Next Lesson - Antibiotics
Core
What is Sepsis? - Identification and Management
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. It can lead to septic shock (see our article on shock for more detail). In septic shock, low blood pressure persists despite fluids. Two features define it. First, vasopressors (drugs that tighten blood vessels) are needed to keep the mean arterial pressure (the average pressure in the arteries) at 65 mmHg or more. Second, the lactate stays above 2 mmol/litre despite adequate fluid replacement. Hospital death rates with this combination are above 40%.
In sepsis, the body's own response to infection injures its organs. Immune cells release cytokines (chemical messengers that drive inflammation) in excessive amounts. The circulation is disrupted and organs are damaged by ischaemia (lack of blood supply):
Endotoxin (the toxic part of the outer wall of Gram-negative bacteria, which stain pink on a Gram stain; it is lipid A, part of the lipopolysaccharide, a large fat and sugar molecule, that makes up this wall) can trigger an excessive immune response with widespread cytokine release. This leads to widespread vasodilation (widening of the blood vessels) and a large fall in blood pressure. This is a form of distributive shock, in which blood is spread too widely in dilated vessels. The fall in blood pressure impairs organ perfusion with blood and so with oxygen. Organs can then stop working properly, and the person can die.
This can be further worsened by complications such as DIC (disseminated intravascular coagulation), where multiple clots form within the vessels, using up clotting factors. Cytokines trigger thrombin production (thrombin is an enzyme that helps blood to clot). This promotes coagulation (clotting) and also inhibits fibrinolysis (the breakdown of clots). The coagulation cascade (the chain of clotting reactions) then leads to microvascular thrombosis (clots in the smallest blood vessels). This ultimately progresses to organ ischaemia, dysfunction and failure.
Sepsis is a medical emergency and patients can easily and quickly deteriorate.
There are a series of measures which can be used to help identify sepsis early and prevent development of septic shock. These include the National Early Warning Score 2 (NEWS2, a score built from routine observations) and the Sepsis Red Flags. The diagram below shows an older version of the red flags:
Diagram: An older list of red flags for sepsis. If any of these are present in a person with suspected infection, measure the lactate, calculate the NEWS2 score and call a doctor to assess them urgently. The current red flag criteria are based on NEWS2 and are listed below. It is worth learning them.
SimpleMed original by Dr. Elena Perez
Start a sepsis screen if NEWS2 has triggered, if the person looks unwell, if a carer or relative is worried, or if there is any other clinical cause for concern. Measure the lactate and calculate the NEWS2 score. Red flag sepsis should be suspected when a person has suspected or confirmed infection and either:
- a NEWS2 score of 7 or more, or
- a NEWS2 score of 5 or 6 together with at least one of these: any single NEWS2 observation scoring 3 points; mottled or ashen skin (blotchy or grey skin); a non-blanching rash (a rash that does not fade when pressed); cyanosis (a blue tinge to the skin, lips or tongue); deterioration since the last assessment or since a recent intervention; a lactate above 2 mmol/litre; or known acute kidney injury (AKI, a sudden fall in kidney function).
NICE guideline NG253 (2025) also stratifies risk by NEWS2: a score of 7 or more is high risk, and a score of 5 or 6 is medium risk, of severe illness or death from sepsis. A person at medium risk who shows poor blood flow to the organs (for example, a lactate above 2 mmol/litre or acute kidney injury) should be treated as if they were at high risk. Every person at medium risk should be reviewed, along with their lactate, within 1 hour by a clinician at FY2 level or above (a doctor in at least their second foundation year). That clinician may consider deferring antibiotics for up to 3 hours while looking for a more specific diagnosis, after discussion with a senior decision maker. Once the decision to give antibiotics is made, do not delay them any further.
The management of sepsis is known as the Sepsis Six Care Bundle:
Diagram: The six steps of the Sepsis Six, to be completed within one hour when red flag sepsis is recognised. The list below gives the current oxygen target and fluid details. A useful mnemonic is BUFALO - Blood Cultures, Urine Output, Fluids, Antibiotics, Lactate, Oxygen.
SimpleMed original by Dr. Elena Perez
For red flag sepsis, the Sepsis Six actions should all be completed within one hour. Take the blood cultures before the first dose of antibiotic, but do not delay the antibiotic any further once the decision to give it has been made. Not every person with a red flag needs the Sepsis Six urgently: a senior decision maker (a doctor at ST3 level, specialty training year 3, or above, or equivalent) may look for another diagnosis or decide to de-escalate care, and this should be recorded. The Sepsis Six can also be remembered as "give 3, take 3": give oxygen, antibiotics and fluids, and take blood cultures, a lactate sample and urine output measurements.
- Give oxygen (O2) if needed, adjusting the flow to keep the oxygen saturation at 94% to 98%. Use a lower target of 88% to 92% in people at risk of hypercapnic respiratory failure (failure to clear carbon dioxide from the blood)
- Take urgent blood cultures (blood samples sent to the laboratory to grow any infecting organisms), ideally before the antibiotics, to help find the cause
- Give broad-spectrum IV antibiotics (active against many types of bacteria) within one hour, in line with your local antibiotic guidelines
- Give an intravenous fluid bolus (a quick dose) without delay to a person at high risk, unless there is a reason not to, for example heart or kidney failure. Use a balanced crystalloid (salt solution) such as Hartmann's, or 0.9% saline if a balanced solution is not available. Give 250 ml, ideally over 10 to 15 minutes, and reassess after each bolus. Repeat if needed, up to 1,000 ml in total. If the person has not improved after 1,000 ml, get advice from a senior decision maker
- Measure the serum lactate, for example on a blood gas sample. A lactate above 2 mmol/litre suggests hypoperfusion (poor blood flow to the tissues). Repeat it at least hourly if it is raised
- Measure the urine output. A urinary catheter (a tube into the bladder) may be needed to do this
Details of each step and the pathway for diagnosis are outlined on the Sepsis Six form used when giving treatment. Some further investigations may be useful. These include a full blood count (a count of the blood cells), urea and electrolytes (kidney function and blood salts) and blood glucose. They also include liver function tests (LFTs), C-reactive protein (CRP, a marker of inflammation), a blood gas (venous or arterial) and clotting tests. Further microbiology samples (tests that look for infecting organisms) may include CSF (cerebrospinal fluid, taken by lumbar puncture, a needle test in the lower back, if indicated), urine and organism-specific blood PCR (polymerase chain reaction, a test that detects the DNA of the organism). These tests allow more precise identification of the causative organism and give more information for specific antibiotic treatment. However, they take time. Empirical antibiotics (chosen before the organism is known) should be given intravenously without waiting for the results, as part of the Sepsis Six bundle.
The most likely causative organism (the microbe causing the infection) varies with the age of the patient. This guides the choice of antibiotic.
The example of Neisseria meningitidis
Neisseria meningitidis is one bacterial cause of sepsis. It is a Gram-negative bacterium (it stains pink on a Gram stain), often found as a diplococcus (a pair of round bacteria). It is part of the normal flora (bacteria that usually live on the body without causing harm). It lives in the nasopharynx (the upper throat behind the nose) of about 10% of the population. Carriage is most common in teenagers and young adults. However, if it gets into the bloodstream it can cause meningococcal septicaemia (sepsis), meningococcal meningitis (infection of the layers around the brain and spinal cord), or both. There are different serogroups (types) of N. meningitidis. They are classified by their polysaccharide capsular antigen (the sugar coat around the bacterium, which the immune system recognises). The capsule is one of its main virulence factors (features that help it to cause disease), and different serogroups vary in how likely they are to cause disease. In the UK, the MenB vaccine (against group B) is given to babies at 8 weeks, 12 weeks and 1 year old. The MenACWY vaccine (against groups A, C, W and Y) is usually given in school year 9 (age 13 to 14). It can still be given up to the age of 25 if it was missed.
Prevention consists of vaccination and antibiotic prophylaxis (antibiotics given to prevent illness) for close contacts of the patient. A close contact is someone who has had prolonged close contact with the patient in a household type setting during the 7 days before the illness began, for example by living or sleeping in the same home, sharing a dormitory, being their partner, or sharing a kitchen in a university hall of residence. In the UK, ciprofloxacin is the antibiotic of choice, and rifampicin is a suitable alternative. Health protection teams arrange contact tracing.
Symptoms of meningococcal disease can include fever, a severe headache, vomiting, a stiff neck, confusion, dislike of bright lights (photophobia), drowsiness, and aching muscles and joints. A non-blanching rash (one that does not fade when a glass is pressed against it, the glass or tumbler test) is an important warning sign. It usually starts as small red pinpricks and spreads into red or purple blotches (purpura). It can be harder to see on brown or black skin. However, not everyone with meningococcal disease has a rash, so the absence of a rash does not rule it out. In babies, the fontanelle (the soft spot on the top of the head) may bulge. For suspected meningococcal disease or suspected bacterial meningitis, the empirical antibiotic (chosen before the organism is known) is ceftriaxone (a cephalosporin, a class of antibiotic related to penicillin). It penetrates well into the CSF, which is the site of infection in meningitis. NICE advises adding amoxicillin if there are risk factors for Listeria, and newborn babies follow separate neonatal guidance.
Figure: Gram-negative (pink) diplococci (pairs of circular bacteria). These are most likely N. meningitidis, the cause of meningococcal meningitis.
Image credit: Dr. Brodsky [Public domain]
For other cases of sepsis without signs of meningitis, empirical (best-guess) antibiotic treatment should follow the guidelines of your local NHS trust (the hospital organisation you work for). It usually involves a broad-spectrum beta-lactam (an antibiotic active against many types of bacteria, such as a penicillin or cephalosporin) tailored to the suspected source of infection. Aminoglycosides (a class of antibiotic that includes gentamicin) may be added in selected cases but are not used as sole first-line therapy. Reserve agents, such as meropenem (a carbapenem, a very broad-spectrum antibiotic), are typically used only when indicated by local policy or by advice from the microbiology team (the laboratory specialists). Once the culture results are known, the antibiotic should be changed to a narrower-spectrum one (active against fewer types of bacteria) if appropriate. If you are unsure which antibiotic to use, check your trust's guidelines. They list first-line and second-line treatments for a wide range of conditions, including sepsis.
Editor’s note: It is highly recommended to visit sepsistrust.org for up-to-date resources and information to complement this article. Sepsis is a core topic in medical practice, so it is worth knowing the current guidance well.
Edited By: Dr. Marcus Judge and Dr. Ben Appleby
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