Sepsis Recognition and the Sepsis Six

Introduction

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. The key conceptual shift in the modern (Sepsis-3) definition is that sepsis is not simply 'infection plus a fever' - it is infection that has triggered organ dysfunction, and it is that organ dysfunction, not the infection itself, that threatens life.¹

Sepsis is common, frequently under-recognised because its early features overlap with many less serious illnesses, and highly time-sensitive - outcome is strongly linked to how quickly treatment starts. This combination is why UK practice is built around a structured screening and treatment bundle (the Sepsis Six) rather than relying on clinical gestalt alone.³

Pathophysiology

Infection triggers a systemic release of pro-inflammatory cytokines, activating the coagulation cascade, injuring the vascular endothelium and causing widespread vasodilatation and increased capillary permeability. The practical consequences are what produce the clinical picture: vasodilatation causes relative hypotension, capillary leak causes fluid to shift out of the intravascular space (worsening the hypotension and explaining why large fluid volumes are often needed), and microvascular thrombosis and cellular metabolic dysfunction impair oxygen delivery and use at the tissue level even where blood pressure is maintained. This is the same underlying process described in more detail in multi-organ dysfunction syndrome, of which severe sepsis is the commonest cause.

Identifying the source

Recognition

No single sign or symptom reliably identifies sepsis, so recognition relies on structured scoring tools applied to any patient with suspected infection.

• NEWS2 - the standard UK early warning score; a high or rapidly rising score in a patient with suspected infection should trigger sepsis screening
• qSOFA - respiratory rate 22/min or above, altered mentation, systolic blood pressure 100 mmHg or below; two or more of these at the bedside identify patients at higher risk of a poor outcome from sepsis, though it is a prognostic screening tool rather than a diagnostic one and performs poorly in isolation as a rule-in or rule-out test
• Red flag sepsis criteria (UK Sepsis Trust) - includes new confusion, systolic BP under 90 mmHg (or a drop of over 40 from baseline), heart rate over 130/min, respiratory rate 25/min or above, needing oxygen to maintain saturations, non-blanching rash, mottled or ashen skin, and not passed urine in 18 hours (or under 0.5 mL/kg/hour if catheterised)

At-risk groups

• Age under 1 or over 75
• Immunosuppression - chemotherapy, long-term steroids, asplenia, poorly controlled diabetes
• Indwelling lines, catheters or recent surgery/invasive procedure
• Pregnant or recently pregnant women, and IV drug use
• Breach of skin integrity - burns, wounds, skin infection

The Sepsis Six

The Sepsis Six is a bundle of three tests and three treatments, delivered within 1 hour of recognising sepsis, developed and promoted by the UK Sepsis Trust specifically because early, bundled action measurably improves survival.²

Investigations beyond the Sepsis Six

• FBC, U&E, LFTs, CRP, clotting - baseline organ function and inflammatory markers
• Venous or arterial blood gas - lactate, pH and base excess give an immediate read on severity
• Source-directed investigations - chest X-ray, urinalysis and culture, wound swabs, imaging of a suspected abdominal or soft tissue source, lumbar puncture if meningitis is suspected
• Repeat lactate after initial fluid resuscitation - failure to clear lactate suggests ongoing hypoperfusion and the need for further treatment

Choosing antibiotics

Empirical antibiotic choice is broad-spectrum, guided by the likely source, local antimicrobial resistance patterns and hospital policy, and the patient's allergy status - it is not necessary, or appropriate, to wait for a confirmed organism before starting treatment. Local guidelines exist precisely because the right empirical choice varies by trust and by local resistance patterns, so following them (rather than a remembered 'standard' regimen) is the correct approach in practice.

Once culture results and sensitivities are available, typically at 48-72 hours, antibiotics are reviewed and de-escalated to a narrower-spectrum agent where possible - both to reduce the selection pressure driving antimicrobial resistance and to reduce side effects, provided the patient is responding clinically.

Source control

Antibiotics and fluids treat the systemic response, but an ongoing, uncontrolled source of infection will continue to drive it regardless of how well the rest of the bundle is delivered. Identify and, wherever possible, actively control the source in parallel with the Sepsis Six.

• Drain an abscess or infected collection, surgically or radiologically
• Remove an infected line, catheter or other device where it is the likely source
• Relieve obstruction - for example an obstructed, infected renal tract needs urgent decompression alongside antibiotics
• Debride infected or necrotic tissue, particularly in suspected necrotising soft tissue infection, where delay is strongly associated with mortality

Septic shock

Septic shock is sepsis with circulatory and cellular/metabolic abnormality severe enough to substantially increase mortality: persistent hypotension needing vasopressors to maintain a mean arterial pressure of 65 mmHg or above, together with a lactate above 2 mmol/L, despite adequate fluid resuscitation.

• Fluid resuscitation first - crystalloid boluses with reassessment, as in any shocked patient
• Noradrenaline is the first-line vasopressor where hypotension persists despite adequate fluid resuscitation, targeting a mean arterial pressure of 65 mmHg
• Central venous access and arterial monitoring are typically needed for vasopressor infusion and to guide ongoing resuscitation, which usually means critical care involvement
• Reassess repeatedly - fluid responsiveness, lactate clearance and evolving organ dysfunction (see multi-organ dysfunction syndrome) all guide the intensity of ongoing support

Neutropenic sepsis

Neutropenic sepsis is a specific and even more time-critical pathway: any patient who has received chemotherapy in the preceding 6 weeks (or who is otherwise known to be neutropenic) presenting with a fever of 38°C or above, or any other signs of sepsis, must be treated as neutropenic sepsis until proven otherwise.

Mimics of sepsis

Several non-infective conditions produce a similar systemic picture - fever or hypothermia, tachycardia, hypotension - and are worth actively considering, both because they need different treatment and because they can coexist with true sepsis.

• Acute pancreatitis and other severe non-infective inflammatory conditions can produce a near-identical systemic inflammatory picture
• Adrenal crisis - hypotension refractory to fluids in a patient on long-term steroids or with known adrenal insufficiency should prompt empirical hydrocortisone alongside sepsis treatment
• Pulmonary embolism - tachycardia and hypoxia without a clear infective source
• Drug reaction or toxicity - for example neuroleptic malignant syndrome or serotonin syndrome, distinguished by drug history and examination findings such as rigidity or clonus
• Transfusion reaction, in a patient who has recently received blood products

Red flags

Prognosis

Sepsis carries substantial mortality that rises sharply with delayed recognition, delayed antibiotics, and progression to septic shock or multi-organ dysfunction. Systems that reliably screen for sepsis and deliver the Sepsis Six within the first hour have demonstrably better survival than those relying on ad hoc recognition, which is the entire rationale for building sepsis management around a structured, time-bound bundle rather than individual clinical judgement alone.