely unwell patient who meets both
of the following criteria.

1. Has signs or symptoms suggesting infection. In practice, any signs of infection at presentation may be very
subtle and non-specific, so easy to miss. Your initial assessment is therefore key.

• The respiratory tract is the most common site of infection in most people with sepsis.[20] [61] In
people over 65, the most common site is the genitourinary tract.[21] [22]
• Look for any obvious infection source that might need urgent source control.

2. Has vital observations that indicate a risk of deterioration due to organ dysfunction. Use your clinical
judgement alongside a validated early warning score or a structured risk stratification process to assess this.

• 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 and NICE.[3] [41] NEWS2 is also
recommended for use in acute mental health settings and ambulances.[3]

• NICE recommends to use NICE high-risk criteria for stratification of risk (rather than NEWS2)
in an acute setting in patients who are or have recently been pregnant.[3]

See Risk stratification below.

Practical tip

Be aware that patients might not necessarily appear seriously ill at presentation, but their condition may
deteriorate rapidly. The seriousness of a sepsis presentation can be easily underestimated in a busy
environment, such as the emergency department.

Clinical assessment
Careful clinical assessment with a thorough history, examination, and investigations can help you identify sepsis
early. You should consider the possibility of sepsis (i.e., new onset organ dysfunction) whenever an acutely ill
patient presents with a suspected infection.[3]

Presentation
Always interpret signs and symptoms of sepsis in the context of the wider clinical picture as they are often
non-specific and extremely variable. [21] [43] Your initial assessment should focus on:

• Identifying abnormalities of behaviour, circulation, or respiration: in particular, any signs suggestive of septic
shock or serious organ dysfunction

and
• Determining the most likely source of infection and any need for immediate source control.

Common non-specific signs and symptoms include:[21] [43]

• Those associated with a specific source of infection. [Signs and symptoms of possible infection sources]
The most common sources are:[61]

• Respiratory tract (cough/pleuritic chest pain)

DIAGNOSIS

• Urinary tract (flank pain/dysuria)

• Abdominal/upper gastrointestinaI tract (abdominal pain)
• Skin/soft tissue (abscess/wound/catheter site)
• Surgical site or line/drain site

• Tachypnoea
• High (>38°C [>100.4°F]) or low (<36°C [<96.8°F]) temperature, sometimes with rigors
• Tachycardia
• Acutely altered mental status
• Low oxygen saturation
• Hypotension
• Decreased urine output

• Ask the patient when they last passed urine

• Poor capillary refill, mottling of the skin, or ashen appearance

• Cyanosis
• Malaise/lethargy

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Sepsis in adults Diagnosis
• Nausea/vomiting/diarrhoea
• Purpura fulminans (a very late sign but may be seen on presentation)
• Ileus
• Jaundice.

Practical tip

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

DIAGNOSIS

Capillary refill time. Top image: normal skin tone; middle image: pressure
applied for 5 seconds; bottom image: time to hyperaemia measured
From the collection of Ron Daniels, MB, ChB, FRCA; used with permission

Severe purpura fulminans; classically associated with meningococcal sepsis but can occur with pneumococcal sepsis
From the collection of Ron Daniels, MB, ChB, FRCA; used with permission

History
Take a detailed history, focusing on symptoms, recent surgery, underlying disease, history of recent antibiotic
use, other medication history, and travel. Assess patients who might have sepsis with extra care if they cannot
give a good history, for example people with English as a second language or people with communication
DIAGNOSIS

difficulties (such as learning disabilities or autism).[3] 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 seen your general practitioner (GP) or 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:

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Sepsis in adults Diagnosis
• Drug misuse
• Alcohol intake
• Housing situation.

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).

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] [52]
• Immunocompromised (e.g., chemotherapy, sickle cell disease, AIDS, splenectomy, long-term steroids)[3]
[36] [37] [53] [54]

• Suspect neutropenic sepsis in patients who have become unwell and (a) are having or have
had systemic anticancer treatment within the last 30 days or (b) are receiving or have received
immunosuppressant treatment for reasons unrelated to cancer.[3]

• Indwelling lines or catheters[3]

• Recent surgery (in the 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] [55]
• 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 Sepsis in children .

Practical tip

DIAGNOSIS
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:[62]
• 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’.

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] [63]

• Obesity
• Gestational diabetes or diabetes mellitus
• Impaired immune systems (due to illness or drugs)
• Anaemia
• History of pelvic infection

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]

Examination
Follow the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) format to include assessment of
the airway, respiratory, and circulatory sufficiency. Monitor:

• Oxygen saturation

• May show signs of hypoxaemia.

• Respiratory rate
• Heart rate
• Blood pressure
• Temperature
• Hourly fluid balance (including urine output)
• Level of consciousness (Glasgow Coma Scale or AVPU ['Alert, responds to Voice, responds to Pain,
Unresponsive'] scale).

Practical tip
DIAGNOSIS

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 Shock .

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Sepsis in adults Diagnosis
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.[64]
• 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] [65]
• Patients with a spinal cord injury may not develop a raised temperature.[3]
• 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.

Practical tip

Always interpret the vital signs that you take as part of the 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 women, 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)

DIAGNOSIS
• 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.

Pay particular attention to common signs and symptoms:[3] [43]

• Of possible organ dysfunction

• Cyanosis of the skin, lips, or tongue

• Of possible shock [66]

• Hypotension
• Arrhythmia
• Skin changes (mottled, ashen, sweaty; cold or clammy peripheries)
• Fever or hypothermia
• Oliguria

• Of possible circulatory insufficiency

• Oliguria
• Mottled, ashen appearance; sweating
• Prolonged capillary refill times

• Of possible hypovolaemia [67]

• Reduced peripheral skin perfusion and skin temperature

• Reduced skin turgor and dry mucous membranes
• Postural hypotension
• Thirst

• Indicating potential infection/source of infection. [Signs and symptoms of possible infection sources] Most
DIAGNOSIS

commonly:[20] [61]

• Respiratory tract (cough/pleuritic chest pain/tachypnoea/dyspnoea)

• Urinary tract (suprapubic tenderness, loin tenderness, dysuria)
• Abdominal/upper gastrointestinal tract (abdominal pain or guarding/decreased bowel sounds/
diarrhoea/vomiting)
• Skin/soft tissue (breakdown of abscess/wound with redness, swelling, or discharge)
• Post-operative (redness/swelling/discharge/pain at surgical site or line/drain site).

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Sepsis in adults Diagnosis
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 or learning disability, change in mental state may present as irritability
or aggression, but in dementia could also present with hypoactive delirium (e.g., with lethargy,
apathy).[3] [60]
• In addition, sepsis may be signalled by a deterioration in functional ability (e.g., a patient newly unable
to stand from sitting).[3]

Ensure any patient with suspected sepsis has frequent and ongoing monitoring (e.g., using an early warning score
such as the National Early Warning Score 2 [NEWS2]).[3] For advice on when to consult a senior colleague or
escalate to critical care see Management recommendations .

Risk stratification
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 and NICE for use in this setting.[3] [41] NEWS2 is also
recommended for use in acute mental health settings and ambulances.[3]

DIAGNOSIS
• NICE recommends to use the NICE high-risk criteria for stratification of risk (rather than NEWS2) in
an acute setting in patients who are or have recently been pregnant.[3]

2. In the community and in custodial settings: use an early warning score such as NEWS2, which is
recommended by NHS England and supported by the Royal College of General Practitioners in the UK.[41]
[51] An alternative in the UK is to use the NICE high-risk criteria.[3]

• None is validated in primary care.[51]

NEWS2 is the most widely used early warning score in the UK National Health Service and is endorsed by NHS
England and NICE).[3] [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]

In hospital: use the NEWS2 early warning score together with your clinical
judgement
Early warning scores are often used in hospitals to triage patients and to detect clinical deterioration or
improvement over time.[68] [69] NEWS2 is the latest version of the National Early Warning Score (NEWS), first
developed by the UK Royal College of Physicians in 2012 and updated in 2017.[41] [42] [44]

NEWS2 is based on the assessment of six individual parameters, which are each assigned a score of between 0
and 3:[41] [42] [44]

• Respiratory rate
• Oxygen saturations

• There are different scales for oxygen saturation levels based on a patient’s physiological target; use
scale 2 for patients at risk of hypercapnic respiratory failure

• Temperature
• Blood pressure
• Heart rate
• Level of consciousness.

Assess each parameter individually and then add up the final score.
DIAGNOSIS

National Early Warning Score 2 (NEWS2) is an early warning score produced by the Royal College of
Physicians in the UK. It is based on the assessment of six individual parameters, which are assigned a score
of between 0 and 3: respiratory rate, oxygen saturations, temperature, blood pressure, heart rate, and level
of consciousness. There are different scales for oxygen saturation levels based on a patient’s physiological
target (with scale 2 being used for patients at risk of hypercapnic respiratory failure). The score is then
aggregated to give a final total score; the higher the score, the higher the risk of clinical deterioration
Reproduced from: Royal College of Physicians. National Early Warning Score (NEWS) 2: Standardising
the assessment of acute-illness severity in the NHS. Updated report of a working party. London: RCP, 2017.

In an acutely ill patient with symptoms or signs of infection, the NEWS2 score can be an indicator of the
likelihood of sepsis. [3] The higher the resulting aggregate score, the higher the risk of clinical deterioration.

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Sepsis in adults Diagnosis
[41] [42] Use the following approach as a guide alongside your clinical judgement, based on the individual
patient, their history, and their prognosis. [3]

DIAGNOSIS

#7 • Arrange emergency Very likely to be sepsis;

assessment (within 30 significant risk of mortality
minutes of NEWS2
score #7 calculated on
initial assessment in the
accident and emergency
department or on ward
deterioration) by a senior
clinical decision-maker
(e.g., ST3 level doctor in
the UK)

• Although a senior
decision-maker
should be involved
and aware at an
early stage for all
patients at high risk
of severe illness or
death, review may
be carried out by a
clinician with core
competencies in
the care of acutely
ill patients (FY2
level or above in
the UK) to urgently
assess the person's
condition and think
about alternative
diagnoses to
sepsis.[3]
DIAGNOSIS

• Arrange additional
urgent review (within 1
hour) by a senior doctor
or critical care if no
improvement
• Consider transfer to a
high-dependency setting
for continuous monitoring
of vital signs
• Consider immediately
starting investigation
for and, if appropriate,
treatment of sepsis
• Vital observations every
30 minutes

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Sepsis in adults Diagnosis
• Antimicrobials should
be administered within 1
hour

#5 • Arrange urgent review by Likely to be sepsis

a senior clinical decision-
maker (e.g., ST3 level
doctor in the UK) who
should assess whether
escalation to the critical
care team is needed
• A patient is also at high
risk of severe illness or
death from sepsis if they
have a NEWS2 score
below 7 and a single
parameter contributes 3
points to their NEWS2
score and a medical
review has confirmed that
they are at high-risk.

• Although a senior
decision-maker
should be involved
and aware at an
early stage for all
patients at high risk
of severe illness
or death, review
may be carried by a
clinician with core
competencies in

DIAGNOSIS
the care of acutely
ill patients (FY2
level or above in
the UK) to urgently
assess the person's
condition and think
about alternative
diagnoses to
sepsis.[3]

• Consider immediately
initiating investigation
for and, if appropriate,
treatment of sepsis
• Hourly vital observations
• Antimicrobials should
be administered within 3
hours

• A single NEWS2
parameter of 3 or
more
• Non-blanching
rash/mottled/ashen/
cyanotic skin
• Responds only to
voice or pain, or
unresponsive
• Not passed urine
in last 18 hours or
urine output <0.5
mL/kg/hour
• Lactate #2 mmol/L
(#18 mg/dL)

• Registered nurse review

within 1 hour
• Vital observations every 4
to 6 hours if stable
• Escalate if no
improvement
• Identify any source of
DIAGNOSIS

infection within 6 hours

• Administer antimicrobials
within 6 hours if infection
is probable or definite

If a single parameter contributes

3 points to a patient’s NEWS2
score, request a high-priority
review by a clinician with core
competencies in the care of
acutely ill patients (in the UK,
FY2 or above), for a definite
decision on the person's level
of risk of severe illness or death
from sepsis.[3]

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Sepsis in adults Diagnosis
Practical tip

Interpret the initial NEWS2 score in the context of your clinical assessment. Assess patients who might
have sepsis with extra care if they cannot give a good history, for example, people with English as a second
language or people with communication difficulties (such as learning disabilities or autism).[3] Upgrade the
patient’s severity status and your accompanying actions to at least the next NEWS2 level if there is clinical or
carer concern, continuing deterioration or lack of improvement, surgically remediable sepsis, neutropenia, or
blood gas/laboratory evidence of organ dysfunction (including elevated serum lactate).[3] [45] Interpretation
should take into account any NEWS2 score calculated (or intervention carried out) before initial assessment
in the accident and emergency department.[3] A patient’s risk level should be re-evaluated each time new
observations are made or when there is deterioration or an unexpected change.[3]

Practical tip

As part of your initial assessment, consider the influence of comorbid disease, frailty, and patient preferences
(regarding treatment intensity, limits of treatment, and end-of-life care).[3] [45]

Debate: Role of the qSOFA score

Although the sequential organ failure assessment score (SOFA) and quick-SOFA (qSOFA) are accepted as
useful tools for prognostication, they are not recommended by UK or international guidelines as a tool for
early identification of sepsis.

• NHS England and NICE recommend the use of NEWS2 scores in the acute setting. NICE recommends its
own risk stratification criteria in community and custodial settings, and in an acute setting in patients who
are or have recently been pregnant.[3] [41] [70] [NHS England: Sepsis]
• The Surviving Sepsis Campaign advises against using the qSOFA score compared with NEWS or the
Modified Early Warning Score (MEWS) as a single screening tool for sepsis or septic shock.[43]

While the qSOFA score is not a bedside scoring tool, it can be used as an alternative to NEWS to identify any
patient at high risk of an adverse outcome in healthcare systems that don’t use NEWS. qSOFA shares 3 of the 7
NEWS2 criteria; using qSOFA, an acutely ill patient with suspected or confirmed infection is considered to be at
high risk of an adverse outcome (from sepsis) if at least two of the following three criteria are present:[1]

• Altered mental state (Glasgow Coma Scale score <15)

DIAGNOSIS
• Systolic blood pressure #100 mmHg
• Respiratory rate #22 breaths/minute.

Evidence suggests that early warning scores such as NEWS2 have better sensitivity and specificity than
the qSOFA score for predicting deterioration and mortality among patients presenting to the emergency
department with suspected infection. [69]

It is important to be aware that no scoring system has been validated for use in pregnant women or
women who have recently been pregnant(in the 24 hours following a termination of pregnancy or
miscarriage for 4 weeks after giving birth); in practice, seek senior input to determine the best approach in
these patients.
The UK NICE recommends use of the NICE high-risk criteria for stratification of risk (rather than NEWS2)
in an acute setting in patients who are or have recently been pregnant.[3]
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.[71]
• 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.[72]

Ensure there is senior input, with a low threshold to escalate to a consultant, if a patient with suspected sepsis
who is or has recently been pregnant and meets any high-risk criteria, does not respond within 1 hour of any
intervention.[3]

In the community: use the NEWS2 early warning score or the NICE high-risk
criteria, together with your clinical judgement
Primary care has a significant role to play in identifying suspected sepsis at an early stage and to promptly
escalate care where appropriate. [51] A key aspect of this is the consistent use and recording of physiology as
part of the assessment of infection and the deteriorating patient. The method selected for doing this in primary care
is still open to challenge due to a lack of evidence in this setting; no one approach to risk stratification has been
validated in primary care.[51] Therefore, using your clinical judgement in making a decision is paramount.[41]

To identify which acutely ill patients with suspected or confirmed infection are at high risk of deterioration due to
sepsis in the community, use either:

• NEWS2 or an alternative early warning score [41] [42] [51] [NHS England: Sepsis]

• NEWS2 is recommended by NHS England and supported by the Royal College of General
Practitioners in the UK and NICE.[3] [41] [51]
DIAGNOSIS

-or-
• The NICE sepsis high-risk criteria [3]

• NICE recommends to use these criteria for stratification of risk in people aged 16 or above if they are
in community or custodial settings or if they are in an acute setting and are, or have recently been,
pregnant.[3]

If an acutely ill patient presents with symptoms and signs of infection AND meets any one or more of these
criteria, OR is deemed to be at risk of neutropenic sepsis, refer for emergency medical care in hospital
(usually by blue-light ambulance in the UK):

• Objective evidence of new altered mental state (e.g., new deterioration in Glasgow Coma Scale score/
AVPU ['Alert, responds to Voice, responds to Pain, Unresponsive'] scale)
• Respiratory rate: 25 breaths per minute or more OR new need for oxygen (40% or more fraction of
inspired oxygen [FiO 2 ]) to maintain saturation more than 92% (or more than 88% in known chronic
obstructive pulmonary disease)
• Heart rate: more than 130 beats per minute
• Systolic blood pressure 90 mmHg or less or systolic blood pressure more than 40 mmHg below
normal

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Sepsis in adults Diagnosis
• Not passed urine in previous 18 hours, or for catheterised patients passed less than 0.5 mL/kg of urine
per hour
• Mottled or ashen appearance
• Cyanosis of skin, lips, or tongue
• Non-blanching petechial or purpuric rash on skin.

Historically, respiratory rate, blood pressure/perfusion, and cognition are among the least well recorded
values by general practitioners in the UK when assessing patients with sepsis. [61]

Note that NICE recommends to use NEWS2 (rather than the NICE sepsis high-risk criteria) in ambulances.[3]

Practical tip

A systematic approach is key to earlier identification of patients at risk of sepsis. The Royal College of
General Practitioners in the UK highlights the importance of ensuring you have the right equipment available
in every consultation room, including: a thermometer (tympanic and axillary), a pulse oximeter suitable for
use in all age groups, and a sphygmomanometer.[73]

Take a cautious approach when deciding whether it is safe to treat an acutely unwell patient in the
community.

• For more details on managing patients in the community, see Management recommendations .

Practical tip

If you need to refer a patient for emergency medical care in hospital, it is important to inform the hospital
clinical team that the patient is on the way. This will enable the hospital to prepare to start appropriate
management as soon as the patient arrives.

Identifying the infection source

Make intensive efforts to identify the most likely anatomical source of infection as soon as possible, including
sources that might need drainage or other interventions.[3] [43] Consider the need for urgent source control as
soon as the patient is stable.

DIAGNOSIS
• Start with a thorough and focused clinical history and examination, as well as initial investigations
including imaging.[3]
• Early and adequate source control is critical, particularly for:[43]

• Gastrointestinal sources (such as visceral abscesses, cholangitis, or peritonitis secondary to

perforation)
• Severe skin infections (e.g., necrotising fasciitis)
• Infection involving an indwelling device, where a procedure or surgery is likely to be required.

Consider all lines, including Hickman and peripherally inserted central catheter (PICC), and catheters as
potential sources. If you suspect a line infection, is it good practice to remove the line and culture the tip. [43]

• Assume that any intravenous route is likely to either be the source of the infection, or will seed infections in
the bloodstream, making eradication particularly difficult. Therefore, the priority for source control is often
to remove any intravenous devices after vascular access has been obtained.[43]

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]

Sites of infection
The respiratory tract is the most common site of infection in people with sepsis, followed by the abdomen,
urinary tract, soft tissues, and joints, and – rarely – the central nervous system.[20]

• Beware necrotising fasciitis and septic arthritis, which require immediate surgical intervention.

Practical tip

Necrotising fasciitis is notoriously difficult to diagnose. The initial symptoms are non-specific and the clinical
course is often slower than might be expected. Typically, the first sign is pain disproportionate to the
clinical findings, followed or accompanied by fever.[74]
DIAGNOSIS

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Sepsis in adults Diagnosis

Evidence: Infectious causes of sepsis

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.[61]

DIAGNOSIS

The relative frequencies of sources of infection in sepsis

Created by the BMJ Knowledge Centre; based on 'NCEPOD. Just say sepsis! Nov 2015'

Investigations
Start treatment promptly and before test results are available if the patient is critically ill (e.g., septic shock or
NEWS2 score 7 or more).[45]

Above all else, if the patient has suspected sepsis, always:[3] [46] [47]

• Take two sets of blood cultures

• Measure serum lactate
• Start monitoring hourly urine output.

Complete these investigations within 1 hour for patients with a NEWS2 score of 7 or more calculated on initial
assessment in the accident and emergency department or on ward deterioration, or within 3 hours for patients with
a NEWS2 score of 5 or 6.[3] [45]

Take bloods immediately, before antibiotics are started (although sampling should not delay the administration of
antibiotics).[3] [43] [48] [49]

Practical tip

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

Practical tip

Recommended timeframes are not intended to permit delay in treatment, but to offer time to make a safe and
informed clinical decision. If actions can be completed earlier than the proposed time limit, then they should
be.[45]

Blood cultures
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.
DIAGNOSIS

• 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 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.

Lactate
Measure serum lactate, on a blood gas, to determine the severity of the sepsis and monitor response to
treatment. [3] [46] [47]

• 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.[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.

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Sepsis in adults Diagnosis
• 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%.

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 National Early
Warning Score 2 (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).

DIAGNOSIS
Practical tip

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

Urine output
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. [3]

• 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]

Care bundles
Your institution may use a guideline-based care bundle as an aide-memoire to ensure key investigations, and
subsequent interventions, are carried out in a timely way as appropriate for the individual patient. Check
local guidelines for the recommended approach in your area. Examples include the following.

The Sepsis Six resuscitation bundle from the UK Sepsis Trust [47]

Sepsis Six is a practical checklist of interventions that must be completed as quickly as possible, and for the sickest
patients always within 1 hour of identifying suspected sepsis.[47] The original paper outlining this approach,
published in 2011, remains the only published evidence on Sepsis Six, and was subsequently contested.[56] [57]
The six interventions are:[47]

• Inform a senior clinician

• Give oxygen if required
• Obtain intravenous access/take blood cultures
• Give intravenous antibiotics
• Give intravenous fluids
• Monitor.

The 2018 hour-1 bundle from the Surviving Sepsis Campaign (SSC) [46]

The SSC proposes a 1-hour care bundle, based on the premise that the temporal nature of sepsis means benefit from
even more rapid identification and intervention. The SSC identifies the start of the bundle as patient arrival at triage.
It draws out five investigations and interventions to be initiated within the first hour:[46]

• Measure lactate level and remeasure if the initial lactate level is greater than 2 mmol/L (18 mg/dL)
• Obtain blood cultures before administration of antibiotics
• Administer broad-spectrum intravenous antibiotics
• Begin rapid administration of crystalloid at 30 mL/kg for hypotension or lactate level greater than or equal to
4 mmol/L (36 mg/dL)
• Start vasopressors if the patient is hypotensive during or after fluid resuscitation to maintain mean arterial
pressure level greater than or equal to 65 mmHg.
DIAGNOSIS

Subsequent guidance from the SSC and the UK Academy of Medical Royal Colleges supports a more nuanced
approach to investigating and treating patients with suspected sepsis presenting with less severe illness (e.g., without
septic shock, or NEWS2 score less than 7).[43] [45] Although early identification and prompt, tailored treatment
are key to the successful management of sepsis, none of the published protocolised approaches is supported by
evidence.[58] [59] Therefore, your clinical judgement is a key part of any approach.

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Sepsis in adults Diagnosis

Controversy: Protocolised care bundles

Robust evidence to support the use of care bundles, such as Sepsis Six or the SSC hour-1 bundle (2018), to
improve outcomes in people with sepsis is lacking. [58] [59] Available data are from observational studies
only, which come with methodological limitations; in particular, they cannot resolve questions of causality.
[56] [81] [82] [83] [84] [85] [86] Some organised medical societies have declined to support 1-hour target-
based approaches to the management of sepsis, while other current guidelines mandate the importance of
1-hour care bundles. [3] [58] [59] [87] [88] [43] There is agreement across the board that appropriate and
timely recognition and subsequent resuscitation are important for any severely ill patient presenting with
sepsis. [3] [43] [58] [59] [87] [88]

• Sepsis Six was specifically designed to facilitate early intervention in busy hospital and pre-hospital
settings.[89] [90] The original paper outlining the approach, published in 2011, was a prospective
observational cohort study that looked at data from 567 patients.[56] Statistical analysis of the data
did not take into account the differences between the cohorts: most importantly, age and infection
source. The study reported that delivery of the bundle is associated with a 55% relative risk reduction in
mortality.[56] Further evidence has since emerged to contest the delivery of Sepsis Six translating to any
improvement in mortality.[57] In 2022, the Sepsis Six-recommended timeframes for investigation and
treatment of patients with suspected sepsis were amended in line with UK Academy of Medical Royal
Colleges (AOMRC) guidance, with a 1-hour window for patients with the highest-severity illness (e.g.,
septic shock or NEWS2 score 7 or more) and a 3-hour window for patients with less severe illness.[45]
[47] There was a subsequent update in 2024 to reflect updates to NICE guidance.[3] [47]
• Other datasets report clinical improvements associated with earlier completion of sepsis bundles, some
citing an increased mortality for every hour’s delay.[81] [82] [83] [84] [85] [86]

• Commentators have challenged the methodology of these studies, which were all observational
cohorts that separated patients by the time to intervention and usually after a clear start signal,
such as shock or an elevated lactate level – in particular, their inability to:[58] [59]

• Define causation, only association

• Detect the granular differences that 1 hour versus 2 or 3 hours to complete makes on overall
care (for patients with and without sepsis alike).

• The temporal benefits identified in these trials existed in the sickest subset of patients with septic
shock, suggesting that when they are applied to a general population in the emergency department,

DIAGNOSIS
overall benefit will be diluted and net harm (from over-treatment) may occur.[83]

• Owing to these gaps in robust evidence, some organised medical societies have declined to support the
care-bundle-based recommendations, citing the lack of data to support current proposed targets.[58] [59]

• The Infectious Diseases Society of America (IDSA) has withheld its endorsement of the Surviving
Sepsis Campaign guidelines and the 1-hour bundle, as has the American College of Emergency
Physicians.[59] IDSA notes that 40% of patients admitted to intensive care for sepsis ultimately do
not have that condition, leading to adverse consequences of unnecessary antibiotics.[87]
• IDSA and others encourage the gathering of more data to confirm a diagnosis of sepsis and
working to a less rigid time threshold.[88]

• The National Institute for Health and Care Excellence (NICE) in the UK recommends 1-hour targets, as
does NHS England (under specific circumstances).[3] [41]
• Although the SSC still promotes use of a 1-hour care bundle, the SSC 2021 guideline update recommends
stratification of patients with suspected sepsis according to the presence or absence of septic shock,
with initial investigation and treatment to take place within 1 hour if shock is present, or within 3 hours
for patients with less severe illness.[43] This change is based largely on the evidence from a 2018
prospective randomised controlled trial evaluating early antibiotic administration in an undifferentiated

Blood tests
Full blood count
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 white blood cell (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.

Urea and electrolytes (including creatinine)

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]
DIAGNOSIS

• Determine whether the patient would benefit from haemofiltration or intermittent haemodialysis [43]
• Identify sodium, potassium, calcium, magnesium, and chloride abnormalities.

Serum glucose
Measure serum glucose on a 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 of 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.

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Sepsis in adults Diagnosis
Practical tip

Spontaneous or iatrogenic hypoglycaemia also poses significant dangers.[98] [99] Persisting hypoglycaemia
may suggest acute liver failure.[100]

C- reactive protein
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] [101] [102]

Serum procalcitonin
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 SSC suggests using procalcitonin alongside clinical evaluation to decide when to discontinue
antimicrobials.[43]

Clotting screen
Include prothrombin time, partial thromboplastin time, and fibrinogen. [3]

• Use to determine whether the patient has established coagulopathy in the presence of sepsis. This is
associated with a worse prognosis.[106]

Liver function tests

Use liver function tests, notably bilirubin, to evaluate for organ dysfunction.[3] [107] [108] Liver dysfunction may
also be a cause of a coagulopathy.

Blood gas
Request blood gas tests. [3]

DIAGNOSIS
Use either arterial blood gas (ABG) or venous blood gas evaluation. Use ABG to optimise oxygenation and
assess metabolic status (acid-base balance), particularly with regard to the arterial carbon dioxide level
(PaCO 2 ).

• 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 (FiO 2 ).

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.

Investigations to identify source of infection

Tailor investigations to the patient’s history and examination findings. [3]

Urine analysis
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]

Chest x-ray
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.[110] [111]

Cultures from multiple sources

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
DIAGNOSIS

• Ascitic fluid
• Joint fluid
• Abscess aspirate
• Swabs from open wounds or ulcers.

Lumbar puncture
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:

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Sepsis in adults Diagnosis
• 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.

Computed tomography
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 infection
in particular as, in practice, outcomes tend to be worse with gastrointestinal 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]

Ultrasound
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]

• 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

DIAGNOSIS
any given infection source.

Urine antigen testing

Carry out legionella and pneumococcal urine antigen testing in all patients with suspected or confirmed
community-acquired pneumonia.[119]

Viral swabs
Consider rapid respiratory viral polymerase chain reaction in people with suspected respiratory aetiology.[120]

Other investigations for all patients

ECG
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]

Other investigations to consider for some patients

HIV screen
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).

Echocardiogram (echo)
Consider 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]

Procedural videos

History and exam

Key diagnostic factors
risk factors (common)
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] [52]
• Immunocompromised (e.g., chemotherapy, sickle cell disease, AIDS, splenectomy, long-term steroids)[3]
DIAGNOSIS

[36] [37] [53] [54]

• 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] [55]
• 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 Sepsis in children.

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Sepsis in adults Diagnosis
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] [63]

• 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:[62]
• Altered mental state – ‘confused’, ‘drowsy’, ‘not themselves’

DIAGNOSIS
• Fever – ‘warm to touch’, ‘shivery', ‘burning up’
• Hypotension – ‘dizzy’, ‘faint’, ‘lightheaded’
• Tachypnoeic – ‘out of breath’, ‘breathless’
• Tachycardic – ‘heart is racing’, ‘heart is pounding’.

signs associated with specific source of infection (common)

The most common sources of infection are:[61]

• 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]

• 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?

• Ask about the patient’s lifestyle, including:

• Drug misuse
• Alcohol intake
• Housing situation.

Practical tip

• 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).

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Sepsis in adults Diagnosis

Evidence: Infectious causes of sepsis

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.

DIAGNOSIS

The relative frequencies of sources of infection in sepsis

Created by the BMJ Knowledge Centre; based on 'NCEPOD. Just say sepsis! Nov 2015'

high early warning score (e.g., NEWS2 5 or more) (common)

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]

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 and the National Institute for Health and Care Excellence
(NICE) for use in this setting.[3] [41]

• NICE recommends to use NICE high-risk criteria for stratification of risk (rather than NEWS2) in
an acute setting in patients who are or have recently been pregnant.[3]

2. In the community and in custodial settings: use an early warning score such as NEWS2, which is
recommended by NHS England and supported by the Royal College of General Practitioners in the
UK.[41] [51] An alternative in the UK is to use NICE high-risk criteria.[3]

• None is validated in primary care.[51]

NEWS2 is the most widely used early warning score in the UK National Health Service and is endorsed by NHS
England and NICE.[3] [41] [NHS England: Sepsis] In a patient with a known or likely infection, a NEWS2
DIAGNOSIS

score of 5 or more is likely to indicate sepsis. [42]

Arrange urgent assessment by a senior clinical decision-maker (e.g., ST3 level doctor in the UK) 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.[3] [41] [42]
• Although a senior decision-maker should be involved and aware at an early stage for all patients at high
risk of severe illness or death, review may be carried out by a clinician with core competencies in the care
of acutely ill patients (FY2 level or above in the UK) to urgently assess the person's condition and think
about alternative diagnoses to sepsis.[3]
• If necessary (e.g., NEWS2 score of 7 or more, or no response within 1 hour of any interventionsuch
as antibiotics/fluid resuscitation/oxygen), arrange emergency assessment by a critical care specialist.

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Sepsis in adults Diagnosis
Practical tip

It is important to be aware that no scoring system has been validated for use in pregnant women or
women who have recently been pregnant(in the 24 hours following a termination of pregnancy or
miscarriage for 4 weeks after giving birth); in practice, seek senior input to determine the best approach
in these patients.
NICE recommends use of the NICE high-risk criteria for stratification of risk (instead of NEWS2) in an
acute setting in patients who are or have recently been pregnant.[3]
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.[71]
• 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.[72]

Alert a consultant to attend in person if a patient with suspected sepsis, who is or has recently been
pregnant and meets any high-risk criteria, does not respond within 1 hour of any intervention.[3]

tachypnoea (NEWS2) (common)

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

high or low temperature, sometimes with rigors (NEWS2) (common)

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

DIAGNOSIS
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.[64]
• 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] [65]
• Patients with a spinal cord injury may not develop a raised temperature.[3]
• 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.

tachycardia (NEWS2) (common)

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

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 women, 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.
DIAGNOSIS

acutely altered mental status (NEWS2) (common)

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). [3] As well as checking response to cues, you should ask a relative or carer (if
available) about the patient’s recent behaviour.[3]

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Sepsis in adults Diagnosis
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 or learning disability, change in mental state may present as irritability
or aggression, but in dementia, could also present with hypoactive delirium (e.g., with lethargy,
apathy).[3] [60]
• 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 (NEWS2) (common)

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

Practical tip

DIAGNOSIS
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 Shock .

hypotension (NEWS2) (common)

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]

• 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. [3]

• 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]

poor capillary refill, mottling of the skin, or ashen appearance (common)

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

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Sepsis in adults Diagnosis

DIAGNOSIS
Capillary refill time. Top image: normal skin tone; middle image: pressure
applied for 5 seconds; bottom image: time to hyperaemia measured
From the collection of Ron Daniels, MB, ChB, FRCA; used with permission

cyanosis (common)
A common non-specific sign of sepsis.[21]

Other diagnostic factors

malaise/lethargy (common)
Commonly seen in people with sepsis.[21]

nausea/vomiting/diarrhoea (common)
Commonly seen in people with sepsis.[21]

Severe purpura fulminans; classically associated with meningococcal sepsis but can occur with pneumococcal sepsis
From the collection of Ron Daniels, MB, ChB, FRCA; used with permission

ileus (uncommon)
DIAGNOSIS

A sign of possible organ dysfunction.

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

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Sepsis in adults Diagnosis

Investigations
1st test to order

Test Result
blood cultures may be positive for infection-
Take bloods immediately, before antibiotics are started (although causing organism
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.
serum lactate may be elevated; persistent
Measure serum lactate, on a blood gas, to determine the severity of the levels >2 mmol/L (>18 mg/
sepsis and monitor response to treatment. [3] [43] [47] dL) associated with adverse
prognosis; even worse prognosis
• Lactate is a marker of stress and may help to provide an overall
with persistent levels >4 mmol/L

DIAGNOSIS
picture of someone’s prognosis (as a reflection of the degree of
stress).[3] Raised serum lactate highlights the possibility of tissue (>36 mg/dL)
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.

Test Result
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
DIAGNOSIS

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.

hourly urine output may be markedly decreased

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.

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Sepsis in adults Diagnosis

Test Result
• 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]

full blood count WBC count >12×10#/L (12,000/

Carry out a venous blood test to determine the patient’s full blood count.[3] microlitre) (leukocytosis);
WBC count <4×10#/L (4000/
Thrombocytopenia of non-haemorrhagic origin may occur in patients who
are severely ill with sepsis.[92] microlitre) (leukopenia)

• 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.
urea and electrolytes (including creatinine) serum electrolytes frequently
Request urea and electrolyte tests;[3] use to: deranged; blood urea may be
elevated; creatinine may be

DIAGNOSIS
• Evaluate the patient for renal dysfunction
elevated
• 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.

serum glucose may be elevated or, more rarely,

Measure serum glucose on blood gas, in venous blood through low
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

Test Result
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.

Practical tip

Spontaneous or iatrogenic hypoglycaemia also poses significant

dangers.[98] [99] Persisting hypoglycaemia may suggest acute liver
failure.[100]
C-reactive protein elevated
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] [101] [102]

serum procalcitonin may be elevated
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]

clotting screen elevated PT; elevated PTT;

Include prothrombin time (PT), partial thromboplastin time (PTT), and elevated D-dimer; elevated
DIAGNOSIS

fibrinogen. [3] fibrinogen

• Use to determine whether the patient has established coagulopathy

in the presence of sepsis. This is associated with a worse
prognosis.[106]

liver function tests elevated bilirubin, alanine

Use liver function tests, notably bilirubin, to evaluate for organ aminotransferase, aspartate
dysfunction.[3] [107] [108] Liver dysfunction may also be a cause of a aminotransferase, alkaline
coagulopathy.
phosphatase, and gamma
glutamyl transpeptidase

blood gas PaCO# <4.3 kPa (32 mmHg) is

Use either arterial blood gas (ABG) or venous blood gas (VBG) one of the diagnostic criteria for
evaluation. [3] Use ABG to optimise oxygenation and assess metabolic systemic inflammatory response
status (acid-base balance), particularly with regard to the arterial
syndrome; may be hypoxaemia,
carbon dioxide level (PaCO 2 ).
hypercapnia

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Sepsis in adults Diagnosis

Test Result
• 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 (FiO 2 ).

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.

ECG may show evidence of

Request a baseline ECG for any patient with suspected sepsis, as you would ischaemia, atrial fibrillation, or
for all acutely ill presentations, to: other arrhythmia

• 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]

DIAGNOSIS

Other tests to consider

Test Result
urine analysis may show evidence of infection
Consider a dipstick test in any patient who has suspected sepsis to help add (nitrates; leucocytes; blood/
weight to a suspected urinary source of infection.[3] protein)
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]

chest x-ray may show evidence of infection,

Consider a chest x-ray (CXR) in any patient with suspected sepsis to help such as consolidation or pleural
add weight to a suspected respiratory source (the most common source) effusion, cardiac abnormalities,
of infection.[3]
or a pneumothorax
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.[110] [111]
cultures from multiple sources may be positive for infection-
Consider taking cultures from multiple sources to determine the site and/or causing organism
organism responsible for the infection, including:[43]

• Urine
• Sputum (if accepted by the laboratory)
• Stool
• Cerebrospinal fluid
• Pleural fluid
DIAGNOSIS

• Ascitic fluid
• Joint fluid
• Abscess aspirate
• Swabs from open wounds or ulcers.

lumbar puncture elevated WBC count, presence

Perform a lumbar puncture if you suspect meningitis or encephalitis, of organism on microscopy, and
provided there is no suspicion of raised intracranial pressure (a positive culture
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

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Sepsis in adults Diagnosis

Test Result
• 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.

computed tomography findings vary depending on

A computed tomography (CT) scan of the chest and/or abdomen and systems affected but may
pelvis provides cross-sectional imaging of the body to attempt to identify include: a hidden collection
the source of sepsis.[3] Consider early CT if you suspect gastrointestinal
(e.g., a visceral abscess or
(GI) infection in particular as, in practice, outcomes tend to be worse with
GI sepsis compared with other sites of infection. effusion); free air (perforation)

• 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

DIAGNOSIS
soon as possible, in line with the advice received.[3]

ultrasound may identify: abscess; free fluid

Consider ultrasound scanning to help locate the source of the infection, (peritonitis); common bile duct
particularly if you suspect an abdominal source or where the source of dilatation (cholangitis); areas of
infection is not clear after the initial clinical examination and tests.[3] [43]
infarction secondary to emboli
• In particular, use ultrasound to identify: (e.g., infective endocarditis);
hydronephrosis (pyelonephritis)
• 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.

urine antigen testing may show evidence of infection

Carry out legionella and pneumococcal urine antigen testing in all patients
with suspected or confirmed community-acquired pneumonia.[119]

Test Result
viral swabs may show evidence of
Consider rapid respiratory viral polymerase chain reaction in people with respiratory infection
suspected respiratory aetiology.[120]
HIV screen may be positive for HIV
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).

echocardiogram inadequate left ventricular

Consider echocardiogram (echo) for a more detailed assessment of the filling suggests hypovolaemia;
causes of the haemodynamic issues. Use echo to assess (left and/or vegetations, if endocarditis is
right) ventricular dysfunction, which may be caused by sepsis, and to
cause of sepsis
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]
DIAGNOSIS

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Sepsis in adults Diagnosis

Differentials

Condition Differentiating signs / Differentiating tests

symptoms
Non-infectious causes of • SIRS can result as a non- • Specific tests are directed by
systemic inflammatory specific finding from a host of clinical suspicion of underlying
response syndrome (SIRS) other disease states, including cause.
post-operative recovery, • Associated medical
trauma, burns, transplant interventions (e.g.,
rejection, hyperthyroidism, catheterisation, surgical
Addisonian crisis, blood procedures, ventilation)
product transfusion reactions, can subsequently lead to
serum sickness, immunisations, superimposed infections to
and central nervous system make sepsis a continual threat
infarction or haemorrhages. and possibility.

Myocardial infarction (MI) • Symptoms suggesting MI are • Ischaemic changes on ECG.

central, squeezing chest pain or • Elevated creatine kinase-MB
pressure radiating down the left and troponin.
arm or into the jaw. Pain may
be felt in the epigastric region.
• Patients may present in
cardiogenic shock with
breathlessness and hypotension.
A low-grade fever and raised
C-reactive protein may also be
present.

Pericarditis • Patients present with sharp, • ECG may have upward concave
stabbing, pleuritic chest pain ST-segment elevation globally
(typically better on sitting and PR-segment depression.
up and leaning forward, and • Echo may demonstrate a
worse with lying down) and pericardial effusion; absence
sometimes a low-grade fever. of left ventricular wall motion

DIAGNOSIS
abnormalities.

Myocarditis • Patients typically present with • ECG may show non-specific

a viral prodrome (which may ST-segment and T-wave
include a low-grade fever), abnormalities.
dyspnoea, or underlying • Inflammatory markers may be
autoimmune condition, such as elevated.
systemic lupus erythematosus. • Two-dimensional echo
• Medications such as demonstrates global and
antibiotics, thiazide diuretics, regional left ventricular motion
antiepileptics, digoxin, lithium, abnormalities and dilatation.
amitriptyline, and dobutamine
may be suggestive of drug
aetiology.

Acute pancreatitis • May present with abdominal • Elevated serum amylase, lipase,
pain radiating through to the glucose; low calcium.
back, low-grade fever, and
hypovolaemia.
• There may be a history of
gallstones, alcohol use, or viral
infections (e.g., mumps).

Condition Differentiating signs / Differentiating tests

symptoms
Massive pulmonary embolism • Typically presents with acute • CT pulmonary angiogram
dyspnoea and hypotension. shows a filling defect in the
Symptoms may also include pulmonary arteries.
fever, decreased consciousness,
syncope or pre-syncope, and
pleuritic chest pain. Risk factors
for thromboembolic disease
may be evident.

Leukaemia • May present with fever, • Biopsies of blood smear, bone

leukocytosis, anaemia, marrow, tumour, or lymph
tachycardia, multi-organ nodes may identify neoplastic
dysfunction, and dyspnoea and cells.
thus meet diagnostic criteria for • Identification of a specific
(suspected) sepsis. infectious agent is definitive
• The immunocompromise in differentiating sepsis from
may additionally facilitate SIRS.
development of infections or
the increased clinical suspicion
of undiagnosed infection.

Malignant hyperthermia • This is a rare condition • The caffeine-halothane

characterised by severe contracture test (CHCT) is most
hyperthermia (>41.1°C commonly used to screen for
[106°F]) and muscle rigidity susceptibility, as ryanodine
following administration receptor gene (RYR1)
of anaesthetic agents (e.g., identification is gaining in
succinylcholine for intubation). clinical importance.[127]
Lactic acidosis, hyperkalaemia, • The CHCT requires muscle
rhabdomyolysis, hypoxia, biopsy and testing in select
and arrhythmias may also regional laboratories after
occur.[126] resolution of the episode.
• Malignant hyperthermia is an • Neither test is clinically useful
DIAGNOSIS

inherited disorder (autosomal to direct therapy in the acute

dominant) and a high index of situation.
suspicion is necessary if there is
a positive family history.[126]

Drug-induced fever and coma • This includes neuroleptic • Clinical diagnosis. Specific
malignant syndrome, tests are not readily available.
serotonergic syndrome,
delirium tremens, and
metformin lactic acidosis.
• History of causative drug use.

Criteria

There are multiple scoring systems and definitions for sepsis and sepsis with organ dysfunction. None is perfect and
many seek to measure similar variables.

In February 2016, new definitions of sepsis and septic shock were published by the Third International Consensus
group; the so-called ‘Sepsis-3’ definitions.[1] Sepsis was redefined by Sepsis-3 as “life-threatening organ dysfunction
caused by a dysregulated host response to infection”.[1]

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Sepsis in adults Diagnosis
Organ dysfunction is defined as a change of 2 or more points in the Sequential (or Sepsis-related) Organ Failure
Assessment (SOFA) score.[1]

Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) criteria

Created by BMJ, adapted from Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ
Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-
Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22:707-10.

The shift away from the previous definitions (which described sepsis as a systemic inflammatory response syndrome

DIAGNOSIS
[SIRS] arising due to a new infection) aimed to facilitate earlier diagnosis as well as greater consistency for research
outcomes.[1]

In the first international consensus definitions, which date from 1991, severe sepsis was defined as sepsis associated
with organ dysfunction, hypoperfusion, or hypotension; septic shock was defined as sepsis with hypotension despite
adequate fluid replacement.[3] However, the 2016 Third International Consensus Group (Sepsis-3) definitions state that
the term 'severe sepsis' should be made redundant in light of the revisions to the definition of sepsis.[1]

Acute Physiology and Chronic Health Evaluation II score (APACHE II)[128]

The APACHE score is commonly used to establish illness severity in the intensive care unit (ICU) and predict the risk
of death. There is a high risk of death if the score is #25.

Other sepsis risk-scoring models

Several other models have been developed for use in the ICU, including APACHE III, the Simplified Acute Physiology
Score, and Mortality Probability Model II.[129] [130] [131]

Patient group-specific scoring systems have also been developed. For example, the Predisposition Insult Response and
Organ failure and Mortality in Emergency Department Sepsis scores have been developed to risk stratify patients with
sepsis or septic shock who are admitted to the accident and emergency department;[132] the Sepsis in Obstetrics Score

There are numerous ongoing studies investigating techniques for 'staging' the severity of sepsis using a variety of blood-
borne markers.[134] [135] Although some techniques have shown initial promise, the evidence base remains weak, and
they have an unclear role in future clinical practice.

Risk stratification
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.[3] [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.[3] [41] [42]
[44] NEWS2 is endorsed by NHS England and the National Institute for Health and Care Excellence (NICE) for
use in this setting.[3] [41]

• NICE recommends to use the NICE high-risk criteria for stratification of risk (rather than NEWS2) in an
acute setting in patients who are or have recently been pregnant.[3]

2. In the community and in custodial settings: use an early warning score such as NEWS2, which is recommended
by NHS England and supported by the Royal College of General Practitioners in the UK.[41] [51] An alternative
in the UK is to use the NICE high-risk criteria.[3]

• None is validated in primary care.[51]

See Risk stratification under Diagnosis recommendations .

DIAGNOSIS

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Sepsis in adults Management

Recommendations

Urgent
Start treatment immediately if a senior clinical decision-maker (e.g., ST3 level doctor in the UK) makes a diagnosis
of suspected sepsis.[41] [42] [NHS England: Sepsis]

• Sepsis is suspected based on acute deterioration (e.g., National Early Warning Score 2 [NEWS2] score of
5 or more, or a similar trigger using another validated scoring system) in a patient with known or likely
infection.[41] [42] For more detail on when to suspect sepsis, see Diagnosis recommendations .

Treat suspected sepsis (i.e., new organ dysfunction related to severe infection) promptly. Establish venous access
early so you can start initial treatment according to the timeframes below:[3] [41] [45] [47]

• A patient is also at high risk of severe illness or death from sepsis if they have a NEWS2 score
below 7 and a single parameter contributes 3 points to their NEWS2 score and a medical review has
confirmed that they are at high risk.[3]

• Within 3 hours for patients with a NEWS2 score of 5 or 6.

Start the following treatments:[3] [41] [47]

1. Intravenous antibiotics: where there is evidence of a bacterial infection, administer broad-spectrum empirical
intravenous antibiotics before a pathogen is identified.[3] Only give antibiotics if they have not been given
before for this episode of sepsis.[3]

• Follow local policy and consider discussing with microbiology/infectious disease colleagues to
determine the most appropriate choice; use a ‘start smart then focus’ approach[41] [136]
• Target the presumed site of infection if known
• Take bloods immediately, preferably before antibiotics are started (although sampling should not
delay the administration of antibiotics)[3] [43] [48] [49]
• Narrow the choice of antibiotic as soon as a pathogen has been identified and sensitivities are
available[3] [43] [137]

2. Intravenous fluids: 500 mL of crystalloid, with sodium in the range 130 to 154 mmol/L (130 to 154 mEq/
L), over less than 15 minutes, if either lactate is over 2 mmol/L or systolic blood pressure is less than 90
MANAGEMENT

mmHg.[3] [41] [67]

• Give this intravenous fluid bolus, if indicated, without delay (within 1 hour of identifying a patient is
at high risk).[3]

• Repeat if clinically indicated

• Do not exceed 30 mL/kg

3. Oxygen: as needed. An upper SpO 2 limit of 96% is reasonable when administering supplemental oxygen to
most patients with acute illness who are not at risk of hypercapnia.

• Evidence suggests that liberal use of supplemental oxygen (target SpO 2 >96%) in acutely ill adults is
associated with higher mortality than more conservative oxygen therapy.[138]
• A lower target SpO 2 of 88% to 92% is appropriate if the patient is at risk of hypercapnic respiratory
failure.[50]

Carry out the following investigations:

1. Blood cultures
2. Lactate level
3. Hourly urine output.

Consult local protocols for specific routes of escalation. In general, in hospital, if a patient is at high risk of severe
illness or death from sepsis (e.g., NEWS2 score of 7 or more) or does not respond within 1 hour of any intervention
(antibiotics/fluid resuscitation/oxygen):[3]

• Ensure the senior clinical decision-maker attends in person, and

• Refer to or discuss with a critical care consultant or team, and
• Inform the responsible consultant.
• Signs that the person is not responding to resuscitation include lack of improvement or worsening:[3]

• Tachycardia
• Level of consciousness
• Blood pressure
• Respiratory rate
• Blood lactate
• Urine output
• Peripheral perfusion
• Blood gases.

• Consider alerting critical care immediately if the patient is acutely unwell and:

• Has hypotension that does not respond to initial fluid resuscitation within 1 hour.[3]
MANAGEMENT

• Is likely to require central venous access and the initiation of inotropes or vasopressors[3]
• Has any feature of septic shock

• Patients with septic shock are likely to benefit from rapid (within 1 hour of presentation)
empirical broad-spectrum antimicrobials[45]

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Sepsis in adults Management
• See Shock

• Has neutropenia
• Is immunodeficient.

Bear in mind that some patients (e.g., those who are frail) may not be suitable for management in intensive care
settings. Consider the patient’s preferences for future care and their baseline health including their resuscitation
status when determining the limits of treatment. Use this to feed into a personalised care plan appropriate to the
individual patient.[45]

Urgent: in the community

Refer for emergency medical care in hospital (usually by blue-light ambulance in the UK) any patient who is
acutely ill with a suspected infection and is:[3]

• Deemed to be at high risk of deterioration due to organ dysfunction, as measured by a formal risk
stratification process such as NEWS2, which is recommended by NHS England and the UK National
Institute for Health and Care Excellence (NICE).[41] [43]
• At risk of neutropenic sepsis. See Febrile neutropenia .[139]

Communicate your concern to the ambulance service and hospital colleagues by using the words 'suspected sepsis',
and offer the outcome of a physiological assessment (e.g., NEWS2 score).[51]

Start oxygen therapy, if indicated, while awaiting the ambulance if resources are available to do so.[50]

Ensure you have a mechanism in place to administer antibiotics, if needed, to any high-risk patient (either at your
practice or via the ambulance service) if the transfer to hospital is likely to be delayed.

Key Recommendations
Sepsis is a medical emergency. [3] [43] The key to improving outcomes is early recognition and prompt treatment,
as appropriate, of patients with suspected or confirmed infection who are deteriorating and at risk of organ
dysfunction.[3] [43]

• Always use your clinical judgement. [41]

• Take into account the full clinical picture of the individual patient in front of you including their NEWS2
score.

Identify and treat underlying source

Early and adequate source identification and control is critical. Undertake intensive efforts, including imaging, to
attempt to identify the source of infection in all patients with sepsis. [3] [43]
MANAGEMENT

• Consider the need for urgent source control as soon as the patient is stable.
• The respiratory tract is the most common site of infection in most people with sepsis.[20] [61] However, in
people over age 65 years, the most common site is the genitourinary tract.[21] [22]

Protocolised approaches
Your institution may use a guideline-based care bundle as an aide-memoire to ensure key interventions are carried
out in a timely way as appropriate for the individual patient. Check local protocolsfor the recommended approach
in your area. Examples include the following.

The Sepsis Six resuscitation bundle from the UK Sepsis Trust [47]
Sepsis Six is a practical checklist of interventions that must be completed within 1 hour of identifying a patient with
suspected sepsis with a NEWS2 score of 7 or more or other features of critical illness (lactate >2 mmol/L (>18 mg/
dL); chemotherapy in last 6 weeks; other organ failure evident [e.g., acute kidney injury]; patient looks extremely
unwell; patient is actively deteriorating).[45] [47] The original paper outlining this approach, published in 2011,
remains the only published evidence on Sepsis Six and was subsequently contested.[56] [57] The six interventions
are:[47]

• Inform a senior clinician

• Give oxygen if required
• Obtain intravenous access/take blood cultures
• Give intravenous antibiotics
• Give intravenous fluids
• Monitor.

In 2022, the criteria for triggering the Sepsis Six bundle were aligned with UK Academy of Medical Royal Colleges
guidance and in 2024 the bundle was updated to reflect updates to NICE guidance.[3] [45] [47]

Subsequent guidance from the SSC and the UK Academy of Medical Royal Colleges supports a more nuanced
MANAGEMENT

approach to investigating and treating patients with suspected sepsis presenting with less severe illness (e.g., without
septic shock, or NEWS2 score less than 7).[43] [45] Although early identification and prompt, tailored treatment
are key to the successful management of sepsis, none of the published protocolised approaches are supported by
evidence.[58] [59] Therefore, your clinical judgement is a key part of any approach. [41]

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Sepsis in adults Management
Reassess and monitor
Ensure frequent reassessment of the patient’s haemodynamic status throughout the initial resuscitation period. Make
sure any patient with suspected sepsis has frequent and ongoing monitoring (e.g., using an early warning score
such as NEWS2).[3]

• Depending on the facilities available, consider continuous monitoring, or a minimum of once every 30
minutes.[3]
• Include:

• Oxygen saturation
• Respiratory rate
• Heart rate
• Blood pressure
• Temperature
• Hourly fluid balance (including urine output)
• Lactate level.

Consider using a validated scale such as the Glasgow Coma Scale or the AVPU ('Alert, responds to Voice, responds
to Pain, Unresponsive') scale to monitor the mental state of a patient with suspected sepsis. [3]

Be aware that a patient with a NEWS2 score of less than 5 might also have or develop sepsis. In this group, continue
to be aware of the risk of sepsis and specifically look for indicators that suggest the possibility of underlying
infection and sepsis:[3] [41]

• A single NEWS parameter of 3 or more

Full Recommendations
Treatment goals
The overarching goals are to:
MANAGEMENT

• Resuscitate the patient and restore haemodynamic stability using supportive measures to correct hypoxaemia,
hypotension, and impaired tissue oxygenation (hypoperfusion)
• Rapidly identify the source of infection; contain and treat

• Within 1 hour of the risk being recognised in patients who are critically ill (including those with
septic shock, sepsis associated with rapid deterioration, or a NEWS2 score #7 on initial assessment in
the accident and emergency department or on ward deterioration).
• Within 3 hours in patients with suspected sepsis with less severe illness (e.g., NEWS2 score of 5 or
6).

• Switch to a targeted antibiotic once the pathogen has been confirmed[3]

• Maintain organ system function, guided by cardiovascular monitoring, and interrupt the progression of organ
failure.

When to start treatment for sepsis

Early recognition of sepsis is critically important, but this can be challenging as patients often present with subtle
and/or non-specific signs.[141]

In practice, you should make a diagnosis of suspected sepsis and start immediate treatment if the patient is acutely
unwell and meets both of the following criteria:[3] [41]

1. Signs or symptoms suggestive of infectionare present

AND
2. Your clinical assessment of the patient indicates a risk of deteriorationdue to organ dysfunction.

Always use your clinical judgement when assessing the risk of deterioration due to sepsis, alongside a systematic
approach to assessing vital observations.[3] [41] Consult local guidelines for the recommended approach.

• The National Early Warning Score 2 (NEWS2) is the most widely used early warning score in the UK
National Health Service. [NHS England: Sepsis]

• In hospital: use NEWS2 or an alternative early warning score.[41] [42] [44] NEWS2 is endorsed
by NHS England and the National Institute for Health and Care Excellence (NICE) for use in
this setting.[3] [41] NEWS2 is also recommended for use in acute mental health settings and
ambulances.[3]

• NICE recommends to use NICE high-risk criteria for stratification of risk (rather than NEWS2)
in an acute setting in patients who are or have recently been pregnant.[3]

• In the community and in custodial settings: use an early warning score such as NEWS2, which is
recommended by NHS England and supported by the Royal College of General Practitioners in the
UK.[41] [51] An alternative in the UK is to use the NICE high-risk criteria.[3]
MANAGEMENT

• None is validated in primary care.[51]

• NHS England and the Royal College of Physicians in the UK set the threshold for starting immediate sepsis
treatment as a NEWS2 score of 5 or more.[41] [42]

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Sepsis in adults Management
• You should strongly suspect sepsis and consider the need to start immediate treatment if the patient:

• Has any single NEWS2 parameter score of 3 or more OR

• Has a non-blanching rash or has mottled/ashen/cyanotic skin OR
• Is unresponsive or only responds to voice or pain OR
• Has not passed urine for 18 or more hours (or urine output <0.5 mL/kg/hour if catheterised) OR
• Has a lactate level #2 mmol/L (#18 mg/dL).[41]

• The UK’s Academy of Medical Royal Colleges (AOMRC) stratifies the urgency of treatment for sepsis
according to NEWS2 score. The AOMRC and NICE recommend:[3] [45]

• Initial treatment within 1 hour for a patient with a NEWS2 score of 7 or more calculated on initial
assessment in the accident and emergency department or on ward deterioration (or if they meet other
criteria, as per below)

• Initial treatment within 3 hours for a patient with a NEWS2 score of 5 or 6

• Interpreting the initial NEWS2 score in the context of clinical assessment, so that severity status
and corresponding actions are upgraded to at least the next NEWS2 level if there is clinical or carer
concern, continuing deterioration or lack of improvement, surgically remediable sepsis, neutropenia,
or blood gas/laboratory evidence of organ dysfunction (including elevated serum lactate).

For full details of risk stratification, see Diagnosis recommendations .

Prompt management for all patients with suspected sepsis

Start treatment immediatelyif a senior clinical decision-maker (e.g., ST3 level doctor in the UK) makes a diagnosis
of suspected sepsis, based on acute deterioration (e.g., National Early Warning Score 2 [NEWS2] score of 5 or
more, or a similar trigger using another validated scoring system) in a patient with known or likely infection.[41]
[42] [45]

Urgent actions
For any acutely ill and deteriorating patient with a suspected or known bacterial infection andsuspected sepsis,
above all else prioritise (if needed):[3] [47]

• Securing their airway

• Correcting hypoxaemia
• Establishing venous access for the early administration of antibiotics and fluids.
MANAGEMENT

Early and adequate source identification and control is critical.If your examination of the patient identifies a
clear source of infection, consider the need for urgent source control, as soon as the patient is stable, particularly
for:[43]

• Gastrointestinal sources (such as visceral abscesses, cholangitis, or peritonitis secondary to perforation)

Give immediate, targeted intravenous antibiotics in people with sepsis thought to arise from a central nervous
system source (e.g., suspected meningitis or meningococcal sepsis).[3]

• Immediately give a third-generation cephalosporin such as ceftriaxone.

• In community settings, pre-hospital administration of benzylpenicillin is recommended.
• Follow local policy and consider discussing with microbiology/infectious disease colleagues to
determine the most appropriate choice; use a ‘start smart then focus’ approach. [41] [136]

Practical tip

If intravenous access is not feasible or is likely to lead to a delay in starting antibiotics and fluids, use intra-
osseous access as an interim measure.

Intravenous antibiotics
Where there is evidence of a bacterial infection and sepsis is strongly suspected (based on acute deterioration [e.g.,
NEWS2 score of 5 or more, or a similar trigger using another validated scoring system]), give broad-spectrum
intravenous antibiotics promptly. [3] [41] [43] [47] Do this before a pathogen is identified but after blood
cultures have been taken.[3] [41] [43] [47] Only give antibiotics if they have not been given before for this episode
of sepsis.[3]

• The UK Academy of Medical Royal Colleges and NICE recommends administration of antimicrobials:[3]
[45]

• Within 1 hour if the NEWS2 score is 7 or morecalculated on initial assessment in the accident and
emergency department or on ward deterioration, or with a score of 5 or 6 if there is clinical or carer
concern, continuing deterioration or lack of improvement, surgically remediable sepsis, neutropenia,
or blood gas/laboratory evidence of organ dysfunction (including elevated serum lactate)

• If a patient has a NEWS2 score of 5 or 6 calculated on initial assessment in the accident and
emergency department or on ward deterioration and a single parameter contributes 3 points
to the total NEWS2 score, clinical judgement should be used to determine the likely cause of
the 3 points in one parameter. If the likely cause is the current infection, manage as high risk
and give broad-spectrum antibiotics within 1 hour of the NEWS2 score being calculated on
initial assessment in the accident and emergency department or on ward deterioration.[3]

• Within 3 hours if the NEWS2 score is 5 or 6.

• The Surviving Sepsis Campaign international guideline recommends empirical combination therapy (using at
least two antibiotics of different antimicrobial classes covering gram-negative bacilli) for patients at high risk
of infection from multidrug resistant (MDR) organisms, particularly in those with septic shock.[43]
MANAGEMENT

• Initial use of multidrug therapy is often required, given the frequency of MDR bacteria in many parts
of the world and associations between delays in active therapy and worse outcomes.[43]

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Sepsis in adults Management
• Single agents are recommended for patients with a low risk for MDR organisms.[43]

Follow local policy and consider discussing with microbiology/infectious disease colleagues to determine the
most appropriate choice.Once a decision is made to give antibiotics, do not delay administration any further.[3]

• Use a ‘start smart then focus’ approach. [41] [136]

MANAGEMENT

More info: Antimicrobial resistance

NHS England recommends following a ‘start smart then focus’ approach for antibiotic use in people
with sepsis. [41] This is derived from Public Health England guidance, which outlines an evidence-
based approach to improving antimicrobial prescribing and stewardship in hospital settings. [136] The
prevalence of antimicrobial resistance (AMR) has risen alarmingly over the last 50 years and no new classes
of antibiotics have been developed in decades. By 2050 it is estimated that AMR will kill 10 million people
per year, more than cancer and diabetes combined. [142] The relationship between antibiotic exposure and
antibiotic resistance is unambiguous not only at the population level but also in individual patients. [143]
[144]

Start smart– in the context of sepsis:[136]

• Do not start antimicrobial therapy unless there is clear evidence of infection

• Take a thorough drug allergy history
• Initiate prompt effective antibiotic treatment within 1 hour of diagnosis (or as soon as possible) in
patients with sepsis who are critically ill (e.g., septic shock, sepsis associated with rapid deterioration, or
NEWS2 score of 7 or more calculated on initial assessment in the accident and emergency department
or on ward deterioration) or with life-threatening infections. Avoid inappropriate use of broad-spectrum
antibiotics[3] [45]
• Comply with local antimicrobial prescribing guidance
• Document clinical indication (and disease severity if appropriate), drug name, dose, and route on drug
chart and in clinical notes Include review/stop date or duration
• Obtain cultures prior to starting therapy where possible (but do not delay therapy).

Then focus– in the context of sepsis:[136]

• Review the clinical diagnosis and the continuing need for antibiotics at 48 to 72 hours* and document in a
clear plan of action – the ‘antimicrobial prescribing decision
• The ‘antimicrobial prescribing decision’ options are:

1. Stop antibiotics if there is no evidence of infection

2. Switch antibiotics from intravenous to oral
3. Change antibiotics – ideally to a narrower spectrum, or broader if required
4. Continue and document next review date or stop date

• It is essential that the review and subsequent decision is clearly documented in the clinical notes and on
the drug chart where possible (e.g., ‘stop antibiotic’).

*In clinical practice, daily prompting about de-escalation is encouraged.

The UK’s Academy of Medical Royal Colleges recommends stratifying patients with suspected sepsis according
to severity of illness at presentation, allowing a 3-hour window to investigate patients with less severe illness
(e.g., NEWS2 score of 5 or 6). This should improve accuracy of treatment and help to reduce antimicrobial
MANAGEMENT

resistance.[45]

Target the presumed site of infection.[3] [43]

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Sepsis in adults Management
If there is no clinical evidence to suggest a specific site of infection but a senior clinical decision-maker strongly
suspects the presence of a bacterial infection, still give empirical broad-spectrum intravenous antibiotics.[41]
Choose an empirical antibiotic based on:[145] [146]

• Local antibiotic protocols and resistance patterns

• Consult microbiology/infectious disease colleagues to determine the most appropriate choice

• The likely causative organism

• The patient’s immune function.

Practical tip

Check local policies regarding repeat cultures. These are indicated particularly if there are persistent or
repeated fever spikes or if you identify a potential new site of infection. Observations from studies to date
support taking as many as four blood culture sets over a 24-hour period for >99% test sensitivity.[147]

Practical tip

If a patient has a mild allergy (e.g., rash) to an unknown antibiotic, you should still give empirical broad-
spectrum antibiotics if indicated to prevent delays in the treatment of sepsis, which is likely to worsen
outcome. If the antibiotic is known and is part of the empirical protocol for your hospital, discuss potential
alternatives with a microbiologist.

MANAGEMENT

Evidence: 1- and 3-hour antibiotic targets

There is widespread agreement that antibiotics should be offered to people with sepsis, within a timeframe
that depends on their risk of severe illness or death. The UK National Institute for Health and Care
Excellence (NICE), the Surviving Sepsis Campaign (SSC) and the UK Academy of Medical Royal Colleges
(AOMRC) all recommend a 1-hour target time threshold for patients at high risk and a 3-hour target time
threshold for patients at moderate risk. [43] [45]

Two meta-analyses published in 2015 and 2020 compared outcomes for patients with sepsis and septic shock
given either immediate (within 1 hour of onset) or early (between 1 and 3 hours from onset) antibiotics; neither
meta-analysis identified a difference in mortality between these thresholds.[148] [149] One 2021 systematic
review (without meta-analysis) of 35 sepsis studies concluded that two-thirds of studies reported an association
between early administration of antibiotic therapy and patient outcome, but there was widespread variation in
metrics and no robust time thresholds emerged.[150] Almost all of the studies included in these reviews were
observational.[148] [149] [150]

The 2021 update of the SSC guideline recommends that patients with possible sepsis without shock should
receive a time-limited course of rapid investigation with administration of antimicrobials within 3 hours if there
is persisting concern for infection.[43] Similarly, 2022 guidance from the UK’s AOMRC, based largely on the
evidence above, recommends a 3-hour window for investigating and treating patients with less severe illness,
while continuing to recommend a 1-hour target for treating patients with more severe illness (e.g., NEWS2 score
of 7 or more, or septic shock). The recommended timeframes in the Sepsis Trust’s Sepsis Six bundle have since
been adjusted in line with AOMRC guidance.[43] [45] [47]

At the 2024 update of the NICE ‘Suspected sepsis: recognition, diagnosis and early management’ guideline, the
committee agreed by consensus to change NICE guidance to also align with the AOMRC guidance.[3]

• In their discussion, NICE highlighted that the reason for the longer target time threshold for those at
moderate risk was to give more time to establish the diagnosis and guide antibiotic choice, and that the 3-
hour limit is a maximum not an aim.

In intensive care settings only, consider prolonged infusion when giving beta-lactam antibiotics to patients
with sepsis (apart from those with kidney-related complications). [151] Note that prolonged infusion times are
not licensed as most manufacturers advise infusion of beta-lactam antibiotics over 15 to 60 minutes.
MANAGEMENT

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Sepsis in adults Management

Evidence: Prolonged antibiotic infusion

Intravenous antibiotics, administered over 3 hours, are linked to lower death rates in sepsis. [151] Prolonged
infusion should be easy to apply in the intensive care setting, without the need for additional training or
equipment.

• A systematic review and meta-analysis pooled the results of 22 randomised controlled trials involving
1876 adults with sepsis. The trials compared prolonged versus short-term administration of any
antipseudomonal beta-lactam. Carbapenems were studied in nine trials, penicillins in nine trials, and
cephalosporins in eight trials.[151]

• Prolonged infusion was associated with lower all-cause mortality than short-term infusion, with
13.6% deaths compared with 19.8% (risk ratio [RR] 0.70, 95% CI 0.56 to 0.87; 17 studies, 1597
participants).
• There was no significant difference between prolonged and short-term infusion for clinical cure or
improvement (RR 1.06, 95% CI 0.96 to 1.17; 11 studies, 1219 participants).
• There was no difference in reported adverse events between the groups (RR 0.88, 95% CI 0.71
to 1.09; 7 studies, 980 participants).
• Two trials had no incidence of antibiotic resistance, and two trials had no difference in resistance
between the two methods of antibiotic administration (RR 0.60, 95% CI 0.15 to 2.38).

Intravenous fluids
Give 500 mL of crystalloid fluid, with a sodium content between 130 mmol/L and 154 mmol/L (130 to 154
mEq/L) (e.g., 0.9% sodium chloride or Hartmann’s solution), over less than 15 minutes to patients who need
fluid resuscitation (if either lactate is over 2 mmol/L or systolic blood pressure is less than 90 mmHg). [3] [41]
[67]

• Give this intravenous fluid bolus, if indicated, without delay (within 1 hour of identifying a patient is at high
risk).[3]
• Consider giving an intravenous fluid bolus to patients with a high risk of severe illness or death from sepsis if
lactate is 2 mmol/L or lower.[3]

• Reassess the patient’s haemodynamic status after the first bolus to consider whether a second is
required.[3] If there is no response to either the first or second bolus, ensure the senior clinical decision-
maker attends in person.[3]

Intravenous fluid resuscitation may be lifesaving in patients with hypotension. This is because in sepsis there is
vasodilation and capillary leakage, which means that patients can rapidly become intravascularly deplete.[3]

• In patients with sepsis-induced hypoperfusion (as indicated by a systolic blood pressure <90 mmHg, a
MANAGEMENT

raised lactate level, or signs of organ dysfunction), the Surviving Sepsis Campaign international guideline
recommends a total of at least 30 mL/kg of intravenous crystalloid over the first 3 hours.[43]

Practical tip

The delivery of appropriate rapid fluid challenges is intended to restore the imbalance between oxygen
supply and demand to the tissues. Patients who do not respond to rapid delivery of adequate volumes of
intravenous fluids are in septic shock and need immediate referral to critical care. The immediate priority
in this group of patients is to restore the circulation and oxygen delivery.

Practical tip

Monitor patients closely for signs of fluid overload such as pulmonary or systemic oedema before and
after each additional fluid bolus, as they may require large volumes of fluid to support their circulating
volume.[43] [152] [153]

Check local protocols for specific recommendations on fluid choice. There is debate, based on conflicting evidence,
on whether there is a benefit in using normal saline or balanced crystalloid in critically ill patients.

Practical tip

Be aware that large volumes of normal saline as the sole fluid for resuscitation may lead to
hyperchloraemic acidosis.
Also note that use of lactate-containing fluid in a patient with impaired liver metabolism may lead to a
spuriously elevated lactate level, so results need to be interpreted with other markers of volume status.
MANAGEMENT

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Sepsis in adults Management

Evidence: Choice of fluid

Evidence from two large randomised controlled trials (RCTs) suggests there is no difference between normal
saline and a balanced crystalloid for critically ill patients in mortality at 90 days, although results from two
meta-analyses including these RCTs point to a possible small benefit of balanced solutions compared with
normal saline.

There has been extensive debate over the choice between normal saline (an unbalanced crystalloid) versus
a balanced crystalloid (such as Hartmann’s solution [also known as Ringer’s lactate] or Plasma-Lyte®).
Clinical practice varies widely, so you should check local protocols.

• In 2021-2022 two large double-blind RCTs were published assessing intravenous fluid resuscitation
in intensive care unit (ICU) patients with a balanced crystalloid solution (Plasma-Lyte) versus normal
saline: the Plasma-Lyte 148 versus Saline (PLUS) trial (53 ICUs in Australia and New Zealand; N=5037)
and the Balanced Solutions in Intensive Care Study (BaSICS) trial (75 ICUs in Brazil; N=11,052).[154]
[155]

• In the PLUS study, 45.2% of patients were admitted to ICU directly from surgery (emergency
or elective), 42.3% had sepsis, and 79.0% were receiving mechanical ventilation at the time of
randomisation.
• In BaSICS, almost half the patients (48.4%) were admitted to ICU after elective surgery and
around 68% had some form of fluid resuscitation before being randomised.
• Both found no difference in 90-day mortality overall or in prespecified subgroups for patients with
acute kidney injury (AKI), sepsis, or post-surgery. They also found no difference in the risk of
AKI.
• In BaSICS, for patients with traumatic brain injury, there was a small decrease in 90-day mortality
with normal saline; however, the overall number of patients was small (<5% of total included in
the study) so there is some uncertainty about this result. Patients with traumatic brain injury were
excluded from PLUS as the authors felt these patients should be receiving saline or a solution of
similar tonicity.

• A meta-analysis of 13 RCTs (including PLUS and BaSICS) confirmed no overall difference, although
the authors did highlight a non-significant trend towards a benefit of balanced solutions for risk of
death.[156]
• A subsequent individual patient data meta-analysis included 6 RCTs of which only PLUS and BaSICS
were assessed as being at low risk of bias. There was no statistically significant difference in in-hospital
mortality (odds ratio [OR] 0.96, 95% CI 0.91 to 1.02). However, the authors argued that using a Bayesian
analysis there was a high probability that balanced solutions reduced in-hospital mortality, although they
acknowledged that the absolute risk reduction was small.[157]

• A pre-specified sub-group analysis of patients with traumatic brain injury (N=1961) found that
balanced solutions increased the risk of in-hospital mortality compared with normal saline (OR
1.42, 95% CI 1.10 to 1.82).
MANAGEMENT

• Previous evidence has been mixed.

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Sepsis in adults Management
• One 2015 double-blind, cluster randomised, double-crossover trial conducted in 4 ICUs in New
Zealand (N=2278), the 0.9% Saline vs Plasma-Lyte® for ICU fluid Therapy (SPLIT) trial, found
no difference for in-hospital mortality, AKI, or use of renal-replacement therapy.[158]
• However, a 2018 US multicentre unblinded cluster-randomised trial - the isotonic Solutions and
Major Adverse Renal events Trial (SMART), among 15,802 critically ill adults receiving ICU
care - found possible small benefits from balanced crystalloid (Ringer’s lactate or Plasma-Lyte®)
compared with normal saline. The 30-day outcomes showed a non-significant reduced mortality
in the balanced crystalloid group versus the normal saline group (10.3% vs. 11.1%; odds ratio
[OR] 0.90, 95% CI 0.80 to 1.01) and a major adverse kidney event rate of 14.3% versus 15.4%,
respectively (OR 0.91, 95% CI 0.84 to 0.99).[159]

• One 2019 Cochrane review included 21 RCTs (N=20,213) assessing balanced crystalloids versus normal
saline for resuscitation or maintenance in a critical care setting.[160]

• The 3 largest RCTs in the Cochrane review (including SMART and SPLIT) all examined fluid
resuscitation in adults and made up 94.2% of participants (N=19,054).
• There was no difference in in#hospital mortality (OR 0.91, 95% CI 0.83 to 1.01; high-quality
evidence as assessed by GRADE), acute renal injury (OR 0.92, 95% CI 0.84 to 1.00; GRADE
low), or organ system dysfunction (OR 0.80, 95% CI 0.40 to 1.61; GRADE very low).

The Surviving Sepsis Campaign 2021 guideline update makes a weak recommendation (low-quality
evidence) in favour of administering a balanced crystalloid (such as Hartmann's solution [Ringer's
lactate] or Plasma-Lyte®) to patients with sepsis, based on evidence published prior to the BaSICS trial
results.

• Subgroup analysis of patients with sepsis within the BaSICS trial showed no difference in 90-day
mortality between patients given normal saline (an unbalanced crystalloid) versus a balanced crystalloid.
However, the authors comment that the subgroup analysis should be considered as hypothesis-generating
only.[154] Further RCTs are awaited.

Practical tip

To guide the need for further intravenous fluids, it can sometimes be helpful to use bedside ultrasound
to monitor changes in inferior vena cava (IVC) diameter during respiration. [161] [162]
• In the spontaneously breathing patient: consider additional fluid resuscitation if there is a collapsed (or
collapsing) IVC.
• In the mechanically ventilated patient: an increase in IVC size >18% (or visible to the naked eye) with
positive pressure ventilation suggests fluid-responsiveness.
MANAGEMENT

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Sepsis in adults Management
Practical tip

Use the passive leg-raising test to predict fluid-responsiveness if adequate monitoring is available.[67] [163]
• This is a useful indicator of fluid-responsiveness, which should be assessed using devices that can
continuously monitor cardiac output in real time (e.g., Pulse index Continuous Cardiac Output [PiCCO]
monitor or oesophageal Doppler), usually in an intensive care unit rather than a general ward setting.
• Sit the patient upright at 45° and tilt the entire bed through 45°.
• Patients with a positive test have a >10% increase in cardiac output or stroke volume, indicating more
fluids may be required.
• The passive leg-raise response may be misleading in conscious patients who are uncomfortable or in pain
when lying flat.

Oxygen
Monitor controlled oxygen therapy. An upper SpO 2 limit of 96% is reasonable when administering
supplemental oxygen to most patients with acute illness who are not at risk of hypercapnia.

MANAGEMENT

Evidence: Target oxygen saturation in acutely ill adults

Too much supplemental oxygen increases mortality.

Evidence from a large systematic review and meta-analysis supports conservative/controlled oxygen
therapy versus liberal oxygen therapy in acutely ill adults who are not at risk of hypercapnia.

• Guidelines differ in their recommendations on target oxygen saturation in acutely unwell adults who are
receiving supplemental oxygen.

• The 2017 British Thoracic Society (BTS) guideline recommends a target SpO 2 range of 94% to
98% for patients not at risk of hypercapnia, whereas the 2022 Thoracic Society of Australia and
New Zealand (TSANZ) guideline recommends 92% to 96%.[50] [164]
• The 2022 Global Initiative For Asthma (GINA) guidelines recommend a target SpO 2 range of
93% to 96% in the context of acute asthma exacerbations.[165]

• One systematic review including a meta-analysis of data from 25 randomised controlled trials published
in 2018 found that in adults with acute illness, liberal oxygen therapy (broadly equivalent to a target
saturation >96%) is associated with higher mortality than conservative oxygen therapy (broadly
equivalent to a target saturation #96%).[138] In-hospital mortality was 11 per 1000 higher for the liberal
oxygen therapy group versus the conservative therapy group (95% CI 2 to 22 per 1000 more). Mortality
at 30 days was also higher in the group who had received liberal oxygen (relative risk 1.14, 95% CI 1.01
to 1.29). The trials included adults with sepsis, critical illness, stroke, trauma, myocardial infarction, or
cardiac arrest, and patients who had emergency surgery. Studies that were limited to people with chronic
respiratory illness or psychiatric illness, or patients on extracorporeal life support, receiving hyperbaric
oxygen therapy, or having elective surgery, were all excluded from the review.
• An upper SpO 2 limit of 96% is therefore reasonable when administering supplemental oxygen to patients
with acute illness who are not at risk of hypercapnia. However, a higher target may be appropriate for
some specific conditions (e.g., pneumothorax, carbon monoxide poisoning, cluster headache, or sickle
cell crisis).[166]
• In 2019 the BTS reviewed its guidance in response to this systematic review and meta-analysis and
decided an interim update was not required.[167]

• The committee noted that the systematic review supported the use of controlled oxygen therapy to
a target.
• While the systematic review showed an association between higher oxygen saturations and
higher mortality, the BTS committee felt the review was not definitive on what the optimal target
range should be. The suggested range of 94% to 96% in the review was based on the lower 95%
confidence interval and the median baseline SpO 2 from the liberal oxygen groups, along with the
earlier 2015 TSANZ guideline recommendation.

• Subsequently, experience during the COVID-19 pandemic has also made clinicians more aware of the
feasibility of permissive hypoxaemia.[168] The BTS guidance is due for a review in 2022.
MANAGEMENT

• Management of oxygen therapy in patients in intensive care is specialised and informed by further
evidence (not covered in this summary) that is more specific to this setting.[169] [170][171]

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Sepsis in adults Management
There is no specific evidence to show that giving oxygen improves clinical outcomes in sepsis. However,
respiratory failure will lead to tissue hypoxia and anaerobic respiration. This is likely to lead to acidosis and
consequently a poorer outcome.[172]

Reassess and monitor

Ensure frequent and ongoing monitoring. [3]

• Standard monitoring of vital signs, pulse oximetry, level of consciousness, and urinary output is important
for any patient with suspected sepsis.
• The National Institute for Health and Care Excellence (NICE) in the UK recommends continuous or half-
hourly monitoring (depending on setting) for any patient considered to be at high risk of deterioration (e.g.,
using an early warning score such as NEWS2).[3]
• For more information, see Risk stratification under Diagnosis recommendations .

Use a track-and-trigger scoring system such as the National Early Warning Score 2 (NEWS2) to identify any
signs of deterioration. [3] Your monitoring should include:

• Vital signs: heart rate, blood pressure, oxygen saturations, respiratory rate, and temperature

• Measure blood pressure via an arterial line if the patient does not respond to initial treatment or needs
vasoactive drugs. It provides precise, continuous monitoring, and access for arterial blood sampling

• Hourly urine output[3] [47]

• Lactate

• The lactate level should decrease if the patient is clinically improving

• Frequency of repeat lactate measurement depends on cause of sepsis and treatment given.

In the UK, use physiological track-and-trigger systems to monitor all adult patients in acute hospital settings.[3]

Consider using a validated scale such as the Glasgow Coma Scale or AVPU ('Alert, responds to Voice,
responds to Pain, Unresponsive') scale to monitor the mental state of a patient with suspected sepsis . [3]

Practical tip

AVPU should raise concerns if the assessment shows the patient is anything other than 'alert'.

When to escalate
Any patient with sepsis may be at significant risk of severe illness or death so it is vital to consider escalation
of care to senior colleagues and/or healthcare facilities where increased and more advanced monitoring can
be given (e.g., high-dependency unit/intensive care unit). [7] [173] [174]

• Bear in mind that some patients (e.g., those who are frail) may not be suitable for management in intensive
MANAGEMENT

care settings. Consider the patient’s preferences for future care and their baseline health including their
resuscitation status when determining the limits of treatment. Use this to feed into a personalised care plan
appropriate to the individual patient.[45]

Consult local protocols for specific escalation routes but in general:

• Within 30 minutes of initial severity assessment for any patient with an aggregate NEWS2 score of 7
or more; or with a NEWS2 score of 5 or 6 if there is clinical or carer concern, continuing deterioration
or lack of improvement, surgically remediable sepsis, neutropenia, or blood gas/laboratory evidence
of organ dysfunction (including elevated serum lactate - see below)
• Within 1 hour of initial severity assessment for any patient with an aggregate NEWS2 score of 5 or
6.

• Inform the responsible consultant if a patient is at high risk of severe illness or death from sepsis
(e.g., NEWS2 score of 7 or more) does not respond within 1 hour of any intervention (antibiotics/fluid
resuscitation/oxygen).[3] Ensure the senior clinical decision-maker attends in person.

Signs that the person is not responding to resuscitation include lack of improvement or worsening:[3]

• Tachycardia
• Level of consciousness
• Blood pressure
• Respiratory rate
• Blood lactate
• Urine output
• Peripheral perfusion
• Blood gases.

• Consider alerting critical care immediately if the patient is acutely unwell and:

• Is likely to require central venous access and the initiation of inotropes or vasopressors[3]

• This includes any patient with evidence of circulatory dysfunction or shock, or those who do
not respond to initial therapy (as outlined above) including initial fluid resuscitation within 1
hour.

• Has any feature of septic shock

• See Shock .

• Has neutropenia

• See Febrile neutropenia .

MANAGEMENT

• Is immunodeficient

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Sepsis in adults Management
Practical tip

Ensure a clear escalation plan has been discussed and agreed with the clinical team; include specific points
of contact for nursing staff if you are leaving a patient for later review.
Involve a senior colleague and/or consider transferring to critical care sooner rather than later if the
patient is not improving, or deemed high-risk. Examples include if the patient:
• Is not responding to fluids
• Needs inotropic support
• Has a low Glasgow Coma Scale score
• Needs ventilatory support.

Identify the infection source

Make intensive efforts to identify the anatomical source of infection as soon as possible. [3] [43] Consider the
need for urgent source control as soon as the patient is stable.

• Start with a thorough and focused clinical history and examination, as well as initial investigations
including imaging.[3]
• Consider all lines and catheters as potential sources. Remove lines where appropriate.[43]

• Assume that any intravenous route is likely to either be the source of the infection, or will seed
infections in the bloodstream, making eradication particularly difficult. Therefore, the priority for
source control is often to remove any intravenous devices after alternative vascular access has been
obtained.[43]

• 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]

• In practice, this may mean early transfer of the patient to a surgical centre if there are no facilities at
your hospital.

Switch to a targeted antibiotic as soon as culture and sensitivity results are available and a pathogen has been
identified. [43] [137]

Tailor antibiotics based on source

Once a definitive source has been identified, if appropriate to continue treating the patient with antibiotics,
choose a treatment regimen in line with local or national policy (which will take into account specialist
knowledge of resistance patterns). [43] [137] Also consider discussing with microbiology/infectious disease
colleagues to determine the most appropriate choice.

Respiratory
MANAGEMENT

Ensure treatment regimens cover common respiratory pathogens and atypical organisms such as Legionella
pneumophila .

• The respiratory tract is the most common site of infection in people with sepsis.[20] [61]

Abdominal
Ensure gram-positive and gram-negative organisms including anaerobes are covered.[175]

Arrange urgent surgical drainage or percutaneous drainage (where appropriate) for peritonitis or intra-peritoneal
abscesses.[176]

Urinary tract
Ensure gram-negative coliforms and Pseudomonas are covered. Ensuring patency of the urinary tract is vital.

• In people older than 65 years of age, genitourinary tract infections are the most common cause of sepsis.[21]
[22]

Soft tissue and joint

Includes septic arthritis, wound infections, cellulitis, and acute super-infections arising from chronic ulceration.
Most infections are polymicrobial. Ensure gram-positive and gram-negative organisms including anaerobes are
covered.

• Beware necrotising fasciitis, which requires immediate surgical intervention (as does septic arthritis).

Practical tip

Necrotising fasciitis is notoriously difficult to diagnose. The initial symptoms are non-specific and the
clinical course is often slower than might be expected. Typically, the first sign is pain disproportionate to
the clinical findings, followed or accompanied by fever.[74]
See Necrotising fasciitis .

Central nervous system

Relatively uncommon but potentially devastating source of sepsis. Beware meningococcal sepsis, which can be
extremely rapidly fatal; if survived, can lead to greater morbidity than other forms of sepsis.

Give immediate, targeted antibiotics in people with sepsis thought to arise from a central nervous system
source.[3]

• Immediately give a third-generation cephalosporin, such as ceftriaxone, for suspected meningitis or

meningococcal sepsis.[3]
• In community settings, give benzylpenicillin before referring to hospital.[3]

Unknown or unclear
MANAGEMENT

Continue broad-spectrum coverage to include all common pathogens if the source is unknown or unclear. [3]

• Bear in mind that a definite source of infection cannot be found in 20% to 30% of people with sepsis.[9]

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Sepsis in adults Management
Further management by the critical care team
For any patient with suspected sepsis, consider the need for referral to a high-dependency unit for
management by the critical care team. [177] [178]

Refer to critical care as soon as possible any patient who does not respond to initial therapy, and in particular
anyone:

• With hypotension that does not respond to initial fluid resuscitation within 1 hour. [3]
• Who is likely to require central venous access and initiation of inotropes or vasopressors [3]
• With any feature of septic shock

• See Shock

• With neutropenia

• See Febrile neutropenia

• Who is immunodeficient.

The following interventions should only be initiated by experienced members of the critical care team:[179]

• Glycaemic control
• Vasoactive drugs (vasopressors/inotropes)
• Corticosteroids.

Additional intensive care measures that will be considered include:[43] [180] [181]

• Stress ulcer prophylaxis (in people at risk of gastrointestinal bleeding)

• With an H2 antagonist or proton-pump inhibitor

• Deep venous thrombosis prophylaxis

• With heparin and compression stockings

• Enteral or parenteral nutrition

• Administration of human albumin solution 4% to 5% in patients with sepsis and shock[3] [43] who have not
responded to substantial volumes of crystalloids
• Transfusion of packed cells

• Consult local protocols for recommended threshold

• The Surviving Sepsis Campaign recommends using a threshold of 70 g/L (7 g/dL).[43]
MANAGEMENT

Evidence: Threshold for transfusion of packed cells

In the general critical care population there is no improvement with blood transfusions given at a higher
haemoglobin threshold compared with a lower haemoglobin threshold. Overall, a more restrictive transfusion
strategy is recommended; however, individual patient factors should be taken into account.

The 2021 Surviving Sepsis Campaign guideline recommends a restrictive transfusion strategy for adults with
sepsis or septic shock.[43] The guideline identifies the following evidence.

• One multicentre parallel group randomised controlled trial (RCT) in people >16 years of age with
septic shock (N=998) compared blood transfusion at a lower haemoglobin threshold with a higher
threshold.[182]

• There was no difference in 90-day mortality between groups (risk ratio [RR] 0.94, 95% CI 0.78 to
1.09).
• The results were similar using different methods of analysis (adjusted for risk factors at baseline,
and per-protocol analyses).
• Ischaemic events, severe adverse reactions, and need for life support were also similar.

• A second multicentre RCT (838 critically ill adults) compared a restrictive strategy of red-cell transfusion
with a liberal strategy.[183]

• Overall, 30-day mortality was similar in the two groups (18.7% vs. 23.3%, P = 0.11). Results were
similar in the subgroup of patients with sepsis or septic shock (N=218) (22.8% vs. 29.7%, P =
0.36).
• The 30-day mortality rates were significantly lower in patients who were less acutely ill and in
patients younger than 55 years old with the restrictive transfusion strategy. However, this was not
the case in those with clinically significant cardiac disease.
• The mortality rate during hospitalisation was significantly lower in the restrictive-strategy group
(22.3% vs. 28.1%, P = 0.05).

• A single-centre RCT in critically ill adult cancer patients with septic shock (N=300) also compared a
liberal strategy with a restrictive strategy.[184]

• 28-day mortality was less in the liberal group, although this difference was not statistically
significant (45% vs. 56%, hazard ratio [HR] 0.74, 95% CI 0.53 to 1.04). However, 90-day
mortality was significantly reduced in the liberal group (HR 0.72, 95% CI 0.53 to 0.97).
• There was no difference in duration of intensive care or hospital stay between groups.

• Meta-analysis of the three studies found no difference in 28-day mortality (odds ratio 0.99, 95% CI 0.67
to 1.46, quality of evidence as assessed by GRADE moderate).[43]

The guideline concluded that the evidence did not favour one strategy over the other. The authors therefore
MANAGEMENT

based their recommendation on resource use, cost-effectiveness, and health equity concerns.

There may be a case to consider giving transfusions at a higher haemoglobin level in some patients (e.g., those with
myocardial ischaemia, severe hypoxaemia, or acute haemorrhage.[43]

In the initial resuscitative phase, transfusion to achieve a higher haematocrit of #30% may be appropriate.[177]

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Sepsis in adults Management
In patients requiring prolonged ventilatory support, give lung-protective ventilation using minimal peak
inspiratory pressures (<30 cm H 2 O) and permissive hypercapnia to specifically limit pulmonary
compromise.[185]

• Titrate fraction of inspired oxygen (FiO 2 ) to lowest effective levels to prevent oxygen toxicity and maintain
central venous oxygen tension.

Glycaemic control
Although patients with sepsis are often hyperglycaemic, the optimal glucose target is unknown.

The Surviving Sepsis Campaign guideline recommends targeting a blood glucose level <10.0 mmol/L(<180 mg/
dL).[43]

• The National Institute for Health and Care Excellence (NICE) in the UK makes no recommendations on
glycaemic control in sepsis.[3]

Evidence: Glycaemic control

Recent years have seen a shift in opinion and practice regarding glycaemic control in critically ill people.
Since 2001, the use of tight glycaemic control has been advocated in people with sepsis. More recent evidence,
however, suggests an increase in adverse events (e.g., severe hypoglycaemia) in patients managed with
very tight glycaemic control (targeting a blood glucose below 6.1 mmol/L [110 mg/dL]). [186] [187] The
conflicting evidence has led to variations in recommendations in different countries and settings. Follow your
local protocol.

• An international randomised controlled trial (RCT) of 6104 critically ill medical and surgical patients
found increased 90-day mortality (odds ratio 1.14, 95% CI 1.02 to 1.28) with tighter glucose control,
possibly due to more frequent episodes of hypoglycaemia.[188]
• A 2010 systematic review of 6 RCTs and a meta-analysis investigating tight glucose control (4.4 to
6.1 mmol/L [80-110 mg/dL]) versus less strict glucose control in critically ill patients in the intensive
care unit setting found no significant improvement in mortality with tight glucose control, but it
was associated with significantly more hypoglycaemic episodes compared with less strict glucose
control.[189]
• An RCT of critically ill patients in a primarily surgical intensive care setting found lower patient
mortality with tight glucose control, 4.4 to 6.1 mmol/L (80-110 mg/dL), compared with ‘conventional’
more liberal glucose control.[190]

Vasoactive drugs
Selection of appropriate vasoactive agents should only take place under critical care supervision and may vary
according to clinician preference and local practice guidelines.
MANAGEMENT

Vasopressors for persistent haemodynamic instability

Vasopressors are used in a critical care setting to maintain a mean arterial pressure (MAP) #65 mmHg if the
patient is unresponsive to fluid resuscitation. [43] [179]

• Noradrenaline is the vasopressor recommended by the Surviving Sepsis Campaign guideline.[43]

NICE makes no recommendation on the choice of vasopressor.[3]
• If further vasopressor therapy is required to maintain adequate blood pressure, add vasopressin to
noradrenaline.[43]

Practical tip

Vasopressors are usually administered via central venous access due to concerns of extravasation and tissue
ischaemia. However, the Surviving Sepsis Campaign supports short-term (less than 6 hours) peripheral
administration of vasopressors in a vein proximal to the antecubital fossa, depending on local availability, and
expertise in placement, of central venous catheters.[43] Central venous access should be secured as soon as
possible.
These patients should also have an arterial catheter inserted as soon as possible to ensure more accurate
monitoring of arterial blood pressure.[43]

Evidence: Choice of vasopressor

Although a systematic review of 23 randomised trials of patients with shock found no convincing evidence for
the superiority of one vasopressor over another, [191] more recent meta-analyses reported a higher mortality
associated with dopamine than with noradrenaline. [192]

Inotropes
Inotropes can be considered for patients with low cardiac output despite adequate fluid resuscitation and
vasopressor therapy. [3] [43]

• The Surviving Sepsis Campaign guideline recommends either adding dobutamine to noradrenaline or using
adrenaline (epinephrine) alone for people with persistent hypoperfusion despite adequate volume status and
arterial blood pressure.[43]
• NICE makes no specific recommendations on inotrope selection in patients with sepsis.[3]

Practical tip

Suspect low cardiac output if the clinical examination reveals prolonged capillary refill times, low urine
output, or poor peripheral perfusion. Confirm with cardiac output monitoring or by sampling central
venous or pulmonary arterial blood to measure oxygen saturations.
When using inotropes, keep the patient’s heart rate at less than 100 beats per minute to minimise myocardial
ischaemia.[179]
MANAGEMENT

Corticosteroids
The Surviving Sepsis Campaign guideline recommends intravenous hydrocortisone for patients with an ongoing
requirement for vasopressor therapy.[43]

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Sepsis in adults Management
• NICE does not give any recommendations on the use of corticosteroids for managing sepsis in adults.[3]

MANAGEMENT

Evidence: Benefits and harms of corticosteroids

In adults with sepsis, intravenous low-dose corticosteroids may reduce organ failure at 7 days, and duration of
mechanical ventilation, vasopressor therapy, and intensive care stay. However, whether corticosteroids reduce
short or longer-term mortality is unclear. Possible harms include an increased risk of neuromuscular weakness,
hyperglycaemia, and hypernatraemia with corticosteroids compared with no corticosteroids.

The Surviving Sepsis Campaign (SSC) 2021 guideline made a weak recommendation for using intravenous
low-dose corticosteroids for adults with septic shock and an ongoing need for vasopressors (overall evidence
assessed as moderate using GRADE). This was a slight change from the prior 2016 recommendation due to the
publication of three subsequent randomised controlled trials (VANISH, ADRENAL, and APROCHSS) and a
meta-analysis including these studies (22 RCTs, N=7297).[43] [193]

• Duration of shock was reduced in patients who received corticosteroids compared with placebo (mean
difference -1.52 days, 95% CI -1.71 to -1.32 days, quality of evidence as assessed by GRADE moderate).

• Corticosteroids also reduced organ failure at 1 week, duration of mechanical ventilation, and
intensive care stay, and increased vasopressor-free days.

• However, there was no difference in short-term mortality (risk ratio [RR] 0.96, 95% CI 0.91 to 1.02,
GRADE high) with similar results for longer-term mortality (RR 0.96, 95% CI 0.90 to 1.02, GRADE
moderate).
• Corticosteroid use possibly increased neuromuscular weakness (RR 1.21, 95% CI 1.01 to 1.45, GRADE
low).

• Corticosteroids also increased the risk of any adverse event but there was considerable
heterogeneity.

• No trials reported quality-of-life outcomes.

• The guideline also noted that uncertainties remain about the optimal dose, timing of initiation, and
duration of treatment.

Other systematic reviews have considered low-dose corticosteroids in adults and children with sepsis ( with
or without shock). They have included slightly different studies and come to slightly different conclusions,
particularly about mortality.

• A Cochrane review (search date July 2019) included 61 trials (12,192 participants, 53 trials in adults
only). There were no new studies comparing low-dose corticosteroids with placebo since ADRENAL and
APROCHSS.[194]

• 2-day, 90-day, and hospital mortality were reduced with use of corticosteroids (GRADE
moderate). However, there was no difference in mortality at 6 months to 1 year (GRADE low).
• Intensive care and hospital length of stay were significantly reduced with corticosteroids (GRADE
high).
MANAGEMENT

• Corticosteroids increased the risk of hypernatraemia (GRADE high) and probably increased the
risk of hyperglycaemia (GRADE moderate). They also increased the risk of muscle weakness
(GRADE high). They did not seem to increase the risk of superinfection (GRADE moderate).

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Sepsis in adults Management
• There was no significant difference in gastroduodenal bleeding, stroke, cardiac events, or
neuropsychiatric events.

• A rapid clinical practice guideline was published in 2018 triggered by publication of ADRENAL and
APROCHSS.[195] The panel made a weak recommendation for the use of corticosteroids in adults and
children with sepsis ( with and without shock). This guideline was also underpinned by a systematic
review (42 RCTs, N=10,194).[196]

• The guideline panel concluded that it was uncertain whether corticosteroids reduced short-term
mortality at 28 to 31 days (1.8% absolute risk reduction, 95% CI, 4.1% reduction to 0.8% increase,
GRADE low), although they did seem to reduce longer-term mortality at 60 days to 1 year (2.2%
absolute risk reduction; 95% CI, 4.1% reduction to 0%, GRADE moderate).
• Other results were similar to those of the SSC 2021 guideline and the Cochrane systematic review.

MANAGEMENT

BMJ Rapid Recommendations: intravenous corticosteroids plus usual care versus usual care only
Lamontagne F, et al. BMJ 2018;362:k3284

Response to therapy

Antibiotics
Narrow choice of antibiotic as soon as a pathogen has been identified and sensitivities are available. [43] [137]
Assess the need to de-escalate antimicrobial therapy daily. [43]
MANAGEMENT

• Studies have shown that daily prompting about antimicrobial de-escalation is effective and may be associated
with improved outcomes.[197] [198]

Use the shortest effective course of antibiotics. [199]

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Sepsis in adults Management
• Unnecessarily prolonged antibiotic treatment is associated with resistance. See More info: Antimicrobial
resistance in Prompt management for all patients with suspected sepsis above.

Consult local microbiology guidance for other specific recommendations on de-escalation.

• Most protocols will recommend switching from intravenous to oral antibiotics as soon as possible.

The Surviving Sepsis Campaign (SSC) recommends shorter over longer courses of antibiotics for patients
with an initial diagnosis of sepsis or septic shock and adequate source control. [43] The optimal duration of
antibiotic treatment in patients with sepsis remains contentious, with concerns regarding not only under-
treatment but also the potential encouragement of antibiotic resistance. Consider seeking advice from
microbiology/infectious disease colleagues.

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 SSC suggests using procalcitonin alongside clinical evaluation to decide when to discontinue
antimicrobials.[43]

Serum lactate
Measure serum lactate, on a blood gas, to monitor response to treatment. [43] [47]

• 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.[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 35 mg/dL): 25%
• Lactate >4 mmol/L (>36 mg/dL): 38%.

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

account the full clinical picture of the individual patient in front of you including their National Early
Warning Score 2 (NEWS2) score to determine when/whether to escalate treatment.[3]

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 the emergency department setting it is more practical and quicker to use venous blood gas, which
is recommended by NICE.[3] Evidence suggests good agreement at lactate levels <2 mmol/L (<18 mg/dL)
with small disparities at higher lactate levels.[78] [79] [80]

Treating sepsis in the community

Referring to hospital
Use your clinical judgement supported by physiological assessment. [51] Use National Early Warning Score 2
(NEWS2) scoring (encouraged by NHS England) to refer urgently to hospital any acutely unwell patient with
suspected or confirmed infection according to the following triggers: [41] [NHS England: Sepsis]

• Score 7 or more

• Make an emergency referral to hospital (via blue-light ambulance) for immediate critical care input

• Score 5-6 total, or 3 or more on any single parameter

• Make an immediate referral to an acute care setting and ensure the patient is reviewed by an acute
clinician within an hour.

[Track and trigger map developed by the West of England Academic Health Science Network National Early
Warning Score project team]

Alternatively, refer for emergency medical care in hospital (usually by blue-light ambulance in the UK) any
acutely unwell patient with suspected or confirmed infection who:[3]

• Meets one or more of the UK National Institute for Health and Care Excellence (NICE) high-risk
criteria (red flags)

• Objective evidence of new altered mental state (e.g., new deterioration in Glasgow Coma Scale/
AVPU ['Alert, responds to Voice, responds to Pain, Unresponsive'] scale)
• Respiratory rate: #25 breaths per minute OR new need for oxygen (40% or more fraction of inspired
oxygen [FiO 2 ]) to maintain saturation >92% (or >88% in known chronic obstructive pulmonary
disease)
• Heart rate: >130 beats per minute
• Systolic blood pressure #90 mmHg or more than 40 mmHg below normal
• Not passed urine in previous 18 hours, or for catheterised patients passed <0.5 mL/kg of urine per
hour
• Mottled or ashen appearance
MANAGEMENT

• Cyanosis of skin, lips, or tongue

• Non-blanching petechial or purpuric rash of skin

• Is at risk of neutropenic sepsis and presents with symptoms and signs of infection

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Sepsis in adults Management
• See Febrile neutropenia .[139]

Carefully consider whether emergency medical care is required or whether the patient can be safely managed in the
community with safety netting advice.[3] See box below on safety netting advice.

If you have decided to refer the patient for emergency medical care and have called for an emergency ambulance,
you should start oxygen therapy in line with the following recommendations while awaiting the ambulance, if
resources are available to do so.[50] Pulse oximetry should be available in all locations where emergency oxygen is
used.[50]

• Give oxygen immediately; an upper SpO 2 limit of 96% is reasonable when administering supplemental
oxygen to most patients with acute illness who are not at risk of hypercapnia.

MANAGEMENT

Evidence: Target oxygen saturation in acutely ill adults

Too much supplemental oxygen increases mortality.

Evidence from a large systematic review and meta-analysis supports conservative/controlled oxygen
therapy versus liberal oxygen therapy in acutely ill adults who are not at risk of hypercapnia.

• Guidelines differ in their recommendations on target oxygen saturation in acutely unwell adults who are
receiving supplemental oxygen.

• One systematic review including a meta-analysis of data from 25 randomised controlled trials, published
in 2018, found that in adults with acute illness, liberal oxygen therapy (broadly equivalent to a target
saturation >96%) is associated with higher mortality than conservative oxygen therapy (broadly
equivalent to a target saturation #96%).[138] In-hospital mortality was 11 per 1000 higher for the liberal
oxygen therapy group versus the conservative therapy group (95% CI, 2-22 per 1000 more). Mortality
at 30 days was also higher in the group who had received liberal oxygen (relative risk 1.14, 95% CI 1.01
to 1.29). The trials included adults with sepsis, critical illness, stroke, trauma, myocardial infarction, or
cardiac arrest, and patients who had emergency surgery. Studies that were limited to people with chronic
respiratory illness or psychiatric illness, patients on extracorporeal life support, those receiving hyperbaric
oxygen therapy, or patients having elective surgery, were all excluded from the review.
• An upper SpO 2 limit of 96% is therefore reasonable when administering supplemental oxygen to patients
with acute illness who are not at risk of hypercapnia. However, a higher target may be appropriate for
some specific conditions (e.g., pneumothorax, carbon monoxide poisoning, cluster headache, and sickle
cell crisis).[166]
• In 2019 the BTS reviewed its guidance in response to this systematic review and meta-analysis and
decided an interim update was not required.[167]

• Management of oxygen therapy in patients in intensive care is specialised and informed by further
evidence (not covered in this summary) that is more specific to this setting.[169] [170][171]

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Sepsis in adults Management
Ensure you have a mechanism in place to administer antibiotics to any high-risk patient (either at your practice or
via the ambulance service) if the transfer time to hospital is likely to be more than 1 hour.[3]

Ambulance crews should evaluate the risk of severe illness or death from sepsis using NEWS2 and consider a time-
critical transfer and pre-alerting the hospital for patients with suspected or confirmed infection who either have
consecutive NEWS2 scores of 5 or above or show cause for significant clinical concern.[3]

Paramedics who are thinking about giving antibiotics should follow local guidelines or seek advice from more
senior colleagues, if needed.[3]

For patients at high risk of severe illness or death from sepsis who are in an acute mental health setting, follow local
emergency protocols on treatment and ambulance transfer.[3]

Practical tip

If you need to refer a patient for emergency medical care in hospital, it is important to inform the hospital
clinical team that the patient is on the way. This will enable the hospital to initiate appropriate treatment as
soon as the patient arrives.

Management in the community

In a patient with signs and symptoms of an infection and evidence of physiological deterioration, presume
sepsis until it can safely be excluded. Take a cautious approach when deciding whether it is safe to treat
the patient’s infection in the community.Using your clinical judgement in making a decision is paramount. In
particular, carefully consider the need for hospital admission if:[51] [73]

• The patient has one or more NICE high-risk criteria for sepsis
• The patient appears seriously unwell to you, based on experience and clinical judgement
• The patient lives alone with poor access to communication and/or transport
• A carer or parent expresses serious concern about the patient (e.g., “they’re just not right”).

For details of the NICE risk criteria, see Diagnosis recommendations .

Treat the patient’s infection in line with local protocols and accepted practice. Antimicrobial prescribing guidelines
from Public Health England and NICE are available for general practitioners in the UK.[200] [201]

For patients at high risk of severe illness or death from sepsis who are in an acute mental health setting, follow local
emergency protocols on treatment and ambulance transfer.[3]
MANAGEMENT

If you decide that the patient is safe to treat in the community, written and verbal safety netting is vital.[51]
Ensure the information is clear and specific rather than generalised advice; for example, do not say to “come
back if you get worse” – instead specify key symptoms to watch out for (such as a non-blanching rash,
change in behaviour or mental state, mottled skin, or ashen appearance) and explain where and how to access
immediate medical care both in and out of hours.[51]
If you give the patient any safety netting advice, ensure you document this clearly in their medical notes,
along with the patient’s observations and whether you have offered them any antibiotics. The 2015 national
confidential enquiry into sepsis deaths found recorded evidence that safety netting advice had been provided
in fewer than one quarter of cases.[61]
The UK Sepsis Trust advises the following acronym:[47]
• Slurred speech or confusion
• Extreme shivering or muscle pain
• Passing no urine (in a day)
• Severe breathlessness
• ‘ I feel I might die’
• Skin mottled, ashen, blue, or very pale.

Advise the patient to call the emergency services if any of these symptoms develop. If the patient has a
change in condition or deterioration that is not covered by the acronym above, advise them to arrange another
appointment to see their general practitioner or to call their out of hours service provider.
It is also good practice to consider arranging a next-day review appointment or telephone call; if you will be
unable to review the patient yourself, provide a written handover for your colleagues.
MANAGEMENT

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Sepsis in adults Management

Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or
locations. Treatment recommendations are specific to patient groups: see disclaimer

Initial ( summary )
in hospital: sepsis highly suspected and
unknown or unclear source of bacterial
infection

1st broad-spectrum intravenous antibiotics

plus reassess and monitor

plus identify the infection source

consider fluid resuscitation

consider oxygen

consider standard intensive care unit supportive care

consider vasopressor (should only be initiated by

experienced members of the critical care team)

consider inotrope (should only be initiated by experienced

members of the critical care team)

consider corticosteroid (should only be initiated by

experienced members of the critical care team)

in the community: sepsis highly suspected

and bacterial infection confirmed or highly
suspected

1st refer for emergency medical care in hospital

consider oxygen

consider broad-spectrum antibiotics

MANAGEMENT

Acute ( summary )
in hospital: sepsis highly suspected and
clear source of bacterial infection identified

1st targeted antibiotics according to local protocols

plus reassess and monitor

plus urgent source control

consider fluid resuscitation

consider oxygen

consider standard intensive care unit supportive care

consider vasopressor (should only be initiated by

experienced members of the critical care team)

consider inotrope (should only be initiated by experienced

members of the critical care team)

consider corticosteroid (should only be initiated by

experienced members of the critical care team)
MANAGEMENT

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Sepsis in adults Management

Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or
locations. Treatment recommendations are specific to patient groups: see disclaimer

Initial
in hospital: sepsis highly suspected and
unknown or unclear source of bacterial
infection

1st broad-spectrum intravenous antibiotics

» Start treatment immediately if a senior clinical

decision-maker (e.g., ST3 level doctor in the UK)
makes a diagnosis of suspected sepsis,based on
acute deterioration (e.g., National Early Warning
Score 2 [NEWS2] score of 5 or more, or a similar
trigger using another validated scoring system) in a
patient with known or likely infection.[41] [42]

» For any acutely ill and deteriorating patient with a

suspected or known bacterial infection and suspected
sepsis, above all else prioritise (if needed):[3] [47]

• Securing their airway

• Correcting hypoxaemia
• Establishing venous access for the early
administration of antibiotics and fluids.

» Where there is evidence of a bacterial infection

and sepsis is strongly suspected (based on acute
deterioration [e.g., NEWS2 score of 5 or more, or
a similar trigger using another validated scoring
system]), give broad-spectrum intravenous
antibiotics according to the timeframes below:[3] [41]
[43] [45] [47]

• Within 1 hour of initial severity assessment

for patients with a NEWS2 score of 7 or
more calculated on initial assessment in
the accident and emergency department or
on ward deterioration, (or with a score of 5
or 6 if there are additional clinical or carer
concerns, continuing deterioration or lack
of improvement, neutropenia, or blood gas/
laboratory evidence of organ dysfunction)

• A patient is also at high risk of severe

illness or death from sepsis if they have
a NEWS2 score below 7 and a single
MANAGEMENT

parameter contributes 3 points to their

NEWS2 score and a medical review
has confirmed that they are at high
risk.[3]

Initial
• Within 3 hours for patients with a NEWS2
score of 5 or 6.

» Give antibiotics before a pathogen is identified

but after blood cultures have been taken. [3] [41]
[43] [47] Only give antibiotics if they have not been
given before for this episode of sepsis.[3]

• The Surviving Sepsis Campaign international

guideline recommends empirical combination
therapy (using at least two antibiotics of
different antimicrobial classes covering gram-
negative bacilli) for patients at high risk of
infection from multidrug resistant (MDR)
organisms, particularly in those with septic
shock.[43]

• Initial use of multidrug therapy is often

required, given the frequency of MDR
bacteria in many parts of the world and
associations between delays in active
therapy and worse outcomes.[43]
• Single agents are recommended for
patients with a low risk for MDR
organisms.[43]

» Follow local policy and consider discussing

with microbiology/infectious disease colleagues to
determine the most appropriate choice.

• Once a decision is made to give antibiotics, do

not delay administration any further.[3]
• Use a 'start smart then focus' approach.
[41] [136]

More info: Antimicrobial resistance

NHS England recommends following a 'start

will kill 10 million people per year, more than

cancer and diabetes combined. [142] The
relationship between antibiotic exposure and
antibiotic resistance is unambiguous not only
at the population level but also in individual
patients. [143] [144]

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Sepsis in adults Management

Initial
Start smart – in the context of sepsis:[136]

• Do not start antimicrobial therapy unless

there is clear evidence of infection
• Take a thorough drug allergy history
• Initiate prompt effective antibiotic
treatment within 1 hour of diagnosis (or
as soon as possible) in patients with sepsis
who are critically ill (e.g., septic shock,
sepsis associated with rapid deterioration,
or NEWS2 score of 7 or more calculated
on initial assessment in the accident
and emergency department or on ward
deterioration) or with life-threatening
infections. Avoid inappropriate use of
broad-spectrum antibiotics[3] [45]
• Comply with local antimicrobial
prescribing guidance
• Document clinical indication (and disease
severity if appropriate), drug name, dose,
and route on drug chart and in clinical
notes
• Include review/stop date or duration
• Obtain cultures prior to starting therapy
where possible (but do not delay therapy).

Then focus – in the context of sepsis:[136]

• Review the clinical diagnosis and the

continuing need for antibiotics at 48 to
72 hours* and document in a clear plan
of action – the ‘antimicrobial prescribing
decision’
• The ‘antimicrobial prescribing decision’
options are:

1. Stop antibiotics if there is no

evidence of infection
2. Switch antibiotics from intravenous
to oral
3. Change antibiotics – ideally to a
narrower spectrum, or broader if
required
4. Continue and document next review
MANAGEMENT

date or stop date

• It is essential that the review and

subsequent decision is clearly documented

Initial
in the clinical notes and on the drug chart
where possible (e.g., ‘stop antibiotic’).

*In clinical practice, daily prompting about de-

escalation is encouraged.

The UK’s Academy of Medical Royal Colleges

recommends stratifying patients with suspected
sepsis according to severity of illness at
presentation, allowing a 3-hour window to
investigate patients with less severe illness
(e.g., NEWS2 score of 5 or 6). This should
improve accuracy of treatment and help to reduce
antimicrobial resistance.[45]

» Target the presumed site of infection.[3] [43]

» If there is no clinical evidence to suggest a specific

site of infection but a senior clinical decision-maker
strongly suspects the presence of a bacterial infection,
still give empirical broad-spectrum intravenous
antibiotics.[3] [41] Choose an empirical antibiotic
based on:[145] [146]

• Local antibiotic protocols and resistance

patterns

• Consult microbiology/infectious
disease colleagues to determine the
most appropriate choice

• The likely causative organism

• The patient’s immune function.

Practical tip

Check local policies regarding repeat cultures,

which are particularly indicated if there
are persistent or repeated fever spikes
or if you identify a potential new site of
infection. Observations from studies to date
support taking as many as four blood culture
sets over a 24-hour period for >99% test
sensitivity.[147]
MANAGEMENT

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Sepsis in adults Management

Initial
Practical tip

If a patient has a mild allergy (e.g., rash)

to an unknown antibiotic, you should still
give empirical broad-spectrum antibiotics if
indicated to prevent delay in the treatment of
sepsis, which is likely to worsen outcome.
If the antibiotic is known and is part of
the empirical protocol for your hospital,
discuss with potential alternatives with a
microbiologist.

Evidence: 1- and 3-hour antibiotic targets

There is widespread agreement that antibiotics

should be offered to people with sepsis, within
a timeframe that depends on their risk of severe
illness or death. The UK National Institute
for Health and Care Excellence (NICE), the
Surviving Sepsis Campaign (SSC) and the UK
Academy of Medical Royal Colleges (AOMRC)
all recommend a 1-hour target time threshold
for patients at high risk and a 3-hour target time
threshold for patients at moderate risk. [43] [45]

Two meta-analyses published in 2015 and

2020 compared outcomes for patients with
sepsis and septic shock given either immediate
(within 1 hour of onset) or early (between 1 and
3 hours from onset) antibiotics; neither meta-
analysis identified a difference in mortality
between these thresholds.[148] [149] One 2021
systematic review (without meta-analysis) of
35 sepsis studies concluded that two-thirds
of studies reported an association between
early administration of antibiotic therapy and
patient outcome, but there was widespread
variation in metrics and no robust time thresholds
emerged.[150] Almost all of the studies included
in these reviews were observational.[148] [149]
[150]

The 2021 update of the SSC guideline

recommends that patients with possible sepsis
without shock should receive a time-limited
course of rapid investigation with administration
of antimicrobials within 3 hours if there is
persisting concern for infection.[43] Similarly,
2022 guidance from the UK’s AOMRC, based
MANAGEMENT

largely on the evidence above, recommends a

3-hour window for investigating and treating
patients with less severe illness, while continuing
to recommend a 1-hour target for treating patients
with more severe illness (e.g., NEWS2 score of
7 or more, or septic shock). The recommended

Initial
timeframes in the Sepsis Trust’s Sepsis Six bundle
have since been adjusted in line with AOMRC
guidance.[43] [45] [47]

• In their discussion NICE highlighted

that the reason for the longer target time
threshold for those at moderate risk was to
give more time to establish the diagnosis
and guide antibiotic choice, and that the 3-
hour limit is a maximum not an aim.

» In intensive care settings only, consider

prolonged infusion when giving beta-lactam
antibiotics to patients with sepsis (apart from
those with kidney-related complications).
[151] Note that prolonged infusion times are not
licensed, as most manufacturers advise infusion of
beta-lactam antibiotics over 15 to 60 minutes.

Evidence: Prolonged antibiotic infusion

Intravenous antibiotics, administered over 3

hours, are linked to lower death rates in sepsis.
[151] Prolonged infusion should be easy to
apply in the intensive care setting, without the
need for additional training or equipment.

• A systematic review and meta-analysis

pooled the results of 22 randomised
controlled trials involving 1876 adults
with sepsis. The trials compared prolonged
versus short-term administration of
any antipseudomonal beta-lactam.
Carbapenems were studied in nine
trials, penicillins in nine trials, and
cephalosporins in eight trials.[151]

• Prolonged infusion was associated

with lower all-cause mortality
than short-term infusion, with
13.6% deaths compared with
19.8% (risk ratio [RR] 0.70, 95%
CI 0.56 to 0.87; 17 studies, 1597
participants).
• There was no significant difference
between prolonged and short-
term infusion for clinical cure
MANAGEMENT

or improvement (RR 1.06, 95%

CI 0.96 to 1.17; 11 studies, 1219
participants).
• There was no difference in
reported adverse events between

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Sepsis in adults Management

Initial
the groups (RR 0.88, 95% CI 0.71
to 1.09; 7 studies, 980 participants).
• Two trials had no incidence of
antibiotic resistance, and two trials
had no difference in resistance
between the two methods of
antibiotic administration (RR 0.60,
95% CI 0.15 to 2.38).

» Narrow choice of antibiotic as soon as a

pathogen has been identified and sensitivities are
available. [43] [137] Assess the need to de-escalate
antimicrobial therapy daily. [43]

• Studies have shown that daily prompting

about antimicrobial de-escalation is effective
and may be associated with improved
outcomes.[197] [198]

» Continue broad-spectrum coverage to include

all common pathogens if the source is unknown or
unclear. [3]

• Bear in mind that a definite source of infection

cannot be found in 20% to 30% of people with
sepsis.[9]

» Use the shortest effective course of antibiotics.

[199]

• Unnecessarily prolonged antibiotic treatment

is associated with resistance. See More info:
Antimicrobial resistance above.

» Consult local microbiology guidance for other

specific recommendations on de-escalation.

• Most protocols will recommend switching

from intravenous to oralantibiotics as soon
as possible.

» The Surviving Sepsis Campaign (SSC)

recommends shorter over longer courses of
antibiotics for patients with an initial diagnosis
of sepsis or septic shock and adequate source
control.[43]
MANAGEMENT

» The optimal duration of antibiotic treatment

in patients with sepsis remains contentious, with
concerns regarding not only under-treatment but
also the potential encouragement of antibiotic
resistance. Consider seeking advice from
microbiology/infectious disease colleagues.

Initial
» 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 SSC suggests using procalcitonin
alongside clinical evaluation to decide when to
discontinue antimicrobials.[43]

plus reassess and monitor

Treatment recommended for ALL patients in selected
patient group
» Ensure frequent and ongoing monitoring. [3]

• Standard monitoring of vital signs, pulse

oximetry, level of consciousness, and urinary
output is important for any patient with
suspected sepsis.
• The UK National Institute for Health and Care
Excellence (NICE) recommends continuous or
half-hourly monitoring (depending on setting)
for any patient considered to be at high risk
of deterioration (e.g., using an early warning
score such as NEWS2).[3]
• For more information, see Risk stratification
under Diagnosis recommendations .

» Use a track-and-trigger scoring system such

as the National Early Warning Score 2 (NEWS2)
to identify any signs of deterioration. [3] Your
monitoring should include:

• Vital signs: heart rate, blood pressure, oxygen

saturations, respiratory rate, and temperature

• Measure blood pressure via an arterial

line if the patient does not respond to
initial treatment or needs vasoactive
drugs. It provides precise, continuous
monitoring, and access for arterial
blood sampling
MANAGEMENT

• Hourly urine output[3] [47]

• Lactate

• The lactate level should decrease if the

patient is clinically improving

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Sepsis in adults Management

Initial
• Frequency of repeat lactate
measurement depends on the cause of
sepsis and treatment given.

» Measure serum lactate, on a blood gas, to

monitor response to treatment [3] [43] [47]

• 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.[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%.

» 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]
MANAGEMENT

Initial
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 the emergency
department setting it is more practical and
quicker to use venous blood gas, which is
recommended by NICE.[3] Evidence suggests
good agreement at lactate levels <2 mmol/L
(<18 mg/dL) with small disparities at higher
lactate levels.[78] [79] [80]

» In the UK, use physiological track-and-trigger

systems to monitor all adult patients in acute hospital
settings.[3]

» Consider using a validated scale such as the

Glasgow Coma Scale or AVPU ('Alert, responds
to Voice, responds to Pain, Unresponsive') scale
to monitor the mental state of a patient with
suspected sepsis. [3]

Practical tip

AVPU should raise concerns if the assessment

shows the patient is anything other than 'alert'.

» Any patient with sepsis may be at significant

risk of severe illness or death so it is vital to
consider escalation of care to senior colleagues
and/or healthcare facilities where increased and
more advanced monitoring can be given (e.g.,
high-dependency unit/intensive care unit). [7]
[173] [174]

• Bear in mind that some patients (e.g.,

those who are frail) may not be suitable
for management in intensive care settings.
Consider the patient’s preferences for future
care and their baseline health including their
resuscitation status when determining the
limits of treatment. Use this to feed into a
personalised care plan appropriate to the
individual patient.[45]

» Consult local protocols for specific escalation

routes but in general:
MANAGEMENT

• Ensure urgent review by a senior clinician

(e.g., ST3 level doctor or higher in the UK)
of any patient with a NEWS2 score of 5 or
more calculated on initial assessment in the
accident and emergency department or on
ward deterioration:[3] [41] [45]

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Sepsis in adults Management

Initial
• Within 30 minutes of initial severity
assessment for any patient with an
aggregate NEWS2 score of 7 or
more; or with a score of 5 or 6 if
there is clinical or carer concern,
continuing deterioration or lack of
improvement, surgically remediable
sepsis, neutropenia, or blood gas/
laboratory evidence of organ
dysfunction (including elevated serum
lactate - see below)
• Within 1 hour of initial severity
assessment for any patient with an
aggregate NEWS2 score of 5 or 6

• Inform the responsible consultant if a

patient is at high risk of severe illness or
death from sepsis (e.g., NEWS2 score of 7 or
more) does not respond within 1 hour of any
intervention (antibiotics/fluid resuscitation/
oxygen).[3] Ensure the senior clinical
decision-maker attends in person.

» Signs that the person is not responding to

resuscitation include lack of improvement or
worsening:[3]

• Tachycardia
• Level of consciousness
• Blood pressure
• Respiratory rate
• Blood lactate
• Urine output
• Peripheral perfusion
• Blood gases.

» Consider alerting critical care immediately if the

patient is acutely unwell and:

• Is likely to require central venous access and

the initiation of inotropes or vasopressors[3]

• This includes any patient with evidence

of circulatory dysfunction or shock,
or those who do not respond to initial
therapy (as outlined above), including
initial fluid resuscitation within 1 hour.
MANAGEMENT

• Has any feature of septic shock

• See Shock

Initial
• Has neutropenia

• See Febrile neutropenia

• Is immunodeficient

Practical tip

Ensure a clear escalation plan has been

discussed and agreed with the clinical team;
include specific points of contact for nursing
staff if you are leaving a patient for later
review.
Involve a senior colleague and/or consider
transferring to critical care sooner rather
than later if the patient is not improving,
or deemed high-risk. Examples include if the
patient:
• Is not responding to fluids
• Needs inotropic support
• Has a low Glasgow Coma Scale score
• Needs ventilatory support.

plus identify the infection source

Treatment recommended for ALL patients in selected
patient group
» Make intensive efforts to identify the anatomical
site of infection as soon as possible. [3] [43]
Consider the need for urgent source control as
soon as the patient is stable.

• Start with a thorough and focused clinical

history and examination, as well as initial
investigations including imaging.[3]
• Consider all lines and catheters as potential
sources. Remove lines where appropriate.[43]

• Assume that any intravenous route is

likely to either be the source of the
infection, or will seed infections in
the bloodstream, making eradication
particularly difficult. Therefore, the
priority for source control is often to
remove any intravenous devices after
alternative vascular access has been
obtained.[43]
MANAGEMENT

• 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

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Sepsis in adults Management

Initial
as soon as possible, in line with the advice
received.[3]

• In practice, this may mean early

transfer of the patient to a surgical
centre if there are no facilities at your
hospital.

» Common non-specific signs and symptoms

include:[21] [43]

• Those associated with a specific source of

infection. [Signs and symptoms of possible
infection sources] The most common sources
are:[61]

• 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

• Tachypnoea
• High (>38°C [>100.4°F]) or low (<36°C
[<96.8°F]) temperature, sometimes with rigors
• Tachycardia
• Acutely altered mental status
• Low oxygen saturation
• Hypotension
• Decreased urine output

• Ask the patient when they last passed

urine

• Poor capillary refill, mottling of the skin, or

ashen appearance
• Cyanosis
• Malaise/lethargy
• Nausea/vomiting/diarrhoea
MANAGEMENT

• Purpura fulminans (a very late sign but may be

seen on presentation)
• Ileus
• Jaundice.

Initial
Practical tip

Jaundice is a rare sign of sepsis unless it is

associated with a specific source of infection (
biliary sepsis).

Capillary refill time. Top image: normal skin tone;

middle image: pressure applied for 5 seconds;
bottom image: time to hyperaemia measured
From the collection of Ron Daniels,
MB, ChB, FRCA; used with permission
MANAGEMENT

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Sepsis in adults Management

Initial

Severe purpura fulminans; classically

associated with meningococcal sepsis
but can occur with pneumococcal sepsis
From the collection of Ron Daniels,
MB, ChB, FRCA; used with permission

» If your examination of the patient identifies a

clear source of infection, consider the need for
urgent source control, as soon as the patient is
stable, particularly for:[43]

• Gastrointestinal sources (such as visceral

abscesses, cholangitis, or peritonitis secondary
to perforation)
• Severe skin infections (e.g., necrotising
fasciitis)
• Infection involving an indwelling device,
where a procedure or surgery is likely to be
required.

» Give immediate, targeted antibiotics in people

with sepsis thought to arise from a central
nervous system source (e.g., suspected meningitis or
meningococcal sepsis).[3]

• Immediately give a third-generation

cephalosporin such as ceftriaxone.
• In community settings, pre-hospital
administration of benzylpenicillin is
recommended.
• Follow local policy and consider discussing
with microbiology/infectious disease
colleagues to determine the most
MANAGEMENT

appropriate choice; use a 'start smart then

focus' approach. [41] [136]

Initial
Practical tip

If intravenous access is not feasible or is likely

to lead to a delay in starting antibiotics and
fluids, use intra-osseous access as an interim
measure.
consider fluid resuscitation
Treatment recommended for SOME patients in
selected patient group
» Give 500 mL of crystalloid fluid, with a sodium
content between 130 mmol/L and 154 mmol/L
(130 to 154 mEq/L) (e.g., 0.9% sodium chloride or
Hartmann’s solution), over less than 15 minutes
to patients who need fluid resuscitation (if either
lactate is over 2 mmol/L or systolic blood pressure
is less than 90 mmHg). [3] [41] [67]

• Give this intravenous fluid bolus, if indicated,

without delay (within 1 hour of identifying a
patient is at high risk).[3]
• Consider giving an intravenous fluid bolus
to patients with a high risk of severe illness
or death from sepsis if lactate is 2 mmol/L or
lower.[3]
• Reassess the patient’s haemodynamic status
after the first bolus to consider whether a
second is required.[3] If there is no response
to either the first or second bolus, ensure the
senior clinical decision-maker attends in
person.[3]

» Intravenous fluid resuscitation may be

lifesaving in patients with hypotension. This is
because in sepsis there is vasodilation and capillary
leakage, which means that patients can rapidly
become intravascularly deplete.[3]

• In patients with sepsis-induced hypoperfusion

(as indicated by a systolic blood pressure <90
mmHg, a raised lactate level, or signs of organ
dysfunction), the Surviving Sepsis Campaign
international guideline recommends a total of
at least 30 mL/kg of intravenous crystalloid
over the first 3 hours.[43]

• If the patient’s initial lactate level is

raised, the guideline recommends serial
lactate measurements to guide the need
for further intravenous fluids (with the
MANAGEMENT

goal of normalising lactate levels).[43]

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Sepsis in adults Management

Initial
Practical tip

The delivery of appropriate rapid fluid

challenges is intended to restore the
imbalance between oxygen supply and
demand to the tissues. Patients who do not
respond to rapid delivery of adequate volumes
of intravenous fluids are in septic shock and
need immediate referral to critical care. The
immediate priority in this group of patients
is to restore the circulation and oxygen
delivery.

Practical tip

Monitor patients closely for signs of fluid

overload such as pulmonary or systemic
oedema before and after each additional fluid
bolus, as they may require large volumes of
fluid to support their circulating volume.[43]
[152] [153]

• Check local protocols for specific

recommendations on fluid choice. There is
debate, based on conflicting evidence, on
whether there is a benefit in using normal
saline or balanced crystalloid in critically ill
patients.

Practical tip

Be aware that large volumes of normal saline

as the sole fluid for resuscitation may lead to
hyperchloremic acidosis.
Also note that use of lactate-containing fluid
in a patient with impaired liver metabolism
may lead to a spuriously elevated lactate level,
so results need to be interpreted with other
markers of volume status.

Evidence: Choice of fluid

Evidence from two large randomised controlled

trials (RCTs) suggests there is no difference
between normal saline and a balanced
crystalloid for critically ill patients in mortality
at 90 days, although results from two meta-
analyses including these RCTs point to a
MANAGEMENT

possible small benefit of balanced solutions

compared with normal saline.

There has been extensive debate over the

choice between normal saline (an unbalanced
crystalloid) versus a balanced crystalloid

Initial
(such as Hartmann’s solution [also known as
Ringer’s lactate] or Plasma-Lyte®). Clinical
practice varies widely, so you should check
local protocols.

• In 2021-2022 two large double-blind RCTs

were published assessing intravenous
fluid resuscitation in intensive care unit
(ICU) patients with a balanced crystalloid
solution (Plasma-Lyte) versus normal
saline: the Plasma-Lyte 148 versus
Saline (PLUS) trial (53 ICUs in Australia
and New Zealand; N=5037) and the
Balanced Solutions in Intensive Care
Study (BaSICS) trial (75 ICUs in Brazil;
N=11,052).[154] [155]

• In the PLUS study, 45.2% of

patients were admitted to ICU
directly from surgery (emergency
or elective), 42.3% had sepsis,
and 79.0% were receiving
mechanical ventilation at the time
of randomisation.
• In BaSICS, almost half the patients
(48.4%) were admitted to ICU after
elective surgery and around 68%
had some form of fluid resuscitation
before being randomised.
• Both found no difference in 90-day
mortality overall or in prespecified
subgroups for patients with acute
kidney injury (AKI), sepsis, or
post-surgery. They also found no
difference in the risk of AKI.
• In BaSICS, for patients with
traumatic brain injury, there
was a small decrease in 90-day
mortality with normal saline;
however, the overall number of
patients was small (<5% of total
included in the study) so there is
some uncertainty about this result.
Patients with traumatic brain injury
MANAGEMENT

were excluded from PLUS as the

authors felt these patients should
be receiving saline or a solution of
similar tonicity.

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Sepsis in adults Management

Initial
• A meta-analysis of 13 RCTs (including
PLUS and BaSICS) confirmed no overall
difference, although the authors did
highlight a non-significant trend towards
a benefit of balanced solutions for risk of
death.[156]
• A subsequent individual patient data
meta-analysis included 6 RCTs of which
only PLUS and BaSICS were assessed
as being at low risk of bias. There was
no statistically significant difference in
in-hospital mortality (odds ratio [OR]
0.96, 95% CI 0.91 to 1.02). However,
the authors argued that using a Bayesian
analysis there was a high probability that
balanced solutions reduced in-hospital
mortality, although they acknowledged that
the absolute risk reduction was small.[157]

• A pre-specified sub-group analysis

of patients with traumatic brain
injury (N=1961) found that
balanced solutions increased
the risk of in-hospital mortality
compared with normal saline (OR
1.42, 95% CI 1.10 to 1.82)

• Previous evidence has been mixed.

• One 2015 double-blind, cluster

randomised, double-crossover
trial conducted in 4 ICUs in New
Zealand (N=2278), the 0.9% Saline
vs Plasma-Lyte® for ICU fluid
Therapy (SPLIT) trial, found no
difference for in-hospital mortality,
AKI, or use of renal-replacement
therapy.[158]
• However, a 2018 US multicentre
unblinded cluster-randomised
trial - the isotonic Solutions and
Major Adverse Renal events Trial
(SMART), among 15,802 critically
ill adults receiving ICU care -
found possible small benefits from
balanced crystalloid (Ringer’s
lactate or Plasma-Lyte®) compared
with normal saline. The 30-day
outcomes showed a non-significant
reduced mortality in the balanced
MANAGEMENT

crystalloid group versus the normal

saline group (10.3% vs. 11.1%;
odds ratio [OR] 0.90, 95% CI 0.80
to 1.01) and a major adverse kidney
event rate of 14.3% versus 15.4%,

Initial
respectively (OR 0.91, 95% CI 0.84
to 0.99).[159]

• One 2019 Cochrane review included 21

RCTs (N=20,213) assessing balanced
crystalloids versus normal saline for
resuscitation or maintenance in a critical
care setting.[160]

• The 3 largest RCTs in the Cochrane

review (including SMART
and SPLIT) all examined fluid
resuscitation in adults and made up
94.2% of participants (N=19,054).
• There was no difference in in#
hospital mortality (OR 0.91, 95%
CI 0.83 to 1.01; high-quality
evidence as assessed by GRADE),
acute renal injury (OR 0.92, 95%
CI 0.84 to 1.00; GRADE low), or
organ system dysfunction (OR 0.80,
95% CI 0.40 to 1.61; GRADE very
low).

The Surviving Sepsis Campaign 2021 guideline

update makes a weak recommendation (low-
quality evidence) in favour of administering
a balanced crystalloid (such as Hartmann's
solution [Ringer's lactate] or Plasma-Lyte®)
to patients with sepsis, based on evidence
published prior to the BaSICS trial results.

• Subgroup analysis of patients with

sepsis within the BaSICS trial showed
no difference in 90-day mortality
between patients given normal saline
(an unbalanced crystalloid) versus a
balanced crystalloid. However, the authors
comment that the subgroup analysis should
be considered as hypothesis-generating
only.[154] Further RCTs are awaited.
MANAGEMENT

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Sepsis in adults Management

Initial
Practical tip

To guide the need for further intravenous

fluids, it can sometimes be helpful to use
bedside ultrasound to monitor changes in
inferior vena cava (IVC) diameter during
respiration. [161] [162]
• In the spontaneously breathing patient:
consider additional fluid resuscitation if
there is a collapsed (or collapsing) IVC.
• In the mechanically ventilated patient:
an increase in IVC size >18% (or visible
to the naked eye) with positive pressure
ventilation suggests fluid-responsiveness.

Practical tip

Use the passive leg-raising test to predict

fluid-responsiveness if adequate monitoring is
available.[67] [163]
• This is a useful indicator of fluid-
responsiveness, which should be assessed
using devices that can continuously
monitor cardiac output in real time (e.g.,
Pulse index Continuous Cardiac Output
[PiCCO] monitor or oesophageal Doppler),
usually in an intensive care unit rather than
a general ward setting.
• Sit the patient upright at 45° and tilt the
entire bed through 45°.
• Patients with a positive test have a >10%
increase in cardiac output or stroke volume,
indicating more fluids may be required.
• The passive leg-raise response may be
misleading in conscious patients who are
uncomfortable or in pain when lying flat.

consider oxygen
Treatment recommended for SOME patients in
selected patient group
» If indicated, give oxygen. Monitor controlled
oxygen therapy. An upper SpO 2 limit of 96% is
MANAGEMENT

reasonable when administering supplemental oxygen

to most patients with acute illness who are not at risk
of hypercapnia.

• Evidence suggests that liberal use of

supplemental oxygen (target SpO 2 >96%)

Initial
in acutely ill adults is associated with higher
mortality than more conservative oxygen
therapy.[138]
• A lower target SpO 2 of 88% to 92%
is appropriate if the patient is at risk of
hypercapnic respiratory failure.[50]

Evidence: Target oxygen saturation in acutely

ill adults

Too much supplemental oxygen increases

mortality.

Evidence from a large systematic review and

meta-analysis supports conservative/controlled
oxygen therapy versus liberal oxygen therapy
in acutely ill adults who are not at risk of
hypercapnia.

• Guidelines differ in their recommendations

on target oxygen saturation in acutely
unwell adults who are receiving
supplemental oxygen.

• The 2017 British Thoracic Society

(BTS) guideline recommends
a target SpO 2 range of 94% to
98% for patients not at risk of
hypercapnia, whereas the 2022
Thoracic Society of Australia and
New Zealand (TSANZ) guideline
recommends 92% to 96%.[50]
[164]
• The 2022 Global Initiative For
Asthma (GINA) guidelines
recommend a target SpO 2 range of
93% to 96% in the context of acute
asthma exacerbations.[165]

• One systematic review including a meta-

analysis of data from 25 randomised
controlled trials published in 2018 found
that in adults with acute illness, liberal
oxygen therapy (broadly equivalent to
a target saturation >96%) is associated
with higher mortality than conservative
oxygen therapy (broadly equivalent to a
target saturation #96%).[138] In-hospital
mortality was 11 per 1000 higher for the
MANAGEMENT

liberal oxygen therapy group versus the

conservative therapy group (95% CI 2-22
per 1000 more). Mortality at 30 days was
also higher in the group who had received
liberal oxygen (relative risk 1.14, 95% CI
1.01 to 1.29). The trials included adults

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Sepsis in adults Management

Initial
with sepsis, critical illness, stroke, trauma,
myocardial infarction, or cardiac arrest,
and patients who had emergency surgery.
Studies that were limited to people with
chronic respiratory illness or psychiatric
illness, or patients on extracorporeal life
support, receiving hyperbaric oxygen
therapy, or having elective surgery, were
all excluded from the review.
• An upper SpO 2 limit of 96% is
therefore reasonable when administering
supplemental oxygen to patients with
acute illness who are not at risk of
hypercapnia. However, a higher target may
be appropriate for some specific conditions
(e.g., pneumothorax, carbon monoxide
poisoning, cluster headache, or sickle cell
crisis).[166]
• In 2019 the BTS reviewed its guidance
in response to this systematic review and
meta-analysis and decided an interim
update was not required.[167]

• The committee noted that the

systematic review supported the use
of controlled oxygen therapy to a
target.
• While the systematic review
showed an association between
higher oxygen saturations
and higher mortality, the BTS
committee felt the review was not
definitive on what the optimal target
range should be. The suggested
range of 94% to 96% in the review
was based on the lower 95%
confidence interval and the median
baseline SpO 2 from the liberal
oxygen groups, along with the
earlier 2015 TSANZ guideline
recommendation.

• Subsequently, experience during the

COVID-19 pandemic has also made
clinicians more aware of the feasibility of
permissive hypoxaemia.[168] The BTS
guidance is due for a review in 2022.

• Management of oxygen therapy in patients

MANAGEMENT

in intensive care is specialised and

informed by further evidence (not covered
in this summary) that is more specific to
this setting.[169] [170][171]

Initial
» There is no specific evidence to show that giving
oxygen improves clinical outcomes in sepsis.
However, respiratory failure will lead to tissue
hypoxia and anaerobic respiration. This is likely
to lead to acidosis and consequently a poorer
outcome.[172]
consider standard intensive care unit supportive care
Treatment recommended for SOME patients in
selected patient group
» Any patient with sepsis may be at significant
risk of severe illness or death so it is vital to
consider escalation of care to senior colleagues
and/or healthcare facilities where increased and
more advanced monitoring can be given (e.g.,
high-dependency unit/intensive care unit). [7]
[173] [174]

• Bear in mind that some patients (e.g.,

» Consult local protocols for specific escalation

routes but in general:

• Ensure urgent review by a senior clinician

(e.g., ST3 level doctor or higher in the
UK) of any patient with a National Early
Warning Score 2 (NEWS2) score of 5 or
more calculated on initial assessment in the
accident and emergency department or on
ward deterioration:[3] [41] [45]

• Within 30 minutes of initial severity

assessment for any patient with an
aggregate NEWS2 score of 7 or
more; or with a score of 5 or 6 if
there is clinical or carer concern,
continuing deterioration or lack of
improvement, surgically remediable
sepsis, neutropenia, or blood gas/
laboratory evidence of organ
dysfunction (including elevated serum
lactate)
MANAGEMENT

• Within 1 hour of initial severity

assessment for any patient with an
aggregate NEWS2 score of 5 or 6

• Inform the responsible consultantif a patient

is at high risk of severe illness or death from

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Sepsis in adults Management

Initial
sepsis (e.g., NEWS2 score of 7 or more) does
not respond within 1 hour of any intervention
(antibiotics/fluid resuscitation/oxygen).[3]
Ensure the senior clinical decision-maker
attends in person.

• Signs that the person is not responding

to resuscitation include lack of
improvement or worsening:[3]

• Tachycardia
• Level of consciousness
• Blood pressure
• Respiratory rate
• Blood lactate
• Urine output
• Peripheral perfusion
• Blood gases.

• Consider alerting critical care immediately

if the patient is acutely unwell and:

• Is likely to require central venous

access and the initiation of inotropes or
vasopressors[3]

• This includes any patient

with evidence of circulatory
dysfunction or shock, or
those who do not respond to
initial therapy (as outlined
above) including initial fluid
resuscitation within 1 hour.

• Has any feature of septic shock

• See Shock

• Has neutropenia

• See Febrile neutropenia

• Is immunodeficient.
MANAGEMENT

Initial
Practical tip

Ensure a clear escalation plan has been

» For any patient with suspected sepsis, consider

the need for referral to a high-dependency unit for
management by the critical care team.[177] [178]

» The following interventions should only be

initiated by experienced members of the critical
care team:[179]

• Glycaemic control
• Vasoactive drugs (vasopressors/inotropes)
• Corticosteroids.

» Additional intensive care measures that will be

considered include:[43] [180] [181]

• Stress ulcer prophylaxis (in people at risk of

gastrointestinal bleeding)

• With an H2 antagonist or proton-pump

inhibitor

• Deep venous thrombosis prophylaxis

• With heparin and compression

stockings

• Enteral or parenteral nutrition

• Administration of human albumin solution 4%
to 5% in patients with sepsis and shock who
MANAGEMENT

have not responded to substantial volumes of

crystalloids [3] [43]
• Transfusion of packed cells

• Consult local protocols for

recommended threshold

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Sepsis in adults Management

Initial
• The Surviving Sepsis Campaign
recommends using a threshold of 70 g/
L (7 g/dL).[43]

Evidence: Threshold for transfusion of packed

cells

In the general critical care population there is

no improvement with blood transfusions given at
a higher haemoglobin threshold compared with
a lower haemoglobin threshold. Overall, a more
restrictive transfusion strategy is recommended;
however, individual patient factors should be
taken into account.

The 2021 Surviving Sepsis Campaign guideline

recommends a restrictive transfusion strategy
for adults with sepsis or septic shock.[43] The
guideline identifies the following evidence.

• One multicentre parallel group randomised

controlled trial (RCT) in people >16
years of age with septic shock (N=998)
compared blood transfusion at a lower
haemoglobin threshold with a higher
threshold.[182]

• There was no difference in 90-day

mortality between groups (risk ratio
[RR] 0.94, 95% CI 0.78 to 1.09).
• The results were similar using
different methods of analysis
(adjusted for risk factors at baseline,
and per-protocol analyses).
• Ischaemic events, severe adverse
reactions, and need for life support
were also similar.

• A second multicentre RCT (838 critically

ill adults) compared a restrictive strategy
of red-cell transfusion with a liberal
strategy.[183]

• Overall, 30-day mortality was

similar in the two groups (18.7%
vs. 23.3%, P = 0.11). Results were
MANAGEMENT

similar in the subgroup of patients

with sepsis or septic shock (N=218)
(22.8% vs. 29.7%, P = 0.36).
• The 30-day mortality rates were
significantly lower in patients who

Initial
were less acutely ill and in patients
younger than 55 years old with
the restrictive transfusion strategy.
However, this was not the case in
those with clinically significant
cardiac disease.
• The mortality rate during
hospitalisation was significantly
lower in the restrictive-strategy
group (22.3% vs. 28.1%, P = 0.05).

• One single-centre RCT in critically ill

adult cancer patients with septic shock
(N=300) also compared a liberal with a
restrictive strategy.[184]

• 28-day mortality was less in

the liberal group, although this
difference was not statistically
significant (45% vs. 56%, HR 0.74,
95% CI 0.53 to 1.04). However
90-day mortality was significantly
reduced in the liberal group (HR
0.72, 95% CI 0.53 to 0.97).
• There was no difference in duration
of intensive care or hospital stay
between groups.

• Meta-analysis of the three studies found no

difference in 28-day mortality (OR 0.99,
95% CI 0.67 to 1.46, quality of evidence as
assessed by GRADE moderate).[43]

The guideline concluded that the evidence did

not favour one strategy over the other. The
authors therefore based their recommendation on
resource use, cost-effectiveness, and health equity
concerns.

» There may be a case to consider giving transfusions

at a higher haemoglobin level in some patients
(e.g., people with myocardial ischaemia, severe
hypoxaemia, or acute haemorrhage).[43]
MANAGEMENT

» In the initial resuscitative phase, transfusion

to achieve a higher haematocrit of #30% may be
appropriate.[177]

» In patients requiring prolonged ventilatory support,

give lung-protective ventilation using minimal

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Sepsis in adults Management

Initial
peak inspiratory pressures (<30 cm H 2 O) and
permissive hypercapnia to specifically limit
pulmonary compromise.[185]

• Titrate fraction of inspired oxygen (FiO 2 )

to lowest effective levels to prevent oxygen
toxicity and maintain central venous oxygen
tension.

Glycaemic control
Although patients with sepsis are often
hyperglycaemic, the optimal glucose target is
unknown.

The Surviving Sepsis Campaign guideline

recommends targeting a blood glucose level <10.0
mmol/L (<180 mg/dL).[43]

• The UK National Institute for Health and Care

Excellence makes no recommendations on
glycaemic control in sepsis.[3]

Evidence: Glycaemic control

Recent years have seen a shift in opinion

and practice regarding glycaemic control in
critically ill people. Since 2001, the use of tight
glycaemic control has been advocated in people
with sepsis. More recent evidence, however,
suggests an increase in adverse events (e.g.,
severe hypoglycaemia) in patients managed
with very tight glycaemic control (targeting
a blood glucose below 6.1 mmol/L [110 mg/
dL]). [186] [187] The conflicting evidence
has led to variations in recommendations in
different countries and settings. Follow your
local protocol.

• An international randomised controlled

trial (RCT) of 6104 critically ill medical
and surgical patients found increased 90-
day mortality (odds ratio 1.14, 95% CI
1.02 to 1.28) with tighter glucose control,
possibly due to more frequent episodes of
hypoglycaemia.[188]
• A 2010 systematic review of 6 RCTs and
a meta-analysis investigating tight glucose
MANAGEMENT

control (4.4 to 6.1 mmol/L [80-110 mg/

dL]) versus less strict glucose control
in critically ill patients in the intensive
care unit setting found no significant
improvement in mortality with tight
glucose control, but it was associated

Initial
with significantly more hypoglycaemic
episodes compared with less strict glucose
control.[189]
• An RCT of critically ill patients in a
primarily surgical intensive care setting
found lower patient mortality with tight
glucose control, 4.4 to 6.1 mmol/L (80-110
mg/dL), compared with ‘conventional’
more liberal glucose control.[190]

consider vasopressor (should only be initiated by

experienced members of the critical care team)
Treatment recommended for SOME patients in
selected patient group
Primary options

» noradrenaline (norepinephrine): 0.4 to 0.8 mg/

hour intravenous infusion initially, adjust dose
according to response
Dose refers to noradrenaline base.

Secondary options

» noradrenaline (norepinephrine): 0.4 to 0.8 mg/

hour intravenous infusion initially, adjust dose
according to response
Dose refers to noradrenaline base.

-and-
» vasopressin: 0.01 units/minute intravenous
infusion initially, adjust dose according to
response, maximum 0.03 units/minute

» Vasopressors are used in a critical care setting

to maintain a mean arterial pressure (MAP)
#65 mmHg if the patient is unresponsive to fluid
resuscitation. [3] [43] [179]

• Failure to respond to initial fluid resuscitation

is a sign of septic shock.[1]
• Selection of appropriate vasoactive agents
should only take place under critical care
supervision and may vary according to
clinician preference and local practice
guidelines.
• Noradrenaline (norepinephrine) is the
MANAGEMENT

vasopressor of choice, mainly because it

increases MAP.[43]

• Noradrenaline is the vasopressor

recommended by the Surviving Sepsis
Campaign guideline.[43] The UK
National Institute for Health and Care

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Sepsis in adults Management

Initial
Excellence makes no recommendation
on the choice of vasopressor.[3]
• If further vasopressor therapy is
required to maintain adequate
blood pressure, add vasopressin to
noradrenaline.[43]

Practical tip

Vasopressors are usually administered via

central venous access due to concerns of
extravasation and tissue ischaemia. However,
the Surviving Sepsis Campaign supports
short-term (less than 6 hours) peripheral
administration of vasopressors in a vein
proximal to the antecubital fossa, depending on
local availability, and expertise in placement,
of central venous catheters.[43] Central venous
access should be secured as soon as possible
These patients should also have an arterial
catheter inserted as soon as possible to ensure
more accurate monitoring of arterial blood
pressure.[43]

Evidence: Choice of vasopressor

Although a systematic review of 23 randomised

trials of patients with shock found no convincing
evidence for the superiority of one vasopressor
over another, more recent meta-analyses
reported a higher mortality associated with
dopamine than with noradrenaline. [191] [192]

consider inotrope (should only be initiated by experienced

members of the critical care team)
Treatment recommended for SOME patients in
selected patient group
Primary options

» dobutamine: 2.5 to 10 micrograms/kg/minute

intravenous infusion initially, adjust dose
according to response, maximum 40 micrograms/
kg/minute

» adrenaline (epinephrine): 2-10 micrograms/

MANAGEMENT

minute intravenous infusion initially, adjust dose

according to response

» Inotropes can be considered for patients

with low cardiac output despite adequate fluid
resuscitation and vasopressor therapy. [3] [43]

Initial
• Selection of appropriate vasoactive agents
should only take place under critical care
supervision and may vary according to
clinician preference and local practice
guidelines.
• The Surviving Sepsis Campaign guideline
recommends either adding dobutamine
to noradrenaline or using adrenaline
(epinephrine) alone for people with persistent
hypoperfusion despite adequate volume status
and arterial blood pressure.[43]

• The UK National Institute for Health

and Care Excellence makes no specific
recommendations on inotrope selection in
patients with sepsis.[3]

Practical tip

Suspect low cardiac output if the clinical

examination reveals prolonged capillary refill
times, low urine output, or poor peripheral
perfusion. Confirm with cardiac output
monitoring or by sampling central venous or
pulmonary arterial blood to measure oxygen
saturations.
When using inotropes, keep the patient’s
heart rate at less than 100 beats per minute to
minimise myocardial ischaemia.[179]
consider corticosteroid (should only be initiated by
experienced members of the critical care team)
Treatment recommended for SOME patients in
selected patient group
Primary options

» hydrocortisone sodium succinate: 50 mg

intravenously every 6 hours

» The Surviving Sepsis Campaign guideline

recommends intravenous hydrocortisone for
patients with an ongoing requirement for vasopressor
therapy.[43]

• The UK National Institute for Health

and Care Excellence does not give any
recommendations on the use of corticosteroids
for managing sepsis in adults.[3]
MANAGEMENT

Evidence: Benefits and harms of

corticosteroids

In adults with sepsis, intravenous low-dose

corticosteroids may reduce organ failure at 7

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Sepsis in adults Management

Initial
days, and duration of mechanical ventilation,
vasopressor therapy, and intensive care stay.
However, whether corticosteroids reduce
short or longer-term mortality is unclear.
Possible harms include an increased risk of
neuromuscular weakness, hyperglycaemia, and
hypernatraemia with corticosteroids compared
with no corticosteroids .

The Surviving Sepsis Campaign (SSC) 2021

guideline made a weak recommendation for
using intravenous low-dose corticosteroids for
adults with septic shock and an ongoing need
for vasopressors (overall evidence assessed as
moderate using GRADE). This was a slight
change from the prior 2016 recommendation due
to the publication of three subsequent randomised
controlled trials (VANISH, ADRENAL, and
APROCHSS) and a meta-analysis including these
studies (22 RCTs, N=7297).[43] [193]

• Duration of shock was reduced in patients

who received corticosteroids compared
with placebo (mean difference -1.52
days, 95% CI -1.71 to -1.32 days, quality
of evidence as assessed by GRADE
moderate).

• Corticosteroids also reduced

organ failure at 1 week, duration
of mechanical ventilation, and
intensive care stay, and increased
vasopressor-free days.

• However, there was no difference in short-

term mortality (risk ratio [RR] 0.96, 95%
CI 0.91 to 1.02, GRADE high) with similar
results for longer-term mortality (RR 0.96,
95% CI 0.90 to 1.02, GRADE moderate).
• Corticosteroid use possibly increased
neuromuscular weakness (RR 1.21, 95%
CI 1.01 to 1.45, GRADE low).

• Corticosteroids also increased the

risk of any adverse event but there
MANAGEMENT

was considerable heterogeneity.

• No trials reported quality-of-life outcomes.

Initial
• The guideline also noted that uncertainties
remain about the optimal dose, timing of
initiation, and duration of treatment.

Other systematic reviews have considered low-

dose corticosteroids in adults and children with
sepsis ( with or without shock). They have
included slightly different studies and come to
slightly different conclusions, particularly about
mortality.

• A Cochrane review (search date July 2019)

included 61 trials (12,192 participants, 53
trials in adults only). There were no new
studies comparing low-dose corticosteroids
with placebo since ADRENAL and
APROCHSS.[194]

• 2-day, 90-day, and hospital

mortality were reduced with use of
corticosteroids (GRADE moderate).
However, there was no difference
in mortality at 6 months to 1 year
(GRADE low).
• Intensive care and hospital length of
stay were significantly reduced with
corticosteroids (GRADE high).
• Corticosteroids increased the
risk of hypernatraemia (GRADE
high) and probably increased the
risk of hyperglycaemia (GRADE
moderate). They also increased the
risk of muscle weakness (GRADE
high). They did not seem to increase
the risk of superinfection (GRADE
moderate).
• There was no significant difference
in gastroduodenal bleeding, stroke,
cardiac events, or neuropsychiatric
events.

• A rapid clinical practice guideline was

published in 2018 triggered by publication
of ADRENAL and APROCHSS.[195]
MANAGEMENT

The panel made a weak recommendation

for the use of corticosteroids in adults
and children with sepsis ( with and
without shock). This guideline was also
underpinned by a systematic review (42
RCTs, N=10,194).[196]

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Sepsis in adults Management

Initial
• The guideline panel concluded
that it was uncertain whether
corticosteroids reduced short-
term mortality at 28 to 31 days
(1.8% absolute risk reduction,
95% CI, 4.1% reduction to 0.8%
increase, GRADE low), although
they did seem to reduce longer-
term mortality at 60 days to 1 year
(2.2% absolute risk reduction; 95%
CI, 4.1% reduction to 0%, GRADE
moderate).
• Other results were similar to those
of the SSC 2021 guideline and the
Cochrane systematic review.

BMJ Rapid Recommendations:

intravenous corticosteroids plus
usual care versus usual care only
Lamontagne F, et al.
BMJ 2018;362:k3284

in the community: sepsis highly suspected

and bacterial infection confirmed or highly
suspected

1st refer for emergency medical care in hospital

» Use your clinical judgement supported by

physiological assessment. [51] Use National Early
MANAGEMENT

Warning Score 2 (NEWS2) scoring (encouraged

by NHS England) to refer urgently to hospital
any acutely unwell patient with suspected or
confirmed infection according to the following
triggers: [41] [NHS England: Sepsis]

• Score 7 or more

Initial
• Make an emergency referral to
hospital (via blue-light ambulance) for
immediate critical care input.

• Score 5-6 total, or 3 or more on any single

parameter

• Make an immediate referral to an acute

care setting and ensure the patient is
reviewed by an acute clinician within
an hour.

» [Track and trigger map developed by the West of

England Academic Health Science Network National
Early Warning Score project team]

» Alternatively, refer for emergency medical care

in hospital (usually by blue-light ambulance in the
UK) any acutely unwell patient with suspected or
confirmed infection who:[3]

• Meets one or more of the UK National

Institute for Health and Care Excellence
(NICE) high-risk criteria (red flags)

• Objective evidence of new altered

mental state (e.g., new deterioration
in Glasgow Coma Scale score/AVPU
['Alert, responds to Voice, responds to
Pain, Unresponsive'] scale)
• Respiratory rate: #25 breaths per
minute OR new need for oxygen (40%
or more fraction of inspired oxygen
[FiO 2 ]) to maintain saturation >92%
(or >88% in known chronic obstructive
pulmonary disease)
• Heart rate: >130 beats per minute
• Systolic blood pressure #90 mmHg or
more than 40 mmHg below normal
• Not passed urine in previous 18 hours,
or for catheterised patients passed <0.5
mL/kg of urine per hour
• Mottled or ashen appearance
• Cyanosis of skin, lips, or tongue
MANAGEMENT

• Non-blanching petechial or purpuric

rash of skin

• Is at risk of neutropenic sepsis and presents

with symptoms and signs of infection

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Sepsis in adults Management

Initial
• See Febrile neutropenia .

» Carefully consider whether emergency medical

care is required or whether the patient can be safely
managed in the community with safety netting
advice.[3] See box below on safety netting advice.

Practical tip

If you need to refer a patient for emergency

medical care in hospital, it is important to
inform the hospital clinical team that the
patient is on the way. This will enable the
hospital to initiate appropriate treatment as
soon as the patient arrives.

» In a patient with signs and symptoms of

an infection and evidence of physiological
deterioration, presume sepsis until it can safely
be excluded. Take a cautious approach when
deciding whether it is safe to treat the patient’s
infection in the community.Using your clinical
judgement in making a decision is paramount. In
particular, carefully consider the need for hospital
admission if:[51] [73] [202]

• The patient has one or more NICE high-risk

criteria for sepsis
• The patient appears seriously unwell to you,
based on experience and clinical judgement
• The patient lives alone with poor access to
communication and/or transport
• A carer or parent expresses serious concern
about the patient (e.g., “they’re just not
right”).

» For details of the NICE risk criteria, see Diagnosis

recommendations .

» Treat the patient’s infection in line with local

protocols and accepted practice. Antimicrobial
MANAGEMENT

prescribing guidelines from Public Health England

and NICE are available for general practitioners in
the UK.[200] [201]

Initial
Practical tip

If you decide that the patient is safe to treat

in the community, written and verbal safety
netting is vital.[51] Ensure the information
is clear and specific rather than generalised
advice; for example, do not say “come back
if you get worse” – instead, specify key
symptoms to watch out for (such as a non-
blanching rash, change in behaviour or mental
state, mottled skin, or ashen appearance) and
explain where and how to access immediate
medical care both in and out of hours.[51]
If you give the patient any safety netting
advice, ensure you document this clearly in
their medical notes, along with the patient’s
observations and whether you have offered
them any antibiotics. The 2015 national
confidential enquiry into sepsis deaths found
recorded evidence that safety netting advice
had been provided in fewer than one quarter of
cases.[61]
The UK Sepsis Trust advises the following
acronym:[47]
• Slurred speech or confusion
• Extreme shivering or muscle pain
• Passing no urine (in a day)
• Severe breathlessness
• ‘ I feel I might die’
• Skin mottled, ashen, blue, or very pale.

Advise the patient to call the emergency

services if any of these symptoms develop.If
the patient has a change in condition or
deterioration that is not covered by the
acronym above, advise them to arrange another
appointment to see their general practitioner or
to call their out of hours service provider.
It is also good practice to consider arranging
a next-day review appointment or telephone
call; if you will be unable to review the patient
yourself, provide a written handover for your
colleagues.

» Ambulance crews should evaluate the risk of

severe illness or death from sepsis using NEWS2
and consider a time-critical transfer and pre-
alerting the hospital for patients with suspected or
confirmed infection who either have consecutive
NEWS2 scores of 5 or above or show cause for
MANAGEMENT

significant clinical concern.[3] Paramedics who

are thinking about giving antibiotics should follow
local guidelines or seek advice from more senior
colleagues, if needed.[3]

» For patients at high risk of severe illness or death

from sepsis who are in an acute mental health setting,

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Sepsis in adults Management

Initial
follow local emergency protocols on treatment and
ambulance transfer.[3]
consider oxygen
Treatment recommended for SOME patients in
selected patient group
» If you have decided to refer the patient for
emergency medical care and have called for an
emergency ambulance, you should start oxygen
therapy while awaiting the ambulance if resources
are available to do so.[50] Pulse oximetry should be
available in all locations where emergency oxygen is
used.[50]

» Monitor controlled oxygen therapy. An upper

SpO 2 limit of 96% is reasonable when administering
supplemental oxygen to most patients with acute
illness who are not at risk of hypercapnia.

• Evidence suggests that liberal use of

supplemental oxygen (target SpO 2 >96%)
in acutely ill adults is associated with higher
mortality than more conservative oxygen
therapy.[138]
• A lower target SpO 2 of 88% to 92%
is appropriate if the patient is at risk of
hypercapnic respiratory failure.[50]

Evidence: Target oxygen saturation in acutely

ill adults

Too much supplemental oxygen increases

mortality.

Evidence from a large systematic review and

meta-analysis supports conservative/controlled
oxygen therapy versus liberal oxygen therapy
in acutely ill adults who are not at risk of
hypercapnia.

• Guidelines differ in their recommendations

on target oxygen saturation in acutely
unwell adults who are receiving
supplemental oxygen.

• The 2017 British Thoracic Society

(BTS) guideline recommends
a target SpO 2 range of 94% to
98% for patients not at risk of
MANAGEMENT

hypercapnia, whereas the 2022

Thoracic Society of Australia and
New Zealand (TSANZ) guideline
recommends 92% to 96%.[50]
[164]

Initial
• The 2022 Global Initiative For
Asthma (GINA) guidelines
recommend a target SpO 2 range of
93% to 96% in the context of acute
asthma exacerbations.[165]

• One systematic review including a meta-

analysis of data from 25 randomised
controlled trials, published in 2018, found
that in adults with acute illness, liberal
oxygen therapy (broadly equivalent to
a target saturation >96%) is associated
with higher mortality than conservative
oxygen therapy (broadly equivalent to a
target saturation #96%).[138] In-hospital
mortality was 11 per 1000 higher for
the liberal oxygen therapy versus the
conservative therapy group (95% CI, 2-22
per 1000 more). Mortality at 30 days was
also higher in the group who had received
liberal oxygen (relative risk 1.14, 95% CI
1.01 to 1.29). The trials included adults
with sepsis, critical illness, stroke, trauma,
myocardial infarction, or cardiac arrest,
and patients who had emergency surgery.
Studies that were limited to people with
chronic respiratory illness or psychiatric
illness, or patients on extracorporeal life
support, receiving hyperbaric oxygen
therapy, or having elective surgery, were
all excluded from the review.
• An upper SpO 2 limit of 96% is
therefore reasonable when administering
supplemental oxygen to patients with
acute illness who are not at risk of
hypercapnia. However, a higher target may
be appropriate for some specific conditions
(e.g., pneumothorax, carbon monoxide
poisoning, cluster headache, or sickle cell
crisis).[166]
• In 2019 the BTS reviewed its guidance
in response to this systematic review and
meta-analysis and decided an interim
update was not required.[167]

• The committee noted that the

systematic review supported the use
of controlled oxygen therapy to a
MANAGEMENT

target.
• While the systematic review
showed an association between
higher oxygen saturations
and higher mortality, the BTS
committee felt the review was not

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Sepsis in adults Management

Initial
definitive on what the optimal target
range should be. The suggested
range of 94% to 96% in the review
was based on the lower 95%
confidence interval and the median
baseline SpO 2 from the liberal
oxygen groups, along with the
earlier 2015 TSANZ guideline
recommendation.

• Subsequently, experience during the

COVID-19 pandemic has also made
clinicians more aware of the feasibility of
permissive hypoxaemia.[168] The BTS
guidance is due for a review in 2022.
• Management of oxygen therapy in patients
in intensive care is specialised and
informed by further evidence (not covered
in this summary) that is more specific to
this setting.[169] [170][171]

consider broad-spectrum antibiotics

Treatment recommended for SOME patients in
selected patient group
» Ensure you have a mechanism in place to
administer antibiotics to any high-risk patient
(either at your practice or via the ambulance service)
if the transfer time to hospital is likely to be more
than 1 hour.[3] Paramedics who are thinking about
giving antibiotics should follow local guidelines
or seek advice from more senior colleagues, if
needed.[3]

» Give immediate, targeted antibiotics in people

with sepsis thought to arise from a central nervous
system source.[3]

• Give benzylpenicillin before referring to

hospital.[3]
MANAGEMENT

Acute
in hospital: sepsis highly suspected and
clear source of bacterial infection identified

1st targeted antibiotics according to local protocols

» Once a definitive source has been identified,

if appropriate to continue treating the patient
with antibiotics, choose a treatment regimen in
line with local or national policy (which will take
into account specialist knowledge of resistance
patterns). [43] [137] Also consider discussing
with microbiology/infectious disease colleagues to
determine the most appropriate choice.

» Assess the need to de-escalate antimicrobial

therapy daily. [43]

• Studies have shown that daily prompting

about antimicrobial de-escalation is effective
and may be associated with improved
outcomes.[197] [198]

» Use the shortest effective course of antibiotics.

[199]

• Unnecessarily prolonged antibiotic treatment

is associated with resistance.

More info: Antimicrobial resistance

NHS England recommends following a 'start

smart then focus’ approach for antibiotic use
in people with sepsis. [41] This is derived from
Public Health England guidance, which outlines
an evidence-based approach to improving
antimicrobial prescribing and stewardship
in hospital settings. [136] The prevalence
of antimicrobial resistance (AMR) has risen
alarmingly over the last 50 years and no new
classes of antibiotics have been developed in
decades. By 2050 it is estimated that AMR
will kill 10 million people per year, more than
cancer and diabetes combined. [142] The
relationship between antibiotic exposure and
antibiotic resistance is unambiguous not only
at the population level but also in individual
patients. [143] [144]

Start smart – in the context of sepsis:[136]

MANAGEMENT

• Do not start antimicrobial therapy unless

there is clear evidence of infection
• Take a thorough drug allergy history
• Initiate prompt effective antibiotic
treatment within 1 hour of diagnosis (or

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Sepsis in adults Management

Acute
as soon as possible) in patients with sepsis
who are critically ill (e.g., septic shock,
sepsis associated with rapid deterioration,
or NEWS2 score of 7 or more calculated
on initial assessment in the accident
and emergency department or on ward
deterioration) or with life-threatening
infections. Avoid inappropriate use of
broad-spectrum antibiotics[3] [45]
• Comply with local antimicrobial
prescribing guidance
• Document clinical indication (and disease
severity if appropriate), drug name, dose,
and route on drug chart and in clinical
notes
• Include review/stop date or duration
• Obtain cultures prior to starting therapy
where possible (but do not delay therapy).

Then focus – in the context of sepsis:[136]

• Review the clinical diagnosis and the

1. Stop antibiotics if there is no

evidence of infection
2. Switch antibiotics from intravenous
to oral
3. Change antibiotics – ideally to a
narrower spectrum, or broader if
required
4. Continue and document next review
date or stop date

• It is essential that the review and

subsequent decision is clearly documented
in the clinical notes and on the drug chart
where possible (e.g., ‘stop antibiotic’).
MANAGEMENT

*In clinical practice, daily prompting about de-

escalation is encouraged.

The UK’s Academy of Medical Royal Colleges

recommends stratifying patients with suspected

Acute
sepsis according to severity of illness at
presentation, allowing a 3-hour window to
investigate patients with less severe illness
(e.g., NEWS2 score of 5 or 6). This should
improve accuracy of treatment and help to reduce
antimicrobial resistance.[45]

» Consult local microbiology guidance for other

specific recommendations on de-escalation.

• Most protocols will recommend switching

from intravenous to oral antibiotics as soon
as possible.

» The Surviving Sepsis Campaign (SSC)

recommends shorter over longer courses of
antibiotics for patients with an initial diagnosis of
sepsis or septic shock and adequate source control.
[43] The optimal duration of antibiotic treatment
in patients with sepsis remains contentious, with
concerns regarding not only under-treatment but
also the potential encouragement of antibiotic
resistance. Consider seeking advice from
microbiology/infectious disease colleagues.

» 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 SSC suggests using procalcitonin
alongside clinical evaluation to decide when to
discontinue antimicrobials.[43]

Respiratory
Ensure treatment regimens cover common
respiratory pathogens and atypical organisms such
as Legionella pneumophila .

• The respiratory tract is the most common site

of infection in people with sepsis.[20] [61]
• See Overview of pneumonia .

Abdominal
MANAGEMENT

Ensure gram-positive and gram-negative

organisms including anaerobes are covered.[175]

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Sepsis in adults Management

Acute
Arrange urgent surgical drainage or percutaneous
drainage (where appropriate) for peritonitis or intra-
peritoneal abscesses.[176]

Urinary tract
Ensure gram-negative coliforms and Pseudomonas
are covered. Ensuring patency of the urinary tract
is vital.

• In people older than 65 years of age,

genitourinary tract infections are the most
common cause of sepsis.[21] [22]

Soft tissue and joint

Includes septic arthritis, wound infections, cellulitis,
and acute super-infections arising from chronic
ulceration. Most infections are polymicrobial. Ensure
gram-positive and gram-negative organisms
including anaerobes are covered.

• Beware necrotising fasciitis, which requires

immediate surgical intervention (as does
septic arthritis).

Practical tip

Necrotising fasciitis is notoriously difficult

to diagnose. The initial symptoms are non-
specific and the clinical course is often slower
than might be expected. Typically, the first
sign is pain disproportionate to the clinical
findings, followed or accompanied by
fever.[74]
See Necrotising fasciitis .

Central nervous system

Relatively uncommon but potentially devastating
source of sepsis. Beware meningococcal sepsis,
which can be extremely rapidly fatal; if survived,
can lead to greater morbidity than other forms of
sepsis.

Give immediate, targeted antibiotics in people

with sepsis thought to arise from a central nervous
system source.[3]

• Immediately give a third-generation

MANAGEMENT

cephalosporin, such as ceftriaxone, for

suspected meningitis or meningococcal
sepsis.[3]

plus reassess and monitor

Acute
Treatment recommended for ALL patients in selected
patient group
» Ensure frequent and ongoing monitoring. [3]

• Standard monitoring of vital signs, pulse

oximetry, level of consciousness, and urinary
output is important for any patient with
suspected sepsis.
• The UK National Institute for Health and Care
Excellence (NICE) recommends continuous or
half-hourly monitoring (depending on setting)
for any patient considered to be at high risk of
deterioration.[3]
• For more information, see Risk
stratificationunder Diagnosis
recommendations .

» Use a track-and-trigger scoring system such

as National Early Warning Score 2 (NEWS2)
to identify any signs of deterioration. [3] Your
monitoring should include:

• Vital signs: heart rate, blood pressure, oxygen

saturations, respiratory rate, and temperature

• Measure blood pressure via an arterial

line if the patient does not respond to
initial treatment or needs vasoactive
drugs. It provides precise, continuous
monitoring, and access for arterial
blood sampling

• Hourly urine output[3] [47]

• Lactate

• The lactate level should decrease if the

patient is clinically improving
• Frequency of repeat lactate
measurement depends on the cause of
sepsis and treatment given.

» Measure serum lactate, on a blood gas, to

monitor response to treatment. [43] [47]
MANAGEMENT

• Lactate is a marker of stressand 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.[75] [76]

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Sepsis in adults Management

Acute
• 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%.

» Do not be falsely reassured by a normal lactate

(<2 mmol/L [<18 mg/dL]).

• This does not rule out the patient being acutely

Practical tip

Lactate is typically measured using a blood gas

» In the UK, use physiological track-and-trigger

MANAGEMENT

systems to monitor all adult patients in acute hospital

settings.[3]

» Consider using a validated scale such as the

Glasgow Coma Scale or AVPU ('Alert, responds
to Voice, responds to Pain, Unresponsive') scale

Acute
to monitor the mental state of a patient with
suspected sepsis. [3]

Practical tip

AVPU should raise concerns if the assessment

shows the patient is anything other than 'alert'.

» Any patient with sepsis may be at significant

• Bear in mind that some patients (e.g.,

» Consult local protocols for specific escalation

routes but in general:

• Ensure urgent review by a senior clinician

• Within 30 minutes of initial severity

• Inform the responsible consultantif a patient

is at high risk of severe illness or death from
sepsis (e.g., NEWS2 score of 7 or more) does
not respond within 1 hour of any intervention
(antibiotics/fluid resuscitation/oxygen).[3]

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Sepsis in adults Management

Acute
Ensure the senior clinical decision-maker
attends in person.

• Signs that the person is not responding

to resuscitation include lack of
improvement or worsening:[3]

• Tachycardia
• Level of consciousness
• Blood pressure
• Respiratory rate
• Blood lactate
• Urine output
• Peripheral perfusion
• Blood gases.

• Consider alerting critical care immediately

if the patient is acutely unwell and:

• Is likely to require central venous

access and the initiation of inotropes or
vasopressors[3]

• This includes any patient

with evidence of circulatory
dysfunction or shock, or
those who do not respond to
initial therapy (as outlined
above) including initial fluid
resuscitation within 1 hour.

• Has any feature of septic shock

• See Shock

• Has neutropenia

• See Febrile neutropenia

• Is immunodeficient
MANAGEMENT

Acute
Practical tip

Ensure a clear escalation plan has been

plus urgent source control

Treatment recommended for ALL patients in selected
patient group
» Once a site of infection has been identified, early
and adequate source control is critical. Consider
the need for urgent source control, as soon as the
patient is stable, particularly for: [43]

• Gastrointestinal sources (such as visceral

» Give immediate, targeted antibiotics in people

with sepsis thought to arise from a central
nervous system source (e.g., suspected meningitis or
meningococcal sepsis).[3]

• Immediately give a third-generation

cephalosporin such as ceftriaxone.
• In community settings, pre-hospital
administration of benzylpenicillin is
recommended.
MANAGEMENT

• Follow local policy and consider discussing

with microbiology/infectious disease
colleagues to determine the most
appropriate choice; use a ‘start smart then
focus’ approach. [41] [136]

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Sepsis in adults Management

Acute
Practical tip

If intravenous access is not feasible or is likely

• Give this intravenous fluid bolus, if indicated,

• Reassess the patient’s haemodynamic status

after the first bolus to consider whether a
second is required.[3] If there is no response
to either the first or second bolus, ensure the
senior clinical decision-maker attends in
person.[3]

» Intravenous fluid resuscitation may be

lifesaving in patients with hypotension.This is
because in sepsis there is vasodilation and capillary
leakage, which means that patients can rapidly
become intravascularly deplete.[3]

• In patients with sepsis-induced hypoperfusion

• If the patient’s initial lactate level is

raised, the guideline recommends serial
lactate measurements to guide the need
MANAGEMENT

for further intravenous fluids (with the

goal of normalising lactate levels).[43]

Acute
Practical tip

The delivery of appropriate rapid fluid

Practical tip

Monitor patients closely for signs of fluid

overload such as pulmonary or systemic
oedema before and after each additional fluid
bolus, as they may require large volumes of
fluid to support their circulating volume.[43]
[152] [153]

• Check local protocols for specific

recommendations on fluid choice. There is
debate, based on conflicting evidence, on
whether there is a benefit in using normal
saline or balanced crystalloid in critically ill
patients.

Practical tip

Be aware that large volumes of normal saline

as the sole fluid for resuscitation may lead to
hyperchloraemic acidosis.
Also note that use of lactate-containing fluid
in a patient with impaired liver metabolism
may lead to a spuriously elevated lactate level,
so results need to be interpreted with other
markers of volume status.

Evidence: Choice of fluid

Evidence from two large randomised controlled

possible small benefit of balanced solutions

compared with normal saline.

There has been extensive debate over the

choice between normal saline (an unbalanced
crystalloid) versus a balanced crystalloid

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Sepsis in adults Management

Acute
(such as Hartmann’s solution [also known as
Ringer’s lactate] or Plasma-Lyte®). Clinical
practice varies widely, so you should check
local protocols.

• In 2021-2022 two large double-blind RCTs

• In the PLUS study, 45.2% of

were excluded from PLUS as the

authors felt these patients should
be receiving saline or a solution of
similar tonicity.

Acute
• A meta-analysis of 13 RCTs (including
PLUS and BaSICS) confirmed no overall
difference, although the authors did
highlight a non-significant trend towards
a benefit of balanced solutions for risk of
death.[156]
• A subsequent individual patient data
meta-analysis included 6 RCTs of which
only PLUS and BaSICS were assessed
as being at low risk of bias. There was
no statistically significant difference in
in-hospital mortality (OR 0.96, 95% CI
0.91 to 1.02). However, the authors argued
that using a Bayesian analysis there was
a high probability that balanced solutions
reduced in-hospital mortality, although
they acknowledged that the absolute risk
reduction was small.[157]

• A pre-specified sub-group analysis

of patients with traumatic brain
injury (N=1961) found that
balanced solutions increased
the risk of in-hospital mortality
compared with normal saline (OR
1.42, 95% CI 1.10 to 1.82).

• Previous evidence has been mixed.

• One 2015 double-blind, cluster

crystalloid group versus the normal

saline group (10.3% vs. 11.1%;
odds ratio [OR] 0.90, 95% CI 0.80
to 1.01) and a major adverse kidney
event rate of 14.3% versus 15.4%,

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Sepsis in adults Management

Acute
respectively (OR 0.91, 95% CI 0.84
to 0.99).[159]

• One 2019 Cochrane review included 21

RCTs (N=20,213) assessing balanced
crystalloids versus normal saline for
resuscitation or maintenance in a critical
care setting.[160]

• The 3 largest RCTs in the Cochrane

The Surviving Sepsis Campaign 2021 guideline

• Subgroup analysis of patients with

Acute
Practical tip

To guide the need for further intravenous

Practical tip

Use the passive leg-raising test to predict

fluid-responsiveness if adequate monitoring is
available.[67] [163]
• This is a useful indicator of fluid-
responsiveness, which should be assessed
using devices that can continuously
monitor cardiac output in real time (e.g.,
Pulse index Continuous Cardiac Output
(PiCCO) monitor or oesophageal Doppler),
usually in an intensive care unit rather than
general ward setting.
• Sit the patient upright at 45° and tilt the
entire bed through 45°.
• Patients with a positive test have a >10%
increase in cardiac output or stroke volume,
indicating more fluids may be required.
• The passive leg-raise response may be
misleading in conscious patients who are
uncomfortable or in pain when lying flat.

consider oxygen
Treatment recommended for SOME patients in
selected patient group
» Monitor controlled oxygen therapy. An upper
MANAGEMENT

SpO 2 limit of 96% is reasonable when administering

supplemental oxygen to most patients with acute
illness who are not at risk of hypercapnia.

• Evidence suggests that liberal use of

supplemental oxygen (target SpO 2 >96%)
in acutely ill adults is associated with higher

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Sepsis in adults Management

Acute
mortality than more conservative oxygen
therapy.[138]
• A lower target SpO 2 of 88% to 92%
is appropriate if the patient is at risk of
hypercapnic respiratory failure.[50]

Evidence: Target oxygen saturation in acutely

ill adults

Too much supplemental oxygen increases

mortality.

Evidence from a large systematic review and

meta-analysis supports conservative/controlled
oxygen therapy versus liberal oxygen therapy
in acutely ill adults who are not at risk of
hypercapnia.

• Guidelines differ in their recommendations

on target oxygen saturation in acutely
unwell adults who are receiving
supplemental oxygen.

• The 2017 British Thoracic Society

• A systematic review including a meta-

conservative therapy group (95% CI, 2-22

per 1000 more). Mortality at 30 days was
also higher in the group who had received
liberal oxygen (relative risk 1.14, 95% CI
1.01 to 1.29). The trials included adults
with sepsis, critical illness, stroke, trauma,

Acute
myocardial infarction, or cardiac arrest,
and patients who had emergency surgery.
Studies that were limited to people with
chronic respiratory illness or psychiatric
illness, or patients on extracorporeal life
support, receiving hyperbaric oxygen
therapy, or having elective surgery were all
excluded from the review.
• An upper SpO 2 limit of 96% is
therefore reasonable when administering
supplemental oxygen to patients with
acute illness who are not at risk of
hypercapnia. However, a higher target may
be appropriate for some specific conditions
(e.g., pneumothorax, carbon monoxide
poisoning, cluster headache, or sickle cell
crisis).[166]
• In 2019 the BTS reviewed its guidance
in response to this systematic review and
meta-analysis and decided an interim
update was not required.[167]

• The committee noted that the

• Subsequently, experience during the

in this summary) that is more specific to

this setting.[169] [170][171]

» There is no specific evidence to show that giving

oxygen improves clinical outcomes in sepsis.
However, respiratory failure will lead to tissue

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Sepsis in adults Management

Acute
hypoxia and anaerobic respiration. This is likely
to lead to acidosis and consequently a poorer
outcome.[172]
consider standard intensive care unit supportive care
Treatment recommended for SOME patients in
selected patient group
» Any patient with sepsis may be at significant
risk of severe illness or death so it is vital to
consider escalation of care to senior colleagues
and/or healthcare facilities where increased and
more advanced monitoring can be given (e.g.,
high-dependency unit/intensive care unit). [7]
[173] [174]

• Bear in mind that some patients (e.g.,

» Consult local protocols for specific escalation

routes but in general:

• Ensure urgent review by a senior clinician

• Within 30 minutes of initial severity

assessment for any patient with an
aggregate NEWS2 score of 7 or
more; or with a NEWS2 score of
5 or 6 if there is clinical or carer
concern, continuing deterioration
or lack of improvement, surgically
remediable sepsis, neutropenia, or
blood gas/laboratory evidence of organ
dysfunction (including elevated serum
lactate - see below)
• Within 1 hour of initial severity
assessment for any patient with an
aggregate NEWS2 score of 5 or 6
MANAGEMENT

• Inform the responsible consultantif a patient

is at high risk of severe illness or death from
sepsis (e.g., NEWS2 score of 7 or more) does
not respond within 1 hour of any intervention
(antibiotics/fluid resuscitation/oxygen).[3]

Acute
Ensure the senior clinical decision-maker
attends in person.

• Signs that the person is not responding

to resuscitation include lack of
improvement or worsening:[3]

• Tachycardia
• Level of consciousness
• Blood pressure
• Respiratory rate
• Blood lactate
• Urine output
• Peripheral perfusion
• Blood gases.

• Consider alerting critical care immediately

if the patient is acutely unwell and:

• Is likely to require central venous

access and the initiation of inotropes or
vasopressors[3]

• This includes any patient

with evidence of circulatory
dysfunction or shock, or those
who do not respond to initial
therapy (as outlined above)
including fluid resuscitation
within 1 hour.

• Has any feature of septic shock

• See Shock

• Has neutropenia

• See Febrile neutropenia

• Is immunodeficient.
MANAGEMENT

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Sepsis in adults Management

Acute
Practical tip

Ensure a clear escalation plan has been

discussed and agreed with the clinical team;
include specific points of contact for nursing
staff if you are leaving a patient for later
review.
Involve a senior colleague and/or consider
transferring to critical care sooner rather
than later if the patient is not improving,
or deemed high-risk.Examples include if the
patient:
• Is not responding to fluids
• Needs inotropic support
• Has a low Glasgow Coma Scale score
• Needs ventilatory support.

» For any patient with suspected sepsis, consider

the need for referral to a high-dependency unit for
management by the critical care team. [177] [178]

» The following interventions should only be

initiated by experienced members of the critical
care team: [179]

• Glycaemic control
• Vasoactive drugs (vasopressors/inotropes)
• Corticosteroids.

» Additional intensive care measures that will be

considered include:[43] [180] [181]

• Stress ulcer prophylaxis (in people at risk of

gastrointestinal bleeding)

• With an H2 antagonist or proton-pump

inhibitor

• Deep venous thrombosis prophylaxis

• With heparin and compression

stockings

• Enteral or parenteral nutrition

• Administration of human albumin solution 4%
to 5% in patients with sepsis and shock who
MANAGEMENT

have not responded to substantial volumes of

crystalloids [3] [43]
• Transfusion of packed cells

• Consult local protocols for

recommended threshold

Acute
• The Surviving Sepsis Campaign
recommends using a threshold of 70 g/
L (7 g/dL).[43]

Evidence: Threshold for transfusion of packed

cells

In the general critical care population there is

The 2021 Surviving Sepsis Campaign guideline

recommends a restrictive transfusion strategy
for adults with sepsis or septic shock.[43] The
guideline identifies the following evidence.

• One multicentre parallel group randomised

controlled trial (RCT) in people >16
years of age with septic shock (N=998)
compared blood transfusion at a lower
haemoglobin threshold with a higher
threshold.[182]

• There was no difference in 90-day

• A second multicentre RCT (838 critically

ill adults) compared a restrictive strategy
of red-cell transfusion with a liberal
strategy.[183]

• Overall, 30-day mortality was

similar in the two groups (18.7%
vs. 23.3%, P = 0.11). Results were
MANAGEMENT

similar in the subgroup of patients

with sepsis or septic shock (N=218)
(22.8% vs. 29.7%, P = 0.36).
• The 30-day mortality rates were
significantly lower in patients who

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Sepsis in adults Management

Acute
were less acutely ill and in patients
younger than 55 years old with
the restrictive transfusion strategy.
However, this was not the case in
those with clinically significant
cardiac disease.
• The mortality rate during
hospitalisation was significantly
lower in the restrictive-strategy
group (22.3% vs. 28.1%, P = 0.05).

• A single-centre RCT in critically ill adult

cancer patients with septic shock (N=300)
also compared a liberal with a restrictive
strategy.[184]

• 28-day mortality was less in

the liberal group, although this
difference was not statistically
significant (45% vs. 56%, HR 0.74,
95% CI 0.53 to 1.04). However
90-day mortality was significantly
reduced in the liberal group (hazard
ratio [HR] 0.72, 95% CI 0.53 to
0.97).
• There was no difference in duration
of intensive care or hospital stay
between groups.

• Meta-analysis of the three studies found

no difference in 28-day mortality (odds
ratio [OR] 0.99, 95% CI 0.67 to 1.46,
quality of evidence as assessed by GRADE
moderate).[43]

The guideline concluded that the evidence did

not favour one strategy over the other. The
authors therefore based their recommendation on
resource use, cost-effectiveness, and health equity
concerns.

» There may be a case to consider giving transfusions

at a higher haemoglobin level in some patients
MANAGEMENT

(e.g., people with myocardial ischaemia, severe

hypoxaemia, or acute haemorrhage).[43]

» In the initial resuscitative phase, transfusion

to achieve a higher haematocrit of #30% may be
appropriate.[177]

Acute
» In patients requiring prolonged ventilatory support,
give lung-protective ventilation using minimal
peak inspiratory pressures (<30 cm H 2 O) and
permissive hypercapnia to specifically limit
pulmonary compromise.[185]

• Titrate fraction of inspired oxygen (FiO 2 )

to lowest effective levels to prevent oxygen
toxicity and maintain central venous oxygen
tension.

Glycaemic control
Although patients with sepsis are often
hyperglycaemic, the optimal glucose target is
unknown.

The Surviving Sepsis Campaign guideline

recommends targeting a blood glucose level <10.0
mmol/L(<180 mg/dL).[43]

• NICE makes no recommendations on

glycaemic control in sepsis.[3]

Evidence: Glycaemic control

Recent years have seen a shift in opinion

• An international randomised controlled

a meta-analysis investigating tight glucose

control (4.4 to 6.1 mmol/L [80-110 mg/
dL]) versus less strict glucose control
in critically ill patients in the intensive
care unit setting found no significant
improvement in mortality with tight

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Sepsis in adults Management

Acute
glucose control, but it was associated
with significantly more hypoglycaemic
episodes compared with less strict glucose
control.[189]
• An RCT of critically ill patients in a
primarily surgical intensive care setting
found lower patient mortality with tight
glucose control, 4.4 to 6.1 mmol/L (80-110
mg/dL), compared with ‘conventional’
more liberal glucose control.[190]

consider vasopressor (should only be initiated by

experienced members of the critical care team)
Treatment recommended for SOME patients in
selected patient group
Primary options

» noradrenaline (norepinephrine): 0.4 to 0.8 mg/

hour intravenous infusion initially, adjust dose
according to response
Dose refers to noradrenaline base.

Secondary options

» noradrenaline (norepinephrine): 0.4 to 0.8 mg/

hour intravenous infusion initially, adjust dose
according to response
Dose refers to noradrenaline base.

-and-
» vasopressin: 0.01 units/minute intravenous
infusion initially, adjust dose according to
response, maximum 0.03 units/minute

» Vasopressors are used in a critical care setting

to maintain a mean arterial pressure (MAP)
#65 mmHg if the patient is unresponsive to fluid
resuscitation. [3] [43] [179]

• Failure to respond to initial fluid resuscitation

• Noradrenaline (norepinephrine) is the

vasopressor of choice, mainly because it
increases MAP.[43]

• Noradrenaline is the vasopressor

recommended by the Surviving Sepsis
Campaign guideline.[43] The UK

Acute
National Institute for Health and Care
Excellence makes no recommendation
on the choice of vasopressor.[3]
• If further vasopressor therapy is
required to maintain adequate
blood pressure, add vasopressin to
noradrenaline.

Practical tip

Vasopressors are usually administered via

central venous access due to concerns of
extravasation and tissue ischaemia. However,
the Surviving Sepsis Campaign supports
short-term (less than 6 hours) peripheral
administration of vasopressors in a vein
proximal to the antecubital fossa, depending on
local availability, and expertise in placement,
of central venous catheters.[43] Central venous
access should be secured as soon as possible.
These patients should also have an arterial
catheter inserted as soon as possible to ensure
more accurate monitoring of arterial blood
pressure.[43]

Evidence: Choice of vasopressor

Although a systematic review of 23 randomised

consider inotrope (should only be initiated by experienced

members of the critical care team)
Treatment recommended for SOME patients in
selected patient group
Primary options

» dobutamine: 2.5 to 10 micrograms/kg/minute

intravenous infusion initially, adjust dose
according to response, maximum 40 micrograms/
kg/minute

OR
MANAGEMENT

» adrenaline (epinephrine): 2-10 micrograms/

minute intravenous infusion initially, adjust dose
according to response

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Sepsis in adults Management

Acute
» Inotropes can be considered for patients
with low cardiac output despite adequate fluid
resuscitation and vasopressor therapy. [3] [43]

• Selection of appropriate vasoactive agents

should only take place under critical care
supervision and may vary according to
clinician preference and local practice
guidelines.
• The Surviving Sepsis Campaign guideline
recommends either adding dobutamine
to noradrenaline or using adrenaline
(epinephrine) alone for people with persistent
hypoperfusion despite adequate volume status
and arterial blood pressure.[43]
• The UK National Institute for Health
and Care Excellence makes no specific
recommendations on inotrope selection in
patients with sepsis.[3]

Practical tip

Suspect low cardiac output if the clinical

» hydrocortisone sodium succinate: 50 mg

intravenously every 6 hours

» The Surviving Sepsis Campaign guideline

recommends intravenous hydrocortisone for
patients with an ongoing requirement for vasopressor
therapy.[43]

• The UK National Institute for Health

and Care Excellence does not give any
MANAGEMENT

recommendations on the use of corticosteroids

for managing sepsis in adults.[3]

Evidence: Benefits and harms of

corticosteroids

Acute
In adults with sepsis, intravenous low-dose
corticosteroids may reduce organ failure at 7
days, and duration of mechanical ventilation,
vasopressor therapy, and intensive care stay.
However, whether corticosteroids reduce
short or longer-term mortality is unclear.
Possible harms include an increased risk of
neuromuscular weakness, hyperglycaemia, and
hypernatraemia with corticosteroids compared
with no corticosteroids .

The Surviving Sepsis Campaign (SSC) 2021

• Duration of shock was reduced in patients

who received corticosteroids compared
with placebo (mean difference -1.52
days, 95% CI -1.71 to -1.32 days, quality
of evidence as assessed by GRADE
moderate).

• Corticosteroids also reduced

organ failure at 1 week, duration
of mechanical ventilation, and
intensive care stay; and increased
vasopressor-free days.

• However, there was no difference in short-

• Corticosteroids also increased the

MANAGEMENT

risk of any adverse event but there

was considerable heterogeneity.

• No trials reported quality-of-life outcomes.

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Sepsis in adults Management

Acute
• The guideline also noted that uncertainties
remain about the optimal dose, timing of
initiation, and duration of treatment.

Other systematic reviews have considered low-

• A Cochrane review (search date July 2019)

included 61 trials (12,192 participants, 53
trials in adults only). There were no new
studies comparing low-dose corticosteroids
with placebo since ADRENAL and
APROCHSS.[194]

• 28-day, 90-day, and hospital

• A rapid clinical practice guideline was

published in 2018 triggered by publication
of ADRENAL and APROCHSS.[195]
MANAGEMENT

The panel made a weak recommendation

for the use of corticosteroids in adults
and children with sepsis ( with and
without shock). This guideline was also
underpinned by a systematic review (42
RCTs, N=10,194).[196]

Acute
• The guideline panel concluded
that it was uncertain whether
corticosteroids reduced short-
term mortality at 28 to 31 days
(1.8% absolute risk reduction,
95% CI, 4.1% reduction to 0.8%
increase, GRADE low), although
they did seem to reduce longer-
term mortality at 60 days to 1 year
(2.2% absolute risk reduction; 95%
CI, 4.1% reduction to 0%, GRADE
moderate).
• Other results were similar to those
of the SSC 2021 guideline and the
Cochrane systematic review.

BMJ Rapid Recommendations:

intravenous corticosteroids plus
usual care versus usual care only
Lamontagne F, et al.
BMJ 2018;362:k3284
MANAGEMENT

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Sepsis in adults Follow up

Monitoring
Monitoring

FOLLOW UP
Ensure frequent and ongoing monitoring. [3]

Use a track-and-trigger scoring system such as the National Early Warning Score 2 (NEWS2) to identify any
signs of deterioration. [3] Your monitoring should include:

• Vital signs: heart rate, blood pressure, oxygen saturations, respiratory rate, and temperature

• Hourly urine output[3] [47]

• Lactate

• The lactate level should decrease if the patient is clinically improving

• Frequency of repeat lactate measurement depends on the cause of sepsis and treatment given.

Re-calculate the NEWS2 score and re-evaluate risk of sepsis periodically: [3] [45]

• Every 30 minutes, for those at high risk of severe illness or death from sepsis
• Every hour, for those at moderate risk of severe illness or death from sepsis
• Every 4 to 6 hours, for those at low risk of severe illness or death from sepsis
• When standard observations are carried out, in line with local protocol, for those at very low risk of severe
illness or death from sepsis.

Ensure a senior clinical decision-maker (e.g., ST3 level doctor in the UK) attends in person within 1 hour of any
intervention if there is no improvement in the patient’s condition. Refer to or discuss with a critical care consultant
or team.[3] Inform the responsible consultant.[3]

• AVPU should raise concerns if the assessment shows the patient is anything other than 'alert'.

Complications
FOLLOW UP

Complications Timeframe Likelihood

renal dysfunction short term high

Transient oliguria is common and is related to hypotension. Rarely, anuria occurs.[210] Acute kidney injury is
relatively common but is rarely associated with histological change or with any need for long-term renal replacement
therapy.

Correction of volume depletion and hypotension generally reverses oliguria.[210]

hypotension short term high

Volume depletion is caused by reduced oral intake, increased venous capacitance, increased fluid losses due to
pyrexia, capillary leakage leading to oedema, tachypnoea, diarrhoea, and possibly bleeding. Persistent hypotension is
often due to a combination of low systemic vascular resistance, hypovolaemia and reductions in cardiac output from
myocardial failure, excessive positive end-expiratory pressure, or acidosis.

Fluid resuscitation is given with either colloids or crystalloids, and early central venous pressure monitoring is
indicated if rapid response is not achieved. Vasopressors can be started for persistent hypotension or inotropes for
myocardial failure. Caution is required to prevent tachyarrhythmia.

acute respiratory distress syndrome (ARDS) short term medium

Respiratory failure often progresses quickly and is indicated by a respiratory rate >30/minute, even though arterial
oxygen levels may be normal.

ARDS may resolve completely or can progress to fibrosing alveolitis with persistent hypoxaemia.[209]

Intubation and ventilation reduce respiratory muscle oxygen demand and the risk of aspiration and cerebral
anoxia.[210] Lung protective ventilation (low tidal volumes) should be used.[203] Tidal volumes should be reduced
over 1 to 2 hours to a target of 6 mL/kg of predicted body weight. Minimum positive end-expiratory pressure is
recommended to prevent lung collapse at end expiration.[43]

myocardial dysfunction and failure short term medium

Myocardial dysfunction with biventricular dilatation is a recognised complication of sepsis, but is usually transient
and not commonly severe. Death from myocardial failure is rare.[178] Circulating myocardial depressant factors are
thought responsible.

After adequate filling pressures have been achieved, inotropic agents should be considered to maintain an adequate
cardiac index, mean arterial pressure, mixed venous oxygen saturation, and urine output.

Clinicians should define specific goals and desired end points of inotropic therapy in patients with sepsis and titrate
therapy to those end points. These end points should be refined at frequent intervals as patient's clinical status
changes.[178]

multiple organ system failure short term medium

The inflammatory response in sepsis causes widespread tissue injury. Multi-organ dysfunction may be partly caused
by apoptosis of immune, epithelial, and endothelial cells and a shift to an anti-inflammatory phenotype, compounded
by impaired organ perfusion due to hypotension, low cardiac output states, circulatory microthrombi, a disordered
microcirculation, and tissue oedema.[203]

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Sepsis in adults Follow up

Complications Timeframe Likelihood

Failure of each additional organ increases the average risk of death by 15% to 20%. Lung dysfunction tends to occur
early and persists. Serious central nervous system dysfunction or liver function often occur hours to days after sepsis

FOLLOW UP
onset and persists for variable periods of time. Most organ failures resolve within a month in surviving patients.[210]

Treatment of multi-organ failure in sepsis is primarily supportive. It includes effective antibiotic therapy, goal-
directed therapy (to reverse hypotension, anaemia, coagulopathy, bleeding, and shock), and standard supportive
intensive care setting care. This may include dialysis, ventilatory support, and sedation.

hepatic encephalopathy short term low

Liver dysfunction may lead to hepatic encephalopathy, especially in those with established chronic liver
disease.[206] Hepatic encephalopathy is thought to result primarily from ammonia entering the brain due to
absorption from the gut bypassing effective hepatic clearance. This causes intracellular cerebral oedema and
electrolyte abnormalities.[207]

The mainstay of therapy includes laxatives to empty the bowel, prevention of GI bleeding, and avoidance of sedative
drugs, which further suppress consciousness. A low-protein diet is not recommended as these patients are often
malnourished with muscle wasting, which is an important negative prognostic indicator for hepatic encephalopathy
and cirrhosis. These patients’ protein requirements are also relatively higher than those of healthy patients. Protein
intake should be 1.2-1.5g/kg/day.[208]

disseminated intravascular coagulation (DIC) short term low

Occurs in sepsis when leukocytes and endothelial cells are activated or injured by toxic substances released during
infection or shock. The injured cells generate tissue factor on the cell surface, activating the coagulation cascade. In
acute DIC, an explosive generation of thrombin depletes clotting factors and platelets. This activates the fibrinolytic
system.

DIC leads to bleeding into the subcutaneous tissues, skin, and mucous membranes occurs, along with occlusion of
blood vessels caused by fibrin in the microcirculation.

Treatment of the underlying disease is the mainstay of management of either acute or chronic DIC, with blood
products to control bleeding.[211]

neurological sequelae long term medium

The incidence and severity of complications from sepsis depend on the pathogen, duration of disease, age, and
presence of comorbidities.

Focal neurological deficits and hearing loss occur in up to 30% of patients with bacterial meningitis. The mortality
and morbidity is higher for pneumococcal meningitis than for meningococcal meningitis.

Polyneuropathy occurs in 70% of patients with sepsis and multi-organ failure. The use of neuromuscular blocking
agents may increase the severity of polyneuropathy.[212] [213]

Prognosis

Multi-organ compromise is common in advanced sepsis with variable residual morbidity.[203] [204]
FOLLOW UP

In a cohort study of 94,748 adult sepsis survivors, age, male sex, one or more severe comorbidities, pre-hospitalisation
dependency, non-surgical status, acute severity of illness, site of infection, and organ dysfunction were independently
associated with long-term mortality.[205]

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Sepsis in adults Guidelines

Diagnostic guidelines

United Kingdom

Statement on the initial antimicrobial treatment of sepsis

Published by: Academy of Medical Royal Colleges Last published: 2022

Suspected sepsis: recognition, diagnosis and early management

Published by: National Institute for Health and Care Excellence Last published: 2024

Sepsis guidance implementation advice for adults

Published by: NHS England Last published: 2017

Asia

GUIDELINES
The Japanese clinical practice guidelines for management of sepsis and septic shock 2020
Published by: Japanese Society of Intensive Care Medicine; Japanese Last published: 2021
Association for Acute Medicine

Oceania

Sepsis tools
Published by: Clinical Excellence Commission Last published: 2022

Treatment guidelines

United Kingdom

Statement on the initial antimicrobial treatment of sepsis

Published by: Academy of Medical Royal Colleges Last published: 2022

Sepsis guidance implementation advice for adults

Published by: NHS England Last published: 2017

Suspected sepsis: recognition, diagnosis and early management

Published by: National Institute for Health and Care Excellence Last published: 2024

Intravenous fluid therapy in adults in hospital

Published by: National Institute for Health and Care Excellence Last published: 2017

International

Surviving sepsis campaign guidelines for management of sepsis and septic shock
Published by: International Surviving Sepsis Campaign Guidelines Committee Last published: 2021

Asia

The Japanese clinical practice guidelines for management of sepsis and septic shock 2020
Published by: Japanese Society of Intensive Care Medicine; Japanese Last published: 2021
Association for Acute Medicine
GUIDELINES

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Sepsis in adults Online resources

Online resources
1. NHS England: Sepsis (external link)

2. Signs and symptoms of possible infection sources (external link)

3. Track and trigger map developed by the West of England Academic Health Science Network National Early
Warning Score project team (external link)

ONLINE RESOURCES

Key articles
REFERENCES

• National Institute for Health and Care Excellence. Suspected sepsis: recognition, diagnosis and early
management. Mar 2024 [internet publication]. Full text

• NHS England. Sepsis guidance implementation advice for adults. Sep 2017 [internet publication]. Full text

• Royal College of Physicians. National early warning score (NEWS) 2: standardising the assessment of acute-
illness severity in the NHS. December 2017 [internet publication]. Full text

• Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of
sepsis and septic shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-143. Full text Abstract

• Academy of Medical Royal Colleges. Statement on the initial antimicrobial treatment of sepsis. Oct 2022
[internet publication]. Full text

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This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jun 12, 2024.
194 BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on
bestpractice.bmj.com . Use of this content is subject to our disclaimer. © BMJ Publishing Group Ltd 2025. All rights reserved.
Sepsis in adults Images

Images

Figure 1: Capillary refill time. Top image: normal skin tone; middle image: pressure applied for 5 seconds; bottom IMAGES
image: time to hyperaemia measured
From the collection of Ron Daniels, MB, ChB, FRCA; used with permission

Figure 2: Severe purpura fulminans; classically associated with meningococcal sepsis but can occur with
pneumococcal sepsis
From the collection of Ron Daniels, MB, ChB, FRCA; used with permission

This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jun 12, 2024.
196 BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on
bestpractice.bmj.com . Use of this content is subject to our disclaimer. © BMJ Publishing Group Ltd 2025. All rights reserved.
Sepsis in adults Images

IMAGES
Figure 3: National Early Warning Score 2 (NEWS2) is an early warning score produced by the Royal College of
Physicians in the UK. It is based on the assessment of six individual parameters, which are assigned a score of between
0 and 3: respiratory rate, oxygen saturations, temperature, blood pressure, heart rate, and level of consciousness.
There are different scales for oxygen saturation levels based on a patient’s physiological target (with scale 2 being
used for patients at risk of hypercapnic respiratory failure). The score is then aggregated to give a final total score; the
higher the score, the higher the risk of clinical deterioration
Reproduced from: Royal College of Physicians. National Early Warning Score (NEWS) 2: Standardising the
assessment of acute-illness severity in the NHS. Updated report of a working party. London: RCP, 2017.

Figure 4: The relative frequencies of sources of infection in sepsis

Created by the BMJ Knowledge Centre; based on 'NCEPOD. Just say sepsis! Nov 2015'

This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jun 12, 2024.
198 BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on
bestpractice.bmj.com . Use of this content is subject to our disclaimer. © BMJ Publishing Group Ltd 2025. All rights reserved.
Sepsis in adults Images

IMAGES
Figure 5: Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) criteria
Created by BMJ, adapted from Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure
Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems
of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22:707-10.

Figure 6: BMJ Rapid Recommendations: intravenous corticosteroids plus usual care versus usual care only
Lamontagne F, et al. BMJ 2018;362:k3284

This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jun 12, 2024.
200 BMJ Best Practice topics are regularly updated and the most recent version of the topics can be found on
bestpractice.bmj.com . Use of this content is subject to our disclaimer. © BMJ Publishing Group Ltd 2025. All rights reserved.
Sepsis in adults Disclaimer

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// Expert Advisers:

Alexander Alexiou, MB, BS, BSc, DCH, FRCEM, Dip IMC RCSEd
Emergency Medicine Consultant
Physician Response Unit Consultant, Barts Health NHS Trust, London’s Air Ambulance, Royal London Hospital,
London, UK
DISCLOSURES: AA declares that he has no competing interests.

Clovis Rau, MBBS, BSc, FRCEM, DipIMC

Specialty Registrar Emergency Medicine (ST6)
Barnet Hospital, Royal Free NHS Foundation Trust, London, UK
DISCLOSURES: CR declares that he has no competing interests.

Acknowledgements,
BMJ Best Practice would like to gratefully acknowledge the previous team of expert contributors, whose work has
been retained in parts of the content:
Ron Daniels MBChB, FRCA, Chief Executive, United Kingdom Sepsis Trust, Chief Executive, Global Sepsis
Alliance, Programme Director, Survive Sepsis, Consultant in Critical Care and Anaesthesia, Heart of England
NHS Foundation Trust, Birmingham, UK, Matt Inada-Kim MBBS, FRCP, Consultant Acute Physician & Sepsis
Lead, Department of Acute Medicine, Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation
Trust, Winchester, UK, Aamir Saifuddin BMBCh, BA, MRCP, AFFMLM, Specialty Registrar in Gastroenterology
and General Medicine, Maidstone and Tunbridge Wells NHS Trust, UK, Tim Nutbeam MSc, Dip IMC FRCEM,
Consultant in Emergency Medicine, Clinical Academic, University of Plymouth, Lead Doctor, Devon Air Ambulance
Trust, Derriford Hospital, Plymouth, UK, Edward Berry MBChB, MCEM, Specialty Registrar in Emergency
Medicine, Derriford Hospital, Plymouth, UK
DISCLOSURES: RD has received payment for consultancy on sepsis from Kimal Plc, manufacturers of vascular
access devices, from the Northumbria Partnership, a patient safety collaborative, and, where annual leave or other
income was compromised in fulfilling his charity duties, from the UK Sepsis Trust. RD has received sponsorship
to attend and speak at one meeting from Abbott Diagnostics. He is CEO of the UK Sepsis Trust and Global Sepsis
Alliance, and advises HM Government, the World Health Organization, and NHS England on sepsis. Each of these
positions demands that he express opinion on strategies around the recognition and management of sepsis. MIK
is a national clinical advisor on sepsis to NHS England and a national clinical advisor on deterioration to NHS
Improvement. He was reimbursed for a slide set by Relias Learning. AS is the clinical fellow to the National Medical
Director at NHS Improvement. AS has been sponsored on two occasions by Dr Falk Pharma UK to attend specialist
gastroenterology conferences abroad; there was no contractual obligation to disseminate product information. TN is a
clinical adviser to the UK Sepsis Trust. EB declares that he has no competing interests.

// Peer Reviewers:

Matt Inada-Kim, MBBS, FRCP

Consultant Acute Physician & Sepsis Lead
Department of Acute Medicine, Royal Hampshire County Hospital, Hampshire Hospitals NHS Foundation Trust,
Winchester, UK
DISCLOSURES: MIK is a national clinical advisor on sepsis to NHS England and a national clinical advisor on
deterioration to NHS Improvement. He was reimbursed for a slide set by Relias Learning.

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