The mortality rate for severe sepsis still approaches 50% despite antimicrobial therapy and supportive care. The mortality rate depends on the pathogen and the source of bacteraemia.

There is an array of terminology, such as septicaemia or sepsis syndrome, which may have different meanings to different individuals but bacteraemia, sepsis and septic shock can be considered as overlapping clinical states in a progressively serious septic process of infection and immune system activation.

Microorganisms in the blood are exposed to a host of immune system chemical and cellular mediators and can trigger extensive, rapid and severe immune responses which may quickly result in septic shock, multiple organ failure and death.

Three factors combine to increase the potential for septic shock in the seriously septic patient:

• Host immune status
• Bacterial load
• Incorrect choice, dose and route of administration of antibiotics.

Presentation of the septic patient

Patients may be being investigated/treated for a known infection and suddenly deteriorate with systemic symptoms, or they can present with PUO. The clinical manifestations of bacteraemia and sepsis may overlap but include:

The dominant haemodynamic feature in septic shock is peripheral vascular failure leading to persistent hypotension. There is usually an element of cardiac dysfunction which may be affected by acidosis, hypoxaemia and myocardial oedema.

Pulmonary insufficiency is a common feature often requiring intubation and assisted ventilation. Organ failure (possibly multiple organ failure) and DIC are associated with septic shock.

SIRS criteria may help identify patients at increased risk of death. The presence of four or more criteria doubles the risk of death compared to the presence of only two criteria.

The clinical course is highly variable, being influenced by the microbial pathogen, endotoxin release, host defences and host inflammatory response.

Process of managing the acutely ill septic patient

The management of the septic patient involves three facets:

• Rapid investigation and monitoring
• Early empirical antibiotic therapy
• Aggressive supportive treatment.

Patients with severe sepsis or septic shock should be admitted to ICU or a high dependency unit.

Rapid investigation and monitoring

Clinical investigations and initial management often need to be undertaken concurrently, especially if septic shock is suspected.

• If not already known, determine the source of infection by clinical examination and culture of specific body fluids (eg. urine, sputum, or CSF).
• Take blood and other clinically appropriate cultures before starting antibiotic therapy. However, in order to avoid septic shock and possibly death:
• Do not delay initiation of antibiotics to undertake these tests
• Do not wait for laboratory results before administering antibiotics
• The blood samples (usually two from different peripheral sites) should be taken using good aseptic technique to avoid contamination with skin commensals. The volume of blood in the samples should be appropriate for the system used
• Blood cultures are particularly important for hospital-acquired bacteraemias because the range of possible pathogens is large and difficult to predict clinically
• Interpret blood culture results carefully. Do not rush to dismiss certain findings as ‘contaminants’.
• Implement intensive patient monitoring for signs of organ failure (possibly multiple organ failure):
  • Cardiovascular (blood pressure, pulmonary arterial wedge pressures, tissue perfusion)
  • Pulmonary (frequent blood gas analyses)
  • Renal (renal perfusion/urine output)
  • Liver.
• Blood pressure and blood gases are key early monitoring steps in septic patients.

Empirical antibiotic therapy

• Eradicate the source of infection with appropriate antibiotics and surgical drainage or debridement of the focus whenever possible.
• The choice of antibiotic, dose and route of administration are critical. Mortality is 2–3 times greater in bacteraemic patients who remain on ineffective empirical therapy. Even when the antibiotic regimen is corrected after 48 hours, patients are still more likely to die than those treated adequately from the outset.
• The choice of antibiotic, route of administration and duration of treatment will be influenced by the probable source of infection, patient co-morbid factors and the likelihood of infection with a resistant organism (based on local susceptibility patterns and recent exposure to antibiotics).
  • Follow hospital antibiotic guidelines where available.
  • Use high doses (>100 times the MIC/MBC for the pathogen) or the upper end of the ranges given in the British National Formulary. The regimen should be capable of achieving high concentrations at the infection site.
  • Indications for IV administration include:
  • Serious or severe sepsis
  • Febrile patients with neutropenia or immunosuppression
  • Specific serious or deep seated infections.
  • Change to most appropriate agent once the sensitivities of the causative organism(s) are known.

Clinical history and examination will usually give some clues to the likely aetiology. If the history and examination provide no clues to the possible source of infection, consult your microbiologist.

If the source of infection is known, antibiotic therapy can be based on the most suitable empirical therapy for the infection:

• Fungaemia should be considered if patients have persistent fever despite administration of broad-spectrum antibiotics, especially if the patient is immunocompromised or has received:
• A blood transfusion
• Parenteral nutrition
Intra-abdominal surgery.

Supportive therapy

Patients with severe sepsis or septic shock should be admitted to ICU or a high dependency unit.

• Fluid resuscitation and adequate oxygenation are two of the most important initial steps in suspected septic shock. Incipient renal failure can usually be managed initially by an adequate fluid load and support of the circulation.
• The respiratory status must be monitored closely via frequent arterial blood gas analysis, and hypoxia or acid-base disturbance may require the initiation of ventilatory support and increased oxygen in the inspired gas.
• Metabolic acidosis may be due to lactic acidosis as a consequence of hypoxia and underperfusion, and blood lactate is a useful indicator of the effectiveness of resuscitation.
• Adequate urine output, a falling blood lactate level, and acid-base homeostasis are the indicators of restored tissue perfusion. Circulatory support with inotropes is preferable to vasoconstrictors.
• Vasoconstriction has a negative effect on organ perfusion and can reduce cardiac output if myocardial function is impaired, exacerbating hypoxic effects in the tissues.