Editing Sepsis/SIRS

== '''Definition''' ==

* Sepsis is defined as '''life-threatening organ dysfunction''' caused by a dysregulated host response to infection
** SEPSIS 3 (2016) defines '''organ dysfunction''' as an acute change in total SOFA score of two or more points consequent to infection
** This was found to have superior predictive value than SIRS score alone (only 0.74 vs 0.64 though, so SIRS score does retain some validity)
* Septic shock - a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality

== '''Risk factors''' ==

* Extremes of age
* Indwelling devices/breach of skin integrity
* IVDU
* ICU/HDU
* Immunosuppression
* Surgery in past 6/52

== '''Pathophysiology:''' ==

=== '''Normal response to infection''' ===

** Host response initiated when innate immune cells (especially macrophages) recognise and to microbial components
*** Pattern-recognition receptors (PRRs) on the surface of immune cells recognise and bind to microbial pathogen-associated molecular patterns (PAMPs) or endogenous danger signals
**** PRRs include toll-like receptors (TLRs) and others
*** Neutrophils begin to defend against pathogens - phagocytosis, secretion of antimicrobial peptides, and the release of neutrophil extracellular traps (NETs)
*** Signalling cascade developed via the activation of cytosolic nuclear factor-kb (NF-kb), which leads to activation of genes involved in host inflammatory response such as TNF-a, IL-1, IL-6, chemokines, vascular adhesion molecule-1, and nitric oxide
*** Polymorphonuclear leucocytes become activated and aggregate at site of infection, causing warmth and erythema due to local vasodilation and hyperaemia
*** Pro-coagulant status causes micro-thrombosis
*** Some anti-inflammatory mediators balance this activation
*** If the inflammatory process is balanced, haemostasis is restored, leading to tissue repair and healing

=== '''Transition to sepsis''' ===

** Sepsis occurs when the release of pro-inflammatory mediators exceeds the boundaries of the local environment, leading to a more generalised response (can also occur without sepsis, as SIRS). This can also be characterised as malignant intra-vascular inflammation
** It is unclear why this happens, but likely multifactorial
*** Direct effects of invading micro-organisms and their toxins
*** Release of large quantities of pro-inflammatory mediators - mainly IL-1 and TNF-a
*** Complement activation
*** Possible genetic susceptibility
*** Loss or reduction of Compensatory Anti-inflammatory Response Syndrome (CARS) which includes factors like IL-4 and 10
** Excessive and prolonged activation of these pathways probably contributes to the development of multiple organ dysfunction
** Leads to vasodilation, enhanced capillary leak and eventually myocardial depression

=== '''Systemic effects of sepsis''' ===

** Organ dysfunction
*** Circulation - hypotension due to diffuse vasodilation - distributive shock, largely mediated by NO and prostacyclin
*** Lung - endothelial injury leads to pulmonary oedema and ARDS
*** GIT - depressed function allowing translocation
*** Liver dysfunction
*** Kidney - pre-renal injury, including ATN
*** CNS - often fails before other organs - encephalopathy
** Multiple organ dysfunction syndrome (MODS) - see below
** Tissue ischaemia - due to derangements in metabolic autoregulation, and also endothelial injury
** Cytopathic injury
** Cell death pathways activated
** Immunosuppression
** Activation of coagulation system and vascular endothelium - DIC

== '''Diagnosis:''' ==

=== '''New criteria''' ===

** '''qSOFA''' (recommended by CCrISP, and was initially thought to be a good way of approximating SOFA score by Sepsis 3, but the data to back up that use has been highly conflicted, and it is probably less useful than first thought) - Breathing, BP, Brain
*** Two or more of:
**** RR >22
**** SBP<100
**** Altered mentation
** SOFA - Sequential Organ Failure Assessment score - more complicated points calculator, up to 4 points in each category, best for ICU patients
*** Respiratory failure
*** Platelet level
*** Bilirubin
*** BP/vasopressors
*** GCS
*** Creatinine
** Septic shock - patients who, after adequate fluid resuscitation and antibiotics, meet the following criteria:
*** Persistent lactate >2
*** Vasopressors required to maintain MAP >65
*** ''40% risk of mortality in this group, compared to 10% in those who do not''

=== '''''Old criteria:''''' ===

** '''''SIRS''''' ''(no longer recommended for clinical use by sepsis 3 - think of it as an appropriate, regulated non-specific response to infection)''':'''''
*** ''Two or more of:''
**** ''Temp >38 or <36''
**** ''HR >90''
**** ''RR>20''
**** ''WCC >12 or <4''
**** ''Acutely altered mental state''
**** ''BGL > 6.6 in absence of diabetes''
** '''''Sepsis = SIRS + documented source of infection'''''
*** ''Alternative definition from CCrISP is of 'a life-threatening organ dysfunction caused by a dysregulated host response to infection'''
** '''''Severe sepsis = SIRS + altered organ perfusion''''' ''(no longer a clinically useful definition according to CCrISP)''
*** ''CVS (lactate > 1.2)''
*** ''Pa02/Fi02 < 30 or Pa02 < 9.3kPa''
*** ''Urine output < 120ml over 4 hours''
*** ''GCS < 15 acutely''
** '''''Septic shock:''''' ''infection plus''
*** ''Definition 1:''
**** ''Vasopressors to maintain MAP >65, '''and'''''
**** ''Lactate >2''
*** ''Associated with 40% mortality''

=== '''MODS''' ===

** Progressive organ dysfunction in an acutely ill patient, such that homeostasis cannot be maintained without intervention.
** Primary - organ dysfunction is directly attributable to the insult itself
** Secondary - organ dysfunction is a consequence of the host's response
** Typically lungs, liver and kidneys affected most
** Early MODS (<3 days) is usually inadequate fluid resuscitation. Late MODS is usually infection.
** Treatment is via generalised approach
*** Resuscitate
*** Treat infections
*** Maintain tissue oxygenation
*** Debride devitalised tissue
*** Early enteral nutrition
*** Early mobilisation

== Approach when seeing a patient with possible sepsis on ward/ED: ==

* CCrISP ABCD
* Use qSOFA to evaluate for organ dysfunction
* Intervene as below
* Consider ICU if goal-directed resuscitation is required
* Identify likely source of sepsis
** Chest
** Abdomen
** CNS - headache/neck stiffness
** Lines - >48 hours old or being used for TPN
** Urinary

== Intervention ==

* '''Within one hour - the Sepsis Six: (three in, three out)'''
** High-flow oxygen
** IV Abx
** IVF - be aggressive if patient is hypotensive and there isn't a contraindication - bolus of 20mL/kg, or 30mL/kg if lactate >4
** BCs
** Hb, lactate
** Hourly UO
* '''Within three hours:'''
** If persistent hypotension or increased lactate, apply goal-directed resuscitation
** Consider need for escalation of monitoring and level of care
* '''Within six hours:'''
** Apply vasopressors for hypotension that does not respond to initial fluid, aiming MAP>65
** Reassess volume status and tissue perfusion and document findings
** Remeasure lactate if it was initially elevated
* '''Definitive control:'''
** Septic screen - CXR, urine, stool, sputum, review and culture all lines

== Follow-up: ==

* Consider and anticipate risk of multi-organ failure:
** ARDS - respiratory support almost always needed, usually mechanical ventilation. Vague clinical picture, so suspicion is needed, and escalation for critical care input.
** Cardiovascular failure 
*** Loss of peripheral vascular tone
*** Loss of circulating volume
*** Myocardial depression secondary to cytokines
** Renal failure
*** Often established early on during hypotension
** Gut
** Brain
** Clotting system
*** Thrombocytopaenia
*** Coagulopathies
** Liver


[[Category:Critical care]]
[[Category:Intern education]]