Sepsis and reversible illness in palliative care

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

Infection in advanced disease may be curable, temporarily reversible or part of irreversible decline. Immunosuppression, devices, obstruction, aspiration, wounds and repeated healthcare exposure increase risk, while frailty reduces physiological reserve. Sepsis can present as delirium, falls, reduced intake or sleepiness without fever. The clinical task is to recognise danger and judge proportionality simultaneously, not sequentially.

Establish the baseline and tempo. Ask what the person could do yesterday, how quickly cognition and intake changed, focal respiratory, urinary, abdominal, skin or line symptoms and recent antibiotics or resistant organisms. Review corticosteroids, chemotherapy, immunotherapy, opioids and sedatives. Examine observations, perfusion, lungs, abdomen, urine or catheter, skin, wounds, devices and neurological function and check bedside glucose.

Use NEWS2 and NICE high, moderate-to-high and low risk criteria to structure escalation, while remembering that a familiar low blood pressure or chronic hypoxia needs clinical interpretation. Neutropenia after anticancer treatment, possible meningitis, rapidly progressive soft-tissue infection and immunotherapy toxicity have dedicated emergency pathways. A normal temperature or initially normal lactate does not by itself exclude serious infection.

For high-risk suspected sepsis, obtain blood culture and lactate with full blood count, renal, liver and clotting tests and administer an appropriate intravenous broad-spectrum antibiotic urgently, ordinarily within one hour of identifying high risk. Moderate-to-high risk permits focused assessment and senior review within the NICE pathway before antibiotics when safe. Use local microbiology guidance based on source, allergy, organ function and resistance history.

Fluid is prescribed to physiology. For hypotension or raised lactate, current NICE guidance uses a 250 mL isotonic crystalloid bolus over about 10 to 15 minutes followed by reassessment, with further boluses up to the pathway limit when response and safety support them. Review breathing, oxygen, capillary refill, pressure, pulse, urine and congestion after each bolus; use critical-care or renal input rather than forcing fluid into non-responsive overload.

Identify and control the source. Drain an abscess or infected pleural collection, relieve an obstructed infected kidney or biliary tree, remove or exchange a responsible line or catheter and seek surgery for perforation or necrotising infection. Microbiology narrows therapy and prevents unnecessary toxicity. Review daily for clinical response, culture results, route, duration, Clostridioides difficile risk and whether the original goal is being achieved.

Treatment decisions must be individual. Clarify capacity and any valid advance refusal, the likely reversibility, burdens of transfer and monitoring, time to benefit and the person's priority. DNACPR alone does not set a treatment ceiling. A trial might aim for wakeful conversation, recovery of oral intake or return home within 48 to 72 hours; failure of that target should trigger a planned conversation, not automatic escalation.

When antimicrobial or hospital treatment is not proportionate, explain the reasoning and expected course. Continue oxygen for hypoxaemia when comfortable, opioid for breathlessness or pain, antipyretic for distress, delirium care, mouth care and family support. Avoid implying certainty about timing and review if the pattern changes or the person requests reconsideration.

Key points

Palliative status does not exclude reversible illness. New confusion, hypotension, tachypnoea, hypoxia, reduced urine, rigors or functional collapse requires active assessment rather than automatic attribution to dying.
Sepsis is life-threatening organ dysfunction from infection; fever may be absent in older, neutropenic, corticosteroid-treated or dying patients.
First-line assessment combines ABCDE, NEWS2, infection source, perfusion, cognition, urine output, medicines and baseline trajectory with immediate review of the person's goals.
Use the current NICE adult sepsis risk criteria. High-risk suspected sepsis needs urgent bloods, cultures when they do not delay care, intravenous broad-spectrum antibiotics and senior review within the recommended emergency timeframe.
Measure lactate, blood culture, full blood count, renal and liver function, clotting and glucose and image or sample the likely source when results will change treatment.
Give small reassessed crystalloid boluses for sepsis-related hypoperfusion, not automatic litres; heart failure, kidney failure and frailty increase overload risk.
Source control—drainage, catheter change, surgery or relief of obstruction—may determine recovery more than repeated antibiotic escalation.
A DNACPR decision applies to cardiopulmonary resuscitation after arrest and does not itself refuse antibiotics, fluid, oxygen, hospital transfer or intensive care.
When benefit is uncertain, offer a time-limited treatment trial with an agreed target, review time and stopping rule instead of vague treatment 'for now'.
If active treatment is not wanted or cannot achieve recovery, relieve breathlessness, fever discomfort, pain, delirium and secretions and communicate that comfort care remains active treatment.

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

Respiratory and aspiration infection

Weak cough, dysphagia, tumour obstruction, immobility and altered consciousness increase pneumonia and aspiration-related infection in advanced illness.

Urinary and obstructive infection

Indwelling catheters, retention, stones, tumour obstruction and instrumentation allow ascending urinary infection, pyelonephritis and infected hydronephrosis.

Device, wound and abdominal sources

Vascular lines, drains, pressure injuries, fungating tumours, biliary obstruction, perforation and collections provide persistent sources requiring mechanical control.

Impaired host defence

Neutropenia, corticosteroids, marrow failure, malnutrition and anticancer treatment blunt fever and inflammatory signs while accelerating progression.

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

1
Dysregulated host response
Infection triggers an excessive and disordered immune response that injures endothelium and organs beyond the local source.
2
Vasodilatation and leak
Loss of vascular tone and increased permeability reduce effective circulating volume, causing hypotension, oedema and impaired tissue perfusion.
3
Microcirculatory dysfunction
Endothelial activation, coagulation and altered cellular oxygen use produce organ injury even when global oxygen measurements appear acceptable.
4
Organ dysfunction
Brain, kidney, lung, liver and coagulation failure manifests as delirium, oliguria, hypoxia, jaundice, thrombocytopenia and escalating lactate.
5
Reduced physiological reserve
Frailty and advanced organ disease narrow the margin between compensated infection and irreversible shock and increase treatment burden.

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

Physiological deterioration

New tachypnoea, hypoxia, tachycardia, hypotension, altered temperature, mottling or prolonged capillary refill suggests systemic illness.

Brain and kidney dysfunction

New confusion, reduced alertness, oliguria or rising creatinine may be the earliest organ manifestations in advanced disease.

Hidden infection

Neutropenia, corticosteroids and frailty can suppress fever and leucocytosis, so focal symptoms and deterioration carry greater weight.

Source pattern

Cough, dysuria, abdominal pain, line inflammation, wound change or focal tenderness helps direct cultures, imaging and source control.

Potential reversibility

Abrupt change from a stable baseline, a treatable source and preserved functional reserve increase the chance of meaningful recovery.

High-risk sepsisRed flag

NICE high-risk criteria, marked lactate elevation, severe hypotension, respiratory failure or rapidly progressive infection requires emergency treatment and senior review.

Red flags requiring action

New confusion, reduced consciousness or a sudden major functional fall can be organ dysfunction even without fever.
Systolic hypotension, rising lactate, mottling, prolonged capillary refill or oliguria suggests impaired perfusion and possible shock.
Marked tachypnoea, new oxygen need, cyanosis or exhaustion indicates respiratory organ dysfunction.
Recent systemic anticancer treatment with fever or deterioration requires immediate neutropenic-sepsis assessment.
Pain out of proportion, rapidly spreading erythema, crepitus or bullae suggests necrotising soft-tissue infection.
Obstructed infected kidney or biliary system will not be cured reliably by antibiotics without urgent drainage review.
DNACPR must not be used as shorthand to withhold reversible treatment that the person would want.

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
ABCDE, NEWS2 and bedside glucoseFirst step
Why
Quantify immediate airway, breathing, circulation, cognition and temperature risk and identify hypoglycaemia as a rapid alternative.
Interpretation and limitations
High-risk criteria trigger emergency treatment; scores support but do not replace judgement in chronic abnormal physiology or immunosuppression.
02
Venous or arterial lactate
Why
Assess tissue stress and contribute to sepsis risk classification while establishing a baseline for response.
Interpretation and limitations
Elevation increases urgency, but a normal value does not exclude serious infection or replace source and organ assessment.
03
Blood culture before antibiotics when feasible
Why
Obtain appropriate sets from peripheral and device sites without delaying time-critical antimicrobial administration.
Interpretation and limitations
Growth enables narrowing and source attribution; contamination and prior treatment require clinical interpretation.
04
Organ and coagulation blood panel
Why
Check full blood count, renal and liver function, clotting, CRP and other tests specified by the current sepsis pathway.
Interpretation and limitations
Results show neutropenia and organ dysfunction and guide antimicrobial dose, fluid, transfusion and escalation decisions.
05
Source-specific samples
Why
Collect urine, sputum, wound, line, stool or cerebrospinal material only when safe and likely to direct care.
Interpretation and limitations
A positive sample should fit the syndrome; asymptomatic colonisation, catheter bacteriuria and chronic wounds can mislead.
06
Source-directed imaging
Why
Use chest imaging, ultrasound or CT to identify pneumonia, obstruction, abscess, perforation, infected fluid or device complication.
Interpretation and limitations
Anatomical definition is the gold standard for planning drainage or surgery; imaging should be omitted when intervention is not wanted and results cannot help comfort.

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

Expected dying process

Progressive sleepiness, reduced intake, cool peripheries and altered breathing may reflect dying, but new focal or abrupt change still warrants review.

Medicine toxicity

Opioid accumulation, sedatives, anticholinergics and withdrawal can cause acute delirium, hypotension or clinically important respiratory change without infection.

Metabolic emergency

Hypercalcaemia, hypoglycaemia, adrenal crisis, kidney failure and sodium disturbance commonly mimic septic weakness, hypotension and acute confusion.

Thromboembolic or cardiac disease

Pulmonary embolism, acute coronary syndrome, arrhythmia and heart failure can produce tachypnoea, hypoxia, hypotension and inflammatory markers.

Treatment-related inflammation

Immune-related toxicity, transfusion reaction, tumour fever and drug reaction may resemble infection and require different urgent treatment.

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

01High-risk sepsisTreat physiology and source immediatelyFirst stepSuspected infection meets current NICE high-risk criteria or causes rapidly progressive organ dysfunction.

1EscalationUse ABCDE and NEWS2, obtain lactate, cultures and organ bloods, call senior help and confirm any known escalation limits without delaying rescue.
2Give source-appropriate intravenous antibiotics within the emergency timeframe and 250 mL reassessed crystalloid boluses for hypoperfusion when safe.
3Arrange urgent source control and critical-care review if within goals, then narrow treatment and revise fluid and organ support from response and results.

02Uncertain deteriorationTest reversible hypotheses proportionatelyInfection is possible but high-risk criteria are absent and dying, medicine or metabolic causes also fit.

1Establish baseline, pace and goals and perform focused examination, bedside tests and selected blood, culture or imaging that could change treatment.
2Use senior review within the NICE moderate-risk timeframe to decide antibiotic, fluid, route and care setting rather than giving automatic broad treatment.
3EscalationTreat the most likely reversible contributors and reassess physiology and function at a named interval, escalating promptly if high-risk features emerge.

03Time-limited trialDefine success before starting treatmentAntibiotic or hospital benefit is uncertain but a reversible infection could restore an outcome valued by the person.

1Explain expected chance, burden and alternatives and agree a measurable aim such as improved alertness, oral intake or transfer ability by 48 to 72 hours.
2Choose the least burdensome effective route and include fluid and source control only when necessary, with clear ceilings for vasopressor or intensive care.
3Review at the preset time with the patient or lawful decision-maker and continue, narrow, change or stop according to response and the original goal.

04Comfort-only careRelieve infection-related suffering without burdensome rescueThe person declines active treatment or dying is advanced and antimicrobial or hospital treatment cannot achieve a valued recovery.

1Explain that the plan treats suffering rather than abandoning care, document capacity or best-interests reasoning and communicate across settings.
2Treat pain, breathlessness, fever discomfort, delirium and secretions through a reliable route and provide mouth, skin and family support.
3Review if symptoms or wishes change, avoid non-beneficial observations and tests and prepare carers for likely decline and whom to contact.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Provides immediate infection control while cultures, imaging and source-control planning clarify the organism and anatomy.

Empiric intravenous antimicrobial for high-risk sepsis

Give the source-specific local broad-spectrum regimen within the NICE emergency timeframe, using allergy, previous microbiology, healthcare exposure, weight and renal and hepatic function to select and dose treatment.

Obtain cultures first only if this causes no harmful delay; review daily for narrowing, route and duration and monitor kidney, liver, cytopenia, interaction and Clostridioides difficile risk.

Restores circulating volume and perfusion while avoiding an unmonitored large-volume prescription.

Reassessed isotonic crystalloid bolus

For sepsis-related hypoperfusion in an adult, give 250 mL isotonic crystalloid over about 10 to 15 minutes and reassess before each further bolus, using the current NICE maximum and senior review.

Heart failure, renal failure and frailty increase pulmonary-oedema risk; stop and escalate for worsening breathing, oxygenation, crackles or non-responsive shock.

Relieves pain, rigors and fever discomfort but does not treat infection or improve organ perfusion.

Paracetamol for fever-related discomfort

Use 500 mg to 1 g orally, rectally or intravenously up to four times daily when fever causes distress, reducing the maximum in low body weight, malnutrition, hepatic disease or heavy alcohol use.

Count all combination products, adjust the daily maximum to liver and weight risk and do not use temperature normalisation as proof of antimicrobial response.

Reduces distress from breathlessness when physiological treatment is taking effect or when escalation is not wanted.

Opioid for refractory infection-related breathlessness

Use a low immediate-release dose selected from prior opioid exposure and kidney function or an agreed proportion of the existing rescue dose, then review comfort and alertness.

Monitor sedation, respiratory rate, delirium and accumulation, especially in acute kidney injury; oxygen is reserved for hypoxaemia or an individually demonstrated benefit.

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

Septic shock

Persistent hypotension and tissue hypoperfusion despite appropriate fluid requires vasopressor and critical-care assessment when escalation is wanted.

Multiple-organ failure

Progressive respiratory, renal, hepatic, neurological and coagulation dysfunction can make recovery increasingly unlikely despite microbiological control.

Fluid and medicine harm

Excessive fluid resuscitation causes pulmonary oedema, while renally unadjusted antibiotics cause neurological, renal and serious gastrointestinal toxicity.

Clostridioides difficile and resistance

Broad or repeated antimicrobials disrupt flora, select resistant organisms and can cause severe diarrhoea and future treatment limitation.

Goal-discordant escalation

Unplanned transfer, invasive monitoring or intensive care can consume remaining time without achieving the recovery the person values.

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

In emergency treatment repeat NEWS2 and ABCDE variables at the frequency required by risk and local sepsis pathway.
After each fluid bolus reassess pressure, pulse, capillary refill, lungs, oxygen need, urine and signs of venous congestion.
Trend lactate, renal, liver, coagulation and blood counts only as needed to guide active organ and antimicrobial treatment.
Review culture and imaging results promptly and document source control, narrowing, route and planned antibiotic duration.
Track a patient-valued outcome such as alert conversation, drinking, transfer or return home during a time-limited trial.
Watch for diarrhoea, rash, kidney injury, cytopenia, delirium and medicine interaction during antimicrobial treatment.
If the plan becomes comfort focused, monitor symptom relief and family understanding rather than continuing burdensome physiological observations.

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

Palliative is not irreversible

A person may have incurable disease and still gain meaningful time or function from treatment of a discrete infection.

No fever does not reassure

Neutropenia, corticosteroids, age and frailty can blunt temperature response while organ dysfunction progresses.

Fluid needs a question

Each bolus should answer whether perfusion improves without congestion, rather than fulfilling a predetermined litre target.

Antibiotics cannot drain pus

An obstructed system, infected device or collection may continue driving sepsis until mechanical source control occurs.

A trial needs an endpoint

Naming the desired recovery and review time prevents uncertain treatment from continuing indefinitely by default.

DNACPR is not a ceiling

The decision not to attempt CPR after arrest leaves antibiotics, fluid, transfer and intensive-care decisions to separate judgement.

11Common pitfallsFrequent interpretation and management errors.

01
Labelling abrupt delirium as expected dying without assessing infection, medicines and metabolic causes.
02
Waiting for fever before considering sepsis in a neutropenic or steroid-treated patient.
03
Using NEWS2 as a substitute for clinical judgement in chronically abnormal physiology.
04
Delaying high-risk antibiotics for non-essential imaging or cultures.
05
Giving unmonitored litres of fluid to a frail patient with heart or kidney failure.
06
Repeating broad antibiotics while ignoring an obstructed or drainable source.
07
Using DNACPR status to refuse a treatment the person would value.
08
Starting a time-limited trial without defining success, review time or stopping rule.
09
Continuing antibiotics despite toxicity and no prospect of the agreed recovery.
10
Stopping disease treatment without replacing it with active symptom and family care.