Sepsis recognition and the deteriorating patient

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Suspected sepsis is a syndrome assessment, not a synonym for infection. The clinician first recognises acute illness, asks whether infection is plausible, and then determines whether organ function or perfusion is threatened. This approach reduces both dangerous delay and indiscriminate antibiotic use. NEWS2 structures observations but cannot replace concern about trajectory, immune suppression, pregnancy, recent surgery or an obviously compromised source.

The immediate decision sequence is physiology, risk category, samples, treatment and response. Oxygen is used for hypoxaemia with an appropriate saturation target; intravenous access, laboratory tests and cultures are obtained promptly; fluid is given in reassessed boluses when hypoperfusion is present; and the antimicrobial regimen is matched to source and patient factors. Each intervention requires a documented time and response.

Sepsis labels should be revisited. Positive cultures can represent contamination, fever can be non-infectious, and infection may exist without sepsis. At every review ask whether an alternative diagnosis, resistant pathogen, undrained focus, device infection, inappropriate drug exposure or treatment complication better explains the course.

Key points

Sepsis is life-threatening organ dysfunction caused by a dysregulated response to infection; fever and a positive culture are neither necessary nor sufficient for the diagnosis.
Begin with ABCDE, observations, NEWS2 and clinical trajectory. A normal temperature, modest inflammatory markers or apparently reassuring blood pressure does not exclude dangerous deterioration.
Look deliberately for new confusion, increased oxygen requirement, tachypnoea, hypotension, poor peripheral perfusion, reduced urine output, non-blanching rash and inability to maintain normal activity.
Identify likely source and host modifiers in parallel: recent procedures, devices, immune suppression, pregnancy, frailty, antimicrobial exposure, resistant-organism history and travel all change the pathway.
Obtain blood cultures and appropriate source samples before antimicrobials when this causes no clinically significant delay; never postpone urgent treatment in a high-risk patient to complete sampling.
For adults meeting high-risk criteria, NICE prioritises broad-spectrum intravenous antimicrobial treatment within one hour of risk recognition, selected from the suspected source, allergy history and local resistance data.
Treatment is a cycle rather than a bundle completed once: stabilise, measure response, review source control, narrow therapy when results arrive and escalate when physiology fails to improve.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Bacterial infection

Pneumonia, urinary, abdominal, skin, device and bloodstream infections commonly precipitate sepsis, with pathogen likelihood shaped by source, healthcare exposure and host factors.

Viral or fungal infection

Influenza, COVID-19 and invasive fungal disease can cause the same organ-dysfunction syndrome, especially during immune suppression or critical illness.

Host vulnerability

Extremes of age, pregnancy, frailty, immune suppression, recent surgery and major comorbidity reduce reserve and may blunt typical inflammatory signs.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Dysregulated host response
Microbial signals trigger innate immune, endothelial and coagulation pathways that become disproportionate and injure host tissues beyond the original focus.
2
Microvascular dysfunction
Vasodilatation, endothelial leak, maldistributed flow and microthrombi impair tissue oxygen delivery even when global haemodynamic measurements initially appear acceptable.
3
Cellular and organ injury
Inflammation, impaired perfusion and mitochondrial dysfunction disrupt kidney, brain, lung, liver, heart and coagulation function in variable combinations.
4
Self-amplifying shock
Falling vascular tone and myocardial performance reduce perfusion, while acidosis and organ failure further impair cardiovascular responsiveness and antimicrobial handling.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

High-risk physiologyRed flag

New hypotension, marked tachypnoea, increased oxygen need, altered mental state, mottled or ashen skin, cyanosis, non-blanching rash or very low urine output indicates threatened organ function and demands immediate senior assessment.

Subtle high-risk presentationRed flag

Older, frail, pregnant, immunosuppressed or recently treated patients may lack fever or tachycardia. Acute functional decline, delirium, reduced intake, falls or caregiver concern may be the earliest signal.

Probable source

Cough, dysuria, abdominal pain, cellulitis, line inflammation, wound discharge, spinal pain or meningism directs examination, sampling, imaging and initial antimicrobial spectrum without requiring certainty before stabilisation.

Failure after initial treatmentRed flag

Persistent shock, rising lactate, increasing oxygen need or worsening confusion after initial measures suggests inadequate resuscitation, wrong diagnosis, resistant infection or a source requiring urgent drainage or surgery.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Complete observations, NEWS2 and bedside glucoseFirst step
Why
Quantify physiological disturbance, find hypoglycaemia and establish a repeatable baseline.
Interpretation and limitations
Trend respiratory rate, oxygen requirement, blood pressure, heart rate, consciousness, temperature and urine output. NEWS2 supports escalation, but a single low score cannot overrule a concerning trajectory or high-risk host.
02
Venous or arterial blood gas with lactate
Why
Assess perfusion, acid-base status, ventilation and severity while resuscitation begins.
Interpretation and limitations
Raised lactate is not specific for infection and may reflect adrenergic stress, seizures, liver dysfunction or medicines. A normal result does not exclude sepsis; persistent elevation despite treatment increases concern.
03
Blood cultures before antimicrobials when feasible
Why
Identify bloodstream pathogens and enable susceptibility-directed treatment.
Interpretation and limitations
Collect correctly filled peripheral sets using aseptic technique and label source and time. Do not delay urgent antibiotics; interpret skin flora using number of positive bottles, timing, devices and clinical context.
04
FBC, U&E, creatinine, liver tests, CRP and coagulation
Why
Identify organ dysfunction, treatment modifiers and complications and provide monitoring baselines.
Interpretation and limitations
Leucopenia can be as concerning as leucocytosis. Renal and hepatic impairment change antimicrobial exposure; thrombocytopenia or coagulopathy may indicate severe disease but none of these tests establishes sepsis alone.
05
Source-directed microbiology and imaging
Why
Locate the focus and decide whether source control or a different regimen is required.
Interpretation and limitations
Use urine, sputum, wound, device, cerebrospinal-fluid or other sampling only when clinically indicated and safe. Ultrasound, radiography or CT should answer a specific question and not delay stabilisation.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Haemorrhagic or cardiogenic shock

Bleeding, myocardial infarction, arrhythmia and decompensated heart failure may cause hypotension and lactataemia without infection; focused history, examination and imaging discriminate.

Pulmonary embolism

Abrupt dyspnoea, pleuritic pain, right-heart strain and thrombosis risk can mimic septic physiology and require a probability-led vascular pathway.

Adrenal or metabolic crisis

Adrenal insufficiency, diabetic ketoacidosis, thyroid crisis and severe hypoglycaemia can produce shock, fever or altered consciousness and need immediate biochemical assessment.

Drug or inflammatory syndrome

Anaphylaxis, overdose, serotonin toxicity, pancreatitis and autoimmune inflammation may resemble sepsis; exposure history and syndrome-specific findings prevent antibiotic-only management.

Additional chapter-specific clues

Important mimicRed flag

Pulmonary embolism, haemorrhage, pancreatitis, adrenal crisis, anaphylaxis, toxic ingestion and inflammatory disease can reproduce shock and raised inflammatory markers; parallel assessment prevents diagnostic closure.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01High-risk suspected sepsisTreat physiological danger and infection togetherFirst stepSuspected infection plus NICE high-risk criteria, shock, rapidly worsening organ dysfunction or strong clinician concern.

1Call senior help, perform ABCDE, secure monitoring and intravenous access, measure lactate and obtain cultures and source samples without delaying treatment.
2Give oxygen only when needed, use small reassessed crystalloid boluses for hypoperfusion, and administer source-appropriate broad-spectrum intravenous antimicrobials within the nationally recommended high-risk timeframe.
3Reassess after every intervention; measure urine output, repeat lactate when relevant, seek critical-care support for ongoing shock and arrange urgent source control when obstruction, infected material or a device is suspected.

02Moderate-risk presentationComplete a time-bounded diagnostic reviewAlternativePossible infection with abnormal physiology but no current high-risk feature and no immediate alternative emergency.

1Obtain a clinician assessment promptly, repeat observations, review comorbidity and medicines, examine for a focus and order discriminating tests rather than an untargeted panel.
2Decide and document whether antimicrobials are indicated, the intended source and review time; use intravenous treatment only when severity, absorption or the infection site requires it.
3EscalationEscalate immediately if physiology worsens, and ensure discharge occurs only with a credible diagnosis, explicit red-flag advice and arrangements for pending microbiology results.

03No improvementRe-open diagnosis and source controlPhysiology, lactate, organ function or symptoms fail to improve as expected after initial treatment.

1Repeat ABCDE and verify delivery, fluid response, antimicrobial timing, dose, renal adjustment and vascular access while supporting failing organs.
2Review cultures and imaging, repeat examination for hidden collections, obstruction, necrotic tissue or infected devices, and contact microbiology and the relevant procedural team.
3EscalationConsider non-infectious shock and treatment harm, narrow or change antimicrobials only from the revised evidence, and document the next reassessment point and escalation ceiling.

Key medicines and prescribing safety1 treatment · regimens, roles and cautions

Restores circulating volume when suspected sepsis causes hypoperfusion or hypotension.

Balanced isotonic crystalloid

Give 250 mL intravenously over 10 to 15 minutes, then reassess before any repeat bolus.

Use smaller reassessed volumes in cardiac or renal impairment; stop and seek senior support if pulmonary oedema, worsening oxygenation or absent haemodynamic response develops.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Refractory shock

Persistent vasodilatation, capillary leak and myocardial depression can require vasopressor and critical-care support despite fluids and appropriate source-directed treatment.

Acute respiratory failure

Pneumonia, aspiration, permeability oedema and respiratory muscle fatigue may cause severe hypoxaemia or ventilatory failure requiring advanced support.

Kidney and coagulation injury

Renal hypoperfusion and inflammation cause acute kidney injury, while endothelial coagulation activation may produce thrombocytopenia, bleeding or disseminated intravascular coagulation.

Long-term morbidity

Survivors may experience weakness, cognitive change, psychological distress, recurrent infection and loss of independence after prolonged inflammation and critical illness.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record the exact time of risk recognition, cultures, lactate, first antimicrobial dose, fluid boluses, senior review and any source-control referral so delay is visible and correctable.
Repeat respiratory rate, oxygen requirement, blood pressure, perfusion, consciousness and urine output after each intervention; worsening physiology overrides an earlier reassuring score.
Trend creatinine, electrolytes, liver tests, platelets, coagulation and lactate according to severity, and adjust antimicrobial exposure promptly when organ function changes.
Review preliminary and final microbiology every day, including negative results, and document stop, narrow, switch or duration decisions rather than allowing empirical therapy to continue automatically.
Reassess device necessity, wounds, abdominal findings and focal pain because a source-control problem may become clinically apparent only after initial resuscitation.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Temperature is an unreliable gatekeeper

Severe infection may present with normothermia or hypothermia, especially in older or immunosuppressed adults; clinical trajectory and organ dysfunction carry greater weight.

Lactate is a risk marker

Hyperlactataemia supports concern about impaired perfusion or metabolic stress but is neither required for sepsis nor specific enough to establish an infectious cause.

Cultures change later decisions

A well-collected pretreatment culture can permit narrower safer therapy, but sampling has negative value when it delays life-saving treatment in a high-risk patient.

Source control is treatment

Drainage, debridement, relief of obstruction and removal of an infected device may determine survival when antimicrobial therapy cannot penetrate or sterilise the focus.

Antibiotic review protects patients

Once risk falls and data accumulate, stopping unnecessary therapy is active care that reduces toxicity, Clostridioides difficile infection and resistance selection.

11Common pitfallsFrequent interpretation and management errors.

01
Calling every infection sepsis and thereby obscuring which patients have acute organ dysfunction.
02
Waiting for fever, CRP elevation, imaging or a positive culture before treating high-risk physiology.
03
Completing a sepsis checklist without reassessing whether circulation, consciousness or oxygenation improved.
04
Choosing an antibiotic without recording the suspected source, allergy phenotype, previous resistant organisms or renal function.
05
Escalating antimicrobial breadth repeatedly while overlooking an abscess, obstruction, ischaemic tissue or infected device.