Definitions revised in 2016 – SIRS, severe sepsis etc. no longer used.
Sepsis is life threatening organ dysfunction resulting from a dysregulated host response to infection.
The SOFA score is used to stratify the level of organ dysfunction but is reasonably complex to use.
Therefore, in practice, the quick SOFA (qSOFA) variables are used.
Any two of the three following suggest a high risk of sepsis – this replaces SIRS criteria:
- Mental state alteration
- Systolic BP < 100 mmHg
- Resp rate > 22
Septic shock is defined as sepsis with persisting hypotension requiring vasopressors to maintain MAP > 65 mmHg and elevated serum lactate > 2 mmol/L.
Risk factors for urosepsis:
- Immunosuppression
- Frailty
- Extremes of age (> 75)
- Recent surgery
- IVDU
- Indwelling catheters
- Skin breaches
- Underlying malignancy
- Pregnancy
- Dialysis / renal failure
- Diabetes
- Urinary tract obstruction
- Urinary tract interventions
- Stones
Pathophysiology of (uro)sepsis:
The septic response is initiated by the pathogen, but the dysregulated host response then drives the sepsis.
Different pathogens have different ways of initiating a host response – classically described are lipopolysaccharide (LPS) endotoxins in the cell wall of gram -ve bacteria but can also be exotoxins such as in pseudomonas species.
These bacterial toxins, or the bacteria themselves, bind to cellular receptors (eg Toll like receptors) of innate immune cells such as macrophages, neutrophils and endothelial cells.
This triggers a cascade of cytokine release (interleukins, TNF-a) and synergistic activation of complement system which produces an overwhelming inflammatory response – resulting in widespread vasodilation and increased vessel permeability secondary to mediators like nitric oxide which can lead to shock.
After this initial overwhelming inflammatory response, there is a subsequent immunosuppressive response due to leukocytes and lymphocytes no longer working or undergoing apoptosis, which leaves patients vulnerable to secondary infections, and relapse of dormant viruses.
Other systems outside the immunological system can be involved – for example complement system activation is intimately connected to coagulation system and leads to hypercoagulability and risk of DIC.
- Toxins/mediators produced by bugs bind to receptors of innate immune system cells
- Massive inflammatory response driven by cytokine cascade
- Secondary immunosuppression
Management of sepsis
Prompt simultaneous assessment and management as per CCrISP algorithm.
Initial management:
- History/examination/investigations.
- Large IV access, fluid bolus (up to 30 ml/kg) and high flow oxygen.
- Multidisciplinary management with ED/ICU/anaesthetics/ID etc
- Blood cultures and urine cultures prior to early broad spectrum antibiotics (e.g. amp/gent or piptaz).
- Catheterisation and appropriate monitoring
- Early review by ICU
Diagnosis (imaging) and source control – i.e. nephrostomy/stent/abscess drainage..